US20110024043A1 - Continuous analyte sensors and methods of making same - Google Patents

Continuous analyte sensors and methods of making same Download PDF

Info

Publication number
US20110024043A1
US20110024043A1 US12/829,337 US82933710A US2011024043A1 US 20110024043 A1 US20110024043 A1 US 20110024043A1 US 82933710 A US82933710 A US 82933710A US 2011024043 A1 US2011024043 A1 US 2011024043A1
Authority
US
United States
Prior art keywords
conductive body
elongated conductive
coating
layer
elongated
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US12/829,337
Inventor
Robert Boock
Jeff Jackson
Huashi Zhang
Jason Mitchell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dexcom Inc
Original Assignee
Dexcom Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dexcom Inc filed Critical Dexcom Inc
Priority to US12/829,337 priority Critical patent/US20110024043A1/en
Assigned to DEXCOM, INC. reassignment DEXCOM, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BOOCK, ROBERT, JACKSON, JEFF, ZHANG, HUASHI, MITCHELL, JASON
Publication of US20110024043A1 publication Critical patent/US20110024043A1/en
Priority to US14/155,814 priority patent/US20140123893A1/en
Priority to US14/451,332 priority patent/US20140343386A1/en
Priority to US16/452,364 priority patent/US20190307371A1/en
Priority to US17/867,608 priority patent/US20220346674A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14503Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14507Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood
    • A61B5/1451Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood for interstitial fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14507Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood
    • A61B5/14517Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood for sweat
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1486Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
    • A61B5/14865Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05CAPPARATUS FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05C3/00Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material
    • B05C3/02Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material the work being immersed in the liquid or other fluent material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05CAPPARATUS FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05C3/00Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material
    • B05C3/02Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material the work being immersed in the liquid or other fluent material
    • B05C3/09Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material the work being immersed in the liquid or other fluent material for treating separate articles
    • B05C3/10Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material the work being immersed in the liquid or other fluent material for treating separate articles the articles being moved through the liquid or other fluent material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05CAPPARATUS FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05C3/00Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material
    • B05C3/02Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material the work being immersed in the liquid or other fluent material
    • B05C3/12Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material the work being immersed in the liquid or other fluent material for treating work of indefinite length
    • B05C3/125Apparatus in which the work is brought into contact with a bulk quantity of liquid or other fluent material the work being immersed in the liquid or other fluent material for treating work of indefinite length the work being a web, band, strip or the like
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B23MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23KSOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K26/00Working by laser beam, e.g. welding, cutting or boring
    • B23K26/36Removing material
    • B23K26/362Laser etching
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2560/00Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
    • A61B2560/02Operational features
    • A61B2560/0223Operational features of calibration, e.g. protocols for calibrating sensors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0209Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/04Arrangements of multiple sensors of the same type
    • A61B2562/043Arrangements of multiple sensors of the same type in a linear array
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/12Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A61B2562/125Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05CAPPARATUS FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05C5/00Apparatus in which liquid or other fluent material is projected, poured or allowed to flow on to the surface of the work
    • B05C5/02Apparatus in which liquid or other fluent material is projected, poured or allowed to flow on to the surface of the work the liquid or other fluent material being discharged through an outlet orifice by pressure, e.g. from an outlet device in contact or almost in contact, with the work
    • B05C5/0241Apparatus in which liquid or other fluent material is projected, poured or allowed to flow on to the surface of the work the liquid or other fluent material being discharged through an outlet orifice by pressure, e.g. from an outlet device in contact or almost in contact, with the work for applying liquid or other fluent material to elongated work, e.g. wires, cables, tubes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05DPROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D1/00Processes for applying liquids or other fluent materials
    • B05D1/18Processes for applying liquids or other fluent materials performed by dipping
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05DPROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D3/00Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials
    • B05D3/06Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials by exposure to radiation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B23MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23KSOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K26/00Working by laser beam, e.g. welding, cutting or boring
    • B23K26/08Devices involving relative movement between laser beam and workpiece
    • B23K26/0823Devices involving rotation of the workpiece
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C2791/00Shaping characteristics in general
    • B29C2791/004Shaping under special conditions
    • B29C2791/009Using laser
    • CCHEMISTRY; METALLURGY
    • C23COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23CCOATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C2/00Hot-dipping or immersion processes for applying the coating material in the molten state without affecting the shape; Apparatus therefor

Definitions

  • the embodiments described herein relate generally to continuous analyte sensors and systems and methods for making these sensors.
  • Diabetes mellitus is a chronic disease, which occurs when the pancreas does not produce enough insulin (Type I), or when the body cannot effectively use the insulin it produces (Type II).
  • This condition typically leads to an increased concentration of glucose in the blood (hyperglycemia), which can cause an array of physiological derangements (e.g., kidney failure, skin ulcers, or bleeding into the vitreous of the eye) associated with the deterioration of small blood vessels.
  • a hypoglycemic reaction low blood sugar
  • a variety of implantable continuous electrochemical analyte sensors have been developed for continuously measuring blood glucose concentrations.
  • these types of sensors have been made by batch processes, which may not be suitable for large-scale, low-cost manufacturing, and which often result in batch-to-batch variations, thereby resulting in property variations among the sensors produced.
  • a method for manufacturing a continuous analyte sensor comprising applying an insulating material to an elongated conductive body comprising a conductive surface by advancing the elongated conductive body through a meniscus comprising the insulating material; and drying or curing the applied insulating material to form a coating of the insulating material on the elongated conductive body, the coating comprising a portion of the continuous analyte sensor, whereby a continuous analyte sensor configured for in vivo use is obtained.
  • the method further comprises continuously circulating a liquid comprising the insulating material in a vessel, whereby the meniscus is provided at a wall of the vessel.
  • the method further comprises removing a fraction of the insulating material applied to the elongated conductive body.
  • removing is performed by advancing the elongated conductive body through a die.
  • the method further comprises determining whether a thickness of the coating is within a predetermined range; and repeating applying the insulating material to the elongated conductive body if the thickness of the coating is outside of the predetermined range.
  • the predetermined range of the thickness of the coating is from about 5 microns to about 50 microns.
  • the method further comprises applying an adhesion promoter to the elongated conductive body before applying the insulating material.
  • the method further comprises etching a portion of the coating.
  • the method further comprises cutting the elongated conductive body into a plurality of sections.
  • each section is associated with an individual continuous analyte sensor.
  • the insulating material is selected from the group consisting of polyurethane, polyethylene, and polyimide.
  • the elongated conductive body is a wire with a circular cross-sectional shape or a substantially circular cross-sectional shape.
  • the conductive surface of the elongated conductive body comprises platinum.
  • the conductive surface of the elongated conductive body comprises at least one conductive material selected from the group consisting of platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and combinations thereof.
  • advancing the elongated conductive body through the meniscus is performed by a reel-to-reel system.
  • a method for manufacturing a continuous analyte sensor comprising applying a conductive material to an elongated conductive body by advancing the elongated conductive body through a liquid comprising the conductive material; drying or curing the applied liquid to form a coating of the conductive material on the elongated conductive body, the coating comprising a portion of the continuous analyte sensor; determining whether a thickness of the coating is within a predetermined range; and, if the thickness is below the predetermined range, repeating steps of applying a conductive material and drying or curing the applied liquid until the thickness of the coating is determined to be within the predetermined range, whereby a continuous analyte sensor configured for in vivo use is obtained.
  • the method further comprises removing a fraction of the conductive material applied to the elongated conductive body.
  • removing is performed by advancing the elongated conductive body through a die.
  • the conductive material is Ag/AgCl.
  • the predetermined range of the thickness of the coating is from about 1 micron to about 20 microns.
  • the conductive material is platinum.
  • the predetermined range is from about 1 micron to about 10 microns.
  • the method further comprises applying an adhesion promoter to the elongated conductive body before applying the conductive material.
  • the method further comprises etching a portion of the coating.
  • the method further comprises cutting the elongated conductive body into a plurality of sections.
  • each section is associated with an individual continuous analyte sensor.
  • the conductive material is Ag/AgCl.
  • the conductive material has a particle size associated with a maximum particle dimension that is less than about 100 microns.
  • the elongated conductive body is a wire with a circular cross-sectional shape or a substantially circular cross-sectional shape.
  • the elongated conductive body comprises an outer surface comprising an insulating material selected from the group consisting of polyurethane, polyethylene, and polyimide.
  • applying a conductive material is performed by a reel-to-reel system.
  • a system for manufacturing a continuous analyte sensor, the system comprising a coating vessel configured to hold a coating material in liquid form; a reel-to-reel system configured to advance an elongated conductive body through the coating material, whereby the coating material is applied to the elongated conductive body; a thickness measurement sensor configured to measure a dimension indicative of a thickness of a coating formed from the coating material applied to the elongated conductive body; an etching system configured to remove a portion of the coating material applied to the elongated conductive body; and a cutter configured to cut the elongated conductive body into a plurality of sections, wherein each section is associated with an individual continuous analyte sensor.
  • system further comprises a die configured to remove a portion of the coating material applied to the elongated conductive body.
  • the elongated conductive body is a wire with a circular cross-sectional shape or a substantially circular cross-sectional shape.
  • the coating material comprises an insulating material selected from the group consisting of polyurethane, polyethylene, and polyimide.
  • the coating material comprises a conductive material selected from the group consisting of platinum, silver/silver chloride, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and alloys and combinations thereof.
  • system further comprises a pump and conduit system configured to circulate the coating material in liquid form in the coating vessel to provide a meniscus at a wall of the coating vessel.
  • coating material is a component of a solution, wherein the solution is controlled to have a predetermined viscosity.
  • the viscosity is controlled by selecting a concentration of the coating material in the solution or by selecting a solution temperature.
  • FIG. 1A is a schematic diagram of one embodiment of an automated, continuous system for manufacturing continuous analyte sensors
  • FIG. 1B is a schematic diagram of another embodiment of an automated, continuous system for manufacturing continuous analyte sensors
  • FIG. 1C is a schematic diagram of yet another embodiment of an automated, continuous system for manufacturing continuous analyte sensors
  • FIG. 1D is a schematic diagram of yet another embodiment of an automated, continuous system for manufacturing continuous analyte sensors
  • FIG. 1E is a schematic diagram of yet another embodiment of an automated, continuous system for manufacturing continuous analyte sensors.
  • FIG. 2A is a side view of one embodiment of a transport mechanism
  • FIG. 2B is a front view of the embodiment illustrated in FIG. 2A .
  • FIG. 3A is a schematic diagram of one embodiment of a coating station
  • FIG. 3B is a schematic diagram providing a detailed view of the interface between the elongated conductive body and the meniscus, of the embodiment illustrated in FIG. 3A
  • FIG. 3C is a schematic diagram of another embodiment of a coating station
  • FIG. 3D is a schematic diagram of yet another embodiment of a coating station
  • FIG. 3E is a schematic diagram of yet another embodiment of a coating station
  • FIG. 3F is a schematic diagram of yet another embodiment of a coating station
  • FIG. 3G is a schematic diagram of an embodiment of a coating station comprising a coating vessel with a die
  • FIG. 3H is a close side view of the die illustrated in FIG. 3G
  • FIG. 3I provides a view of the coating chamber illustrated FIG. 3G on lines 3 I- 3 I;
  • FIG. 3J illustrates various examples of cross-sectional shapes of a die orifice;
  • FIG. 3K is a schematic diagram of yet another embodiment of a coating station.
  • FIG. 4A is side view of an elongated conductive body having portions that are covered by one or more layers of material and portions that are uncovered;
  • FIG. 4B is a side view of the elongated conductive body of FIG. 4A after it has been coated with a layer of coating material.
  • FIG. 5 is a flowchart summarizing the steps of one embodiment of a method for continuously manufacturing analyte sensors.
  • FIGS. 6A and 6B are cross-sectional views through one embodiment of the elongated conductive body of FIG. 4B on lines 6 A- 6 A and 6 B- 6 B, respectively.
  • FIG. 7A illustrates one embodiment of an elongated conductive body
  • FIG. 7B illustrates the embodiment of FIG. 7A after it has undergone laser ablation treatment
  • FIG. 7C illustrates another embodiment of an elongated conductive body
  • FIG. 7D illustrates the embodiment of FIG. 7C after it has undergone laser ablation treatment.
  • FIG. 8A illustrates one embodiment of an elongated conductive body
  • FIG. 8B illustrates the embodiment of FIG. 8A after it has undergone laser ablation treatment
  • FIG. 8C illustrates another embodiment of an elongated conductive body
  • FIG. 8D illustrates the embodiment of FIG. 8C after it has undergone laser ablation treatment.
  • FIG. 9A illustrates a recessed region formed with a curved edge
  • FIG. 9B illustrates a recessed region formed with a sharp edge.
  • FIG. 10A illustrates one embodiment of a die
  • FIG. 10B provides a view of the die on lines 10 B- 10 B of FIG. 10A .
  • FIG. 11 illustrates one embodiment of a system that integrates etching and singulation of the elongated conductive body.
  • analyte is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to a substance or chemical constituent in a biological fluid (for example, blood, interstitial fluid, cerebral spinal fluid, lymph fluid, urine, sweat, saliva, etc.) that can be analyzed. Analytes can include naturally occurring substances, artificial substances, metabolites, or reaction products. In some embodiments, the analyte for measurement by the sensing regions, devices, and methods is glucose.
  • acarboxyprothrombin acylcarnitine
  • adenine phosphoribosyl transferase adenosine deaminase
  • albumin alpha-fetoprotein
  • amino acid profiles arginine (Krebs cycle), histidine/urocanic acid, homocysteine, phenylalanine/tyrosine, tryptophan); andrenostenedione
  • antipyrine arabinitol enantiomers
  • arginase benzoylecgonine (cocaine); biotinidase; biopterin; c-reactive protein; carnitine; carnosinase; CD4; ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol; cholinesterase; conjugated 1- ⁇ hydroxy-cholic acid; cortisol; creatine kinase; creatine kinas
  • Salts, sugar, protein, fat, vitamins, and hormones naturally occurring in blood or interstitial fluids can also constitute analytes in certain embodiments.
  • the analyte can be naturally present in the biological fluid or endogenous, for example, a metabolic product, a hormone, an antigen, an antibody, and the like.
  • the analyte can be introduced into the body or exogenous, for example, a contrast agent for imaging, a radioisotope, a chemical agent, a fluorocarbon-based synthetic blood, or a drug or pharmaceutical composition, including but not limited to: insulin; ethanol; cannabis (marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide, amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine (crack cocaine); stimulants (amphetamines, methamphetamines, Ritalin, Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegine); depressants (barbituates, methaqualone, tranquilizers such as Valium, Librium, Miltown, Serax, Equanil, Tranxene); hallucinogens (phencyclidine, lysergic acid, mescaline, peyo
  • Analytes such as neurochemicals and other chemicals generated within the body can also be analyzed, such as, for example, ascorbic acid, uric acid, dopamine, noradrenaline, 3-methoxytyramine (3MT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5HT), and 5-hydroxyindoleacetic acid (FHIAA).
  • continuous as used herein in reference to analyte sensing, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the continuous, continual, or intermittent (e.g., regular) monitoring of analyte concentration, such as, for example, performing a measurement about every 1 to 10 minutes.
  • an “elongated conductive body,” as used herein is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to an elongated body formed at least in part of a conductive material and includes any number of coatings that may be formed thereon.
  • an “elongated conductive body” can mean a bare elongated core (e.g., a conductive metal wire, a non-conductive polymer rod) or an elongated core coated with one, two, three, four, five, or more layers of material that may be or may not be conductive.
  • electrochemically reactive surface and “electroactive surface,” as used herein, are broad terms, and are to be given their ordinary and customary meaning to a person of ordinary skill in the art (and are not to be limited to a special or customized meaning), and refer without limitation to the surface of an electrode where an electrochemical reaction is to take place.
  • H 2 O 2 hydrogen peroxide
  • glucose oxidase produces H 2 O 2 as a byproduct.
  • the H 2 O 2 reacts with the surface of the working electrode to produce two protons (2H + ), two electrons (2e ⁇ ) and one molecule of oxygen (O 2 ), which produces the electric current being detected.
  • a reducible species for example, O 2 is reduced at the electrode surface in order to balance the current being generated by the working electrode.
  • sensing region is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the region of a monitoring device responsible for the detection of a particular analyte.
  • a sensor includes a membrane system having a diffusion resistance layer and an enzyme layer. If the sensor is deemed to be the point of reference and the diffusion resistance layer is positioned farther from the sensor than the enzyme layer, then the diffusion resistance layer is more distal to the sensor than the enzyme layer.
  • proximal to is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the spatial relationship between various elements in comparison to a particular point of reference.
  • some embodiments of a device include a membrane system having a diffusion resistance layer and an enzyme layer. If the sensor is deemed to be the point of reference and the enzyme layer is positioned nearer to the sensor than the diffusion resistance layer, then the enzyme layer is more proximal to the sensor than the diffusion resistance layer.
  • interferents is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to effects or species that interfere with the measurement of an analyte of interest in a sensor to produce a signal that does not accurately represent the analyte measurement.
  • interferents can include compounds with an oxidation potential that overlaps with that of the analyte to be measured.
  • membrane system and “membrane,” as used herein, are broad terms, and are to be given their ordinary and customary meaning to a person of ordinary skill in the art (and are not to be limited to a special or customized meaning), and refer without limitation to a permeable or semi-permeable membrane that can comprise one or more layers and constructed of materials, which are permeable to oxygen and may or may not be permeable to an analyte of interest.
  • the membrane system comprises an immobilized glucose oxidase enzyme, which enables an electrochemical reaction to occur to measure a concentration of glucose.
  • coefficient of variation is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the ratio of the standard deviation of a distribution to its arithmetic mean.
  • sensitivity is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to an amount of electrical current produced by a predetermined amount (unit) of the measured analyte.
  • a sensor has a sensitivity (or slope) of from about 1 to about 300 picoAmps of current for every 1 mg/dL of glucose analyte.
  • a sensor has a sensitivity (or slope) of from about 3 to about 1,000 picoAmps of current per mm 2 of electroactive surface, for every 1 mg/dL of glucose analyte.
  • chamber is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to a partially or fully enclosed space (e.g., chambers, conduits, channels, capillaries, tubes, wells, cells, vessels, microchannels, or the like).
  • FIG. 1A provides a schematic diagram of one embodiment of an automated, continuous system 100 for manufacturing continuous analyte sensors, whereby an elongated conductive body 110 is continuously advanced through a series of stations, each of which treats the elongated conductive body 110 .
  • these stations can include, but are not required to include, a coating station 120 for depositing coating material (e.g., insulating, conductive, or membrane material) onto the elongated conductive body 110 , a thickness control station 130 for removing excess coating material from the elongated conductive body 110 , a drying/curing station 140 for curing the coating material on the elongated conductive body 110 , and a thickness measurement station 150 for measuring the thickness of the elongated conductive body 110 (including any coatings thereon).
  • the elongated conductive body 110 can be advanced through this series of stations repeatedly, i.e., by making multiple repeated passes, until a preselected thickness has been formed on the elongated conductive body.
  • the system 100 described herein is merely exemplary, and some stations may be omitted or replaced by other stations.
  • the system can also include an etching station for removing or stripping portions of a coated assembly structure on the elongated conductive body (e.g., to create window regions corresponding to working electrodes on the elongated conductive body). Etching to create window regions can be achieved by removing a portion of the insulating layer, conductive layer, or the like, from the elongated conductive body, using ablation (e.g., laser skiving), chemical etching, or other known techniques. Additionally or optionally, the system can also include a pre-coating treatment station for pre-cleaning the elongated conductive body before the coating process, and a post-coating treatment station for post-cleaning after the coating process. Additionally or optionally, the system can also include a singulation station for cutting the elongated conductive body into individual pieces corresponding individual sensors.
  • an etching station for removing or stripping portions of a coated assembly structure on the elongated conductive body (e.g., to create window regions corresponding to working electrodes
  • the system 100 can also be equipped with an automated control system comprising detector elements, control elements, and a processor 160 .
  • the detector and control elements can be embedded in the stations and disposed anywhere on or near the pathway of the elongated conductive body 110 .
  • the detector elements are configured to transmit to the processor 160 signals relating to certain process conditions of the system 100 , such as, for example, the temperature of the coating solution, the humidity of the atmosphere immediately around a region of the elongated conductive body which is undergoing or about to undergo meniscus coating or laser ablation, the rate at which the elongated conductive body 110 is advancing, or the last measured thickness of the elongated conductive body 110 .
  • the processor 160 is programmed to process these input signals and transmit output signals to control operation of the control elements, e.g., valves, motors, pumps, agitators, heat lamps, die opening, etc., so that preselected process conditions for optimum controlled coating processing can be achieved and maintained.
  • control elements e.g., valves, motors, pumps, agitators, heat lamps, die opening, etc.
  • a detector element in the form of a temperature transducer e.g., a thermistor
  • a control element in the form of a heat source e.g., a heat lamp
  • the temperature transducer detects a temperature that is less than a preselected temperature range
  • the temperature transducer is configured to transmit a signal to the processor 160 , which in turn responds by transmitting a signal to activate the heat source to heat the elongated conductive body 110 to the preselected temperature.
  • the heat source is positioned near the entrance of the coating station 120 , so that the elongated conductive body 110 is heated to a preselected temperature that facilitates the coating process.
  • a heat source can be provided near the exit of the coating station 120 to speed the evaporation of residual solvent on the elongated conductive body 110 .
  • the system 100 comprises a transport mechanism 170 for sequentially advancing the elongated conductive body 110 through the various stations.
  • the system 100 employs a reel-to-reel mechanism comprising a motor (not shown in FIG. 1A ), a rotatable supply spool 172 , and a rotatable return spool 174 .
  • the elongated conductive body 110 is attached to both the supply spool 172 and the return spool 174 .
  • the elongated conductive body is configured to sequentially advance through the stations in a horizontal or substantially horizontal arrangement
  • a vertical or substantially vertical arrangement can also be used for one or more of the stations, for example, to address any gravity-induced sagging issues with respect to a fresh coating on the elongated conductive body.
  • FIGS. 2A and 2B illustrate a side view and a front view, respectively, of one embodiment of a transport mechanism 270 comprising a spool 276 , suitable for use as a supply spool, a return spool, or any other spool employed by the system.
  • the spool 276 can include a reel 278 mechanically connected to a motor 271 via a rotatable shaft 273 .
  • the motor 271 can be any of a variety of conventional motors suitable for the applications contemplated.
  • the reel 278 can be any type of reel upon which the elongated conductive body can be wound, and can comprise a soft material, such as silicone rubber, polyurethane, or nylon, for example, that will not cut away at coatings on the elongated conductive body and will not allow the elongated conductive body to slide freely over the reel when the reel is rotated.
  • the diameter and width of the reel 278 can be varied depending in part on the dimensions of the elongated conductive body and other design considerations. In some embodiments, reels with a small width can be employed where there are tight space constraints. In these embodiments, coils of the elongated conductive body on the reel can overlap and touch portions of adjacent coils.
  • reels having a large width can be desirable, such that the coils can be arranged to not touch each other.
  • reels with large diameters can be used, resulting in a smaller bend radius, thereby minimizing the risk that materials on the elongated conductive body will crack or chip off
  • the system 100 comprises one supply spool 172 and one return spool 174
  • the system can comprise any number of spools.
  • the system can comprise two, three, four, five, or more supply spools associated with an equal number or a different number of return spools.
  • the system can comprise any number of stations. As illustrated in FIG. 1C , in one exemplary embodiment, the system can comprise three supply spools 173 a, 173 b, 173 c that provide three elongated conductive bodies 110 a, 110 b, 110 c, each of which are wound into a single take-up spool 175 .
  • the system comprises one coating station 120 , three thickness control stations 130 a, 130 b, 130 c, one drying/curing station 140 , and three thickness measurement stations 150 a, 150 b, 150 c.
  • the system can comprise any number of station combinations. For instance, in one embodiment, the system can comprise five coating stations, five thickness control stations, one drying/curing station, and one thickness measurement station. In another embodiment, the system can comprise three coating stations, three thickness stations, three drying/curing stations, and one thickness measurement station.
  • the system can comprise four stations, each of which is configured to treat multiple portions of the elongated conductive body 110 .
  • the elongated conductive body 110 is unwound from a supply spool 173 and becomes engaged with a first guide roller 178 that guides the elongated conductive body 110 to a coating station 120 . Thereafter, the elongated conductive body 110 is advanced through a thickness control station 130 , a drying/curing station 140 , and a thickness measurement station 150 . After exiting the measurement station 150 , the elongated conductive body 110 engages a second guide roller 179 , by which it is returned to the first guide roller 178 . As illustrated in FIG.
  • the elongated conductive body 110 is then advanced through additional coating station/thickness control station/drying/curing station/thickness measurement station series/sequences. After passing through a preselected number of the aforementioned series/sequences, the elongated conductive body 110 is advanced to the second guide roller 179 , by which it is wound into the take-up spool 175 .
  • the system is configured to provide five series/sequences of stations; in other embodiments the system can comprise a different number of series/sequences. For example, the system can be configured to provide two, three, five, six, seven, or more series/sequences of stations.
  • the system can include one or more pulleys or guide rollers 177 , 178 , 179 for guiding the elongated conductive body 110 as it advances through the various stations of the system 100 .
  • the guide rollers can be positioned at any suitable location along the pathway of the elongated conductive body 110 .
  • a guide roller can be disposed at a position near the entrance of a certain station, such as the coating station 120 .
  • a guide roller can be disposed at a position near the exit of a certain station, such as a thickness control station 130 .
  • guide rollers can be disposed near both the entrance and exit of a certain station.
  • the system does not use guide rollers, but instead uses the tension present in the elongated conductive body 110 (derived from the transport mechanism 170 ) to guide it along its pathway as it advances through the various stations.
  • the pathway of the elongated conductive body 110 is a cyclical pathway, i.e., the pathway extends from the supply spool 172 to the return spool 174 , and then extends back to the supply spool 172 from the return spool 174 .
  • the pathway may not be cyclical, but is single directional instead.
  • the elongated conductive body 110 is unwound from a supply spool 173 and wound into a take-up spool 175 , after which it can be retrieved by an operator and loaded onto another system for further processing.
  • each of the spools is associated with a motor configured to drive the spool.
  • one or more of the spools is not associated with a motor.
  • the transport mechanism can comprise a take-up spool driven by a motor to rotate at a preselected speed of rotation, while a corresponding supply spool is maintained effectively freely rotatable. More specifically, in this embodiment, whereas rotation of the take-up spool is actively driven by a motor, rotation of the supply spool is driven by translational forces from the moving elongated conductive body, as it is driven by the rotating take-up spool.
  • the torque exerted by the take-up spool provides tension to the elongated conductive body as it unwinds from the supply spool, advances through the various stations of the system, and eventually winds into the take-up spool.
  • An increase in the torque exerted by the take-up spool may also increase the tension present in the elongated conductive body.
  • the tension present in the elongated conductive body 110 can be measured by any of a variety of tension detectors.
  • a tension detector is disposed at various positions along the pathway of the elongated conductive body 110 to directly measure its tension.
  • the tension is indirectly measured by measuring the torques exerted by the various spools and calculating the torque differences between the spools. If the tension is determined to be greater or less than a preselected value, the tension detector can be configured to transmit a signal to the processor, which is programmed to determine whether a problem exists (e.g., a severed elongated conductive body or one detached from the reel). If the determination is positive, the system can optionally respond with an alert or alarm to notify an operator.
  • a problem e.g., a severed elongated conductive body or one detached from the reel.
  • the transport mechanism 170 is configured to advance the elongated conductive body 110 at a constant or substantially constant preselected speed. Selection of the preselected speed can depend in part on design considerations associated with certain preselected process conditions (e.g., the preselected viscosity and solids content of the coating solution, suspension, dispersion, or other liquid comprising the coating material) that will provide optimal coating thickness control.
  • the elongated conductive body is configured to advance at a preselected speed greater than about 0.5 cm per minute, or greater than about 10 cm per minute, or greater than about 25 cm per minute, or greater than about 50 cm per minute, or even greater than about 250 cm per minute.
  • a variable-speed transport mechanism can be used to advance the elongated conductive body at varying speeds. For example, in some embodiments, the transport mechanism can be configured to periodically halt the advancement of the elongated conductive body.
  • a speed measurement system e.g., a vision system
  • a vision system can be employed to measure the elongated conductive body's actual speed. If the measured speed is not within a certain range of the preselected speed, the vision system is configured to transmit a signal to the processor, which in turn can adjust motor settings in response.
  • the elongated conductive body 110 may also be advanced through the series of stations with any of a variety of other transport mechanisms, such as, for example, a robotic system, a conveyor system, and other like systems. These other transport mechanisms may be used in combination with (or as an alternative to) a reel-to-reel system.
  • a reel-to-reel system is used to move the elongated conductive body 110 before it is singulated into individual pieces 110 ′, and a robotic system is used to move the individual pieces 110 ′ after the singulation process.
  • FIG. 1E illustrates one embodiment of a robotic system 180 , which can range in size from a large device suitable for industrial scale use to a small device suitable for laboratory bench tops.
  • Robotic systems may be advantageous in certain instances because they can provide accurate, precise positioning of the elongated conductive body 110 ′ in two or three dimensions.
  • they are highly flexible and reconfigurable, which can be advantageous for facilitating the physical transfer of individual pieces to/from a variety of stations, vessels, containers, chambers, or the like.
  • the robotic system 180 comprises an elongated conductive body holder 182 (e.g., a robot arm) designed to move an elongated conductive body 110 ′ through variable programmed motions for performance of a variety of tasks (e.g., for transferring the elongated conductive body 110 ′ from one coating vessel 184 to another 186 for different coating applications, and from one station to another for a variety of treatments).
  • an elongated conductive body holder 182 e.g., a robot arm
  • the elongated conductive body holder 182 is shown holding a four elongated conductive bodies 110 ′, in alternative embodiments, the elongated conductive body holder 182 may be capable of holding any number of of elongated conductive bodies 110 ′.
  • the elongated conductive body holder 182 is capable of both vertical movements and horizontal movements (e.g., linear or rotational), thereby allowing not only for movement between stations, vessels, containers, chambers, or the like, but also for movement that causes the elongated conductive body 110 ′ to be submerged or dipped in a coating solution of a coating vessel 184 , or movement that causes the elongated conductive body 110 ′ to be placed into a curing or drying chamber 188 .
  • both the number of times and the length of time that an elongated conductive body 110 ′ is in a station or is being coated, cured, dried, or treated in a vessel or chamber can be controlled.
  • the robot's elongated conductive body holder 182 can be instructed to dip the elongated conductive body 110 ′ (i.e., post-singulation in the form of an individual piece) into the coating vessel 184 for a plurality of dips, with each dip interspersed by drying or curing of the coating.
  • the elongated conductive body holder 182 is instructed to place the elongated conductive body 110 ′ in a position for one or more spraying sessions with a certain coating material to form a particular layer of the membrane, and then to dip the elongated conductive body 110 ′ for one or more coating sessions in a coating solution to form another layer.
  • the length of time of each dip/spray session and the length of time between each session can be varied or constant.
  • the elongated conductive body 110 ′ (in the form of an individual piece) is dipped one or more times for a predetermined time period in a pretreatment solution, then dipped one or more times for a predetermined time period into a solution containing a material that is to form the electrode and/or interference layer, then dipped one or more times for a predetermined time period into a solution containing a material that is to form the enzyme layer, and then dipped one or more times (for a predetermined time period) into a solution containing a material that is to form the diffusion resistance layer.
  • the elongated conductive body 110 ′ may be treated (e.g., conditioned, cleaned, cured, dried, etc.) or else maintained under normal ambient conditions. It should be understood that the process described above is merely exemplary, and some steps may be omitted or replaced by other steps.
  • FIG. 7A illustrates one embodiment of an elongated conductive body comprising an elongated core 710 , a first layer 720 that at least partially surrounds the core 710 , a second layer 730 that at least partially surrounds the first layer 720 , and a third layer 740 that at least partially surrounds the second layer 730 .
  • These layers which collectively form a coating assembly structure, can be deposited onto the elongated core by any of a variety of techniques, such as, for example, by employing the coating processes described elsewhere herein.
  • the first layer 720 can comprise a conductive material, such as, for example, platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, a conductive polymer, an alloy, and/or the like, configured to provide suitable electroactive surfaces for one or more working electrodes.
  • the second layer 730 can correspond to an insulator and comprise an insulating material, such as a non-conductive (e.g., dielectric) polymer, such as polyurethane, polyimide, polyolefin (e.g., polyethylene), for example.
  • the third layer 740 can correspond to a reference electrode and comprise a conductive material, for example, a silver-containing material, including, but not limited to, a polymer-based conducting mixture.
  • FIG. 7C illustrates another embodiment of an elongated conductive body.
  • the elongated conductive body in addition to an elongated core 710 , a first layer 720 , a second layer 730 , and a third layer 740 , the elongated conductive body further comprises a fourth layer 750 and a fifth layer 760 .
  • the first layer 720 and the second layer 730 can be formed of a conductive material and an insulating material, respectively, similar to those described in the embodiment of FIG. 7A .
  • the third layer 740 can be configured to provide the sensor with a second working electrode, in addition to the first working electrode provided by the first layer 720 .
  • the fourth layer 750 can comprise an insulating material and provide insulation between the third layer 740 and the fifth layer 760 , which can correspond to a reference electrode and comprise the aforementioned silver-containing material. It is contemplated that other similar embodiments are possible.
  • the elongated conductive body can have 6, 7, 8, 9, 10, or more layers, each of which can be formed of conductive or non-conductive material.
  • FIGS. 8A and 8C illustrate other embodiments of the elongated conductive body.
  • the elongated conductive body comprises three elongated cores 810 A, 810 B, and 810 C located in (e.g., embedded in, coated with) the insulator 830 .
  • FIG. 8C illustrates another embodiment of the elongated conductive body comprising three insulated conductive bodies, wherein each insulated conductive body includes an elongated core 810 A, 810 B, and 810 C coated with an insulator 804 A, 804 B, and 804 C).
  • the elongated cores are bundled together, such as by an elastic band, an adhesive, wrapping, a shrink-wrap or C-clip, as is known in the art.
  • the inner bodies e.g., coated with insulator
  • the inner bodies are twisted, such as into a triple-helix or similar configuration.
  • two of the elongated cores e.g., coated with insulator
  • a third core e.g., with insulator
  • the sensor can comprise additional elongated cores.
  • the elongated core is shaped like a wire and has a circular cross-section
  • the cross-section of the elongated core can be oval, square, rectangular, triangular, polyhedral, star-shaped, C-shaped, T-shaped, X-shaped, Y-Shaped, irregular, or the like.
  • the elongated core can be formed of any of a variety of suitable material, such as, platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive or non-conductive polymer, alloys, glass, for example.
  • the elongated core comprises an inner core and a first layer, wherein an exposed electroactive surface of the first layer provides the working electrode of the continuous analyte sensor being manufactured.
  • the inner core comprises stainless steel, titanium, tantalum and/or a polymer
  • the first layer comprises platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, a conductive polymer, and/or an alloy.
  • the elongated conductive body can be designed (e.g., by material selection, by diameter selection, by treatment) to have certain mechanical properties.
  • an elongated conductive body may be designed to meet a certain minimal level of tensile strength or minimal length of diameter, so that the elongated conductive body will not be prone to breakage during a reel-to-reel processing.
  • the tensile strength of the elongated conductive body is at least about 200 MPa, or at least about 500 MPa, or at least about 1,000 MPa, or at least about 2,000 MPa, or even at least about 5,000 MPa.
  • the diameter of the elongated conductive body is at least about 5 microns, or at least about 15 microns, or at least about 25 microns, or at least about 50 microns, or at least about 75 microns, or at least about 100 microns, and or even at least about 200 microns.
  • Other possible embodiments and features of the elongated conductive body are described in U.S. Provisional Application No. 61/222,751, the contents of which are incorporated by reference herein in its entirety.
  • the material that eventually forms the elongated conductive body may initially be in the form of one or more workpieces.
  • the workpiece may be formed of any of a variety of materials, such as, for example, platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and alloys or combinations thereof.
  • the initial workpiece possesses the desired dimensions, shapes, and mechanical specifications, and thus minimal (or no) substantial mechanical or structural changes need to be made to the workpiece before it is treated and processed (e.g., coated, dried, etched, singulated, etc.) to form a continuous analyte sensor.
  • the initial workpiece may already possess the desired shape (e.g., wire, tube, planar substrate, etc), but not the desired dimensions. In these embodiments, processing may involve resizing the workpiece to the desired dimensions.
  • the initial workpiece does not possess any of the above-described desired specifications and properties, and thus the workpiece has to undergo processing, whereby the workpiece itself is worked on by machine or hand tools to impart structural and/or mechanical changes.
  • These changes may involve, for example, cutting or shaping of the workpiece. They can also involve the addition of a layer (e.g., coating, cladding, plating, etc.) that circumscribes the outer surface of the workpiece.
  • the elongated conductive body may be fabricated to include a core and a cladding surrounding the core, both of which are formed from different materials.
  • fabricating the elongated conductive body to have a core formed with a less expensive, yet strong and flexible material (e.g., palladium, tantalum, stainless steel, or the like) and a thin layer of a more expensive material (e.g., platinum) to form the electroactive surface of the continuous analyte sensor can enable a substantial reduction in the material costs required to build the continuous analyte sensor.
  • a less expensive, yet strong and flexible material e.g., palladium, tantalum, stainless steel, or the like
  • a thin layer of a more expensive material e.g., platinum
  • fabrication of the elongated conductive body can be performed by inserting (e.g., by slip fitting) a rod or wire into a tube, the combination of which forms an initial structure of an elongated conductive body.
  • the rod or wire may be formed of any of a variety of materials including, but not limited to, stainless steel, titanium, tantalum, and/or a polymer.
  • the tube may be formed of a conductive material, such as, for example, platinum, platinum-iridium, gold, palladium, iridium, alloys thereof, graphite, carbon, or a conductive polymer.
  • a layer of conductive material may be deposited onto the core.
  • Deposition of the conductive material may be performed by any of a variety of techniques, such as, for example, chemical vapor deposition, physical vapor deposition (e.g., sputtering, vacuum deposition), chemical and electrochemical techniques, dip coating, spray coating, and optical coating.
  • chemical vapor deposition physical vapor deposition (e.g., sputtering, vacuum deposition)
  • chemical and electrochemical techniques dip coating, spray coating, and optical coating.
  • dip coating and spray coating processes described elsewhere herein may be used to deposit a coating layer onto the outer surface of the rod or wire.
  • the elongated conductive body can then be passed through a series of dies to draw down the diameter of the elongated conductive body from a large diameter to a small diameter.
  • the die e.g., a diamond die
  • the cross-sectional profile of the elongated conductive body is compressed, and the diameter associated therewith is reduced. It has been found that while compression tends to increase the tensile strength of the elongated conductive body, compression also tends to increase susceptibility of the elongated conductive body to brittleness, stress cracking, and even breakage.
  • an annealing step is used to cause changes in the mechanical and structural properties of the elongated conductive body, and more specifically, to relieve internal stresses, refine the structure by making it homogeneous, and improve cold working properties. It has also been found that drawing down the diameter of the elongated conductive body through large numbers of dies in small incremental steps, instead of through one or a few number of large incremental step(s), can result in better mechanical and structural properties. Accordingly, in some embodiments, the elongated conductive body is passed through a series of dies, with each successive die having a progressively smaller diameter. Between each die passing, the elongated conductive body may undergo an annealing treatment (e.g., by using an annealing oven), through which the elongated conductive body is softened and its ductility increased.
  • an annealing treatment e.g., by using an annealing oven
  • FIG. 10A illustrates one embodiment of a die 1050 used to compress the elongated conductive body, so as to reduce its cross-sectional profile.
  • FIG. 10B provides a view of the die on lines 10 B- 10 B of FIG. 10A .
  • the die 1050 comprises an orifice 1020 , a front portion 1012 , through which an elongated conductive body 1010 enters the die 1050 , and a back portion 1014 , through which the elongated conductive body 1010 exits.
  • the edge 1016 of the front portion 1012 may have a tapering angle a defined by the longitudinal axis 1018 of die 1050 and the front edge 1016 .
  • the elongated conductive body 1010 is drawn through a die 1050 (e.g., diamond die, etc.) and through its orifice 1020 .
  • a die 1050 e.g., diamond die, etc.
  • the shape and dimensions of the orifice 1020 may be changed, so that the elongated conductive body can be shaped and sized to have any desired cross sectional shape and dimensions.
  • the elongated conductive body 1010 As the elongated conductive body 1010 is forced through the die orifice 1050 to impart a shape or to reduce dimensions, the elongated conductive body 1010 becomes deformed. Drawing the elongated conductive body 1010 through a die with a large tapering angle will cause greater compression of the elongated conductive body 1010 than a die with a smaller tapering angle. Accordingly, drawing the elongated conductive body 1010 through a series of dies with large tapering angles may minimize the number of dies that an elongated conductive body has to be drawn through.
  • the tapering angle a of the die is less than about 60 degrees, sometimes less than about 45 degrees, sometimes less than about 30 degrees, sometimes less than about 30 degrees, and sometimes less than about 10 degrees.
  • obtaining and maintaining concentricity of the elongated conductive body is important. Without concentricity of the elongated conductive body, subsequent coatings of the conductive, insulating, and membrane materials may not be uniform, and consequently performance of the fabricated continuous analyte sensor may be negatively impacted.
  • the die 1050 is configured to cause the elongated conductive body 1010 to compress in a way such that compressive forces exerted on the cross-sectional circumference of the elongated conductive body are substantially uniform across the circumference, so that concentricity can be maintained.
  • the risk of concentricity loss may also be reduced by use of a positioning system (e.g., a vision system) that may be disposed near or along the die 1050 .
  • the positioning system can be used to confirm that the elongated conductive body 110 is aligned correctly during its entry into and exit out of the die 1050 , and that it is moving along a certain predetermined path (e.g., a path that is perpendicular to the plane defined by the orifice 1020 ).
  • portions of the die 1050 may be coated with a lubricant (e.g., oil) to reduce any buildup of friction associated with the advancement of the elongated conductive body 1010 through the die 1050 .
  • a lubricant e.g., oil
  • the workpiece station comprises a series of dies, which collectively are capable of reducing the thickness of the elongated conductive body, while still substantially maintaining the concentricity of the elongated conduct body.
  • the reduction in thickness corresponds to the reduction from an original elongated conductive body diameter of up to about 250 microns, sometimes up to about 500 microns, sometimes up to about 1,000 microns, and sometimes up to about 2,500 microns, to a final diameter no less than about 100 microns, sometimes no less than about 50 microns, sometimes no less than about 25 microns, and sometimes no less than about 13 microns.
  • the elongated conductive body can undergo any of a variety of processing to change its physical (and sometimes chemical) properties.
  • the elongated conductive body can undergo annealing, quenching, tempering, drawing, rolling, normalizing, work hardening, and/or work softening processes, so that the elongated conductive body acquires certain desired physical properties.
  • the automated, continuous system for manufacturing continuous analyte sensors may comprise an etching station, whereby portions of the coated assembly structure is stripped or otherwise removed. In some embodiments, removal of portions of deposited layers of coating can be performed to expose the one or more electroactive surface(s) of the elongated conductive body, thereby forming recessed regions or window regions/surfaces 420 corresponding to working electrodes.
  • etching and “etched” as used herein are broad terms, and are to be given their ordinary and customary meaning to a person of ordinary skill in the art (and are not to be limited to a special or customized meaning), and refer without limitation to a mechanism for forming one or more recessed regions within the elongated conducted body.
  • etching and “etched” as used herein is not limited to chemical etching. Rather, as used herein, “etching” and “etched” can also include, but are not limited to, techniques, such as laser etching/ablation/skiving, grit-blasting (e.g., with sodium bicarbonate or other suitable grit), or the like, that can be employed to expose certain surfaces of the elongated conductive body (e.g., the electroactive surfaces corresponding to a conductive layer or a surface corresponding to an insulating layer).
  • techniques such as laser etching/ablation/skiving, grit-blasting (e.g., with sodium bicarbonate or other suitable grit), or the like, that can be employed to expose certain surfaces of the elongated conductive body (e.g., the electroactive surfaces corresponding to a conductive layer or a surface corresponding to an insulating layer).
  • Achieving accuracy and precision with respect to the particular depth of one or more materials of a coated assembly which are removed by etching can be important. Without precision and accuracy (e.g., for certain embodiments involving an elongated conductive body with a circular or substantially circular cross-section), uniformity of ablation depth may not be achieved, and thus concentricity of the elongated conductive body may be lost. Without achieving and maintaining concentricity with a proximal layer of the elongated conductive body, any subsequent (i.e., distal) layers coated over the proximal layer would also not have concentricity. Loss of concentricity can result in certain portions of the elongated conductive body being thicker than other portions, which in turn, can negatively affect sensor performance (e.g., accuracy).
  • the etching process involves etching a single layer of material (e.g., etching only an insulating layer or a conductive layer), but in other embodiments, the etching process involves etching a plurality of layers (e.g., both a conductive layer and an insulating layer), such as two, three, four, five, or more layers. In certain embodiments, portions of the elongated conductive body can be masked prior to depositing the insulating layer in order to maintain an exposed electroactive surface area.
  • laser ablation is used to remove certain layers that have been deposited on the elongated conductive body. Removal of layers can be performed to expose electroactive surfaces on the elongated conductive body or else merely to remove certain insulating or conductive layers or portions thereof.
  • a laser beam which can be pulsed and have a particular wavelength and power selected to ablate the desired layers, portions, or patterns, is directed at certain portions of the elongated conductive body to irradiate the layers in accordance with a preselected pattern.
  • the pattern can be controlled by the processor to provide for spacings between the portions of the elongated conductive body that are ablated. In certain embodiments, these spacings are from about 5 mm to about 50 mm, or from about 10 mm to about 30 mm, or even from about 20 mm to about 25 mm.
  • the power, duration of the laser pulse, repetition rate of the laser pulse, and speed of the laser can be varied to control the speed of the ablation, the amount of material ablated, and the depth of the ablation.
  • the selected ablation settings may depend on the shape, size, and other physical properties of the elongated conductive body. They may also depend on the ablation depth, area, or shape desired. By controlling the parameters described above, the risk of the ablation process leaving a substantial amount of residual ablation debris on the elongated conductive body can be minimized.
  • the laser beam has a wavelength of from about 100 nm to about 800 nm, or from about 200 nm to about 300 nm, or from about 220 nm to about 265 nm, or even from about 245 nm to about 250 nm.
  • the elongated conductive body is spun around its longitudinal axis as a laser beam is directed on the elongated conductive body.
  • the rotation rate is greater than about 0.5 revolutions per second, or greater than about 1 revolution per second, or greater than about 2 revolutions per minute, or greater than about 5 revolutions per minute, or even greater than about 10 revolutions per minute.
  • the laser beam can be generated by any of a variety of laser sources, such as, an excimer laser, YAG laser, CO2 laser, diode laser, for example.
  • the laser beam energy beam density can be established to be sufficient to ablate or remove a layer or portion from the elongated conductive body at a certain predetermined depth and area, but low enough so as to not damage the layers and materials outside the predetermined depth and area.
  • the laser beam energy beam setting can also selected in consideration of the type of material(s) that is the target of the ablation.
  • the laser ablation process involves directing a beam to remove a small fraction of the total thickness (e.g., a few microns) of a layer with every pulse or pass. Multiple passes are then performed, so that the desired ablated depth is achieved.
  • a coating material corresponding to a depth of 0.5 microns from the surface is removed, or a coating material corresponding to a depth of 1 micron from the surface is removed, or a coating material corresponding to a depth of 1.5 micron from the surface is removed, or a coating material corresponding to a depth of 2 microns from the surface is removed, or a coating material corresponding to a depth of 2.5 microns from the surface is removed, or a coating material corresponding to a depth of 3 microns from the surface is removed, or a coating material corresponding to a depth of 5 microns from the surface is removed, or even a coating material corresponding to a depth of 10 micron from the surface is removed.
  • multiple laser beams can be distributed around the elongated conductive body.
  • the elongated conductive body may not be configured to rotate during the laser ablation process.
  • the plurality of laser beams around the elongated conductive body can be configured to turn on simultaneously, sequentially, or in some preselected pattern to remove the desired portion or pattern.
  • a multi-beam arrangement can be obtained by using multiple laser sources, or by using one laser source and dividing the laser beam from this source into multiple branches with use of beamsplitters.
  • Each of the smaller beams can then be guided or redirected with individual optical components such as mirrors and lenses, so that the beams are directed to the elongated conductive body from different directions or angles. From this, multiple laser beams can be distributed around a perimeter or circumference of a cross section of the elongated conductive body to remove a layer all around the perimeter or circumference of the elongated conductive body. In alternative embodiments, only certain preselected sections of a perimeter or circumference of the elongated conductive body cross section are removed.
  • FIG. 7B illustrates one embodiment of the elongated conductive body of FIG. 7A , after it has undergone laser ablation treatment.
  • a window region 722 is formed when the ablation removes the second and third layers 730 , 740 , to expose an electroactive surface of the first conductive layer 720 , wherein the exposed electroactive surface of the first conductive layer 720 correspond to a working electrode.
  • the laser ablation treatment of the elongated conductive body is carried out in steps, as evidenced by the multi-stepped topography. In a first step, a segment of the third layer 740 is ablated, and in a second step, a segment of the second layer 730 is ablated.
  • the segment of the third layer 740 removed is longer than the segment of the second layer 730 removed. Accordingly, the risk of third layer material falling onto the exposed electroactive surfaces of the first layer 720 may be minimized.
  • a single step ablation method can be employed, whereby both the second and third layers 730 , 740 , are removed simultaneously.
  • FIG. 7D illustrates one embodiment of the elongated conductive body of FIG. 7C , after it has undergone laser ablation treatment.
  • two window regions a first window region 722 and a second window region 742 , are formed, with each window region having a different depth and corresponding to a working electrode distinct from the other.
  • a multi-step laser ablation treatment can be employed.
  • a segment of the third, fourth, and fifth layers 740 , 750 , 760 are simultaneously removed.
  • a segment of the second layer 730 is removed to expose electroactive surfaces of the first conductive layer 720 . As illustrated in FIG.
  • the segment of the second layer 720 that is removed is shorter than that removed of the third, fourth, and fifth layers 740 , 750 , 760 , to minimize the risk of third, fourth, and fifth layer materials falling onto the exposed electroactive surfaces of the first layer 720 .
  • a segment of the fifth layer 760 is removed, and in a second step, a segment of the fourth layer 750 shorter than that of the fifth layer 760 is removed.
  • FIGS. 8B and 8D illustrate the elongated conductive bodies illustrated in FIGS. 8A and 8C , respectively, after they have undergone ablation treatment.
  • the ablation treatment removes portions of the insulator from the elongated conductive body illustrated in FIG. 8A to form a plurality of window regions, thereby exposing a portion of the elongated cores 810 A, 810 B, and 810 C.
  • window region 822 A is formed in the insulator such that a portion of elongated 810 A is exposed.
  • window region 822 B is formed in the insulator such that a portion of elongated core 810 B is exposed.
  • the window regions can be staggered and/or non-staggered along the longitudinal length of the sensor.
  • the elongated conductive body illustrated in FIG. 8C is formed with a first window region 822 A configured to expose an electroactive portion of the first elongated core 810 A and with a second window region 822 B configured to expose an electroactive portion of the second elongated core 810 B.
  • the first and second elongated cores are configured to function as first and second working electrodes, respectively, and the third elongated core is configured to function as a reference or counter electrode.
  • grit blasting is implemented to expose the electroactive surfaces of an elongated core or conductive layer. This can be performed by using a grit material that is sufficiently hard to ablate the coated material, while being sufficiently soft so as to minimize or avoid damage to the underlying elongated core or conductive layer.
  • grit materials e.g., sand, talc, walnut shell, ground plastic, sea salt, and the like
  • sodium bicarbonate can be used as a grit-material because it is sufficiently hard to ablate a certain coating (e.g., a polyurethane, polyimide, or polyethylene insulating layer) without damaging an underlying core (e.g., platinum conductor).
  • sodium bicarbonate blasting includes its polishing action on certain metals as it strips the polymer layer, thereby potentially eliminating a cleaning step that might otherwise be necessary.
  • mechanical skiving can be used.
  • Mechanical skiving can involve using a scribe, a high speed grinder, mechanical machining, mechanical wheels, or other tools to impart a recess on the elongated conductive body to expose electroactive surfaces.
  • mechanical skiving can be advantageous because mechanical skiving typically results in a recessed region with a curved edge (as illustrated in FIG. 9A ), instead of a recessed region with a sharp edge (as illustrated in FIG. 9B ), as is typically created by a laser ablation process.
  • a recessed region with a curved edge and surface may provide for better control of coating thickness and/or coating thickness profile in the window region.
  • chemical etching is used to expose the electroactive surfaces.
  • a mask typically formed of an organic film, is deposited onto selected regions of the elongated conductive body, i.e., the regions not intended to be etched. The sections between the masked regions are then etched, and the mask is subsequently removed.
  • the elongated conductive body 110 can be cleaned to remove organics or other surface contaminants that may interfere with the coating process.
  • any known suitable cleaning method can be used.
  • the system uses an ultrasonic cleaning device comprising a cleaning vessel and a roller or pulley, for guiding the elongated conductive body inside the cleaning vessel.
  • the cleaning vessel can be filled with a cleaning solvent, such as isopropanol, acetone, tetrahydrofuran (THF), or citric acid, for example.
  • the elongated conductive body is drawn through the cleaning vessel, where it is cleaned by ultrasonic sound waves and the cleaning solvent, such that when the elongated conductive body exits the ultrasonic cleaning device, it is cleaned essentially free of surface contaminants.
  • a drying chamber can be provided adjacent to the exit of the cleaning vessel.
  • the elongated conductive body exits the drying chamber it passes through the drying chamber, where residual solvent on the surface can be removed, for example, by evaporating the solvent at a higher rate than that under ambient conditions.
  • Use of a drying chamber can drive out the solvent using any conventional methods known, such as by using heat from an evaporator or an inlet supply of heated inert gas (e.g., nitrogen), or by using vacuum evaporation, for example.
  • the elongated conductive body can be cleaned by a plasma device, as an alternative or in addition to the ultrasonic cleaning device.
  • the elongated conductive body can be treated within a vacuum chamber filled with an inert gas (e.g., Argon), which is electrically charged to bombard the surface of the elongated conductive body with sufficient energy for contaminant removal.
  • an inert gas e.g., Argon
  • the resulting contaminant effluent can then be removed from the drying chamber by a vacuum pump. Because plasma cleaning does not involve chemical reactions, under certain conditions, it may remove certain inorganic contaminants that are not easily removed by ultrasonic cleaning or chemical processes.
  • the elongated conductive body can also undergo surface treatment prior to the coating process to enhance uniformity of the subsequent coating deposition.
  • the surface treatment can be carried out by any of a variety of known techniques. For example, electrostatic charging and/or plasma surface treatment can be used to modify the surface energy of the elongated conductive body. Using ionizing gases such as argon or nitrogen, plasma surface treatment can create highly reactive species even at low temperatures. Typically, only a few atomic layers on the surface are involved in the process, so the bulk properties of the elongated conductive body remain substantially unaltered by the chemistry. In some instances, plasma surface treatment may reduce surface contact angles and provide adequate surface activation for enhanced wetting and adhesive bonding. Other known surface treatments that can be used include, but are not limited to, surface washing with a solvent and corona discharge and UV/ozone treatment.
  • FIG. 3A provides a schematic diagram of one embodiment of a coating station 320 .
  • the elongated conductive body 310 advances through a meniscus 326 comprising a coating solution formed of a solvent and a coating material, the elongated conductive body's surface becomes immersed in the coating solution.
  • the elongated conductive body 310 retains a coating with a layer of substantially uniform thickness on its outer surface, as illustrated in FIG. 3B .
  • a solid layer of coating material is then formed on the surface, as the solvent portion of the coating solution evaporates.
  • the coating station 320 can include a coating vessel 322 with an opening 324 at its top configured for establishing a meniscus 326 .
  • the coating vessel 322 can be formed of any of a variety of known inert materials (e.g., ordinary glass or ceramic ware or an inert polymer such as polyethylene) suitable for the coating processes contemplated.
  • the coating vessel 322 can comprise a collecting section 328 for collecting overflow.
  • the coating station 320 can comprise an inert gas source, which introduces inert gas (e.g., nitrogen, argon) into the coating station. The inert gas is subsequently removed, so as to purge certain sections of the coating station.
  • inert gas e.g., nitrogen, argon
  • the coating station 320 can also comprise a heat source (e.g., a heat lamp) disposed somewhere near the meniscus to speed solvent evaporation.
  • a heat source e.g., a heat lamp
  • the environment in or surrounding the coating station 320 can be controlled.
  • the coating station 320 can comprise a temperature control unit disposed near or surrounding the coating vessel 322 to control the vapor pressure of the evaporating solvent.
  • the coating station 320 can also comprise a humidity control unit configured to maintain a relatively constant humidity in the coating station 320 .
  • the temperature and humidity inside the coating vessel 320 can each be independently above, below, or substantially the same as the ambient temperature and humidity outside of the coating station 320 .
  • the coating vessel 322 can also comprise various elements for detecting and controlling certain coating solution conditions, such as solids content (also commonly referred to as concentration of coating material), viscosity, and temperature.
  • the coating vessel 322 can include a temperature detector, a coating material concentration detector, a viscosity detector, a heat exchanger, and an agitator (e.g., a stirrer).
  • the processor is operatively connected to detectors configured to transmit signals indicative of certain coating solution conditions to the processor.
  • the processor is also operatively connected to various control elements (e.g., a heater, stirrer, control valve, etc.) that can be used to adjust certain coating solution conditions.
  • the embodiments described herein are capable of producing coatings of a precise thickness. This may be achieved in part by controlling certain coating solution conditions, which in turn allows for thickness control of the coating layer deposited onto the elongated conductive body. For example, controlling the temperature of the coating solution may facilitate thickness control, given that certain properties of the coating solution, such viscosity, will vary with temperature changes. As another example, controlling the viscosity may also facilitate thickness control, given that a highly viscous coating solution (e.g., with a high solids content) may sometimes present technical challenges with respect to thickness uniformity. Additionally, inconsistency in the viscosity and solids content of the coating solution between different periods of the coating process may cause inconsistencies in coating thickness between various segments of the elongated conductive body.
  • a meniscus 326 is established at the opening 324 at the top of the coating vessel 322 , by activating the pump 321 which drives the solution to continuously circulate at a precisely controlled rate.
  • the opening 324 of the coating vessel 322 can have any of a variety of shapes and dimensions, depending in part on the system's preselected process parameters (e.g., the solution used, the temperature of the solution, the speed at which the elongated conductive body advances through the coating station, etc.).
  • the opening 324 of the coating vessel 322 can be formed with a circular or substantially circular shape, but in other embodiments, the opening can be formed with a shape that resembles an ellipse, a polygon (e.g., triangle, square, rectangle, parallelogram, trapezoid, pentagon, hexagon, octagon), or the like.
  • the coating vessel 322 can also have any suitable dimension.
  • the coating vessel can have large dimensions, so as to accommodate a plurality (e.g., 3, 4, 5, or 5) of elongated conductive bodies.
  • the coating vessel 322 can be provided with an agitator 323 (e.g., a stirrer) to ensure that the coating solution is well mixed.
  • the agitator 323 can also be used to prevent possible sedimentation of coating material particles at the bottom of the coating vessel 322 .
  • the coating vessel can be configured to be in fluid communication with a solvent source and a coating material source.
  • the processor can respond by making adjustments to various control element setting, for example, by opening a control valve to introduce a solvent or coating material into the coating vessel, to return the coating solution to a preselected concentration.
  • the coating station 320 comprises a supply vat 325 that continuously feeds solution into the coating vessel 322 at a precisely controlled, consistent rate via a line 327 and a pump 329 . Accordingly, as the coating process progresses, the solution held in the coating vessel 322 can be continuously replenished from the supply vat 325 . By maintaining a controlled, consistent rate of flow of the coating solution from the supply vat 325 to the coating vessel 322 , a continuous, consistent overflow flowing out of the opening 324 is sustained. In addition, this flow control may allow for control of the contour and dimensions of the meniscus, which in turn may provide consistency of coating thickness between different segments of the elongated conductive body. Overflow flowing out of the coating vessel can be collected by a collecting section 328 , so that the overflow fluid can be further processed, such as, recycled, replenished by combining it with solvent and/or coating material, discarded, etc.
  • the supply vat 325 can be connected to one or more storage tanks that feed coating material and solvent into the supply vat 325 .
  • the coating solution can be formed of one coating material and one solvent.
  • the supply vat 325 can be connected to one storage tank holding one solvent and another storage tank holding another coating material.
  • the coating solution can be formed of a plurality of coating materials and/or a plurality of solvents.
  • the supply vat 325 can be connected to a plurality of storage tanks each holding a different solvent and/or a plurality of storage tanks each holding a different coating material.
  • the supply vat 325 can also be provided with an agitator (e.g., a stirrer) to agitate the solution and mix the coating material with the solvent, to prevent possible agglomeration of coating material particles in the supply vat 325 , and to prevent possible sedimentation of coating material particles at the bottom of the supply vat 325 .
  • the supply vat 325 can include a level indicator for monitoring the level of the coating solution in the supply vat 325 . If the fluid level falls below a certain preselected level, the level indicator is configured to transmit a signal to the processor, so that new coating solution can be prepared.
  • the elongated conductive body selected to undergo the membrane coating process may already have been coated with one or more layers of one or more materials (e.g., an elongated core covered with an insulating layer and/or a conductive layer).
  • the surface of the elongated conductive body can have a stepped topography configuration with a plurality of window regions 420 , where portions of the insulating and/or conductive layers were previously removed.
  • the window regions 420 are associated with a diameter 422 (also referred to herein as a window diameter 422 ) that is less than the diameter 432 associated with the outer surface 430 of the elongated conductive body 410 .
  • a diameter 422 also referred to herein as a window diameter 422
  • controlling the coating thickness on the elongated conductive body 410 , particularly the thickness in the window region 420 presents various technical challenges when conventional dip coating techniques are used.
  • the embodiments described herein are configured to overcome these challenges by providing a mechanism that provides precise control of certain process parameters.
  • the system may be provided with a thickness control station 130 configured to control the coating thickness of certain portions (i.e., the unetched and/or unablated portions) of the elongated conductive body, by removing excess coating material from its outer surface 430 .
  • a thickness control station 130 configured to control the coating thickness of certain portions (i.e., the unetched and/or unablated portions) of the elongated conductive body, by removing excess coating material from its outer surface 430 .
  • a different mechanism can be used to control the coating thickness and thickness profile of the window regions 420 . As illustrated in FIG. 4B , depositing a coating onto a windows region 420 with a stepped topography may result in a coating thickness profile resembling a curve.
  • the embodiments described herein allow for precise control over the thickness and the thickness profile of the layers residing in the window regions.
  • the meniscus coating process described herein can be used, whereby the viscosity of the coating solution, the solids content of the coating solution, the temperature of the coating solution, the speed at which the elongated conductive body advances through the coating station, and/or the flow rate of the coating solution into the coating vessel are precisely controlled.
  • Each of the aforementioned process parameters affects the thickness and the thickness profile of the material coated on the elongated conductive body. Because the thickness of the coating directly affects certain properties (e.g., permeability of the membrane system) of the continuous analyte sensor, achieving tight control of the thickness may also provide for tight control of these properties.
  • the coating thickness and the uniformity of the thickness may be controlled by solvent selection.
  • solvent selection any of a variety of solvents can be used, each of which is associated with a vapor pressure.
  • the vapor pressure of a solvent affects the rate at which the solvent evaporates. Accordingly, solvent selection may affect the thickness and/or thickness control.
  • Control of the viscosity can involve selection of a polymer forming the coating material, molecular weight selection for the polymer, control of polymer concentration of the solution, and solution temperature control.
  • a coating may sometimes considerably sag to the bottom surface of the elongated conductive body, resulting in a variable layer thickness.
  • the coating material may be difficult to coat onto the elongated conductive body. Accordingly, it is contemplated that the system can use a coating solution with an appropriate viscosity which will allow for deposition, but will yet still provide for control over coating thickness and thickness profile.
  • the molecular weight of a polymeric coating material may also affect the viscosity of the coating solution, with viscosity generally increasing with molecular weight. Viscosity also often correlates with temperature. Thus, in some embodiments, the temperature of the coating solution may be controlled so that the viscosity may be controlled. In some embodiments, the coating solution is controlled to have a preselected viscosity of from about 0.1 to about 500 cP, or from about 1 to about 30 cP, or from about 50 to about 100 cP.
  • Control of the solids content of the coating solution may be achieved by preparing a coating solution with a preselected concentration level, and sustaining this concentration level by constantly monitoring the concentration and adjusting as needed.
  • the coating solution is controlled to have a preselected solids content of from about 0.1 to about 60 weight percent, or from about 1 to about 35 weight percent, and or from about 5 to about 20 weight percent.
  • Control of the coating solution temperature may be achieved by use of a thermistor and a heating element (e.g., a heat exchanger).
  • the coating solution is controlled to have a preselected temperature from about 20° C. to about 100° C., and or from about 22° C. to about 35° C.
  • Control of the speed at which the elongated conductive body advances through the coating station can be controlled by the motor of the transport mechanism. Generally, a slower rate of withdrawal from the meniscus results in a thicker coating along the surface of the elongated conductive body.
  • the elongated conductive body may be controlled to have a rate of advancement from about 1 inch/min to about 1,000 ft/min, and or from about 1 ft/min to about 50 ft/min.
  • Control of the flow rate of the coating solution into the coating vessel may be achieved by controlling the output from the one or more pumps that pump coating solution into the coating vessel.
  • the flow rate into the coating vessel is from about 1 mL/min to about 25 mL/sec, and or from about 3 mL/min to about 7 mL/min.
  • the elongated conductive body 310 can be configured to advance into the coating vessel 322 , where it can dwell for a preselected period of time.
  • a plurality of rollers or pulley 372 , 374 , 376 can be disposed near or in the coating vessel 322 to provide guidance to the elongated conductive body 310 as it advances along its predetermined path.
  • a coating process employing a vertical arrangement is employed.
  • the elongated conductive body 310 can be advanced vertically upwards through a septum 330 disposed at the bottom of a coating vessel 322 , through the coating vessel 322 , whereupon the elongated conductive body 310 is coated with the coating solution, and then through a thickness control device (e.g., a die 332 with an orifice 334 ) whereby excess coating material is removed.
  • the septum can comprise a sealing member (e.g., a gasket or a plenum) for preventing the coating solution from leaking out of the bottom of the coating vessel 332 .
  • the excess coating material falls back into the coating vessel 322 .
  • the coating vessel 322 of these embodiments can be connected to a pump 321 for circulating the coating solution and a supply vat 325 for feeding coating solution into the coating vessel 322 .
  • the coating vessel 322 can be equipped with a level indicator for monitoring the level of the coating solution therein. If the fluid level falls below a certain preselected level, the level indicator is configured to transmit a signal to the processor, so that additional coating solution is drawn from the supply vat 325 to the coating vessel 322 via pump 329 .
  • the coating station can employ any of a variety of other types of coating processes, such as spray coating or vapor deposition.
  • the elongated conductive body is advanced through a spraying tunnel. While passing through the spraying tunnel, the elongated conductive body is coated with a coating material, which can be applied using any of a variety of known spray coating techniques, such as fog spraying or electrostatic spraying, for example.
  • a continuous manufacturing process is contemplated that utilizes physical vapor deposition to deposit a coating material. Physical vapor deposition can be used to coat one or more layers of material onto the elongated conductive body.
  • FIG. 3E illustrates one embodiment of a coating station that employs spray coating.
  • the coating station comprises a circulation pump 321 and a supply vat 325 configured to feed coating solution via a pump 329 .
  • this embodiment also comprises a nozzle 338 for spraying a coating solution and a receiving container 336 for collecting coating solution.
  • a jet of coating solution from the nozzle 338 .
  • Coating solution that falls off of the elongated conductive body is collected by the receiving container 336 . From there, the coating solution is pumped via circulation pump 321 to the nozzle 338 .
  • coating solution from the supply vat 325 can also be pumped into the nozzle 338 via pump 329 .
  • a plurality of nozzles can be provided at various angles and positions with respect to the pathway of the elongated conductive body, so as to spray the elongated conductive body with jets of coating solution from multiple positions and angles (e.g., from an angle that directs coating solution at the underside of the elongated conductive body).
  • FIGS. 3A-3E involve a reel-to-reel system for moving a long, continuous strand of elongated conductive body 310 for coating
  • the elongated conductive body being coated may be in the form of individual pieces 310 ′, e.g., pieces formed after a singulation process whereby a long, continuous strand of elongated conductive body 310 is cut into individual pieces 310 ′.
  • FIG. 3F illustrates one embodiment of a transport mechanism that can be used to move elongated conductive bodies 310 ′ that are in the form of individual pieces.
  • the transport system 300 includes a conveyor that supports a plurality of robotic units 380 .
  • Each robotic unit 380 comprises a retractable arm 386 secured to the conveyor 384 .
  • the retractable arm 386 comprises an elongated conductive body holder 388 that supports the elongated conductive body 310 ′.
  • the elongated conductive body holder 388 is shown holding four elongated conductive bodies 310 ′, in alternative embodiments, an elongated conductive body holder capable of holding any other number of elongated conductive bodies 110 ′ may be used instead.
  • the retractable arm 386 is extended, the elongated conductive body 310 ′ is moved downwards, and the elongated conductive body 310 ′ is partially or wholly submerged in a coating solution.
  • the retractable arm is retracted, and the elongated conductive body 310 ′ is pulled out of the coating solution.
  • the elongated conductive body 310 ′ is then allowed to dry as the solvent of the coating solution evaporates.
  • a heater or dryer may be disposed along the path of the conveyor or on the robotic unit to accelerate evaporation of the coating solution.
  • the conveyor 384 is designed to advance the elongated conductive body 310 ′ from one coating vessel 392 to another coating vessel 394 , and then to another coating vessel 396 . Additionally, the conveyor 384 is designed to advance the elongated conductive body 310 ′ from one station 340 to a coating station 350 , and then to another station 360 . Although with the transport system 300 shown in FIG. 3F , the conveyor 384 is shown moving the elongated conductive body 310 ′ between three stations (including the coating station 350 ) and three coating vessels, it should be understood that in other embodiments, the conveyor 384 may be configured to move elongated conductive body 310 ′ between any number of coating vessels and any number of stations.
  • a coating chamber 360 that includes both a coating vessel 362 for holding a coating solution 364 and a die 366 (e.g., a diamond die) with an orifice 368 configured to control the coating thickness of the elongated conductive body 310 as it exits the coating chamber 360 .
  • FIG. 3H is a close side view of the die 366 and illustrates a tapering mechanism of the die.
  • the coating solution 364 may comprise a solvent and a coating material, such as a conductive material (e.g., platinum, Ag/AgCl, etc.), an insulating material (e.g., polyurethane, polyimide, polyethylene), or a membrane material (e.g., a material used to form the electrode layer, enzyme layer, diffusion resistance layer, interference layer, etc.)
  • a coating material such as a conductive material (e.g., platinum, Ag/AgCl, etc.), an insulating material (e.g., polyurethane, polyimide, polyethylene), or a membrane material (e.g., a material used to form the electrode layer, enzyme layer, diffusion resistance layer, interference layer, etc.)
  • FIG. 3I provides a view of the coating chamber 360 on lines 3 I- 3 I of FIG. 3G . It has been found that the tapering mechanism illustrated in FIG. 3H facilitates a certain fluid dynamic that keeps the elongated conductive body centered along the longitudinal axi
  • 3J illustrates various other non-limiting examples of cross-sectional shapes of the die orifice 368 that can be used to mold the elongated conductive body to a desired shape. It should be understood that the die 366 can not only be used to coat an elongated conductive body formed of a single core or an elongated conductive body formed of a plurality of cores, but that it can also simultaneously coat a plurality of elongated conductive bodies in parallel.
  • the entrance passage of the coating chamber 360 includes an opening 370 that permits the elongated conductive body 310 to pass therethrough.
  • a sealing member 342 is used to prevent the coating solution from leaking out of the opening 370 .
  • the sealing member 342 may be any of a variety of seals capable of preventing or reducing liquid leakage. Seals that can be used include, for example, o-rings, hydraulic seals, polypak seals, quad rings, radial shaft seals, v-ring seals, and the like.
  • the coating chamber 360 may include an opening 352 for introduction of the coating solution into the coating vessel 362 . Although the coating solution is shown in FIG.
  • the coating chamber 360 may also include a level indicator 344 that communicates with a control system, so that a predetermined level of coating solution 364 in the coating chamber 360 is maintained.
  • the system is capable of depositing a coating layer having a substantially uniform thickness along the outer surface 430 of the elongated conductive body, wherein the thickness is less than about 35 microns, or less than about 25 microns, or less than about 10 micron, or less than about 5 microns, or less than about 1 microns, or even less than 0.1 microns.
  • the thickness uniformity of the outer diameter is better than about ⁇ 50% of the average thickness, or better than about ⁇ 30%, or better than about ⁇ 10%, or better than about ⁇ 5%, or even better than about ⁇ 1%.
  • the coefficient of variation of the outer diameter thickness is less than about 0.2, or less than about 0.1, or less than about 0.07, or less than about 0.05, or less than about 0.02, or even less than about 0.01.
  • the system is also capable of depositing a coating layer with a thickness profile that is substantially uniform among the plurality of window regions 420 of the elongated conductive body. More specifically, in some embodiments, the coating layer deposited onto each window region can have a thickness profile that is consistent with those of the other window regions of the elongated conductive body.
  • the mean coating thickness of each window region can be measured and compared with those of the other window regions.
  • the coefficient of variation (of the 10 or more window regions) of the mean coating thickness is less than about 0.5, or less than about 0.2, or less than about 0.1, or less than about 0.05, or even less than about 0.01.
  • Thickness profile uniformity may also be determined by measuring coating thickness at certain locations (e.g., at a first distance one fifth from one end of the window region, at a second distance two fifths from one end of the window region, etc.) inside each window region, and comparing it with other window regions.
  • the coefficient of variation (of the 10 or more window regions) of the coating thickness at a first distance one fifth from one end of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or still less than about 0.05, or even less than about 0.01.
  • the coefficient of variation (of the 10 or more window regions) of the coating thickness at a second distance two fifths from one end of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or still less than about 0.05, or even less than about 0.01.
  • the coefficient of variation (of the 10 or more window regions) of the coating thickness at a third distance three fifths from one end of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or still less than about 0.05, or even less than about 0.01.
  • the coefficient of variation (of the 10 or more window regions) of the coating thickness at a fourth distance fourth fifths from one end of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or less than about 0.05, or even less than about 0.01.
  • the coefficient of variation (of the 10 or more window regions) of the coating thickness at a midpoint between two ends of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or less than about 0.05, or even less than about 0.01.
  • the embodiments also provide the capability of achieving substantial uniformity with respect to certain sensor properties, such as sensitivity and current density.
  • certain sensor properties such as sensitivity and current density.
  • the coefficient of variation (of the 10 or more window regions) of in vivo sensor sensitivity and/or in vitro sensor sensitivity at about 100 mg/dL glucose concentration is less than about 0.5, or less than about 0.25, or less than about 0.1, or less than about 0.05, or even less than about 0.01.
  • the coefficient of variation (of the 10 or more window regions) of in vivo sensor current density and/or in vitro sensor current density at about 100 mg/dL glucose concentration is less than about 0.5, or less than about 0.25, or less than about 0.1, or less than about 0.05, or even less than about 0.01.
  • FIG. 3K illustrates one embodiment of a coating device 390 comprising two absorption pads 398 , 399 that are soaked with a solution comprising the coating material.
  • One or more of absorption pads may be in communication with a reservoir 378 holding a solution with the coating material.
  • the two absorption pads are arranged in an abutting relationship, such that as the elongated conductive body is advanced in a path along a plane defined by the interface between the two absorption pads.
  • the solution with the coating material is applied to the elongated conductive body.
  • the concentration gradient that exists at the interface 358 the amount of coating that is applied to the elongated conductive body 310 can be controlled.
  • Other ways of controlling the thickness of the elongated conductive body include, but are not limited to, controlling the surface energy of the elongated conductive body, controlling the speed at which the elongated conductive body is advanced, and controlling the viscosity of the solution comprising the coating material. Accordingly, with multiple passes through the coating device 390 , an elongated conductive body 310 with a certain preselected thickness of a coating material can be obtained.
  • the pads may be formed of any material, such as a fibrous material, that is capable of absorbing the solution.
  • FIG. 3K includes two absorption pads, it should be understood that in other embodiments, a different number of absorption pads (e.g., three, four, five, ten, or more) having the same or different shapes or dimensions can also be used.
  • the thickness control station 130 comprises a die (not shown) mounted transverse to the elongated conductive body. As the elongated conductive body advances through an orifice of the die, excess coating material is removed to form on the treated surface a coating layer having a substantially consistent thickness. As described above, the excess coating material removed is from the outer surface 430 of the elongated conductive body, and not from the window surface 420 .
  • the dimensions of the die orifice can vary depending on the type of coating being formed on the elongated conductive body.
  • the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the insulating layer, or from about 5 to about 15 microns larger, or even from about 10 to about 14 microns larger.
  • the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the conductive layer, or from about 1 to about 15 microns larger, or even from about 5 to about 10 microns larger.
  • the die orifice can have a radius from about 0.1 to about 25 microns larger than that of the elongated conductive body without the electrode layer, or from about 0.2 and 10 microns larger, or even from about 0.5 to about 1.5 microns larger.
  • the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the interference layer, or from about 0.2 to about 10 microns larger, or even from about 0.5 to about 1.5 microns larger.
  • the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the enzyme layer, or from about 0.2 to about 10 microns larger, or even from about 0.5 to about 1.5 microns larger.
  • the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the diffusion resistance layer, or from about 1 to about 15 microns larger, or even from about 5 to about 10 microns larger.
  • the die orifice has a circular or substantially circular shape
  • the die orifice can have a shape that is oval, square, rectangular, triangular, polyhedral, star-shaped, C-shaped, T-shaped, X-shaped, Y-Shaped, irregular, or the like.
  • the thickness control station can comprise a plurality of dies, each or some of which comprise an orifice with a shape or dimension different from that of the other dies.
  • the thickness control station can comprise three dies arranged in a series, with each die comprising a circular orifice, wherein a first die orifice comprises a larger diameter than that of a second die, and the second die orifice comprises a larger diameter than that of a third die.
  • the thickness control station can comprise one die with a plurality of orifices formed therein, with each orifice configured to receive an elongated conductive body.
  • the die can comprise a plurality of movable members configured to collectively define the outline of an orifice, through which the elongated conductive body is configured to advance.
  • the movable members can be controlled by the processor to move to different positions and arrangements to form orifices of different shapes and dimensions. This feature provides the system with the capability to adjust the shape and dimension of the orifice to conform to certain preselected process parameters (e.g., preselected shape or thickness of the elongated conductive body).
  • guide rollers or pulleys can be disposed near the entrance and/or exit of the die, to provide precise guidance to the moving elongated conductive body.
  • the thickness control station can include a solvent source that periodically or continuously sends solvent to the orifice.
  • the thickness control station can comprise a pan for collecting excess coating material that falls from the elongated conductive body or the die. The excess coating material may be discarded or reused if suitable.
  • a gas knife using impinging jets of inert gas (e.g., nitrogen) can be used.
  • inert gas e.g., nitrogen
  • the system 100 comprises a drying or curing station 140 for drying and curing the coating material deposited onto the elongated conductive body 110 .
  • a drying or curing station 140 for drying and curing the coating material deposited onto the elongated conductive body 110 .
  • residual solvent on the surface of the elongated conductive body 110 is evaporated.
  • crosslinkable components of the coating material can be substantially crosslinked.
  • the curing process can be carried out by any of a variety of conventional drying techniques, such as by UV, infrared, microwave, x-ray, gamma ray, or electron beam radiation, whereby radiation is directed at the coating material, or alternatively by heat, such as by conduction drying or convection drying, for example, by hot air convection drying using a hot air convection oven.
  • conventional drying techniques such as by UV, infrared, microwave, x-ray, gamma ray, or electron beam radiation, whereby radiation is directed at the coating material, or alternatively by heat, such as by conduction drying or convection drying, for example, by hot air convection drying using a hot air convection oven.
  • conduction drying or convection drying for example, by hot air convection drying using a hot air convection oven.
  • one or more of the above-mentioned techniques may be used as an alternative (or in addition) to other techniques.
  • a high energy radiation curing mechanism e.g., short wavelength UV
  • Radiation-based curing may also be used in some embodiments because it provides tight control over the level of radiation, thereby allowing for better control of the curing process.
  • the curing process may take place under a variety of process conditions.
  • the drying or curing process occurs in a curing chamber and/or oven at a temperature of from about 20° C. to about 500° C., or from about 50° C. to about 150° C., or even from about 200° C. to about 400° C.
  • the system can include a humidifier/dehumidifier for maintaining proper relative humidity in the drying/curing station.
  • the system 100 includes a thickness measurement station 150 comprising a thickness measurement sensor or micrometer configured for measuring the thickness of the elongated conductive body 110 (with or without coating), as it passes through the thickness measurement station 150 .
  • the micrometer is configured to transmit to the processor 160 a signal indicative of the measured thickness. If the measured thickness is determined to be less than the preselected thickness, the system is configured to repeat the coating process until a layer having the preselected thickness is formed.
  • the thickness measurement sensor or micrometer can be any of a variety of devices capable of measuring a dimension indicative of a thickness of a coating formed on the elongated conductive body.
  • the micrometer can be an optical micrometer, but in other embodiments the micrometer can be a gauge device or other similar device configured to contact the elongated conductive body for thickness measurement.
  • Optical micrometers that can be used include light emitting diode (LED) devices, laser devices, or other similar devices capable of measuring certain elongated bodies (e.g., wires and webs) at suitable sampling rates.
  • LED light emitting diode
  • the micrometer itself is positioned near the pathway of the elongated conductive body and configured to measure the thickness of the elongated conductive body without actually contacting it.
  • the thickness measurement sensor is configured to periodically measure the outside diameter of the elongated conductive body.
  • the thickness measurement sensor can also be operatively connected to the processor, which is programmed to compare the latest measurement value of the diameter with a prior measurement value corresponding to the diameter prior to the latest coating sequence.
  • the processor may also be programmed to calculate the thickness of the latest coating by subtracting the prior measurement value from the latest measurement value. The thickness of the coated elongated conductive body will of course progressively increase with each successive layer of coating material deposited onto the elongated conductive body.
  • the processor is programmed to instruct the thickness measurement sensor to measure another segment of the elongated conductive body as it advances into the thickness measurement sensor.
  • the thickness measurement sensor may be set to make a thickness measurement about every 100 cm of the elongated conductive body, or less than about every 50 cm, or less than about every 25 cm, or still less than about every 10 cm, or less than about every 5 cm, or less than about every 2.5 cm, or less than about every 1 cm, or less than about every 1 mm, or even less than about every 100 microns.
  • the measurements made by the thickness measurement sensor can be for the outer surface of the elongated conductive body, the window surface, or both.
  • the processor 160 may control certain parameters of the coating process. For example, if a particular coating thickness (e.g., thickness of the electrode layer, enzyme layer, and/or diffusion resistance layer) is measured to be less than the preselected thickness, the system may be programmed to repeat the coating process once, twice, or more times, until the preselected thickness has been achieved.
  • a particular coating thickness e.g., thickness of the electrode layer, enzyme layer, and/or diffusion resistance layer
  • the system may be programmed to run the coating process for a preselected number of iterations, instead of programmed to run the coating process repeatedly until a certain preselected thickness is achieved.
  • thickness control can still be achieved because of the high level of precision of thickness control provided by the system.
  • the thickness measurement station 150 may not be configured to measure the exact thickness of the elongated conductive body.
  • the thickness measurement station may include a vision system that is configured to detect certain surface irregularities on the elongated conductive body. Irregularities can include, but are not limited to, exposed patches that resemble an undercoating (e.g., an insulating coating underlying a conductive coating) and that indicate a section of the elongated conductive body in which coating is very thin or nonexistent. The exposed patches can show up on the vision system with a color or reflection that is different than that expected.
  • the coating process can be stopped. Alternatively, the process can be continued, with the section of the detected surface irregularity recorded, and the recorded section can be removed in subsequent processing.
  • the elongated conductive body After the elongated conductive body has been coated with at least one layer of material, such as a conductive material, insulating material, or membrane material (e.g., materials that form the electrode, interference, enzyme, and/or diffusion resistance layers), with each layer having been determined as having the preselected thickness, the elongated conductive body can then be advanced to a post-coating treatment station, where the elongated conductive body is cleaned and further processed, for example, through an another surface treatment process (e.g., plasma treatment).
  • the ends or tips of the singulated individual sensors may have various exposed metal portions not covered by a membrane or an insulating layer.
  • a sensor formed without a seal covering these end portions may pick up various levels of unwanted signals.
  • the exposed portions are sealed off using any of a variety of known techniques, such as, for example, by dipping, spraying, shrink tubing, or crimp wrapping an insulating, membrane, or other isolating material onto the sensor tip.
  • the tip in which the sensor tip is capped with a membrane material, the tip can serve as a working electrode.
  • certain portions (e.g., the back ends) of the singulated sensors can be etched to expose a conductive material, to provide the sensors with electrical connection.
  • a mechanical connector may be clamped onto the elongated conductive body's conductive surface, cutting through the membrane in the process. Thereafter, the sensors can be delivered to other stations for further processing.
  • the sensors are then packaged into containers or boxes for shipping to a patient, hospital, or retailer.
  • the containers or boxes may be formed of special materials that are capable of protecting the sensors from harsh environmental conditions.
  • the elongated conductive body can be cut for singulation into individual pieces.
  • singulation can be performed before coating of conductive and/or insulating materials.
  • singulation can be performed after coating of the conductive and/or insulating materials, but before coating of membrane materials.
  • singulation can be performed after coating of conductive and/or insulating materials and after coating of membrane materials. Any of a variety of known cutting systems, such as a system comprising a hydraulic cutting device, for example, can be used.
  • FIG. 11 illustrates one embodiment of a system 1100 that integrates etching (to remove or strip portions of a coated assembly structure) and singulation of the elongated conductive body into individual pieces.
  • the cutting system 1100 includes a supply spool 1120 which feeds an elongated conductive body 1110 into an elongated conductive body straightener 1130 (e.g., a wire straightener). The elongated conductive body 1110 is then fed into a rotating mandrel 1140 , which rotates the elongated conductive body 1110 .
  • an elongated conductive body gripping device 1150 moves forward and grasps the end of the elongated conductive body 1110 and then moves backwards to position the elongated conductive body 1110 for etching by any of the etching processes described elsewhere herein (e.g., by laser ablation 1190 ).
  • Rotation of the elongated conductive body 1110 can involve a complete rotation (i.e., a rotation of 360 degrees or more), through which a portion associated with the entire circumference of the elongated conductive body 1110 is etched.
  • rotation of the elongated conductive body can be partial and controlled such that only certain sections associated with the elongated conduct body's circumference is etched.
  • a section of the elongated conductive body 1110 is cut by a cutter 1160 .
  • the steps described are then continuously repeated. It should be understood that the system described above is merely exemplary, and some components (e.g., the mandrel 1140 or the etching mechanism) may be omitted or replaced by other components (e.g., a drying or curing mechanism).
  • FIG. 5 is a flowchart summarizing the steps of one embodiment of a method for continuously manufacturing analyte sensors.
  • an elongated conductive body is provided.
  • the elongated conductive body can be a bare elongated core (e.g., a metal wire), a cladded elongated core, or a bare or cladded elongated core coated with one, two, three, four, five, or more layers of material.
  • step 510 can be preceded by one or more steps, wherein the above-described elongated conductive body (as shown in FIG.
  • an elongated core e.g., a wire
  • one or more layers of material e.g., an insulating layer and a conductive layer
  • the elongated core is advanced through a coating station/thickness control station/drying/curing station/thickness measurement station series/sequence, whereby it is coated with an insulating material.
  • the series/sequence may be repeated until an insulating layer having a preselected thickness has been deposited, as measured by the thickness measurement sensor.
  • the elongated conductive body is then advanced through a coating station/thickness control station/drying/curing station/thickness measurement station sequence, whereby it is coated with a conductive material. Again, the sequence may be repeated until a conductive layer having a preselected thickness has been deposited. After the insulating and conductive layers have been deposited onto the elongated core, the elongated conductive body can then be advanced to an etching station, where portions of the coated assembly structure is stripped or otherwise removed (e.g., to expose the electroactive surfaces of the elongated core, thereby creating window regions corresponding to electroactive surface areas).
  • step 520 the elongated conductive body is advanced through a pre-coating treatment station, where it is cleaned with a solvent to remove surface contaminants.
  • an additional drying step can be provided to evaporate any residual solvents left on the surface of the elongated conductive body.
  • the elongated conductive body is advanced through a coating station, where a coating solution comprising a solvent and a coating material (e.g., a material to form a conductive layer, insulating layer, or a membrane) is deposited onto the elongated conductive body.
  • a coating solution comprising a solvent and a coating material (e.g., a material to form a conductive layer, insulating layer, or a membrane) is deposited onto the elongated conductive body.
  • a coating solution comprising a solvent and a coating material (e.g., a material to form a conductive layer, insulating layer, or a membrane) is deposited onto the elongated conductive body.
  • a coating solution comprising a solvent and a coating material (e.g., a material to form a conductive layer, insulating layer, or a membrane) is deposited onto the elongated conductive body.
  • a coating solution comprising a solvent and a coating
  • step 540 the elongated conductive body is advanced through a thickness control station, where excess coating material can be removed to form on the treated surface a layer of coating having a substantially consistent thickness.
  • the coating station and the thickness control station may be integrated into one station.
  • the elongated conductive body is advanced through the drying or curing station, where it may be dried under ambient conditions or heated to remove residual solvent on the surface of the elongated conductive body.
  • crosslinkable components of the coating material are substantially crosslinked.
  • the curing process can be carried out by any of a variety of conventional drying techniques including, but not limited to, by UV, infrared, microwave, x-ray, gamma ray, or electron beam radiation, or by heat.
  • step 560 the elongated conductive body is advanced through the thickness measurement station, where a measurement is made of the thickness of the elongated conductive body, and a signal indicative of the measurement is transmitted to the processor.
  • the processor compares the measured thickness with a preselected thickness. If the measured thickness is determined to be less than the preselected thickness, the system is programmed to repeat the coating process until a layer having the preselected thickness is formed.
  • step 570 after being coated with multiple layers of material (e.g., insulating, conductive, electrode, interference, enzyme, and/or diffusion resistance material), with each layer having the preselected thickness, the elongated conductive body is advanced into the post-coating treatment station, where it can be cleaned and/or undergo further treatment. Thereafter, the individual sensors can be delivered to other stations for further processing.
  • material e.g., insulating, conductive, electrode, interference, enzyme, and/or diffusion resistance material
  • an elongated conductive body is provided, as indicated by step 510 . Thereafter, it undergoes processing, as indicated by steps 520 , 530 , 540 , 550 , and 560 , whereby a coating forming a first layer (e.g., an insulating layer) with a preselected thickness is deposited on the elongated conductive body.
  • a first layer e.g., an insulating layer
  • the coating process (i.e., the sequence formed of steps 520 , 530 , 540 , 550 , and 560 ) can be repeated several times, with each passing sequence resulting in a successive layer (e.g., a second layer comprising an enzyme layer, a third layer comprising a diffusion resistance layer, etc.) with a preselected thickness being deposited onto the elongated conductive body.
  • a successive layer e.g., a second layer comprising an enzyme layer, a third layer comprising a diffusion resistance layer, etc.
  • the elongated conductive body can then be transferred to a station for post-coating treatment, as indicated by step 570 .
  • polyurethane an insulating material
  • insulating material e.g., polyethylene, polyimide, etc.
  • an elongated conductive body which has an outer conductive layer formed of platinum and an inner core formed of another material (e.g., stainless steel, titanium, tantalum, glass, polymeric material, non-conductive material, etc.).
  • the entire elongated conductive body may be monolithic and formed of a conductive material, such as platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and combinations thereof.
  • the elongated conductive body is treated (e.g., washed with alcohol or treated with plasma).
  • an adhesion promoter may be applied to the outer surface of the elongated conductive body.
  • the adhesion promoter may be used to cause surface reaction to improve adhesion of the polyurethane to the conductive surface of the elongated conductive body, and thereby reduce the risk of delamination.
  • the adhesion promoters in a non-limiting embodiment, can be monomers, oligomers and/or polymers.
  • Such materials include, but are not limited to, organometallics such as silanes, (e.g., mercapto silanes, acrylate or methacrylate functional silanes, vinyl silanes, amino silanes, epoxy silanes, isocyanate silanes, fluoro silanes, and alkyl silanes), siloxanes, titanates, zirconates, aluminates, metal containing compounds, zirconium aluminates, hydrolysates thereof and mixtures thereof.
  • silane is used as an adhesion promoter, and it is used as a component of a solution.
  • the solution comprises from about 90% to 98% organic solvent (e.g., ethanol, tetrahydrofuran), about 1% to 5% water, and about 1 to 5% silane onto the outer surface of the elongated conductive body.
  • organic solvent e.g., ethanol, tetrahydrofuran
  • the solvents may then be removed by air drying and/or by using an oven.
  • the polyurethane is coated onto the elongated conductive body using any of the coating techniques described elsewhere herein, such as a meniscus coating method.
  • the polyurethane coating is then dried or cured.
  • the polyurethane may have a thickness of from about 5 microns to about 50 microns, or from about 12 microns to about 25 microns, or even from about 18 microns to about 23 microns. Excess coating materials of polyurethane are then removed by use of a die, in accordance with step 540 .
  • the cycle from step 510 to step 550 can then be repeated until a preselected thickness of the polyurethane layer has been achieved.
  • this particular example describes one embodiment of coating a platinum material onto the elongated core or an Ag/AgCl material (i.e., a conductive material) onto the polyurethane layer described in the example above.
  • a platinum material i.e., platinum, Ag/AgCl, and polyurethane, it should be understood that other conductive materials and insulating materials may also be used in accordance with the method described herein.
  • the coating material can involve an Ag/AgCl solution or paste which can be purchased from commercially available sources or alternatively prepared to have certain specified properties.
  • an AgCl layer is consumed during a period when the Ag/AgCl electrode is used as a cathode.
  • the effective lifespan of a sensor i.e., the period of time that it can function properly
  • the silver grain and the silver chloride grain can have any of a variety of shapes, such as a shape similar to a sphere, plate, flake, a polyhedron, or combinations thereof.
  • the silver grain in the Ag/AgCl solution or paste can have an average particle size associated with a maximum particle dimension that is less than about 100 microns, or less than about 50 microns, or less than about 30 microns, or less than about 20 microns, or less than about 10 microns, or even less than about 5 microns.
  • the silver chloride grain in the Ag/AgCl solution or paste can have an average particle size associated with a maximum particle dimension that is less than about 100 microns, or less than about 80 microns, or less than about 60 microns, or less than about 50 microns, or less than about 20 microns, or even less than about 10 microns.
  • the silver grain and the silver chloride grain may be incorporated at a ratio of the silver chloride grain: silver grain of from about 0.01:1 to 2:1 by weight, and sometimes from about 0.1:1 to 1:1.
  • the silver grains and the silver chloride grains are then mixed with a carrier (e.g., a polyurethane) to form a solution or paste.
  • a carrier e.g., a polyurethane
  • the Ag/AgCl component comprises from about 10% to about 65% by weight of the total Ag/AgCl solution or paste, or from about 20% to about 50% by weight of the total Ag/AgCl solution or paste, or even from about 23% to about 37% by weight of the total Ag/AgCl solution or paste.
  • the Ag/AgCl solution or paste has a viscosity (under ambient conditions) that is from about 1 to about 500 centipoise, or from about 10 to about 300 centipoise, or even from about 50 to about 150 centipoise.
  • an elongated conductive body is provided in step 510 .
  • the elongated conductive body is only an elongated core.
  • the elongated conductive body has an outer conductive layer formed of platinum with an inner elongated core formed of another material (e.g., stainless steel, titanium, tantalum, polymeric material, non-conductive material, etc.). Disposed over the platinum layer is a layer of polyurethane deposited using the method described in the example above.
  • the entire elongated conductive body may be monolithic and formed of a conductive material, such as platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and combinations thereof.
  • a conductive material such as platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and combinations thereof.
  • step 520 the elongated conductive body is treated (e.g., washed with an alcohol wash, treated with plasma, or corona treatment). Similar to the example described above regarding the coating of polyurethane, an adhesion promoter may optionally be applied to the polyurethane to improve the adhesion of the polyurethane to the Ag/AgCl material being deposited or of the elongated core material (e.g., stainless steel, tantalum) to the platinum material being deposited.
  • an adhesion promoter may optionally be applied to the polyurethane to improve the adhesion of the polyurethane to the Ag/AgCl material being deposited or of the elongated core material (e.g., stainless steel, tantalum) to the platinum material being deposited.
  • step 530 the platinum solution or Ag/AgCl solution or paste is coated onto the elongated conductive body using any of the coating techniques described elsewhere herein.
  • the coating chamber 360 illustrated in FIG. 3G is used to perform the coating step 530 .
  • the die 366 in the coating chamber is used to perform the step 540 of removing excess platinum, Ag/AgCl, or other material from the elongated conductive body.
  • the coated platinum layer may have a thickness of from a thickness corresponding to a layer formed from a few platinum atoms to about 200 microns, or from about 1 micron to about 10 microns, or even from about 3 microns to about 5 microns.
  • the coated Ag/AgCl layer can have a thickness of from about 0.5 microns to about 30 microns, or from about 1 micron to about 20 microns, or even from about 5 microns to about 15 microns.
  • step 510 to step 550 is then be repeated until a preselected thickness of the platinum layer or Ag/AgCl layer has been achieved.
  • the ratio of the thickness of the Ag/AgCl layer to the thickness of the polyurethane layer can be controlled, so as to allow for a certain error margin (e.g., an error margin associated with the etching process) that would not result in a defective sensor (e.g., due to a defect resulting from an etching process that cuts into a depth more than intended, thereby unintentionally exposing an electroactive surface).
  • This ratio may be different depending on the type of etching process used, e.g., whether it is laser ablation, grit blasting, chemical etching, or some other etching method.
  • the ratio of the thickness of the Ag/AgCl layer to the thickness of the polyurethane layer can be from about 1:5 to about 1:1, or from about 1:3 to about 1:2.
  • the membrane systems described herein can be formed using the systems and methods described above, and are suitable for use with implantable sensors in contact with a biological fluid.
  • the membrane system can be utilized with sensors for measuring analyte levels in a biological fluid, such as sensors for monitoring glucose levels for individuals having diabetes.
  • the analyte-measuring sensor is a continuous sensor.
  • a wide variety of sensor configurations are contemplated with respect to sensor placement.
  • the sensor can be configured for transdermal (e.g., transcutaneous) placement, but in other embodiments the sensor can be configured for intravascular placement, subcutaneous placement, intramuscular placement, or intraosseous placement.
  • the sensor can use any method to provide an output signal indicative of the concentration of the analyte of interest; these methods can include, for example, invasive, minimally invasive, or non-invasive sensing techniques.
  • membrane systems described herein are not limited to use in devices that measure or monitor glucose. Rather, these membrane systems are suitable for use in any of a variety of devices, including, for example, devices that detect and quantify other analytes present in biological fluids (e.g., cholesterol, amino acids, alcohol, galactose, and lactate), cell transplantation devices, drug delivery devices, and the like.
  • biological fluids e.g., cholesterol, amino acids, alcohol, galactose, and lactate
  • cell transplantation devices e.g., cell transplantation devices, drug delivery devices, and the like.
  • FIG. 6A is a cross-sectional view through one embodiment of the elongated conductive body of FIG. 4B on line 6 A- 6 A, illustrating one embodiment of the membrane system 600 .
  • the cross-section illustrated in FIG. 6A corresponds to the window surface of the elongated conductive body.
  • the window surface can correspond to a working electrode formed in part, for example, by removing a portion of the insulating material and conductive material from an electroactive surface the elongated conductive body by ablation, etching, or other like techniques.
  • FIG. 6B is a cross-sectional view through the elongated conductive body of FIG. 4B on line 6 B- 6 B.
  • the membrane system 600 comprises an electrode layer 620 , interference layer 630 , enzyme layer 640 , and a diffusion resistance layer 650 , located around the core 610 of the elongated conductive body.
  • the membrane system can have any of a variety of layer arrangements, with some arrangements having more or less layers than other arrangements.
  • the membrane system can comprise one interference layer, one enzyme layer, and two diffusion resistance layers, but in other embodiments, the membrane system can comprise one electrode layer, one enzyme layer, and one diffusion resistance layer.
  • FIGS. 6A and 6B involve circumferentially extending membrane systems covering an elongated conductive body with a circular cross-section
  • the membranes described herein can be applied to any planar or non-planar surface and an elongated conductive body with any variety of cross-sectional shapes, such as oval, square, rectangular, triangular, polyhedral, star-shaped, C-shaped, T-shaped, X-shaped, Y-Shaped, irregular, or the like, for example.
  • the portion of the elongated conductive body corresponding to the section illustrated in FIG. 6B comprises an additional conductive layer 670 and an insulating layer 660 that separates the core 610 from the conductive layer 670 .
  • one or more layers of the membrane system can be formed from materials such as silicone, polytetrafluoroethylene, polyethylene-co-tetrafluoroethylene, polyolefin, polyester, polycarbonate, biostable polytetrafluoroethylene, homopolymers, copolymers, terpolymers of polyurethanes, polypropylene (PP), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutylene terephthalate (PBT), polymethylmethacrylate (PMMA), polyether ether ketone (PEEK), polyamides, polyimides, polystyrenes, polyurethanes, cellulosic polymers, poly(ethylene oxide), poly(propylene oxide) and copolymers and blends thereof, polysulfones and block copolymers thereof including, for example, di-block, tri-block, alternating, random and graft copolymers.
  • silicone polytetrafluoroethylene,
  • one or more layers of the membrane system are formed from a silicone polymer.
  • the silicone composition can have molecular weight of from about 50,000 to about 800,000 g/mol. It has been found that having the polymers formed with this molecular weight range facilitates the preparation of cross-linked membranes that provide the strength, tear resistance, stability, and toughness advantageous for use in vivo.
  • the silicone polymer is a liquid silicone rubber that may be vulcanized using a metal- (e.g., platinum), peroxide-, heat-, ultraviolet-, or other radiation-catalyzed process.
  • the silicone polymer is a dimethyl- and methylhydrogen-siloxane copolymer.
  • the copolymer has vinyl substituents.
  • commercially available silicone polymers can be used.
  • commercially available silicone polymer precursor compositions can be used to prepare the blends, such as described below.
  • MED-4840 available from NUSIL® Technology LLC is used as a precursor to the silicone polymer used in the blend.
  • MED-4840 consists of a 2-part silicone elastomer precursor including vinyl-functionalized dimethyl- and methylhydrogen-siloxane copolymers, amorphous silica, a platinum catalyst, a crosslinker, and an inhibitor. The two components can be mixed together and heated to initiate vulcanization, thereby forming an elastomeric solid material.
  • Other suitable silicone polymer precursor systems include, but are not limited to, MED-2174 peroxide-cured liquid silicone rubber available from NUSIL® Technology LLC, SILASTIC® MDX4-4210 platinum-cured biomedical grade elastomer available from DOW CORNING®, and Implant Grade Liquid Silicone Polymer (durometers 10-50) available from Applied Silicone Corporation.
  • one or more layer of the membrane system is formed from a blend of a silicone polymer and a hydrophilic polymer.
  • hydrophilic polymer it is meant that the polymer has a substantially hydrophilic domain in which aqueous substances can easily dissolve. It has been found that use of such a blend may provide high oxygen solubility and allow for the transport of glucose or other such water-soluble molecules (for example, drugs) through the membrane.
  • the hydrophilic polymer comprises both a hydrophilic domain and a partially hydrophobic domain (e.g., a copolymer), whereby the partially hydrophobic domain facilitates the blending of the hydrophilic polymer with the hydrophobic silicone polymer.
  • the hydrophobic domain is itself a polymer (i.e., a polymeric hydrophobic domain).
  • the hydrophobic domain is not a simple molecular head group but is rather polymeric.
  • the silicone polymer for use in the silicone/hydrophilic polymer blend can be any suitable silicone polymer, include those described above.
  • the hydrophilic polymer for use in the silicone/hydrophilic polymer blend can be any suitable hydrophilic polymer, including but not limited to components such as polyvinylpyrrolidone (PVP), polyhydroxyethyl methacrylate, polyvinylalcohol, polyacrylic acid, polyethers such as polyethylene glycol or polypropylene oxide, and copolymers thereof, including, for example, di-block, tri-block, alternating, random, comb, star, dendritic, and graft copolymers (block copolymers are discussed in U.S. Pat. No. 4,803,243 and U.S. Pat. No.
  • the hydrophilic polymer is a copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), such as PEO-PPO diblock copolymers, PPO-PEO-PPO triblock copolymers, PEO-PPO-PEO triblock copolymers, alternating block copolymers of PEO-PPO, random copolymers of ethylene oxide and propylene oxide, and blends thereof, for example.
  • the copolymers can be optionally substituted with hydroxy substituents.
  • PEO and PPO copolymers include the PLURONIC® brand of polymers available from BASF®.
  • Some PLURONIC® polymers are triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) having the general molecular structure:
  • the repeat units x and y vary among various PLURONIC® products.
  • the poly(ethylene oxide) blocks act as a hydrophilic domain allowing the dissolution of aqueous agents in the polymer.
  • the poly(propylene oxide) block acts as a hydrophobic domain facilitating the blending of the PLURONIC® polymer with a silicone polymer.
  • PLURONIC® F-127 is used having x of approximately 100 and y of approximately 65.
  • the molecular weight of PLURONIC® F-127 is approximately 12,600 g/mol as reported by the manufacture.
  • Other PLURONIC® polymers include PPO-PEO-PPO triblock copolymers (e.g., PLURONIC® R products).
  • Other suitable commercial polymers include, but are not limited to, SYNPERONICS® products available from UNIQEMA®.
  • the membrane system of some embodiments can comprise at least one polymer containing a surface-active group.
  • surface-active group and “surface-active end group” as used herein are broad terms and are used in their ordinary sense, including, without limitation, surface-active oligomers or other surface-active moieties having surface-active properties, such as alkyl groups, which are inclined to migrate towards a surface of a membrane formed thereof.
  • the surface-active group-containing polymer is a surface-active end group-containing polymer.
  • the surface-active end group-containing polymer is a polymer having covalently bonded surface-active end groups.
  • surface-active group-containing polymers may also be used and can be formed by modification of fully-reacted base polymers via the grafting of side chain structures, surface treatments or coatings applied after membrane fabrication (e.g., via surface-modifying additives), blending of a surface-modifying additive to a base polymer before membrane fabrication, immobilization of the surface-active-group-containing soft segments by physical entrainment during synthesis, or the like.
  • Base polymers useful for certain embodiments can include any linear or branched polymer on the backbone structure of the polymer.
  • Suitable base polymers can include, but are not limited to, epoxies, polyolefins, polysiloxanes, polyethers, acrylics, polyesters, carbonates, and polyurethanes, wherein polyurethanes can include polyurethane copolymers such as polyether-urethane-urea, polycarbonate-urethane, polyether-urethane, silicone-polyether-urethane, silicone-polycarbonate-urethane, polyester-urethane, and the like.
  • base polymers can be selected for their bulk properties, such as, but not limited to, tensile strength, flex life, modulus, and the like.
  • polyurethanes are known to be relatively strong and to provide numerous reactive pathways, which properties may be advantageous as bulk properties for a membrane layer of the continuous sensor.
  • a base polymer synthesized to have hydrophilic segments can be used to form at least a portion of the membrane system.
  • a linear base polymer including biocompatible segmented block polyurethane copolymers comprising hard and soft segments can be used.
  • polyisocyanates can be used for the preparation of the hard segments of the copolymer and may be aromatic or aliphatic diisocyanates.
  • the soft segments used in the preparation of the polyurethane can be derived from a polyfunctional aliphatic polyol, a polyfunctional aliphatic or aromatic amine, or the like that can be useful for creating permeability of the analyte (e.g., glucose) therethrough, and can include, for example, polyvinyl acetate (PVA), poly(ethylene glycol) (PEG), polyacrylamide, acetates, polyethylene oxide (PEO), polyethylacrylate (PEA), polyvinylpyrrolidone (PVP), and variations thereof (e.g., PVP vinyl acetate).
  • PVA polyvinyl acetate
  • PEG poly(ethylene glycol)
  • PEO polyethylene oxide
  • PEA polyethylacrylate
  • PVP polyvinylpyrrolidone
  • variations thereof e.g., PVP vinyl acetate
  • the membrane system can comprise a combination of a base polymer (e.g., polyurethane) and one or more hydrophilic polymers, such as, PVA, PEG, polyacrylamide, acetates, PEO, PEA, PVP, and variations thereof (e.g., PVP vinyl acetate), as a physical blend or admixture, wherein each polymer maintains its unique chemical nature.
  • a base polymer e.g., polyurethane
  • hydrophilic polymers such as, PVA, PEG, polyacrylamide, acetates, PEO, PEA, PVP, and variations thereof (e.g., PVP vinyl acetate)
  • the membrane can comprise a blend of a polycarbonate-urethane base polymer and PVP, but in other embodiments, a blend of a polyurethane, or another base polymer, and one or more hydrophilic polymers can be used instead.
  • the PVP portion of the polymer blend can comprise from about 5% to about 50% by weight of the polymer blend, or from about 15% to 20%, or even from about 25% to 40%. It is contemplated that PVP of various molecular weights may be used.
  • the molecular weight of the PVP used can be from about 25,000 daltons to about 5,000,000 daltons, or from about 50,000 daltons to about 2,000,000 daltons, or even greater than 5,000,000 daltons, for example, from 6,000,000 daltons to about 10,000,000 daltons.
  • Coating solutions that include at least two surface-active group-containing polymers can be made using any of the methods of forming polymer blends known in the art.
  • a solution of a polyurethane containing silicone end groups is mixed with a solution of a polyurethane containing fluorine end groups (e.g., wherein the solutions include the polymer dissolved in a suitable solvent such as acetone, ethyl alcohol, DMAC, THF, 2-butanone, and the like).
  • the mixture can then be coated onto to the surface of the elongated conductive body using the coating process described elsewhere herein.
  • the coating can then be cured under high temperature (e.g., about 50-150° C.), as the elongated conductive body is advanced through the drying/curing station.
  • cross-linking agent can also be included in the mixture to induce cross-linking between polymer molecules.
  • suitable cross-linking agents include isocyanate, carbodiimide, gluteraldehyde or other aldehydes, epoxy, acrylates, free-radical based agents, ethylene glycol diglycidyl ether (EGDE), poly(ethylene glycol) diglycidyl ether (PEGDE), or dicumyl peroxide (DCP).
  • EGDE ethylene glycol diglycidyl ether
  • PEGDE poly(ethylene glycol) diglycidyl ether
  • DCP dicumyl peroxide
  • from about 0.1% to about 15% w/w of cross-linking agent is added relative to the total dry weights of cross-linking agent and polymers added when blending the ingredients (in one example, about 1% to about 10%).
  • substantially all of the cross-linking agent is believed to react, leaving substantially no detectable unreacted cross-linking agent in the final film.
  • Described below are examples of layers that can be coated onto the elongated conductive body to form the membrane system.
  • the membrane system comprises a diffusion resistance layer, which may be disposed more distal to the elongated core than the other layers.
  • a molar excess of glucose relative to the amount of oxygen exists in blood, i.e., for every free oxygen molecule in extracellular fluid, there are typically more than 100 glucose molecules present (see Updike et al., Diabetes Care 5:207-21(1982)).
  • a semipermeable membrane situated over the enzyme layer to control the flux of glucose and oxygen a linear response to glucose levels can sometimes be obtained only up to about 40 mg/dL.
  • a linear response to glucose levels is desirable up to at least about 500 mg/dL.
  • the diffusion resistance layer serves to address these issues by controlling the flux of oxygen and other analytes (for example, glucose) to the underlying enzyme layer.
  • the diffusion resistance layer can include a semipermeable membrane that controls the flux of oxygen and glucose to the underlying enzyme layer, thereby rendering oxygen in non-rate-limiting excess.
  • the diffusion resistance layer exhibits an oxygen-to-glucose permeability ratio of approximately 200:1, but in other embodiments the oxygen-to-glucose permeability ratio can be approximately 100:1, 125:1, 130:1, 135:1, 150:1, 175:1, 225:1, 250:1, 275:1, 300:1, or 500:1.
  • one-dimensional reactant diffusion may provide sufficient excess oxygen at all reasonable glucose and oxygen concentrations found in the subcutaneous matrix (See Rhodes et al., Anal. Chem., 66:1520-1529 (1994)).
  • the diffusion resistance layer is formed of a base polymer synthesized to include a polyurethane membrane with both hydrophilic and hydrophobic regions to control the diffusion of glucose and oxygen to an analyte sensor.
  • a suitable hydrophobic polymer component can be a polyurethane or polyether urethane urea.
  • Polyurethane is a polymer produced by the condensation reaction of a diisocyanate and a difunctional hydroxyl-containing material.
  • a polyurea is a polymer produced by the condensation reaction of a diisocyanate and a difunctional amine-containing material.
  • Diisocyanates that can be used include aliphatic diisocyanates containing from about 4 to about 8 methylene units.
  • Diisocyanates containing cycloaliphatic moieties can also be useful in the preparation of the polymer and copolymer components of the membranes of some embodiments.
  • the material that forms the basis of the hydrophobic matrix of the diffusion resistance layer can be any of those known in the art that is suitable for use as membranes in sensor devices and as having sufficient permeability to allow relevant compounds to pass through it, for example, to allow an oxygen molecule to pass through the membrane from the sample under examination in order to reach the active enzyme or electrochemical electrodes.
  • non-polyurethane type membranes examples include vinyl polymers, polyethers, polyesters, polyamides, inorganic polymers such as polysiloxanes and polycarbosiloxanes, natural polymers such as cellulosic and protein based materials, and mixtures or combinations thereof.
  • the diffusion resistance layer can comprise a blend of a base polymer (e.g., polyurethane) and one or more hydrophilic polymers (e.g., PVA, PEG, polyacrylamide, acetates, PEO, PEA, PVP, and variations thereof). It is contemplated that any of a variety of combination of polymers may be used to yield a blend with desired glucose, oxygen, and interference permeability properties.
  • the diffusion resistance layer can be formed from a blend of a silicone polycarbonate-urethane base polymer and a PVP hydrophilic polymer, but in other embodiments, a blend of a polyurethane, or another base polymer, and one or more hydrophilic polymers can be used instead.
  • the PVP portion of the polymer blend can comprise from about 5% to about 50% by weight of the polymer blend, or from about 15% to 20%, and or from about 25% to 40%. It is contemplated that PVP of various molecular weights may be used. For example, in some embodiments, the molecular weight of the PVP used can be from about 25,000 daltons to about 5,000,000 daltons, or from about 50,000 daltons to about 2,000,000 daltons, or even greater than about 5,000,000 daltons, e.g., from 6,000,000 daltons to about 10,000,000 daltons.
  • the thickness of the diffusion resistance layer can be from about 0.05 microns or less to about 200 microns or more. In some of these embodiments, the thickness of the diffusion resistance layer can be from about 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 microns to about 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 19.5, 20, 30, 40, 50, 60, 70, 75, 80, 85, 90, 95, or 100 microns.
  • the thickness of the diffusion resistance layer is from about 2, 2.5 or 3 microns to about 3.5, 4, 4.5, or 5 microns in the case of a transcutaneously implanted sensor or from about 20 or 25 microns to about 40 or 50 microns in the case of a wholly implanted sensor.
  • diffusion resistance layer is not intended to be applicable only to the diffusion resistance layer; rather the description can also be applicable to any other layer of the membrane system, such as the enzyme layer, electrode layer, or interference layer, for example.
  • the membrane system comprises an enzyme layer, which may be disposed more proximal to the elongated core than the diffusion resistance layer.
  • the enzyme layer comprises a catalyst configured to react with an analyte.
  • the enzyme layer is an immobilized enzyme layer including glucose oxidase.
  • the enzyme layer can be impregnated with other oxidases, for example, alcohol dehydrogenase, galactose oxidase, cholesterol oxidase, amino acid oxidase, alcohol oxidase, lactate oxidase, or uricase.
  • oxidases for example, alcohol dehydrogenase, galactose oxidase, cholesterol oxidase, amino acid oxidase, alcohol oxidase, lactate oxidase, or uricase.
  • the sensor's response should neither be limited by enzyme activity nor cofactor concentration.
  • the catalyst can be impregnated or otherwise immobilized into the diffusion resistance layer such that a separate enzyme layer is not required (e.g., wherein a unitary layer is provided including the functionality of the diffusion resistance layer and enzyme layer).
  • the enzyme layer is formed from a polyurethane, for example, aqueous dispersions of colloidal polyurethane polymers including the enzyme.
  • the thickness of the enzyme layer can be from about 0.01, 0.05, 0.6, 0.7, or 0.8 microns to about 1, 1.2, 1.4, 1.5, 1.6, 1.8, 2, 2.1, 2.2, 2.5, 3, 4, 5, 10, 20, 30 40, 50, 60, 70, 80, 90, or 100 microns.
  • the thickness of the enzyme layer is from about 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 1.5, 2, 2.5, 3, 4, or 5 microns to about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 19.5, 20, 25, or 30 microns, or from about 2, 2.5, or 3 microns to about 3.5, 4, 4.5, or 5 microns in the case of a transcutaneously implanted sensor or from about 6, 7, or 8 microns to about 9, 10, 11, or 12 microns in the case of a wholly implanted sensor.
  • the description herein of the enzyme layer is not intended to be applicable only to the enzyme layer; rather the description can also be applicable to any other layer of the membrane system, such as the diffusion resistance layer, electrode layer, or interference layer, for example.
  • the membrane system comprises an electrode layer, which may be disposed more proximal to the elongated core than any other layer.
  • the electrode layer is configured to facilitate electrochemical reaction on the electroactive surface and can include a semipermeable coating for maintaining hydrophilicity at the electrochemically reactive surfaces of the sensor interface.
  • the functionality of the electrode layer can be incorporated into the diffusion resistance layer, so as to provide a unitary layer that includes the functionality of the diffusion resistance layer, enzyme layer, and/or electrode layer.
  • the electrode layer can enhance the stability of an adjacent layer by protecting and supporting the material that makes up the adjacent layer.
  • the electrode layer may also assist in stabilizing the operation of the device by overcoming electrode start-up problems and drifting problems caused by inadequate electrolyte.
  • the buffered electrolyte solution contained in the electrode layer may also protect against pH-mediated damage that can result from the formation of a large pH gradient between the substantially hydrophobic interference layer and the electrodes due to the electrochemical activity of the electrodes.
  • the electrode domain includes hydrophilic polymer film (e.g., a flexible, water-swellable, hydrogel) having a “dry film” thickness of from about 0.05 microns or less to about 20 microns or more, or from about 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 1.5, 2, 2.5, 3, or 3.5 microns to about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 19.5 microns, or even from about 3, 2.5, 2, or 1 microns, or less, to about 3.5, 4, 4.5, or 5 microns or more.
  • “Dry film” thickness refers to the thickness of a cured film cast from a coating formulation by standard coating techniques.
  • the electrode layer can be formed of a curable mixture of a urethane polymer and a hydrophilic polymer.
  • coatings are formed of a polyurethane polymer having anionic carboxylate functional groups and non-ionic hydrophilic polyether segments, wherein the polyurethane polymer undergoes aggregation with a water-soluble carbodiimide (e.g., 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)) in the presence of polyvinylpyrrolidone and cured at a moderate temperature of about 50° C.
  • a water-soluble carbodiimide e.g., 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)
  • aqueous dispersions of fully-reacted colloidal polyurethane polymers having cross-linkable carboxyl functionality are e.g., BAYBOND®; Mobay Corporation. These polymers are supplied in dispersion grades having a polycarbonate-polyurethane backbone containing carboxylate groups identified as XW-121 and XW-123; and a polyester-polyurethane backbone containing carboxylate groups, identified as XW-110-2.
  • BAYBOND® 123 an aqueous anionic dispersion of an aliphatic polycarbonate urethane polymer sold as a 35 weight percent solution in water and co-solvent N-methyl-2-pyrrolidone, can be used.
  • the electrode layer is formed from a hydrophilic polymer that renders the electrode layer substantially more hydrophilic than an overlying layer (e.g., interference layer, enzyme layer).
  • hydrophilic polymers can include, a polyamide, a polylactone, a polyimide, a polylactam, a functionalized polyamide, a functionalized polylactone, a functionalized polyimide, a functionalized polylactam or combinations thereof, for example.
  • the electrode layer is formed primarily from a hydrophilic polymer, and in some of these embodiments, the electrode layer is formed substantially from PVP.
  • PVP is a hydrophilic water-soluble polymer and is available commercially in a range of viscosity grades and average molecular weights ranging from about 18,000 to about 500,000, under the PVP homopolymer series by BASF Wyandotte and by GAF Corporation.
  • a PVP homopolymer having an average molecular weight of about 360,000 identified as PVP-K90 (BASF Wyandotte) can be used to form the electrode layer.
  • hydrophilic, film-forming copolymers of N-vinylpyrrolidone such as a copolymer of N-vinylpyrrolidone and vinyl acetate, a copolymer of N-vinylpyrrolidone, ethylmethacrylate and methacrylic acid monomers, and the like.
  • the electrode layer is formed entirely from a hydrophilic polymer.
  • hydrophilic polymers contemplated include, but are not limited to, poly-N-vinylpyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone, poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole, poly-N,N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid, polyethylene oxide, poly-2-ethyl-oxazoline, copolymers thereof and mixtures thereof.
  • the hydrophilic polymer used may not be crosslinked, but in other embodiments, crosslinking may be used and achieved by any of a variety of methods, for example, by adding a crosslinking agent.
  • a polyurethane polymer can be crosslinked in the presence of PVP by preparing a premix of the polymers and adding a cross-linking agent just prior to the production of the membrane.
  • Suitable cross-linking agents contemplated include, but are not limited to, carbodiimides (e.g., 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, UCARLNK®.
  • crosslinking can be achieved by irradiation at a wavelength sufficient to promote crosslinking between the hydrophilic polymer molecules, which is believed to create a more tortuous diffusion path through the layer.
  • the flexibility and hardness of the coating can be varied as desired by varying the dry weight solids of the components in the coating formulation.
  • dry weight solids as used herein is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the dry weight percent based on the total coating composition after the time the crosslinker is included.
  • a coating formulation can contain from about 6 to about 20 dry weight percent, or about 8 dry weight percent, PVP; from about 3 to about 10 dry weight percent, or about 5 dry weight percent cross-linking agent; and from about 70 to about 91 weight percent, or about 87 weight percent of a polyurethane polymer, such as a polycarbonate-polyurethane polymer, for example.
  • the reaction product of such a coating formulation is referred to herein as a water-swellable cross-linked matrix of polyurethane and PVP.
  • an electrolyte phase that when hydrated is a free-fluid phase including a solution containing at least one compound, typically a soluble chloride salt, which conducts electric current.
  • the electrolyte phase flows over the electrodes and is in contact with the electrode layer. It is contemplated that certain embodiments can use any suitable electrolyte solution, including standard, commercially available solutions.
  • the electrolyte phase can have the same osmotic pressure or a lower osmotic pressure than the sample being analyzed.
  • the electrolyte phase comprises normal saline.
  • the description herein of the electrode layer is not intended to be applicable only to the electrode layer; rather the description can also be applicable to any other layer of the membrane system, such as the diffusion resistance layer, enzyme layer, or interference layer, for example.
  • the membrane system may comprise an interference layer configured to substantially reduce the permeation of one or more interferents into the electrochemically reactive surfaces.
  • the interference layer may be configured to be substantially less permeable to one or more of the interferents than to the measured species. It is also contemplated that in some embodiments, where interferent blocking may be provided by the diffusion resistance layer (e.g., via a surface-active group-containing polymer of the diffusion resistance layer), a separate interference layer may not be used.
  • the interference layer is formed from a silicone-containing polymer, such as a polyurethane containing silicone, or a silicone polymer. While not wishing to be bound by theory, it is believed that, in order for an enzyme-based glucose sensor to function properly, glucose would not have to permeate the interference layer, where the interference layer is located more proximal to the electroactive surfaces than the enzyme layer. Accordingly, in some embodiments, a silicone-containing interference layer, comprising a greater percentage of silicone by weight than the diffusion resistance layer, can be used without substantially affecting glucose concentration measurements.
  • the silicone-containing interference layer can comprise a polymer with a high percentage of silicone (e.g., from about 25%, 30%, 35%, 40%, 45%, or 50% to about 60%, 70%, 80%, 90% or 95%).
  • the interference layer can include ionic components incorporated into a polymeric matrix to reduce the permeability of the interference layer to ionic interferents having the same charge as the ionic components.
  • the interference layer can include a catalyst (for example, peroxidase) for catalyzing a reaction that removes interferents.
  • the interference layer can include a thin membrane that is designed to limit diffusion of certain species, for example, those greater than 34 kD in molecular weight.
  • the interference layer permits certain substances (for example, hydrogen peroxide) that are to be measured by the electrodes to pass through, and prevents passage of other substances, such as potentially interfering substances.
  • the interference layer is constructed of polyurethane.
  • the interference layer comprises a high oxygen soluble polymer, such as silicone.
  • the interference layer is formed from one or more cellulosic derivatives.
  • cellulosic derivatives can include polymers such as cellulose acetate, cellulose acetate butyrate, 2-hydroxyethyl cellulose, cellulose acetate phthalate, cellulose acetate propionate, cellulose acetate trimellitate, or blends and combinations thereof.
  • the interference layer includes a thin, hydrophobic membrane that is non-swellable and restricts diffusion of low molecular weight species.
  • the interference layer is permeable to relatively low molecular weight substances, such as hydrogen peroxide, but restricts the passage of higher molecular weight substances, including glucose and ascorbic acid.
  • the thickness of the interference layer can be from about 0.01 microns or less to about 20 microns or more. In some of these embodiments, the thickness of the interference layer can be from about 0.01, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 1.5, 2, 2.5, 3, or 3.5 microns to about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 19.5 microns. In some of these embodiments, the thickness of the interference layer can be from about 0.2, 0.4, 0.5, or 0.6, microns to about 0.8, 0.9, 1, 1.5, 2, 3, or 4 microns.
  • interference layer is not intended to be applicable only to the interference layer; rather the description can also be applicable to any other layer of the membrane system, such as the diffusion resistance layer, enzyme layer, or electrode layer, for example.
  • the therapeutic agent is an anticoagulant for preventing coagulation within or on the sensor.
  • the therapeutic agent is an antimicrobial, such as but not limited to an antibiotic or antifungal compound.
  • the therapeutic agent is an antiseptic and/or disinfectant.
  • Therapeutic agents can be used alone or in combination of two or more agents. The therapeutic agents can be dispersed throughout the material of the sensor.
  • the membrane system can include a therapeutic agent that is incorporated into a portion of the membrane system, or which is incorporated into the device and adapted to diffuse through the membrane.
  • the therapeutic agent can be incorporated into the membrane system.
  • the therapeutic agent is incorporated at the time of manufacture of the membrane system.
  • the therapeutic agent can be blended prior to curing the membrane system.
  • the therapeutic agent is incorporated subsequent to membrane system manufacture, for example, by coating, imbibing, solvent-casting, or sorption of the bioactive agent into the membrane system.
  • the therapeutic agent can be incorporated into the membrane system, in some embodiments the therapeutic agent can be administered concurrently with, prior to, or after insertion of the device intravascularly, for example, by oral administration, or locally, for example, by subcutaneous injection near the implantation site.
  • a combination of therapeutic agent incorporated in the membrane system and therapeutic agent administration locally and/or systemically can be used.
  • a group of items linked with the conjunction “and” should not be read as requiring that each and every one of those items be present in the grouping, but rather should be read as “and/or” unless expressly stated otherwise.
  • a group of items linked with the conjunction “or” should not be read as requiring mutual exclusivity among that group, but rather should be read as “and/or” unless expressly stated otherwise.
  • the articles “a” and “an” should be construed as referring to one or more than one (i.e., to at least one) of the grammatical objects of the article.
  • an element means one element or more than one element.

Abstract

Described here are embodiments of processes and systems for the continuous manufacturing of implantable continuous analyte sensors. In some embodiments, a method is provided for sequentially advancing an elongated conductive body through a plurality of stations, each configured to treat the elongated conductive body. In some of these embodiments, one or more of the stations is configured to coat the elongated conductive body using a meniscus coating process, whereby a solution formed of a polymer and a solvent is prepared, the solution is continuously circulated to provide a meniscus on a top portion of a vessel holding the solution, and the elongated conductive body is advanced through the meniscus. The method may also comprise the step of removing excess coating material from the elongated conductive body by advancing the elongated conductive body through a die orifice. For example, a provided elongated conductive body 510 is advanced through a pre-coating treatment station 520, through a coating station 530, through a thickness control station 540, through a drying or curing station 550, through a thickness measurement station 560, and through a post-coating treatment station 570.

Description

    CROSS-REFERENCE TO RELATED APPLICATIONS
  • This application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 61/222,716 filed on Jul. 2, 2009, U.S. Provisional Application No. 61/222,815 filed on Jul. 2, 2009, and U.S. Provisional Application No. 61/222,751 filed on Jul. 2, 2009, the disclosures of which are hereby expressly incorporated by reference in their entireties and are hereby expressly made a portion of this application.
  • FIELD OF THE INVENTION
  • The embodiments described herein relate generally to continuous analyte sensors and systems and methods for making these sensors.
  • BACKGROUND OF THE INVENTION
  • Diabetes mellitus is a chronic disease, which occurs when the pancreas does not produce enough insulin (Type I), or when the body cannot effectively use the insulin it produces (Type II). This condition typically leads to an increased concentration of glucose in the blood (hyperglycemia), which can cause an array of physiological derangements (e.g., kidney failure, skin ulcers, or bleeding into the vitreous of the eye) associated with the deterioration of small blood vessels. Sometimes, a hypoglycemic reaction (low blood sugar) is induced by an inadvertent overdose of insulin, or after a normal dose of insulin or glucose-lowering agent accompanied by extraordinary exercise or insufficient food intake.
  • A variety of implantable continuous electrochemical analyte sensors have been developed for continuously measuring blood glucose concentrations. Typically, these types of sensors have been made by batch processes, which may not be suitable for large-scale, low-cost manufacturing, and which often result in batch-to-batch variations, thereby resulting in property variations among the sensors produced.
  • SUMMARY OF THE INVENTION
  • Accordingly, there is a need for a process and system that will reduce production costs through labor reduction and minimize variations among the sensors produced, by providing automated, continuous manufacturing of continuous analyte sensors.
  • In a first aspect, a method is provided for manufacturing a continuous analyte sensor, the method comprising applying an insulating material to an elongated conductive body comprising a conductive surface by advancing the elongated conductive body through a meniscus comprising the insulating material; and drying or curing the applied insulating material to form a coating of the insulating material on the elongated conductive body, the coating comprising a portion of the continuous analyte sensor, whereby a continuous analyte sensor configured for in vivo use is obtained.
  • In an embodiment of the first aspect, the method further comprises continuously circulating a liquid comprising the insulating material in a vessel, whereby the meniscus is provided at a wall of the vessel.
  • In an embodiment of the first aspect, the method further comprises removing a fraction of the insulating material applied to the elongated conductive body.
  • In an embodiment of the first aspect, removing is performed by advancing the elongated conductive body through a die.
  • In an embodiment of the first aspect, the method further comprises determining whether a thickness of the coating is within a predetermined range; and repeating applying the insulating material to the elongated conductive body if the thickness of the coating is outside of the predetermined range.
  • In an embodiment of the first aspect, the predetermined range of the thickness of the coating is from about 5 microns to about 50 microns.
  • In an embodiment of the first aspect, the method further comprises applying an adhesion promoter to the elongated conductive body before applying the insulating material.
  • In an embodiment of the first aspect, the method further comprises etching a portion of the coating.
  • In an embodiment of the first aspect, the method further comprises cutting the elongated conductive body into a plurality of sections.
  • In an embodiment of the first aspect, each section is associated with an individual continuous analyte sensor.
  • In an embodiment of the first aspect, the insulating material is selected from the group consisting of polyurethane, polyethylene, and polyimide.
  • In an embodiment of the first aspect, the elongated conductive body is a wire with a circular cross-sectional shape or a substantially circular cross-sectional shape.
  • In an embodiment of the first aspect, the conductive surface of the elongated conductive body comprises platinum.
  • In an embodiment of the first aspect, the conductive surface of the elongated conductive body comprises at least one conductive material selected from the group consisting of platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and combinations thereof.
  • In an embodiment of the first aspect, advancing the elongated conductive body through the meniscus is performed by a reel-to-reel system.
  • In a second aspect, a method is provided for manufacturing a continuous analyte sensor, the method comprising applying a conductive material to an elongated conductive body by advancing the elongated conductive body through a liquid comprising the conductive material; drying or curing the applied liquid to form a coating of the conductive material on the elongated conductive body, the coating comprising a portion of the continuous analyte sensor; determining whether a thickness of the coating is within a predetermined range; and, if the thickness is below the predetermined range, repeating steps of applying a conductive material and drying or curing the applied liquid until the thickness of the coating is determined to be within the predetermined range, whereby a continuous analyte sensor configured for in vivo use is obtained.
  • In an embodiment of the second aspect, the method further comprises removing a fraction of the conductive material applied to the elongated conductive body.
  • In an embodiment of the second aspect, removing is performed by advancing the elongated conductive body through a die.
  • In an embodiment of the second aspect, the conductive material is Ag/AgCl.
  • In an embodiment of the second aspect, the predetermined range of the thickness of the coating is from about 1 micron to about 20 microns.
  • In an embodiment of the second aspect, the conductive material is platinum.
  • In an embodiment of the second aspect, the predetermined range is from about 1 micron to about 10 microns.
  • In an embodiment of the second aspect, the method further comprises applying an adhesion promoter to the elongated conductive body before applying the conductive material.
  • In an embodiment of the second aspect, the method further comprises etching a portion of the coating.
  • In an embodiment of the second aspect, the method further comprises cutting the elongated conductive body into a plurality of sections.
  • In an embodiment of the second aspect, each section is associated with an individual continuous analyte sensor.
  • In an embodiment of the second aspect, the conductive material is Ag/AgCl.
  • In an embodiment of the second aspect, the conductive material has a particle size associated with a maximum particle dimension that is less than about 100 microns.
  • In an embodiment of the second aspect, the elongated conductive body is a wire with a circular cross-sectional shape or a substantially circular cross-sectional shape.
  • In an embodiment of the second aspect, the elongated conductive body comprises an outer surface comprising an insulating material selected from the group consisting of polyurethane, polyethylene, and polyimide.
  • In an embodiment of the second aspect, applying a conductive material is performed by a reel-to-reel system.
  • In a third aspect, a system is provided for manufacturing a continuous analyte sensor, the system comprising a coating vessel configured to hold a coating material in liquid form; a reel-to-reel system configured to advance an elongated conductive body through the coating material, whereby the coating material is applied to the elongated conductive body; a thickness measurement sensor configured to measure a dimension indicative of a thickness of a coating formed from the coating material applied to the elongated conductive body; an etching system configured to remove a portion of the coating material applied to the elongated conductive body; and a cutter configured to cut the elongated conductive body into a plurality of sections, wherein each section is associated with an individual continuous analyte sensor.
  • In an embodiment of the third aspect, the system further comprises a die configured to remove a portion of the coating material applied to the elongated conductive body.
  • In an embodiment of the third aspect, the elongated conductive body is a wire with a circular cross-sectional shape or a substantially circular cross-sectional shape.
  • In an embodiment of the third aspect, the coating material comprises an insulating material selected from the group consisting of polyurethane, polyethylene, and polyimide.
  • In an embodiment of the third aspect, the coating material comprises a conductive material selected from the group consisting of platinum, silver/silver chloride, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and alloys and combinations thereof.
  • In an embodiment of the third aspect, the system further comprises a pump and conduit system configured to circulate the coating material in liquid form in the coating vessel to provide a meniscus at a wall of the coating vessel.
  • In an embodiment of the third aspect, coating material is a component of a solution, wherein the solution is controlled to have a predetermined viscosity.
  • In an embodiment of the third aspect, the viscosity is controlled by selecting a concentration of the coating material in the solution or by selecting a solution temperature.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1A is a schematic diagram of one embodiment of an automated, continuous system for manufacturing continuous analyte sensors; FIG. 1B is a schematic diagram of another embodiment of an automated, continuous system for manufacturing continuous analyte sensors; FIG. 1C is a schematic diagram of yet another embodiment of an automated, continuous system for manufacturing continuous analyte sensors; FIG. 1D is a schematic diagram of yet another embodiment of an automated, continuous system for manufacturing continuous analyte sensors; FIG. 1E is a schematic diagram of yet another embodiment of an automated, continuous system for manufacturing continuous analyte sensors.
  • FIG. 2A is a side view of one embodiment of a transport mechanism; FIG. 2B is a front view of the embodiment illustrated in FIG. 2A.
  • FIG. 3A is a schematic diagram of one embodiment of a coating station; FIG. 3B is a schematic diagram providing a detailed view of the interface between the elongated conductive body and the meniscus, of the embodiment illustrated in FIG. 3A; FIG. 3C is a schematic diagram of another embodiment of a coating station; FIG. 3D is a schematic diagram of yet another embodiment of a coating station; FIG. 3E is a schematic diagram of yet another embodiment of a coating station; FIG. 3F is a schematic diagram of yet another embodiment of a coating station; FIG. 3G is a schematic diagram of an embodiment of a coating station comprising a coating vessel with a die; FIG. 3H is a close side view of the die illustrated in FIG. 3G; FIG. 3I provides a view of the coating chamber illustrated FIG. 3G on lines 3I-3I; FIG. 3J illustrates various examples of cross-sectional shapes of a die orifice; FIG. 3K is a schematic diagram of yet another embodiment of a coating station.
  • FIG. 4A is side view of an elongated conductive body having portions that are covered by one or more layers of material and portions that are uncovered; FIG. 4B is a side view of the elongated conductive body of FIG. 4A after it has been coated with a layer of coating material.
  • FIG. 5 is a flowchart summarizing the steps of one embodiment of a method for continuously manufacturing analyte sensors.
  • FIGS. 6A and 6B are cross-sectional views through one embodiment of the elongated conductive body of FIG. 4B on lines 6A-6A and 6B-6B, respectively.
  • FIG. 7A illustrates one embodiment of an elongated conductive body; FIG. 7B illustrates the embodiment of FIG. 7A after it has undergone laser ablation treatment; FIG. 7C illustrates another embodiment of an elongated conductive body; FIG. 7D illustrates the embodiment of FIG. 7C after it has undergone laser ablation treatment.
  • FIG. 8A illustrates one embodiment of an elongated conductive body; FIG. 8B illustrates the embodiment of FIG. 8A after it has undergone laser ablation treatment; FIG. 8C illustrates another embodiment of an elongated conductive body; FIG. 8D illustrates the embodiment of FIG. 8C after it has undergone laser ablation treatment.
  • FIG. 9A illustrates a recessed region formed with a curved edge; FIG. 9B illustrates a recessed region formed with a sharp edge.
  • FIG. 10A illustrates one embodiment of a die; FIG. 10B provides a view of the die on lines 10B-10B of FIG. 10A.
  • FIG. 11 illustrates one embodiment of a system that integrates etching and singulation of the elongated conductive body.
  • It should be understood that the figures shown herein are not necessarily drawn to scale.
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
  • The following description and examples describe in detail some exemplary embodiments of systems and methods for manufacturing continuous analyte sensors. It should be understood that there are numerous variations and modifications of the systems, methods, and devices described herein that are encompassed by the present invention. Accordingly, the description of a certain exemplary embodiment should not be deemed to limit the scope of the present invention.
  • Definitions
  • In order to facilitate an understanding of the devices and methods described herein, a number of terms are defined below.
  • The term “analyte,” as used herein, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to a substance or chemical constituent in a biological fluid (for example, blood, interstitial fluid, cerebral spinal fluid, lymph fluid, urine, sweat, saliva, etc.) that can be analyzed. Analytes can include naturally occurring substances, artificial substances, metabolites, or reaction products. In some embodiments, the analyte for measurement by the sensing regions, devices, and methods is glucose. However, other analytes are contemplated as well, including, but not limited to: acarboxyprothrombin; acylcarnitine; adenine phosphoribosyl transferase; adenosine deaminase; albumin; alpha-fetoprotein; amino acid profiles (arginine (Krebs cycle), histidine/urocanic acid, homocysteine, phenylalanine/tyrosine, tryptophan); andrenostenedione; antipyrine; arabinitol enantiomers; arginase; benzoylecgonine (cocaine); biotinidase; biopterin; c-reactive protein; carnitine; carnosinase; CD4; ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol; cholinesterase; conjugated 1-β hydroxy-cholic acid; cortisol; creatine kinase; creatine kinase MM isoenzyme; cyclosporin A; d-penicillamine; de-ethylchloroquine; dehydroepiandrosterone sulfate; DNA (acetylator polymorphism, alcohol dehydrogenase, alpha 1-antitrypsin, cystic fibrosis, Duchenne/Becker muscular dystrophy, glucose-6-phosphate dehydrogenase, hemoglobin A, hemoglobin S, hemoglobin C, hemoglobin D, hemoglobin E, hemoglobin F, D-Punjab, beta-thalassemia, hepatitis B virus, HCMV, HIV-1, HTLV-1, Leber hereditary optic neuropathy, MCAD, RNA, PKU, Plasmodium vivax, sexual differentiation, 21-deoxycortisol); desbutylhalofantrine; dihydropteridine reductase; diptheria/tetanus antitoxin; erythrocyte arginase; erythrocyte protoporphyrin; esterase D; fatty acids/acylglycines; free β-human chorionic gonadotropin; free erythrocyte porphyrin; free thyroxine (FT4); free tri-iodothyronine (FT3); fumarylacetoacetase; galactose/gal-1-phosphate; galactose-1-phosphate uridyltransferase; gentamicin; glucose-6-phosphate dehydrogenase; glutathione; glutathione perioxidase; glycocholic acid; glycosylated hemoglobin; halofantrine; hemoglobin variants; hexosaminidase A; human erythrocyte carbonic anhydrase I; 17-alpha-hydroxyprogesterone; hypoxanthine phosphoribosyl transferase; immunoreactive trypsin; lactate; lead; lipoproteins ((a), B/A-1, β); lysozyme; mefloquine; netilmicin; phenobarbitone; phenytoin; phytanic/pristanic acid; progesterone; prolactin; prolidase; purine nucleoside phosphorylase; quinine; reverse tri-iodothyronine (rT3); selenium; serum pancreatic lipase; sissomicin; somatomedin C; specific antibodies (adenovirus, anti-nuclear antibody, anti-zeta antibody, arbovirus, Aujeszky's disease virus, dengue virus, Dracunculus medinensis, Echinococcus granulosus, Entamoeba histolytica, enterovirus, Giardia duodenalisa, Helicobacter pylori, hepatitis B virus, herpes virus, HIV-1, IgE (atopic disease), influenza virus, Leishmania donovani, leptospira, measles/mumps/rubella, Mycobacterium leprae, Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, parainfluenza virus, Plasmodium falciparum, poliovirus, Pseudomonas aeruginosa, respiratory syncytial virus, rickettsia (scrub typhus), Schistosoma mansoni, Toxoplasma gondii, Trepenoma pallidium, Trypanosoma cruzi/rangeli, vesicular stomatis virus, Wuchereria bancrofti, yellow fever virus); specific antigens (hepatitis B virus, HIV-1); succinylacetone; sulfadoxine; theophylline; thyrotropin (TSH); thyroxine (T4); thyroxine-binding globulin; trace elements; transferrin; UDP-galactose-4-epimerase; urea; uroporphyrinogen I synthase; vitamin A; white blood cells; and zinc protoporphyrin. Salts, sugar, protein, fat, vitamins, and hormones naturally occurring in blood or interstitial fluids can also constitute analytes in certain embodiments. The analyte can be naturally present in the biological fluid or endogenous, for example, a metabolic product, a hormone, an antigen, an antibody, and the like. Alternatively, the analyte can be introduced into the body or exogenous, for example, a contrast agent for imaging, a radioisotope, a chemical agent, a fluorocarbon-based synthetic blood, or a drug or pharmaceutical composition, including but not limited to: insulin; ethanol; cannabis (marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide, amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine (crack cocaine); stimulants (amphetamines, methamphetamines, Ritalin, Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegine); depressants (barbituates, methaqualone, tranquilizers such as Valium, Librium, Miltown, Serax, Equanil, Tranxene); hallucinogens (phencyclidine, lysergic acid, mescaline, peyote, psilocybin); narcotics (heroin, codeine, morphine, opium, meperidine, Percocet, Percodan, Tussionex, Fentanyl, Darvon, Talwin, Lomotil); designer drugs (analogs of fentanyl, meperidine, amphetamines, methamphetamines, and phencyclidine, for example, Ecstasy); anabolic steroids; and nicotine. The metabolic products of drugs and pharmaceutical compositions are also contemplated analytes. Analytes such as neurochemicals and other chemicals generated within the body can also be analyzed, such as, for example, ascorbic acid, uric acid, dopamine, noradrenaline, 3-methoxytyramine (3MT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5HT), and 5-hydroxyindoleacetic acid (FHIAA).
  • The term “continuous,” as used herein in reference to analyte sensing, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the continuous, continual, or intermittent (e.g., regular) monitoring of analyte concentration, such as, for example, performing a measurement about every 1 to 10 minutes.
  • The term “elongated conductive body,” as used herein is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to an elongated body formed at least in part of a conductive material and includes any number of coatings that may be formed thereon. By way of example, an “elongated conductive body” can mean a bare elongated core (e.g., a conductive metal wire, a non-conductive polymer rod) or an elongated core coated with one, two, three, four, five, or more layers of material that may be or may not be conductive.
  • The terms “electrochemically reactive surface” and “electroactive surface,” as used herein, are broad terms, and are to be given their ordinary and customary meaning to a person of ordinary skill in the art (and are not to be limited to a special or customized meaning), and refer without limitation to the surface of an electrode where an electrochemical reaction is to take place. As one example, in a working electrode, H2O2 (hydrogen peroxide) produced by an enzyme-catalyzed reaction of an analyte being detected reacts and thereby creates a measurable electric current. For example, in the detection of glucose, glucose oxidase produces H2O2 as a byproduct. The H2O2 reacts with the surface of the working electrode to produce two protons (2H+), two electrons (2e) and one molecule of oxygen (O2), which produces the electric current being detected. In the case of the counter electrode, a reducible species, for example, O2 is reduced at the electrode surface in order to balance the current being generated by the working electrode.
  • The term “sensing region,” as used herein, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the region of a monitoring device responsible for the detection of a particular analyte.
  • The phrase “distal to,” as used herein, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the spatial relationship between various elements in comparison to a particular point of reference. For example, some embodiments of a sensor include a membrane system having a diffusion resistance layer and an enzyme layer. If the sensor is deemed to be the point of reference and the diffusion resistance layer is positioned farther from the sensor than the enzyme layer, then the diffusion resistance layer is more distal to the sensor than the enzyme layer.
  • The phrase “proximal to,” as used herein, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the spatial relationship between various elements in comparison to a particular point of reference. For example, some embodiments of a device include a membrane system having a diffusion resistance layer and an enzyme layer. If the sensor is deemed to be the point of reference and the enzyme layer is positioned nearer to the sensor than the diffusion resistance layer, then the enzyme layer is more proximal to the sensor than the diffusion resistance layer.
  • The term “interferents,” as used herein, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to effects or species that interfere with the measurement of an analyte of interest in a sensor to produce a signal that does not accurately represent the analyte measurement. In an exemplary electrochemical sensor, interferents can include compounds with an oxidation potential that overlaps with that of the analyte to be measured.
  • The terms “membrane system” and “membrane,” as used herein, are broad terms, and are to be given their ordinary and customary meaning to a person of ordinary skill in the art (and are not to be limited to a special or customized meaning), and refer without limitation to a permeable or semi-permeable membrane that can comprise one or more layers and constructed of materials, which are permeable to oxygen and may or may not be permeable to an analyte of interest. In one example, the membrane system comprises an immobilized glucose oxidase enzyme, which enables an electrochemical reaction to occur to measure a concentration of glucose.
  • The term “coefficient of variation,” as used herein, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the ratio of the standard deviation of a distribution to its arithmetic mean. The coefficient of variation can be calculated by the equation: coefficient of variation=standard deviation/mean.
  • The term “sensitivity,” as used herein, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to an amount of electrical current produced by a predetermined amount (unit) of the measured analyte. For example, in one embodiment, a sensor has a sensitivity (or slope) of from about 1 to about 300 picoAmps of current for every 1 mg/dL of glucose analyte.
  • The term “current density,” as used herein, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to an amount of electrical current per area produced by a predetermined amount (unit) of the measured analyte. For example, in one embodiment, a sensor has a sensitivity (or slope) of from about 3 to about 1,000 picoAmps of current per mm2 of electroactive surface, for every 1 mg/dL of glucose analyte.
  • The term “chamber,” as used herein, is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to a partially or fully enclosed space (e.g., chambers, conduits, channels, capillaries, tubes, wells, cells, vessels, microchannels, or the like).
  • Overview
  • FIG. 1A provides a schematic diagram of one embodiment of an automated, continuous system 100 for manufacturing continuous analyte sensors, whereby an elongated conductive body 110 is continuously advanced through a series of stations, each of which treats the elongated conductive body 110. As shown, these stations can include, but are not required to include, a coating station 120 for depositing coating material (e.g., insulating, conductive, or membrane material) onto the elongated conductive body 110, a thickness control station 130 for removing excess coating material from the elongated conductive body 110, a drying/curing station 140 for curing the coating material on the elongated conductive body 110, and a thickness measurement station 150 for measuring the thickness of the elongated conductive body 110 (including any coatings thereon). During the coating process, the elongated conductive body 110 can be advanced through this series of stations repeatedly, i.e., by making multiple repeated passes, until a preselected thickness has been formed on the elongated conductive body. The system 100 described herein is merely exemplary, and some stations may be omitted or replaced by other stations.
  • Although not shown in FIG. 1A, in some embodiments, the system can also include an etching station for removing or stripping portions of a coated assembly structure on the elongated conductive body (e.g., to create window regions corresponding to working electrodes on the elongated conductive body). Etching to create window regions can be achieved by removing a portion of the insulating layer, conductive layer, or the like, from the elongated conductive body, using ablation (e.g., laser skiving), chemical etching, or other known techniques. Additionally or optionally, the system can also include a pre-coating treatment station for pre-cleaning the elongated conductive body before the coating process, and a post-coating treatment station for post-cleaning after the coating process. Additionally or optionally, the system can also include a singulation station for cutting the elongated conductive body into individual pieces corresponding individual sensors.
  • The system 100 can also be equipped with an automated control system comprising detector elements, control elements, and a processor 160. The detector and control elements can be embedded in the stations and disposed anywhere on or near the pathway of the elongated conductive body 110. The detector elements are configured to transmit to the processor 160 signals relating to certain process conditions of the system 100, such as, for example, the temperature of the coating solution, the humidity of the atmosphere immediately around a region of the elongated conductive body which is undergoing or about to undergo meniscus coating or laser ablation, the rate at which the elongated conductive body 110 is advancing, or the last measured thickness of the elongated conductive body 110. The processor 160 is programmed to process these input signals and transmit output signals to control operation of the control elements, e.g., valves, motors, pumps, agitators, heat lamps, die opening, etc., so that preselected process conditions for optimum controlled coating processing can be achieved and maintained. By managing the processing conditions at a predetermined optimal level, the yield and reproducibility of the continuous analyte sensors fabricated can be increased.
  • In some embodiments, a detector element in the form of a temperature transducer (e.g., a thermistor) and a control element in the form of a heat source (e.g., a heat lamp) is disposed at certain positions along the pathway of the elongated conductive body 110 to provide temperature control of the elongated conductive body 110. During operation, if the temperature transducer detects a temperature that is less than a preselected temperature range, the temperature transducer is configured to transmit a signal to the processor 160, which in turn responds by transmitting a signal to activate the heat source to heat the elongated conductive body 110 to the preselected temperature. In further embodiments, the heat source is positioned near the entrance of the coating station 120, so that the elongated conductive body 110 is heated to a preselected temperature that facilitates the coating process. Alternatively or additionally, a heat source can be provided near the exit of the coating station 120 to speed the evaporation of residual solvent on the elongated conductive body 110.
  • In the embodiment shown in FIG. 1A, the system 100 comprises a transport mechanism 170 for sequentially advancing the elongated conductive body 110 through the various stations. In this particular embodiment, the system 100 employs a reel-to-reel mechanism comprising a motor (not shown in FIG. 1A), a rotatable supply spool 172, and a rotatable return spool 174. During operation, the elongated conductive body 110 is attached to both the supply spool 172 and the return spool 174. Although in some embodiments, the elongated conductive body is configured to sequentially advance through the stations in a horizontal or substantially horizontal arrangement, in other embodiments, a vertical or substantially vertical arrangement can also be used for one or more of the stations, for example, to address any gravity-induced sagging issues with respect to a fresh coating on the elongated conductive body.
  • It is contemplated that any of a variety of transport mechanisms can be used to advance the elongated conductive body 110. For example, FIGS. 2A and 2B, illustrate a side view and a front view, respectively, of one embodiment of a transport mechanism 270 comprising a spool 276, suitable for use as a supply spool, a return spool, or any other spool employed by the system. The spool 276 can include a reel 278 mechanically connected to a motor 271 via a rotatable shaft 273. The motor 271 can be any of a variety of conventional motors suitable for the applications contemplated. The reel 278 can be any type of reel upon which the elongated conductive body can be wound, and can comprise a soft material, such as silicone rubber, polyurethane, or nylon, for example, that will not cut away at coatings on the elongated conductive body and will not allow the elongated conductive body to slide freely over the reel when the reel is rotated. The diameter and width of the reel 278 can be varied depending in part on the dimensions of the elongated conductive body and other design considerations. In some embodiments, reels with a small width can be employed where there are tight space constraints. In these embodiments, coils of the elongated conductive body on the reel can overlap and touch portions of adjacent coils. In other embodiments, however, reels having a large width can be desirable, such that the coils can be arranged to not touch each other. In some embodiments, reels with large diameters can be used, resulting in a smaller bend radius, thereby minimizing the risk that materials on the elongated conductive body will crack or chip off
  • Although in the embodiment shown in FIG. 1A, the system 100 comprises one supply spool 172 and one return spool 174, in other embodiments the system can comprise any number of spools. For example, in other embodiments, the system can comprise two, three, four, five, or more supply spools associated with an equal number or a different number of return spools.
  • In addition, the system can comprise any number of stations. As illustrated in FIG. 1C, in one exemplary embodiment, the system can comprise three supply spools 173 a, 173 b, 173 c that provide three elongated conductive bodies 110 a, 110 b, 110 c, each of which are wound into a single take-up spool 175. In this particular embodiment, the system comprises one coating station 120, three thickness control stations 130 a, 130 b, 130 c, one drying/curing station 140, and three thickness measurement stations 150 a, 150 b, 150 c. In other embodiments, the system can comprise any number of station combinations. For instance, in one embodiment, the system can comprise five coating stations, five thickness control stations, one drying/curing station, and one thickness measurement station. In another embodiment, the system can comprise three coating stations, three thickness stations, three drying/curing stations, and one thickness measurement station.
  • In yet another embodiment, as illustrated in FIG. 1D, the system can comprise four stations, each of which is configured to treat multiple portions of the elongated conductive body 110. In this particular embodiment, the elongated conductive body 110 is unwound from a supply spool 173 and becomes engaged with a first guide roller 178 that guides the elongated conductive body 110 to a coating station 120. Thereafter, the elongated conductive body 110 is advanced through a thickness control station 130, a drying/curing station 140, and a thickness measurement station 150. After exiting the measurement station 150, the elongated conductive body 110 engages a second guide roller 179, by which it is returned to the first guide roller 178. As illustrated in FIG. 1D, the elongated conductive body 110 is then advanced through additional coating station/thickness control station/drying/curing station/thickness measurement station series/sequences. After passing through a preselected number of the aforementioned series/sequences, the elongated conductive body 110 is advanced to the second guide roller 179, by which it is wound into the take-up spool 175. Although in the embodiment illustrated in FIG. 1D, the system is configured to provide five series/sequences of stations; in other embodiments the system can comprise a different number of series/sequences. For example, the system can be configured to provide two, three, five, six, seven, or more series/sequences of stations.
  • As shown in FIGS. 1C and 1D, in some embodiments, the system can include one or more pulleys or guide rollers 177, 178, 179 for guiding the elongated conductive body 110 as it advances through the various stations of the system 100. The guide rollers can be positioned at any suitable location along the pathway of the elongated conductive body 110. For example, in one embodiment, a guide roller can be disposed at a position near the entrance of a certain station, such as the coating station 120. In another embodiment, a guide roller can be disposed at a position near the exit of a certain station, such as a thickness control station 130. In yet another embodiment, guide rollers can be disposed near both the entrance and exit of a certain station. In other embodiments, the system does not use guide rollers, but instead uses the tension present in the elongated conductive body 110 (derived from the transport mechanism 170) to guide it along its pathway as it advances through the various stations.
  • In the embodiment shown in FIG. 1A, the pathway of the elongated conductive body 110 is a cyclical pathway, i.e., the pathway extends from the supply spool 172 to the return spool 174, and then extends back to the supply spool 172 from the return spool 174. In other embodiments, however, the pathway may not be cyclical, but is single directional instead. As illustrated in FIG. 1B, in some of these embodiments, the elongated conductive body 110 is unwound from a supply spool 173 and wound into a take-up spool 175, after which it can be retrieved by an operator and loaded onto another system for further processing.
  • In some embodiments, each of the spools is associated with a motor configured to drive the spool. In other embodiments, one or more of the spools is not associated with a motor. For example, in one embodiment, wherein the pathway is single direction, the transport mechanism can comprise a take-up spool driven by a motor to rotate at a preselected speed of rotation, while a corresponding supply spool is maintained effectively freely rotatable. More specifically, in this embodiment, whereas rotation of the take-up spool is actively driven by a motor, rotation of the supply spool is driven by translational forces from the moving elongated conductive body, as it is driven by the rotating take-up spool. When the transport mechanism is activated, the torque exerted by the take-up spool provides tension to the elongated conductive body as it unwinds from the supply spool, advances through the various stations of the system, and eventually winds into the take-up spool. An increase in the torque exerted by the take-up spool may also increase the tension present in the elongated conductive body.
  • The tension present in the elongated conductive body 110 can be measured by any of a variety of tension detectors. For example, in some embodiments, a tension detector is disposed at various positions along the pathway of the elongated conductive body 110 to directly measure its tension. In other embodiments, the tension is indirectly measured by measuring the torques exerted by the various spools and calculating the torque differences between the spools. If the tension is determined to be greater or less than a preselected value, the tension detector can be configured to transmit a signal to the processor, which is programmed to determine whether a problem exists (e.g., a severed elongated conductive body or one detached from the reel). If the determination is positive, the system can optionally respond with an alert or alarm to notify an operator.
  • In some of the embodiments described herein, the transport mechanism 170 is configured to advance the elongated conductive body 110 at a constant or substantially constant preselected speed. Selection of the preselected speed can depend in part on design considerations associated with certain preselected process conditions (e.g., the preselected viscosity and solids content of the coating solution, suspension, dispersion, or other liquid comprising the coating material) that will provide optimal coating thickness control. In some embodiments, the elongated conductive body is configured to advance at a preselected speed greater than about 0.5 cm per minute, or greater than about 10 cm per minute, or greater than about 25 cm per minute, or greater than about 50 cm per minute, or even greater than about 250 cm per minute. In alternative embodiments, a variable-speed transport mechanism can be used to advance the elongated conductive body at varying speeds. For example, in some embodiments, the transport mechanism can be configured to periodically halt the advancement of the elongated conductive body.
  • To confirm that the elongated conductive body is advancing at the preselected speed, a speed measurement system (e.g., a vision system) can be employed to measure the elongated conductive body's actual speed. If the measured speed is not within a certain range of the preselected speed, the vision system is configured to transmit a signal to the processor, which in turn can adjust motor settings in response.
  • While the transport mechanism has been described hereinabove with respect to a reel-to-reel embodiment, the elongated conductive body 110 may also be advanced through the series of stations with any of a variety of other transport mechanisms, such as, for example, a robotic system, a conveyor system, and other like systems. These other transport mechanisms may be used in combination with (or as an alternative to) a reel-to-reel system. For example, in one embodiment, a reel-to-reel system is used to move the elongated conductive body 110 before it is singulated into individual pieces 110′, and a robotic system is used to move the individual pieces 110′ after the singulation process.
  • FIG. 1E illustrates one embodiment of a robotic system 180, which can range in size from a large device suitable for industrial scale use to a small device suitable for laboratory bench tops. Robotic systems may be advantageous in certain instances because they can provide accurate, precise positioning of the elongated conductive body 110′ in two or three dimensions. In addition, they are highly flexible and reconfigurable, which can be advantageous for facilitating the physical transfer of individual pieces to/from a variety of stations, vessels, containers, chambers, or the like. Referring back to FIG. 1E, the robotic system 180 comprises an elongated conductive body holder 182 (e.g., a robot arm) designed to move an elongated conductive body 110′ through variable programmed motions for performance of a variety of tasks (e.g., for transferring the elongated conductive body 110′ from one coating vessel 184 to another 186 for different coating applications, and from one station to another for a variety of treatments). Although in the embodiment illustrated in FIG. 1E, the elongated conductive body holder 182 is shown holding a four elongated conductive bodies 110′, in alternative embodiments, the elongated conductive body holder 182 may be capable of holding any number of of elongated conductive bodies 110′.
  • In certain embodiments, the elongated conductive body holder 182 is capable of both vertical movements and horizontal movements (e.g., linear or rotational), thereby allowing not only for movement between stations, vessels, containers, chambers, or the like, but also for movement that causes the elongated conductive body 110′ to be submerged or dipped in a coating solution of a coating vessel 184, or movement that causes the elongated conductive body 110′ to be placed into a curing or drying chamber 188. By using an elongated conductive body holder 182 capable of various programmed movements, both the number of times and the length of time that an elongated conductive body 110′ is in a station or is being coated, cured, dried, or treated in a vessel or chamber can be controlled. By way of example and not to be limiting, the robot's elongated conductive body holder 182 can be instructed to dip the elongated conductive body 110′ (i.e., post-singulation in the form of an individual piece) into the coating vessel 184 for a plurality of dips, with each dip interspersed by drying or curing of the coating. While the coating process has been described hereinabove primarily with respect to a dipping technique, it should be understood that any of a variety of other coating techniques, such as, for example, spraying, electro-depositing, dipping, or casting, may also be used in addition to (or as an alternative to) dipping. For instance, in certain embodiments, the elongated conductive body holder 182 is instructed to place the elongated conductive body 110′ in a position for one or more spraying sessions with a certain coating material to form a particular layer of the membrane, and then to dip the elongated conductive body 110′ for one or more coating sessions in a coating solution to form another layer. The length of time of each dip/spray session and the length of time between each session can be varied or constant.
  • In one embodiment involving the robotic system 180, the elongated conductive body 110′ (in the form of an individual piece) is dipped one or more times for a predetermined time period in a pretreatment solution, then dipped one or more times for a predetermined time period into a solution containing a material that is to form the electrode and/or interference layer, then dipped one or more times for a predetermined time period into a solution containing a material that is to form the enzyme layer, and then dipped one or more times (for a predetermined time period) into a solution containing a material that is to form the diffusion resistance layer. Before, after, and between the dips/sprays, the elongated conductive body 110′ may be treated (e.g., conditioned, cleaned, cured, dried, etc.) or else maintained under normal ambient conditions. It should be understood that the process described above is merely exemplary, and some steps may be omitted or replaced by other steps.
  • Elongated Conductive Body
  • Any of a variety of elongated conductive bodies can be treated by the systems and methods described herein. FIG. 7A illustrates one embodiment of an elongated conductive body comprising an elongated core 710, a first layer 720 that at least partially surrounds the core 710, a second layer 730 that at least partially surrounds the first layer 720, and a third layer 740 that at least partially surrounds the second layer 730. These layers, which collectively form a coating assembly structure, can be deposited onto the elongated core by any of a variety of techniques, such as, for example, by employing the coating processes described elsewhere herein. In some embodiments, the first layer 720 can comprise a conductive material, such as, for example, platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, a conductive polymer, an alloy, and/or the like, configured to provide suitable electroactive surfaces for one or more working electrodes. In certain embodiments, the second layer 730 can correspond to an insulator and comprise an insulating material, such as a non-conductive (e.g., dielectric) polymer, such as polyurethane, polyimide, polyolefin (e.g., polyethylene), for example. In some embodiments, the third layer 740 can correspond to a reference electrode and comprise a conductive material, for example, a silver-containing material, including, but not limited to, a polymer-based conducting mixture.
  • FIG. 7C illustrates another embodiment of an elongated conductive body. In this embodiment, in addition to an elongated core 710, a first layer 720, a second layer 730, and a third layer 740, the elongated conductive body further comprises a fourth layer 750 and a fifth layer 760. In a further embodiment, the first layer 720 and the second layer 730 can be formed of a conductive material and an insulating material, respectively, similar to those described in the embodiment of FIG. 7A. However, unlike the embodiment of FIG. 7A, in this particular embodiment, the third layer 740 can be configured to provide the sensor with a second working electrode, in addition to the first working electrode provided by the first layer 720. In this particular embodiment, the fourth layer 750 can comprise an insulating material and provide insulation between the third layer 740 and the fifth layer 760, which can correspond to a reference electrode and comprise the aforementioned silver-containing material. It is contemplated that other similar embodiments are possible. For example, in alternative embodiments, the elongated conductive body can have 6, 7, 8, 9, 10, or more layers, each of which can be formed of conductive or non-conductive material.
  • FIGS. 8A and 8C illustrate other embodiments of the elongated conductive body. In the embodiment illustrated in FIG. 8A, the elongated conductive body comprises three elongated cores 810A, 810B, and 810C located in (e.g., embedded in, coated with) the insulator 830. FIG. 8C illustrates another embodiment of the elongated conductive body comprising three insulated conductive bodies, wherein each insulated conductive body includes an elongated core 810A, 810B, and 810C coated with an insulator 804A, 804B, and 804C). In some embodiments, the elongated cores (e.g., coated with insulator) are bundled together, such as by an elastic band, an adhesive, wrapping, a shrink-wrap or C-clip, as is known in the art. In other embodiments, the inner bodies (e.g., coated with insulator) are twisted, such as into a triple-helix or similar configuration. In one embodiment, two of the elongated cores (e.g., coated with insulator) are twisted together to form a twisted pair, and then a third core (e.g., with insulator) and/or elongated conductive body is twisted around the twisted pair. In some embodiments, the sensor can comprise additional elongated cores.
  • While in some embodiments described herein, the elongated core is shaped like a wire and has a circular cross-section, in other embodiments the cross-section of the elongated core can be oval, square, rectangular, triangular, polyhedral, star-shaped, C-shaped, T-shaped, X-shaped, Y-Shaped, irregular, or the like. The elongated core can be formed of any of a variety of suitable material, such as, platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive or non-conductive polymer, alloys, glass, for example. In some embodiments, the elongated core comprises an inner core and a first layer, wherein an exposed electroactive surface of the first layer provides the working electrode of the continuous analyte sensor being manufactured. For example, in some embodiments, the inner core comprises stainless steel, titanium, tantalum and/or a polymer, and the first layer comprises platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, a conductive polymer, and/or an alloy.
  • The elongated conductive body can be designed (e.g., by material selection, by diameter selection, by treatment) to have certain mechanical properties. For instance, an elongated conductive body may be designed to meet a certain minimal level of tensile strength or minimal length of diameter, so that the elongated conductive body will not be prone to breakage during a reel-to-reel processing. In some embodiments, the tensile strength of the elongated conductive body is at least about 200 MPa, or at least about 500 MPa, or at least about 1,000 MPa, or at least about 2,000 MPa, or even at least about 5,000 MPa. In certain embodiments, the diameter of the elongated conductive body is at least about 5 microns, or at least about 15 microns, or at least about 25 microns, or at least about 50 microns, or at least about 75 microns, or at least about 100 microns, and or even at least about 200 microns. Other possible embodiments and features of the elongated conductive body are described in U.S. Provisional Application No. 61/222,751, the contents of which are incorporated by reference herein in its entirety.
  • Workpiece Station
  • The material that eventually forms the elongated conductive body may initially be in the form of one or more workpieces. The workpiece may be formed of any of a variety of materials, such as, for example, platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and alloys or combinations thereof. In some embodiments, the initial workpiece possesses the desired dimensions, shapes, and mechanical specifications, and thus minimal (or no) substantial mechanical or structural changes need to be made to the workpiece before it is treated and processed (e.g., coated, dried, etched, singulated, etc.) to form a continuous analyte sensor. In certain embodiments, the initial workpiece may already possess the desired shape (e.g., wire, tube, planar substrate, etc), but not the desired dimensions. In these embodiments, processing may involve resizing the workpiece to the desired dimensions.
  • In other embodiments, however, the initial workpiece does not possess any of the above-described desired specifications and properties, and thus the workpiece has to undergo processing, whereby the workpiece itself is worked on by machine or hand tools to impart structural and/or mechanical changes. These changes may involve, for example, cutting or shaping of the workpiece. They can also involve the addition of a layer (e.g., coating, cladding, plating, etc.) that circumscribes the outer surface of the workpiece. For example, the elongated conductive body may be fabricated to include a core and a cladding surrounding the core, both of which are formed from different materials. In some instances, fabricating the elongated conductive body to have a core formed with a less expensive, yet strong and flexible material (e.g., palladium, tantalum, stainless steel, or the like) and a thin layer of a more expensive material (e.g., platinum) to form the electroactive surface of the continuous analyte sensor, can enable a substantial reduction in the material costs required to build the continuous analyte sensor.
  • In one embodiment, fabrication of the elongated conductive body can be performed by inserting (e.g., by slip fitting) a rod or wire into a tube, the combination of which forms an initial structure of an elongated conductive body. The rod or wire may be formed of any of a variety of materials including, but not limited to, stainless steel, titanium, tantalum, and/or a polymer. The tube may be formed of a conductive material, such as, for example, platinum, platinum-iridium, gold, palladium, iridium, alloys thereof, graphite, carbon, or a conductive polymer. Alternatively, instead of using a tube to form the cladding, a layer of conductive material may be deposited onto the core. Deposition of the conductive material may be performed by any of a variety of techniques, such as, for example, chemical vapor deposition, physical vapor deposition (e.g., sputtering, vacuum deposition), chemical and electrochemical techniques, dip coating, spray coating, and optical coating. In some embodiments, the dip coating and spray coating processes described elsewhere herein may be used to deposit a coating layer onto the outer surface of the rod or wire.
  • After a cladding/plating/layer has been formed around the rod or wire, the elongated conductive body can then be passed through a series of dies to draw down the diameter of the elongated conductive body from a large diameter to a small diameter. With each pass through the die (e.g., a diamond die), the cross-sectional profile of the elongated conductive body is compressed, and the diameter associated therewith is reduced. It has been found that while compression tends to increase the tensile strength of the elongated conductive body, compression also tends to increase susceptibility of the elongated conductive body to brittleness, stress cracking, and even breakage. Accordingly, in some embodiments, an annealing step is used to cause changes in the mechanical and structural properties of the elongated conductive body, and more specifically, to relieve internal stresses, refine the structure by making it homogeneous, and improve cold working properties. It has also been found that drawing down the diameter of the elongated conductive body through large numbers of dies in small incremental steps, instead of through one or a few number of large incremental step(s), can result in better mechanical and structural properties. Accordingly, in some embodiments, the elongated conductive body is passed through a series of dies, with each successive die having a progressively smaller diameter. Between each die passing, the elongated conductive body may undergo an annealing treatment (e.g., by using an annealing oven), through which the elongated conductive body is softened and its ductility increased.
  • FIG. 10A illustrates one embodiment of a die 1050 used to compress the elongated conductive body, so as to reduce its cross-sectional profile. FIG. 10B provides a view of the die on lines 10B-10B of FIG. 10A. As shown, the die 1050 comprises an orifice 1020, a front portion 1012, through which an elongated conductive body 1010 enters the die 1050, and a back portion 1014, through which the elongated conductive body 1010 exits. The edge 1016 of the front portion 1012 may have a tapering angle a defined by the longitudinal axis 1018 of die 1050 and the front edge 1016. The elongated conductive body 1010 is drawn through a die 1050 (e.g., diamond die, etc.) and through its orifice 1020. In some embodiments, the shape and dimensions of the orifice 1020 may be changed, so that the elongated conductive body can be shaped and sized to have any desired cross sectional shape and dimensions.
  • As the elongated conductive body 1010 is forced through the die orifice 1050 to impart a shape or to reduce dimensions, the elongated conductive body 1010 becomes deformed. Drawing the elongated conductive body 1010 through a die with a large tapering angle will cause greater compression of the elongated conductive body 1010 than a die with a smaller tapering angle. Accordingly, drawing the elongated conductive body 1010 through a series of dies with large tapering angles may minimize the number of dies that an elongated conductive body has to be drawn through. However, it has been found that drawing the elongated conductive body 1010 through a successive number of dies, each with a smaller tapering angle, can substantially reduce the risk of breakage, brittleness, stress cracking, or other mechanical deficiencies that may be imparted on the elongated conductive body 1010. In some embodiments, the tapering angle a of the die is less than about 60 degrees, sometimes less than about 45 degrees, sometimes less than about 30 degrees, sometimes less than about 30 degrees, and sometimes less than about 10 degrees.
  • With certain embodiments (e.g., an elongated conductive body in the form of a wire), obtaining and maintaining concentricity of the elongated conductive body is important. Without concentricity of the elongated conductive body, subsequent coatings of the conductive, insulating, and membrane materials may not be uniform, and consequently performance of the fabricated continuous analyte sensor may be negatively impacted. For elongated conductive bodies with circular (or substantially circular) cross-sectional shape, a lack of uniformity of compressive forces exerted on the cross-sectional circumference of the elongated conductive body, can lead to loss of concentricity between the core and the clad/plate/layer and thereby cause certain portions of the elongated conductive body to be thicker than other portions. Accordingly, in some embodiments, the die 1050 is configured to cause the elongated conductive body 1010 to compress in a way such that compressive forces exerted on the cross-sectional circumference of the elongated conductive body are substantially uniform across the circumference, so that concentricity can be maintained. The risk of concentricity loss may also be reduced by use of a positioning system (e.g., a vision system) that may be disposed near or along the die 1050. The positioning system can be used to confirm that the elongated conductive body 110 is aligned correctly during its entry into and exit out of the die 1050, and that it is moving along a certain predetermined path (e.g., a path that is perpendicular to the plane defined by the orifice 1020). As an additional measure to minimize the risk of concentricity loss, portions of the die 1050, such as the orifice 1020, may be coated with a lubricant (e.g., oil) to reduce any buildup of friction associated with the advancement of the elongated conductive body 1010 through the die 1050.
  • In some embodiments involving a wire-shaped elongated conductive body with a substantially circular cross-sectional profile, the workpiece station comprises a series of dies, which collectively are capable of reducing the thickness of the elongated conductive body, while still substantially maintaining the concentricity of the elongated conduct body. In these embodiments, the reduction in thickness corresponds to the reduction from an original elongated conductive body diameter of up to about 250 microns, sometimes up to about 500 microns, sometimes up to about 1,000 microns, and sometimes up to about 2,500 microns, to a final diameter no less than about 100 microns, sometimes no less than about 50 microns, sometimes no less than about 25 microns, and sometimes no less than about 13 microns.
  • In addition (or as an alternative) to the treatments described above, the elongated conductive body can undergo any of a variety of processing to change its physical (and sometimes chemical) properties. For example, the elongated conductive body can undergo annealing, quenching, tempering, drawing, rolling, normalizing, work hardening, and/or work softening processes, so that the elongated conductive body acquires certain desired physical properties.
  • Etching Station
  • The automated, continuous system for manufacturing continuous analyte sensors may comprise an etching station, whereby portions of the coated assembly structure is stripped or otherwise removed. In some embodiments, removal of portions of deposited layers of coating can be performed to expose the one or more electroactive surface(s) of the elongated conductive body, thereby forming recessed regions or window regions/surfaces 420 corresponding to working electrodes. The terms “etching” and “etched” as used herein are broad terms, and are to be given their ordinary and customary meaning to a person of ordinary skill in the art (and are not to be limited to a special or customized meaning), and refer without limitation to a mechanism for forming one or more recessed regions within the elongated conducted body. It should be understood that the terms “etching” and “etched” as used herein is not limited to chemical etching. Rather, as used herein, “etching” and “etched” can also include, but are not limited to, techniques, such as laser etching/ablation/skiving, grit-blasting (e.g., with sodium bicarbonate or other suitable grit), or the like, that can be employed to expose certain surfaces of the elongated conductive body (e.g., the electroactive surfaces corresponding to a conductive layer or a surface corresponding to an insulating layer).
  • Achieving accuracy and precision with respect to the particular depth of one or more materials of a coated assembly which are removed by etching can be important. Without precision and accuracy (e.g., for certain embodiments involving an elongated conductive body with a circular or substantially circular cross-section), uniformity of ablation depth may not be achieved, and thus concentricity of the elongated conductive body may be lost. Without achieving and maintaining concentricity with a proximal layer of the elongated conductive body, any subsequent (i.e., distal) layers coated over the proximal layer would also not have concentricity. Loss of concentricity can result in certain portions of the elongated conductive body being thicker than other portions, which in turn, can negatively affect sensor performance (e.g., accuracy).
  • In some embodiments, the etching process involves etching a single layer of material (e.g., etching only an insulating layer or a conductive layer), but in other embodiments, the etching process involves etching a plurality of layers (e.g., both a conductive layer and an insulating layer), such as two, three, four, five, or more layers. In certain embodiments, portions of the elongated conductive body can be masked prior to depositing the insulating layer in order to maintain an exposed electroactive surface area.
  • As noted above, in some embodiments, laser ablation is used to remove certain layers that have been deposited on the elongated conductive body. Removal of layers can be performed to expose electroactive surfaces on the elongated conductive body or else merely to remove certain insulating or conductive layers or portions thereof. During the laser ablation process, a laser beam, which can be pulsed and have a particular wavelength and power selected to ablate the desired layers, portions, or patterns, is directed at certain portions of the elongated conductive body to irradiate the layers in accordance with a preselected pattern. The pattern can be controlled by the processor to provide for spacings between the portions of the elongated conductive body that are ablated. In certain embodiments, these spacings are from about 5 mm to about 50 mm, or from about 10 mm to about 30 mm, or even from about 20 mm to about 25 mm.
  • The power, duration of the laser pulse, repetition rate of the laser pulse, and speed of the laser can be varied to control the speed of the ablation, the amount of material ablated, and the depth of the ablation. The selected ablation settings may depend on the shape, size, and other physical properties of the elongated conductive body. They may also depend on the ablation depth, area, or shape desired. By controlling the parameters described above, the risk of the ablation process leaving a substantial amount of residual ablation debris on the elongated conductive body can be minimized. In some embodiments relating to laser etching of polyurethane, the laser beam has a wavelength of from about 100 nm to about 800 nm, or from about 200 nm to about 300 nm, or from about 220 nm to about 265 nm, or even from about 245 nm to about 250 nm.
  • In certain embodiments, the elongated conductive body is spun around its longitudinal axis as a laser beam is directed on the elongated conductive body. In further embodiments, the rotation rate is greater than about 0.5 revolutions per second, or greater than about 1 revolution per second, or greater than about 2 revolutions per minute, or greater than about 5 revolutions per minute, or even greater than about 10 revolutions per minute. The laser beam can be generated by any of a variety of laser sources, such as, an excimer laser, YAG laser, CO2 laser, diode laser, for example. The laser beam energy beam density can be established to be sufficient to ablate or remove a layer or portion from the elongated conductive body at a certain predetermined depth and area, but low enough so as to not damage the layers and materials outside the predetermined depth and area. The laser beam energy beam setting can also selected in consideration of the type of material(s) that is the target of the ablation. In some embodiments, the laser ablation process involves directing a beam to remove a small fraction of the total thickness (e.g., a few microns) of a layer with every pulse or pass. Multiple passes are then performed, so that the desired ablated depth is achieved. In certain embodiments, with every pulse or pass, a coating material corresponding to a depth of 0.5 microns from the surface is removed, or a coating material corresponding to a depth of 1 micron from the surface is removed, or a coating material corresponding to a depth of 1.5 micron from the surface is removed, or a coating material corresponding to a depth of 2 microns from the surface is removed, or a coating material corresponding to a depth of 2.5 microns from the surface is removed, or a coating material corresponding to a depth of 3 microns from the surface is removed, or a coating material corresponding to a depth of 5 microns from the surface is removed, or even a coating material corresponding to a depth of 10 micron from the surface is removed.
  • In certain embodiments, instead of using a single laser beam, multiple laser beams (e.g., two, three, four, or five laser beams) can be distributed around the elongated conductive body. In some of these embodiments, the elongated conductive body may not be configured to rotate during the laser ablation process. Instead, the plurality of laser beams around the elongated conductive body can be configured to turn on simultaneously, sequentially, or in some preselected pattern to remove the desired portion or pattern. A multi-beam arrangement can be obtained by using multiple laser sources, or by using one laser source and dividing the laser beam from this source into multiple branches with use of beamsplitters. Each of the smaller beams can then be guided or redirected with individual optical components such as mirrors and lenses, so that the beams are directed to the elongated conductive body from different directions or angles. From this, multiple laser beams can be distributed around a perimeter or circumference of a cross section of the elongated conductive body to remove a layer all around the perimeter or circumference of the elongated conductive body. In alternative embodiments, only certain preselected sections of a perimeter or circumference of the elongated conductive body cross section are removed.
  • FIG. 7B illustrates one embodiment of the elongated conductive body of FIG. 7A, after it has undergone laser ablation treatment. As shown, a window region 722 is formed when the ablation removes the second and third layers 730, 740, to expose an electroactive surface of the first conductive layer 720, wherein the exposed electroactive surface of the first conductive layer 720 correspond to a working electrode. In the embodiment illustrated in FIG. 7B, the laser ablation treatment of the elongated conductive body is carried out in steps, as evidenced by the multi-stepped topography. In a first step, a segment of the third layer 740 is ablated, and in a second step, a segment of the second layer 730 is ablated. In this embodiment, the segment of the third layer 740 removed is longer than the segment of the second layer 730 removed. Accordingly, the risk of third layer material falling onto the exposed electroactive surfaces of the first layer 720 may be minimized. Alternatively, in other embodiments, a single step ablation method can be employed, whereby both the second and third layers 730, 740, are removed simultaneously.
  • FIG. 7D illustrates one embodiment of the elongated conductive body of FIG. 7C, after it has undergone laser ablation treatment. Here, two window regions, a first window region 722 and a second window region 742, are formed, with each window region having a different depth and corresponding to a working electrode distinct from the other. As previously described, a multi-step laser ablation treatment can be employed. In forming the first window region 722, in a first step, a segment of the third, fourth, and fifth layers 740, 750, 760 are simultaneously removed. In a second step, a segment of the second layer 730 is removed to expose electroactive surfaces of the first conductive layer 720. As illustrated in FIG. 7D, in this particular embodiment, the segment of the second layer 720 that is removed is shorter than that removed of the third, fourth, and fifth layers 740, 750, 760, to minimize the risk of third, fourth, and fifth layer materials falling onto the exposed electroactive surfaces of the first layer 720. Similarly, in forming the second window region 744, in a first step, a segment of the fifth layer 760 is removed, and in a second step, a segment of the fourth layer 750 shorter than that of the fifth layer 760 is removed.
  • FIGS. 8B and 8D illustrate the elongated conductive bodies illustrated in FIGS. 8A and 8C, respectively, after they have undergone ablation treatment. As shown in FIG. 8B, the ablation treatment removes portions of the insulator from the elongated conductive body illustrated in FIG. 8A to form a plurality of window regions, thereby exposing a portion of the elongated cores 810A, 810B, and 810C. In this particular embodiment, window region 822A is formed in the insulator such that a portion of elongated 810A is exposed. Similarly, window region 822B is formed in the insulator such that a portion of elongated core 810B is exposed. In other embodiments, the window regions can be staggered and/or non-staggered along the longitudinal length of the sensor.
  • As shown in FIG. 8D, after ablation treatment, the elongated conductive body illustrated in FIG. 8C is formed with a first window region 822A configured to expose an electroactive portion of the first elongated core 810A and with a second window region 822B configured to expose an electroactive portion of the second elongated core 810B. In some embodiments, the first and second elongated cores are configured to function as first and second working electrodes, respectively, and the third elongated core is configured to function as a reference or counter electrode.
  • In other embodiments, grit blasting is implemented to expose the electroactive surfaces of an elongated core or conductive layer. This can be performed by using a grit material that is sufficiently hard to ablate the coated material, while being sufficiently soft so as to minimize or avoid damage to the underlying elongated core or conductive layer. Although a variety of “grit” materials can be used (e.g., sand, talc, walnut shell, ground plastic, sea salt, and the like), in some embodiments, sodium bicarbonate can be used as a grit-material because it is sufficiently hard to ablate a certain coating (e.g., a polyurethane, polyimide, or polyethylene insulating layer) without damaging an underlying core (e.g., platinum conductor). One additional advantage of sodium bicarbonate blasting includes its polishing action on certain metals as it strips the polymer layer, thereby potentially eliminating a cleaning step that might otherwise be necessary.
  • In yet other embodiments, mechanical skiving can be used. Mechanical skiving can involve using a scribe, a high speed grinder, mechanical machining, mechanical wheels, or other tools to impart a recess on the elongated conductive body to expose electroactive surfaces. In some instances, mechanical skiving can be advantageous because mechanical skiving typically results in a recessed region with a curved edge (as illustrated in FIG. 9A), instead of a recessed region with a sharp edge (as illustrated in FIG. 9B), as is typically created by a laser ablation process. In some instances, a recessed region with a curved edge and surface may provide for better control of coating thickness and/or coating thickness profile in the window region.
  • In yet other embodiments, chemical etching is used to expose the electroactive surfaces. During the chemical etching process, a mask, typically formed of an organic film, is deposited onto selected regions of the elongated conductive body, i.e., the regions not intended to be etched. The sections between the masked regions are then etched, and the mask is subsequently removed.
  • Pre-Coating Treatment Station
  • Prior to the coating process, the elongated conductive body 110 can be cleaned to remove organics or other surface contaminants that may interfere with the coating process. It is contemplated that any known suitable cleaning method can be used. For example, in some embodiments, the system uses an ultrasonic cleaning device comprising a cleaning vessel and a roller or pulley, for guiding the elongated conductive body inside the cleaning vessel. During the cleaning process, the cleaning vessel can be filled with a cleaning solvent, such as isopropanol, acetone, tetrahydrofuran (THF), or citric acid, for example. Next, the elongated conductive body is drawn through the cleaning vessel, where it is cleaned by ultrasonic sound waves and the cleaning solvent, such that when the elongated conductive body exits the ultrasonic cleaning device, it is cleaned essentially free of surface contaminants.
  • In some embodiments, a drying chamber can be provided adjacent to the exit of the cleaning vessel. In these embodiments, as the elongated conductive body exits the drying chamber, it passes through the drying chamber, where residual solvent on the surface can be removed, for example, by evaporating the solvent at a higher rate than that under ambient conditions. Use of a drying chamber can drive out the solvent using any conventional methods known, such as by using heat from an evaporator or an inlet supply of heated inert gas (e.g., nitrogen), or by using vacuum evaporation, for example.
  • In some embodiments, the elongated conductive body can be cleaned by a plasma device, as an alternative or in addition to the ultrasonic cleaning device. In these embodiments, the elongated conductive body can be treated within a vacuum chamber filled with an inert gas (e.g., Argon), which is electrically charged to bombard the surface of the elongated conductive body with sufficient energy for contaminant removal. The resulting contaminant effluent can then be removed from the drying chamber by a vacuum pump. Because plasma cleaning does not involve chemical reactions, under certain conditions, it may remove certain inorganic contaminants that are not easily removed by ultrasonic cleaning or chemical processes.
  • In certain embodiments, the elongated conductive body can also undergo surface treatment prior to the coating process to enhance uniformity of the subsequent coating deposition. The surface treatment can be carried out by any of a variety of known techniques. For example, electrostatic charging and/or plasma surface treatment can be used to modify the surface energy of the elongated conductive body. Using ionizing gases such as argon or nitrogen, plasma surface treatment can create highly reactive species even at low temperatures. Typically, only a few atomic layers on the surface are involved in the process, so the bulk properties of the elongated conductive body remain substantially unaltered by the chemistry. In some instances, plasma surface treatment may reduce surface contact angles and provide adequate surface activation for enhanced wetting and adhesive bonding. Other known surface treatments that can be used include, but are not limited to, surface washing with a solvent and corona discharge and UV/ozone treatment.
  • Coating Station
  • FIG. 3A provides a schematic diagram of one embodiment of a coating station 320. As the elongated conductive body 310 advances through a meniscus 326 comprising a coating solution formed of a solvent and a coating material, the elongated conductive body's surface becomes immersed in the coating solution. As it separates from the meniscus 326, the elongated conductive body 310 retains a coating with a layer of substantially uniform thickness on its outer surface, as illustrated in FIG. 3B. A solid layer of coating material is then formed on the surface, as the solvent portion of the coating solution evaporates.
  • As shown in the embodiment illustrated in FIGS. 3A and 3B, the coating station 320 can include a coating vessel 322 with an opening 324 at its top configured for establishing a meniscus 326. The coating vessel 322 can be formed of any of a variety of known inert materials (e.g., ordinary glass or ceramic ware or an inert polymer such as polyethylene) suitable for the coating processes contemplated. In addition, the coating vessel 322 can comprise a collecting section 328 for collecting overflow. In some embodiments, the coating station 320 can comprise an inert gas source, which introduces inert gas (e.g., nitrogen, argon) into the coating station. The inert gas is subsequently removed, so as to purge certain sections of the coating station. It is contemplated that in some embodiments the coating station 320 can also comprise a heat source (e.g., a heat lamp) disposed somewhere near the meniscus to speed solvent evaporation. In some embodiments, the environment in or surrounding the coating station 320 can be controlled. For example, in one system, the coating station 320 can comprise a temperature control unit disposed near or surrounding the coating vessel 322 to control the vapor pressure of the evaporating solvent. Additionally or alternatively, the coating station 320 can also comprise a humidity control unit configured to maintain a relatively constant humidity in the coating station 320. The temperature and humidity inside the coating vessel 320 can each be independently above, below, or substantially the same as the ambient temperature and humidity outside of the coating station 320.
  • The coating vessel 322 can also comprise various elements for detecting and controlling certain coating solution conditions, such as solids content (also commonly referred to as concentration of coating material), viscosity, and temperature. For example, the coating vessel 322 can include a temperature detector, a coating material concentration detector, a viscosity detector, a heat exchanger, and an agitator (e.g., a stirrer). The processor is operatively connected to detectors configured to transmit signals indicative of certain coating solution conditions to the processor. The processor is also operatively connected to various control elements (e.g., a heater, stirrer, control valve, etc.) that can be used to adjust certain coating solution conditions. Collectively, these various elements and the processor provide a closed-loop feedback mechanism for controlling coating solution conditions.
  • The embodiments described herein are capable of producing coatings of a precise thickness. This may be achieved in part by controlling certain coating solution conditions, which in turn allows for thickness control of the coating layer deposited onto the elongated conductive body. For example, controlling the temperature of the coating solution may facilitate thickness control, given that certain properties of the coating solution, such viscosity, will vary with temperature changes. As another example, controlling the viscosity may also facilitate thickness control, given that a highly viscous coating solution (e.g., with a high solids content) may sometimes present technical challenges with respect to thickness uniformity. Additionally, inconsistency in the viscosity and solids content of the coating solution between different periods of the coating process may cause inconsistencies in coating thickness between various segments of the elongated conductive body.
  • During the coating process, a meniscus 326 is established at the opening 324 at the top of the coating vessel 322, by activating the pump 321 which drives the solution to continuously circulate at a precisely controlled rate. To facilitate formation of the meniscus 326, the opening 324 of the coating vessel 322 can have any of a variety of shapes and dimensions, depending in part on the system's preselected process parameters (e.g., the solution used, the temperature of the solution, the speed at which the elongated conductive body advances through the coating station, etc.). For example, in some embodiments, the opening 324 of the coating vessel 322 can be formed with a circular or substantially circular shape, but in other embodiments, the opening can be formed with a shape that resembles an ellipse, a polygon (e.g., triangle, square, rectangle, parallelogram, trapezoid, pentagon, hexagon, octagon), or the like. The coating vessel 322 can also have any suitable dimension. For example, in some embodiments, the coating vessel can have large dimensions, so as to accommodate a plurality (e.g., 3, 4, 5, or 5) of elongated conductive bodies.
  • To prevent possible agglomeration of coating material particles in the coating vessel 322, the coating vessel 322 can be provided with an agitator 323 (e.g., a stirrer) to ensure that the coating solution is well mixed. The agitator 323 can also be used to prevent possible sedimentation of coating material particles at the bottom of the coating vessel 322. Although not shown in FIG. 3A or 3B, in some embodiments, the coating vessel can be configured to be in fluid communication with a solvent source and a coating material source. During the coating process, if the concentration of the coating material is measured to be outside a preselected range, the processor can respond by making adjustments to various control element setting, for example, by opening a control valve to introduce a solvent or coating material into the coating vessel, to return the coating solution to a preselected concentration.
  • Referring back to FIG. 3A, in some embodiments, the coating station 320 comprises a supply vat 325 that continuously feeds solution into the coating vessel 322 at a precisely controlled, consistent rate via a line 327 and a pump 329. Accordingly, as the coating process progresses, the solution held in the coating vessel 322 can be continuously replenished from the supply vat 325. By maintaining a controlled, consistent rate of flow of the coating solution from the supply vat 325 to the coating vessel 322, a continuous, consistent overflow flowing out of the opening 324 is sustained. In addition, this flow control may allow for control of the contour and dimensions of the meniscus, which in turn may provide consistency of coating thickness between different segments of the elongated conductive body. Overflow flowing out of the coating vessel can be collected by a collecting section 328, so that the overflow fluid can be further processed, such as, recycled, replenished by combining it with solvent and/or coating material, discarded, etc.
  • Although not shown, the supply vat 325 can be connected to one or more storage tanks that feed coating material and solvent into the supply vat 325. In some embodiments, the coating solution can be formed of one coating material and one solvent. In these embodiments the supply vat 325 can be connected to one storage tank holding one solvent and another storage tank holding another coating material. In other embodiments, the coating solution can be formed of a plurality of coating materials and/or a plurality of solvents. In these embodiments, the supply vat 325 can be connected to a plurality of storage tanks each holding a different solvent and/or a plurality of storage tanks each holding a different coating material. Similar to the coating vessel 322, the supply vat 325 can also be provided with an agitator (e.g., a stirrer) to agitate the solution and mix the coating material with the solvent, to prevent possible agglomeration of coating material particles in the supply vat 325, and to prevent possible sedimentation of coating material particles at the bottom of the supply vat 325. In some embodiments, the supply vat 325 can include a level indicator for monitoring the level of the coating solution in the supply vat 325. If the fluid level falls below a certain preselected level, the level indicator is configured to transmit a signal to the processor, so that new coating solution can be prepared.
  • As described elsewhere herein, in some embodiments, the elongated conductive body selected to undergo the membrane coating process may already have been coated with one or more layers of one or more materials (e.g., an elongated core covered with an insulating layer and/or a conductive layer). Following the ablation/etching process described elsewhere herein, as illustrated in FIG. 4A, the surface of the elongated conductive body can have a stepped topography configuration with a plurality of window regions 420, where portions of the insulating and/or conductive layers were previously removed. As shown, the window regions 420 are associated with a diameter 422 (also referred to herein as a window diameter 422) that is less than the diameter 432 associated with the outer surface 430 of the elongated conductive body 410. Because of the stepped topography configuration, controlling the coating thickness on the elongated conductive body 410, particularly the thickness in the window region 420, presents various technical challenges when conventional dip coating techniques are used. The embodiments described herein are configured to overcome these challenges by providing a mechanism that provides precise control of certain process parameters.
  • As described elsewhere herein, the system may be provided with a thickness control station 130 configured to control the coating thickness of certain portions (i.e., the unetched and/or unablated portions) of the elongated conductive body, by removing excess coating material from its outer surface 430. However, because the dimensions of the die orifice of the thickness control station 130 are constrained by the outer diameter of the elongated conductive body, a different mechanism can be used to control the coating thickness and thickness profile of the window regions 420. As illustrated in FIG. 4B, depositing a coating onto a windows region 420 with a stepped topography may result in a coating thickness profile resembling a curve. By controlling certain process parameters, the embodiments described herein allow for precise control over the thickness and the thickness profile of the layers residing in the window regions. To achieve this control, in some embodiments, the meniscus coating process described herein can be used, whereby the viscosity of the coating solution, the solids content of the coating solution, the temperature of the coating solution, the speed at which the elongated conductive body advances through the coating station, and/or the flow rate of the coating solution into the coating vessel are precisely controlled. Each of the aforementioned process parameters affects the thickness and the thickness profile of the material coated on the elongated conductive body. Because the thickness of the coating directly affects certain properties (e.g., permeability of the membrane system) of the continuous analyte sensor, achieving tight control of the thickness may also provide for tight control of these properties.
  • The coating thickness and the uniformity of the thickness may be controlled by solvent selection. Depending on the application contemplated, any of a variety of solvents can be used, each of which is associated with a vapor pressure. The vapor pressure of a solvent affects the rate at which the solvent evaporates. Accordingly, solvent selection may affect the thickness and/or thickness control.
  • Control of the viscosity can involve selection of a polymer forming the coating material, molecular weight selection for the polymer, control of polymer concentration of the solution, and solution temperature control. With a low viscosity, a coating may sometimes considerably sag to the bottom surface of the elongated conductive body, resulting in a variable layer thickness. In contrast, with a high viscosity, the coating material may be difficult to coat onto the elongated conductive body. Accordingly, it is contemplated that the system can use a coating solution with an appropriate viscosity which will allow for deposition, but will yet still provide for control over coating thickness and thickness profile. The molecular weight of a polymeric coating material may also affect the viscosity of the coating solution, with viscosity generally increasing with molecular weight. Viscosity also often correlates with temperature. Thus, in some embodiments, the temperature of the coating solution may be controlled so that the viscosity may be controlled. In some embodiments, the coating solution is controlled to have a preselected viscosity of from about 0.1 to about 500 cP, or from about 1 to about 30 cP, or from about 50 to about 100 cP.
  • Control of the solids content of the coating solution may be achieved by preparing a coating solution with a preselected concentration level, and sustaining this concentration level by constantly monitoring the concentration and adjusting as needed. In some embodiments, the coating solution is controlled to have a preselected solids content of from about 0.1 to about 60 weight percent, or from about 1 to about 35 weight percent, and or from about 5 to about 20 weight percent.
  • Control of the coating solution temperature may be achieved by use of a thermistor and a heating element (e.g., a heat exchanger). In some embodiments, the coating solution is controlled to have a preselected temperature from about 20° C. to about 100° C., and or from about 22° C. to about 35° C.
  • Control of the speed at which the elongated conductive body advances through the coating station can be controlled by the motor of the transport mechanism. Generally, a slower rate of withdrawal from the meniscus results in a thicker coating along the surface of the elongated conductive body. In some embodiments, the elongated conductive body may be controlled to have a rate of advancement from about 1 inch/min to about 1,000 ft/min, and or from about 1 ft/min to about 50 ft/min.
  • Control of the flow rate of the coating solution into the coating vessel may be achieved by controlling the output from the one or more pumps that pump coating solution into the coating vessel. In some embodiments, the flow rate into the coating vessel is from about 1 mL/min to about 25 mL/sec, and or from about 3 mL/min to about 7 mL/min.
  • Although a meniscus coating process is used coat the elongated conductive body in some embodiments, it is contemplated that in other embodiments, other types of coating processes can be used as an alternative or in addition to the meniscus coating process. For example, as illustrated in FIG. 3C, in some embodiments, instead of being configured to advance through a meniscus, the elongated conductive body 310 can be configured to advance into the coating vessel 322, where it can dwell for a preselected period of time. A plurality of rollers or pulley 372, 374, 376 can be disposed near or in the coating vessel 322 to provide guidance to the elongated conductive body 310 as it advances along its predetermined path. By precisely controlling certain process parameters, the embodiment of the system illustrated in FIG. 3C may be capable of achieving the thickness control characteristics associated with the meniscus coating process described elsewhere herein.
  • In yet other embodiments, a coating process employing a vertical arrangement is employed. For example, as illustrated in FIG. 3D, in some embodiments, the elongated conductive body 310 can be advanced vertically upwards through a septum 330 disposed at the bottom of a coating vessel 322, through the coating vessel 322, whereupon the elongated conductive body 310 is coated with the coating solution, and then through a thickness control device (e.g., a die 332 with an orifice 334) whereby excess coating material is removed. The septum can comprise a sealing member (e.g., a gasket or a plenum) for preventing the coating solution from leaking out of the bottom of the coating vessel 332. In these particular embodiments, the excess coating material falls back into the coating vessel 322. Similar to other embodiments described herein, the coating vessel 322 of these embodiments can be connected to a pump 321 for circulating the coating solution and a supply vat 325 for feeding coating solution into the coating vessel 322. In further embodiments, the coating vessel 322 can be equipped with a level indicator for monitoring the level of the coating solution therein. If the fluid level falls below a certain preselected level, the level indicator is configured to transmit a signal to the processor, so that additional coating solution is drawn from the supply vat 325 to the coating vessel 322 via pump 329.
  • Although the methods and systems described herein relate to dip coating processes, it should be understood that the coating station can employ any of a variety of other types of coating processes, such as spray coating or vapor deposition. For example, in one embodiment, the elongated conductive body is advanced through a spraying tunnel. While passing through the spraying tunnel, the elongated conductive body is coated with a coating material, which can be applied using any of a variety of known spray coating techniques, such as fog spraying or electrostatic spraying, for example. In another embodiment, a continuous manufacturing process is contemplated that utilizes physical vapor deposition to deposit a coating material. Physical vapor deposition can be used to coat one or more layers of material onto the elongated conductive body.
  • It is contemplated that in some instances, employing physical vapor deposition to coat the elongated conductive body may result in consistent deposition and enhanced reproducibility.
  • FIG. 3E illustrates one embodiment of a coating station that employs spray coating. Similar to some of the other embodiments described herein, in this particular embodiment, the coating station comprises a circulation pump 321 and a supply vat 325 configured to feed coating solution via a pump 329. In addition, this embodiment also comprises a nozzle 338 for spraying a coating solution and a receiving container 336 for collecting coating solution. During operation, as the elongated conductive body 310 is advanced through the coating station, it is sprayed with a jet of coating solution from the nozzle 338. Coating solution that falls off of the elongated conductive body is collected by the receiving container 336. From there, the coating solution is pumped via circulation pump 321 to the nozzle 338. In some embodiments, periodically (e.g., when the amount of coating solution in the receiving container 336 is low) coating solution from the supply vat 325 can also be pumped into the nozzle 338 via pump 329. In further embodiments, a plurality of nozzles can be provided at various angles and positions with respect to the pathway of the elongated conductive body, so as to spray the elongated conductive body with jets of coating solution from multiple positions and angles (e.g., from an angle that directs coating solution at the underside of the elongated conductive body).
  • While the transport mechanisms illustrated in FIGS. 3A-3E involve a reel-to-reel system for moving a long, continuous strand of elongated conductive body 310 for coating, in other embodiments, the elongated conductive body being coated may be in the form of individual pieces 310′, e.g., pieces formed after a singulation process whereby a long, continuous strand of elongated conductive body 310 is cut into individual pieces 310′. FIG. 3F illustrates one embodiment of a transport mechanism that can be used to move elongated conductive bodies 310′ that are in the form of individual pieces. In the embodiment shown in FIG. 3F, the transport system 300 includes a conveyor that supports a plurality of robotic units 380. Each robotic unit 380 comprises a retractable arm 386 secured to the conveyor 384. The retractable arm 386 comprises an elongated conductive body holder 388 that supports the elongated conductive body 310′. Although in the embodiment illustrated in FIG. 3F, the elongated conductive body holder 388 is shown holding four elongated conductive bodies 310′, in alternative embodiments, an elongated conductive body holder capable of holding any other number of elongated conductive bodies 110′ may be used instead. As the retractable arm 386 is extended, the elongated conductive body 310′ is moved downwards, and the elongated conductive body 310′ is partially or wholly submerged in a coating solution. After a predetermined time, the retractable arm is retracted, and the elongated conductive body 310′ is pulled out of the coating solution. The elongated conductive body 310′ is then allowed to dry as the solvent of the coating solution evaporates. Although not shown, a heater or dryer may be disposed along the path of the conveyor or on the robotic unit to accelerate evaporation of the coating solution.
  • As shown in FIG. 3F, the conveyor 384 is designed to advance the elongated conductive body 310′ from one coating vessel 392 to another coating vessel 394, and then to another coating vessel 396. Additionally, the conveyor 384 is designed to advance the elongated conductive body 310′ from one station 340 to a coating station 350, and then to another station 360. Although with the transport system 300 shown in FIG. 3F, the conveyor 384 is shown moving the elongated conductive body 310′ between three stations (including the coating station 350) and three coating vessels, it should be understood that in other embodiments, the conveyor 384 may be configured to move elongated conductive body 310′ between any number of coating vessels and any number of stations.
  • In certain embodiments, the step of depositing a coating material on the elongated conductive body and the step of controlling the thickness of the coating can be combined. For example, referring to FIG. 3G, a coating chamber 360 is shown that includes both a coating vessel 362 for holding a coating solution 364 and a die 366 (e.g., a diamond die) with an orifice 368 configured to control the coating thickness of the elongated conductive body 310 as it exits the coating chamber 360. FIG. 3H is a close side view of the die 366 and illustrates a tapering mechanism of the die. The coating solution 364 may comprise a solvent and a coating material, such as a conductive material (e.g., platinum, Ag/AgCl, etc.), an insulating material (e.g., polyurethane, polyimide, polyethylene), or a membrane material (e.g., a material used to form the electrode layer, enzyme layer, diffusion resistance layer, interference layer, etc.) FIG. 3I provides a view of the coating chamber 360 on lines 3I-3I of FIG. 3G. It has been found that the tapering mechanism illustrated in FIG. 3H facilitates a certain fluid dynamic that keeps the elongated conductive body centered along the longitudinal axis of the die orifice 368. FIG. 3J illustrates various other non-limiting examples of cross-sectional shapes of the die orifice 368 that can be used to mold the elongated conductive body to a desired shape. It should be understood that the die 366 can not only be used to coat an elongated conductive body formed of a single core or an elongated conductive body formed of a plurality of cores, but that it can also simultaneously coat a plurality of elongated conductive bodies in parallel.
  • The entrance passage of the coating chamber 360 includes an opening 370 that permits the elongated conductive body 310 to pass therethrough. A sealing member 342 is used to prevent the coating solution from leaking out of the opening 370. The sealing member 342 may be any of a variety of seals capable of preventing or reducing liquid leakage. Seals that can be used include, for example, o-rings, hydraulic seals, polypak seals, quad rings, radial shaft seals, v-ring seals, and the like. The coating chamber 360 may include an opening 352 for introduction of the coating solution into the coating vessel 362. Although the coating solution is shown in FIG. 3G as being introduced from the top of the coating vessel 362, it should be understood that in other embodiments the coating solution may be introduced into coating vessel from other entry points (e.g., from the side or bottom of the coating vessel) and by using various other mechanisms (e.g., via a conduit connected to a pump and a storage tank). The coating chamber 360 may also include a level indicator 344 that communicates with a control system, so that a predetermined level of coating solution 364 in the coating chamber 360 is maintained.
  • In some embodiments, the system is capable of depositing a coating layer having a substantially uniform thickness along the outer surface 430 of the elongated conductive body, wherein the thickness is less than about 35 microns, or less than about 25 microns, or less than about 10 micron, or less than about 5 microns, or less than about 1 microns, or even less than 0.1 microns. In some embodiments, the thickness uniformity of the outer diameter is better than about ±50% of the average thickness, or better than about ±30%, or better than about ±10%, or better than about ±5%, or even better than about ±1%. In some embodiments, the coefficient of variation of the outer diameter thickness is less than about 0.2, or less than about 0.1, or less than about 0.07, or less than about 0.05, or less than about 0.02, or even less than about 0.01.
  • In addition to being capable of depositing a coating layer having a substantially uniform thickness along the outer surface of the elongated conductive body, the system is also capable of depositing a coating layer with a thickness profile that is substantially uniform among the plurality of window regions 420 of the elongated conductive body. More specifically, in some embodiments, the coating layer deposited onto each window region can have a thickness profile that is consistent with those of the other window regions of the elongated conductive body.
  • To determine thickness profile uniformity, the mean coating thickness of each window region can be measured and compared with those of the other window regions. In some embodiments, wherein the elongated conductive body comprises 10 or more window regions, the coefficient of variation (of the 10 or more window regions) of the mean coating thickness is less than about 0.5, or less than about 0.2, or less than about 0.1, or less than about 0.05, or even less than about 0.01.
  • Thickness profile uniformity may also be determined by measuring coating thickness at certain locations (e.g., at a first distance one fifth from one end of the window region, at a second distance two fifths from one end of the window region, etc.) inside each window region, and comparing it with other window regions. In certain embodiments, wherein the elongated conductive body comprises 10 or more window regions, the coefficient of variation (of the 10 or more window regions) of the coating thickness at a first distance one fifth from one end of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or still less than about 0.05, or even less than about 0.01. In certain embodiments, wherein the elongated conductive body comprises 10 or more window regions, the coefficient of variation (of the 10 or more window regions) of the coating thickness at a second distance two fifths from one end of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or still less than about 0.05, or even less than about 0.01. In certain embodiments, wherein the elongated conductive body comprises 10 or more window regions, the coefficient of variation (of the 10 or more window regions) of the coating thickness at a third distance three fifths from one end of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or still less than about 0.05, or even less than about 0.01. In certain embodiments, wherein the elongated conductive body comprises 10 or more window regions, the coefficient of variation (of the 10 or more window regions) of the coating thickness at a fourth distance fourth fifths from one end of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or less than about 0.05, or even less than about 0.01. In certain embodiments, wherein the elongated conductive body comprises 10 or more window regions, the coefficient of variation (of the 10 or more window regions) of the coating thickness at a midpoint between two ends of each of the 10 or more window regions is less than about 0.3, or less than about 0.2, or less than about 0.1, or less than about 0.05, or even less than about 0.01.
  • By providing the capability of achieving a substantially uniform thickness profile among the plurality of window regions and a substantially uniform thickness along the outside surface of the elongated conductive body, the embodiments also provide the capability of achieving substantial uniformity with respect to certain sensor properties, such as sensitivity and current density. For example, in some embodiments, wherein the elongated conductive body comprises 10 or more window regions, the coefficient of variation (of the 10 or more window regions) of in vivo sensor sensitivity and/or in vitro sensor sensitivity at about 100 mg/dL glucose concentration is less than about 0.5, or less than about 0.25, or less than about 0.1, or less than about 0.05, or even less than about 0.01. In certain embodiments, wherein the elongated conductive body comprises 10 or more window regions, the coefficient of variation (of the 10 or more window regions) of in vivo sensor current density and/or in vitro sensor current density at about 100 mg/dL glucose concentration is less than about 0.5, or less than about 0.25, or less than about 0.1, or less than about 0.05, or even less than about 0.01.
  • Although certain thickness control mechanisms (e.g., die, a gas knife, etc.) are described elsewhere herein for controlling the thickness of the coating applied onto the elongated conductive body, it is contemplated that in some embodiments these control mechanism may not be necessary. FIG. 3K illustrates one embodiment of a coating device 390 comprising two absorption pads 398, 399 that are soaked with a solution comprising the coating material. One or more of absorption pads may be in communication with a reservoir 378 holding a solution with the coating material. In this particular embodiment, the two absorption pads are arranged in an abutting relationship, such that as the elongated conductive body is advanced in a path along a plane defined by the interface between the two absorption pads. The solution with the coating material is applied to the elongated conductive body. By controlling the concentration gradient that exists at the interface 358, the amount of coating that is applied to the elongated conductive body 310 can be controlled. Other ways of controlling the thickness of the elongated conductive body include, but are not limited to, controlling the surface energy of the elongated conductive body, controlling the speed at which the elongated conductive body is advanced, and controlling the viscosity of the solution comprising the coating material. Accordingly, with multiple passes through the coating device 390, an elongated conductive body 310 with a certain preselected thickness of a coating material can be obtained. The pads may be formed of any material, such as a fibrous material, that is capable of absorbing the solution. In addition, although the embodiment illustrated in FIG. 3K includes two absorption pads, it should be understood that in other embodiments, a different number of absorption pads (e.g., three, four, five, ten, or more) having the same or different shapes or dimensions can also be used.
  • Thickness Control Station
  • Referring back to FIGS. 1A-1D, After advancing through the coating station 120, the elongated conductive body 110 is then advanced to a thickness control station 130. In some embodiments, the thickness control station 130 comprises a die (not shown) mounted transverse to the elongated conductive body. As the elongated conductive body advances through an orifice of the die, excess coating material is removed to form on the treated surface a coating layer having a substantially consistent thickness. As described above, the excess coating material removed is from the outer surface 430 of the elongated conductive body, and not from the window surface 420. The dimensions of the die orifice can vary depending on the type of coating being formed on the elongated conductive body. With respect to the coating process involving the insulating layer, the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the insulating layer, or from about 5 to about 15 microns larger, or even from about 10 to about 14 microns larger. With respect to the coating process involving the conductive layer, the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the conductive layer, or from about 1 to about 15 microns larger, or even from about 5 to about 10 microns larger. With respect to the coating process involving the electrode layer, the die orifice can have a radius from about 0.1 to about 25 microns larger than that of the elongated conductive body without the electrode layer, or from about 0.2 and 10 microns larger, or even from about 0.5 to about 1.5 microns larger. With respect to the coating process involving the interference layer, the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the interference layer, or from about 0.2 to about 10 microns larger, or even from about 0.5 to about 1.5 microns larger. With respect to the coating process involving the enzyme layer, the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the enzyme layer, or from about 0.2 to about 10 microns larger, or even from about 0.5 to about 1.5 microns larger. With respect to the coating process involving the diffusion resistance layer, the die orifice can have a radius of from about 0.1 to about 25 microns larger than that of the elongated conductive body without the diffusion resistance layer, or from about 1 to about 15 microns larger, or even from about 5 to about 10 microns larger.
  • While in some embodiments the die orifice has a circular or substantially circular shape, in other embodiments the die orifice can have a shape that is oval, square, rectangular, triangular, polyhedral, star-shaped, C-shaped, T-shaped, X-shaped, Y-Shaped, irregular, or the like.
  • In some embodiments, the thickness control station can comprise a plurality of dies, each or some of which comprise an orifice with a shape or dimension different from that of the other dies. For example, in one embodiment, the thickness control station can comprise three dies arranged in a series, with each die comprising a circular orifice, wherein a first die orifice comprises a larger diameter than that of a second die, and the second die orifice comprises a larger diameter than that of a third die. Alternatively, in some embodiments, the thickness control station can comprise one die with a plurality of orifices formed therein, with each orifice configured to receive an elongated conductive body.
  • In one embodiment, the die can comprise a plurality of movable members configured to collectively define the outline of an orifice, through which the elongated conductive body is configured to advance. The movable members can be controlled by the processor to move to different positions and arrangements to form orifices of different shapes and dimensions. This feature provides the system with the capability to adjust the shape and dimension of the orifice to conform to certain preselected process parameters (e.g., preselected shape or thickness of the elongated conductive body). In some embodiments, to make certain that the elongated conductive body is centered with respect to its entry into the die orifice, guide rollers or pulleys can be disposed near the entrance and/or exit of the die, to provide precise guidance to the moving elongated conductive body.
  • As the process progresses, a buildup of coating material may form in the region of the orifice. To remove this buildup, the thickness control station can include a solvent source that periodically or continuously sends solvent to the orifice. In some embodiments, the thickness control station can comprise a pan for collecting excess coating material that falls from the elongated conductive body or the die. The excess coating material may be discarded or reused if suitable.
  • In addition to the die described above, it is contemplated that other known techniques for removing excess coating material can also be used. For example, in some embodiments, as an alternative or in addition to the die, a gas knife, using impinging jets of inert gas (e.g., nitrogen) can be used.
  • Drying Curing Station
  • As shown in FIG. 1A, the system 100 comprises a drying or curing station 140 for drying and curing the coating material deposited onto the elongated conductive body 110. As the elongated conductive body 110 advances through the drying/curing station 140, residual solvent on the surface of the elongated conductive body 110 is evaporated. Furthermore, crosslinkable components of the coating material can be substantially crosslinked. The curing process can be carried out by any of a variety of conventional drying techniques, such as by UV, infrared, microwave, x-ray, gamma ray, or electron beam radiation, whereby radiation is directed at the coating material, or alternatively by heat, such as by conduction drying or convection drying, for example, by hot air convection drying using a hot air convection oven. Depending in part on the particular coating material used and the coating thickness, one or more of the above-mentioned techniques may be used as an alternative (or in addition) to other techniques. For example, while not wishing to be bound by theory, it is believed that a high energy radiation curing mechanism (e.g., short wavelength UV) may sometimes be used when the deposited layer is thick, because high energy radiation typically penetrates coating material better than infrared light, and thus may provide more curing uniformity along the entire thickness of the coated material. Radiation-based curing may also be used in some embodiments because it provides tight control over the level of radiation, thereby allowing for better control of the curing process. The curing process may take place under a variety of process conditions. In one embodiment, the drying or curing process occurs in a curing chamber and/or oven at a temperature of from about 20° C. to about 500° C., or from about 50° C. to about 150° C., or even from about 200° C. to about 400° C. In some embodiments, the system can include a humidifier/dehumidifier for maintaining proper relative humidity in the drying/curing station.
  • Thickness Measurement Station
  • Referring back to the embodiment illustrated in FIG. 1A, the system 100 includes a thickness measurement station 150 comprising a thickness measurement sensor or micrometer configured for measuring the thickness of the elongated conductive body 110 (with or without coating), as it passes through the thickness measurement station 150. After obtaining a reading, the micrometer is configured to transmit to the processor 160 a signal indicative of the measured thickness. If the measured thickness is determined to be less than the preselected thickness, the system is configured to repeat the coating process until a layer having the preselected thickness is formed.
  • It is contemplated that the thickness measurement sensor or micrometer can be any of a variety of devices capable of measuring a dimension indicative of a thickness of a coating formed on the elongated conductive body. For example, in some embodiments, the micrometer can be an optical micrometer, but in other embodiments the micrometer can be a gauge device or other similar device configured to contact the elongated conductive body for thickness measurement. Optical micrometers that can be used include light emitting diode (LED) devices, laser devices, or other similar devices capable of measuring certain elongated bodies (e.g., wires and webs) at suitable sampling rates. Typically, with an optical micrometer, the micrometer itself is positioned near the pathway of the elongated conductive body and configured to measure the thickness of the elongated conductive body without actually contacting it.
  • In some embodiments, the thickness measurement sensor is configured to periodically measure the outside diameter of the elongated conductive body. The thickness measurement sensor can also be operatively connected to the processor, which is programmed to compare the latest measurement value of the diameter with a prior measurement value corresponding to the diameter prior to the latest coating sequence. The processor may also be programmed to calculate the thickness of the latest coating by subtracting the prior measurement value from the latest measurement value. The thickness of the coated elongated conductive body will of course progressively increase with each successive layer of coating material deposited onto the elongated conductive body. Once a determination has been made as to the layer thickness of a certain segment of the elongated conductive body, the processor is programmed to instruct the thickness measurement sensor to measure another segment of the elongated conductive body as it advances into the thickness measurement sensor. In some embodiments, the thickness measurement sensor may be set to make a thickness measurement about every 100 cm of the elongated conductive body, or less than about every 50 cm, or less than about every 25 cm, or still less than about every 10 cm, or less than about every 5 cm, or less than about every 2.5 cm, or less than about every 1 cm, or less than about every 1 mm, or even less than about every 100 microns. The measurements made by the thickness measurement sensor can be for the outer surface of the elongated conductive body, the window surface, or both. Based upon the signal transmitted from the thickness measurement sensor, the processor 160 may control certain parameters of the coating process. For example, if a particular coating thickness (e.g., thickness of the electrode layer, enzyme layer, and/or diffusion resistance layer) is measured to be less than the preselected thickness, the system may be programmed to repeat the coating process once, twice, or more times, until the preselected thickness has been achieved.
  • Alternatively, in other embodiments, the system may be programmed to run the coating process for a preselected number of iterations, instead of programmed to run the coating process repeatedly until a certain preselected thickness is achieved. In these embodiments, thickness control can still be achieved because of the high level of precision of thickness control provided by the system.
  • In some embodiments, the thickness measurement station 150 may not be configured to measure the exact thickness of the elongated conductive body. Instead, the thickness measurement station may include a vision system that is configured to detect certain surface irregularities on the elongated conductive body. Irregularities can include, but are not limited to, exposed patches that resemble an undercoating (e.g., an insulating coating underlying a conductive coating) and that indicate a section of the elongated conductive body in which coating is very thin or nonexistent. The exposed patches can show up on the vision system with a color or reflection that is different than that expected. After a surface irregularity has been detected, the coating process can be stopped. Alternatively, the process can be continued, with the section of the detected surface irregularity recorded, and the recorded section can be removed in subsequent processing.
  • Post-Coating Treatment Station
  • After the elongated conductive body has been coated with at least one layer of material, such as a conductive material, insulating material, or membrane material (e.g., materials that form the electrode, interference, enzyme, and/or diffusion resistance layers), with each layer having been determined as having the preselected thickness, the elongated conductive body can then be advanced to a post-coating treatment station, where the elongated conductive body is cleaned and further processed, for example, through an another surface treatment process (e.g., plasma treatment). In some embodiments, after singulation of the elongated conductive body into individual sensors, the ends or tips of the singulated individual sensors may have various exposed metal portions not covered by a membrane or an insulating layer. A sensor formed without a seal covering these end portions may pick up various levels of unwanted signals. Thus, in some embodiments, the exposed portions are sealed off using any of a variety of known techniques, such as, for example, by dipping, spraying, shrink tubing, or crimp wrapping an insulating, membrane, or other isolating material onto the sensor tip. In certain embodiments, in which the sensor tip is capped with a membrane material, the tip can serve as a working electrode. After the end sealing process, certain portions (e.g., the back ends) of the singulated sensors can be etched to expose a conductive material, to provide the sensors with electrical connection. Alternatively or additionally, a mechanical connector may be clamped onto the elongated conductive body's conductive surface, cutting through the membrane in the process. Thereafter, the sensors can be delivered to other stations for further processing.
  • After the continuous analyte sensors have been completely built, the sensors are then packaged into containers or boxes for shipping to a patient, hospital, or retailer. The containers or boxes may be formed of special materials that are capable of protecting the sensors from harsh environmental conditions.
  • Singulation Station
  • During any time of the sensor manufacturing process, the elongated conductive body can be cut for singulation into individual pieces. For example, in some embodiments, singulation can be performed before coating of conductive and/or insulating materials. In other embodiments, singulation can be performed after coating of the conductive and/or insulating materials, but before coating of membrane materials. In yet other embodiments, singulation can be performed after coating of conductive and/or insulating materials and after coating of membrane materials. Any of a variety of known cutting systems, such as a system comprising a hydraulic cutting device, for example, can be used.
  • FIG. 11 illustrates one embodiment of a system 1100 that integrates etching (to remove or strip portions of a coated assembly structure) and singulation of the elongated conductive body into individual pieces. In this embodiment, the cutting system 1100 includes a supply spool 1120 which feeds an elongated conductive body 1110 into an elongated conductive body straightener 1130 (e.g., a wire straightener). The elongated conductive body 1110 is then fed into a rotating mandrel 1140, which rotates the elongated conductive body 1110. Periodically, an elongated conductive body gripping device 1150 moves forward and grasps the end of the elongated conductive body 1110 and then moves backwards to position the elongated conductive body 1110 for etching by any of the etching processes described elsewhere herein (e.g., by laser ablation 1190). Rotation of the elongated conductive body 1110 can involve a complete rotation (i.e., a rotation of 360 degrees or more), through which a portion associated with the entire circumference of the elongated conductive body 1110 is etched. Alternatively, rotation of the elongated conductive body can be partial and controlled such that only certain sections associated with the elongated conduct body's circumference is etched. After the etching process is completed, a section of the elongated conductive body 1110 is cut by a cutter 1160. The steps described are then continuously repeated. It should be understood that the system described above is merely exemplary, and some components (e.g., the mandrel 1140 or the etching mechanism) may be omitted or replaced by other components (e.g., a drying or curing mechanism).
  • Sensor Manufacturing Process
  • FIG. 5 is a flowchart summarizing the steps of one embodiment of a method for continuously manufacturing analyte sensors. In step 510, an elongated conductive body is provided. The elongated conductive body can be a bare elongated core (e.g., a metal wire), a cladded elongated core, or a bare or cladded elongated core coated with one, two, three, four, five, or more layers of material. Although not shown in FIG. 5, in some embodiments, step 510 can be preceded by one or more steps, wherein the above-described elongated conductive body (as shown in FIG. 4A) is built by coating an elongated core (e.g., a wire) with one or more layers of material (e.g., an insulating layer and a conductive layer) to form a coated assembly structure, and then removing portions of the coated assembly structure. For example, in one embodiment, the elongated core is advanced through a coating station/thickness control station/drying/curing station/thickness measurement station series/sequence, whereby it is coated with an insulating material. The series/sequence may be repeated until an insulating layer having a preselected thickness has been deposited, as measured by the thickness measurement sensor. The elongated conductive body is then advanced through a coating station/thickness control station/drying/curing station/thickness measurement station sequence, whereby it is coated with a conductive material. Again, the sequence may be repeated until a conductive layer having a preselected thickness has been deposited. After the insulating and conductive layers have been deposited onto the elongated core, the elongated conductive body can then be advanced to an etching station, where portions of the coated assembly structure is stripped or otherwise removed (e.g., to expose the electroactive surfaces of the elongated core, thereby creating window regions corresponding to electroactive surface areas).
  • In step 520, the elongated conductive body is advanced through a pre-coating treatment station, where it is cleaned with a solvent to remove surface contaminants. In some embodiments, an additional drying step can be provided to evaporate any residual solvents left on the surface of the elongated conductive body.
  • In step 530, the elongated conductive body is advanced through a coating station, where a coating solution comprising a solvent and a coating material (e.g., a material to form a conductive layer, insulating layer, or a membrane) is deposited onto the elongated conductive body. The layers that may form the membrane system are described in greater detail below. As the solvent portion of the coating solution evaporates, a solid layer of the coating material is formed on the elongated conductive body. In some embodiments, the coating solution is deposited by a meniscus coating process, whereby the elongated conductive body is advanced through a meniscus established at an opening of a coating vessel. The meniscus coating process described herein provides the system with the capability of precisely controlling the thickness and thickness profile of the coating deposited.
  • In step 540, the elongated conductive body is advanced through a thickness control station, where excess coating material can be removed to form on the treated surface a layer of coating having a substantially consistent thickness. In some embodiments, the coating station and the thickness control station may be integrated into one station.
  • In step 550, the elongated conductive body is advanced through the drying or curing station, where it may be dried under ambient conditions or heated to remove residual solvent on the surface of the elongated conductive body. In certain embodiments, at the drying or curing station, crosslinkable components of the coating material are substantially crosslinked. The curing process can be carried out by any of a variety of conventional drying techniques including, but not limited to, by UV, infrared, microwave, x-ray, gamma ray, or electron beam radiation, or by heat.
  • In step 560, the elongated conductive body is advanced through the thickness measurement station, where a measurement is made of the thickness of the elongated conductive body, and a signal indicative of the measurement is transmitted to the processor. The processor then compares the measured thickness with a preselected thickness. If the measured thickness is determined to be less than the preselected thickness, the system is programmed to repeat the coating process until a layer having the preselected thickness is formed.
  • In step 570, after being coated with multiple layers of material (e.g., insulating, conductive, electrode, interference, enzyme, and/or diffusion resistance material), with each layer having the preselected thickness, the elongated conductive body is advanced into the post-coating treatment station, where it can be cleaned and/or undergo further treatment. Thereafter, the individual sensors can be delivered to other stations for further processing.
  • It should be understood that the method described above is merely exemplary, and some steps may be omitted or replaced by other steps. Furthermore, although the steps of the method are described in a particular order, the various steps need not be performed sequentially or in the order described. For example, in some embodiments, an elongated conductive body is provided, as indicated by step 510. Thereafter, it undergoes processing, as indicated by steps 520, 530, 540, 550, and 560, whereby a coating forming a first layer (e.g., an insulating layer) with a preselected thickness is deposited on the elongated conductive body. The coating process (i.e., the sequence formed of steps 520, 530, 540, 550, and 560) can be repeated several times, with each passing sequence resulting in a successive layer (e.g., a second layer comprising an enzyme layer, a third layer comprising a diffusion resistance layer, etc.) with a preselected thickness being deposited onto the elongated conductive body. After the preselected layers have been deposited, the elongated conductive body can then be transferred to a station for post-coating treatment, as indicated by step 570.
  • To demonstrate the method described in FIG. 5, an example is provided herein describing one embodiment of coating polyurethane (an insulating material) onto the outer conductive surface of an elongated conductive body. Although the material described in this example is polyurethane, it should be understood that other insulating materials (e.g., polyethylene, polyimide, etc.) may be also be used in accordance with the method described herein.
  • In step 510, an elongated conductive body is provided which has an outer conductive layer formed of platinum and an inner core formed of another material (e.g., stainless steel, titanium, tantalum, glass, polymeric material, non-conductive material, etc.). In an alternative embodiment, the entire elongated conductive body may be monolithic and formed of a conductive material, such as platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and combinations thereof.
  • Next, in step 520 the elongated conductive body is treated (e.g., washed with alcohol or treated with plasma). In some embodiments, an adhesion promoter may be applied to the outer surface of the elongated conductive body. The adhesion promoter may be used to cause surface reaction to improve adhesion of the polyurethane to the conductive surface of the elongated conductive body, and thereby reduce the risk of delamination. The adhesion promoters, in a non-limiting embodiment, can be monomers, oligomers and/or polymers. Such materials include, but are not limited to, organometallics such as silanes, (e.g., mercapto silanes, acrylate or methacrylate functional silanes, vinyl silanes, amino silanes, epoxy silanes, isocyanate silanes, fluoro silanes, and alkyl silanes), siloxanes, titanates, zirconates, aluminates, metal containing compounds, zirconium aluminates, hydrolysates thereof and mixtures thereof. In one embodiment, silane is used as an adhesion promoter, and it is used as a component of a solution. In a further embodiment, the solution comprises from about 90% to 98% organic solvent (e.g., ethanol, tetrahydrofuran), about 1% to 5% water, and about 1 to 5% silane onto the outer surface of the elongated conductive body. The solvents may then be removed by air drying and/or by using an oven.
  • Thereafter, in step 530, the polyurethane is coated onto the elongated conductive body using any of the coating techniques described elsewhere herein, such as a meniscus coating method. The polyurethane coating is then dried or cured. In certain embodiments, the polyurethane may have a thickness of from about 5 microns to about 50 microns, or from about 12 microns to about 25 microns, or even from about 18 microns to about 23 microns. Excess coating materials of polyurethane are then removed by use of a die, in accordance with step 540. The cycle from step 510 to step 550 can then be repeated until a preselected thickness of the polyurethane layer has been achieved.
  • To further demonstrate the method described in FIG. 5, another example is provided herein. This particular example describes one embodiment of coating a platinum material onto the elongated core or an Ag/AgCl material (i.e., a conductive material) onto the polyurethane layer described in the example above. Although the materials used in this example are platinum, Ag/AgCl, and polyurethane, it should be understood that other conductive materials and insulating materials may also be used in accordance with the method described herein.
  • With respect to coating of Ag/AgCl onto the polyurethane, the coating material can involve an Ag/AgCl solution or paste which can be purchased from commercially available sources or alternatively prepared to have certain specified properties. Typically, an AgCl layer is consumed during a period when the Ag/AgCl electrode is used as a cathode. Accordingly, by controlling the composition, thickness, or other properties of the Ag/AgCl layer, the effective lifespan of a sensor (i.e., the period of time that it can function properly) can be controlled by the manufacturing method. The silver grain and the silver chloride grain can have any of a variety of shapes, such as a shape similar to a sphere, plate, flake, a polyhedron, or combinations thereof.
  • In some embodiments, the silver grain in the Ag/AgCl solution or paste can have an average particle size associated with a maximum particle dimension that is less than about 100 microns, or less than about 50 microns, or less than about 30 microns, or less than about 20 microns, or less than about 10 microns, or even less than about 5 microns. The silver chloride grain in the Ag/AgCl solution or paste can have an average particle size associated with a maximum particle dimension that is less than about 100 microns, or less than about 80 microns, or less than about 60 microns, or less than about 50 microns, or less than about 20 microns, or even less than about 10 microns. The silver grain and the silver chloride grain may be incorporated at a ratio of the silver chloride grain: silver grain of from about 0.01:1 to 2:1 by weight, and sometimes from about 0.1:1 to 1:1. The silver grains and the silver chloride grains are then mixed with a carrier (e.g., a polyurethane) to form a solution or paste. In certain embodiments, the Ag/AgCl component comprises from about 10% to about 65% by weight of the total Ag/AgCl solution or paste, or from about 20% to about 50% by weight of the total Ag/AgCl solution or paste, or even from about 23% to about 37% by weight of the total Ag/AgCl solution or paste. In some embodiments, the Ag/AgCl solution or paste has a viscosity (under ambient conditions) that is from about 1 to about 500 centipoise, or from about 10 to about 300 centipoise, or even from about 50 to about 150 centipoise.
  • Prior to the coating step 530, an elongated conductive body is provided in step 510. In one embodiment associated with coating of platinum onto the elongated core, the elongated conductive body is only an elongated core. In one embodiment associated with coating of Ag/AgCl onto polyurethane, the elongated conductive body has an outer conductive layer formed of platinum with an inner elongated core formed of another material (e.g., stainless steel, titanium, tantalum, polymeric material, non-conductive material, etc.). Disposed over the platinum layer is a layer of polyurethane deposited using the method described in the example above. In alternative embodiments, the entire elongated conductive body may be monolithic and formed of a conductive material, such as platinum, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and combinations thereof.
  • Next, in step 520 the elongated conductive body is treated (e.g., washed with an alcohol wash, treated with plasma, or corona treatment). Similar to the example described above regarding the coating of polyurethane, an adhesion promoter may optionally be applied to the polyurethane to improve the adhesion of the polyurethane to the Ag/AgCl material being deposited or of the elongated core material (e.g., stainless steel, tantalum) to the platinum material being deposited.
  • Thereafter, in step 530, the platinum solution or Ag/AgCl solution or paste is coated onto the elongated conductive body using any of the coating techniques described elsewhere herein. In one embodiment, the coating chamber 360 illustrated in FIG. 3G is used to perform the coating step 530. In addition, the die 366 in the coating chamber is used to perform the step 540 of removing excess platinum, Ag/AgCl, or other material from the elongated conductive body. In one embodiment associated with coating of platinum onto the elongated core, the coated platinum layer may have a thickness of from a thickness corresponding to a layer formed from a few platinum atoms to about 200 microns, or from about 1 micron to about 10 microns, or even from about 3 microns to about 5 microns. In one embodiment associated with the coating of Ag/AgCl onto the elongated core, the coated Ag/AgCl layer can have a thickness of from about 0.5 microns to about 30 microns, or from about 1 micron to about 20 microns, or even from about 5 microns to about 15 microns. The cycle from step 510 to step 550 is then be repeated until a preselected thickness of the platinum layer or Ag/AgCl layer has been achieved. It is contemplated that the ratio of the thickness of the Ag/AgCl layer to the thickness of the polyurethane layer can be controlled, so as to allow for a certain error margin (e.g., an error margin associated with the etching process) that would not result in a defective sensor (e.g., due to a defect resulting from an etching process that cuts into a depth more than intended, thereby unintentionally exposing an electroactive surface). This ratio may be different depending on the type of etching process used, e.g., whether it is laser ablation, grit blasting, chemical etching, or some other etching method. For laser ablation, the ratio of the thickness of the Ag/AgCl layer to the thickness of the polyurethane layer can be from about 1:5 to about 1:1, or from about 1:3 to about 1:2.
  • Membrane System
  • The membrane systems described herein can be formed using the systems and methods described above, and are suitable for use with implantable sensors in contact with a biological fluid. For example, the membrane system can be utilized with sensors for measuring analyte levels in a biological fluid, such as sensors for monitoring glucose levels for individuals having diabetes. In some embodiments, the analyte-measuring sensor is a continuous sensor. A wide variety of sensor configurations are contemplated with respect to sensor placement. For example, in some embodiments, the sensor can be configured for transdermal (e.g., transcutaneous) placement, but in other embodiments the sensor can be configured for intravascular placement, subcutaneous placement, intramuscular placement, or intraosseous placement. The sensor can use any method to provide an output signal indicative of the concentration of the analyte of interest; these methods can include, for example, invasive, minimally invasive, or non-invasive sensing techniques.
  • Although some of the description that follows is directed at glucose-measuring devices, the membrane systems described herein are not limited to use in devices that measure or monitor glucose. Rather, these membrane systems are suitable for use in any of a variety of devices, including, for example, devices that detect and quantify other analytes present in biological fluids (e.g., cholesterol, amino acids, alcohol, galactose, and lactate), cell transplantation devices, drug delivery devices, and the like.
  • FIG. 6A is a cross-sectional view through one embodiment of the elongated conductive body of FIG. 4B on line 6A-6A, illustrating one embodiment of the membrane system 600. The cross-section illustrated in FIG. 6A corresponds to the window surface of the elongated conductive body. As described above, the window surface can correspond to a working electrode formed in part, for example, by removing a portion of the insulating material and conductive material from an electroactive surface the elongated conductive body by ablation, etching, or other like techniques. FIG. 6B is a cross-sectional view through the elongated conductive body of FIG. 4B on line 6B-6B.
  • In the particular embodiment shown in FIGS. 6A and 6B, the membrane system 600 comprises an electrode layer 620, interference layer 630, enzyme layer 640, and a diffusion resistance layer 650, located around the core 610 of the elongated conductive body. It should be understood that any of the layers described herein, e.g., the electrode, interference, enzyme, or diffusion resistance layer, may be omitted. In addition, it should be understood the membrane system can have any of a variety of layer arrangements, with some arrangements having more or less layers than other arrangements. For example, in some embodiments, the membrane system can comprise one interference layer, one enzyme layer, and two diffusion resistance layers, but in other embodiments, the membrane system can comprise one electrode layer, one enzyme layer, and one diffusion resistance layer. Additionally, it should be understood that although the exemplary embodiments illustrated in FIGS. 6A and 6B involve circumferentially extending membrane systems covering an elongated conductive body with a circular cross-section, the membranes described herein can be applied to any planar or non-planar surface and an elongated conductive body with any variety of cross-sectional shapes, such as oval, square, rectangular, triangular, polyhedral, star-shaped, C-shaped, T-shaped, X-shaped, Y-Shaped, irregular, or the like, for example. As shown, the portion of the elongated conductive body corresponding to the section illustrated in FIG. 6B comprises an additional conductive layer 670 and an insulating layer 660 that separates the core 610 from the conductive layer 670.
  • In some embodiments, one or more layers of the membrane system can be formed from materials such as silicone, polytetrafluoroethylene, polyethylene-co-tetrafluoroethylene, polyolefin, polyester, polycarbonate, biostable polytetrafluoroethylene, homopolymers, copolymers, terpolymers of polyurethanes, polypropylene (PP), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutylene terephthalate (PBT), polymethylmethacrylate (PMMA), polyether ether ketone (PEEK), polyamides, polyimides, polystyrenes, polyurethanes, cellulosic polymers, poly(ethylene oxide), poly(propylene oxide) and copolymers and blends thereof, polysulfones and block copolymers thereof including, for example, di-block, tri-block, alternating, random and graft copolymers.
  • In some embodiments, one or more layers of the membrane system are formed from a silicone polymer. In further embodiments, the silicone composition can have molecular weight of from about 50,000 to about 800,000 g/mol. It has been found that having the polymers formed with this molecular weight range facilitates the preparation of cross-linked membranes that provide the strength, tear resistance, stability, and toughness advantageous for use in vivo.
  • In some embodiments, the silicone polymer is a liquid silicone rubber that may be vulcanized using a metal- (e.g., platinum), peroxide-, heat-, ultraviolet-, or other radiation-catalyzed process. In some embodiments, the silicone polymer is a dimethyl- and methylhydrogen-siloxane copolymer. In some embodiments, the copolymer has vinyl substituents. In some embodiments, commercially available silicone polymers can be used. For example, commercially available silicone polymer precursor compositions can be used to prepare the blends, such as described below. In one embodiment, MED-4840 available from NUSIL® Technology LLC is used as a precursor to the silicone polymer used in the blend. MED-4840 consists of a 2-part silicone elastomer precursor including vinyl-functionalized dimethyl- and methylhydrogen-siloxane copolymers, amorphous silica, a platinum catalyst, a crosslinker, and an inhibitor. The two components can be mixed together and heated to initiate vulcanization, thereby forming an elastomeric solid material. Other suitable silicone polymer precursor systems include, but are not limited to, MED-2174 peroxide-cured liquid silicone rubber available from NUSIL® Technology LLC, SILASTIC® MDX4-4210 platinum-cured biomedical grade elastomer available from DOW CORNING®, and Implant Grade Liquid Silicone Polymer (durometers 10-50) available from Applied Silicone Corporation.
  • In some embodiments, one or more layer of the membrane system is formed from a blend of a silicone polymer and a hydrophilic polymer. By “hydrophilic polymer,” it is meant that the polymer has a substantially hydrophilic domain in which aqueous substances can easily dissolve. It has been found that use of such a blend may provide high oxygen solubility and allow for the transport of glucose or other such water-soluble molecules (for example, drugs) through the membrane. In one embodiment, the hydrophilic polymer comprises both a hydrophilic domain and a partially hydrophobic domain (e.g., a copolymer), whereby the partially hydrophobic domain facilitates the blending of the hydrophilic polymer with the hydrophobic silicone polymer. In one embodiment, the hydrophobic domain is itself a polymer (i.e., a polymeric hydrophobic domain). For example, in one embodiment, the hydrophobic domain is not a simple molecular head group but is rather polymeric.
  • The silicone polymer for use in the silicone/hydrophilic polymer blend can be any suitable silicone polymer, include those described above. The hydrophilic polymer for use in the silicone/hydrophilic polymer blend can be any suitable hydrophilic polymer, including but not limited to components such as polyvinylpyrrolidone (PVP), polyhydroxyethyl methacrylate, polyvinylalcohol, polyacrylic acid, polyethers such as polyethylene glycol or polypropylene oxide, and copolymers thereof, including, for example, di-block, tri-block, alternating, random, comb, star, dendritic, and graft copolymers (block copolymers are discussed in U.S. Pat. No. 4,803,243 and U.S. Pat. No. 4,686,044). In one embodiment, the hydrophilic polymer is a copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), such as PEO-PPO diblock copolymers, PPO-PEO-PPO triblock copolymers, PEO-PPO-PEO triblock copolymers, alternating block copolymers of PEO-PPO, random copolymers of ethylene oxide and propylene oxide, and blends thereof, for example. In some embodiments, the copolymers can be optionally substituted with hydroxy substituents. Commercially available examples of PEO and PPO copolymers include the PLURONIC® brand of polymers available from BASF®. Some PLURONIC® polymers are triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) having the general molecular structure:

  • HO—(CH2CH2O)x—(CH2CH2CH2O)y—(CH2CH2O)x—OH
  • wherein the repeat units x and y vary among various PLURONIC® products. The poly(ethylene oxide) blocks act as a hydrophilic domain allowing the dissolution of aqueous agents in the polymer. The poly(propylene oxide) block acts as a hydrophobic domain facilitating the blending of the PLURONIC® polymer with a silicone polymer. In one embodiment, PLURONIC® F-127 is used having x of approximately 100 and y of approximately 65. The molecular weight of PLURONIC® F-127 is approximately 12,600 g/mol as reported by the manufacture. Other PLURONIC® polymers include PPO-PEO-PPO triblock copolymers (e.g., PLURONIC® R products). Other suitable commercial polymers include, but are not limited to, SYNPERONICS® products available from UNIQEMA®.
  • The membrane system of some embodiments can comprise at least one polymer containing a surface-active group. The term “surface-active group” and “surface-active end group” as used herein are broad terms and are used in their ordinary sense, including, without limitation, surface-active oligomers or other surface-active moieties having surface-active properties, such as alkyl groups, which are inclined to migrate towards a surface of a membrane formed thereof. In some embodiments, the surface-active group-containing polymer is a surface-active end group-containing polymer. In some of these embodiments, the surface-active end group-containing polymer is a polymer having covalently bonded surface-active end groups. However, it is contemplated that other surface-active group-containing polymers may also be used and can be formed by modification of fully-reacted base polymers via the grafting of side chain structures, surface treatments or coatings applied after membrane fabrication (e.g., via surface-modifying additives), blending of a surface-modifying additive to a base polymer before membrane fabrication, immobilization of the surface-active-group-containing soft segments by physical entrainment during synthesis, or the like.
  • Base polymers useful for certain embodiments can include any linear or branched polymer on the backbone structure of the polymer. Suitable base polymers can include, but are not limited to, epoxies, polyolefins, polysiloxanes, polyethers, acrylics, polyesters, carbonates, and polyurethanes, wherein polyurethanes can include polyurethane copolymers such as polyether-urethane-urea, polycarbonate-urethane, polyether-urethane, silicone-polyether-urethane, silicone-polycarbonate-urethane, polyester-urethane, and the like. In some embodiments, base polymers can be selected for their bulk properties, such as, but not limited to, tensile strength, flex life, modulus, and the like. For example, polyurethanes are known to be relatively strong and to provide numerous reactive pathways, which properties may be advantageous as bulk properties for a membrane layer of the continuous sensor.
  • In some embodiments, a base polymer synthesized to have hydrophilic segments can be used to form at least a portion of the membrane system. For example, a linear base polymer including biocompatible segmented block polyurethane copolymers comprising hard and soft segments can be used. It is contemplated that polyisocyanates can be used for the preparation of the hard segments of the copolymer and may be aromatic or aliphatic diisocyanates. The soft segments used in the preparation of the polyurethane can be derived from a polyfunctional aliphatic polyol, a polyfunctional aliphatic or aromatic amine, or the like that can be useful for creating permeability of the analyte (e.g., glucose) therethrough, and can include, for example, polyvinyl acetate (PVA), poly(ethylene glycol) (PEG), polyacrylamide, acetates, polyethylene oxide (PEO), polyethylacrylate (PEA), polyvinylpyrrolidone (PVP), and variations thereof (e.g., PVP vinyl acetate).
  • Alternatively, in some embodiments, the membrane system can comprise a combination of a base polymer (e.g., polyurethane) and one or more hydrophilic polymers, such as, PVA, PEG, polyacrylamide, acetates, PEO, PEA, PVP, and variations thereof (e.g., PVP vinyl acetate), as a physical blend or admixture, wherein each polymer maintains its unique chemical nature. It is contemplated that any of a variety of combination of polymers can be used to yield a blend with desired glucose, oxygen, and interference permeability properties. For example, in some embodiments, the membrane can comprise a blend of a polycarbonate-urethane base polymer and PVP, but in other embodiments, a blend of a polyurethane, or another base polymer, and one or more hydrophilic polymers can be used instead. In some of the embodiments involving use of PVP, the PVP portion of the polymer blend can comprise from about 5% to about 50% by weight of the polymer blend, or from about 15% to 20%, or even from about 25% to 40%. It is contemplated that PVP of various molecular weights may be used. For example, in some embodiments, the molecular weight of the PVP used can be from about 25,000 daltons to about 5,000,000 daltons, or from about 50,000 daltons to about 2,000,000 daltons, or even greater than 5,000,000 daltons, for example, from 6,000,000 daltons to about 10,000,000 daltons.
  • Coating solutions that include at least two surface-active group-containing polymers can be made using any of the methods of forming polymer blends known in the art. In one exemplary embodiment, a solution of a polyurethane containing silicone end groups is mixed with a solution of a polyurethane containing fluorine end groups (e.g., wherein the solutions include the polymer dissolved in a suitable solvent such as acetone, ethyl alcohol, DMAC, THF, 2-butanone, and the like). The mixture can then be coated onto to the surface of the elongated conductive body using the coating process described elsewhere herein. The coating can then be cured under high temperature (e.g., about 50-150° C.), as the elongated conductive body is advanced through the drying/curing station.
  • Some amount of cross-linking agent can also be included in the mixture to induce cross-linking between polymer molecules. Non-limiting examples of suitable cross-linking agents include isocyanate, carbodiimide, gluteraldehyde or other aldehydes, epoxy, acrylates, free-radical based agents, ethylene glycol diglycidyl ether (EGDE), poly(ethylene glycol) diglycidyl ether (PEGDE), or dicumyl peroxide (DCP). In one embodiment, from about 0.1% to about 15% w/w of cross-linking agent is added relative to the total dry weights of cross-linking agent and polymers added when blending the ingredients (in one example, about 1% to about 10%). During the curing process, substantially all of the cross-linking agent is believed to react, leaving substantially no detectable unreacted cross-linking agent in the final film.
  • Described below are examples of layers that can be coated onto the elongated conductive body to form the membrane system.
  • Diffusion Resistance Layer
  • In some embodiments, the membrane system comprises a diffusion resistance layer, which may be disposed more distal to the elongated core than the other layers. A molar excess of glucose relative to the amount of oxygen exists in blood, i.e., for every free oxygen molecule in extracellular fluid, there are typically more than 100 glucose molecules present (see Updike et al., Diabetes Care 5:207-21(1982)). Accordingly, without a semipermeable membrane situated over the enzyme layer to control the flux of glucose and oxygen, a linear response to glucose levels can sometimes be obtained only up to about 40 mg/dL. However, in a clinical setting, a linear response to glucose levels is desirable up to at least about 500 mg/dL. The diffusion resistance layer serves to address these issues by controlling the flux of oxygen and other analytes (for example, glucose) to the underlying enzyme layer.
  • The diffusion resistance layer can include a semipermeable membrane that controls the flux of oxygen and glucose to the underlying enzyme layer, thereby rendering oxygen in non-rate-limiting excess. As a result, the upper limit of linearity of glucose measurement is extended to a much higher value than that which is achieved without the diffusion resistance layer. In some embodiments, the diffusion resistance layer exhibits an oxygen-to-glucose permeability ratio of approximately 200:1, but in other embodiments the oxygen-to-glucose permeability ratio can be approximately 100:1, 125:1, 130:1, 135:1, 150:1, 175:1, 225:1, 250:1, 275:1, 300:1, or 500:1. As a result of the high oxygen-to-glucose permeability ratio, one-dimensional reactant diffusion may provide sufficient excess oxygen at all reasonable glucose and oxygen concentrations found in the subcutaneous matrix (See Rhodes et al., Anal. Chem., 66:1520-1529 (1994)).
  • In some embodiments, the diffusion resistance layer is formed of a base polymer synthesized to include a polyurethane membrane with both hydrophilic and hydrophobic regions to control the diffusion of glucose and oxygen to an analyte sensor. A suitable hydrophobic polymer component can be a polyurethane or polyether urethane urea. Polyurethane is a polymer produced by the condensation reaction of a diisocyanate and a difunctional hydroxyl-containing material. A polyurea is a polymer produced by the condensation reaction of a diisocyanate and a difunctional amine-containing material. Diisocyanates that can be used include aliphatic diisocyanates containing from about 4 to about 8 methylene units. Diisocyanates containing cycloaliphatic moieties can also be useful in the preparation of the polymer and copolymer components of the membranes of some embodiments. The material that forms the basis of the hydrophobic matrix of the diffusion resistance layer can be any of those known in the art that is suitable for use as membranes in sensor devices and as having sufficient permeability to allow relevant compounds to pass through it, for example, to allow an oxygen molecule to pass through the membrane from the sample under examination in order to reach the active enzyme or electrochemical electrodes. Examples of materials which can be used to make non-polyurethane type membranes include vinyl polymers, polyethers, polyesters, polyamides, inorganic polymers such as polysiloxanes and polycarbosiloxanes, natural polymers such as cellulosic and protein based materials, and mixtures or combinations thereof.
  • In some embodiments, the diffusion resistance layer can comprise a blend of a base polymer (e.g., polyurethane) and one or more hydrophilic polymers (e.g., PVA, PEG, polyacrylamide, acetates, PEO, PEA, PVP, and variations thereof). It is contemplated that any of a variety of combination of polymers may be used to yield a blend with desired glucose, oxygen, and interference permeability properties. For example, in some embodiments, the diffusion resistance layer can be formed from a blend of a silicone polycarbonate-urethane base polymer and a PVP hydrophilic polymer, but in other embodiments, a blend of a polyurethane, or another base polymer, and one or more hydrophilic polymers can be used instead. In some of the embodiments involving the use of PVP, the PVP portion of the polymer blend can comprise from about 5% to about 50% by weight of the polymer blend, or from about 15% to 20%, and or from about 25% to 40%. It is contemplated that PVP of various molecular weights may be used. For example, in some embodiments, the molecular weight of the PVP used can be from about 25,000 daltons to about 5,000,000 daltons, or from about 50,000 daltons to about 2,000,000 daltons, or even greater than about 5,000,000 daltons, e.g., from 6,000,000 daltons to about 10,000,000 daltons.
  • In certain embodiments, the thickness of the diffusion resistance layer can be from about 0.05 microns or less to about 200 microns or more. In some of these embodiments, the thickness of the diffusion resistance layer can be from about 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 microns to about 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 19.5, 20, 30, 40, 50, 60, 70, 75, 80, 85, 90, 95, or 100 microns. In some embodiments, the thickness of the diffusion resistance layer is from about 2, 2.5 or 3 microns to about 3.5, 4, 4.5, or 5 microns in the case of a transcutaneously implanted sensor or from about 20 or 25 microns to about 40 or 50 microns in the case of a wholly implanted sensor.
  • The description herein of the diffusion resistance layer is not intended to be applicable only to the diffusion resistance layer; rather the description can also be applicable to any other layer of the membrane system, such as the enzyme layer, electrode layer, or interference layer, for example.
  • Enzyme Layer
  • In some embodiments, the membrane system comprises an enzyme layer, which may be disposed more proximal to the elongated core than the diffusion resistance layer. The enzyme layer comprises a catalyst configured to react with an analyte. In one embodiment, the enzyme layer is an immobilized enzyme layer including glucose oxidase. In other embodiments, the enzyme layer can be impregnated with other oxidases, for example, alcohol dehydrogenase, galactose oxidase, cholesterol oxidase, amino acid oxidase, alcohol oxidase, lactate oxidase, or uricase. For example, for an enzyme-based electrochemical glucose sensor to perform well, the sensor's response should neither be limited by enzyme activity nor cofactor concentration.
  • In some embodiments, the catalyst (enzyme) can be impregnated or otherwise immobilized into the diffusion resistance layer such that a separate enzyme layer is not required (e.g., wherein a unitary layer is provided including the functionality of the diffusion resistance layer and enzyme layer). In some embodiments, the enzyme layer is formed from a polyurethane, for example, aqueous dispersions of colloidal polyurethane polymers including the enzyme.
  • In some embodiments, the thickness of the enzyme layer can be from about 0.01, 0.05, 0.6, 0.7, or 0.8 microns to about 1, 1.2, 1.4, 1.5, 1.6, 1.8, 2, 2.1, 2.2, 2.5, 3, 4, 5, 10, 20, 30 40, 50, 60, 70, 80, 90, or 100 microns. In some embodiments, the thickness of the enzyme layer is from about 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 1.5, 2, 2.5, 3, 4, or 5 microns to about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 19.5, 20, 25, or 30 microns, or from about 2, 2.5, or 3 microns to about 3.5, 4, 4.5, or 5 microns in the case of a transcutaneously implanted sensor or from about 6, 7, or 8 microns to about 9, 10, 11, or 12 microns in the case of a wholly implanted sensor.
  • It should be understood that the description herein of the enzyme layer is not intended to be applicable only to the enzyme layer; rather the description can also be applicable to any other layer of the membrane system, such as the diffusion resistance layer, electrode layer, or interference layer, for example.
  • Electrode Layer
  • In some embodiments, the membrane system comprises an electrode layer, which may be disposed more proximal to the elongated core than any other layer. The electrode layer is configured to facilitate electrochemical reaction on the electroactive surface and can include a semipermeable coating for maintaining hydrophilicity at the electrochemically reactive surfaces of the sensor interface. In other embodiments, the functionality of the electrode layer can be incorporated into the diffusion resistance layer, so as to provide a unitary layer that includes the functionality of the diffusion resistance layer, enzyme layer, and/or electrode layer.
  • The electrode layer can enhance the stability of an adjacent layer by protecting and supporting the material that makes up the adjacent layer. The electrode layer may also assist in stabilizing the operation of the device by overcoming electrode start-up problems and drifting problems caused by inadequate electrolyte. The buffered electrolyte solution contained in the electrode layer may also protect against pH-mediated damage that can result from the formation of a large pH gradient between the substantially hydrophobic interference layer and the electrodes due to the electrochemical activity of the electrodes.
  • In one embodiment, the electrode domain includes hydrophilic polymer film (e.g., a flexible, water-swellable, hydrogel) having a “dry film” thickness of from about 0.05 microns or less to about 20 microns or more, or from about 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 1.5, 2, 2.5, 3, or 3.5 microns to about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 19.5 microns, or even from about 3, 2.5, 2, or 1 microns, or less, to about 3.5, 4, 4.5, or 5 microns or more. “Dry film” thickness refers to the thickness of a cured film cast from a coating formulation by standard coating techniques.
  • In certain embodiments, the electrode layer can be formed of a curable mixture of a urethane polymer and a hydrophilic polymer. In some of these embodiments, coatings are formed of a polyurethane polymer having anionic carboxylate functional groups and non-ionic hydrophilic polyether segments, wherein the polyurethane polymer undergoes aggregation with a water-soluble carbodiimide (e.g., 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)) in the presence of polyvinylpyrrolidone and cured at a moderate temperature of about 50° C.
  • Particularly suitable for this purpose are aqueous dispersions of fully-reacted colloidal polyurethane polymers having cross-linkable carboxyl functionality (e.g., BAYBOND®; Mobay Corporation). These polymers are supplied in dispersion grades having a polycarbonate-polyurethane backbone containing carboxylate groups identified as XW-121 and XW-123; and a polyester-polyurethane backbone containing carboxylate groups, identified as XW-110-2. In some embodiments, BAYBOND® 123, an aqueous anionic dispersion of an aliphatic polycarbonate urethane polymer sold as a 35 weight percent solution in water and co-solvent N-methyl-2-pyrrolidone, can be used.
  • In some embodiments, the electrode layer is formed from a hydrophilic polymer that renders the electrode layer substantially more hydrophilic than an overlying layer (e.g., interference layer, enzyme layer). Such hydrophilic polymers can include, a polyamide, a polylactone, a polyimide, a polylactam, a functionalized polyamide, a functionalized polylactone, a functionalized polyimide, a functionalized polylactam or combinations thereof, for example.
  • In some embodiments, the electrode layer is formed primarily from a hydrophilic polymer, and in some of these embodiments, the electrode layer is formed substantially from PVP. PVP is a hydrophilic water-soluble polymer and is available commercially in a range of viscosity grades and average molecular weights ranging from about 18,000 to about 500,000, under the PVP homopolymer series by BASF Wyandotte and by GAF Corporation. In certain embodiments, a PVP homopolymer having an average molecular weight of about 360,000 identified as PVP-K90 (BASF Wyandotte) can be used to form the electrode layer. Also suitable are hydrophilic, film-forming copolymers of N-vinylpyrrolidone, such as a copolymer of N-vinylpyrrolidone and vinyl acetate, a copolymer of N-vinylpyrrolidone, ethylmethacrylate and methacrylic acid monomers, and the like.
  • In certain embodiments, the electrode layer is formed entirely from a hydrophilic polymer. Useful hydrophilic polymers contemplated include, but are not limited to, poly-N-vinylpyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone, poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole, poly-N,N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid, polyethylene oxide, poly-2-ethyl-oxazoline, copolymers thereof and mixtures thereof. A blend of two or more hydrophilic polymers can be used in some embodiments.
  • It is contemplated that in certain embodiments, the hydrophilic polymer used may not be crosslinked, but in other embodiments, crosslinking may be used and achieved by any of a variety of methods, for example, by adding a crosslinking agent. In some embodiments, a polyurethane polymer can be crosslinked in the presence of PVP by preparing a premix of the polymers and adding a cross-linking agent just prior to the production of the membrane. Suitable cross-linking agents contemplated include, but are not limited to, carbodiimides (e.g., 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, UCARLNK®. XL-25 (Union Carbide)), epoxides and melamine/formaldehyde resins. Alternatively, it is also contemplated that crosslinking can be achieved by irradiation at a wavelength sufficient to promote crosslinking between the hydrophilic polymer molecules, which is believed to create a more tortuous diffusion path through the layer.
  • The flexibility and hardness of the coating can be varied as desired by varying the dry weight solids of the components in the coating formulation. The term “dry weight solids” as used herein is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to the dry weight percent based on the total coating composition after the time the crosslinker is included. In one embodiment, a coating formulation can contain from about 6 to about 20 dry weight percent, or about 8 dry weight percent, PVP; from about 3 to about 10 dry weight percent, or about 5 dry weight percent cross-linking agent; and from about 70 to about 91 weight percent, or about 87 weight percent of a polyurethane polymer, such as a polycarbonate-polyurethane polymer, for example. The reaction product of such a coating formulation is referred to herein as a water-swellable cross-linked matrix of polyurethane and PVP.
  • In some embodiments, underlying the electrode layer is an electrolyte phase that when hydrated is a free-fluid phase including a solution containing at least one compound, typically a soluble chloride salt, which conducts electric current. In one embodiment wherein the membrane system is used with a glucose sensor such as is described herein, the electrolyte phase flows over the electrodes and is in contact with the electrode layer. It is contemplated that certain embodiments can use any suitable electrolyte solution, including standard, commercially available solutions. Generally, the electrolyte phase can have the same osmotic pressure or a lower osmotic pressure than the sample being analyzed. In some embodiments, the electrolyte phase comprises normal saline.
  • It should be understood that the description herein of the electrode layer is not intended to be applicable only to the electrode layer; rather the description can also be applicable to any other layer of the membrane system, such as the diffusion resistance layer, enzyme layer, or interference layer, for example.
  • Interference Layer
  • In some embodiments, the membrane system may comprise an interference layer configured to substantially reduce the permeation of one or more interferents into the electrochemically reactive surfaces. The interference layer may be configured to be substantially less permeable to one or more of the interferents than to the measured species. It is also contemplated that in some embodiments, where interferent blocking may be provided by the diffusion resistance layer (e.g., via a surface-active group-containing polymer of the diffusion resistance layer), a separate interference layer may not be used.
  • In some embodiments, the interference layer is formed from a silicone-containing polymer, such as a polyurethane containing silicone, or a silicone polymer. While not wishing to be bound by theory, it is believed that, in order for an enzyme-based glucose sensor to function properly, glucose would not have to permeate the interference layer, where the interference layer is located more proximal to the electroactive surfaces than the enzyme layer. Accordingly, in some embodiments, a silicone-containing interference layer, comprising a greater percentage of silicone by weight than the diffusion resistance layer, can be used without substantially affecting glucose concentration measurements. For example, in some embodiments, the silicone-containing interference layer can comprise a polymer with a high percentage of silicone (e.g., from about 25%, 30%, 35%, 40%, 45%, or 50% to about 60%, 70%, 80%, 90% or 95%).
  • In one embodiment, the interference layer can include ionic components incorporated into a polymeric matrix to reduce the permeability of the interference layer to ionic interferents having the same charge as the ionic components. In another embodiment, the interference layer can include a catalyst (for example, peroxidase) for catalyzing a reaction that removes interferents.
  • In certain embodiments, the interference layer can include a thin membrane that is designed to limit diffusion of certain species, for example, those greater than 34 kD in molecular weight. In these embodiments, the interference layer permits certain substances (for example, hydrogen peroxide) that are to be measured by the electrodes to pass through, and prevents passage of other substances, such as potentially interfering substances. In one embodiment, the interference layer is constructed of polyurethane. In an alternative embodiment, the interference layer comprises a high oxygen soluble polymer, such as silicone.
  • In some embodiments, the interference layer is formed from one or more cellulosic derivatives. In general, cellulosic derivatives can include polymers such as cellulose acetate, cellulose acetate butyrate, 2-hydroxyethyl cellulose, cellulose acetate phthalate, cellulose acetate propionate, cellulose acetate trimellitate, or blends and combinations thereof.
  • In some alternative embodiments, other polymer types that can be utilized as a base material for the interference layer include polyurethanes, polymers having pendant ionic groups, and polymers having controlled pore size, for example. In one such alternative embodiment, the interference layer includes a thin, hydrophobic membrane that is non-swellable and restricts diffusion of low molecular weight species. The interference layer is permeable to relatively low molecular weight substances, such as hydrogen peroxide, but restricts the passage of higher molecular weight substances, including glucose and ascorbic acid.
  • It is contemplated that in some embodiments, the thickness of the interference layer can be from about 0.01 microns or less to about 20 microns or more. In some of these embodiments, the thickness of the interference layer can be from about 0.01, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 1.5, 2, 2.5, 3, or 3.5 microns to about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 19.5 microns. In some of these embodiments, the thickness of the interference layer can be from about 0.2, 0.4, 0.5, or 0.6, microns to about 0.8, 0.9, 1, 1.5, 2, 3, or 4 microns.
  • It should be understood that the description herein of the interference layer is not intended to be applicable only to the interference layer; rather the description can also be applicable to any other layer of the membrane system, such as the diffusion resistance layer, enzyme layer, or electrode layer, for example.
  • Therapeutic Agents
  • A variety of therapeutic (bioactive) agents can be used with the analyte sensor system. In some embodiments, the therapeutic agent is an anticoagulant for preventing coagulation within or on the sensor. In some embodiments, the therapeutic agent is an antimicrobial, such as but not limited to an antibiotic or antifungal compound. In some embodiments, the therapeutic agent is an antiseptic and/or disinfectant. Therapeutic agents can be used alone or in combination of two or more agents. The therapeutic agents can be dispersed throughout the material of the sensor. In some embodiments, the membrane system can include a therapeutic agent that is incorporated into a portion of the membrane system, or which is incorporated into the device and adapted to diffuse through the membrane.
  • There are a variety of systems and methods by which the therapeutic agent can be incorporated into the membrane system. In some embodiments, the therapeutic agent is incorporated at the time of manufacture of the membrane system. For example, the therapeutic agent can be blended prior to curing the membrane system. In other embodiments, the therapeutic agent is incorporated subsequent to membrane system manufacture, for example, by coating, imbibing, solvent-casting, or sorption of the bioactive agent into the membrane system. Although the therapeutic agent can be incorporated into the membrane system, in some embodiments the therapeutic agent can be administered concurrently with, prior to, or after insertion of the device intravascularly, for example, by oral administration, or locally, for example, by subcutaneous injection near the implantation site. In some embodiments, a combination of therapeutic agent incorporated in the membrane system and therapeutic agent administration locally and/or systemically can be used.
  • To the extent publications and patents or patent applications incorporated by reference herein contradict the disclosure contained in the specification, the specification is intended to supersede and/or take precedence over any such contradictory material.
  • Terms and phrases used in this document, and variations thereof, unless otherwise expressly stated, should be construed as open ended as opposed to limiting. As examples of the foregoing, the term “including” should be read to mean “including, without limitation” or the like; the term “comprising” as used herein is synonymous with “including”, “containing”, or “characterized by”, and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps; the term “example” is used to provide exemplary instances of the item in discussion, not an exhaustive or limiting list thereof; adjectives such as “known”, “conventional”, “normal”, “standard”, and terms of similar meaning should not be construed as limiting the item described to a given time period or to an item available as of a given time, but instead should be read to encompass known, normal, or standard technologies that may be available or known now or at any time in the future; and use of terms like “preferred”, “desired”, or “desirable”, and terms of similar meaning should not be understood as implying that certain features are critical, essential, or even important to the structure or function of the invention, but instead as merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the invention. Likewise, a group of items linked with the conjunction “and” should not be read as requiring that each and every one of those items be present in the grouping, but rather should be read as “and/or” unless expressly stated otherwise. Similarly, a group of items linked with the conjunction “or” should not be read as requiring mutual exclusivity among that group, but rather should be read as “and/or” unless expressly stated otherwise. In addition, as used in this application, the articles “a” and “an” should be construed as referring to one or more than one (i.e., to at least one) of the grammatical objects of the article. By way of example, “an element” means one element or more than one element.
  • The presence in some instances of broadening words and phrases such as “one or more”, “at least”, “but not limited to”, or other like phrases should not be read to mean that the narrower case is intended or required in instances where such broadening phrases may be absent.
  • All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth herein are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of any claims in any application claiming priority to the present application, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.
  • Furthermore, although the foregoing has been described in some detail by way of illustrations and examples for purposes of clarity and understanding, it is apparent to those skilled in the art that certain changes and modifications may be practiced. Therefore, the description and examples should not be construed as limiting the scope of the invention to the specific embodiments and examples described herein, but rather to also cover all modification and alternatives coming with the true scope and spirit of the invention.

Claims (8)

1. A system for manufacturing a continuous analyte sensor, the system comprising:
a coating vessel configured to hold a coating material in liquid form;
a reel-to-reel system configured to advance an elongated conductive body through the coating material, whereby the coating material is applied to the elongated conductive body;
a thickness measurement sensor configured to measure a dimension indicative of a thickness of a coating formed from the coating material applied to the elongated conductive body;
an etching system configured to remove a portion of the coating material applied to the elongated conductive body; and
a cutter configured to cut the elongated conductive body into a plurality of sections, wherein each section is associated with an individual continuous analyte sensor.
2. The system of claim 1, further comprising a die configured to remove a portion of the coating material applied to the elongated conductive body.
3. The system of claim 1, wherein the elongated conductive body is a wire with a circular cross-sectional shape or a substantially circular cross-sectional shape.
4. The system of claim 1, wherein the coating material comprises an insulating material selected from the group consisting of polyurethane, polyethylene, and polyimide.
5. The system of claim 1, wherein the coating material comprises a conductive material selected from the group consisting of platinum, silver/silver chloride, platinum-iridium, gold, palladium, iridium, graphite, carbon, conductive polymers, and alloys and combinations thereof.
6. The system of claim 1, further comprising a pump and conduit system configured to circulate the coating material in liquid form in the coating vessel to provide a meniscus at a wall of the coating vessel.
7. The system of claim 1, wherein coating material is a component of a solution, wherein the solution is controlled to have a predetermined viscosity.
8. The system of claim 7, wherein the viscosity is controlled by selecting a concentration of the coating material in the solution or by selecting a solution temperature.
US12/829,337 2009-07-02 2010-07-01 Continuous analyte sensors and methods of making same Abandoned US20110024043A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US12/829,337 US20110024043A1 (en) 2009-07-02 2010-07-01 Continuous analyte sensors and methods of making same
US14/155,814 US20140123893A1 (en) 2009-07-02 2014-01-15 Continuous analyte sensors and methods of making same
US14/451,332 US20140343386A1 (en) 2009-07-02 2014-08-04 Continuous analyte sensors and methods of making same
US16/452,364 US20190307371A1 (en) 2009-07-02 2019-06-25 Continuous analyte sensors and methods of making same
US17/867,608 US20220346674A1 (en) 2009-07-02 2022-07-18 Continuous analyte sensors and methods of making same

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US22271609P 2009-07-02 2009-07-02
US22275109P 2009-07-02 2009-07-02
US22281509P 2009-07-02 2009-07-02
US12/829,337 US20110024043A1 (en) 2009-07-02 2010-07-01 Continuous analyte sensors and methods of making same

Related Child Applications (3)

Application Number Title Priority Date Filing Date
US14/155,814 Continuation US20140123893A1 (en) 2009-07-02 2014-01-15 Continuous analyte sensors and methods of making same
US14/451,332 Continuation US20140343386A1 (en) 2009-07-02 2014-08-04 Continuous analyte sensors and methods of making same
US16/452,364 Continuation US20190307371A1 (en) 2009-07-02 2019-06-25 Continuous analyte sensors and methods of making same

Publications (1)

Publication Number Publication Date
US20110024043A1 true US20110024043A1 (en) 2011-02-03

Family

ID=43411768

Family Applications (21)

Application Number Title Priority Date Filing Date
US12/829,340 Abandoned US20110027458A1 (en) 2009-07-02 2010-07-01 Continuous analyte sensors and methods of making same
US12/829,296 Active 2030-12-27 US8828201B2 (en) 2009-07-02 2010-07-01 Analyte sensors and methods of manufacturing same
US12/829,337 Abandoned US20110024043A1 (en) 2009-07-02 2010-07-01 Continuous analyte sensors and methods of making same
US12/829,264 Abandoned US20110024307A1 (en) 2009-07-02 2010-07-01 Analyte sensor
US12/829,306 Active 2034-03-23 US9237864B2 (en) 2009-07-02 2010-07-01 Analyte sensors and methods of manufacturing same
US12/829,339 Abandoned US20110027453A1 (en) 2009-07-02 2010-07-01 Continuous analyte sensors and methods of making same
US12/829,318 Active 2034-04-15 US9131885B2 (en) 2009-07-02 2010-07-01 Analyte sensors and methods of manufacturing same
US14/058,091 Active US9320466B2 (en) 2009-07-02 2013-10-18 Analyte sensor
US14/057,720 Active US9907497B2 (en) 2009-07-02 2013-10-18 Analyte sensor
US14/155,814 Abandoned US20140123893A1 (en) 2009-07-02 2014-01-15 Continuous analyte sensors and methods of making same
US14/451,332 Abandoned US20140343386A1 (en) 2009-07-02 2014-08-04 Continuous analyte sensors and methods of making same
US14/960,011 Active US9763608B2 (en) 2009-07-02 2015-12-04 Analyte sensors and methods of manufacturing same
US15/683,657 Abandoned US20180000388A1 (en) 2009-07-02 2017-08-22 Analyte sensors and methods of manufacturing same
US15/877,682 Active US10420494B2 (en) 2009-07-02 2018-01-23 Analyte sensor
US16/250,992 Abandoned US20190167163A1 (en) 2009-07-02 2019-01-17 Analyte sensors and methods of manufacturing same
US16/452,364 Abandoned US20190307371A1 (en) 2009-07-02 2019-06-25 Continuous analyte sensors and methods of making same
US16/537,419 Active 2032-05-30 US11559229B2 (en) 2009-07-02 2019-08-09 Analyte sensor
US17/444,148 Abandoned US20210353185A1 (en) 2009-07-02 2021-07-30 Analyte sensors and methods of manufacturing same
US17/867,608 Pending US20220346674A1 (en) 2009-07-02 2022-07-18 Continuous analyte sensors and methods of making same
US18/145,220 Pending US20230129853A1 (en) 2009-07-02 2022-12-22 Analyte sensor
US18/182,941 Pending US20230301563A1 (en) 2009-07-02 2023-03-13 Analyte sensors and methods of manufacturing same

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US12/829,340 Abandoned US20110027458A1 (en) 2009-07-02 2010-07-01 Continuous analyte sensors and methods of making same
US12/829,296 Active 2030-12-27 US8828201B2 (en) 2009-07-02 2010-07-01 Analyte sensors and methods of manufacturing same

Family Applications After (18)

Application Number Title Priority Date Filing Date
US12/829,264 Abandoned US20110024307A1 (en) 2009-07-02 2010-07-01 Analyte sensor
US12/829,306 Active 2034-03-23 US9237864B2 (en) 2009-07-02 2010-07-01 Analyte sensors and methods of manufacturing same
US12/829,339 Abandoned US20110027453A1 (en) 2009-07-02 2010-07-01 Continuous analyte sensors and methods of making same
US12/829,318 Active 2034-04-15 US9131885B2 (en) 2009-07-02 2010-07-01 Analyte sensors and methods of manufacturing same
US14/058,091 Active US9320466B2 (en) 2009-07-02 2013-10-18 Analyte sensor
US14/057,720 Active US9907497B2 (en) 2009-07-02 2013-10-18 Analyte sensor
US14/155,814 Abandoned US20140123893A1 (en) 2009-07-02 2014-01-15 Continuous analyte sensors and methods of making same
US14/451,332 Abandoned US20140343386A1 (en) 2009-07-02 2014-08-04 Continuous analyte sensors and methods of making same
US14/960,011 Active US9763608B2 (en) 2009-07-02 2015-12-04 Analyte sensors and methods of manufacturing same
US15/683,657 Abandoned US20180000388A1 (en) 2009-07-02 2017-08-22 Analyte sensors and methods of manufacturing same
US15/877,682 Active US10420494B2 (en) 2009-07-02 2018-01-23 Analyte sensor
US16/250,992 Abandoned US20190167163A1 (en) 2009-07-02 2019-01-17 Analyte sensors and methods of manufacturing same
US16/452,364 Abandoned US20190307371A1 (en) 2009-07-02 2019-06-25 Continuous analyte sensors and methods of making same
US16/537,419 Active 2032-05-30 US11559229B2 (en) 2009-07-02 2019-08-09 Analyte sensor
US17/444,148 Abandoned US20210353185A1 (en) 2009-07-02 2021-07-30 Analyte sensors and methods of manufacturing same
US17/867,608 Pending US20220346674A1 (en) 2009-07-02 2022-07-18 Continuous analyte sensors and methods of making same
US18/145,220 Pending US20230129853A1 (en) 2009-07-02 2022-12-22 Analyte sensor
US18/182,941 Pending US20230301563A1 (en) 2009-07-02 2023-03-13 Analyte sensors and methods of manufacturing same

Country Status (3)

Country Link
US (21) US20110027458A1 (en)
EP (4) EP3970610A3 (en)
WO (3) WO2011003036A2 (en)

Cited By (143)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040171921A1 (en) * 1998-04-30 2004-09-02 James Say Analyte monitoring device and methods of use
US20060189863A1 (en) * 1998-04-30 2006-08-24 Abbott Diabetes Care, Inc. Analyte monitoring device and methods of use
US20070191699A1 (en) * 1998-04-30 2007-08-16 Abbott Diabetes Care, Inc. Analyte Monitoring Device and Methods of Use
US20080086039A1 (en) * 2001-01-02 2008-04-10 Abbott Diabetes Care, Inc. Analyte Monitoring Device And Methods Of Use
US20080200897A1 (en) * 2007-02-19 2008-08-21 Abbott Diabetes Care, Inc. Modular combination of medication infusion and analyte monitoring
US20080300476A1 (en) * 2007-05-31 2008-12-04 Abbott Diabetes Care, Inc. Insertion devices and methods
US20090054746A1 (en) * 2005-09-30 2009-02-26 Abbott Diabetes Care, Inc. Device for channeling fluid and methods of use
US20090063402A1 (en) * 2007-08-31 2009-03-05 Abbott Diabetes Care, Inc. Method and System for Providing Medication Level Determination
US20100057042A1 (en) * 2008-08-31 2010-03-04 Abbott Diabetes Care, Inc. Closed Loop Control With Improved Alarm Functions
US20100056992A1 (en) * 2008-08-31 2010-03-04 Abbott Diabetes Care, Inc. Variable Rate Closed Loop Control And Methods
US20100081906A1 (en) * 2008-09-30 2010-04-01 Abbott Diabetes Care, Inc. Analyte Sensor Sensitivity Attenuation Mitigation
US20100204557A1 (en) * 2007-02-18 2010-08-12 Abbott Diabetes Care Inc. Multi-Function Analyte Test Device and Methods Therefor
US20100234710A1 (en) * 2008-03-28 2010-09-16 Abbott Diabetes Care Inc. Analyte Sensor Calibration Management
US20110021889A1 (en) * 2009-07-23 2011-01-27 Abbott Diabetes Care Inc. Continuous Analyte Measurement Systems and Systems and Methods for Implanting Them
US20110027458A1 (en) * 2009-07-02 2011-02-03 Dexcom, Inc. Continuous analyte sensors and methods of making same
US20110054275A1 (en) * 2009-08-31 2011-03-03 Abbott Diabetes Care Inc. Mounting Unit Having a Sensor and Associated Circuitry
US8287454B2 (en) 1998-04-30 2012-10-16 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8346337B2 (en) 1998-04-30 2013-01-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8465425B2 (en) 1998-04-30 2013-06-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8478557B2 (en) 2009-07-31 2013-07-02 Abbott Diabetes Care Inc. Method and apparatus for providing analyte monitoring system calibration accuracy
US8497777B2 (en) 2009-04-15 2013-07-30 Abbott Diabetes Care Inc. Analyte monitoring system having an alert
US8514086B2 (en) 2009-08-31 2013-08-20 Abbott Diabetes Care Inc. Displays for a medical device
US8512243B2 (en) 2005-09-30 2013-08-20 Abbott Diabetes Care Inc. Integrated introducer and transmitter assembly and methods of use
US8532935B2 (en) 2009-01-29 2013-09-10 Abbott Diabetes Care Inc. Method and device for providing offset model based calibration for analyte sensor
US8545403B2 (en) 2005-12-28 2013-10-01 Abbott Diabetes Care Inc. Medical device insertion
WO2013152090A2 (en) 2012-04-04 2013-10-10 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US8560038B2 (en) 2007-05-14 2013-10-15 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8571808B2 (en) 2007-05-14 2013-10-29 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8602991B2 (en) 2005-08-30 2013-12-10 Abbott Diabetes Care Inc. Analyte sensor introducer and methods of use
WO2013184566A2 (en) 2012-06-05 2013-12-12 Dexcom, Inc. Systems and methods for processing analyte data and generating reports
US8612163B2 (en) 2007-05-14 2013-12-17 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
WO2014004460A1 (en) 2012-06-29 2014-01-03 Dexcom, Inc. Use of sensor redundancy to detect sensor failures
WO2014011488A2 (en) 2012-07-09 2014-01-16 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
US8635046B2 (en) 2010-06-23 2014-01-21 Abbott Diabetes Care Inc. Method and system for evaluating analyte sensor response characteristics
US8676513B2 (en) 2009-01-29 2014-03-18 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US8682615B2 (en) 2007-05-14 2014-03-25 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8688188B2 (en) 1998-04-30 2014-04-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
WO2014052080A1 (en) 2012-09-28 2014-04-03 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
US8710993B2 (en) 2011-11-23 2014-04-29 Abbott Diabetes Care Inc. Mitigating single point failure of devices in an analyte monitoring system and methods thereof
US8718739B2 (en) 2008-03-28 2014-05-06 Abbott Diabetes Care Inc. Analyte sensor calibration management
US20140134335A1 (en) * 2012-11-09 2014-05-15 Evonik Industries Ag Use and production of coated filaments for extrusion-based 3d printing processes
US8764657B2 (en) 2010-03-24 2014-07-01 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US8795252B2 (en) 2008-08-31 2014-08-05 Abbott Diabetes Care Inc. Robust closed loop control and methods
US8798934B2 (en) 2009-07-23 2014-08-05 Abbott Diabetes Care Inc. Real time management of data relating to physiological control of glucose levels
US8834366B2 (en) 2007-07-31 2014-09-16 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor calibration
WO2014158405A2 (en) 2013-03-14 2014-10-02 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
WO2014158327A2 (en) 2013-03-14 2014-10-02 Dexcom, Inc. Advanced calibration for analyte sensors
US8852101B2 (en) 2005-12-28 2014-10-07 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US8862198B2 (en) 2006-09-10 2014-10-14 Abbott Diabetes Care Inc. Method and system for providing an integrated analyte sensor insertion device and data processing unit
US9008743B2 (en) 2007-04-14 2015-04-14 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US9031630B2 (en) 2006-02-28 2015-05-12 Abbott Diabetes Care Inc. Analyte sensors and methods of use
US9066695B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9113828B2 (en) 2006-10-25 2015-08-25 Abbott Diabetes Care Inc. Method and system for providing analyte monitoring
US9125548B2 (en) 2007-05-14 2015-09-08 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
WO2015156966A1 (en) 2014-04-10 2015-10-15 Dexcom, Inc. Sensors for continuous analyte monitoring, and related methods
US9204827B2 (en) 2007-04-14 2015-12-08 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US20160033199A1 (en) * 2014-07-29 2016-02-04 Hitachi Metals, Ltd. Method and apparatus for manufacturing enameled wire
US9259175B2 (en) 2006-10-23 2016-02-16 Abbott Diabetes Care, Inc. Flexible patch for fluid delivery and monitoring body analytes
US9310230B2 (en) 2009-04-29 2016-04-12 Abbott Diabetes Care Inc. Method and system for providing real time analyte sensor calibration with retrospective backfill
US9320461B2 (en) 2009-09-29 2016-04-26 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
US9320468B2 (en) 2008-01-31 2016-04-26 Abbott Diabetes Care Inc. Analyte sensor with time lag compensation
US9326727B2 (en) 2006-01-30 2016-05-03 Abbott Diabetes Care Inc. On-body medical device securement
US9326707B2 (en) 2008-11-10 2016-05-03 Abbott Diabetes Care Inc. Alarm characterization for analyte monitoring devices and systems
US9332934B2 (en) 2007-10-23 2016-05-10 Abbott Diabetes Care Inc. Analyte sensor with lag compensation
US9339217B2 (en) 2011-11-25 2016-05-17 Abbott Diabetes Care Inc. Analyte monitoring system and methods of use
US9351669B2 (en) 2009-09-30 2016-05-31 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
US9357959B2 (en) 2006-10-02 2016-06-07 Abbott Diabetes Care Inc. Method and system for dynamically updating calibration parameters for an analyte sensor
US9392969B2 (en) 2008-08-31 2016-07-19 Abbott Diabetes Care Inc. Closed loop control and signal attenuation detection
US9398882B2 (en) 2005-09-30 2016-07-26 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor and data processing device
US9402544B2 (en) 2009-02-03 2016-08-02 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US9402570B2 (en) 2011-12-11 2016-08-02 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
US9408566B2 (en) 2006-08-09 2016-08-09 Abbott Diabetes Care Inc. Method and system for providing calibration of an analyte sensor in an analyte monitoring system
US9439586B2 (en) 2007-10-23 2016-09-13 Abbott Diabetes Care Inc. Assessing measures of glycemic variability
US9474475B1 (en) 2013-03-15 2016-10-25 Abbott Diabetes Care Inc. Multi-rate analyte sensor data collection with sample rate configurable signal processing
US9483608B2 (en) 2007-05-14 2016-11-01 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9521968B2 (en) 2005-09-30 2016-12-20 Abbott Diabetes Care Inc. Analyte sensor retention mechanism and methods of use
US9541556B2 (en) 2008-05-30 2017-01-10 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US9558325B2 (en) 2007-05-14 2017-01-31 Abbott Diabetes Care Inc. Method and system for determining analyte levels
US9572534B2 (en) 2010-06-29 2017-02-21 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
CN106475268A (en) * 2016-12-22 2017-03-08 苏州振瑞昌材料科技有限公司 A kind of strengthening core masking liquid equipment
US9615780B2 (en) 2007-04-14 2017-04-11 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US9622691B2 (en) 2011-10-31 2017-04-18 Abbott Diabetes Care Inc. Model based variable risk false glucose threshold alarm prevention mechanism
US9662056B2 (en) 2008-09-30 2017-05-30 Abbott Diabetes Care Inc. Optimizing analyte sensor calibration
US9675290B2 (en) 2012-10-30 2017-06-13 Abbott Diabetes Care Inc. Sensitivity calibration of in vivo sensors used to measure analyte concentration
US20170173735A1 (en) * 2015-12-18 2017-06-22 Illinois Tool Works Inc. Wire manufactured by additive manufacturing methods
US9721063B2 (en) 2011-11-23 2017-08-01 Abbott Diabetes Care Inc. Compatibility mechanisms for devices in a continuous analyte monitoring system and methods thereof
US9743862B2 (en) 2011-03-31 2017-08-29 Abbott Diabetes Care Inc. Systems and methods for transcutaneously implanting medical devices
US9788771B2 (en) 2006-10-23 2017-10-17 Abbott Diabetes Care Inc. Variable speed sensor insertion devices and methods of use
US9882660B2 (en) 2006-10-26 2018-01-30 Abbott Diabetes Care Inc. Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors
US9907492B2 (en) 2012-09-26 2018-03-06 Abbott Diabetes Care Inc. Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data
US9913600B2 (en) 2007-06-29 2018-03-13 Abbott Diabetes Care Inc. Analyte monitoring and management device and method to analyze the frequency of user interaction with the device
US9931075B2 (en) 2008-05-30 2018-04-03 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US9943644B2 (en) 2008-08-31 2018-04-17 Abbott Diabetes Care Inc. Closed loop control with reference measurement and methods thereof
US9980670B2 (en) 2002-11-05 2018-05-29 Abbott Diabetes Care Inc. Sensor inserter assembly
US10002233B2 (en) 2007-05-14 2018-06-19 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10031002B2 (en) 2007-05-14 2018-07-24 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10028680B2 (en) 2006-04-28 2018-07-24 Abbott Diabetes Care Inc. Introducer assembly and methods of use
US10078380B2 (en) 2010-03-10 2018-09-18 Abbott Diabetes Care Inc. Systems, devices and methods for managing glucose levels
US10076285B2 (en) 2013-03-15 2018-09-18 Abbott Diabetes Care Inc. Sensor fault detection using analyte sensor data pattern comparison
US10092229B2 (en) 2010-06-29 2018-10-09 Abbott Diabetes Care Inc. Calibration of analyte measurement system
US10111608B2 (en) 2007-04-14 2018-10-30 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US10117606B2 (en) 2009-10-30 2018-11-06 Abbott Diabetes Care Inc. Method and apparatus for detecting false hypoglycemic conditions
US10117614B2 (en) 2006-02-28 2018-11-06 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US10132793B2 (en) 2012-08-30 2018-11-20 Abbott Diabetes Care Inc. Dropout detection in continuous analyte monitoring data during data excursions
US10136845B2 (en) 2011-02-28 2018-11-27 Abbott Diabetes Care Inc. Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same
US10173007B2 (en) 2007-10-23 2019-01-08 Abbott Diabetes Care Inc. Closed loop control system with safety parameters and methods
US10194863B2 (en) 2005-09-30 2019-02-05 Abbott Diabetes Care Inc. Integrated transmitter unit and sensor introducer mechanism and methods of use
US10194850B2 (en) 2005-08-31 2019-02-05 Abbott Diabetes Care Inc. Accuracy of continuous glucose sensors
US10213139B2 (en) 2015-05-14 2019-02-26 Abbott Diabetes Care Inc. Systems, devices, and methods for assembling an applicator and sensor control device
US10226207B2 (en) 2004-12-29 2019-03-12 Abbott Diabetes Care Inc. Sensor inserter having introducer
US20190152713A1 (en) * 2017-11-21 2019-05-23 Chemcut Holdings LLC Lightweight roller
US10328201B2 (en) 2008-07-14 2019-06-25 Abbott Diabetes Care Inc. Closed loop control system interface and methods
US10433773B1 (en) 2013-03-15 2019-10-08 Abbott Diabetes Care Inc. Noise rejection methods and apparatus for sparsely sampled analyte sensor data
US10555695B2 (en) 2011-04-15 2020-02-11 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US10561349B2 (en) 2016-03-31 2020-02-18 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
EP3654348A1 (en) 2012-11-07 2020-05-20 Dexcom, Inc. Systems and methods for managing glycemic variability
US10674944B2 (en) 2015-05-14 2020-06-09 Abbott Diabetes Care Inc. Compact medical device inserters and related systems and methods
US10685749B2 (en) 2007-12-19 2020-06-16 Abbott Diabetes Care Inc. Insulin delivery apparatuses capable of bluetooth data transmission
USD902408S1 (en) 2003-11-05 2020-11-17 Abbott Diabetes Care Inc. Analyte sensor control unit
US10856736B2 (en) 2012-12-31 2020-12-08 Dexcom, Inc. Remote monitoring of analyte measurements
US10860687B2 (en) 2012-12-31 2020-12-08 Dexcom, Inc. Remote monitoring of analyte measurements
US10874338B2 (en) 2010-06-29 2020-12-29 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US10932672B2 (en) 2015-12-28 2021-03-02 Dexcom, Inc. Systems and methods for remote and host monitoring communications
US10985804B2 (en) 2013-03-14 2021-04-20 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
US11000215B1 (en) 2003-12-05 2021-05-11 Dexcom, Inc. Analyte sensor
USD924406S1 (en) 2010-02-01 2021-07-06 Abbott Diabetes Care Inc. Analyte sensor inserter
US11071478B2 (en) 2017-01-23 2021-07-27 Abbott Diabetes Care Inc. Systems, devices and methods for analyte sensor insertion
US11112377B2 (en) 2015-12-30 2021-09-07 Dexcom, Inc. Enzyme immobilized adhesive layer for analyte sensors
EP3925522A1 (en) 2017-06-23 2021-12-22 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US11213226B2 (en) 2010-10-07 2022-01-04 Abbott Diabetes Care Inc. Analyte monitoring devices and methods
US11229382B2 (en) 2013-12-31 2022-01-25 Abbott Diabetes Care Inc. Self-powered analyte sensor and devices using the same
US11298058B2 (en) 2005-12-28 2022-04-12 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US11331022B2 (en) 2017-10-24 2022-05-17 Dexcom, Inc. Pre-connected analyte sensors
US11350862B2 (en) 2017-10-24 2022-06-07 Dexcom, Inc. Pre-connected analyte sensors
USD961778S1 (en) 2006-02-28 2022-08-23 Abbott Diabetes Care Inc. Analyte sensor device
EP4046571A1 (en) 2015-10-21 2022-08-24 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
USD962446S1 (en) 2009-08-31 2022-08-30 Abbott Diabetes Care, Inc. Analyte sensor device
US11553883B2 (en) 2015-07-10 2023-01-17 Abbott Diabetes Care Inc. System, device and method of dynamic glucose profile response to physiological parameters
US11596330B2 (en) 2017-03-21 2023-03-07 Abbott Diabetes Care Inc. Methods, devices and system for providing diabetic condition diagnosis and therapy
USD982762S1 (en) 2020-12-21 2023-04-04 Abbott Diabetes Care Inc. Analyte sensor inserter
US11717225B2 (en) 2014-03-30 2023-08-08 Abbott Diabetes Care Inc. Method and apparatus for determining meal start and peak events in analyte monitoring systems
USD1002852S1 (en) 2019-06-06 2023-10-24 Abbott Diabetes Care Inc. Analyte sensor device
US11892426B2 (en) 2012-06-29 2024-02-06 Dexcom, Inc. Devices, systems, and methods to compensate for effects of temperature on implantable sensors

Families Citing this family (134)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7920906B2 (en) 2005-03-10 2011-04-05 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US9247900B2 (en) 2004-07-13 2016-02-02 Dexcom, Inc. Analyte sensor
US20060020192A1 (en) 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US8251907B2 (en) * 2005-02-14 2012-08-28 Optiscan Biomedical Corporation System and method for determining a treatment dose for a patient
WO2009051901A2 (en) 2007-08-30 2009-04-23 Pepex Biomedical, Llc Electrochemical sensor and method for manufacturing
WO2009032760A2 (en) 2007-08-30 2009-03-12 Pepex Biomedical Llc Electrochmical sensor and method for manufacturing
US11730407B2 (en) 2008-03-28 2023-08-22 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8583204B2 (en) * 2008-03-28 2013-11-12 Dexcom, Inc. Polymer membranes for continuous analyte sensors
WO2010056878A2 (en) 2008-11-14 2010-05-20 Pepex Biomedical, Llc Electrochemical sensor module
US8506740B2 (en) 2008-11-14 2013-08-13 Pepex Biomedical, Llc Manufacturing electrochemical sensor module
US8951377B2 (en) 2008-11-14 2015-02-10 Pepex Biomedical, Inc. Manufacturing electrochemical sensor module
US9351677B2 (en) 2009-07-02 2016-05-31 Dexcom, Inc. Analyte sensor with increased reference capacity
AU2011288968B2 (en) * 2010-08-13 2015-04-16 Cathrx Ltd A catheter sheath and a method of manufacturing
US20130211219A1 (en) * 2010-08-24 2013-08-15 Micro CHIPS ,Inc. Implantable Biosensor Device and Methods of Use Thereof
US9090114B1 (en) * 2010-09-08 2015-07-28 Brian A Stumm Machine including LED-based UV radiation sources to process coatings
US20120097554A1 (en) * 2010-10-18 2012-04-26 Medtronic Minimed, Inc. Analyte sensors comprising electrodes having selected electrochemical and mechanical properties
US8652860B2 (en) 2011-01-09 2014-02-18 Bridgelux, Inc. Packaging photon building blocks having only top side connections in a molded interconnect structure
US8536605B2 (en) * 2011-11-28 2013-09-17 Bridgelux, Inc. Micro-bead blasting process for removing a silicone flash layer
US9504162B2 (en) 2011-05-20 2016-11-22 Pepex Biomedical, Inc. Manufacturing electrochemical sensor modules
CA2843008A1 (en) 2011-07-26 2013-01-31 Glysens Incorporated Tissue implantable sensor with hermetically sealed housing
EP2747650B1 (en) 2011-08-26 2023-04-05 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US20130060099A1 (en) * 2011-08-30 2013-03-07 Abbott Diabetes Care Inc. Methods for Subcutaneously Positioning an Analyte Sensing Device
WO2013138369A1 (en) 2012-03-16 2013-09-19 Dexcom, Inc. Systems and methods for processing analyte sensor data
US10111588B2 (en) 2012-03-29 2018-10-30 Senseonics, Incorporated Analyte sensor transceiver configured to provide tactile, visual, and/or aural feedback
US10327714B2 (en) 2012-03-29 2019-06-25 Senseonics, Incorporated Analyte concentration alert function for analyte sensor system
EP2664354B1 (en) * 2012-05-16 2015-09-16 Sorin CRM SAS Medical lead with a ring electrode for implantation in a cardiac or cerebral blood vessel and a method for its manufacture
US10660550B2 (en) 2015-12-29 2020-05-26 Glysens Incorporated Implantable sensor apparatus and methods
US10561353B2 (en) * 2016-06-01 2020-02-18 Glysens Incorporated Biocompatible implantable sensor apparatus and methods
US10462898B2 (en) 2012-09-11 2019-10-29 L.I.F.E. Corporation S.A. Physiological monitoring garments
US11246213B2 (en) 2012-09-11 2022-02-08 L.I.F.E. Corporation S.A. Physiological monitoring garments
US9743871B2 (en) * 2012-09-24 2017-08-29 Dexcom, Inc. Multiple electrode system for a continuous analyte sensor, and related methods
BR112015012958B1 (en) 2012-12-03 2022-03-15 Pepex Biomedical, Inc Sensor module to detect an analyte in a blood sample
US9211092B2 (en) * 2013-01-03 2015-12-15 Dexcom, Inc. End of life detection for analyte sensors
WO2014145745A1 (en) * 2013-03-15 2014-09-18 Lannutti John Core-shell nanofiber-based sensors
KR101297791B1 (en) * 2013-03-22 2013-08-19 이기세 Tip structure for a skin care apparatus
WO2015009385A1 (en) 2013-07-19 2015-01-22 Dexcom, Inc. Time averaged basal rate optimizer
WO2015021273A1 (en) * 2013-08-09 2015-02-12 Senseonics Incorporated Analyte sensor transceiver configured to provide tactile, visual, and / or aural feedback
WO2015065922A1 (en) 2013-10-28 2015-05-07 Dexcom, Inc. Devices used in connection with continuous analyte monitoring that provide the user with one or more notifications, and related methods
US9940846B2 (en) 2013-10-31 2018-04-10 Dexcom, Inc. Adaptive interface for continuous monitoring devices
US9480401B2 (en) 2013-11-14 2016-11-01 Dexcom, Inc. Indicator and analytics for sensor insertion in a continuous analyte monitoring system and related methods
EP3069279B1 (en) 2013-11-14 2020-10-28 Dexcom, Inc. Devices and methods for continuous analyte monitoring
EP3091864B8 (en) 2014-01-06 2018-12-19 L.I.F.E. Corporation S.A. Systems and methods to automatically determine garment fit
WO2015113044A1 (en) 2014-01-27 2015-07-30 Angiometrix Corporation Methods and apparatus for electrically stable connectors
WO2015122964A1 (en) 2014-02-11 2015-08-20 Dexcom, Inc. Packaging system for analyte sensors
US20150289788A1 (en) 2014-04-10 2015-10-15 Dexcom, Inc. Sensors for continuous analyte monitoring, and related methods
EP3434184B1 (en) 2014-04-10 2021-10-27 DexCom, Inc. Glycemic urgency assessment and alerts interface
US10232167B2 (en) * 2014-05-07 2019-03-19 Medtronic, Inc. Electrode construction for implantable medical electrical leads
US11045124B2 (en) 2014-06-04 2021-06-29 Pepex Biomedical, Inc. Electrochemical sensors and methods for making electrochemical sensors using advanced printing technology
EP3197356B1 (en) 2014-09-22 2020-12-16 Dexcom, Inc. Method for mode switching
WO2016054079A1 (en) 2014-09-29 2016-04-07 Zyomed Corp. Systems and methods for blood glucose and other analyte detection and measurement using collision computing
EP3200680A1 (en) * 2014-10-01 2017-08-09 L.I.F.E. Corporation S.A. Devices and methods for use with physiological monitoring garments
US10118035B2 (en) 2015-02-24 2018-11-06 Elira, Inc. Systems and methods for enabling appetite modulation and/or improving dietary compliance using an electro-dermal patch
US10335302B2 (en) 2015-02-24 2019-07-02 Elira, Inc. Systems and methods for using transcutaneous electrical stimulation to enable dietary interventions
US10864367B2 (en) 2015-02-24 2020-12-15 Elira, Inc. Methods for using an electrical dermal patch in a manner that reduces adverse patient reactions
US9956393B2 (en) 2015-02-24 2018-05-01 Elira, Inc. Systems for increasing a delay in the gastric emptying time for a patient using a transcutaneous electro-dermal patch
US10765863B2 (en) 2015-02-24 2020-09-08 Elira, Inc. Systems and methods for using a transcutaneous electrical stimulation device to deliver titrated therapy
US10376145B2 (en) 2015-02-24 2019-08-13 Elira, Inc. Systems and methods for enabling a patient to achieve a weight loss objective using an electrical dermal patch
US10410538B2 (en) 2015-05-07 2019-09-10 Dexcom, Inc. System and method for educating users, including responding to patterns
US11259842B2 (en) 2015-05-22 2022-03-01 Dexcom, Inc. Needle for transcutaneous analyte sensor delivery
US10575767B2 (en) * 2015-05-29 2020-03-03 Medtronic Minimed, Inc. Method for monitoring an analyte, analyte sensor and analyte monitoring apparatus
EP3304565A4 (en) * 2015-06-01 2019-01-02 Autonomix Medical, Inc. Elongated conductors and methods of making and using the same
WO2016196516A1 (en) 2015-06-03 2016-12-08 William Kenneth Ward Measurement of glucose in an insulin delivery catheter by minimizing the adverse effects of insulin preservatives
US10426555B2 (en) * 2015-06-03 2019-10-01 Covidien Lp Medical instrument with sensor for use in a system and method for electromagnetic navigation
CA2994362C (en) 2015-07-20 2023-12-12 L.I.F.E. Corporation S.A. Flexible fabric ribbon connectors for garments with sensors and electronics
US10470661B2 (en) 2015-09-10 2019-11-12 Dexcom, Inc. Transcutaneous analyte sensors and monitors, calibration thereof, and associated methods
CN113974619A (en) 2015-09-10 2022-01-28 德克斯康公司 Transcutaneous analyte sensors and monitors, calibrations thereof, and associated methods
US9903755B2 (en) * 2015-10-05 2018-02-27 Microsoft Technology Licensing, Llc Indoors / outdoors detection
CN108697322A (en) * 2015-10-23 2018-10-23 外分泌腺系统公司 The device that can carry out sample concentration of extension sensing for sweat analyte
EP3922172A1 (en) 2015-12-30 2021-12-15 Dexcom, Inc. Transcutaneous analyte sensor systems and methods
US10213144B2 (en) 2016-01-25 2019-02-26 International Business Machines Corporation Nanopatterned biosensor electrode for enhanced sensor signal and sensitivity
US9554738B1 (en) 2016-03-30 2017-01-31 Zyomed Corp. Spectroscopic tomography systems and methods for noninvasive detection and measurement of analytes using collision computing
US10152947B2 (en) 2016-04-06 2018-12-11 Microsoft Technology Licensing, Llc Display brightness updating
EP3451926A4 (en) 2016-05-02 2019-12-04 Dexcom, Inc. System and method for providing alerts optimized for a user
US11272868B2 (en) * 2016-05-06 2022-03-15 The Johns Hopkins University Potentiometric wearable sweat sensor
US11298059B2 (en) * 2016-05-13 2022-04-12 PercuSense, Inc. Analyte sensor
US10638962B2 (en) 2016-06-29 2020-05-05 Glysens Incorporated Bio-adaptable implantable sensor apparatus and methods
WO2018002722A1 (en) 2016-07-01 2018-01-04 L.I.F.E. Corporation S.A. Biometric identification by garments having a plurality of sensors
CN109716485A (en) * 2016-07-15 2019-05-03 布鲁尔科技公司 Laser ablation dielectric material
US10376193B2 (en) * 2016-07-25 2019-08-13 International Business Machines Corporation Embedded sacrificial layer to enhance biosensor stability and lifetime for nanopatterned electrodes
CN110049711A (en) * 2016-09-21 2019-07-23 辛辛那提大学 Accurate sweat enzyme sensing analysis
WO2018107013A1 (en) * 2016-12-09 2018-06-14 Abbott Point Of Care Inc. Dual range cardiac troponin immunoassay devices and methods using immunosensor and magnetic immunosensor
US10161898B2 (en) 2017-01-30 2018-12-25 International Business Machines Corporation Nanopatterned biosensor electrode for enhanced sensor signal and sensitivity
US10548530B2 (en) 2017-03-01 2020-02-04 International Business Machines Corporation Biosensor calibration structure containing different sensing surface area
WO2018172619A1 (en) * 2017-03-22 2018-09-27 Aalto University Foundation Sr Electrochemical assay for the detection of opioids
CN108968976B (en) 2017-05-31 2022-09-13 心脏起搏器股份公司 Implantable medical device with chemical sensor
CA3067825C (en) 2017-06-19 2023-10-24 Dexcom, Inc. Applicators for applying transcutaneous analyte sensors and associated methods of manufacture
US10638979B2 (en) 2017-07-10 2020-05-05 Glysens Incorporated Analyte sensor data evaluation and error reduction apparatus and methods
CN109381195B (en) 2017-08-10 2023-01-10 心脏起搏器股份公司 Systems and methods including electrolyte sensor fusion
WO2019036300A1 (en) * 2017-08-14 2019-02-21 Senseonics, Incorporated Methods and systems for calculating analyte levels
CA3072853A1 (en) 2017-08-21 2019-02-28 Dexcom, Inc. Continuous glucose monitors and related sensors utilizing mixed model and bayesian calibration algorithms
CN109419515B (en) 2017-08-23 2023-03-24 心脏起搏器股份公司 Implantable chemical sensor with staged activation
WO2019046853A1 (en) * 2017-09-02 2019-03-07 Biocrede Inc. Medical device with integrated biosensor
WO2019081462A1 (en) * 2017-10-24 2019-05-02 Roche Diabetes Care Gmbh Electrochemical sensor and method for producing thereof
US10734505B2 (en) * 2017-11-30 2020-08-04 International Business Machines Corporation Lateral bipolar junction transistor with dual base region
CN109864746B (en) 2017-12-01 2023-09-29 心脏起搏器股份公司 Multimode analyte sensor for medical devices
CN109864747B (en) 2017-12-05 2023-08-25 心脏起搏器股份公司 Multimode analyte sensor optoelectronic interface
US11278668B2 (en) 2017-12-22 2022-03-22 Glysens Incorporated Analyte sensor and medicant delivery data evaluation and error reduction apparatus and methods
US11255839B2 (en) 2018-01-04 2022-02-22 Glysens Incorporated Apparatus and methods for analyte sensor mismatch correction
CA3089642A1 (en) 2018-02-09 2019-08-15 Dexcom, Inc. System and method for decision support
US11013438B2 (en) 2018-04-06 2021-05-25 Zense-Life Inc. Enhanced enzyme membrane for a working electrode of a continuous biological sensor
WO2019195661A1 (en) 2018-04-06 2019-10-10 Zense-Life Inc. Continuous glucose monitoring device
US11714060B2 (en) 2018-05-03 2023-08-01 Dexcom, Inc. Automatic analyte sensor calibration and error detection
WO2019217199A1 (en) * 2018-05-09 2019-11-14 President And Fellows Of Harvard College Luminescent devices
EP3603721B1 (en) 2018-07-31 2022-05-11 Heraeus Deutschland GmbH & Co. KG Catheter with segmented electrodes and methods of making same
US20200205694A1 (en) * 2018-12-28 2020-07-02 Dexcom, Inc. Analyte sensor with impedance determination
CN109893140B (en) * 2019-02-28 2021-08-03 孙云峰 Needle-shaped enzyme sensor
EP3766414A1 (en) * 2019-07-16 2021-01-20 Heraeus Deutschland GmbH & Co KG Process for preparing a processed filament, processed filament and its use
SG10202006835UA (en) * 2019-08-01 2021-03-30 Heraeus Deutschland Gmbh & Co Kg A device for processing a filament, the device comprising a processing beam source and a guiding means
EP3798628A1 (en) 2019-09-27 2021-03-31 Heraeus Deutschland GmbH & Co KG Method for manufacturing an electrochemical sensor
CN112570198B (en) * 2019-09-30 2022-06-17 天津恩泰智能装备有限公司 Overhead bare conductor insulating material coating device
US20220412961A1 (en) * 2019-11-15 2022-12-29 President And Fellows Of Harvard College Device and method for analyte detection
JP2023511708A (en) * 2020-01-28 2023-03-22 ジャイラス エーシーエムアイ インク ディー/ビー/エー オリンパス サージカル テクノロジーズ アメリカ Medical device with biliary diagnostic device
EP3905462A1 (en) * 2020-04-30 2021-11-03 Heraeus Deutschland GmbH & Co KG Wire handling system and method for laser ablation
DE102020119187A1 (en) 2020-07-21 2022-01-27 Heinrich Kuper Gmbh Device and method for producing an adhesive thread and for connecting workpieces with the adhesive thread
GB2608290B (en) 2020-07-29 2023-07-26 Biolinq Incorporated Continuous analyte monitoring system with microneedle array
US11612779B2 (en) * 2020-11-04 2023-03-28 Timothy Karl Schumacher Water jug/ water can exercise device/ equipment system
US11776714B2 (en) * 2020-11-13 2023-10-03 E-Wireligner Co., Ltd. Device for coating a wire with polymer fibers and method thereof
CN112450918B (en) * 2020-11-27 2022-12-06 浙江凯立特医疗器械有限公司 Implanting device of implantable biosensor
ES2915406A1 (en) * 2020-12-21 2022-06-22 Bioquochem S L Method for measuring a concentration of an analysis compound or an enzymatic activity in a complex sample by selectively (Machine-translation by Google Translate, not legally binding)
AU2022238919A1 (en) 2021-03-19 2023-10-19 Dexcom, Inc. Drug releasing membrane for analyte sensor
AU2022249311A1 (en) 2021-03-31 2023-11-02 Dexcom, Inc. Filtering of continuous glucose monitor (cgm) signals with a kalman filter
WO2022212867A1 (en) 2021-04-02 2022-10-06 Dexcom, Inc. Personalized modeling of blood glucose concentration impacted by individualized sensor characteristics and individualized physiological characteristics
CA3199431A1 (en) 2021-04-15 2022-10-20 Dexcom, Inc. Global configuration service
JP7341583B6 (en) 2021-05-08 2023-09-29 バイオリンク インコーポレイテッド Fault detection for microneedle array-based continuous analyte monitoring devices
EP4137047A1 (en) * 2021-08-18 2023-02-22 Roche Diabetes Care GmbH Insertion device for transcutaneous insertion
WO2023043908A1 (en) 2021-09-15 2023-03-23 Dexcom, Inc. Bioactive releasing membrane for analyte sensor
US20230140055A1 (en) 2021-11-02 2023-05-04 Dexcom, Inc. Prediction funnel for generation of hypo- and hyper-glycemic alerts based on continuous glucose monitoring data
US20230181065A1 (en) 2021-12-13 2023-06-15 Dexcom, Inc. End-of-life detection for analyte sensors experiencing progressive sensor decline
WO2023177862A1 (en) 2022-03-18 2023-09-21 Dexcom, Inc. Continuous analyte monitoring sensor systems
WO2023177896A1 (en) 2022-03-18 2023-09-21 Dexcom, Inc. Continuous multi-analyte sensor systems
WO2023235442A1 (en) 2022-06-01 2023-12-07 Dexcom, Inc. Systems and methods for monitoring, diagnosis, and decision support for diabetes in patients with kidney disease
US20230397845A1 (en) 2022-06-10 2023-12-14 Dexcorn, Inc. Apparatuses, systems, and methods of controlling sensor deployment
CN114767105B (en) * 2022-06-22 2022-10-14 苏州百孝医疗科技有限公司 Implantable electrochemical biosensor, testing method and implantable medical device
EP4316372A1 (en) * 2022-08-05 2024-02-07 PharmaSens AG Electrochemical analyte sensor having improved reproducibility and associated fabrication process

Citations (83)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1966575A (en) * 1931-04-23 1934-07-17 E M F Electric Company Proprie Automatic weld rod manufacturing apparatus
US2489456A (en) * 1945-08-21 1949-11-29 Robert A Liebel Method of applying uniform coating by immersion
US2497894A (en) * 1944-10-14 1950-02-21 Nat Standard Co Method of electroplating fine wire of low elastic limit
US2728831A (en) * 1951-11-09 1955-12-27 Phys Chemical Res Corp Electric hygrometer
US2889239A (en) * 1958-03-12 1959-06-02 Bell Telephone Labor Inc Method for making a transposed conductor structure
US3658571A (en) * 1970-04-29 1972-04-25 Owens Corning Fiberglass Corp Glass fiber reinforced elastomers
US3930462A (en) * 1975-05-08 1976-01-06 United Technologies Corporation Slurry dip tank
US3933593A (en) * 1971-02-22 1976-01-20 Beckman Instruments, Inc. Rate sensing batch analysis method
US4126510A (en) * 1977-10-06 1978-11-21 Rca Corporation Etching a succession of articles from a strip of sheet metal
US4422583A (en) * 1981-12-14 1983-12-27 Usm Corporation Wire feeder
US4644898A (en) * 1985-04-19 1987-02-24 U.S. Philips Corporation Arrangement for coating optical fibres
US4726381A (en) * 1986-06-04 1988-02-23 Solutech, Inc. Dialysis system and method
US4736748A (en) * 1986-04-05 1988-04-12 Kuraray Co., Ltd. Blood component monitoring system
US4826706A (en) * 1981-04-29 1989-05-02 Phelps Dodge Industries, Inc. Method and apparatus for manufacturing magnet wire
US4832034A (en) * 1987-04-09 1989-05-23 Pizziconi Vincent B Method and apparatus for withdrawing, collecting and biosensing chemical constituents from complex fluids
US4886562A (en) * 1987-03-31 1989-12-12 The Boeing Company Method of manufacturing reinforced optical fiber
US4890621A (en) * 1988-01-19 1990-01-02 Northstar Research Institute, Ltd. Continuous glucose monitoring and a system utilized therefor
US5200051A (en) * 1988-11-14 1993-04-06 I-Stat Corporation Wholly microfabricated biosensors and process for the manufacture and use thereof
US5212050A (en) * 1988-11-14 1993-05-18 Mier Randall M Method of forming a permselective layer
US5310469A (en) * 1991-12-31 1994-05-10 Abbott Laboratories Biosensor with a membrane containing biologically active material
US5312590A (en) * 1989-04-24 1994-05-17 National University Of Singapore Amperometric sensor for single and multicomponent analysis
US5372293A (en) * 1992-11-23 1994-12-13 Carrar Apparatus for degolding or tinning conductive portions of a microelectronic device
US5380422A (en) * 1991-07-18 1995-01-10 Agency Of Industrial Science And Technology Micro-electrode and method for preparing it
US5497772A (en) * 1993-11-19 1996-03-12 Alfred E. Mann Foundation For Scientific Research Glucose monitoring system
US5524338A (en) * 1991-10-22 1996-06-11 Pi Medical Corporation Method of making implantable microelectrode
US5683514A (en) * 1992-12-15 1997-11-04 Weirton Steel Corporation Coating control apparatus
US5879828A (en) * 1997-10-10 1999-03-09 Minnesota Mining And Manufacturing Company Membrane electrode assembly
US5928571A (en) * 1997-08-29 1999-07-27 E. I. Du Pont De Nemours And Company Thick film compositions for making medical electrodes
US6063637A (en) * 1995-12-13 2000-05-16 California Institute Of Technology Sensors for sugars and other metal binding analytes
US6103033A (en) * 1998-03-04 2000-08-15 Therasense, Inc. Process for producing an electrochemical biosensor
US6175752B1 (en) * 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
US6187378B1 (en) * 1998-10-01 2001-02-13 Lucent Technologies Inc. Automated system and method for electroless plating of optical fibers
US6214115B1 (en) * 1998-07-21 2001-04-10 Biocompatibles Limited Coating
US20010008187A1 (en) * 1994-07-05 2001-07-19 Hans Hanssen Coaxial cable
US6341232B1 (en) * 1998-05-13 2002-01-22 Cygnus, Inc. Methods of producing collection assemblies, laminates, and autosensor assemblies for use in transdermal sampling systems
US20020023852A1 (en) * 1999-02-25 2002-02-28 Minimed Inc. Glucose sensor package system
US6368658B1 (en) * 1999-04-19 2002-04-09 Scimed Life Systems, Inc. Coating medical devices using air suspension
US6413393B1 (en) * 1999-07-07 2002-07-02 Minimed, Inc. Sensor including UV-absorbing polymer and method of manufacture
US20030009093A1 (en) * 2000-05-15 2003-01-09 Silver James H. Implantable sensor
US6560471B1 (en) * 2001-01-02 2003-05-06 Therasense, Inc. Analyte monitoring device and methods of use
US6558321B1 (en) * 1997-03-04 2003-05-06 Dexcom, Inc. Systems and methods for remote monitoring and modulation of medical devices
US6558320B1 (en) * 2000-01-20 2003-05-06 Medtronic Minimed, Inc. Handheld personal data assistant (PDA) with a medical device and method of using the same
US20030088166A1 (en) * 1998-03-04 2003-05-08 Therasense, Inc. Electrochemical analyte sensor
US6561978B1 (en) * 1999-02-12 2003-05-13 Cygnus, Inc. Devices and methods for frequent measurement of an analyte present in a biological system
US20030100040A1 (en) * 1997-12-05 2003-05-29 Therasense Inc. Blood analyte monitoring through subcutaneous measurement
US20030188965A1 (en) * 2002-04-05 2003-10-09 3M Innovative Properties Company Web processing method and apparatus
US20040010207A1 (en) * 2002-07-15 2004-01-15 Flaherty J. Christopher Self-contained, automatic transcutaneous physiologic sensing system
US20040039298A1 (en) * 1996-09-04 2004-02-26 Abreu Marcio Marc Noninvasive measurement of chemical substances
US20040078219A1 (en) * 2001-12-04 2004-04-22 Kimberly-Clark Worldwide, Inc. Healthcare networks with biosensors
US20040074785A1 (en) * 2002-10-18 2004-04-22 Holker James D. Analyte sensors and methods for making them
US6740214B1 (en) * 1998-05-08 2004-05-25 Isis Innovation Limited Microelectrode biosensor and method therefor
US20040258915A1 (en) * 2003-06-18 2004-12-23 Takeshi Hasui Method of forming corrosion protection double coatings on prestressing strand and prestressing strand produced by the method
US20050028731A1 (en) * 2003-08-04 2005-02-10 Fitel Usa Corp. Systems and methods for coating optical fiber
US20050065464A1 (en) * 2002-07-24 2005-03-24 Medtronic Minimed, Inc. System for providing blood glucose measurements to an infusion device
US6895263B2 (en) * 2000-02-23 2005-05-17 Medtronic Minimed, Inc. Real time self-adjusting calibration algorithm
US20060001550A1 (en) * 1998-10-08 2006-01-05 Mann Alfred E Telemetered characteristic monitor system and method of using the same
US20060015020A1 (en) * 2004-07-06 2006-01-19 Dexcom, Inc. Systems and methods for manufacture of an analyte-measuring device including a membrane system
US6989891B2 (en) * 2001-11-08 2006-01-24 Optiscan Biomedical Corporation Device and method for in vitro determination of analyte concentrations within body fluids
US20060019327A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060016700A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US6998247B2 (en) * 2002-03-08 2006-02-14 Sensys Medical, Inc. Method and apparatus using alternative site glucose determinations to calibrate and maintain noninvasive and implantable analyzers
US7003336B2 (en) * 2000-02-10 2006-02-21 Medtronic Minimed, Inc. Analyte sensor method of making the same
US20060052745A1 (en) * 2004-09-08 2006-03-09 Van Antwerp Nannette M Blood contacting sensor
US20060079740A1 (en) * 2000-05-15 2006-04-13 Silver James H Sensors for detecting substances indicative of stroke, ischemia, or myocardial infarction
US20070014124A1 (en) * 2005-07-18 2007-01-18 Peter Gerets Device for coupling the light of multiple light sources
US20070016381A1 (en) * 2003-08-22 2007-01-18 Apurv Kamath Systems and methods for processing analyte sensor data
US20070027370A1 (en) * 2004-07-13 2007-02-01 Brauker James H Analyte sensor
US20070027385A1 (en) * 2003-12-05 2007-02-01 Mark Brister Dual electrode system for a continuous analyte sensor
US20070032706A1 (en) * 2003-08-22 2007-02-08 Apurv Kamath Systems and methods for replacing signal artifacts in a glucose sensor data stream
US20070038044A1 (en) * 2004-07-13 2007-02-15 Dobbles J M Analyte sensor
US20070084560A1 (en) * 1999-09-29 2007-04-19 Fuentes Ricardo I Wet processing using a fluid meniscus, apparatus and method
US20070141245A1 (en) * 2005-12-20 2007-06-21 Steve Tsai System and method for coating filaments
US20080033254A1 (en) * 2003-07-25 2008-02-07 Dexcom, Inc. Systems and methods for replacing signal data artifacts in a glucose sensor data stream
US20080086044A1 (en) * 2006-10-04 2008-04-10 Dexcom, Inc. Analyte sensor
US7366566B2 (en) * 2003-12-29 2008-04-29 Ela Medical S.A.S. Automatic commutations of AAI/DDD mode in the presence of paroxystic AVB in an active implantable medical device, in particular a cardiac pacemaker
US20080115727A1 (en) * 2005-08-05 2008-05-22 David R Otis Prothesis Having a Coating and Systems and Methods of Making the Same
US20090018424A1 (en) * 2006-10-04 2009-01-15 Dexcom, Inc. Analyte sensor
US20090030294A1 (en) * 2004-05-03 2009-01-29 Dexcom, Inc. Implantable analyte sensor
US20090062633A1 (en) * 2004-05-03 2009-03-05 Dexcorn, Inc. Implantable analyte sensor
US20090076360A1 (en) * 2007-09-13 2009-03-19 Dexcom, Inc. Transcutaneous analyte sensor
US7519408B2 (en) * 2003-11-19 2009-04-14 Dexcom, Inc. Integrated receiver for continuous analyte sensor
US7651596B2 (en) * 2005-04-08 2010-01-26 Dexcom, Inc. Cellulosic-based interference domain for an analyte sensor
US20110027458A1 (en) * 2009-07-02 2011-02-03 Dexcom, Inc. Continuous analyte sensors and methods of making same

Family Cites Families (349)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2008A (en) 1841-03-18 Gas-lamp eok conducting gas pkom ah elevated buhner to one below it
US119703A (en) 1871-10-10 Improvement in ironing-tables
US3957613A (en) 1974-11-01 1976-05-18 General Electric Company Miniature probe having multifunctional electrodes for sensing ions and gases
FR2387659A1 (en) * 1977-04-21 1978-11-17 Armines GLYCEMIA CONTROL AND REGULATION DEVICE
US4190040A (en) * 1978-07-03 1980-02-26 American Hospital Supply Corporation Resealable puncture housing for surgical implantation
US4225410A (en) * 1978-12-04 1980-09-30 Technicon Instruments Corporation Integrated array of electrochemical sensors
DE2932761A1 (en) 1979-08-13 1981-02-26 Akzo Gmbh POLYCARBONATE-POLYAETHER-COPOLYMER MEMBRANE
IE51643B1 (en) 1980-10-15 1987-01-21 Smith & Nephew Ass Coated articles and materials suitable for coating
US4442841A (en) * 1981-04-30 1984-04-17 Mitsubishi Rayon Company Limited Electrode for living bodies
EP0098592A3 (en) 1982-07-06 1985-08-21 Fujisawa Pharmaceutical Co., Ltd. Portable artificial pancreas
US4614514A (en) 1983-02-16 1986-09-30 M/A Com, Inc. Microwave sterilizer
US5682884A (en) 1983-05-05 1997-11-04 Medisense, Inc. Strip electrode with screen printing
CA1219040A (en) 1983-05-05 1987-03-10 Elliot V. Plotkin Measurement of enzyme-catalysed reactions
CA1226036A (en) 1983-05-05 1987-08-25 Irving J. Higgins Analytical equipment and sensor electrodes therefor
US4655880A (en) * 1983-08-01 1987-04-07 Case Western Reserve University Apparatus and method for sensing species, substances and substrates using oxidase
US4848348A (en) * 1983-11-14 1989-07-18 Minnesota Mining And Manufacturing Company Coated films
US6846654B1 (en) 1983-11-29 2005-01-25 Igen International, Inc. Catalytic antibodies as chemical sensors
US4739380A (en) * 1984-01-19 1988-04-19 Integrated Ionics, Inc. Integrated ambient sensing devices and methods of manufacture
JPS60231156A (en) * 1984-04-30 1985-11-16 Kuraray Co Ltd Liquid junction type reference electrode
CA1258496A (en) 1984-07-30 1989-08-15 Teruyoshi Uchida Insulated noble metal wire and porous membrane as po.sub.2 bioelectrode
US4671288A (en) 1985-06-13 1987-06-09 The Regents Of The University Of California Electrochemical cell sensor for continuous short-term use in tissues and blood
US4680268A (en) 1985-09-18 1987-07-14 Children's Hospital Medical Center Implantable gas-containing biosensor and method for measuring an analyte such as glucose
JPS62225513A (en) 1986-03-26 1987-10-03 Shin Etsu Chem Co Ltd Block-graft copolymer and production thereof
US4685463A (en) 1986-04-03 1987-08-11 Williams R Bruce Device for continuous in vivo measurement of blood glucose concentrations
US4908115A (en) 1986-04-22 1990-03-13 Toray Industries, Inc. Minute electrode for electrochemical analysis
US4703756A (en) 1986-05-06 1987-11-03 The Regents Of The University Of California Complete glucose monitoring system with an implantable, telemetered sensor module
US4837049A (en) * 1986-06-17 1989-06-06 Alfred E. Mann Foundation For Scientific Research Method of making an electrode array
US5190040A (en) 1986-12-26 1993-03-02 Nihon Kohden Corporation Apparatus for measuring the change in the concentration of a pigment in blood
US4935345A (en) * 1987-04-07 1990-06-19 Arizona Board Of Regents Implantable microelectronic biochemical sensor incorporating thin film thermopile
US4759828A (en) 1987-04-09 1988-07-26 Nova Biomedical Corporation Glucose electrode and method of determining glucose
US5286364A (en) * 1987-06-08 1994-02-15 Rutgers University Surface-modified electochemical biosensor
US4777205A (en) * 1987-07-22 1988-10-11 Wacker Silicones Corporation Electrically conductive compositions
US4925444A (en) * 1987-08-07 1990-05-15 Baxter Travenol Laboratories, Inc. Closed multi-fluid delivery system and method
GB8725936D0 (en) 1987-11-05 1987-12-09 Genetics Int Inc Sensing system
ZA889546B (en) 1987-12-24 1990-08-29 Igen Inc Chemical sensors employing catalytic antibodies
US5362307A (en) * 1989-01-24 1994-11-08 The Regents Of The University Of California Method for the iontophoretic non-invasive-determination of the in vivo concentration level of an inorganic or organic substance
DE3812584A1 (en) * 1988-04-13 1989-10-26 Mic Medical Instr Corp DEVICE FOR BIOFEEDBACK CONTROL OF BODY FUNCTIONS
DK409188D0 (en) 1988-07-21 1988-07-21 Radiometer As PROCEDURE FOR MEASURING A CHARACTERISTICS IN A FLUIDUM
US6306594B1 (en) 1988-11-14 2001-10-23 I-Stat Corporation Methods for microdispensing patterened layers
US4974592A (en) 1988-11-14 1990-12-04 American Sensor Systems Corporation Continuous on-line blood monitoring system
US5063081A (en) 1988-11-14 1991-11-05 I-Stat Corporation Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor
WO1990007575A1 (en) 1988-12-30 1990-07-12 Anderson David M Stabilized microporous materials and hydrogel materials
AT392847B (en) 1989-01-27 1991-06-25 Avl Verbrennungskraft Messtech SENSOR ELECTRODE ARRANGEMENT
JPH02298855A (en) 1989-03-20 1990-12-11 Assoc Univ Inc Electrochemical biosensor using immobilized enzyme and redox polymer
GB8909613D0 (en) 1989-04-27 1989-06-14 Pickup John C Glucose-sensing electrode
US5431160A (en) 1989-07-19 1995-07-11 University Of New Mexico Miniature implantable refillable glucose sensor and material therefor
US5101814A (en) 1989-08-11 1992-04-07 Palti Yoram Prof System for monitoring and controlling blood glucose
CA2024548C (en) 1989-09-05 2002-05-28 David Issachar Analyte specific chemical sensor
US5512246A (en) 1989-09-21 1996-04-30 Anthony P. Russell Method and means for detecting polyhydroxyl compounds
US5067491A (en) 1989-12-08 1991-11-26 Becton, Dickinson And Company Barrier coating on blood contacting devices
US5985129A (en) 1989-12-14 1999-11-16 The Regents Of The University Of California Method for increasing the service life of an implantable sensor
CA2071829C (en) 1989-12-14 2001-11-13 David A. Gough Method for increasing the service life of an implantable sensor
US5165407A (en) * 1990-04-19 1992-11-24 The University Of Kansas Implantable glucose sensor
NL9002764A (en) 1990-12-14 1992-07-01 Tno ELECTRODE, FITTED WITH A POLYMER COATING WITH A REDOX ENZYM BOND TO IT.
US5593852A (en) 1993-12-02 1997-01-14 Heller; Adam Subcutaneous glucose electrode
US5773270A (en) 1991-03-12 1998-06-30 Chiron Diagnostics Corporation Three-layered membrane for use in an electrochemical sensor system
CA2069537A1 (en) 1991-06-07 1992-12-08 Thomas A. Cook Multiple output referencing system for evanescent wave sensor
US5322063A (en) 1991-10-04 1994-06-21 Eli Lilly And Company Hydrophilic polyurethane membranes for electrochemical glucose sensors
GB2278235B (en) 1991-10-21 1996-05-08 Holm Kennedy James W Method and device for biochemical sensing
US5683366A (en) 1992-01-07 1997-11-04 Arthrocare Corporation System and method for electrosurgical tissue canalization
US5985693A (en) 1994-09-30 1999-11-16 Elm Technology Corporation High density three-dimensional IC interconnection
GB9212302D0 (en) 1992-06-10 1992-07-22 Applied Research Systems Method for improving measurement precision in evanescent wave optical biosensor assays
US5324328A (en) 1992-08-05 1994-06-28 Siemens Pacesetter, Inc. Conductor for a defibrillator patch lead
US5676651A (en) 1992-08-06 1997-10-14 Electric Boat Corporation Surgically implantable pump arrangement and method for pumping body fluids
US5311013A (en) 1992-10-15 1994-05-10 Abbott Laboratories Optical fiber distribution system for an optical fiber sensor in a luminescent sensor system
EP0721360A1 (en) 1992-11-09 1996-07-17 SIPIN, Anatole J. Controlled fluid transfer system
US5270079A (en) * 1992-12-18 1993-12-14 Specialty Coatings Systems, Inc. Methods of meniscus coating
SE9301270D0 (en) 1993-04-19 1993-04-17 BIOSENSOR
JP3204980B2 (en) 1993-04-22 2001-09-04 アンドケア,インコーポレイテッド Peroxidase colloidal gold oxidase biosensor for mediator-free glucose measurement
WO1996005501A1 (en) 1993-05-14 1996-02-22 Igen, Inc. Apparatus and methods for carrying out electrochemiluminescence test measurements
JP2704046B2 (en) 1993-06-08 1998-01-26 ベーリンガー マンハイム コーポレーション Biosensing meter that detects the appropriate electrode connection and distinguishes between sample and check pieces
US5366609A (en) 1993-06-08 1994-11-22 Boehringer Mannheim Corporation Biosensing meter with pluggable memory key
US5352351A (en) 1993-06-08 1994-10-04 Boehringer Mannheim Corporation Biosensing meter with fail/safe procedures to prevent erroneous indications
DE4329898A1 (en) * 1993-09-04 1995-04-06 Marcus Dr Besson Wireless medical diagnostic and monitoring device
JP3457322B2 (en) 1993-10-21 2003-10-14 アボツト・ラボラトリーズ Apparatus and method for detecting target ligand
US5494562A (en) * 1994-06-27 1996-02-27 Ciba Corning Diagnostics Corp. Electrochemical sensors
US5509888A (en) * 1994-07-26 1996-04-23 Conceptek Corporation Controller valve device and method
US5513636A (en) * 1994-08-12 1996-05-07 Cb-Carmel Biotechnology Ltd. Implantable sensor chip
AT402452B (en) 1994-09-14 1997-05-26 Avl Verbrennungskraft Messtech PLANAR SENSOR FOR DETECTING A CHEMICAL PARAMETER OF A SAMPLE
US5624537A (en) * 1994-09-20 1997-04-29 The University Of British Columbia - University-Industry Liaison Office Biosensor and interface membrane
US5676820A (en) 1995-02-03 1997-10-14 New Mexico State University Technology Transfer Corp. Remote electrochemical sensor
US5517313A (en) 1995-02-21 1996-05-14 Colvin, Jr.; Arthur E. Fluorescent optical sensor
KR100449615B1 (en) * 1995-03-10 2004-12-08 메소 스케일 테크놀러지즈, 엘엘시 Multi-array, multi-specific electrochemiluminescence test
US5571401A (en) * 1995-03-27 1996-11-05 California Institute Of Technology Sensor arrays for detecting analytes in fluids
US5565143A (en) * 1995-05-05 1996-10-15 E. I. Du Pont De Nemours And Company Water-based silver-silver chloride compositions
EP0744779A3 (en) 1995-05-17 1998-10-21 Matsushita Battery Industrial Co Ltd A manufacturing method of compound semiconductor thinfilms and photoelectric device or solar cell using the same compound semiconductor thinfilms
US6060640A (en) 1995-05-19 2000-05-09 Baxter International Inc. Multiple-layer, formed-in-place immunoisolation membrane structures for implantation of cells in host tissue
US5995860A (en) * 1995-07-06 1999-11-30 Thomas Jefferson University Implantable sensor and system for measurement and control of blood constituent levels
US5611900A (en) * 1995-07-20 1997-03-18 Michigan State University Microbiosensor used in-situ
US6689265B2 (en) 1995-10-11 2004-02-10 Therasense, Inc. Electrochemical analyte sensors using thermostable soybean peroxidase
US5972199A (en) 1995-10-11 1999-10-26 E. Heller & Company Electrochemical analyte sensors using thermostable peroxidase
US5711861A (en) 1995-11-22 1998-01-27 Ward; W. Kenneth Device for monitoring changes in analyte concentration
ES2236759T3 (en) * 1995-12-19 2005-07-16 Abbott Laboratories DETECTION DEVICE OF AN ANALYTIC AND ADMINISTRATION OF A THERAPEUTIC SUBSTANCE.
US5863460A (en) * 1996-04-01 1999-01-26 Chiron Diagnostics Corporation Oxygen sensing membranes and methods of making same
US6407195B2 (en) 1996-04-25 2002-06-18 3M Innovative Properties Company Tackified polydiorganosiloxane oligourea segmented copolymers and a process for making same
US5707502A (en) * 1996-07-12 1998-01-13 Chiron Diagnostics Corporation Sensors for measuring analyte concentrations and methods of making same
WO1998003431A1 (en) * 1996-07-23 1998-01-29 Medisense, Inc. Silver chloride particles
US5772903A (en) * 1996-09-27 1998-06-30 Hirsch; Gregory Tapered capillary optics
AU5461298A (en) 1996-12-04 1998-06-29 Enact Health Management Systems System for downloading and reporting medical information
US5964993A (en) 1996-12-19 1999-10-12 Implanted Biosystems Inc. Glucose sensor
US5914026A (en) 1997-01-06 1999-06-22 Implanted Biosystems Inc. Implantable sensor employing an auxiliary electrode
US7899511B2 (en) 2004-07-13 2011-03-01 Dexcom, Inc. Low oxygen in vivo analyte sensor
US7192450B2 (en) 2003-05-21 2007-03-20 Dexcom, Inc. Porous membranes for use with implantable devices
US6001067A (en) 1997-03-04 1999-12-14 Shults; Mark C. Device and method for determining analyte levels
GB9704737D0 (en) 1997-03-07 1997-04-23 Optel Instr Limited Biological measurement system
US6270455B1 (en) 1997-03-28 2001-08-07 Health Hero Network, Inc. Networked system for interactive communications and remote monitoring of drug delivery
US6186765B1 (en) 1997-03-31 2001-02-13 Toshiba Kikai Kabushiki Kaisha Apparatus for forming a molded multilayer product
KR100397227B1 (en) 1997-04-04 2003-09-13 유니버시티 오브 써던 캘리포니아 Electroplating article, method and apparatus for electrochemical fabrication
AT404992B (en) 1997-04-17 1999-04-26 Avl List Gmbh SENSOR FOR DETERMINING AN ENZYME SUBSTRATE
US5954643A (en) * 1997-06-09 1999-09-21 Minimid Inc. Insertion set for a transcutaneous sensor
US6558351B1 (en) 1999-06-03 2003-05-06 Medtronic Minimed, Inc. Closed loop system for controlling insulin infusion
US7267665B2 (en) * 1999-06-03 2007-09-11 Medtronic Minimed, Inc. Closed loop system for controlling insulin infusion
US7006871B1 (en) * 1997-07-16 2006-02-28 Metacure N.V. Blood glucose level control
US5904666A (en) * 1997-08-18 1999-05-18 L.Vad Technology, Inc. Method and apparatus for measuring flow rate and controlling delivered volume of fluid through a valve aperture
US5917346A (en) 1997-09-12 1999-06-29 Alfred E. Mann Foundation Low power current to frequency converter circuit for use in implantable sensors
US5999848A (en) 1997-09-12 1999-12-07 Alfred E. Mann Foundation Daisy chainable sensors and stimulators for implantation in living tissue
US6117290A (en) * 1997-09-26 2000-09-12 Pepex Biomedical, Llc System and method for measuring a bioanalyte such as lactate
US6007775A (en) 1997-09-26 1999-12-28 University Of Washington Multiple analyte diffusion based chemical sensor
US5967986A (en) 1997-11-25 1999-10-19 Vascusense, Inc. Endoluminal implant with fluid flow sensing capability
US6088608A (en) * 1997-10-20 2000-07-11 Alfred E. Mann Foundation Electrochemical sensor and integrity tests therefor
US6081736A (en) 1997-10-20 2000-06-27 Alfred E. Mann Foundation Implantable enzyme-based monitoring systems adapted for long term use
US6032667A (en) * 1997-10-30 2000-03-07 Instrumentarium Corporation Variable orifice pulse valve
US6070093A (en) 1997-12-02 2000-05-30 Abbott Laboratories Multiplex sensor and method of use
US6106486A (en) * 1997-12-22 2000-08-22 Radi Medical Systems Ab Guide wire
US6432050B1 (en) * 1997-12-30 2002-08-13 Remon Medical Technologies Ltd. Implantable acoustic bio-sensing system and method
US5904708A (en) * 1998-03-19 1999-05-18 Medtronic, Inc. System and method for deriving relative physiologic signals
US6175767B1 (en) * 1998-04-01 2001-01-16 James H. Doyle, Sr. Multichannel implantable inner ear stimulator
US6091975A (en) * 1998-04-01 2000-07-18 Alza Corporation Minimally invasive detecting device
US6223080B1 (en) * 1998-04-29 2001-04-24 Medtronic, Inc. Power consumption reduction in medical devices employing multiple digital signal processors and different supply voltages
US8974386B2 (en) 1998-04-30 2015-03-10 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6949816B2 (en) 2003-04-21 2005-09-27 Motorola, Inc. Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same
US6662030B2 (en) 1998-05-18 2003-12-09 Abbott Laboratories Non-invasive sensor having controllable temperature feature
TW495608B (en) 1998-08-26 2002-07-21 Sensors For Med & Science Inc Optical-based sensing devices
US6254586B1 (en) 1998-09-25 2001-07-03 Minimed Inc. Method and kit for supplying a fluid to a subcutaneous placement site
US6201980B1 (en) 1998-10-05 2001-03-13 The Regents Of The University Of California Implantable medical sensor system
US6591125B1 (en) 2000-06-27 2003-07-08 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US6338790B1 (en) 1998-10-08 2002-01-15 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US6016448A (en) * 1998-10-27 2000-01-18 Medtronic, Inc. Multilevel ERI for implantable medical devices
US6164921A (en) 1998-11-09 2000-12-26 Moubayed; Ahmad Maher Curvilinear peristaltic pump having insertable tubing assembly
US6353226B1 (en) 1998-11-23 2002-03-05 Abbott Laboratories Non-invasive sensor capable of determining optical parameters in a sample having multiple layers
CA2352571C (en) 1998-12-02 2007-02-27 Gary S. Sayler In vivo biosensor apparatus and method of use
US7405149B1 (en) 1998-12-21 2008-07-29 Megica Corporation Post passivation method for semiconductor chip or wafer
WO2000038570A1 (en) * 1998-12-31 2000-07-06 Ball Semiconductor, Inc. Miniature implanted orthopedic sensors
IT1307750B1 (en) 1999-02-04 2001-11-19 Saicom S R L PH REACTIVE AMPEROMETRIC BIOSENSOR
US6424847B1 (en) 1999-02-25 2002-07-23 Medtronic Minimed, Inc. Glucose monitor calibration methods
US6230059B1 (en) * 1999-03-17 2001-05-08 Medtronic, Inc. Implantable monitor
US6400992B1 (en) 1999-03-18 2002-06-04 Medtronic, Inc. Co-extruded, multi-lumen medical lead
US6585876B2 (en) 1999-04-08 2003-07-01 Applied Materials Inc. Flow diffuser to be used in electro-chemical plating system and method
US6223083B1 (en) * 1999-04-16 2001-04-24 Medtronic, Inc. Receiver employing digital filtering for use with an implantable medical device
US6465066B1 (en) 1999-05-11 2002-10-15 The Coca-Cola Company Packaged potable liquid and packaging for potable liquid
US6546268B1 (en) * 1999-06-02 2003-04-08 Ball Semiconductor, Inc. Glucose sensor
AU5747100A (en) 1999-06-18 2001-01-09 Therasense, Inc. Mass transport limited in vivo analyte sensor
DE60031427T2 (en) 1999-08-31 2007-09-20 NIR Diagnostics Inc., Campbellville METHOD FOR CALIBRATING A SPECTROSCOPY DEVICE
US6616819B1 (en) 1999-11-04 2003-09-09 Therasense, Inc. Small volume in vitro analyte sensor and methods
US7257328B2 (en) * 1999-12-13 2007-08-14 Finisar Corporation System and method for transmitting data on return path of a cable television system
WO2003008014A2 (en) 2000-01-21 2003-01-30 Medical Research Group Ambulatory medical apparatus with hand held communication device
DK1248660T3 (en) 2000-01-21 2012-07-23 Medtronic Minimed Inc Microprocessor controlled outpatient medical device with handheld communication device
US6974437B2 (en) 2000-01-21 2005-12-13 Medtronic Minimed, Inc. Microprocessor controlled ambulatory medical apparatus with hand held communication device
WO2001058348A2 (en) 2000-02-10 2001-08-16 Minimed Inc. Improved analyte sensor and method of making the same
US6528318B1 (en) 2000-03-06 2003-03-04 The Johns Hopkins University Scatter controlled emission for optical taggants and chemical sensors
AU2001263022A1 (en) 2000-05-12 2001-11-26 Therasense, Inc. Electrodes with multilayer membranes and methods of using and making the electrodes
US7181261B2 (en) * 2000-05-15 2007-02-20 Silver James H Implantable, retrievable, thrombus minimizing sensors
US6885883B2 (en) 2000-05-16 2005-04-26 Cygnus, Inc. Methods for improving performance and reliability of biosensors
WO2001091218A2 (en) 2000-05-22 2001-11-29 Acumentrics Corporation Electrode-supported solid state electrochemical cell
US6400974B1 (en) * 2000-06-29 2002-06-04 Sensors For Medicine And Science, Inc. Implanted sensor processing system and method for processing implanted sensor output
US6609071B2 (en) * 2000-12-06 2003-08-19 Project Cd System for monitoring and controlling pressure and concentration values in a fluid conduit
DE60045740D1 (en) 2000-12-12 2011-04-28 Sony Deutschland Gmbh Selective chemical sensors based on chained nanoparticle accumulations
US6642015B2 (en) 2000-12-29 2003-11-04 Minimed Inc. Hydrophilic polymeric material for coating biosensors
US6968743B2 (en) 2001-01-22 2005-11-29 Integrated Sensing Systems, Inc. Implantable sensing device for physiologic parameter measurement
US7268562B2 (en) 2001-02-15 2007-09-11 Integral Technologies, Inc. Low cost detectible pipe and electric fencing manufactured from conductive loaded resin-based materials
US6749587B2 (en) * 2001-02-22 2004-06-15 Insulet Corporation Modular infusion device and method
WO2002090948A1 (en) 2001-05-03 2002-11-14 Delta Dansk Elektronik, Lys & Akustik Apparatus and sensing devices for measuring fluorescence lifetimes of fluorescence sensors
US7135342B2 (en) 2001-05-04 2006-11-14 Sensors For Medicine And Science, Inc. Electro-optical sensing device with reference channel
US6613379B2 (en) * 2001-05-08 2003-09-02 Isense Corp. Implantable analyte sensor
US20020179457A1 (en) 2001-05-18 2002-12-05 Adam Heller Electrochemical method for high-throughput screening of minute quantities of candidate compounds
US6960466B2 (en) 2001-05-31 2005-11-01 Instrumentation Laboratory Company Composite membrane containing a cross-linked enzyme matrix for a biosensor
US6872297B2 (en) 2001-05-31 2005-03-29 Instrumentation Laboratory Company Analytical instruments, biosensors and methods thereof
US6501976B1 (en) 2001-06-12 2002-12-31 Lifescan, Inc. Percutaneous biological fluid sampling and analyte measurement devices and methods
WO2003000127A2 (en) * 2001-06-22 2003-01-03 Cygnus, Inc. Method for improving the performance of an analyte monitoring system
US6986739B2 (en) 2001-08-23 2006-01-17 Sciperio, Inc. Architecture tool and methods of use
EP1288308A1 (en) 2001-08-28 2003-03-05 Roche Diagnostics GmbH A method for the determination of multiple analytes
US7166208B2 (en) 2004-03-03 2007-01-23 Stephen Eliot Zweig Apoenzyme reactivation electrochemical detection method and assay
US6915147B2 (en) 2001-09-07 2005-07-05 Medtronic Minimed, Inc. Sensing apparatus and process
JP2003084101A (en) * 2001-09-17 2003-03-19 Dainippon Printing Co Ltd Resin composition for optical device, optical device and projection screen
US7425877B2 (en) 2001-09-21 2008-09-16 Ultrasource, Inc. Lange coupler system and method
US6809507B2 (en) 2001-10-23 2004-10-26 Medtronic Minimed, Inc. Implantable sensor electrodes and electronic circuitry
US7061593B2 (en) 2001-11-08 2006-06-13 Optiscan Biomedical Corp. Device and method for in vitro determination of analyte concentrations within body fluids
US6814845B2 (en) 2001-11-21 2004-11-09 University Of Kansas Method for depositing an enzyme on an electrically conductive substrate
US20030113573A1 (en) 2001-12-19 2003-06-19 Pepin John Graeme Thick film composition yielding magnetic properties
DE10163972B4 (en) 2001-12-22 2005-10-27 Roche Diagnostics Gmbh Method and device for determining a light transport parameter and an analyte in a biological matrix
US7022072B2 (en) 2001-12-27 2006-04-04 Medtronic Minimed, Inc. System for monitoring physiological characteristics
US20050027182A1 (en) 2001-12-27 2005-02-03 Uzair Siddiqui System for monitoring physiological characteristics
US7399277B2 (en) 2001-12-27 2008-07-15 Medtronic Minimed, Inc. System for monitoring physiological characteristics
US7613491B2 (en) 2002-05-22 2009-11-03 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US7828728B2 (en) 2003-07-25 2010-11-09 Dexcom, Inc. Analyte sensor
US8364229B2 (en) 2003-07-25 2013-01-29 Dexcom, Inc. Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise
US8010174B2 (en) 2003-08-22 2011-08-30 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US7419821B2 (en) 2002-03-05 2008-09-02 I-Stat Corporation Apparatus and methods for analyte measurement and immunoassay
CA2480550C (en) 2002-03-22 2011-07-12 Cygnus, Inc. Improving performance of an analyte monitoring device
JP2003297163A (en) * 2002-04-03 2003-10-17 Hitachi Cable Ltd Method for manufacturing enameled wire
US20070227907A1 (en) 2006-04-04 2007-10-04 Rajiv Shah Methods and materials for controlling the electrochemistry of analyte sensors
US7813780B2 (en) 2005-12-13 2010-10-12 Medtronic Minimed, Inc. Biosensors and methods for making and using them
US7069078B2 (en) 2002-04-22 2006-06-27 Medtronic, Inc. Insulin-mediated glucose uptake monitor
US6743635B2 (en) 2002-04-25 2004-06-01 Home Diagnostics, Inc. System and methods for blood glucose sensing
US7368190B2 (en) 2002-05-02 2008-05-06 Abbott Diabetes Care Inc. Miniature biological fuel cell that is operational under physiological conditions, and associated devices and methods
US20060258761A1 (en) 2002-05-22 2006-11-16 Robert Boock Silicone based membranes for use in implantable glucose sensors
US7226978B2 (en) * 2002-05-22 2007-06-05 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
EP1514096B1 (en) 2002-06-03 2011-02-02 Arizona Board Of Regents Acting for Northern Arizona University Hybrid microcantilever sensors
US7288368B2 (en) 2002-06-17 2007-10-30 Stephen Eliot Zweig Membrane receptor reagent and assay
AU2003279777A1 (en) * 2002-06-28 2004-01-19 November Aktiengesellschaft Gesellschaft Fur Molekulare Medizin Electrochemical detection method and device
US7171312B2 (en) 2002-07-19 2007-01-30 Smiths Detection, Inc. Chemical and biological agent sensor array detectors
US7312040B2 (en) 2002-09-20 2007-12-25 Agilent Technologies, Inc. Microcapsule biosensors and methods of using the same
US8303511B2 (en) 2002-09-26 2012-11-06 Pacesetter, Inc. Implantable pressure transducer system optimized for reduced thrombosis effect
US7303875B1 (en) 2002-10-10 2007-12-04 Nanosys, Inc. Nano-chem-FET based biosensors
US20040180391A1 (en) 2002-10-11 2004-09-16 Miklos Gratzl Sliver type autonomous biosensors
US9237865B2 (en) 2002-10-18 2016-01-19 Medtronic Minimed, Inc. Analyte sensors and methods for making and using them
US20050272989A1 (en) 2004-06-04 2005-12-08 Medtronic Minimed, Inc. Analyte sensors and methods for making and using them
US7228160B2 (en) * 2002-11-13 2007-06-05 Sorenson Medical, Inc. System, apparatus and method for inferring glucose levels within the peritoneum with implantable sensors
US7062385B2 (en) 2002-11-25 2006-06-13 Tufts University Intelligent electro-optical nucleic acid-based sensor array and method for detecting volatile compounds in ambient air
US6918982B2 (en) 2002-12-09 2005-07-19 International Business Machines Corporation System and method of transfer printing an organic semiconductor
US7120483B2 (en) * 2003-01-13 2006-10-10 Isense Corporation Methods for analyte sensing and measurement
US8003374B2 (en) 2003-03-25 2011-08-23 The Regents Of The University Of California Reagentless, reusable, bioelectronic detectors
US6965791B1 (en) 2003-03-26 2005-11-15 Sorenson Medical, Inc. Implantable biosensor system, apparatus and method
WO2004106891A2 (en) 2003-05-22 2004-12-09 University Of Hawaii Ultrasensitive biochemical sensor
US8460243B2 (en) 2003-06-10 2013-06-11 Abbott Diabetes Care Inc. Glucose measuring module and insulin pump combination
US7146202B2 (en) * 2003-06-16 2006-12-05 Isense Corporation Compound material analyte sensor
US7108733B2 (en) * 2003-06-20 2006-09-19 Massachusetts Institute Of Technology Metal slurry for electrode formation and production method of the same
EP1642125B1 (en) 2003-06-20 2017-09-27 Roche Diabetes Care GmbH Biosensor with multiple electrical functionalities
ES2683013T3 (en) 2003-06-20 2018-09-24 F. Hoffmann-La Roche Ag Reagent band for test strip
WO2005010518A1 (en) * 2003-07-23 2005-02-03 Dexcom, Inc. Rolled electrode array and its method for manufacture
US7366556B2 (en) * 2003-12-05 2008-04-29 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US20050176136A1 (en) 2003-11-19 2005-08-11 Dexcom, Inc. Afinity domain for analyte sensor
US7424318B2 (en) * 2003-12-05 2008-09-09 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
WO2007120442A2 (en) 2003-07-25 2007-10-25 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
EP1648298A4 (en) 2003-07-25 2010-01-13 Dexcom Inc Oxygen enhancing membrane systems for implantable devices
EP1649260A4 (en) 2003-07-25 2010-07-07 Dexcom Inc Electrode systems for electrochemical sensors
US7467003B2 (en) 2003-12-05 2008-12-16 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US8275437B2 (en) 2003-08-01 2012-09-25 Dexcom, Inc. Transcutaneous analyte sensor
US8845536B2 (en) 2003-08-01 2014-09-30 Dexcom, Inc. Transcutaneous analyte sensor
US20070208245A1 (en) 2003-08-01 2007-09-06 Brauker James H Transcutaneous analyte sensor
US8886273B2 (en) 2003-08-01 2014-11-11 Dexcom, Inc. Analyte sensor
US7774145B2 (en) 2003-08-01 2010-08-10 Dexcom, Inc. Transcutaneous analyte sensor
US8160669B2 (en) 2003-08-01 2012-04-17 Dexcom, Inc. Transcutaneous analyte sensor
US6931327B2 (en) 2003-08-01 2005-08-16 Dexcom, Inc. System and methods for processing analyte sensor data
US7591801B2 (en) 2004-02-26 2009-09-22 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US7529574B2 (en) * 2003-08-14 2009-05-05 Isense Corporation Method of constructing a biosensor
US7920906B2 (en) 2005-03-10 2011-04-05 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US7632234B2 (en) 2003-08-29 2009-12-15 Medtronic, Inc. Implantable biosensor devices for monitoring cardiac marker molecules
US7214190B1 (en) 2003-09-09 2007-05-08 Kitchener Clark Wilson Apparatus and method for noninvasive monitoring of analytes in body fluids
US7682833B2 (en) 2003-09-10 2010-03-23 Abbott Point Of Care Inc. Immunoassay device with improved sample closure
US7723099B2 (en) 2003-09-10 2010-05-25 Abbott Point Of Care Inc. Immunoassay device with immuno-reference electrode
US7433727B2 (en) * 2003-09-24 2008-10-07 Legacy Good Samaritan Hospital And Medical Center Implantable biosensor
US7970466B2 (en) 2003-10-07 2011-06-28 Medtronic, Inc. Method and apparatus for optimization and assessment of response to extra-systolic stimulation (ESS) therapy
US20050090607A1 (en) 2003-10-28 2005-04-28 Dexcom, Inc. Silicone composition for biocompatible membrane
WO2005048834A1 (en) 2003-11-13 2005-06-02 Medtronic Minimed, Inc. Long term analyte sensor array
US8414489B2 (en) 2003-11-13 2013-04-09 Medtronic Minimed, Inc. Fabrication of multi-sensor arrays
US20050158356A1 (en) 2003-11-20 2005-07-21 Angiotech International Ag Implantable sensors and implantable pumps and anti-scarring agents
US7524455B2 (en) * 2003-11-24 2009-04-28 General Electric Company Methods for deposition of sensor regions onto optical storage media substrates and resulting devices
US8425417B2 (en) 2003-12-05 2013-04-23 Dexcom, Inc. Integrated device for continuous in vivo analyte detection and simultaneous control of an infusion device
US20080197024A1 (en) 2003-12-05 2008-08-21 Dexcom, Inc. Analyte sensor
US8364230B2 (en) * 2006-10-04 2013-01-29 Dexcom, Inc. Analyte sensor
ATE480761T1 (en) 2003-12-05 2010-09-15 Dexcom Inc CALIBRATION METHODS FOR A CONTINUOUSLY WORKING ANALYTICAL SENSOR
US8425416B2 (en) 2006-10-04 2013-04-23 Dexcom, Inc. Analyte sensor
US8423114B2 (en) 2006-10-04 2013-04-16 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US20080200788A1 (en) 2006-10-04 2008-08-21 Dexcorn, Inc. Analyte sensor
ATE474219T1 (en) 2003-12-08 2010-07-15 Dexcom Inc SYSTEMS AND METHODS FOR IMPROVING ELECTROCHEMICAL ANALYT SENSORS
WO2005057175A2 (en) 2003-12-09 2005-06-23 Dexcom, Inc. Signal processing for continuous analyte sensor
US20050136500A1 (en) * 2003-12-19 2005-06-23 Kimberly-Clark Worldwide; Inc. Flow-through assay devices
US7553625B2 (en) * 2003-12-22 2009-06-30 John Wayne Cancer Institute Method and apparatus for in vivo collection of circulating biological components
DE60315691D1 (en) 2003-12-22 2007-09-27 Sgs Thomson Microelectronics Method of producing sensors with barriers of photoresist material
US8948836B2 (en) 2003-12-26 2015-02-03 Medtronic Minimed, Inc. Implantable apparatus for sensing multiple parameters
US7637868B2 (en) 2004-01-12 2009-12-29 Dexcom, Inc. Composite material for implantable device
US20050182451A1 (en) 2004-01-12 2005-08-18 Adam Griffin Implantable device with improved radio frequency capabilities
US20070027284A1 (en) 2004-01-13 2007-02-01 Kuang-Hwa Wei Covalently bonded polyhedral oligomeric silsesquioxane/polyimide nanocomposites and process for synthesizing the same
WO2005079257A2 (en) 2004-02-12 2005-09-01 Dexcom, Inc. Biointerface with macro- and micro- architecture
CA2556331A1 (en) 2004-02-17 2005-09-29 Therasense, Inc. Method and system for providing data communication in continuous glucose monitoring and management system
US20050196974A1 (en) * 2004-03-02 2005-09-08 Weigel Scott J. Compositions for preparing low dielectric materials containing solvents
CN101124472A (en) 2004-03-17 2008-02-13 夏威夷大学 Sensor constructs and detection methods
US7280879B2 (en) 2004-05-20 2007-10-09 Sap Ag Interfaces from external systems to time dependent process parameters in integrated process and product engineering
US20080242961A1 (en) 2004-07-13 2008-10-02 Dexcom, Inc. Transcutaneous analyte sensor
US8452368B2 (en) 2004-07-13 2013-05-28 Dexcom, Inc. Transcutaneous analyte sensor
US7783333B2 (en) * 2004-07-13 2010-08-24 Dexcom, Inc. Transcutaneous medical device with variable stiffness
JP2008510154A (en) 2004-08-16 2008-04-03 ノボ ノルディスク アクティーゼルスカブ Multiphase biocompatible semipermeable membrane for biosensors
WO2006127023A2 (en) 2004-08-24 2006-11-30 University Of South Florida Epoxy enhanced polymer membrane to increase durability of biosensors
US7519433B2 (en) * 2004-08-25 2009-04-14 Medtronic Transneuronix, Inc. Gastrointestinal stimulation lead
US7387811B2 (en) 2004-09-21 2008-06-17 Superpower, Inc. Method for manufacturing high temperature superconducting conductors using chemical vapor deposition (CVD)
US7384532B2 (en) 2004-11-16 2008-06-10 Lacks Enterprises, Inc. Platable coating and plating process
US20060122864A1 (en) 2004-12-02 2006-06-08 Gottesman Janell M Patient management network
CN100367906C (en) 2004-12-08 2008-02-13 圣美迪诺医疗科技(湖州)有限公司 Endermic implantating biological sensors
US7625596B2 (en) * 2004-12-15 2009-12-01 General Electric Company Adhesion promoter, electroactive layer and electroactive device comprising same, and method
US9259175B2 (en) 2006-10-23 2016-02-16 Abbott Diabetes Care, Inc. Flexible patch for fluid delivery and monitoring body analytes
WO2006076603A2 (en) * 2005-01-14 2006-07-20 Cabot Corporation Printable electrical conductors
US8133178B2 (en) 2006-02-22 2012-03-13 Dexcom, Inc. Analyte sensor
WO2006097934A2 (en) 2005-03-18 2006-09-21 Metacure Limited Pancreas lead
US8744546B2 (en) 2005-05-05 2014-06-03 Dexcom, Inc. Cellulosic-based resistance domain for an analyte sensor
US20060249381A1 (en) 2005-05-05 2006-11-09 Petisce James R Cellulosic-based resistance domain for an analyte sensor
WO2006113618A1 (en) 2005-04-15 2006-10-26 Dexcom, Inc. Analyte sensing biointerface
US7308292B2 (en) 2005-04-15 2007-12-11 Sensors For Medicine And Science, Inc. Optical-based sensing devices
US8060174B2 (en) 2005-04-15 2011-11-15 Dexcom, Inc. Analyte sensing biointerface
US20060263839A1 (en) 2005-05-17 2006-11-23 Isense Corporation Combined drug delivery and analyte sensor apparatus
JP4690115B2 (en) 2005-05-31 2011-06-01 株式会社リコー Control apparatus and image processing apparatus
US8021299B2 (en) 2005-06-01 2011-09-20 Medtronic, Inc. Correlating a non-polysomnographic physiological parameter set with sleep states
US7905999B2 (en) 2005-06-08 2011-03-15 Abbott Laboratories Biosensor strips and methods of preparing same
CA2612635C (en) 2005-07-14 2013-03-12 I-Stat Corporation Photoformed silicone sensor membrane
US7725148B2 (en) 2005-09-23 2010-05-25 Medtronic Minimed, Inc. Sensor with layered electrodes
US20080112853A1 (en) * 2006-08-15 2008-05-15 Hall W Dale Method and apparatus for analyte measurements in the presence of interferents
EP1785085A1 (en) 2005-11-12 2007-05-16 Roche Diagnostics GmbH Implantable electrode system, method and device for measuring the concentration of an analyte in a human or animal body
EP1954190A4 (en) 2005-11-15 2010-10-13 Luminous Medical Inc Blood analyte determinations
US20070135699A1 (en) 2005-12-12 2007-06-14 Isense Corporation Biosensor with antimicrobial agent
US7955484B2 (en) * 2005-12-14 2011-06-07 Nova Biomedical Corporation Glucose biosensor and method
US20070173712A1 (en) 2005-12-30 2007-07-26 Medtronic Minimed, Inc. Method of and system for stabilization of sensors
US7774038B2 (en) 2005-12-30 2010-08-10 Medtronic Minimed, Inc. Real-time self-calibrating sensor system and method
EP1973503B1 (en) * 2006-01-04 2013-09-25 The Trustees of the University of Pennsylvania Oxygen sensor for internal monitoring of tissue oxygen in vivo
EP2004796B1 (en) 2006-01-18 2015-04-08 DexCom, Inc. Membranes for an analyte sensor
EP3649925A1 (en) 2006-02-22 2020-05-13 DexCom, Inc. Analyte sensor
US20070202562A1 (en) 2006-02-27 2007-08-30 Curry Kenneth M Flux limiting membrane for intravenous amperometric biosensor
US7885698B2 (en) * 2006-02-28 2011-02-08 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US7826879B2 (en) 2006-02-28 2010-11-02 Abbott Diabetes Care Inc. Analyte sensors and methods of use
US20070227633A1 (en) * 2006-04-04 2007-10-04 Basol Bulent M Composition control for roll-to-roll processed photovoltaic films
US7684872B2 (en) 2006-04-26 2010-03-23 Medtronic, Inc. Contactless interconnect for transducers
US7855653B2 (en) 2006-04-28 2010-12-21 Medtronic, Inc. External voiding sensor system
US20070255126A1 (en) 2006-04-28 2007-11-01 Moberg Sheldon B Data communication in networked fluid infusion systems
US9119582B2 (en) 2006-06-30 2015-09-01 Abbott Diabetes Care, Inc. Integrated analyte sensor and infusion device and methods therefor
US8114023B2 (en) * 2006-07-28 2012-02-14 Legacy Emanuel Hospital & Health Center Analyte sensing and response system
WO2008017042A1 (en) * 2006-08-03 2008-02-07 Microchips, Inc. Cardiac biosensor devices and methods
WO2009008892A1 (en) * 2006-08-15 2009-01-15 Optiscan Biomedical Corporation Accurate and timely body fluid analysis
CA2701006C (en) * 2006-09-27 2016-07-12 University Of Connecticut Implantable biosensor and methods of use thereof
US7831287B2 (en) 2006-10-04 2010-11-09 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US8449464B2 (en) 2006-10-04 2013-05-28 Dexcom, Inc. Analyte sensor
US8298142B2 (en) 2006-10-04 2012-10-30 Dexcom, Inc. Analyte sensor
US8447376B2 (en) * 2006-10-04 2013-05-21 Dexcom, Inc. Analyte sensor
US8478377B2 (en) 2006-10-04 2013-07-02 Dexcom, Inc. Analyte sensor
US8275438B2 (en) 2006-10-04 2012-09-25 Dexcom, Inc. Analyte sensor
US8562528B2 (en) * 2006-10-04 2013-10-22 Dexcom, Inc. Analyte sensor
DE602007008278D1 (en) 2006-10-15 2010-09-16 Roche Diagnostics Gmbh DIAGNOSTIC TEST ELEMENT AND METHOD FOR THE PRODUCTION THEREOF
EP2097750A2 (en) 2006-10-26 2009-09-09 Abbott Laboratories Immunoassay of analytes in samples containing endogenous anti-analyte antibodies
AU2007308804A1 (en) 2006-10-26 2008-05-02 Abbott Diabetes Care, Inc. Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors
WO2008076868A2 (en) 2006-12-18 2008-06-26 Abbott Laboratories Methods and compositions related to modulation of receptor tyrosine kinase orphan receptor-1 (ror-1)
WO2008082979A2 (en) 2006-12-29 2008-07-10 Abbott Laboratories Diagnostic test for the detection of a molecule or drug in whole blood
US7914999B2 (en) 2006-12-29 2011-03-29 Abbott Laboratories Non-denaturing lysis reagent
US7946985B2 (en) 2006-12-29 2011-05-24 Medtronic Minimed, Inc. Method and system for providing sensor redundancy
US10154804B2 (en) 2007-01-31 2018-12-18 Medtronic Minimed, Inc. Model predictive method and system for controlling and supervising insulin infusion
US20080269723A1 (en) 2007-04-25 2008-10-30 Medtronic Minimed, Inc. Closed loop/semi-closed loop therapy modification system
EP1987761B1 (en) 2007-05-03 2019-10-23 F. Hoffmann-La Roche AG Tube-like sensor for proving an analyte
WO2008150917A1 (en) 2007-05-31 2008-12-11 Abbott Diabetes Care, Inc. Insertion devices and methods
US9839395B2 (en) 2007-12-17 2017-12-12 Dexcom, Inc. Systems and methods for processing sensor data
US20090247855A1 (en) 2008-03-28 2009-10-01 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8700114B2 (en) * 2008-07-31 2014-04-15 Medtronic Minmed, Inc. Analyte sensor apparatuses comprising multiple implantable sensor elements and methods for making and using them
TW201111452A (en) * 2009-06-12 2011-04-01 Du Pont Ink jettable silver/silver-chloride compositions

Patent Citations (123)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1966575A (en) * 1931-04-23 1934-07-17 E M F Electric Company Proprie Automatic weld rod manufacturing apparatus
US2497894A (en) * 1944-10-14 1950-02-21 Nat Standard Co Method of electroplating fine wire of low elastic limit
US2489456A (en) * 1945-08-21 1949-11-29 Robert A Liebel Method of applying uniform coating by immersion
US2728831A (en) * 1951-11-09 1955-12-27 Phys Chemical Res Corp Electric hygrometer
US2889239A (en) * 1958-03-12 1959-06-02 Bell Telephone Labor Inc Method for making a transposed conductor structure
US3658571A (en) * 1970-04-29 1972-04-25 Owens Corning Fiberglass Corp Glass fiber reinforced elastomers
US3933593A (en) * 1971-02-22 1976-01-20 Beckman Instruments, Inc. Rate sensing batch analysis method
US3930462A (en) * 1975-05-08 1976-01-06 United Technologies Corporation Slurry dip tank
US4126510A (en) * 1977-10-06 1978-11-21 Rca Corporation Etching a succession of articles from a strip of sheet metal
US4826706A (en) * 1981-04-29 1989-05-02 Phelps Dodge Industries, Inc. Method and apparatus for manufacturing magnet wire
US4422583A (en) * 1981-12-14 1983-12-27 Usm Corporation Wire feeder
US4644898A (en) * 1985-04-19 1987-02-24 U.S. Philips Corporation Arrangement for coating optical fibres
US4736748A (en) * 1986-04-05 1988-04-12 Kuraray Co., Ltd. Blood component monitoring system
US4726381A (en) * 1986-06-04 1988-02-23 Solutech, Inc. Dialysis system and method
US4886562A (en) * 1987-03-31 1989-12-12 The Boeing Company Method of manufacturing reinforced optical fiber
US4832034A (en) * 1987-04-09 1989-05-23 Pizziconi Vincent B Method and apparatus for withdrawing, collecting and biosensing chemical constituents from complex fluids
US4890621A (en) * 1988-01-19 1990-01-02 Northstar Research Institute, Ltd. Continuous glucose monitoring and a system utilized therefor
US5200051A (en) * 1988-11-14 1993-04-06 I-Stat Corporation Wholly microfabricated biosensors and process for the manufacture and use thereof
US5212050A (en) * 1988-11-14 1993-05-18 Mier Randall M Method of forming a permselective layer
US5312590A (en) * 1989-04-24 1994-05-17 National University Of Singapore Amperometric sensor for single and multicomponent analysis
US5380422A (en) * 1991-07-18 1995-01-10 Agency Of Industrial Science And Technology Micro-electrode and method for preparing it
US5524338A (en) * 1991-10-22 1996-06-11 Pi Medical Corporation Method of making implantable microelectrode
US5310469A (en) * 1991-12-31 1994-05-10 Abbott Laboratories Biosensor with a membrane containing biologically active material
US5372293A (en) * 1992-11-23 1994-12-13 Carrar Apparatus for degolding or tinning conductive portions of a microelectronic device
US5683514A (en) * 1992-12-15 1997-11-04 Weirton Steel Corporation Coating control apparatus
US5497772A (en) * 1993-11-19 1996-03-12 Alfred E. Mann Foundation For Scientific Research Glucose monitoring system
US20010008187A1 (en) * 1994-07-05 2001-07-19 Hans Hanssen Coaxial cable
US6063637A (en) * 1995-12-13 2000-05-16 California Institute Of Technology Sensors for sugars and other metal binding analytes
US20040039298A1 (en) * 1996-09-04 2004-02-26 Abreu Marcio Marc Noninvasive measurement of chemical substances
US6558321B1 (en) * 1997-03-04 2003-05-06 Dexcom, Inc. Systems and methods for remote monitoring and modulation of medical devices
US5928571A (en) * 1997-08-29 1999-07-27 E. I. Du Pont De Nemours And Company Thick film compositions for making medical electrodes
US5879828A (en) * 1997-10-10 1999-03-09 Minnesota Mining And Manufacturing Company Membrane electrode assembly
US20030100040A1 (en) * 1997-12-05 2003-05-29 Therasense Inc. Blood analyte monitoring through subcutaneous measurement
US6103033A (en) * 1998-03-04 2000-08-15 Therasense, Inc. Process for producing an electrochemical biosensor
US20030088166A1 (en) * 1998-03-04 2003-05-08 Therasense, Inc. Electrochemical analyte sensor
US7190988B2 (en) * 1998-04-30 2007-03-13 Abbott Diabetes Care, Inc. Analyte monitoring device and methods of use
US6565509B1 (en) * 1998-04-30 2003-05-20 Therasense, Inc. Analyte monitoring device and methods of use
US6990366B2 (en) * 1998-04-30 2006-01-24 Therasense, Inc. Analyte monitoring device and methods of use
US7003341B2 (en) * 1998-04-30 2006-02-21 Abbott Diabetes Care, Inc. Analyte monitoring devices and methods of use
US6175752B1 (en) * 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
US6740214B1 (en) * 1998-05-08 2004-05-25 Isis Innovation Limited Microelectrode biosensor and method therefor
US6393318B1 (en) * 1998-05-13 2002-05-21 Cygnus, Inc. Collection assemblies, laminates, and autosensor assemblies for use in transdermal sampling systems
US6341232B1 (en) * 1998-05-13 2002-01-22 Cygnus, Inc. Methods of producing collection assemblies, laminates, and autosensor assemblies for use in transdermal sampling systems
US6214115B1 (en) * 1998-07-21 2001-04-10 Biocompatibles Limited Coating
US6187378B1 (en) * 1998-10-01 2001-02-13 Lucent Technologies Inc. Automated system and method for electroless plating of optical fibers
US20060001550A1 (en) * 1998-10-08 2006-01-05 Mann Alfred E Telemetered characteristic monitor system and method of using the same
US7163511B2 (en) * 1999-02-12 2007-01-16 Animas Technologies, Llc Devices and methods for frequent measurement of an analyte present in a biological system
US6561978B1 (en) * 1999-02-12 2003-05-13 Cygnus, Inc. Devices and methods for frequent measurement of an analyte present in a biological system
US6520326B2 (en) * 1999-02-25 2003-02-18 Medtronic Minimed, Inc. Glucose sensor package system
US20020023852A1 (en) * 1999-02-25 2002-02-28 Minimed Inc. Glucose sensor package system
US20030078481A1 (en) * 1999-02-25 2003-04-24 Minimed Inc. Glucose sensor package system
US6892085B2 (en) * 1999-02-25 2005-05-10 Medtronic Minimed, Inc. Glucose sensor package system
US6360888B1 (en) * 1999-02-25 2002-03-26 Minimed Inc. Glucose sensor package system
US6368658B1 (en) * 1999-04-19 2002-04-09 Scimed Life Systems, Inc. Coating medical devices using air suspension
US6413393B1 (en) * 1999-07-07 2002-07-02 Minimed, Inc. Sensor including UV-absorbing polymer and method of manufacture
US20070084560A1 (en) * 1999-09-29 2007-04-19 Fuentes Ricardo I Wet processing using a fluid meniscus, apparatus and method
US6558320B1 (en) * 2000-01-20 2003-05-06 Medtronic Minimed, Inc. Handheld personal data assistant (PDA) with a medical device and method of using the same
US7003336B2 (en) * 2000-02-10 2006-02-21 Medtronic Minimed, Inc. Analyte sensor method of making the same
US6895263B2 (en) * 2000-02-23 2005-05-17 Medtronic Minimed, Inc. Real time self-adjusting calibration algorithm
US6895265B2 (en) * 2000-05-15 2005-05-17 James H. Silver Implantable sensor
US7033322B2 (en) * 2000-05-15 2006-04-25 Silver James H Implantable sensor
US20060079740A1 (en) * 2000-05-15 2006-04-13 Silver James H Sensors for detecting substances indicative of stroke, ischemia, or myocardial infarction
US20030009093A1 (en) * 2000-05-15 2003-01-09 Silver James H. Implantable sensor
US20080091094A1 (en) * 2001-01-02 2008-04-17 Abbott Diabetes Care, Inc. Analyte Monitoring Device And Methods Of Use
US6560471B1 (en) * 2001-01-02 2003-05-06 Therasense, Inc. Analyte monitoring device and methods of use
US20030100821A1 (en) * 2001-01-02 2003-05-29 Therasense, Inc. Analyte monitoring device and methods of use
US20080086043A1 (en) * 2001-01-02 2008-04-10 Abbott Diabetes Care, Inc. Analyte Monitoring Device And Methods Of Use
US20080086041A1 (en) * 2001-01-02 2008-04-10 Abbott Diabetes Care, Inc. Analyte Monitoring Device And Methods Of Use
US20080086040A1 (en) * 2001-01-02 2008-04-10 Abbott Diabetes Care, Inc. Analyte Monitoring Device And Methods Of Use
US20080091095A1 (en) * 2001-01-02 2008-04-17 Abbott Diabetes Care, Inc. Analyte Monitoring Device And Methods Of Use
US6989891B2 (en) * 2001-11-08 2006-01-24 Optiscan Biomedical Corporation Device and method for in vitro determination of analyte concentrations within body fluids
US20040078219A1 (en) * 2001-12-04 2004-04-22 Kimberly-Clark Worldwide, Inc. Healthcare networks with biosensors
US6998247B2 (en) * 2002-03-08 2006-02-14 Sensys Medical, Inc. Method and apparatus using alternative site glucose determinations to calibrate and maintain noninvasive and implantable analyzers
US20030188965A1 (en) * 2002-04-05 2003-10-09 3M Innovative Properties Company Web processing method and apparatus
US20040010207A1 (en) * 2002-07-15 2004-01-15 Flaherty J. Christopher Self-contained, automatic transcutaneous physiologic sensing system
US20050065464A1 (en) * 2002-07-24 2005-03-24 Medtronic Minimed, Inc. System for providing blood glucose measurements to an infusion device
US20040074785A1 (en) * 2002-10-18 2004-04-22 Holker James D. Analyte sensors and methods for making them
US20040258915A1 (en) * 2003-06-18 2004-12-23 Takeshi Hasui Method of forming corrosion protection double coatings on prestressing strand and prestressing strand produced by the method
US20080033254A1 (en) * 2003-07-25 2008-02-07 Dexcom, Inc. Systems and methods for replacing signal data artifacts in a glucose sensor data stream
US20050028731A1 (en) * 2003-08-04 2005-02-10 Fitel Usa Corp. Systems and methods for coating optical fiber
US20070016381A1 (en) * 2003-08-22 2007-01-18 Apurv Kamath Systems and methods for processing analyte sensor data
US20070032706A1 (en) * 2003-08-22 2007-02-08 Apurv Kamath Systems and methods for replacing signal artifacts in a glucose sensor data stream
US20070066873A1 (en) * 2003-08-22 2007-03-22 Apurv Kamath Systems and methods for processing analyte sensor data
US7519408B2 (en) * 2003-11-19 2009-04-14 Dexcom, Inc. Integrated receiver for continuous analyte sensor
US7927274B2 (en) * 2003-11-19 2011-04-19 Dexcom, Inc. Integrated receiver for continuous analyte sensor
US20070027385A1 (en) * 2003-12-05 2007-02-01 Mark Brister Dual electrode system for a continuous analyte sensor
US7366566B2 (en) * 2003-12-29 2008-04-29 Ela Medical S.A.S. Automatic commutations of AAI/DDD mode in the presence of paroxystic AVB in an active implantable medical device, in particular a cardiac pacemaker
US20090030294A1 (en) * 2004-05-03 2009-01-29 Dexcom, Inc. Implantable analyte sensor
US20090062633A1 (en) * 2004-05-03 2009-03-05 Dexcorn, Inc. Implantable analyte sensor
US20060015020A1 (en) * 2004-07-06 2006-01-19 Dexcom, Inc. Systems and methods for manufacture of an analyte-measuring device including a membrane system
US20070038044A1 (en) * 2004-07-13 2007-02-15 Dobbles J M Analyte sensor
US20060036141A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20070027370A1 (en) * 2004-07-13 2007-02-01 Brauker James H Analyte sensor
US20070059196A1 (en) * 2004-07-13 2007-03-15 Mark Brister Analyte sensor
US7494465B2 (en) * 2004-07-13 2009-02-24 Dexcom, Inc. Transcutaneous analyte sensor
US20090036763A1 (en) * 2004-07-13 2009-02-05 Dexcom, Inc. Analyte sensor
US20060019327A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060036140A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US7654956B2 (en) * 2004-07-13 2010-02-02 Dexcom, Inc. Transcutaneous analyte sensor
US20060036143A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060016700A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US7497827B2 (en) * 2004-07-13 2009-03-03 Dexcom, Inc. Transcutaneous analyte sensor
US20060036142A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060020192A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060020190A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060020186A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060020188A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20070045902A1 (en) * 2004-07-13 2007-03-01 Brauker James H Analyte sensor
US20090076361A1 (en) * 2004-07-13 2009-03-19 Dexcom, Inc. Transcutaneous analyte sensor
US20060020191A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060052745A1 (en) * 2004-09-08 2006-03-09 Van Antwerp Nannette M Blood contacting sensor
US7651596B2 (en) * 2005-04-08 2010-01-26 Dexcom, Inc. Cellulosic-based interference domain for an analyte sensor
US20070014124A1 (en) * 2005-07-18 2007-01-18 Peter Gerets Device for coupling the light of multiple light sources
US20080115727A1 (en) * 2005-08-05 2008-05-22 David R Otis Prothesis Having a Coating and Systems and Methods of Making the Same
US20070141245A1 (en) * 2005-12-20 2007-06-21 Steve Tsai System and method for coating filaments
US20090018424A1 (en) * 2006-10-04 2009-01-15 Dexcom, Inc. Analyte sensor
US20080119703A1 (en) * 2006-10-04 2008-05-22 Mark Brister Analyte sensor
US20080108942A1 (en) * 2006-10-04 2008-05-08 Dexcom, Inc. Analyte sensor
US20080086042A1 (en) * 2006-10-04 2008-04-10 Dexcom, Inc. Analyte sensor
US20080086044A1 (en) * 2006-10-04 2008-04-10 Dexcom, Inc. Analyte sensor
US20090076360A1 (en) * 2007-09-13 2009-03-19 Dexcom, Inc. Transcutaneous analyte sensor
US20110027458A1 (en) * 2009-07-02 2011-02-03 Dexcom, Inc. Continuous analyte sensors and methods of making same
US20110027453A1 (en) * 2009-07-02 2011-02-03 Dexcom, Inc. Continuous analyte sensors and methods of making same

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Chen et al “A novel drug-eluting stent spray-coated with multi-layers of collagen and sirolimus�, J. Controlled Release, 108, p. 178-189 (2005). *
Chen et al “A novel drug-eluting stent spray-coated with multi-layers of collagen and sirolimus”, J. Controlled Release, 108, p. 178-189 (2005). *

Cited By (483)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8660627B2 (en) 1998-04-30 2014-02-25 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9011331B2 (en) 1998-04-30 2015-04-21 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US20070191699A1 (en) * 1998-04-30 2007-08-16 Abbott Diabetes Care, Inc. Analyte Monitoring Device and Methods of Use
US20070203411A1 (en) * 1998-04-30 2007-08-30 Abbott Diabetes Care, Inc. Analyte Monitoring Device and Methods of Use
US20070203410A1 (en) * 1998-04-30 2007-08-30 Abbott Diabetes Care, Inc. Analyte Monitoring Device and Methods of Use
US20070208247A1 (en) * 1998-04-30 2007-09-06 Abbott Diabetes Care, Inc. Analyte Monitoring Device and Methods of Use
US20070244380A1 (en) * 1998-04-30 2007-10-18 Abbott Diabetes Care, Inc. Analyte monitoring device and methods of use
US20070249919A1 (en) * 1998-04-30 2007-10-25 Abbott Diabetes Care, Inc. Analyte monitoring device and methods of use
US20080033271A1 (en) * 1998-04-30 2008-02-07 Abbott Diabetes Care, Inc. Analyte monitoring device and methods of use
US9326714B2 (en) 1998-04-30 2016-05-03 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US20080091096A1 (en) * 1998-04-30 2008-04-17 Abbott Diabetes Care, Inc. Analyte Monitoring Device and Methods of Use
US20040171921A1 (en) * 1998-04-30 2004-09-02 James Say Analyte monitoring device and methods of use
US9072477B2 (en) 1998-04-30 2015-07-07 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9066694B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9066695B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US20090171179A1 (en) * 1998-04-30 2009-07-02 Abbott Diabetes Care, Inc. Analyte Monitoring Device and Methods of Use
US20090177064A1 (en) * 1998-04-30 2009-07-09 Abbott Diabetes Care, Inc. Analyte Monitoring Device and Methods of Use
US20090187088A1 (en) * 1998-04-30 2009-07-23 Abbott Diabetes Care Inc. Analyte Monitoring Device and Methods of Use
US9066697B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9042953B2 (en) 1998-04-30 2015-05-26 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US20060189863A1 (en) * 1998-04-30 2006-08-24 Abbott Diabetes Care, Inc. Analyte monitoring device and methods of use
US9014773B2 (en) 1998-04-30 2015-04-21 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8974386B2 (en) 1998-04-30 2015-03-10 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US20100268047A1 (en) * 1998-04-30 2010-10-21 Abbott Diabetes Care Inc. Analyte Monitoring Device and Methods of Use
US20100274111A1 (en) * 1998-04-30 2010-10-28 Abbott Diabetes Care Inc. Analyte Monitoring Device and Methods of Use
US8880137B2 (en) 1998-04-30 2014-11-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8840553B2 (en) 1998-04-30 2014-09-23 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8774887B2 (en) 1998-04-30 2014-07-08 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8162829B2 (en) 1998-04-30 2012-04-24 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8666469B2 (en) 1998-04-30 2014-03-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8177716B2 (en) 1998-04-30 2012-05-15 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8224413B2 (en) 1998-04-30 2012-07-17 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8226557B2 (en) 1998-04-30 2012-07-24 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8226558B2 (en) 1998-04-30 2012-07-24 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8226555B2 (en) 1998-04-30 2012-07-24 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8231532B2 (en) 1998-04-30 2012-07-31 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8235896B2 (en) 1998-04-30 2012-08-07 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8255031B2 (en) 1998-04-30 2012-08-28 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8260392B2 (en) 1998-04-30 2012-09-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8265726B2 (en) 1998-04-30 2012-09-11 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8273022B2 (en) 1998-04-30 2012-09-25 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8275439B2 (en) 1998-04-30 2012-09-25 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8287454B2 (en) 1998-04-30 2012-10-16 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8306598B2 (en) 1998-04-30 2012-11-06 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8346336B2 (en) 1998-04-30 2013-01-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8346337B2 (en) 1998-04-30 2013-01-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8353829B2 (en) 1998-04-30 2013-01-15 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8357091B2 (en) 1998-04-30 2013-01-22 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8366614B2 (en) 1998-04-30 2013-02-05 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8372005B2 (en) 1998-04-30 2013-02-12 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8380273B2 (en) 1998-04-30 2013-02-19 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8391945B2 (en) 1998-04-30 2013-03-05 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8409131B2 (en) 1998-04-30 2013-04-02 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8465425B2 (en) 1998-04-30 2013-06-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8473021B2 (en) 1998-04-30 2013-06-25 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8744545B2 (en) 1998-04-30 2014-06-03 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8480580B2 (en) 1998-04-30 2013-07-09 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8738109B2 (en) 1998-04-30 2014-05-27 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8734346B2 (en) 1998-04-30 2014-05-27 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8734348B2 (en) 1998-04-30 2014-05-27 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10478108B2 (en) 1998-04-30 2019-11-19 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8688188B2 (en) 1998-04-30 2014-04-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8672844B2 (en) 1998-04-30 2014-03-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8670815B2 (en) 1998-04-30 2014-03-11 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8175673B2 (en) 1998-04-30 2012-05-08 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8649841B2 (en) 1998-04-30 2014-02-11 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8597189B2 (en) 1998-04-30 2013-12-03 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8641619B2 (en) 1998-04-30 2014-02-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8622906B2 (en) 1998-04-30 2014-01-07 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8612159B2 (en) 1998-04-30 2013-12-17 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8617071B2 (en) 1998-04-30 2013-12-31 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9498159B2 (en) 2001-01-02 2016-11-22 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8668645B2 (en) 2001-01-02 2014-03-11 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9610034B2 (en) 2001-01-02 2017-04-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US20080086039A1 (en) * 2001-01-02 2008-04-10 Abbott Diabetes Care, Inc. Analyte Monitoring Device And Methods Of Use
US9011332B2 (en) 2001-01-02 2015-04-21 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8652043B2 (en) 2001-01-02 2014-02-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9980670B2 (en) 2002-11-05 2018-05-29 Abbott Diabetes Care Inc. Sensor inserter assembly
US10973443B2 (en) 2002-11-05 2021-04-13 Abbott Diabetes Care Inc. Sensor inserter assembly
US11116430B2 (en) 2002-11-05 2021-09-14 Abbott Diabetes Care Inc. Sensor inserter assembly
US11141084B2 (en) 2002-11-05 2021-10-12 Abbott Diabetes Care Inc. Sensor inserter assembly
USD914881S1 (en) 2003-11-05 2021-03-30 Abbott Diabetes Care Inc. Analyte sensor electronic mount
USD902408S1 (en) 2003-11-05 2020-11-17 Abbott Diabetes Care Inc. Analyte sensor control unit
US11020031B1 (en) 2003-12-05 2021-06-01 Dexcom, Inc. Analyte sensor
US11000215B1 (en) 2003-12-05 2021-05-11 Dexcom, Inc. Analyte sensor
US11627900B2 (en) 2003-12-05 2023-04-18 Dexcom, Inc. Analyte sensor
US10226207B2 (en) 2004-12-29 2019-03-12 Abbott Diabetes Care Inc. Sensor inserter having introducer
US11160475B2 (en) 2004-12-29 2021-11-02 Abbott Diabetes Care Inc. Sensor inserter having introducer
US8602991B2 (en) 2005-08-30 2013-12-10 Abbott Diabetes Care Inc. Analyte sensor introducer and methods of use
US10194850B2 (en) 2005-08-31 2019-02-05 Abbott Diabetes Care Inc. Accuracy of continuous glucose sensors
US9398882B2 (en) 2005-09-30 2016-07-26 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor and data processing device
US9521968B2 (en) 2005-09-30 2016-12-20 Abbott Diabetes Care Inc. Analyte sensor retention mechanism and methods of use
US9480421B2 (en) 2005-09-30 2016-11-01 Abbott Diabetes Care Inc. Integrated introducer and transmitter assembly and methods of use
USD979766S1 (en) 2005-09-30 2023-02-28 Abbott Diabetes Care Inc. Analyte sensor device
US20090054746A1 (en) * 2005-09-30 2009-02-26 Abbott Diabetes Care, Inc. Device for channeling fluid and methods of use
US8512243B2 (en) 2005-09-30 2013-08-20 Abbott Diabetes Care Inc. Integrated introducer and transmitter assembly and methods of use
US9775563B2 (en) 2005-09-30 2017-10-03 Abbott Diabetes Care Inc. Integrated introducer and transmitter assembly and methods of use
US8880138B2 (en) 2005-09-30 2014-11-04 Abbott Diabetes Care Inc. Device for channeling fluid and methods of use
US10194863B2 (en) 2005-09-30 2019-02-05 Abbott Diabetes Care Inc. Integrated transmitter unit and sensor introducer mechanism and methods of use
US11457869B2 (en) 2005-09-30 2022-10-04 Abbott Diabetes Care Inc. Integrated transmitter unit and sensor introducer mechanism and methods of use
US10342489B2 (en) 2005-09-30 2019-07-09 Abbott Diabetes Care Inc. Integrated introducer and transmitter assembly and methods of use
US11363975B2 (en) 2005-11-01 2022-06-21 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9326716B2 (en) 2005-11-01 2016-05-03 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8920319B2 (en) 2005-11-01 2014-12-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10231654B2 (en) 2005-11-01 2019-03-19 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US11103165B2 (en) 2005-11-01 2021-08-31 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US11399748B2 (en) 2005-11-01 2022-08-02 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10201301B2 (en) 2005-11-01 2019-02-12 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10952652B2 (en) 2005-11-01 2021-03-23 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US11272867B2 (en) 2005-11-01 2022-03-15 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US11911151B1 (en) 2005-11-01 2024-02-27 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9078607B2 (en) 2005-11-01 2015-07-14 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8915850B2 (en) 2005-11-01 2014-12-23 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10307091B2 (en) 2005-12-28 2019-06-04 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US11298058B2 (en) 2005-12-28 2022-04-12 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US9332933B2 (en) 2005-12-28 2016-05-10 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US8545403B2 (en) 2005-12-28 2013-10-01 Abbott Diabetes Care Inc. Medical device insertion
US8852101B2 (en) 2005-12-28 2014-10-07 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US9795331B2 (en) 2005-12-28 2017-10-24 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US9326727B2 (en) 2006-01-30 2016-05-03 Abbott Diabetes Care Inc. On-body medical device securement
US9844329B2 (en) 2006-02-28 2017-12-19 Abbott Diabetes Care Inc. Analyte sensors and methods of use
US10117614B2 (en) 2006-02-28 2018-11-06 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US11872039B2 (en) 2006-02-28 2024-01-16 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US9031630B2 (en) 2006-02-28 2015-05-12 Abbott Diabetes Care Inc. Analyte sensors and methods of use
USD961778S1 (en) 2006-02-28 2022-08-23 Abbott Diabetes Care Inc. Analyte sensor device
US10736547B2 (en) 2006-04-28 2020-08-11 Abbott Diabetes Care Inc. Introducer assembly and methods of use
US10028680B2 (en) 2006-04-28 2018-07-24 Abbott Diabetes Care Inc. Introducer assembly and methods of use
US10278630B2 (en) 2006-08-09 2019-05-07 Abbott Diabetes Care Inc. Method and system for providing calibration of an analyte sensor in an analyte monitoring system
US9408566B2 (en) 2006-08-09 2016-08-09 Abbott Diabetes Care Inc. Method and system for providing calibration of an analyte sensor in an analyte monitoring system
US9833181B2 (en) 2006-08-09 2017-12-05 Abbot Diabetes Care Inc. Method and system for providing calibration of an analyte sensor in an analyte monitoring system
US11864894B2 (en) 2006-08-09 2024-01-09 Abbott Diabetes Care Inc. Method and system for providing calibration of an analyte sensor in an analyte monitoring system
US9808186B2 (en) 2006-09-10 2017-11-07 Abbott Diabetes Care Inc. Method and system for providing an integrated analyte sensor insertion device and data processing unit
US10362972B2 (en) 2006-09-10 2019-07-30 Abbott Diabetes Care Inc. Method and system for providing an integrated analyte sensor insertion device and data processing unit
US8862198B2 (en) 2006-09-10 2014-10-14 Abbott Diabetes Care Inc. Method and system for providing an integrated analyte sensor insertion device and data processing unit
US10342469B2 (en) 2006-10-02 2019-07-09 Abbott Diabetes Care Inc. Method and system for dynamically updating calibration parameters for an analyte sensor
US9357959B2 (en) 2006-10-02 2016-06-07 Abbott Diabetes Care Inc. Method and system for dynamically updating calibration parameters for an analyte sensor
US9839383B2 (en) 2006-10-02 2017-12-12 Abbott Diabetes Care Inc. Method and system for dynamically updating calibration parameters for an analyte sensor
US9629578B2 (en) 2006-10-02 2017-04-25 Abbott Diabetes Care Inc. Method and system for dynamically updating calibration parameters for an analyte sensor
US10363363B2 (en) 2006-10-23 2019-07-30 Abbott Diabetes Care Inc. Flexible patch for fluid delivery and monitoring body analytes
US10070810B2 (en) 2006-10-23 2018-09-11 Abbott Diabetes Care Inc. Sensor insertion devices and methods of use
US9259175B2 (en) 2006-10-23 2016-02-16 Abbott Diabetes Care, Inc. Flexible patch for fluid delivery and monitoring body analytes
US11724029B2 (en) 2006-10-23 2023-08-15 Abbott Diabetes Care Inc. Flexible patch for fluid delivery and monitoring body analytes
US9788771B2 (en) 2006-10-23 2017-10-17 Abbott Diabetes Care Inc. Variable speed sensor insertion devices and methods of use
US11234621B2 (en) 2006-10-23 2022-02-01 Abbott Diabetes Care Inc. Sensor insertion devices and methods of use
US11282603B2 (en) 2006-10-25 2022-03-22 Abbott Diabetes Care Inc. Method and system for providing analyte monitoring
US9113828B2 (en) 2006-10-25 2015-08-25 Abbott Diabetes Care Inc. Method and system for providing analyte monitoring
US9814428B2 (en) 2006-10-25 2017-11-14 Abbott Diabetes Care Inc. Method and system for providing analyte monitoring
US10194868B2 (en) 2006-10-25 2019-02-05 Abbott Diabetes Care Inc. Method and system for providing analyte monitoring
US9882660B2 (en) 2006-10-26 2018-01-30 Abbott Diabetes Care Inc. Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors
US11722229B2 (en) 2006-10-26 2023-08-08 Abbott Diabetes Care Inc. Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors
US10903914B2 (en) 2006-10-26 2021-01-26 Abbott Diabetes Care Inc. Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors
US20100204557A1 (en) * 2007-02-18 2010-08-12 Abbott Diabetes Care Inc. Multi-Function Analyte Test Device and Methods Therefor
US8930203B2 (en) 2007-02-18 2015-01-06 Abbott Diabetes Care Inc. Multi-function analyte test device and methods therefor
US9636450B2 (en) 2007-02-19 2017-05-02 Udo Hoss Pump system modular components for delivering medication and analyte sensing at seperate insertion sites
US20080200897A1 (en) * 2007-02-19 2008-08-21 Abbott Diabetes Care, Inc. Modular combination of medication infusion and analyte monitoring
US9204827B2 (en) 2007-04-14 2015-12-08 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US11039767B2 (en) 2007-04-14 2021-06-22 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US10111608B2 (en) 2007-04-14 2018-10-30 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US9615780B2 (en) 2007-04-14 2017-04-11 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US9008743B2 (en) 2007-04-14 2015-04-14 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US10349877B2 (en) 2007-04-14 2019-07-16 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US10119956B2 (en) 2007-05-14 2018-11-06 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9801571B2 (en) 2007-05-14 2017-10-31 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US11125592B2 (en) 2007-05-14 2021-09-21 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10031002B2 (en) 2007-05-14 2018-07-24 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10634662B2 (en) 2007-05-14 2020-04-28 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9483608B2 (en) 2007-05-14 2016-11-01 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10045720B2 (en) 2007-05-14 2018-08-14 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US11076785B2 (en) 2007-05-14 2021-08-03 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10653344B2 (en) 2007-05-14 2020-05-19 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US11300561B2 (en) 2007-05-14 2022-04-12 Abbott Diabetes Care, Inc. Method and apparatus for providing data processing and control in a medical communication system
US10820841B2 (en) 2007-05-14 2020-11-03 Abbot Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9558325B2 (en) 2007-05-14 2017-01-31 Abbott Diabetes Care Inc. Method and system for determining analyte levels
US10991456B2 (en) 2007-05-14 2021-04-27 Abbott Diabetes Care Inc. Method and system for determining analyte levels
US10261069B2 (en) 2007-05-14 2019-04-16 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US11828748B2 (en) 2007-05-14 2023-11-28 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10463310B2 (en) 2007-05-14 2019-11-05 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9125548B2 (en) 2007-05-14 2015-09-08 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9804150B2 (en) 2007-05-14 2017-10-31 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10002233B2 (en) 2007-05-14 2018-06-19 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10976304B2 (en) 2007-05-14 2021-04-13 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9797880B2 (en) 2007-05-14 2017-10-24 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8571808B2 (en) 2007-05-14 2013-10-29 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US11119090B2 (en) 2007-05-14 2021-09-14 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9060719B2 (en) 2007-05-14 2015-06-23 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8682615B2 (en) 2007-05-14 2014-03-25 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8560038B2 (en) 2007-05-14 2013-10-15 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10143409B2 (en) 2007-05-14 2018-12-04 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9737249B2 (en) 2007-05-14 2017-08-22 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8612163B2 (en) 2007-05-14 2013-12-17 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8613703B2 (en) 2007-05-31 2013-12-24 Abbott Diabetes Care Inc. Insertion devices and methods
US20080300476A1 (en) * 2007-05-31 2008-12-04 Abbott Diabetes Care, Inc. Insertion devices and methods
US9913600B2 (en) 2007-06-29 2018-03-13 Abbott Diabetes Care Inc. Analyte monitoring and management device and method to analyze the frequency of user interaction with the device
US11678821B2 (en) 2007-06-29 2023-06-20 Abbott Diabetes Care Inc. Analyte monitoring and management device and method to analyze the frequency of user interaction with the device
US10856785B2 (en) 2007-06-29 2020-12-08 Abbott Diabetes Care Inc. Analyte monitoring and management device and method to analyze the frequency of user interaction with the device
US8834366B2 (en) 2007-07-31 2014-09-16 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor calibration
US9398872B2 (en) 2007-07-31 2016-07-26 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor calibration
US20090063402A1 (en) * 2007-08-31 2009-03-05 Abbott Diabetes Care, Inc. Method and System for Providing Medication Level Determination
US9439586B2 (en) 2007-10-23 2016-09-13 Abbott Diabetes Care Inc. Assessing measures of glycemic variability
US11083843B2 (en) 2007-10-23 2021-08-10 Abbott Diabetes Care Inc. Closed loop control system with safety parameters and methods
US10173007B2 (en) 2007-10-23 2019-01-08 Abbott Diabetes Care Inc. Closed loop control system with safety parameters and methods
US9743865B2 (en) 2007-10-23 2017-08-29 Abbott Diabetes Care Inc. Assessing measures of glycemic variability
US9332934B2 (en) 2007-10-23 2016-05-10 Abbott Diabetes Care Inc. Analyte sensor with lag compensation
US9804148B2 (en) 2007-10-23 2017-10-31 Abbott Diabetes Care Inc. Analyte sensor with lag compensation
US10685749B2 (en) 2007-12-19 2020-06-16 Abbott Diabetes Care Inc. Insulin delivery apparatuses capable of bluetooth data transmission
US9770211B2 (en) 2008-01-31 2017-09-26 Abbott Diabetes Care Inc. Analyte sensor with time lag compensation
US9320468B2 (en) 2008-01-31 2016-04-26 Abbott Diabetes Care Inc. Analyte sensor with time lag compensation
US10463288B2 (en) 2008-03-28 2019-11-05 Abbott Diabetes Care Inc. Analyte sensor calibration management
US8583205B2 (en) 2008-03-28 2013-11-12 Abbott Diabetes Care Inc. Analyte sensor calibration management
US11779248B2 (en) 2008-03-28 2023-10-10 Abbott Diabetes Care Inc. Analyte sensor calibration management
US20100234710A1 (en) * 2008-03-28 2010-09-16 Abbott Diabetes Care Inc. Analyte Sensor Calibration Management
US9730623B2 (en) 2008-03-28 2017-08-15 Abbott Diabetes Care Inc. Analyte sensor calibration management
US9320462B2 (en) 2008-03-28 2016-04-26 Abbott Diabetes Care Inc. Analyte sensor calibration management
US8718739B2 (en) 2008-03-28 2014-05-06 Abbott Diabetes Care Inc. Analyte sensor calibration management
US10327682B2 (en) 2008-05-30 2019-06-25 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US9795328B2 (en) 2008-05-30 2017-10-24 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US11735295B2 (en) 2008-05-30 2023-08-22 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US9541556B2 (en) 2008-05-30 2017-01-10 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US9931075B2 (en) 2008-05-30 2018-04-03 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US11621073B2 (en) 2008-07-14 2023-04-04 Abbott Diabetes Care Inc. Closed loop control system interface and methods
US10328201B2 (en) 2008-07-14 2019-06-25 Abbott Diabetes Care Inc. Closed loop control system interface and methods
US8622988B2 (en) 2008-08-31 2014-01-07 Abbott Diabetes Care Inc. Variable rate closed loop control and methods
US10188794B2 (en) 2008-08-31 2019-01-29 Abbott Diabetes Care Inc. Closed loop control and signal attenuation detection
US9392969B2 (en) 2008-08-31 2016-07-19 Abbott Diabetes Care Inc. Closed loop control and signal attenuation detection
US9943644B2 (en) 2008-08-31 2018-04-17 Abbott Diabetes Care Inc. Closed loop control with reference measurement and methods thereof
US9572934B2 (en) 2008-08-31 2017-02-21 Abbott DiabetesCare Inc. Robust closed loop control and methods
US11679200B2 (en) 2008-08-31 2023-06-20 Abbott Diabetes Care Inc. Closed loop control and signal attenuation detection
US20100057042A1 (en) * 2008-08-31 2010-03-04 Abbott Diabetes Care, Inc. Closed Loop Control With Improved Alarm Functions
US9610046B2 (en) 2008-08-31 2017-04-04 Abbott Diabetes Care Inc. Closed loop control with improved alarm functions
US8734422B2 (en) 2008-08-31 2014-05-27 Abbott Diabetes Care Inc. Closed loop control with improved alarm functions
US20100056992A1 (en) * 2008-08-31 2010-03-04 Abbott Diabetes Care, Inc. Variable Rate Closed Loop Control And Methods
US8795252B2 (en) 2008-08-31 2014-08-05 Abbott Diabetes Care Inc. Robust closed loop control and methods
US20100081906A1 (en) * 2008-09-30 2010-04-01 Abbott Diabetes Care, Inc. Analyte Sensor Sensitivity Attenuation Mitigation
US11464434B2 (en) 2008-09-30 2022-10-11 Abbott Diabetes Care Inc. Optimizing analyte sensor calibration
US9662056B2 (en) 2008-09-30 2017-05-30 Abbott Diabetes Care Inc. Optimizing analyte sensor calibration
US10045739B2 (en) 2008-09-30 2018-08-14 Abbott Diabetes Care Inc. Analyte sensor sensitivity attenuation mitigation
US11202592B2 (en) 2008-09-30 2021-12-21 Abbott Diabetes Care Inc. Optimizing analyte sensor calibration
US11484234B2 (en) 2008-09-30 2022-11-01 Abbott Diabetes Care Inc. Optimizing analyte sensor calibration
US8986208B2 (en) 2008-09-30 2015-03-24 Abbott Diabetes Care Inc. Analyte sensor sensitivity attenuation mitigation
US11013439B2 (en) 2008-09-30 2021-05-25 Abbott Diabetes Care Inc. Optimizing analyte sensor calibration
US10980461B2 (en) 2008-11-07 2021-04-20 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US9326707B2 (en) 2008-11-10 2016-05-03 Abbott Diabetes Care Inc. Alarm characterization for analyte monitoring devices and systems
US11272890B2 (en) 2008-11-10 2022-03-15 Abbott Diabetes Care Inc. Alarm characterization for analyte monitoring devices and systems
US11678848B2 (en) 2008-11-10 2023-06-20 Abbott Diabetes Care Inc. Alarm characterization for analyte monitoring devices and systems
US9730650B2 (en) 2008-11-10 2017-08-15 Abbott Diabetes Care Inc. Alarm characterization for analyte monitoring devices and systems
US8676513B2 (en) 2009-01-29 2014-03-18 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US10089446B2 (en) 2009-01-29 2018-10-02 Abbott Diabetes Care Inc. Method and device for providing offset model based calibration for analyte sensor
US11464430B2 (en) 2009-01-29 2022-10-11 Abbott Diabetes Care Inc. Method and device for providing offset model based calibration for analyte sensor
US9066709B2 (en) 2009-01-29 2015-06-30 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US8532935B2 (en) 2009-01-29 2013-09-10 Abbott Diabetes Care Inc. Method and device for providing offset model based calibration for analyte sensor
US11202591B2 (en) 2009-02-03 2021-12-21 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
USD882432S1 (en) 2009-02-03 2020-04-28 Abbott Diabetes Care Inc. Analyte sensor on body unit
USD957642S1 (en) 2009-02-03 2022-07-12 Abbott Diabetes Care Inc. Analyte sensor inserter
US11006872B2 (en) 2009-02-03 2021-05-18 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11213229B2 (en) 2009-02-03 2022-01-04 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11166656B2 (en) 2009-02-03 2021-11-09 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US9636068B2 (en) 2009-02-03 2017-05-02 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US10786190B2 (en) 2009-02-03 2020-09-29 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
USD955599S1 (en) 2009-02-03 2022-06-21 Abbott Diabetes Care Inc. Analyte sensor inserter
USD957643S1 (en) 2009-02-03 2022-07-12 Abbott Diabetes Care Inc. Analyte sensor device
US11006870B2 (en) 2009-02-03 2021-05-18 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11006871B2 (en) 2009-02-03 2021-05-18 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US9993188B2 (en) 2009-02-03 2018-06-12 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US9402544B2 (en) 2009-02-03 2016-08-02 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US8730058B2 (en) 2009-04-15 2014-05-20 Abbott Diabetes Care Inc. Analyte monitoring system having an alert
US10009244B2 (en) 2009-04-15 2018-06-26 Abbott Diabetes Care Inc. Analyte monitoring system having an alert
US8497777B2 (en) 2009-04-15 2013-07-30 Abbott Diabetes Care Inc. Analyte monitoring system having an alert
US9178752B2 (en) 2009-04-15 2015-11-03 Abbott Diabetes Care Inc. Analyte monitoring system having an alert
US11298056B2 (en) 2009-04-29 2022-04-12 Abbott Diabetes Care Inc. Methods and systems for early signal attenuation detection and processing
US11116431B1 (en) 2009-04-29 2021-09-14 Abbott Diabetes Care Inc. Methods and systems for early signal attenuation detection and processing
US10820842B2 (en) 2009-04-29 2020-11-03 Abbott Diabetes Care Inc. Methods and systems for early signal attenuation detection and processing
US10194844B2 (en) 2009-04-29 2019-02-05 Abbott Diabetes Care Inc. Methods and systems for early signal attenuation detection and processing
US11013431B2 (en) 2009-04-29 2021-05-25 Abbott Diabetes Care Inc. Methods and systems for early signal attenuation detection and processing
US10952653B2 (en) 2009-04-29 2021-03-23 Abbott Diabetes Care Inc. Methods and systems for early signal attenuation detection and processing
US9310230B2 (en) 2009-04-29 2016-04-12 Abbott Diabetes Care Inc. Method and system for providing real time analyte sensor calibration with retrospective backfill
US20110027458A1 (en) * 2009-07-02 2011-02-03 Dexcom, Inc. Continuous analyte sensors and methods of making same
US8798934B2 (en) 2009-07-23 2014-08-05 Abbott Diabetes Care Inc. Real time management of data relating to physiological control of glucose levels
US20110021889A1 (en) * 2009-07-23 2011-01-27 Abbott Diabetes Care Inc. Continuous Analyte Measurement Systems and Systems and Methods for Implanting Them
US9795326B2 (en) 2009-07-23 2017-10-24 Abbott Diabetes Care Inc. Continuous analyte measurement systems and systems and methods for implanting them
US10872102B2 (en) 2009-07-23 2020-12-22 Abbott Diabetes Care Inc. Real time management of data relating to physiological control of glucose levels
US10827954B2 (en) 2009-07-23 2020-11-10 Abbott Diabetes Care Inc. Continuous analyte measurement systems and systems and methods for implanting them
US8718965B2 (en) 2009-07-31 2014-05-06 Abbott Diabetes Care Inc. Method and apparatus for providing analyte monitoring system calibration accuracy
US10660554B2 (en) 2009-07-31 2020-05-26 Abbott Diabetes Care Inc. Methods and devices for analyte monitoring calibration
US11234625B2 (en) 2009-07-31 2022-02-01 Abbott Diabetes Care Inc. Method and apparatus for providing analyte monitoring and therapy management system accuracy
US9936910B2 (en) 2009-07-31 2018-04-10 Abbott Diabetes Care Inc. Method and apparatus for providing analyte monitoring and therapy management system accuracy
US8478557B2 (en) 2009-07-31 2013-07-02 Abbott Diabetes Care Inc. Method and apparatus for providing analyte monitoring system calibration accuracy
US10456091B2 (en) 2009-08-31 2019-10-29 Abbott Diabetes Care Inc. Displays for a medical device
US10772572B2 (en) 2009-08-31 2020-09-15 Abbott Diabetes Care Inc. Displays for a medical device
US20110054275A1 (en) * 2009-08-31 2011-03-03 Abbott Diabetes Care Inc. Mounting Unit Having a Sensor and Associated Circuitry
US9226714B2 (en) 2009-08-31 2016-01-05 Abbott Diabetes Care Inc. Displays for a medical device
US9186113B2 (en) 2009-08-31 2015-11-17 Abbott Diabetes Care Inc. Displays for a medical device
US9814416B2 (en) 2009-08-31 2017-11-14 Abbott Diabetes Care Inc. Displays for a medical device
US8514086B2 (en) 2009-08-31 2013-08-20 Abbott Diabetes Care Inc. Displays for a medical device
US11241175B2 (en) 2009-08-31 2022-02-08 Abbott Diabetes Care Inc. Displays for a medical device
US10123752B2 (en) 2009-08-31 2018-11-13 Abbott Diabetes Care Inc. Displays for a medical device
USRE47315E1 (en) 2009-08-31 2019-03-26 Abbott Diabetes Care Inc. Displays for a medical device
US11202586B2 (en) 2009-08-31 2021-12-21 Abbott Diabetes Care Inc. Displays for a medical device
US10918342B1 (en) 2009-08-31 2021-02-16 Abbott Diabetes Care Inc. Displays for a medical device
US9549694B2 (en) 2009-08-31 2017-01-24 Abbott Diabetes Care Inc. Displays for a medical device
USD962446S1 (en) 2009-08-31 2022-08-30 Abbott Diabetes Care, Inc. Analyte sensor device
US10881355B2 (en) 2009-08-31 2021-01-05 Abbott Diabetes Care Inc. Displays for a medical device
US11730429B2 (en) 2009-08-31 2023-08-22 Abbott Diabetes Care Inc. Displays for a medical device
US8816862B2 (en) 2009-08-31 2014-08-26 Abbott Diabetes Care Inc. Displays for a medical device
US10349874B2 (en) 2009-09-29 2019-07-16 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
US9750439B2 (en) 2009-09-29 2017-09-05 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
US9320461B2 (en) 2009-09-29 2016-04-26 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
US11259725B2 (en) 2009-09-30 2022-03-01 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
US10765351B2 (en) 2009-09-30 2020-09-08 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
US9351669B2 (en) 2009-09-30 2016-05-31 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
US9750444B2 (en) 2009-09-30 2017-09-05 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
US10117606B2 (en) 2009-10-30 2018-11-06 Abbott Diabetes Care Inc. Method and apparatus for detecting false hypoglycemic conditions
US11207005B2 (en) 2009-10-30 2021-12-28 Abbott Diabetes Care Inc. Method and apparatus for detecting false hypoglycemic conditions
USD924406S1 (en) 2010-02-01 2021-07-06 Abbott Diabetes Care Inc. Analyte sensor inserter
US10078380B2 (en) 2010-03-10 2018-09-18 Abbott Diabetes Care Inc. Systems, devices and methods for managing glucose levels
US11061491B2 (en) 2010-03-10 2021-07-13 Abbott Diabetes Care Inc. Systems, devices and methods for managing glucose levels
US11013440B2 (en) 2010-03-24 2021-05-25 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US10010280B2 (en) 2010-03-24 2018-07-03 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
USD997362S1 (en) 2010-03-24 2023-08-29 Abbott Diabetes Care Inc. Analyte sensor inserter
US10292632B2 (en) 2010-03-24 2019-05-21 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US10772547B1 (en) 2010-03-24 2020-09-15 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US10881340B2 (en) 2010-03-24 2021-01-05 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US10881341B1 (en) 2010-03-24 2021-01-05 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US8764657B2 (en) 2010-03-24 2014-07-01 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US11058334B1 (en) 2010-03-24 2021-07-13 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US11064922B1 (en) 2010-03-24 2021-07-20 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US9215992B2 (en) 2010-03-24 2015-12-22 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US9687183B2 (en) 2010-03-24 2017-06-27 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US9186098B2 (en) 2010-03-24 2015-11-17 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US11000216B2 (en) 2010-03-24 2021-05-11 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US10945649B2 (en) 2010-03-24 2021-03-16 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
USD987830S1 (en) 2010-03-24 2023-05-30 Abbott Diabetes Care Inc. Analyte sensor inserter
US9265453B2 (en) 2010-03-24 2016-02-23 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US10952657B2 (en) 2010-03-24 2021-03-23 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US10959654B2 (en) 2010-03-24 2021-03-30 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US8635046B2 (en) 2010-06-23 2014-01-21 Abbott Diabetes Care Inc. Method and system for evaluating analyte sensor response characteristics
US10959653B2 (en) 2010-06-29 2021-03-30 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US11478173B2 (en) 2010-06-29 2022-10-25 Abbott Diabetes Care Inc. Calibration of analyte measurement system
US10966644B2 (en) 2010-06-29 2021-04-06 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US11064921B2 (en) 2010-06-29 2021-07-20 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US10874338B2 (en) 2010-06-29 2020-12-29 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US10973449B2 (en) 2010-06-29 2021-04-13 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US10092229B2 (en) 2010-06-29 2018-10-09 Abbott Diabetes Care Inc. Calibration of analyte measurement system
US9572534B2 (en) 2010-06-29 2017-02-21 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US11213226B2 (en) 2010-10-07 2022-01-04 Abbott Diabetes Care Inc. Analyte monitoring devices and methods
US11627898B2 (en) 2011-02-28 2023-04-18 Abbott Diabetes Care Inc. Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same
US10136845B2 (en) 2011-02-28 2018-11-27 Abbott Diabetes Care Inc. Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same
US11534089B2 (en) 2011-02-28 2022-12-27 Abbott Diabetes Care Inc. Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same
US9743862B2 (en) 2011-03-31 2017-08-29 Abbott Diabetes Care Inc. Systems and methods for transcutaneously implanting medical devices
US10610141B2 (en) 2011-04-15 2020-04-07 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US10722162B2 (en) 2011-04-15 2020-07-28 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US10555695B2 (en) 2011-04-15 2020-02-11 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US10624568B2 (en) 2011-04-15 2020-04-21 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US10835162B2 (en) 2011-04-15 2020-11-17 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US10561354B2 (en) 2011-04-15 2020-02-18 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US10682084B2 (en) 2011-04-15 2020-06-16 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US9913619B2 (en) 2011-10-31 2018-03-13 Abbott Diabetes Care Inc. Model based variable risk false glucose threshold alarm prevention mechanism
US9622691B2 (en) 2011-10-31 2017-04-18 Abbott Diabetes Care Inc. Model based variable risk false glucose threshold alarm prevention mechanism
US11406331B2 (en) 2011-10-31 2022-08-09 Abbott Diabetes Care Inc. Model based variable risk false glucose threshold alarm prevention mechanism
US9289179B2 (en) 2011-11-23 2016-03-22 Abbott Diabetes Care Inc. Mitigating single point failure of devices in an analyte monitoring system and methods thereof
US10939859B2 (en) 2011-11-23 2021-03-09 Abbott Diabetes Care Inc. Mitigating single point failure of devices in an analyte monitoring system and methods thereof
US10136847B2 (en) 2011-11-23 2018-11-27 Abbott Diabetes Care Inc. Mitigating single point failure of devices in an analyte monitoring system and methods thereof
US11205511B2 (en) 2011-11-23 2021-12-21 Abbott Diabetes Care Inc. Compatibility mechanisms for devices in a continuous analyte monitoring system and methods thereof
US9743872B2 (en) 2011-11-23 2017-08-29 Abbott Diabetes Care Inc. Mitigating single point failure of devices in an analyte monitoring system and methods thereof
US11783941B2 (en) 2011-11-23 2023-10-10 Abbott Diabetes Care Inc. Compatibility mechanisms for devices in a continuous analyte monitoring system and methods thereof
US8710993B2 (en) 2011-11-23 2014-04-29 Abbott Diabetes Care Inc. Mitigating single point failure of devices in an analyte monitoring system and methods thereof
US9721063B2 (en) 2011-11-23 2017-08-01 Abbott Diabetes Care Inc. Compatibility mechanisms for devices in a continuous analyte monitoring system and methods thereof
US9339217B2 (en) 2011-11-25 2016-05-17 Abbott Diabetes Care Inc. Analyte monitoring system and methods of use
US10082493B2 (en) 2011-11-25 2018-09-25 Abbott Diabetes Care Inc. Analyte monitoring system and methods of use
US11391723B2 (en) 2011-11-25 2022-07-19 Abbott Diabetes Care Inc. Analyte monitoring system and methods of use
USD915602S1 (en) 2011-12-11 2021-04-06 Abbott Diabetes Care Inc. Analyte sensor device
US11179068B2 (en) 2011-12-11 2021-11-23 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
US9931066B2 (en) 2011-12-11 2018-04-03 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
US9693713B2 (en) 2011-12-11 2017-07-04 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
USD903877S1 (en) 2011-12-11 2020-12-01 Abbott Diabetes Care Inc. Analyte sensor device
US11051725B2 (en) 2011-12-11 2021-07-06 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
USD915601S1 (en) 2011-12-11 2021-04-06 Abbott Diabetes Care Inc. Analyte sensor device
US11051724B2 (en) 2011-12-11 2021-07-06 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
US9402570B2 (en) 2011-12-11 2016-08-02 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
WO2013152090A2 (en) 2012-04-04 2013-10-10 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP4275598A2 (en) 2012-04-04 2023-11-15 DexCom, Inc. Applicator and method for applying a transcutaneous analyte sensor
EP3975192A1 (en) 2012-06-05 2022-03-30 Dexcom, Inc. Systems and methods for processing analyte data and generating reports
US11145410B2 (en) 2012-06-05 2021-10-12 Dexcom, Inc. Dynamic report building
WO2013184566A2 (en) 2012-06-05 2013-12-12 Dexcom, Inc. Systems and methods for processing analyte data and generating reports
US11737692B2 (en) 2012-06-29 2023-08-29 Dexcom, Inc. Implantable sensor devices, systems, and methods
WO2014004460A1 (en) 2012-06-29 2014-01-03 Dexcom, Inc. Use of sensor redundancy to detect sensor failures
EP3915465A2 (en) 2012-06-29 2021-12-01 Dexcom, Inc. Use of sensor redundancy to detect sensor failures
EP4018929A1 (en) 2012-06-29 2022-06-29 Dexcom, Inc. Method and system for processing data from a continuous glucose sensor
US11892426B2 (en) 2012-06-29 2024-02-06 Dexcom, Inc. Devices, systems, and methods to compensate for effects of temperature on implantable sensors
EP4075441A1 (en) 2012-07-09 2022-10-19 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
EP4080517A1 (en) 2012-07-09 2022-10-26 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
WO2014011488A2 (en) 2012-07-09 2014-01-16 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
EP3767633A1 (en) 2012-07-09 2021-01-20 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
US10656139B2 (en) 2012-08-30 2020-05-19 Abbott Diabetes Care Inc. Dropout detection in continuous analyte monitoring data during data excursions
US10345291B2 (en) 2012-08-30 2019-07-09 Abbott Diabetes Care Inc. Dropout detection in continuous analyte monitoring data during data excursions
US10942164B2 (en) 2012-08-30 2021-03-09 Abbott Diabetes Care Inc. Dropout detection in continuous analyte monitoring data during data excursions
US10132793B2 (en) 2012-08-30 2018-11-20 Abbott Diabetes Care Inc. Dropout detection in continuous analyte monitoring data during data excursions
US11896371B2 (en) 2012-09-26 2024-02-13 Abbott Diabetes Care Inc. Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data
US10842420B2 (en) 2012-09-26 2020-11-24 Abbott Diabetes Care Inc. Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data
US9907492B2 (en) 2012-09-26 2018-03-06 Abbott Diabetes Care Inc. Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data
US11179079B2 (en) 2012-09-28 2021-11-23 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
EP3782550A1 (en) 2012-09-28 2021-02-24 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
US11864891B2 (en) 2012-09-28 2024-01-09 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
WO2014052080A1 (en) 2012-09-28 2014-04-03 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
US9675290B2 (en) 2012-10-30 2017-06-13 Abbott Diabetes Care Inc. Sensitivity calibration of in vivo sensors used to measure analyte concentration
US9801577B2 (en) 2012-10-30 2017-10-31 Abbott Diabetes Care Inc. Sensitivity calibration of in vivo sensors used to measure analyte concentration
US10188334B2 (en) 2012-10-30 2019-01-29 Abbott Diabetes Care Inc. Sensitivity calibration of in vivo sensors used to measure analyte concentration
EP4231309A2 (en) 2012-11-07 2023-08-23 DexCom, Inc. Systems and methods for managing glycemic variability
EP3654348A1 (en) 2012-11-07 2020-05-20 Dexcom, Inc. Systems and methods for managing glycemic variability
US9193110B2 (en) * 2012-11-09 2015-11-24 Evonik Industries Ag Use and production of coated filaments for extrusion-based 3D printing processes
US20140134335A1 (en) * 2012-11-09 2014-05-15 Evonik Industries Ag Use and production of coated filaments for extrusion-based 3d printing processes
US11109757B2 (en) 2012-12-31 2021-09-07 Dexcom, Inc. Remote monitoring of analyte measurements
US10869599B2 (en) 2012-12-31 2020-12-22 Dexcom, Inc. Remote monitoring of analyte measurements
US10993617B2 (en) 2012-12-31 2021-05-04 Dexcom, Inc. Remote monitoring of analyte measurements
US11160452B2 (en) 2012-12-31 2021-11-02 Dexcom, Inc. Remote monitoring of analyte measurements
US11213204B2 (en) 2012-12-31 2022-01-04 Dexcom, Inc. Remote monitoring of analyte measurements
US10856736B2 (en) 2012-12-31 2020-12-08 Dexcom, Inc. Remote monitoring of analyte measurements
US11744463B2 (en) 2012-12-31 2023-09-05 Dexcom, Inc. Remote monitoring of analyte measurements
US10860687B2 (en) 2012-12-31 2020-12-08 Dexcom, Inc. Remote monitoring of analyte measurements
US11850020B2 (en) 2012-12-31 2023-12-26 Dexcom, Inc. Remote monitoring of analyte measurements
US11382508B2 (en) 2012-12-31 2022-07-12 Dexcom, Inc. Remote monitoring of analyte measurements
EP4220654A1 (en) 2013-03-14 2023-08-02 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
EP4235684A1 (en) 2013-03-14 2023-08-30 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
US10985804B2 (en) 2013-03-14 2021-04-20 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
WO2014158327A2 (en) 2013-03-14 2014-10-02 Dexcom, Inc. Advanced calibration for analyte sensors
EP3806103A1 (en) 2013-03-14 2021-04-14 Dexcom, Inc. Advanced calibration for analyte sensors
EP3401818A1 (en) 2013-03-14 2018-11-14 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
WO2014158405A2 (en) 2013-03-14 2014-10-02 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
US11677443B1 (en) 2013-03-14 2023-06-13 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
US10076285B2 (en) 2013-03-15 2018-09-18 Abbott Diabetes Care Inc. Sensor fault detection using analyte sensor data pattern comparison
US10874336B2 (en) 2013-03-15 2020-12-29 Abbott Diabetes Care Inc. Multi-rate analyte sensor data collection with sample rate configurable signal processing
US10433773B1 (en) 2013-03-15 2019-10-08 Abbott Diabetes Care Inc. Noise rejection methods and apparatus for sparsely sampled analyte sensor data
US9474475B1 (en) 2013-03-15 2016-10-25 Abbott Diabetes Care Inc. Multi-rate analyte sensor data collection with sample rate configurable signal processing
US11229382B2 (en) 2013-12-31 2022-01-25 Abbott Diabetes Care Inc. Self-powered analyte sensor and devices using the same
US11717225B2 (en) 2014-03-30 2023-08-08 Abbott Diabetes Care Inc. Method and apparatus for determining meal start and peak events in analyte monitoring systems
WO2015156966A1 (en) 2014-04-10 2015-10-15 Dexcom, Inc. Sensors for continuous analyte monitoring, and related methods
EP4257044A2 (en) 2014-04-10 2023-10-11 DexCom, Inc. Sensor for continuous analyte monitoring
US20160033199A1 (en) * 2014-07-29 2016-02-04 Hitachi Metals, Ltd. Method and apparatus for manufacturing enameled wire
US10670335B2 (en) * 2014-07-29 2020-06-02 Hitachi Metals, Ltd. Method and apparatus for manufacturing enameled wire
US10213139B2 (en) 2015-05-14 2019-02-26 Abbott Diabetes Care Inc. Systems, devices, and methods for assembling an applicator and sensor control device
US10674944B2 (en) 2015-05-14 2020-06-09 Abbott Diabetes Care Inc. Compact medical device inserters and related systems and methods
USD980986S1 (en) 2015-05-14 2023-03-14 Abbott Diabetes Care Inc. Analyte sensor inserter
US11553883B2 (en) 2015-07-10 2023-01-17 Abbott Diabetes Care Inc. System, device and method of dynamic glucose profile response to physiological parameters
EP4046571A1 (en) 2015-10-21 2022-08-24 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US20170173735A1 (en) * 2015-12-18 2017-06-22 Illinois Tool Works Inc. Wire manufactured by additive manufacturing methods
US10688596B2 (en) * 2015-12-18 2020-06-23 Illinois Tool Works Inc. Wire manufactured by additive manufacturing methods
US11691198B2 (en) * 2015-12-18 2023-07-04 Illinois Tool Works Inc. Wire manufactured by additive manufacturing methods
TWI712458B (en) * 2015-12-18 2020-12-11 美商伊利諾工具工程公司 Wire manufactured by additive manufacturing methods
CN108367349A (en) * 2015-12-18 2018-08-03 伊利诺斯工具制品有限公司 Device and method for increasing material manufacturing welding wire
US10932672B2 (en) 2015-12-28 2021-03-02 Dexcom, Inc. Systems and methods for remote and host monitoring communications
US11399721B2 (en) 2015-12-28 2022-08-02 Dexcom, Inc. Systems and methods for remote and host monitoring communications
EP4253536A2 (en) 2015-12-30 2023-10-04 DexCom, Inc. Diffusion resistance layer for analyte sensors
EP4292528A1 (en) 2015-12-30 2023-12-20 Dexcom, Inc. Membrane layers for analyte sensors
EP3895614A1 (en) 2015-12-30 2021-10-20 Dexcom, Inc. Enzyme immobilized adhesive layer for analyte sensors
EP4324921A2 (en) 2015-12-30 2024-02-21 Dexcom, Inc. Biointerface layer for analyte sensors
US11112377B2 (en) 2015-12-30 2021-09-07 Dexcom, Inc. Enzyme immobilized adhesive layer for analyte sensors
US10980451B2 (en) 2016-03-31 2021-04-20 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10980453B2 (en) 2016-03-31 2021-04-20 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10980450B2 (en) 2016-03-31 2021-04-20 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10881335B2 (en) 2016-03-31 2021-01-05 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10568552B2 (en) 2016-03-31 2020-02-25 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10561349B2 (en) 2016-03-31 2020-02-18 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10799157B2 (en) 2016-03-31 2020-10-13 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
CN106475268A (en) * 2016-12-22 2017-03-08 苏州振瑞昌材料科技有限公司 A kind of strengthening core masking liquid equipment
US11071478B2 (en) 2017-01-23 2021-07-27 Abbott Diabetes Care Inc. Systems, devices and methods for analyte sensor insertion
US11596330B2 (en) 2017-03-21 2023-03-07 Abbott Diabetes Care Inc. Methods, devices and system for providing diabetic condition diagnosis and therapy
US11504063B2 (en) 2017-06-23 2022-11-22 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP3928688A1 (en) 2017-06-23 2021-12-29 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP4008240A1 (en) 2017-06-23 2022-06-08 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP3925522A1 (en) 2017-06-23 2021-12-22 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US11311241B2 (en) 2017-06-23 2022-04-26 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP4111949A1 (en) 2017-06-23 2023-01-04 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and needle hub comprising anti-rotation feature
US11395631B2 (en) 2017-06-23 2022-07-26 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US11510625B2 (en) 2017-06-23 2022-11-29 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US11382540B2 (en) 2017-10-24 2022-07-12 Dexcom, Inc. Pre-connected analyte sensors
US11350862B2 (en) 2017-10-24 2022-06-07 Dexcom, Inc. Pre-connected analyte sensors
US11331022B2 (en) 2017-10-24 2022-05-17 Dexcom, Inc. Pre-connected analyte sensors
US11706876B2 (en) 2017-10-24 2023-07-18 Dexcom, Inc. Pre-connected analyte sensors
US11078025B2 (en) * 2017-11-21 2021-08-03 Chemcut Holdings LLC Lightweight roller
US20190152713A1 (en) * 2017-11-21 2019-05-23 Chemcut Holdings LLC Lightweight roller
USD1002852S1 (en) 2019-06-06 2023-10-24 Abbott Diabetes Care Inc. Analyte sensor device
USD1006235S1 (en) 2020-12-21 2023-11-28 Abbott Diabetes Care Inc. Analyte sensor inserter
USD982762S1 (en) 2020-12-21 2023-04-04 Abbott Diabetes Care Inc. Analyte sensor inserter
USD999913S1 (en) 2020-12-21 2023-09-26 Abbott Diabetes Care Inc Analyte sensor inserter

Also Published As

Publication number Publication date
US20110027458A1 (en) 2011-02-03
EP2448486A4 (en) 2014-07-09
US20230129853A1 (en) 2023-04-27
WO2011003036A3 (en) 2011-04-14
WO2011003035A3 (en) 2011-04-14
US20190357815A1 (en) 2019-11-28
US20140123893A1 (en) 2014-05-08
US20110028816A1 (en) 2011-02-03
US20110027453A1 (en) 2011-02-03
US20190307371A1 (en) 2019-10-10
US20110027127A1 (en) 2011-02-03
EP4029444A1 (en) 2022-07-20
US9131885B2 (en) 2015-09-15
EP2448485B1 (en) 2021-08-25
EP2448486B1 (en) 2021-08-25
US20180000388A1 (en) 2018-01-04
US8828201B2 (en) 2014-09-09
US20140046148A1 (en) 2014-02-13
US20140046149A1 (en) 2014-02-13
WO2011003035A2 (en) 2011-01-06
US20180146896A1 (en) 2018-05-31
US11559229B2 (en) 2023-01-24
US9237864B2 (en) 2016-01-19
US20110024307A1 (en) 2011-02-03
EP3970610A3 (en) 2022-05-18
US20140343386A1 (en) 2014-11-20
EP2448486A2 (en) 2012-05-09
US20110028815A1 (en) 2011-02-03
US10420494B2 (en) 2019-09-24
US9320466B2 (en) 2016-04-26
US20160081600A1 (en) 2016-03-24
WO2011003039A3 (en) 2011-04-14
EP2448485A4 (en) 2014-07-16
WO2011003039A2 (en) 2011-01-06
WO2011003036A2 (en) 2011-01-06
US20220346674A1 (en) 2022-11-03
EP2448485A2 (en) 2012-05-09
US9907497B2 (en) 2018-03-06
US20190167163A1 (en) 2019-06-06
US20230301563A1 (en) 2023-09-28
US9763608B2 (en) 2017-09-19
US20210353185A1 (en) 2021-11-18
EP3970610A2 (en) 2022-03-23

Similar Documents

Publication Publication Date Title
US20220346674A1 (en) Continuous analyte sensors and methods of making same
US20230293058A1 (en) Analyte sensor with increased reference capacity
EP3895614B1 (en) Enzyme immobilized adhesive layer for analyte sensors
US20190224712A1 (en) Cellulosic-based resistance domain for an analyte sensor
CA2881391C (en) Zwitterion surface modifications for continuous sensors
WO2006121661A2 (en) Cellulosic-based resistance domain for an analyte sensor

Legal Events

Date Code Title Description
AS Assignment

Owner name: DEXCOM, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BOOCK, ROBERT;JACKSON, JEFF;ZHANG, HUASHI;AND OTHERS;SIGNING DATES FROM 20100914 TO 20101014;REEL/FRAME:025172/0708

STPP Information on status: patent application and granting procedure in general

Free format text: FINAL REJECTION MAILED

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION