WO2002064027A2 - Membrane and electrode structure for implantable sensor - Google Patents
Membrane and electrode structure for implantable sensor Download PDFInfo
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- WO2002064027A2 WO2002064027A2 PCT/US2002/006963 US0206963W WO02064027A2 WO 2002064027 A2 WO2002064027 A2 WO 2002064027A2 US 0206963 W US0206963 W US 0206963W WO 02064027 A2 WO02064027 A2 WO 02064027A2
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- measuring device
- hydrophilic region
- membrane
- sensor
- glucose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring 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
Definitions
- the invention relates to the design and use of a biological measuring device containing a novel membrane structure.
- a variety of biomedical measuring devices are routinely used by physicians and clinicians to monitor physiological variables such as respiratory rate, blood pressure and temperature.
- the enzyme electrode In addition to the repertoire of devices listed above is the enzyme electrode. Enzyme electrodes enable the user to determine the concentration of certain biochemicals rapidly and with considerable accuracy by catalyzing the enzyme electrode.
- PATYGOUG02.B14 -1 reaction of a biochemical and a detectable coreactant or producing a product that may be readily sensed by well-known electrodes (e.g. oxygen, H 2 O 2 ).
- electrodes e.g. oxygen, H 2 O 2
- enzyme electrodes that can detect urea, uric acid, glucose, various alcohols, and a number of amino acids when used in certain well-defined situations.
- glucose + O 2 + H 2 O ⁇ lucos ⁇ oxidase > H 2 O 2 + gluconic acid To accurately measure the amount of glucose present, both oxygen and water must be present in excess.
- H 2 O 2 hydrogen peroxide
- Glucose is detected electrochemically using the immobilized enzyme glucose oxidase coupled to an oxygen- or hydrogen peroxide-sensitive electrode. The reaction results in a reduction in oxygen and the production of hydrogen peroxide proportional to the concentration of glucose in the sample medium.
- the electrode can be polarized cathodically to detect residual oxygen not consumed by the enzymatic process, or polarized anodically to detect the product of the enzyme reaction, hydrogen peroxide.
- a functional device is composed of at least two detecting electrodes, or at least one detecting electrode and a reference signal source, to sense the concentration of oxygen or hydrogen peroxide in the presence and absence of enzyme reaction. Additionally, the complete device contains an electronic control means for determining the difference in the concentration of the substances of interest. From this difference, the concentration of glucose can be determined.
- the enzyme catalase may be included in the oxygen-based system in excess in the immobilized-enzyme phase containing the glucose oxidase to catalyze the following reaction: H 2 O 2 catalase > 1 /2 O 2 + H 2 O.
- This mixture of immobilized enzymes can be used in the oxygen-based device, but not the peroxide-based device.
- Catalase prevents the accumulation of hydrogen peroxide which can promote the generation of oxygen free radicals that are detrimental to health.
- Glucose measuring devices for testing of glucose levels in vitro based on this reaction have been described previously (e.g. Hicks et al., US patent 3,542,662) and work satisfactorily as neither oxygen nor water are severely limiting to the reaction when employed in vitro. Additionally, a number of patents have described implantable glucose measuring devices. However, certain such devices for implantation have been limited in their effectiveness due to the relative deficit of oxygen compared to glucose in tissues or the blood stream ( 1 : 50-1000). Previous devices (e.g. Fisher and Abel) have been designed such that the surface of the device is predominantly permeable to oxygen, but not glucose, and is in contact with the enzyme layer.
- Glucose reaches the enzyme layer through a minute hole in the oxygen-permeable outer layer that is in alignment with an electrode sensor beneath it. Hydrogen peroxide produced by the enzyme reaction must diffuse directly to the sensing anode or through a porous membrane adjacent to the electrode, but is otherwise substantially confined within the enzyme layer by the oxygen-permeable layer resulting in unavoidable peroxide-mediated enzyme inactivation and reduced sensor lifetime.
- the strategy of designing devices with differentially permeable surface areas to limit the amount of glucose entering the device, while maximizing the availability of oxygen to the reaction site, is now common (Gough, US Patent 4,484,987).
- An example based on device geometry is seen in Gough, US Patent number 4,671 ,288, which describes a cylindrical device permeable to glucose only at the end, and with both the
- PATYG0UG02.B1 -3 curved surface and end permeable to oxygen.
- Such a device is placed in an artery or vein to measure blood glucose.
- the advantage is direct access to blood glucose, leading to a relatively rapid response.
- the major disadvantage of vascular implantation is the possibility of eliciting blood clots or vascular wall damage. This device is not ideal for implantation in tissues.
- Devices have been developed for implantation in tissue to overcome potential problems of safely inserting into, and operating sensors within, the circulatory system (e.g. Gough, US Patent 4,671 ,288); however, their accuracy may be limited by the lower availability of oxygen in tissues.
- the device membrane is a combination of glucose-permeable area and oxygen-permeable domains. The ratio of the oxygen-permeable areas to the glucose-permeable areas is somewhat limited due to the design.
- membranes that are variably permeable to oxygen and glucose have been developed (Allen, US Patent 5,322,063).
- Membrane compositions are taught in which the relative permeability of oxygen and glucose are manipulated by altering the water content of a polymeric formulation.
- the disadvantages of such a membrane may include sensitivity of the membrane performance to variables during manufacture and that regions of oxygen permeability may not be focused over electrodes within the device.
- PATYGOUG02.B1 -4- An alternative strategy to device construction is to incorporate an enzyme-containing membrane that is hydrophilic and also contains small hydrophobic domains to increase gas solubility, giving rise to differential permeability of the polar and gaseous reactants (e.g. Gough, US Patents 4,484,987 and 4,890,620).
- Such membranes readily allow for the diffusion of small apolar molecules, such as oxygen, while limiting the diffusion of larger polar molecules, such as glucose.
- the disadvantage is that the amount of hydrophobic polymer phase must be relatively large to allow for adequate oxygen permeability, thereby reducing the hydrophilic volume available for enzyme inclusion sufficient to counter inactivation during long-term operation.
- the invention is the design and use of a biological measuring device for implantation into an individual or for use in an external environment.
- the device contains an enzyme electrode to detect the coreactant or product (e.g. oxygen, H 2 O 2 , respectively) of an enzymatic reaction catalyzed by an oxidase (e.g. glucose oxidase, lactate oxidase, cholesterol oxidase) of the biological molecule of interest (e.g. glucose, lactate, cholesterol) with a limiting reagent or coreactant (e.g. oxygen).
- the device contains a differentially permeable membrane that limits the access of the biological molecule of interest, which is present in the device's
- PATYGOUG02.B14 -5- environment at a relatively high concentration as compared to the coreactant, to the enzyme.
- Exected ratios of biological molecule to coreactant concentrations (e.g. glucose concentration to oxygen concentration) in biological samples or environments may be expected to range up to 10: 1 and beyond, expressed in units of mg/dl / mmHg.)
- the biological molecule becomes the limiting reagent in a critical zone within the enzyme-containing region of the membrane, allowing for its quantification by assaying the amount of product produced or the amount of unconsumed coreactant by means of an associated sensor or electrode, responsive to the coreactant or product.
- the membrane is composed of a continuous or nearly continuous restricted-permeability membrane body, permeable to oxygen and essentially impermeable to larger biological molecules (e.g. glucose, lactate, cholesterol), and discrete hydrophilic regions, permeable to both biological molecules and oxygen (FIGURE 1 ).
- the reactants diffuse from the environment into the device through a single surface of the device.
- the size, density, shape, and number of hydrophilic regions may be varied depending upon the bodily fluid, tissue, or environment into which the device is implanted or depending upon the choice of the associated sensor.
- the location, number, shape, and size of the oxygen- and biological molecule-permeable regions may be modified to optimize the performance of the sensor.
- the invention is a biological measuring device containing the composite membrane of the invention.
- the membrane of the invention can be optimized for detection of a number of biochemicals with a single or a plurality of detecting electrodes. Electrodes may be linked in any of a
- PATYGOUG02.B14 -6- number of ways well known to those skilled in the art (e.g. Sargent and Gough, 1 991 , herein incorporated by reference).
- the size, shape, number, and location of the hydrophilic regions can be varied to deliver the appropriate ranges of the biological molecule and oxygen to the enzyme such that a detectable amount of product or consumed coreactant reaches the associated sensor.
- the invention is a method to specify the optimal ratio of restricted- permeability membrane body to hydrophilic regions in the membrane, and to determine the optimal shape and arrangement of the hydrophilic regions in the membrane such that the concentrations of the reactants in the critical zone are limited by diffusion.
- the sensor can be optimized for different reactions and enzymes for use in different tissues, bodily fluids or in an external sensor.
- the invention is the use of the biological measuring device to monitor the level of a biological molecule, either by implantation in an individual or by use of the device in an external environment.
- the device is used to monitor glucose levels in an individual with diabetes.
- FIGURE 1 Schematic of a biological sensor device membrane with a single hydrophilic region and sensor.
- the device comprises a membrane body (2) that communicates with an environment (4) having a first material such as glucose and a second material such as oxygen.
- the surface (8) of the membrane body communicates with the environment
- PATYGOUG02.B14 -7- (4) The membrane body communicates with a hydrophilic region (6) with catalyst.
- the hydrophilic region (6) contains a critical zone (1 2) of average equivalent radius a (14) and length / (1 6) such that a ⁇ l.
- a sensor ( 1 8), with surface (20), is sensitive to the reaction product or residual co-reactant and produces a signal in proportion to the concentration.
- a control (26) responds to the signal, for comparison with a reference (28).
- the diffusion paths of the first material (30) and (34) and of the second material (32) enter the device through the same surface (8).
- R is the radius of the hydrophilic region on the face of the membrane in communication with the environment.
- R 2 is the radius of the hydrophilic region on the face of the membrane in communication with the sensor.
- R 3 is the radius of the sensor.
- FIGURE 2 Schematic of a biological sensor device for implantation.
- the sensor device for implantation comprises a membrane body (2) that communicates with an environment (4) having a first material such as glucose and a second material such as oxygen.
- the surface (8) of the membrane body communicates with the outer layer ( 1 0) to the environment (4).
- the membrane body communicates with a hydrophilic region (6) with catalyst.
- the hydrophilic region (6) contains a critical zone (1 2) of average equivalent radius a ( 14) and length / ( 1 6) such that a ⁇ l.
- a sensor (1 8), with surface (20), is sensitive to the reaction product or residual co-reactant and produces a signal in proportion to the concentration.
- the sensor's surface (20) communicates with the electrolyte layer (24) adjacent to the sensor protective layer (22).
- a control (26) responds to the signal, for comparison with a reference (28).
- FIGURE 3 Schematic of a biological sensor device with an alternative
- a biological sensor device having a hydrophilic region with catalyst with a cross-section in the form of an inverted "T".
- the device comprises a membrane body (2) that communicates with an environment having a first material such as glucose and a second material such as oxygen.
- the surface (8) of the membrane body communicates with the environment.
- the membrane body communicates with a hydrophilic region (6) with catalyst.
- the hydrophilic region (6) contains a critical zone (1 2) of average equivalent radius a and length / such that a ⁇ l.
- a sensor ( 1 8), with surface (20) is sensitive to the reaction product or residual co-reactant and produces a signal in proportion to the concentration.
- a control (26) responds to the signal, for comparison with a reference (28).
- L1 is the length of the narrower cylindrical portion of the hydrophilic region and L2 is the full length of the hydrophilic region.
- L2 is equivalent to T1 as shown in FIGURES 1 and 4.
- FIGURE 4 Schematic of membrane illustrating a plurality of hydrophilic regions.
- This figure describes a sensor device with a membrane body (2) with a plurality of hydrophilic regions (6) with catalyst variously juxtaposed across the sensor surface (20) in communication with the sensor ( 1 8), the hydrophilic regions having respective critical zones ( 1 2).
- the diffusion paths for the first material (30) and (34), and second material (32) enter the device through the same surface (8).
- the sensor ( 1 8) with the surface(20) is sensitive to the reaction product or residual co-reactant and produces a signal in proportion to the concentration.
- the center-to-center spacing (S) and the radius (R) of the hydrophilic regions is shown.
- FIGURE 5 Schematic of a membrane illustrating a funnel shaped
- FIGURE 6 Schematic of a membrane illustrating multiple cylindrical hydrophilic regions as discussed in Example 2 with various specification measurements indicated, including membrane thickness, enzyme region diameter and enzyme region spacing.
- FIGURE 7 The calculated response of an oxygen sensor, in communication with hydrophilic regions, to environmental concentrations of glucose and oxygen for various membrane constructions.
- the electrode current is calculated and shown as i g /l 0 which is the ratio of the glucose modulated oxygen current to the current in the absence of glucose.
- Enzymatic sensor assembly- An electrochemical detector component comprising a noble metal working electrode polarizable as an anode or a cathode, potential reference electrode, a counter electrode and layer of conductive electrolyte forming a thin conductive layer among the electrode sensor structures; an electronic polarization and amplification component consisting of a potentiostat or polarizing amplifier, current recording amplifier and a signal conveyor (e.g. a wire); and a layered or stratified membrane structure composed (1 ) in the case of the oxygen based sensor of an inner, electrode protective layer of a pore-free, oxygen-permeable material such as polydimethylsiloxane that is impermeable to polar compounds, or in the case of a peroxide-based
- PATYG0UG02.B14 -1 0- sensor a porous membrane that is permeable to hydrogen peroxide and less permeable to larger polar molecules; (2) an enzyme region or domain of specified shape and volume containing immobilized enzymes; (3) a membrane structure for differential control of reactant access to the enzyme region by means of a specified pore size, differential permeability reactant solubility or geometric configuration; and (4) an optional biocompatibility membrane or layer to promote development of a biocompatible interface between tissue or blood and the implanted sensor (FIGURE 2).
- a number of such assemblies are well known such as those taught in Schulman, US Patent 5,660, 1 63.
- Hydrophilic region- An intermittent volume in communication with the membrane body that is permeable to both larger biological molecules (e.g. glucose) and oxygen.
- e.g. glucose e.g. glucose
- oxygen e.g. oxygen
- It can be made of any of a number of glucose- and oxygen-permeable materials including, but not limited to, polyacrylamide gels, glutaraldehyde cross-linked proteins, particularly collagen or albumin, vinyl pyrollidone, alginates, ethylene oxide, polyhydroxyethylmethacrylate and its derivatives, and other hydrophilic polymers and co-polymers. Co-polymers, blends, or composites that
- PATYGOUG02.B14 -1 1 - incorporate these types of materials are also suitable.
- An enzyme or catalyst is typically incorporated into this region.
- Critical zone- A volume of the membrane that is coincident with the hydrophilic region, or a portion thereof, through which the reaction of the biological molecule with the oxygen is modulated by limiting the diffusion of the biological molecule from the environment.
- it is a volume that is coincident with a given hydrophilic region, or a portion thereof that is bound between two end planes that are oriented perpendicular to the average vector direction of diffusion of the biological molecule (e.g. glucose) throughout the whole given hydrophilic region, wherein the average vector direction of diffusion of the biological molecule in the critical zone is essentially parallel to the average vector direction of diffusion of the biological molecule in the whole given hydrophilic region.
- a critical zone must have an average equivalent radius that is less than the length of the critical zone.
- An equivalent radius is obtained by first dividing by pi the area of a given cross section of a given hydrophilic region, the area being oriented perpendicular to the average vector direction of diffusion of the biological molecule throughout the whole given hydrophilic region, then taking the square root of the resulting quantity.
- the invention is a novel membrane structure based on a nearly continuous oxygen-permeable, glucose-impermeable membrane body having discrete regions of hydrophilic, glucose-permeable gel in which the enzyme is immobilized. Additionally, the hydrophilic regions communicate through the membrane to one or more underlying electrode sensor structures.
- the materials and methods used for preparing the hydrophilic regions are described in Gough, US Patent No. 4,484,987 which is incorporated herein by reference.
- PATYGOUG02.B14 -12- The desired geometric relationships between the membrane body and the hydrophilic regions and the shape of the hydrophilic regions must function to supply coreactant to the enzyme gel such that the reaction within the gel is limited by the availability of biological molecule rather than coreactant. Any portion of the hydrophilic region that meets the definition of critical zone may provide this function.
- the hydrophilic regions may or may not penetrate the entire thickness of the membrane, but must communicate, either directly or by means of an external membrane having permeability to glucose, with the environment in which the device is operated.
- the device is a flat, disc shape. The glucose and oxygen diffuse into the device through a single face at the device-environment interface.
- the hydrophilic regions may be varied in size, shape, number and spatial distribution to advantage in a given device design.
- Shapes may include: 1 ) a cylinder orthogonal to the plane of the membrane to provide radially uniform oxygen access within the enzyme region, 2) a square or parallelogram, as seen from the face of the membrane, for ease of fabrication by a method of laying one sheet of hydrophobic strips over another, 3) a cone or other shape of tapering radius, as seen from the edge of the membrane with the base at the sensor electrode side to provide a mechanical confinement of the gel and prevent gel extrusion or separation from the membrane body during fabrication or use conformations formed from a combination of such shapes, such as a "funnel, " formed by the combination of conically- and cylindrically-shaped regions (e.g. FIGURES 2-3). The exact conformation of the shapes listed above is not required.
- the size, shape, number, and spatial distribution of the hydrophilic gel regions can be varied (e.g. FIGURE 4).
- the exact patterning of the hydrophilic gel regions is designed to optimize sensor response, sensitivity to biologic molecule, coreactant independence and insensitivity to
- PATYGOUG02.B14 -13- environmental heterogeneity The size of the hydrophilic regions can be varied over different electrodes to provide the sensor with a broader range of sensitivity. It is not necessary for the sensor to be of the same radius as the hydrophilic region. Moreover, it is possible to design a device with multiple sensors associated with a single hydrophilic region, or multiple hydrophilic regions associated with a single sensor. Design choices are based on a variety of factors, such as preference for a particular manufacturing technique, requirements for signal magnitudes based on choice of electronic circuitry, and the vascular density in the tissue of implantation.
- the thickness of the membrane can be controlled to optimize the oxygen independence, diffusional length for glucose within the hydrophilic gel to provide reserve enzyme, and to optimize respective response times to glucose and oxygen changes.
- Regions of the membrane body that can be used to house hydrophilic regions may be fabricated by any of a number of methods well known to those skilled in the art including programmed laser ablation, molding, cutting, punching, etc. Holes can then be filled with uncrosslinked enzyme-containing precursor solutions and then crosslinker is added or activated, to solidify the solution.
- a hydrophobic membrane shown in FIGURE 2, may be inserted between the above-described membrane structure and the oxygen sensing electrode, or directly overlying the oxygen electrode and electrolyte solution.
- Such an intervening membrane protects the oxygen electrode from electrochemical poisoning from polar and diffusable compounds. Its dimensions and material properties can also be varied to advantage depending on the exact sensor design. Preferably such a membrane would readily allow the diffusion of oxygen while preventing the diffusion of larger molecules through the membrane. Additionally, the membrane is thin to maximize the sensitivity of the system to glucose.
- PATYGOUG02.B14 -14- The positioning and arrangement of the hydrophilic gel regions can be varied with regard to the underlying oxygen sensor electrode or electrodes to optimize the sensitivity and range of the device. It is important to note that the sensitivity and response time of the device can be altered simply by varying the amount of electrode surface area of the oxygen sensor, along with the thickness of the membrane over the sensor. The methods for making these adjustments are well known to those skilled in the art.
- the electrodes may be either oxygen or hydrogen peroxide sensing.
- the sensor may be an electrically conductive layer or an electrode connected by a wire to single or multichannel electronics.
- the membrane may be connected directly to the electronics.
- the sensor may be covered with a biocompatible outer membrane that also inhibits exposure of the inner membranes to proteins or other large molecules that may alter the properties of the sensor inner membranes.
- a membrane could be composed of porous polyhydroxyethyl- methacrylate, polyethylene- or polycarbonate-containing polymers, fluorinated polymers, or other suitable materials.
- the device contains at least one hydrophilic region over a single electrode (FIGURES 1 -4).
- the sensor is a disc platinum oxygen electrode closely apposed to a hydrophilic region and the hydrophilic region is surrounded by a material that is essentially impermeable to glucose.
- the hydrophilic region contains immobilized glucose oxidase and optionally, an excess of catalase. For a given glucose concentration in the external medium the sensor response is
- PATYGOUG02.B14 -1 5- determined by the permeability of the hydrophilic region and membrane body, the enzyme activity, and the aspect ratio, or ratio of the average equivalent radius of the critical zone within the hydrophilic region to the height of the critical zone. In order to obtain a useful range of response in biological operating conditions, it is preferred that this aspect ratio be less than one.
- EXAMPLE 1 Sensor membranes were produced by filling the cavities in perforated silicone rubber sheets with a glucose oxidase/albumin mixture and crosslinking the mixture with glutaraldehyde using the method described in Armour et al. 1 990, incorporated herein by reference.
- the membranes were mounted over a membrane-covered electrochemical oxygen sensor, with a circular platinum working electrode of diameter 0.005", formed on an alumina ceramic substrate using conventional thick-film methods.
- the required counter electrode was platinum and the required reference electrode was silver-plated platinum.
- the devices were connected to a potentiostat circuit, and the working electrode was polarized at -500mV with respect to the reference electrode, (see for example: Bard and Faulkner, 2000). Tests were conducted in a simulated biological environment: phosphate-buffered saline, at 37°C, equilibrated with known oxygen concentrations. Known quantities of glucose were added to the solution and the electrode current measured. Two different membrane geometries, schematically represented in Figure 5, with the specifications shown ⁇ below, were tested. As is well-known (see e.g. Gough et al, 1 985), the device's response is suitably analyzed by examination of the normalized electrode current as a function of the glucose-to-oxygen ratio in the environment. Both raw (nanoampere) electrode currents and normalized currents (expressed as a percentage of the value without glucose) are reported below.
- membrane thickness 0.010" hydrophilic region shape: funnel hydrophilic region radius at base (closest to electrode): 0.014" hydrophilic region radius at top, communicating with fluid: 0.002"
- EXAMPLE 2 Sensor membranes were produced by filling the cavities in perforated silicone rubber sheets with a glucose oxidase/albumin mixture and crosslinking the mixture with glutaraldehyde using the method described in Armour et al. 1 990, incorporated herein by reference.
- the membranes were mounted over a membrane-covered electrochemical oxygen sensor, with a rectangular platinum working electrode of dimensions 0.025" (inches) x 0.2", formed on an alumina ceramic substrate using conventional thick-film methods.
- the required counter electrode was platinum and the required reference electrode was silver-plated platinum.
- the devices were connected to a potentiostat circuit, and the working electrode was polarized at -500mV with respect to the reference electrode, following well-known methods (see for example: Bard and
- Tests were conducted in a simulated biological environment: phosphate-buffered saline, at 37°C, equilibrated with known oxygen concentrations. Known quantities of glucose were added to the solution and the electrode current measured. Two different membrane geometries, schematically represented in Figure 6, with the specifications shown below, were tested. As is well-known (see e.g. Gough et al., 1 985), the device's response is suitably analyzed by examination of the normalized electrode current as a function of the glucose-to-oxygen ratio in the environment. Both raw (nanoampere) electrode currents and normalized currents (expressed as a percentage of the value without glucose) are reported below.
- PATYGOUG02.B14 -18- membrane thickness 0.01 0" hydrophilic region shape: cylindrical hydrophilic region radius: 0.005" hydrophilic region spacing: 0.020" center-to-center, offset grid pattern
- membrane thickness 0.01 0" hydrophilic region shape: cylindrical hydrophilic region radius: 0.005" hydrophilic region spacing: 0.010" center-to-center, offset grid pattern Results:
- EXAMPLE 3 Optimization of hydrophilic region shape and size was carried out using computer modeling methods. The analysis is based on the modeling of diffusion and reaction of glucose and oxygen in the presence of glucose oxidase and catalase within the hydrophilic region. The chemical reaction can be summarized as follows: glucose + ! O 2 > gluconic acid
- Computer models of operating devices were constructed using conventional methods (see for example: M. C. Jablecki and D. A. Gough, 2000, incorporated herein by reference) to calculate the response of an oxygen sensor, in communication with one or more hydrophilic regions, to environmental glucose and oxygen concentrations for various membrane constructions.
- the electrode current is calculated and shown as i 9 /l 0 , which is the ratio of the glucose-modulated oxygen current to the current in the absence of glucose (see e.g. Armour, et al 1 990).
- This normalized current equals zero in the absence of glucose and rises to a maximum value of unity as glucose concentration increases.
- useful sensitivities for monitoring glucose in biological media are obtainable only if the average equivalent radius of the hydrophilic region's critical zone is less than the length of the critical zone. If the average equivalent radius is greater than the length, then the critical zone is not adequately supplied with coreactant and the device's dynamic
- PATYGOUG02.B14 -20- response range is too limited for practical use in biological samples.
- the response range and sensitivities were modeled for three different shapes of hydrophilic regions analogous to those shown in FIGURES 4, 1 and 3, respectively.
- the data demonstrate that parameters may be readily modified by altering the shape of the hydrophilic region depending on other device considerations well known to those skilled in the art.
- FIGURE 6A shows the calculated response of an oxygen sensor (radius 62.5 microns) in communication with a membrane containing a cylindrical hydrophilic region, of length 350 microns, for various cylinder radii R. In all cases, the cylinder radius is less than the length, and the modeled devices demonstrate acceptable response to glucose.
- FIGURE 6B shows the calculated response of an oxygen sensor (radius 62.5 microns) in communication with a membrane containing a conical hydrophilic region, with a base radius R2 equal to 250 microns, and various values of top radii R1 .
- the cone base is oriented toward the oxygen sensor and the length is 350 microns. In all cases, the average equivalent radius of the hydrophilic region is less than the length, and the modeled devices demonstrate acceptable response to glucose.
- FIGURE 6C shows the calculated response of an oxygen sensor
- PATYGOUG02.B14 -21 - length the modeled devices demonstrate an acceptable range of response to glucose.
- circular cross-sections are used to determine the preferred size of the hydrophilic regions.
- this does not limit the instant invention to the use of round hydrophilic regions.
- the optimization calculation provides ideal internal and external surface areas and spacing for the hydrophilic regions that may be any shape. The selection of shape is a matter of choice to be made based on any of a number of factors including the shape of the electrodes, the overall shape of the sensor and the ease of manufacture.
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Families Citing this family (211)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE9700384D0 (en) * | 1997-02-04 | 1997-02-04 | Biacore Ab | Analytical method and apparatus |
US7899511B2 (en) | 2004-07-13 | 2011-03-01 | Dexcom, Inc. | Low oxygen in vivo analyte sensor |
US6001067A (en) | 1997-03-04 | 1999-12-14 | Shults; Mark C. | Device and method for determining analyte levels |
US6862465B2 (en) | 1997-03-04 | 2005-03-01 | Dexcom, Inc. | Device and method for determining analyte levels |
US7192450B2 (en) | 2003-05-21 | 2007-03-20 | Dexcom, Inc. | Porous membranes for use with implantable devices |
US7657297B2 (en) | 2004-05-03 | 2010-02-02 | Dexcom, Inc. | Implantable analyte sensor |
US9155496B2 (en) | 1997-03-04 | 2015-10-13 | Dexcom, Inc. | Low oxygen in vivo analyte sensor |
US8527026B2 (en) | 1997-03-04 | 2013-09-03 | Dexcom, Inc. | Device and method for determining analyte levels |
US20050033132A1 (en) | 1997-03-04 | 2005-02-10 | Shults Mark C. | Analyte measuring device |
US6391005B1 (en) | 1998-03-30 | 2002-05-21 | Agilent Technologies, Inc. | Apparatus and method for penetration with shaft having a sensor for sensing penetration depth |
US8974386B2 (en) | 1998-04-30 | 2015-03-10 | 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 |
US6175752B1 (en) | 1998-04-30 | 2001-01-16 | Therasense, 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 |
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 |
US8688188B2 (en) | 1998-04-30 | 2014-04-01 | 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 |
US9066695B2 (en) | 1998-04-30 | 2015-06-30 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
NL1014464C2 (en) * | 2000-02-22 | 2001-08-24 | Tno | Optical sensor for measuring oxygen. |
US8641644B2 (en) | 2000-11-21 | 2014-02-04 | Sanofi-Aventis Deutschland Gmbh | Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means |
US6560471B1 (en) | 2001-01-02 | 2003-05-06 | Therasense, Inc. | Analyte monitoring device and methods of use |
US6721587B2 (en) | 2001-02-15 | 2004-04-13 | Regents Of The University Of California | Membrane and electrode structure for implantable sensor |
TW522127B (en) * | 2001-02-21 | 2003-03-01 | Daifuku Kk | Cargo storage facility |
US7041468B2 (en) | 2001-04-02 | 2006-05-09 | Therasense, Inc. | Blood glucose tracking apparatus and methods |
US7025774B2 (en) | 2001-06-12 | 2006-04-11 | Pelikan Technologies, Inc. | Tissue penetration device |
US9226699B2 (en) | 2002-04-19 | 2016-01-05 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling module with a continuous compression tissue interface surface |
WO2002100254A2 (en) | 2001-06-12 | 2002-12-19 | Pelikan Technologies, Inc. | Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge |
US9427532B2 (en) | 2001-06-12 | 2016-08-30 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
US9795747B2 (en) | 2010-06-02 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Methods and apparatus for lancet actuation |
US8337419B2 (en) * | 2002-04-19 | 2012-12-25 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
US7033371B2 (en) | 2001-06-12 | 2006-04-25 | Pelikan Technologies, Inc. | Electric lancet actuator |
US7344507B2 (en) * | 2002-04-19 | 2008-03-18 | Pelikan Technologies, Inc. | Method and apparatus for lancet actuation |
US6702857B2 (en) | 2001-07-27 | 2004-03-09 | Dexcom, Inc. | Membrane for use with implantable devices |
US20030032874A1 (en) | 2001-07-27 | 2003-02-13 | Dexcom, Inc. | Sensor head for use with implantable devices |
US6966880B2 (en) * | 2001-10-16 | 2005-11-22 | Agilent Technologies, Inc. | Universal diagnostic platform |
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 |
US9282925B2 (en) | 2002-02-12 | 2016-03-15 | Dexcom, Inc. | Systems and methods for replacing signal artifacts in a glucose sensor data stream |
US8364229B2 (en) | 2003-07-25 | 2013-01-29 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US9247901B2 (en) | 2003-08-22 | 2016-02-02 | Dexcom, Inc. | Systems and methods for replacing signal artifacts in a glucose sensor data stream |
US8260393B2 (en) | 2003-07-25 | 2012-09-04 | Dexcom, Inc. | Systems and methods for replacing signal data artifacts in a glucose sensor data stream |
US8010174B2 (en) | 2003-08-22 | 2011-08-30 | Dexcom, Inc. | Systems and methods for replacing signal artifacts in a glucose sensor data stream |
US8858434B2 (en) | 2004-07-13 | 2014-10-14 | Dexcom, Inc. | Transcutaneous analyte sensor |
US7229458B2 (en) | 2002-04-19 | 2007-06-12 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7547287B2 (en) | 2002-04-19 | 2009-06-16 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US8784335B2 (en) | 2002-04-19 | 2014-07-22 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling device with a capacitive sensor |
US8360992B2 (en) | 2002-04-19 | 2013-01-29 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US8702624B2 (en) | 2006-09-29 | 2014-04-22 | Sanofi-Aventis Deutschland Gmbh | Analyte measurement device with a single shot actuator |
US9795334B2 (en) | 2002-04-19 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US8579831B2 (en) | 2002-04-19 | 2013-11-12 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US7901362B2 (en) | 2002-04-19 | 2011-03-08 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US9314194B2 (en) | 2002-04-19 | 2016-04-19 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
US8267870B2 (en) | 2002-04-19 | 2012-09-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for body fluid sampling with hybrid actuation |
US7909778B2 (en) | 2002-04-19 | 2011-03-22 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US9248267B2 (en) | 2002-04-19 | 2016-02-02 | Sanofi-Aventis Deustchland Gmbh | Tissue penetration device |
US8221334B2 (en) | 2002-04-19 | 2012-07-17 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US7713214B2 (en) * | 2002-04-19 | 2010-05-11 | Pelikan Technologies, Inc. | Method and apparatus for a multi-use body fluid sampling device with optical analyte sensing |
US7892185B2 (en) | 2002-04-19 | 2011-02-22 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
US20070227907A1 (en) * | 2006-04-04 | 2007-10-04 | Rajiv Shah | Methods and materials for controlling the electrochemistry of analyte sensors |
US7226978B2 (en) | 2002-05-22 | 2007-06-05 | Dexcom, Inc. | Techniques to improve polyurethane membranes for implantable glucose sensors |
US20060258761A1 (en) * | 2002-05-22 | 2006-11-16 | Robert Boock | Silicone based membranes for use in implantable glucose sensors |
AU2003245862A1 (en) * | 2002-07-12 | 2004-02-02 | Novo Nordisk A/S | Minimising calibration problems of in vivo glucose sensors |
US20050272989A1 (en) * | 2004-06-04 | 2005-12-08 | Medtronic Minimed, Inc. | Analyte sensors and methods for making and using them |
US7248912B2 (en) * | 2002-10-31 | 2007-07-24 | The Regents Of The University Of California | Tissue implantable sensors for measurement of blood solutes |
US8574895B2 (en) * | 2002-12-30 | 2013-11-05 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus using optical techniques to measure analyte levels |
US7134999B2 (en) * | 2003-04-04 | 2006-11-14 | Dexcom, Inc. | Optimized sensor geometry for an implantable glucose sensor |
US7875293B2 (en) | 2003-05-21 | 2011-01-25 | Dexcom, Inc. | Biointerface membranes incorporating bioactive agents |
DE602004028463D1 (en) * | 2003-05-30 | 2010-09-16 | Pelikan Technologies Inc | METHOD AND DEVICE FOR INJECTING LIQUID |
US7850621B2 (en) | 2003-06-06 | 2010-12-14 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
WO2006001797A1 (en) | 2004-06-14 | 2006-01-05 | Pelikan Technologies, Inc. | Low pain penetrating |
US9763609B2 (en) | 2003-07-25 | 2017-09-19 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
EP1648298A4 (en) * | 2003-07-25 | 2010-01-13 | Dexcom Inc | Oxygen enhancing membrane systems for implantable devices |
WO2005019795A2 (en) * | 2003-07-25 | 2005-03-03 | Dexcom, Inc. | Electrochemical sensors including electrode systems with increased oxygen generation |
US8423113B2 (en) | 2003-07-25 | 2013-04-16 | Dexcom, Inc. | Systems and methods for processing sensor data |
US20050176136A1 (en) * | 2003-11-19 | 2005-08-11 | Dexcom, Inc. | Afinity domain for analyte sensor |
US7761130B2 (en) | 2003-07-25 | 2010-07-20 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
WO2005012871A2 (en) * | 2003-07-25 | 2005-02-10 | Dexcom, Inc. | Increasing bias for oxygen production in an electrode system |
WO2005012873A2 (en) * | 2003-07-25 | 2005-02-10 | Dexcom, Inc. | Electrode systems for electrochemical sensors |
US7591801B2 (en) | 2004-02-26 | 2009-09-22 | Dexcom, Inc. | Integrated delivery device for continuous glucose sensor |
US8886273B2 (en) | 2003-08-01 | 2014-11-11 | Dexcom, Inc. | Analyte sensor |
US8761856B2 (en) | 2003-08-01 | 2014-06-24 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US9135402B2 (en) | 2007-12-17 | 2015-09-15 | Dexcom, Inc. | Systems and methods for processing sensor data |
US8060173B2 (en) | 2003-08-01 | 2011-11-15 | Dexcom, Inc. | System and methods for processing analyte sensor data |
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 |
US8845536B2 (en) | 2003-08-01 | 2014-09-30 | Dexcom, Inc. | Transcutaneous analyte sensor |
US7986986B2 (en) | 2003-08-01 | 2011-07-26 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US7494465B2 (en) | 2004-07-13 | 2009-02-24 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8369919B2 (en) | 2003-08-01 | 2013-02-05 | Dexcom, Inc. | Systems and methods for processing sensor data |
US8788006B2 (en) | 2003-08-01 | 2014-07-22 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US8275437B2 (en) | 2003-08-01 | 2012-09-25 | Dexcom, Inc. | Transcutaneous analyte sensor |
US20190357827A1 (en) | 2003-08-01 | 2019-11-28 | Dexcom, Inc. | Analyte sensor |
US7920906B2 (en) | 2005-03-10 | 2011-04-05 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US8233959B2 (en) | 2003-08-22 | 2012-07-31 | Dexcom, Inc. | Systems and methods for processing analyte sensor data |
US20140121989A1 (en) | 2003-08-22 | 2014-05-01 | Dexcom, Inc. | Systems and methods for processing analyte sensor data |
US8282576B2 (en) | 2003-09-29 | 2012-10-09 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for an improved sample capture device |
EP1680014A4 (en) | 2003-10-14 | 2009-01-21 | Pelikan Technologies Inc | Method and apparatus for a variable user interface |
US20050090607A1 (en) * | 2003-10-28 | 2005-04-28 | Dexcom, Inc. | Silicone composition for biocompatible membrane |
ATE476909T1 (en) * | 2003-11-13 | 2010-08-15 | Medtronic Minimed Inc | LONG-TERM ANALYT SENSOR ARRANGEMENT |
US8414489B2 (en) * | 2003-11-13 | 2013-04-09 | Medtronic Minimed, Inc. | Fabrication of multi-sensor arrays |
US9247900B2 (en) | 2004-07-13 | 2016-02-02 | Dexcom, Inc. | Analyte sensor |
US8615282B2 (en) | 2004-07-13 | 2013-12-24 | Dexcom, Inc. | Analyte sensor |
WO2005051170A2 (en) | 2003-11-19 | 2005-06-09 | Dexcom, Inc. | Integrated receiver for continuous analyte sensor |
US8532730B2 (en) | 2006-10-04 | 2013-09-10 | Dexcom, Inc. | Analyte sensor |
US8423114B2 (en) | 2006-10-04 | 2013-04-16 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
DE602004029092D1 (en) | 2003-12-05 | 2010-10-21 | Dexcom Inc | CALIBRATION METHODS FOR A CONTINUOUSLY WORKING ANALYTIC SENSOR |
US8287453B2 (en) | 2003-12-05 | 2012-10-16 | Dexcom, Inc. | Analyte sensor |
US11633133B2 (en) | 2003-12-05 | 2023-04-25 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
US8364231B2 (en) | 2006-10-04 | 2013-01-29 | Dexcom, Inc. | Analyte sensor |
EP3241490A1 (en) * | 2003-12-08 | 2017-11-08 | DexCom, Inc. | Systems and methods for improving electrochemical analyte sensors |
EP2329763B1 (en) | 2003-12-09 | 2017-06-21 | DexCom, Inc. | Signal processing for continuous analyte sensor |
US7146203B2 (en) * | 2003-12-18 | 2006-12-05 | Elliot Botvinick | Implantable biosensor and methods of use thereof |
US7822454B1 (en) | 2005-01-03 | 2010-10-26 | Pelikan Technologies, Inc. | Fluid sampling device with improved analyte detecting member configuration |
EP1706026B1 (en) | 2003-12-31 | 2017-03-01 | Sanofi-Aventis Deutschland GmbH | Method and apparatus for improving fluidic flow and sample capture |
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 |
US20080312555A1 (en) * | 2004-02-06 | 2008-12-18 | Dirk Boecker | Devices and methods for glucose measurement using rechargeable battery energy sources |
US7894870B1 (en) | 2004-02-13 | 2011-02-22 | Glysens, Incorporated | Hermetic implantable sensor |
US8808228B2 (en) * | 2004-02-26 | 2014-08-19 | Dexcom, Inc. | Integrated medicament delivery device for use with continuous analyte sensor |
US8792955B2 (en) | 2004-05-03 | 2014-07-29 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8277713B2 (en) | 2004-05-03 | 2012-10-02 | Dexcom, Inc. | Implantable analyte sensor |
US20050245799A1 (en) * | 2004-05-03 | 2005-11-03 | Dexcom, Inc. | Implantable analyte sensor |
WO2005107852A1 (en) * | 2004-05-04 | 2005-11-17 | University Of Rochester | Leadless implantable intravascular electrophysiologic device for neurologic/cardiovascular sensing and stimulation |
WO2005107864A1 (en) * | 2004-05-04 | 2005-11-17 | University Of Rochester | Leadless implantable cardioverter defibrillator |
WO2005107863A2 (en) | 2004-05-04 | 2005-11-17 | University Of Rochester | Implantable bio-electro-physiologic interface matrix |
US7642076B2 (en) * | 2004-05-07 | 2010-01-05 | Gm Global Technology Operations, Inc. | Process for immobilization of protein catalysts, product, and use |
EP1751546A2 (en) | 2004-05-20 | 2007-02-14 | Albatros Technologies GmbH & Co. KG | Printable hydrogel for biosensors |
EP1765194A4 (en) | 2004-06-03 | 2010-09-29 | Pelikan Technologies Inc | Method and apparatus for a fluid sampling device |
US9775553B2 (en) | 2004-06-03 | 2017-10-03 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for a fluid sampling device |
US20060270922A1 (en) | 2004-07-13 | 2006-11-30 | Brauker James H | Analyte sensor |
US8565848B2 (en) | 2004-07-13 | 2013-10-22 | 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 |
US20080242961A1 (en) * | 2004-07-13 | 2008-10-02 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8652831B2 (en) | 2004-12-30 | 2014-02-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for analyte measurement test time |
US20090076360A1 (en) | 2007-09-13 | 2009-03-19 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8133178B2 (en) | 2006-02-22 | 2012-03-13 | Dexcom, Inc. | Analyte sensor |
US8744546B2 (en) | 2005-05-05 | 2014-06-03 | Dexcom, Inc. | Cellulosic-based resistance domain for an analyte sensor |
US8060174B2 (en) | 2005-04-15 | 2011-11-15 | Dexcom, Inc. | Analyte sensing biointerface |
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 |
US9757061B2 (en) | 2006-01-17 | 2017-09-12 | Dexcom, Inc. | Low oxygen in vivo analyte sensor |
US7653425B2 (en) | 2006-08-09 | 2010-01-26 | Abbott Diabetes Care Inc. | Method and system for providing calibration of an analyte sensor in an analyte monitoring system |
US8224415B2 (en) | 2009-01-29 | 2012-07-17 | Abbott Diabetes Care Inc. | Method and device for providing offset model based calibration for analyte sensor |
US9675290B2 (en) | 2012-10-30 | 2017-06-13 | Abbott Diabetes Care Inc. | Sensitivity calibration of in vivo sensors used to measure analyte concentration |
US8219173B2 (en) | 2008-09-30 | 2012-07-10 | Abbott Diabetes Care Inc. | Optimizing analyte sensor calibration |
US7630748B2 (en) | 2006-10-25 | 2009-12-08 | Abbott Diabetes Care Inc. | Method and system for providing analyte monitoring |
US8346335B2 (en) | 2008-03-28 | 2013-01-01 | Abbott Diabetes Care Inc. | Analyte sensor calibration management |
EP2007278A4 (en) * | 2006-04-14 | 2009-11-18 | Dexcom Inc | Silicone based membranes for use in implantable glucose sensors |
WO2007143225A2 (en) | 2006-06-07 | 2007-12-13 | Abbott Diabetes Care, Inc. | Analyte monitoring system and method |
CN101473225B (en) * | 2006-06-19 | 2016-05-11 | 霍夫曼-拉罗奇有限公司 | Amperometric sensor and manufacture method thereof |
US9700252B2 (en) | 2006-06-19 | 2017-07-11 | Roche Diabetes Care, Inc. | Amperometric sensor and method for its manufacturing |
US7911315B2 (en) * | 2006-07-28 | 2011-03-22 | Honeywell International Inc. | Miniature pressure sensor assembly for catheter |
US7871456B2 (en) * | 2006-08-10 | 2011-01-18 | The Regents Of The University Of California | Membranes with controlled permeability to polar and apolar molecules in solution and methods of making same |
WO2008018879A1 (en) * | 2006-08-10 | 2008-02-14 | The Regents Of The University Of California | Membranes with controlled permeability to polar and apolar molecules in solution and methods of making same |
DE602006004043D1 (en) * | 2006-08-25 | 2009-01-15 | Alcatel Lucent | Digital signal receiver with Q-factor monitoring |
US7831287B2 (en) | 2006-10-04 | 2010-11-09 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
US20080199894A1 (en) | 2007-02-15 | 2008-08-21 | Abbott Diabetes Care, Inc. | Device and method for automatic data acquisition and/or detection |
US7751864B2 (en) * | 2007-03-01 | 2010-07-06 | Roche Diagnostics Operations, Inc. | System and method for operating an electrochemical analyte sensor |
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 |
US8103471B2 (en) | 2007-05-14 | 2012-01-24 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US8600681B2 (en) | 2007-05-14 | 2013-12-03 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US8239166B2 (en) | 2007-05-14 | 2012-08-07 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US20200037874A1 (en) | 2007-05-18 | 2020-02-06 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US20080306444A1 (en) | 2007-06-08 | 2008-12-11 | Dexcom, Inc. | Integrated medicament delivery device for use with continuous analyte sensor |
US20090036760A1 (en) * | 2007-07-31 | 2009-02-05 | Abbott Diabetes Care, Inc. | Method and apparatus for providing data processing and control in a medical communication system |
EP4159114B1 (en) | 2007-10-09 | 2024-04-10 | DexCom, Inc. | Integrated insulin delivery system with continuous glucose sensor |
US8417312B2 (en) | 2007-10-25 | 2013-04-09 | Dexcom, Inc. | Systems and methods for processing sensor data |
US8290559B2 (en) | 2007-12-17 | 2012-10-16 | Dexcom, Inc. | Systems and methods for processing sensor data |
EP2252196A4 (en) | 2008-02-21 | 2013-05-15 | Dexcom Inc | Systems and methods for processing, transmitting and displaying sensor data |
US8396528B2 (en) | 2008-03-25 | 2013-03-12 | Dexcom, Inc. | Analyte sensor |
WO2009121026A1 (en) * | 2008-03-28 | 2009-10-01 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
US8583204B2 (en) | 2008-03-28 | 2013-11-12 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
US8682408B2 (en) | 2008-03-28 | 2014-03-25 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
US11730407B2 (en) | 2008-03-28 | 2023-08-22 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
WO2009126900A1 (en) | 2008-04-11 | 2009-10-15 | Pelikan Technologies, Inc. | Method and apparatus for analyte detecting device |
US8924159B2 (en) | 2008-05-30 | 2014-12-30 | Abbott Diabetes Care Inc. | Method and apparatus for providing glycemic control |
US8591410B2 (en) | 2008-05-30 | 2013-11-26 | Abbott Diabetes Care Inc. | Method and apparatus for providing glycemic control |
US20100025238A1 (en) * | 2008-07-31 | 2010-02-04 | Medtronic Minimed, Inc. | Analyte sensor apparatuses having improved electrode configurations and methods for making and using them |
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 |
EP2163190A1 (en) * | 2008-09-11 | 2010-03-17 | Roche Diagnostics GmbH | Electrode system for measurement of an analyte concentration in-vivo |
EP3795987B1 (en) | 2008-09-19 | 2023-10-25 | Dexcom, Inc. | Particle-containing membrane and particulate electrode for analyte sensors |
EP2329697B1 (en) * | 2008-09-23 | 2018-12-05 | Siemens Healthcare Diagnostics Inc. | Modulating polarization voltage of amperometric sensors |
US9375169B2 (en) | 2009-01-30 | 2016-06-28 | Sanofi-Aventis Deutschland Gmbh | Cam drive for managing disposable penetrating member actions with a single motor and motor and control system |
WO2010099507A1 (en) * | 2009-02-26 | 2010-09-02 | Abbott Diabetes Care Inc. | Improved analyte sensors and methods of making and using the same |
US9446194B2 (en) | 2009-03-27 | 2016-09-20 | Dexcom, Inc. | Methods and systems for promoting glucose management |
ES2950160T3 (en) | 2009-08-31 | 2023-10-05 | Abbott Diabetes Care Inc | Displays for a medical device |
US8631679B2 (en) * | 2009-09-04 | 2014-01-21 | Isense Corporation | Additional calibration for analyte monitor |
WO2011041469A1 (en) | 2009-09-29 | 2011-04-07 | Abbott Diabetes Care Inc. | Method and apparatus for providing notification function in analyte monitoring systems |
US8185181B2 (en) | 2009-10-30 | 2012-05-22 | Abbott Diabetes Care Inc. | Method and apparatus for detecting false hypoglycemic conditions |
US8965476B2 (en) | 2010-04-16 | 2015-02-24 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
US10092229B2 (en) | 2010-06-29 | 2018-10-09 | Abbott Diabetes Care Inc. | Calibration of analyte measurement system |
JP6141827B2 (en) | 2011-04-15 | 2017-06-07 | デックスコム・インコーポレーテッド | Method of operating a system for measuring an analyte and sensor system configured to implement the method |
KR20140082642A (en) | 2011-07-26 | 2014-07-02 | 글리젠스 인코포레이티드 | Tissue implantable sensor with hermetically sealed housing |
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 |
US10561353B2 (en) | 2016-06-01 | 2020-02-18 | Glysens Incorporated | Biocompatible implantable sensor apparatus and methods |
US10660550B2 (en) | 2015-12-29 | 2020-05-26 | Glysens Incorporated | Implantable sensor apparatus and methods |
EP2890297B1 (en) | 2012-08-30 | 2018-04-11 | Abbott Diabetes Care, Inc. | Dropout detection in continuous analyte monitoring data during data excursions |
EP2901153A4 (en) | 2012-09-26 | 2016-04-27 | 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 |
EP2859911A1 (en) | 2013-10-11 | 2015-04-15 | qSTAR Medical SAS | Vascular access port devices with incorporated sensors |
EP3180065A4 (en) | 2014-07-24 | 2018-04-11 | Thomas Jefferson University | Long-term implantable monitoring system & methods of use |
AU2016315838B2 (en) | 2015-09-02 | 2022-07-28 | Metronom Health, Inc. | Systems and methods for continuous health monitoring using an opto-enzymatic analyte sensor |
US10638962B2 (en) | 2016-06-29 | 2020-05-05 | Glysens Incorporated | Bio-adaptable implantable sensor apparatus and methods |
EP3600493A4 (en) | 2017-03-31 | 2020-08-19 | Capillary Biomedical, Inc. | Helical insertion infusion device |
US10638979B2 (en) | 2017-07-10 | 2020-05-05 | Glysens Incorporated | Analyte sensor data evaluation and error reduction apparatus and methods |
US11331022B2 (en) | 2017-10-24 | 2022-05-17 | Dexcom, Inc. | Pre-connected analyte sensors |
AU2018354120A1 (en) | 2017-10-24 | 2020-04-23 | Dexcom, Inc. | Pre-connected analyte sensors |
US10130290B1 (en) | 2017-11-21 | 2018-11-20 | Uxn Co., Ltd. | Non-enzymatic glucose-sensing device with nanoporous structure and conditioning of the nanoporous structure |
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 |
US11718865B2 (en) * | 2019-07-26 | 2023-08-08 | Medtronic Minimed, Inc. | Methods to improve oxygen delivery to implantable sensors |
AU2022249389A1 (en) | 2021-04-02 | 2023-11-02 | Dexcom, Inc. | Personalized modeling of blood glucose concentration impacted by individualized sensor characteristics and individualized physiological characteristics |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4650547A (en) * | 1983-05-19 | 1987-03-17 | The Regents Of The University Of California | Method and membrane applicable to implantable sensor |
US5882494A (en) * | 1995-03-27 | 1999-03-16 | Minimed, Inc. | Polyurethane/polyurea compositions containing silicone for biosensor membranes |
US5964993A (en) * | 1996-12-19 | 1999-10-12 | Implanted Biosystems Inc. | Glucose sensor |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4484987A (en) | 1983-05-19 | 1984-11-27 | The Regents Of The University Of California | Method and membrane applicable to implantable sensor |
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 |
US4890620A (en) | 1985-09-20 | 1990-01-02 | The Regents Of The University Of California | Two-dimensional diffusion glucose substrate sensing electrode |
US5112455A (en) * | 1990-07-20 | 1992-05-12 | I Stat Corporation | Method for analytically utilizing microfabricated sensors during wet-up |
US5322063A (en) | 1991-10-04 | 1994-06-21 | Eli Lilly And Company | Hydrophilic polyurethane membranes for electrochemical glucose sensors |
US5497772A (en) | 1993-11-19 | 1996-03-12 | Alfred E. Mann Foundation For Scientific Research | Glucose monitoring system |
US6721587B2 (en) | 2001-02-15 | 2004-04-13 | Regents Of The University Of California | Membrane and electrode structure for implantable sensor |
-
2002
- 2002-02-15 US US10/078,567 patent/US6721587B2/en not_active Expired - Lifetime
- 2002-02-15 WO PCT/US2002/006963 patent/WO2002064027A2/en not_active Application Discontinuation
- 2002-02-15 AU AU2002248565A patent/AU2002248565A1/en not_active Abandoned
-
2003
- 2003-11-20 US US10/719,541 patent/US7336984B2/en not_active Expired - Lifetime
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4650547A (en) * | 1983-05-19 | 1987-03-17 | The Regents Of The University Of California | Method and membrane applicable to implantable sensor |
US5882494A (en) * | 1995-03-27 | 1999-03-16 | Minimed, Inc. | Polyurethane/polyurea compositions containing silicone for biosensor membranes |
US5964993A (en) * | 1996-12-19 | 1999-10-12 | Implanted Biosystems Inc. | Glucose sensor |
Also Published As
Publication number | Publication date |
---|---|
AU2002248565A1 (en) | 2002-08-28 |
US20020156355A1 (en) | 2002-10-24 |
US7336984B2 (en) | 2008-02-26 |
US6721587B2 (en) | 2004-04-13 |
US20040106857A1 (en) | 2004-06-03 |
WO2002064027A3 (en) | 2003-03-13 |
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