CA2468894C - Apparatus and methods for microfluidic applications - Google Patents

Apparatus and methods for microfluidic applications Download PDF

Info

Publication number
CA2468894C
CA2468894C CA2468894A CA2468894A CA2468894C CA 2468894 C CA2468894 C CA 2468894C CA 2468894 A CA2468894 A CA 2468894A CA 2468894 A CA2468894 A CA 2468894A CA 2468894 C CA2468894 C CA 2468894C
Authority
CA
Canada
Prior art keywords
processing
layer
rigid
tape
exoskeleton
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.)
Expired - Lifetime
Application number
CA2468894A
Other languages
French (fr)
Other versions
CA2468894A1 (en
Inventor
Stuart Polwart
Joel Fearnley
Douglas Roy
Peter Ghazal
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.)
Agilent Technologies Inc
Original Assignee
Agilent Technologies 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 Agilent Technologies Inc filed Critical Agilent Technologies Inc
Publication of CA2468894A1 publication Critical patent/CA2468894A1/en
Application granted granted Critical
Publication of CA2468894C publication Critical patent/CA2468894C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00009—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with a sample supporting tape, e.g. with absorbent zones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/505—Containers for the purpose of retaining a material to be analysed, e.g. test tubes flexible containers not provided for above
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B1/00—Devices without movable or flexible elements, e.g. microcapillary devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44704—Details; Accessories
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44756—Apparatus specially adapted therefor
    • G01N27/44791—Microapparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B01J2219/00317—Microwell devices, i.e. having large numbers of wells
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00495—Means for heating or cooling the reaction vessels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00513—Essentially linear supports
    • B01J2219/00518—Essentially linear supports in the shape of tapes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/0074—Biological products
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/021—Identification, e.g. bar codes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/042—Caps; Plugs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0812—Bands; Tapes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0457—Moving fluids with specific forces or mechanical means specific forces passive flow or gravitation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C2791/00—Shaping characteristics in general
    • B29C2791/004—Shaping under special conditions
    • B29C2791/007—Using fluid under pressure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C51/00—Shaping by thermoforming, i.e. shaping sheets or sheet like preforms after heating, e.g. shaping sheets in matched moulds or by deep-drawing; Apparatus therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44756—Apparatus specially adapted therefor
    • G01N27/44773—Multi-stage electrophoresis, e.g. two-dimensional electrophoresis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44756—Apparatus specially adapted therefor
    • G01N27/44782—Apparatus specially adapted therefor of a plurality of samples
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T156/00—Adhesive bonding and miscellaneous chemical manufacture
    • Y10T156/10—Methods of surface bonding and/or assembly therefor
    • Y10T156/1002—Methods of surface bonding and/or assembly therefor with permanent bending or reshaping or surface deformation of self sustaining lamina
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T29/00—Metal working
    • Y10T29/49—Method of mechanical manufacture
    • Y10T29/494—Fluidic or fluid actuated device making

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Electrochemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Computer Hardware Design (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

Non-rigid tape apparatus and fabrication methods for microfluidic processing applications such as gel electrophoresis are provided, where microfluidic processing is performed on selected areas. Parts of the tape are formed by high pressure plastic film forming. Membranes and other structures are self sealing during and after penetration by pipettes and electrical probes. Rigid exoskeleton elements protect the non-rigid parts during processing and facilitate transport of the tape.

Description

1 Apparatus and. Methods for Microfluidic Applications 3 This invention relates to fabrication and processing 4 technology for microfluidic applications in chemical and biological .processing and analysis, in particular 6 fabrication and application of non-rigid apparatuses 7 optionally in the form of a tape.

9 In the field known as ~~lab-on-a-chip", electronic, microfluidic and bio processes are combined at chip scale 11 to bring dramatic productivity and cost benefits to 12 fields as diverse as high throughput screening, bio-13 molecular assays and point of care diagnostics.

Fabrication technologies are known that have been 16 developed in the microelectronics industry and then 17 -applied to biotechnology and biomedical industries.
18 However, compared to electronic based devices, 19 biotechnology devices are much more diverse in order to enable the manipulation of~a large variety of bio 21 materials, fluids and chemicals. Improvements in 22 performance, throughput and cost have been achieved by 23 reducing the size and volume in miniaturised biosystems.
CONFIRMATION COPY

2 These "Lab-on-a-chip" solutions have increased the amount 3 of functionality. per apparatus by miniaturisation. The 4 problem with increased miniaturisation is the complexity of smaller scale processing and the large cost of 6 equipment for microfabrication. Furthermore, 7 conventional lithographic and etching processes adopted 8 from the microelectronics industry require rigid 9 apparatuses.-11 Glass apparatuses for microfluidic applications are 12 known, such as the LabCHIP from Caliper Technologies Corp 13 (Mountain View, CA), US Patent 6,274,089. The glass 14 apparatus is attached to a plastic moulded cartridge which incorporates wells for loading test samples, 16 reagents and. gel.

18 Rigid plastic apparatuses are known, such as the LabCard 19 from Aclara Biosciences Inc (Mountain View, CA), US
Patent 6,103,199. A tooling process involving patterning 21 and electroplating is used to create embossed 22 microchannels on the card surface.

24 "L,ab-on-a-CD" devices such as from Camera and Gyros use centrifugal force of a rotating disk as the microfluidic 26 pumping mechanism, e.g,, Camera Bioscience Corporation 27 (Medford, MA), US Patent 6,063,589.

29 The above are all discrete devices which require further handling steps for continuous operation. They are also 31 inefficient for single test. operation.
32 Silicon apparatuses are known, such as the Nanogen chip, 33 which is a microfluidic microarray device, where the 1 microarray is selectively doped with biological or 2 chemical probes which can be polarised electrically to 3 attract or repel molecules from the sample material under 4 test.

7 For example, US Patent 5,858,195 to Lockheed Martin 8 Energy Research.Corporation (Oak Ridge, TN) describes a 9 microchip laboratory system and method to provide fluid manipulations. The microchip is fabricated using 11 standard photolithographic procedures and etching, 12 incorporating an apparatus and rigid cover plate joined 13 using die bonding. Capillary electrophoresis and 14 electrochromatography are performed in channels formed in the apparatus. Analytes are loaded into a four-way 16 intersection of channels by electrokinetically pumping 17 the analyte through the intersection.

19 These approaches require time consuming additional steps of picking and placing discrete apparatuses which 21 increases the overall processing cycle time in 22 microfluidic applications.

24 "MicroTape''~~ - A 384 Well Ultra High Throughput Screening System" Journal of the Association for Laboratory 26 Automation, May 1999: Volume 4, Number 2, p. 31, Astle, 21 T.W., teaches of a tape device designed for storage of 2B liquid compounds in smaller volumes (typically 10 ul) 29 than the industry standard 96 or 384 well micro-titer plate (MTP). Tape storage is in a pattern identical to a 31 384 well MTP. In effect, MicroTapeT"' is an alternative 32 passive storage medium to the micro-titer plate.

1 The primary features of MicroTapeT" are:
2 1) bulk compounds typically stored in 96 or 384 well 3 micro-titer plates can be transferred into a smaller 4 volume storage medium, i.e. the MicroTape''M, and then stored within the medium for future use at low 6 temperature. When this array of compounds is required for 7 test, only one section of tape (i.e. a 384 well section) B need be retrieved and defrosted, rather than the whole of 9 the bulk compound medium.
2) the MicroTapeT'" incorporates a separate sealing 11 membrane to protect the compound during storage. This 12 membrane is capable of being de-sealed and re-sealed.
13 3) use of MicroTape'''"' for Polymerase Chain Reaction (PCR) 19 processing. The concept takes a reel/roll of MicroTapeT"
and uses alternate immersion in hot and cold water tanks 16 to perform thermal cycling for the PCR process.

18 The limitations of this approach are:

- It's well capacity is 10u1 which much larger scale is 21 than lab-on-a-chip.

22 - It is not patterned microfluidic annels.
ch 23 - It is not analytical, i.e. does not incorporate gels or 24 analytes through which molecular se paration or purification can be accomplished.

26 - It is not electrically active, i.e. incorporating 27 electrical elements or interfacing with electrical 28 elements i.e. it is simply a carrier.

29 - The PCR processing is performed on the whole reel rather than on selectable areas or segments of the .

31 tape.

1 In the contemporary art of gel electrophoresis, including 2 the emerging field of miniaturised systems, a common 3 means of detection is to capture an image of these layers 4 using electro-optical means. A convenient method is to 5 use a 2 dimensional CCD (Charged Coupled Device) detector 6 array (an area array) to capture the appearance of the 7 permeation layer area in a single "snapshot" image.
8 Another convenient method is to use a 1 dimensional CCD
9 array_(a line array) and move it relative to the permeation layer such that the full image is built up 11 from many adjacent line images_ 13 It would be advantageous to provide an apparatus for 19 microfluidic applications that allowed an increased area for microfluidic processing, without requiring an 16 increase in miniaturisation and the associated complexity 17 of processing.

19 Lt would be further advantageous to provide an apparatus for microfluidic applications that facilitated loading 21 and transport of analytes and reagents both during and 22 after apparatus fabrication.

24 It would be further advantageous to provide an apparatus that allowed continuous processing of a moving apparatus.

27 It would be further advantageous to provide an apparatus 28 that allowed a variable area on one apparatus, while 29 using a fixed size of apparatus handling mechanism.

1 It would further be advantageous to integrate information 2 storage and management systems within or on the apparatus 3 for use with simple detection methods.

S It is an object of at least one aspect of the present 6 invention to provide an apparatus for microfluidic 7 applications.

9 It is a further object of at least one aspect of the present invention to allow an increased area for 11 microfluidic processing and novel dynamic processing 12 steps both within and of the apparatus, while using 13 simple fabrication processes and apparatus handling 14 technigues.
16 In this document, a probe is defined as including 17 mechanical probes, electrical probes and pipettes for 18 fluidic manipulation.

In this document, indexing patterns are defined as 21 including patterns for facilitation mechanical movement, 22 detection of position, detection of movement, and display 23 and recording of information.

In this document, mass transport is defined as transport 26 of mass relative to the apparatus.

28 According to a first aspect of the present invention, 29 there is provided an apparatus for microfluidic processing applications, wherein said microfluidic 31 processing is performed on a selected area of a plurality 32 of areas each individually selectable on said apparatus, 33 characterised in that the apparatus is non-rigid.

2 According to a second aspect of the present invention, 3 there is provided an apparatus for mass transport 4 microfluidic processing applications, characterised in that the apparatus is non-rigid.

7 According to a third aspect of the present invention, 8 there is provided an apparatus for microfluidic 9 processing applications, characterised in that the apparatus comprises at least one rigid member and at 11 least one non-rigid member.

13 Preferably the apparatus comprises at least two non-rigid 14 members.
16 Preferably said non-rigid member is a tape..

18 Preferably there are a plurality of rigid members each 19 associated with one of a plurality of areas each individually selectable on said apparatus.

22 Preferably said rigid member comprises access ports.

24 According to a fourth aspect of the present invention, there is provided a method of fabrication of an apparatus 26 for microfluidic processing applications, comprising the 27 step of attaching at least one rigid member to at least 28 one non-rigid member.

Preferably said method of fabrication further comprises 31 the step of forming at least one non-rigid member.

1 Preferably said step of forming said at least one non-2 rigid member comprises the step of high pressure plastic 3 film forming with said high pressure acting on said 4 apparatus.
6 Alternatively said step of high pressure plastic film 7 forming is arranged with the high pressure acting on a 8 compliant membrane, which is part of a forming tool in 9 contact with said apparatus.
11 Preferably said rigid member has a maximum dimension 12 perpendicular to its plane greater than the maximum 13 dimension perpendicular to the plane of said at least one 14 non-rigid membe r.
16 According to a fifth aspect .of the present invention, 17 there is provided a method of mounting an apparatus for 1B microfludic processing applications, comprising the step 19 of attaching said apparatus to a non-rigid carrier that is in the form of a tape.

22 Preferably said carrier has a maximum dimension 23 perpendicular to its plane greater than the maximum 24 dimension perpendicular to the plane of said apparatus.
26 Preferably said apparatus is attached to said non-rigid 27 carrier by snap fitting into apertures in said carrier.

29 Alternatively said apparatus is attached to said non-rigid carrier by ultrasonic welding, heat sealing, 31 adhesive, chemical or molecular bonding.

33 Preferably said apparatus is a tape.

2 Preferably said apparatus comprises a polymer film.

4 Preferably said apparatus comprises processing elements for microfluidic processing.

1 Typically said processing elements comprise indents of 8 said apparatus.

Optionally said processing elements comprise cavities 11 embedded within said apparatus.

13 Optionally said processing elements comprise processing 14 materials in intimate contact with the surface of said apparatus.

17 Optionally said processing elements comprise processing 18 materials embedded within said apparatus.

Optionally said processing elements comprise opaque, 21 translucent or coloured materials for providing optical 22 isolation between elements or providing indexing marks.

24 Preferably an element of said apparatus is transparent.
26 Preferably a member of said apparatus is transparent.

28 Preferably said apparatus is penetrable.

Preferably said apparatus is. self sealing during 31 penetration.

1 More preferably said apparatus is self sealing after 2 penetration.

4 Preferably said apparatus further comprises an 5 impermeable membrane.

7 Preferably said impermeable membrane is affixed in 8 intimate contact with parts of the surface of said 9 apparatus.
11 Alternatively said impermeable membrane is arranged as 12 discrete areas of impermeable membrane in intimate 13 contact with parts of the surface of said apparatus:

Preferably said impermeable membrane is penetrable.

17 Preferably said impermeable membrane is self sealing 18 during penetration.

More preferably said impermeable membrane is self sealing 21 after penetration.

23 Optionally said impermeable membrane is re-sealed by a 24 capping element after penetration.
26 Preferably said impermeable membrane is supported by 27 support structures.

29 Preferably said apparatus further comprises a non-rigid member.

32 Preferably said non-rigid member is affixed in. intimate 33 contact with parts of the surface of said apparatus.

2 Alternatively said non-rigid member is arranged as 3 discrete areas of non-rigid member in intimate contact 4 with parts of the surface of said apparatus.
6 Preferably said non-rigid member is penetrable.

8 Preferably said non-rigid member is self sealing during 9 penetration.
11 More preferably said non-rigid member is self sealing 12 after penetration.

14 Optionally said non-rigid member is re-sealed by a capping element after penetration.

17 Preferably said non-rigid member is supported by support 1B structures.

According to a sixth aspect of the present invention, 21 there is provided a method of fabrication of an apparatus 22 for mass transport microfluidic processing applications 23 comprising the step of forming an apparatus that is non-24 rigid.
26 According to a seventh aspect of the present invention, 27 there is provided a method of fabrication of an apparatus 28 for mass transport microfluidic processing applications 29 comprising the step of fabricating a tape.
31 Preferably said step of forming said apparatus comprises 32 the step of high pressure plastic film forming with said 33' high pressure acting on said apparatus-2 Alternatively said step of high pressure plastic film 3 forming is arranged with the high pressure acting on a 4 compliant membrane, which is part of the forming tool in S contact with said apparatus.

7 Optionally said step of fabricating said apparatus B further comprises the step of preloading processing 9 materials onto said apparatus before fabrication.
11 Optionally said step of fabricating said apparatus 12 further comprises the step of loading processing 13 materials onto said apparatus during, fabrication.

Typically said step of preloading or loading during 16 fabrication of said apparatus comprises the step of 17 depositing processing materials onto a carrier.

19 Typically said step of preloading or loading during fabrication of said apparatus comprises the step of 21 depositing processing material onto a non-rigid member.

23 Preferably said deposited processing material comprises 24 permeation layers.
26 Alternatively said deposited processing material 27 comprises conductive material.

29 Alternatively said deposited processing material comprises chemically or biologically active material.

32 Alternatively said deposited processing material 33 comprises marks for identity purposes.

2 Alternatively said deposited processing material 3 comprises magnetisable material.

Preferably said step of depositing comprises printing.

7 Alternatively said step of preloading or loading during 8 fabrication of said apparatus is performed by a 9 preloading or loading process selected from a list of processes comprising: deposition and etching, injection 11 into a cavity and injection into an indentation.

13 Preferably said method of fabrication of said apparatus 14 further comprises the steps of depositing patterns on an apparatus and forming said apparatus, wherein the 16 localised formation of said processing elements is 17 responsive to the distortion. by said forming of said 18 deposited pattern.

Preferably said method of fabrication of said apparatus 21 further comprises the steps of depositing patterns on an 22 apparatus and localised formation of said apparatus is 23 responsive to the topography of said deposited pattern, 24 resulting in the formation of said processing elements.
26 Preferably said step of depositing comprises pre-27 printing.

29 According to an eighth aspect of the present invention, there is provided a method of fabrication of an apparatus 31 for mass transport microfluidic processing applications, 32 comprising the step of including an impermeable membrane 33 as part of said apparatus.

2 Preferably said step of including an impermeable membrane 3 comprises the step of affixing an impermeable membrane to 4 a substrate.
6 Optionally, said step of including an impermeable 7 membrane comprises the step of depositing, overlaying or 8 affixing discrete areas of impermeable membrane in 9 intimate contact with parts of the surface of said apparatus.

12 Optionally, said step of including an impermeable 13 membrane comprises the step of depositing, overlaying or 14 affixing an impermeable membrane on said apparatus~and selectively removing areas of said impermeable membrane_ 17 Optionally, said selected removal of said impermeable 18 membrane is performed by the step of cropping.

According to a ninth aspect of the present invention, 21 there is provided a method of fabrication of an apparatus 22 for mass transport microfluidic processing applications, 23 comprising the step of including a non-rigid member as 24 part of said apparatus.
26 Preferably said step of including a non-rigid member 27 comprises the step of affixing a non-rigid member to a 28 substrate.

Optionally, said step of including a non-rigid member 31 comprises the step of depositing, overlaying or affixing 32 discrete areas of non-rigid member in intimate contact 33 with parts of the surface of said apparatus.

2 Optionally, said' step of including a non-rigid member 3 comprises the step of depositing, overlaying or affixing 4 a non-rigid member on said apparatus and selectively 5 removing areas of said non-rigid member.

7 Optionally, said selected removal of said non-rigid 8 member is performed by the-step of cropping.
10 According to a tenth aspect of the present invention, 11 there is provided a method of microfluidic processing, 12 comprising the steps of selecting an area of a plurality 13 of areas of an apparatus and performing microfluidic 14 processing at said selected area, characterised in that 15 said apparatus is non-rigid.
17 Optionally said step of performing microfluidic 18 processing comprises contacting at least one conducting 19 element that connects the exterior of said apparatus to the interior of said apparatus.

22 Preferably said method further comprises the step of 23 providing an electrical potential to at least one 24 conducting element.
26 Preferably said method further comprises the step of 27 enabling an electrical current to pass through said least 28 one conducting element.

Preferably said apparatus is a tape.

32 Preferably said microfluidic processing is mass transport 33 microfluidic processing.

2 Preferably said microfluidic processing is responsive to 3 the deformation of said apparatus.

S Preferably said deformation comprises deformation by a 6 step selected from a list of steps comprising: bending, 7 flexing, folding, twisting, conforming to a rigid 8 surface, mechanical deformation,. deformation by applying 9 a sound pressure, deformation by applying a liquid pressure, and deformation by applying a gas pressure.

12 Typically said gas pressure is a negative pressure.

19 Optionally said deformation may further comprise the step of bringing part of said apparatus back into contact with 16 another part of itself.

18 Alternatively, said step of deformation further comprises-19 the step of bringing a part of said apparatus into contact with another apparatus.

22 Optionally said deformation of said apparatus comprises 23 the step of moving part of said apparatus into a position 29 for processing of said part of said apparatus.
26 Typically said position for processing is a position with 27 said apparatus in contact with a processing tool.

29 Preferably said microfluidic processing is responsive to said deformation of said apparatus, said microfluidic 31 processing being selected from a list comprising pumping, 32 filling, pouring, pressurising, mixing, dispensing, 33 aspirating, separating, combining, heating and cooling.

2 According to an eleventh aspect of the present invention, 3 there is provided a method of processing for microfludic 9 processing applications, characterised in that the processing comprises the step of piercing an impermeable 6 ~ membrane .

8 Preferably said step of piercing an impermeable membrane 9 is performed with at least one probe.
11 Optionally said at least one probe comprises at least one 12 pipette.

14 More preferably said method of processing further comprises the step of providing an electrical potential 16 to at least one,conducting probe that has pierced said 17 membrane.

19 Alternatively said step of processing further comprises the step of enabling an electrical current to pass 21 through at least one conducting probe that has pierced 22 said membrane.

29 According to a twelfth aspect of the present invention, there is provided a method of processing for microfludic 26 processing applications, characterised in that the 27 processing comprises the step of piercing an apparatus.

29 Preferably said apparatus is self sealing during said step of piercing.

32 Preferably said apparatus is self sealing after said step 33 of piercing_ 2 Optionally said apparatus is re-sealed by a capping 3 element after penetration.

S Preferably said step of piercing the apparatus is 6 performed with at least one probe.

B Optionally said at least one probe comprises at least one 9 pipette.
-11 More preferably said method of processing further 12 comprises the step of providing an electrical potential 13 to at least one conducting probe that has pierced said 14 apparatus.
16 Alternatively said step of processing further comprises 17 the step of enabling an electrical current to pass 18 through a conducting probe that has pierced said 19 apparatus.
21 According to a thirteenth aspect of the present 22 invention, there is provided an apparatus for 23 microfluidic processing applications, characterised in 29 that the apparatus is a non-rigid tape comprising a plurality of indexing patterns.

27 Preferably said indexing patterns are rigid members.

29 Preferably said indexing patterns are repeated.
31 Preferably said indexing patterns are arranged to 32 facilitate detection of position.

1 Typically said indexing patterns are arranged to 2 facilitate detection of position using optical detection.

4 According~to a fourteenth aspect of the present invention, there is provided a method of transporting a 6 tape apparatus for microfluidic applications comprising 7 the step of moving said apparatus by interaction of a 8 moving object with at least one rigid member attached to 9 said apparatus.
11 In order to provide a better understanding of the present 12 invention, an embodiment will now be described by way of 13 example only and with reference to the accompanying 14 figures in which:
16 Figure 1 illustrates-in schematic form non-rigid 17 apparatuses, showing a section of tape and an enlargement 18 o.f one area suitable for gel electrophoresis in 19 accordance with the present invention;
21 Figure 2 illustrates in schematic form a variety of 22 processing elements in accordance with the invention;

24 Figure 3 illustrates processing elements incorporating impermeable membranes comprising homogeneous apparatus 26 material;

28 Figure 4 illustrates impermeable processing elements 29 incorporating discrete impermeable membranes and processing elements on hinged tabs;

1 Figure 5 illustrates the insertion and removal of a probe 2 into a processing element through an impermeable self-3 sealing membrane;' 5 Figure 6 illustrates a plan view of an apparatus 6 incorporating an extended impermeable membrane with a 7 variety of support structures;

9 Figure 7 illustrates a cross-section of the same 10 structures illustrated in Figure 6; -12 Figure 8 illustrates some of the same structures in 13 cross-section as Figure 7, but where the processing 14- elements comprise processing materials;
16 Figure 9 illustrates in schematic form a plan view of a 17 structure for probing through an impermeable membrane;

19 Figure 10 illustrates an alternative arrangement.to tha t of Figure 9 where the channel extends into the apparatus;

22 Figure 11 illustrates a cross-section of the structure 23 illustrated in Figure 10;

Figure 12 illustrates a tape apparatus with indexing 26 patterns;

28 Figure 13 illustrates in schematic form a variety of 29 cross-sections of indexing patterns;
31 Figure 14 illustrates a flow chart describing the steps 32 of fabrication of an apparatus;

1 Figures 15 and 16 illustrate arrangements of scanning the 2 optical.detectors for scanning the apparatus;

4 Figure 17 illustrates plan and elevation views of a micro-array configuration of the apparatus;

7 Figure 18 illustrates in schematic form non-rigid 8 apparatuses in accordance with the present invention;

Figure 19 illustrates in schematic form the components of 11 a planned fabrication scheme of one embodiment;

13 Figure 20 illustrates in schematic form a compact 14 fabrication option;

16 Figure 21 illustrates in schematic form an operating mode 17 using a vacuum suction onto a scanner or a 18 heating/cooling plate;

Figure 22 illustrates in schematic form reservoir 21 fabrication showing the option of sample loading through 22 penetration of a cover seal;

24 Figure 23 illustrates in schematic form reservoir fabrication showing the option of electrical probe 26 penetration of a cover seal;

28 Figure 24 illustrates in schematic form an alternative 29 electrical probe option;
31 Figure 25 illustrates in schematic form a .supporting 32 layer of one segment of a tape after preparatory 33 printing;

2 Figure 26 illustrates in schematic form a formed pattern 3 layer after forming;

S Figure 27 illustrates in schematic form a formed pattern 6 layer after a blanking operation;

8 Figure 28 illustrates in schematic form a formed pattern 9 layer assembled to the supporting layer;
11 Figure 29 illustrates in schematic form an exoskeleton;

13 Figure 30 illustrates in schematic form an exoskeleton 14 affixed to the supporting/patterned layer;
16 Figure 31 illustrates in schematic form a section 17 (vertical scale exaggerated for clarity) and plan view 18 through one tape segment and disposition of sealing 19 plugs;
21 Figure 32 illustrates in schematic form loading of 22 electrolyte during manufacture;

24 Figure 33 illustrates in schematic form loading of analyte during manufacture; and 27 Figure 34 illustrates in schematic form loading of a test 28 sample at the point of use.

Figure 35 illustrates in a flowchart of automated 31 processing using the fabricated tape.

1 The invention is a non-rigid apparatus for microfluidic 2 processing applications, which may be in the form of a 3 tape. The use of a non-rigid apparatus allows novel 4 dynamic processing methods. The incorporation of re-sealable impermeable layers allows further novel dynamic 6 processing steps.

8 Figure 1a shows a typical section of tape 1 with an array 9 of microfluidic processing areas or processing segments 2 in accordance with a preferred embodiment of the present 11 invention. Adjacent test segments are spaced to suit-the 12 sample supply vessel. For example, where samples are 13 delivered for test in a 384 well microtiter plate format, 14 the tape segments will be supplied on a 4.5mm pitch, P.
The tape is processed in a vertical plane with the sample 16 loading ports uppermost. The tape width, W, is typically 17 25mm but is configurable in a range of lmm to 100mm.

19 Figure 1b shows an~enlargement of a single processing segment 2, the operation of which follows well-21 established principles of electrophoresis. A DNA test 22 sample is assumed.

29 The apparatus includes a supporting layer 251, a formed pattern layer 265 with a machine readable index mark 254.
26 The pattern layer has formed cavities 266 and a 27 connecting channel 267 filled with gel. The exoskeleton 28 2915 supports plugs 3124 that are used for re-sealable 29 access to the cavities.
31 A DC voltage in the range5 to 500 Volts (typically 32 100V/cm has been found be suitable) will be applied to 33 across negative terminal 252 and positive terminal 253.

1 This will cause the negatively charged DNA sample 3430 to 2 migrate into the gel column 267 and its constituent 3 molecules will then separate into bands in accordance 4 with their molecular weight. An image of the band pattern will be captured by a commercial,CCD camera and the image 6 processed and presented to the user on a computer screen.

8 The electrical terminal pads 252 and 253 are conveniently 9 presented for perpendicular access by external contact pins whose engagement will be controlled by the tape 11 processing instrument. The exoskeleton 2915 may be 12 conveniently employed as the tape transport means, and be 13 driven by, for example, a toothed belt or a drive pinion 19, having the same tooth pitch as the test segments on the tape.

17 The CCD image capture system can also conveniently 18 capture the test segment ID mark, thus avoiding the need 19 for a separate-device such as a bar code reader.
21 Figure illustrates a part of apparatus 20 in cross-2a an 22 section. The apparatus contains variety of processing a 23 elements which are an indent 21, void or cavity in the a 24 apparatus 22 processing materials on the surface of the.

apparatus 23, processing materials embedded within the 26 apparatus 24, and processing mater ials in an indent on 27 the surfa ce of the apparatus 25.

29 Figure 2b illustrates part of an apparatus in cross-section with processing materials partially filling the 31 height of a cavity in the apparatus 26 and processing 32 material 27 embedded in a channel 28 within the 33 apparatus.

2 The processing elements may comprise geometries which 3 have sloping, curved or stepped surfaces. The processing Q materials may be coriformal layers in intimate contact 5 with surfaces of the apparatus. The processing elements 6 may be opaque, translucent or coloured in order to 7 provide optical isolation between elements or, 8 alternatively, to provide indexing marks for allowing 9 detection of movement and position of the apparatus.
11 Several of the processing elements shown in Figures 2a 12 and 2b may be linked together, for example by cavities 13 or indented troughs, which are themselves processing 14 elements such that the linked elements act as a single processing group.

17 Figure 2c illustrates a plan view 210 of processing 18 element groups 211 on part of an apparatus 212. Figure 19 2d illustrates a cross section of one of the processing element groups 211 shown in figure 2c. The formed 21 plastic substrate 212 has a plastic membrane film 213 22 attached 214. The membrane is typically 0.lmm thick, but 23 could be as thin as 0.02mm. An indented trough 215 is 24 provided for processing materials such as materials based on Agarose or polyacrylamide gel. A channel 216 is 26 provided for a plug that can be removed by, for example, 27 laser ablation in order to allow processing material 28 transport between the indented trough 215 and another 29 processing element, indent 217. The substrate indents have pips 218 that are shaped to guide a probe such as a 31 pipette to an area of the lower surface for penetration 32 into the processing elements, for example indent 217.

L The substrate may be self-sealing during and after such 2 penetration.

4 The processing materials can be gases, liquids, solids or semi-solids, e.g. biomolecular samples, fragments of 6 DNA, biochemical polymers, chemical polymers, 1 biomolecular modifiers, catalysts, antibodies, 8 polypeptide molecules, protein molecules, biological 9 organisms such as cells and viruses and permeation layers. The permeation layers may be solid, semi-solid, 11 liquid, viscous, gelatinous or gaseous layers. The 12 permeation.layers may be biomolecular gates which are 13 activated by electrical probes. The function of the 19 biomolecular gates is defined by their particular depth, shape, volume and composition.

17 Figure 3 shows a cross-section 30 of an apparatus for 18 microfluidic processing applications_ The apparatus 19 contains a processing element 31 that is a cavity in the apparatus material. At the top of the cavity the 21 apparatus material is thin; such that there is a membrane 22 32 that is impermeable and acts as an hermetic seal to 23 protect the contents of the cavity.

The apparatus contains another processing element 33, 26 where the membrane is configured as a flap 39, such that 27 the cavity is sealed when the unattached end of the 28 membrane is in contact with the apparatus 35.

Figure 3 illustrates another processing element 36 with a 31 membrane arranged as a flap 37 and distortion of the 32 apparatus 38 resulting in the opening of the flap at its 33 unattached end 39.

2 Figure 4a illustrates an apparatus 40 that includes the 3 same type of processing elements as shown in Figure 3, 4 but in this case the impermeable membrane is deposited, overlaid or affixed as discrete areas of impermeable 6 membrane in intimate contact with parts of the surface of 7 the apparatus. In the first processing element 41, the B impermeable membrane 42 provides a hermetic seal to the 9 cavity 43.
11 Another processing element 44 shows the impermeable 12 membrane 45 in intimate contact and attached to the I3 apparatus at the left hand side 46 and configured as a 19 flap in a sealing contact with the right hand side 47 of an indent in the apparatus 48. This flap may be opened 16 by deforming the apparatus in the same way as described 17 as above with reference to processing element 36.

19 In another processing element 49, the impermeable membrane 410 is deposited as a pluq~in an indent 21 resulting in a cavity 411, the membrane again providing 22 an hermetic seal.

24 Alternatively, the impermeable membrane is continuous with the tape (i.e. not discrete). This continuous 26 configuration can also embody local flaps in the membrane 27 and still be one continuous- membrane.

29 Figure 4b illustrates a plan view and Figure 4c illustrates cross-section views of a strip of apparatus 31 413 where a section of the apparatus had been removed 912 32 by punching out. The shape punched out has left several 33 tabs 414 each with an indent 415 for containing 1 processing materials. The tab 414 may be mechanically 2 folded along the fold line 417.. The fold line may be 3 weakened by perforation or indenting. A second indent 4 for processing materials 418 is positioned on the opposite side of the fold line from the indent 415. When 6 the tab is folded over 419, the indent 415 is tipped over 7 into contact with the indent 418, allowing mixing, 8 pouring or transfer of processing materials between the 9 two indents. This pouring may be assisted by the force of gravity, capillary action or external pressure.
11 Alternative arrangements can be made that tilt through an 12 angle of e.g. 30 degrees to cause pouring.

14 Figure 5 shows a cavity during a sequence of steps before penetration 51, during penetration 52 and after 16 penetration 53. The probe 54, which is a pipette, is to 17 be inserted into the cavity 55 through the membrane 56.
18 When the probe 57 is inserted through the membrane 58, 19 the membrane is self-sealing, such that there is a seal between the probe and the membrane 58. Processing 21 materials 510 are then deposited in the cavity. After 22 removal of the probe 511, the impermeable membrane is 23 self-sealing and a seal 512 is formed at the exit point 24 of the probe. The penetration of the impermeable membrane can allow introduction of processing materials 26 into cavities in the apparatus or removal of processing 27 materials from the apparatus, the penetration of the 28 membrane can allow the introduction of measurement tools 29 into the apparatus or processing tools into the apparatus. When penetration is by a conducting probe, 31 voltages can be applied that cause movement of fluids 32 through processing materials using an electrokinetic 33 method .

2 Large areas of membrane would tend to bend on attempted 3 insertion of a probe. Figure 6 shows a plan view of an 4 apparatus 60 with an extended membrane 61 and support structures that provide support for the membrane adjacent 6 to the location where probes are to penetrate the 7 membrane. Figure 7a shows a cross-section 70 of the same B structure that is shown in the plan view of Figure 6.
9 Figure 7b shows a cross-section 71 of the same structure that is shown in the plan view of Figure 6, but with a 11 continuous membrane 72 affixed to a substrate.

13 . Figures 6 and 7 include support structures that are 14 pillars 62, ribs 63 and an annulus 64. The centre of the annulus contains a membrane that may be penetrated by a 16 probe. The annulus allows a "via" hole 65 to be created 17 all the way through the apparatus and through which a 18 wire or conducting probe can be passed so that a magnetic 19 field can be created to interact with the adjacent processing area of the apparatus.

22 Another useful structure is a circular indent but still 23 connected to adjacent processing elements and an 24 externally configured loop or coil of wire (or other conducting element) around that circular indent. The 26 electrical/magnetic field created can be used to attract 27 or trap or process the liquid in the circular indent.

29 A "U" shaped pillar 66 is shown and a probe that enters in the centre of the U" at point 67, marked " with a plus, 31 may be connected to a probe penetrating impermeable the 32 membrane at the second penetration point by an 33 electrical, liquid or permeation path that is greater in 1 length than the direct distance between the two 2 penetration points.

4 Figure 8 shows a cross-section 80 of similar structures 5 to those in Figure 7, except that the cavities in the 6 apparatus are filled with processing materials 81.

8 Figure 9 shows a plan.view of an apparatus 90 with a 9 membrane that extends from a first penetration point 91 10 to a second penetration point 92 via an indented trough 11 93. A probe inserted through the impermeable membrane at 12 the first penetration point 91 may be connected to a 13 probe penetrating the impermeable membrane at the second 14 penetration point 92 by an electrical, liquid or 15 permeation path that is greater in length than the direct 16 distance between the two penetration points.

18 Figure 10 shows a plan view of an apparatus 100 with two 19 membranes,.each of which are penetration points 101 and 20 102. The dotted lines represent the edges of a buried 21 channel 103 in between the two membranes.
23 Figure 11 shows a cross-section through the line 24 connecting the two penetration points of Figure 10 which 25 can be seen to be two membranes 101 and 102. The channel 26 103 extends into the depth of the apparatus 104. In this 2'1 alternative arrangement the electrical, liquid or 28 permeation path between tips of probes that are inserted 29 through the penetration points are also greater than the 30 direct distance between the two probes.

32 Turning Figures 10 and 11 through 90 degrees, illustrates 33 side entry (rather than top entry) to the apparatus.

1 Then Figure 10 becomes a side view of the tape and Figure 2 11 is a plan view of the plane of a strip of tape.

4 With reference to Figure 12, an apparatus 120 is shown in plan view with a plurality of indexing patterns 121. The 6 indexing patterns may be opaque, translucent ox coloured 7 materials. The indexing patterns may be surface 8 patterns, such as indents or process materials or raised 9 patterns of apparatus material, for example the exoskeleton (2915 in Figures lb and 29). Alternatively, 11 the indexing patterns may be embedded within the 12 apparatus or patterns of magnetism in a magnetic film or 13 perforations through the depth of the apparatus. Indexing 14 patterns are arranged to facilitate traction of the apparatus and detection of position using optical, 16 electromagnetic, electrochemical, electrical or other 17 forms of detection. The indexing patterns may also 18 record information related to the apparatus processing 19 elements or the apparatus processing materials on the apparatus or within it processing results, processing 21 status, processing time, processing location or 22 processing identity. An indexing pattern may be a strip 23 of material which functions as a data recording medium, 29 for example magnetic or magneto-optical tape. Such tape may be written to and read by standard methods.
27 With reference to Figure 13 that shows in schematic form 28 a variety of cross-sections of indexing patterns, an 29 indexing pattern is shown as an indent 130, a raised feature 131, an embedded feature 132 or a hole 133 31 punched through the apparatus.

1 With reference to Figure 14a, a flow chart is shown which 2 describes the general process steps for the fabrication 3 of non-rigid apparatuses for microfluidic processing 4 applications, including apparatuses in the form of a tape or apparatuses of homogeneous material which may be 6 assembled to a tape or discrete microfluidic devices 7 which may be assembled to a tape.

9 Firstly, raw material preparation is provided, 141, the primary material will be a flexible substrate, preferably 11 in the form of a continuous tape but other substrates, 12 membranes, films, mouldings, skeletal structures or pre-13 assembled microfluidic devices may be part of the 14 fabrication "kit".
16 Patterns can be pre-printed 142, preferably on a flat 17 plastic non-rigid substrate. These patterns~may be 18 conductive elements, chemically or biologically active 19 zones, magnetisable zones, or printed marks for identity 20_ purposes.

22 The apparatus, 143, is formed using high pressure thermo-23 forming with the high pressure acting on the apparatus or 24 the high pressure acting on a compliant membrane which is part of the forming tool that is in contact with the 26 apparatus. The high pressure may be delivered by a gas 27 or a fluid. During forming, the pre-printed patterns on 28 the tape surface may be distorted in response to the 29 topography of the formed processing elements. The final position of the pre-printed pattern material may be 31 predicted by calibration test runs or simulation in order 32 to design pre-printed patterns that distort to create 33 processing elements that comprise the processing material 1 that has been pre-printed. Alternatively, the forming of 2 an apparatus may be performed by stereolithography or 3 selective laser sintering. While forming the apparatus 4 by stereolithography or selective laser sintering, processing elements may be-included in the apparatus 6 either by direct patterning or in response to the 7 topography of the pre-printed patterns on the carrier.
B
9 The fabrication of the apparatus can further comprise the step of preloading processing materials '144. These 11 processing materials may be preloaded by processes such 12 as printing, film deposition and etching, stereo-13 lithography, injecting into a cavity and also injection 14 into an indentation. Alternatively, the preloading may be achieved by tilting the apparatus with respect to 16 gravity in order to open flaps of impermeable membrane so 17 as to introduce processing materials through the open 18 flaps into underlying structures. Alternatively these 19 flaps may be opened by the distortion of the apparatus, such as conforming it to a rigid roller or corner.

22 A cropping operation 195 can be incorporated (optionally 23 before the preloading step) to insert apertures in a 24 substrate or finish a substrate to a defined external profile.

27 Apparatus assembly can continue, 146, by attachment or 28 assembly of other layers, for example, a sealing layer or 29 sealing layers, or sealing plugs, or additional supporting layers to improve the robustness of the 31 apparatus, or other pre-assembled devices. The attachment 32 methods may include a mechanical snap-fit, a mechanical 33 interference fit, ultrasonic. welding, heat sealing, 1 molecular, chemical or adhesive bonding. Typically the 2 final layer of apparatus that is affixed results in one 3 or more impermeable membranes as part of the apparatus.
4 Alternatively, the membranes may be formed by depositing, overlaying or affixing discrete areas of impermeable 6 membrane in intimate contact with parts of the surface of 7 the apparatus. Alternatively the formation of the 8 impermeable membrane may be performed by depositing a 9 film of impermeable membrane across the apparatus and selectively removing areas of the impermeable membrane.
11 This selective removal may be performed using 12 cropping/blanking or by lithography, such as 13 photolithography, for patterning combined with wet or dry 14 etching. These membranes are optionally formed of homogeneous apparatus material in the case of formation 16 using stereo-lithography or selective laser sintering.

18 The apparatus can incorporate a further loading sequence, 19 147, of chemical or biological agents such as solvents, electrolytes, gels, stainers, dyes, affinity tags or bio-21 sensors. This loading may be achieved by pipette probe 22 through the apparatus membrane or through an access port 23 or access ports in the apparatus.

These steps 191 to 147 have many possible permutations 26 and Figures 14b, 14c and 14d illustrate by way of 27 example, the fabrication sequence of some of the 28 alternative embodiments described within this document.

Figure 14b shows the general fabrication sequence for the 31 three layer construction method described by Figure 19 32 including the fabrication steps 14191, 19192 and 14193 of 1 the substrate 191 sealing layer 192 and carrier layer 193 2 respectively.

4 Figure 14c shows the general fabrication .sequence for the 5 three layer construction method described by Figure 22, 6 including the fabrication steps 14221, 14222 and 19225 of 7 the substrate 221 sealing layer 222 and carrier layer 225 8 respectively.

10 Figure 14d shows the general fabrication sequence for the 11 construction method described by Figure lb including the 12 fabrication steps 14251, 14265, 142915 and 143124 of the 13 substrate 251 process layer 265, exoskeleton 2915 and 14 sealing caps 3124 respectively.
16 In each of Figures 14a to 14d, the material preparation 17 step 191 is a film forming step, except for the 18 exoskeleton and sealing cap material preparation 1411, 19 which is a moulding step.
21 With reference to Figure 15, the moving apparatus 150 22 with indexing patterns that are permeation (for 23 separation) indents 151, can provide the scanning 24 function of a scanning optical detector with fixed optics 152 and a fixed line scan Charged Coupled Device (CCD) 26 detector 153.

28 Additionally, with reference to Figure 16, when this 29 fixed scanning system 161 is configured to suit a chosen width of tape apparatus 162 (e. g. 100mm, shown in plan 31 view, not to scahe) or multiple transverse separation 32 layers, then it can also image capture, without 33 modification, any other tape apparatus which is of lesser 1 width 163 ( a . g . 50mm or 20mm) , thus providing the 2 advantage of a detection system with flexibility in the 3 handling of different widths of substrate.

Additionally,. where the substrate is configured to have 6 more than one discrete permeation layer in a transverse 7 line across the substrate, each of these more than one 8 discrete permeation layers can be imaged simultaneously.
In the emerging field of biological micro-arrays, the 11 processing substrates are typically comprised of a rigid 12 transparent material (e. g. a glass slide) and whereby 13 bio-material is deposited locally on a rectangular grid 14 whose pitch may be in the range of 50um to 2mm. The present invention provides the advantage that it is 16 equally suitable as a substrate for micro-array 17' fabrication but offers the benefit of having low 1B fabrication cost and a capability for continuous 19 processing due to the flexible nature of the apparatus in its form as a_continuous tape.

22 With reference to Figure 17, the apparatus is illustrated 23 schematically 170 in plan and side views configured to 24 locate each element of a micro-array 171 in a shallow well or dimple 172, on a tape 173, thereby allowing a 26 reduced risk of cross contamination between adjacent 27 elements.

29 The apparatus is thus configured to provide an improved degree of containment for any reaction process which is 31 specified to take place on that micro-array element and 32 that this improved degree of containment can allow 1 operations of mixing, stirring or agitation which would 2 not be achievable with planar micro-arrays.

4 The apparatus is configured such that this shallow well has a thin wall section 174 (e.g. O.lmm, compared to a 6 glass slide of typically 1 to 3mm) that enables the 7 efficient coupling of a conductive heating element 175 8 (for example a~peltier device or similar) to the well for 9 the purpose of, for example, hybridisation of a DNA
sample at a temperature in the range of, for example, 60 11 to 80 degrees centigrade.

13 This thin wall section can readily be transparent and 19 that this enables the efficient coupling of an optical system 175 to detect the bio=reaction state of any 16 element on the micro-array.

18 The apparatus can also have different regions 19 functionalised for the attachment of chemical or biological moieties such as affinity tags or biological 21 probes. Within a microfluidic channel, there can be 22 micro-zones incorporating reactive groups for highly 23 specific functions, e.g. an affinity tag such as a 24 streptavidin coated zone.
26 With reference to Figure 18, an apparatus 10 according to 27 the present invention is shown. The apparatus 11 is non-28 rigid and is shown as being bent, by the apparatus being 29 conformed to the surface of a roller 12.
31 The apparatus is non-rigid in that it is pliant, unlike 32 rigid apparatuses known in the prior art that are made of 33 at least one layer of hard plastic or glass or silicon, 1 or where the composite apparatus is rigid. On 2 deformation of the apparatus according to the present 3 invention, the apparatus can return to its original shape 4 (i.e. flat) after deformation. The apparatus may have a bend radius approaching zero.

7 The apparatus is a tape in that it is substantially 8 longer than it is wide in its larger two dimensions.
9 Hence it is a substantially continuous, narrow, flexible strip. The tape_13 may be arranged in a reel-to-reel 11 arrangement between reels or rollers 14 and 15.

13 With extreme deformation, the apparatus may be folded and 14 remain folded. This may be facilitated by using perforations or indentations to weaken the fold line.
16 Thus the apparatus may be folded into a fanfold 17 arrangement 16 for storage, dispensing and processing.

19 The tape can also be separated into short discrete sections 17. The separation may be performed by 21 guillotining or tearing across perforations or 22 indentations in the tape.

24 A continuous strip of tape 18 may be arranged around rollers l9 into a conveyor belt arrangement. A twist in 26 the tape would provide a Moebius strip arrangement.

28 The apparatus may be formed from a polymer film, that is 29 a thermoplastic polymer film, thermosettable polymer film, elastomeric polymer film or hybrid compositions of 31 each of these films.

1 In another embodiment, the tape comprises three primary 2 construction elements as illustrated with reference to 3 Figure 19. The tape incorporates a thin polymer substrate 4 191 that is formed to create indented wells, channels and junctions. which can be configured to create a wide range 6 of micro-fluidic geometries. This substrate may 7 optionally incorporate one or more surface coating layers 8 on the processing side of the substrate and these 9 layers) may fully cover the substrate surface or be confined to local areas of the substrate. The substrate 11 may incorporate liquid or solid chemicals within the well 12 or channel areas of the substrate.

14 The substrate and its chemical contents may be protected by the attachment of a cover seal 192 membrane. The 16 combined substrate and cover seal will be attached to a 17 carrier layer 193 whose function is to protect the 18 substrate from mechanical stress or damage during 19 handling, shipment, storage or end user processing. The tape may be a one time use consumable item.

22 The tape assembly employs construction materials, 23 fabrication techniques and packaging methods that ensure 24 that the tape will function reliably at its final point of use. The tape will therefore be unaffected by:
26 - Automated and manual handling processes prior to 27 shipment packaging (factory);
28 - Automated and manual handling processes at the point of 29 use (end user);
- Shipment transport (protected by secondary packaging);
31 - Transport temperatures of -40C to +70C (up to 24 32 hours) ;
33 - Storage temperatures of OC to +90C (up to 12 months);

1 - Relative humidity in range loo to 900 (transport and 2 storage); and 3 - Atmospheric pressure (air cargo).
~5 The substrate comprises a thin polymer membrane with a 6 thickness of 50um preferred, but 125um for some 7 applications. The thickness may be selected to match 8 available commercial film grades.
1D The substrate has:
11 - Forming radius equal to thickness without stress 12 cracking;
13 - Feature width to depth ratio, typically in range 2:1 to 14 l:l;
15 - Uniform (consistent) draw during forming.

17 Thermal assist during (or prior to) forming is desirable.
18 Forming may be:
19 1) high pressure in range 1 bar to 200 bar 20 2) Vacuum 21 3) high pressure with vacuum assistance 24 All of these may benefit from a pre-heating cycle.
26 Desirable features of the substrate include.
27 - stable after forming (having no shape memory effects );
28 - Flexible, non rigid, non brittle;
29 - Abrasion Resistant;
- Punchable, to create optional holes for mechanical 31 indexing;
32 - Penetratable by probe (e.g. for liquid delivery or for 33 electrical probing);

1 - High optical clarity;
2 - Adaptable via suitable surface modification to minimise 3 static charge or to locally influence 4 hydrophilic/hydrophobic surface characteristics;
- Chemical Resistance to Aqueous solutions 6 - Analyte material loaded in the substrate channels 7 typically'comprised of Agarose or Polyacrylamide,;
8 - Provide bio-compatible surface (e. g. DNA, proteins, 9 cells, bacteria etc);
- Avoid leeching of metals, anti-oxidants and 11 stabilisers;
12 - Capable of receiving a heat sealable cover layer e.g.
13 polyester/polyethylene cover layer; and 14 - Printable with ink, stroke widths down to 0.lmm.
16 Auxiliary coatings, or deposited layers on the substrate 17 include:
18 - Local conductive tracking;
19 - Local hydrophobic coatings (e. g. PTFE);
- Local hydrophilic coatings (eg titanium oxide); and 21 - Bio-compatible coatings (e. g. parylene).

23 The seal 192 may be a single or composite layer but a 24 dual composite construction may be beneficial in that the .
outer layer can be specified to resist the thermal 26 affects of the heat sealing tool whereas the inner layer 27 is able to melt and create a seal without putting the 28 integrity of the membrane at risk. Properties of the seal 29 layer include:
- Seal Thickness: Typically in range l0um to 50um;
31 - Chemical Resistance: As per substrate above;
32 - Optical : As per substrate above;

1 It is preferred that the seal be suitable for penetration 2 by a probe (typically 0.5-1mm diameter) e.g. for liquid 3 delivery or for electrical probing. A self healing or re-4 sealable penetration hole is preferred.
6 Pre-forming of the seal (schematically as in Figures 22 7 and 23) is optional to enhance rigidity of the sealing 8 layer during penetration and to provide the necessary 9 space within the tape for processing materials.
.
11 The carrier layer 193 can comply with EIA-481-B
12 (Electronic Industries Alliance), the standard for 13 "Embossed carrier Taping" for automated component 14 handling in the electronic industries. A preferred material is either black or translucent polystyrene, 16 preferred thickness is in the range 100um to 300um. This 17 layer will be formed prior to assembly of the 18 substrate/cover such that the substrate/cover will be 19 contained within a recessed channel in the carrier tape and thereby avoid contact with any other surfaces during 21 manufacture or distribution (e_g..in a reel), or at point 22 of use.

24 The przmary functions of the carrier layer are a) to provide a mechanically robust carrier for the more 26 fragile substrate/cover layers b) incorporate punched 27 holes which provide a means of transport drive for the 28 tape c) incorporate registration features which align the 29 substrate/cover layer with the punched drive holes d) incorporate apertures which allow the channels in the 31 substrate to be visible from underneath the tape.

1 With reference to Figure 20, which is a section across 2 the width of the tape, not to scale, a 50um thick 3 microfluidic substrate 201 formed up to 250um deep, is 4 contained within the 300um thickness of the carrier 202 thus affording it protection. The substrate has analyte 6 203 and is capped with the seal 204.

8 . With reference to Figure 21, a negative pressure (vacuum) 9 is applied to the two ports 210 that distorts the substrate onto a tool 211 such as a viewing window of a 11 scanner or a heating/cooling plate.

13 With reference to Figure 22, a sample loading probe 221 14 is positioned ready to penetrate a reservoir in the pre-formed cover seal 222 (that is dimpled for ease of 16 insertion). The substrate contains analyte 223 and the 17 reservoir contains electrolyte 224.

19 With reference to Figure 23, electrokinesis 231 probes are shown penetrating the reservoirs.

22 With reference to Figure 24, probes 241 external to the 23 "wet chemistry" zone are shown connecting to conductive 24 layers on the substrate that are an anode 242 and a cathode 243.

27 For the preferred embodiment, a single segment of tape 28 will be described below, comprising the means of 29 processing one discrete test sample of bio-material such as DNA.

32 Figure 25 shows a supporting layer 251 comprises a thin 33 flat optically clear film of either polycarbonate, 1 polyester, polystyrene, poly methyl methacrylate, or 2 other co-polymers of these materials. This film will 3 typically be 125um thick but other thicknesses in the 4 range 25um to 1000um may be used. This Layer has.a pattern of conductive tracks 252 and 253 applied by 6 screen printing or laser printing or ink jet printing as 7 well as a pattern 254 which can be machine read to 8 indicate the identity of that segment.

Figure 26 shows a formed patterned layer 265 comprising a 11 thin film of either polycarbonate, polyester, 12 polystyrene, polyethylene, polymethyl methacrylate, 13 polypropylene or other co-polymers of these materials.
14 This film will be typically 50um thick but other thicknesses in the range l0um to 200um may be used. This 16 material need not be optically transparent and some 17 advantage may be gained by having it translucent or 1B opaque; translucency offers a means of back-lighting 19 scatter (opposite side from the optical supporting layer) which may be used for illuminating and capturing an image 21 of the tape processes; opaqueness offers the possibility 22 of using a reflected front-lighting source.

24 High pressure thermoforming is preferably used to create formed cavities 266, connecting cf5annels 267, optional 26 side channels 268, primary access ports 269 and secondary 27. optional access ports 2610 . Shallow channels 2611 28 provide entry slots for the conductive tracks 252, 253.
29 Typical relative depths of these formed features is illustrated in typical section Figure 31.

32 Figure 27 shows a further preparative step in 33 manufacturing the formed patterned layer whereby a 1 knifing or blanking process is used to cut apertures or 2 slots in the film. Apertures 2712 provide the access 3 entry slots for the conductive tracks 252, 253. Aperture 4 2713 ensures that the code mark 254 is not obscured by 5 any translucency or opaqueness-in the film 265.

7 Figure 28 shows layer 251 and layer 265 assembled 8 together. This will be effected by either a heat sealing 9 or an adhesive process or both, to ensure that the two 10 layers achieve a tight seal around the profile of the 11 various patterned recesses 266, 267, 2611 etc. in Layer 12 265. Heat sealing can be achieved by the contact surface 13 material of Layer 265 comprising a thin layer of low-14 melting point polymer such as poly-ethylene;
15 alternatively adhesive bonding can comprise the use of 16 commercial cyano-acrylate or, in the case of sealing 17 zones .2814, a commercial silicone rubber compound may be 18 used.

20 Figure 29 shows an exoskeleton component 2915 whose 21 purpose is to protect layer 265 as well as providing 22 rigid access ports 2916, 2917 for loading and unloading 23 the tape. Apertures 2918 protect the cavities 266 and an 29 aperture 2919 protects the channe7_ 267.
26 The exoskeleton material is preferably a rigid polymer 27 such as polycarbonate, ABS, polyester, polystyrene, 28 polyethylene,. polymethyl methacrylate, polypropylene or 29 other co-polymers of these materials. This exoskeleton will be typically l.Omm thick but other thicknesses in 31 the range 0.5mm to 3mm may be used.

1 Figure 30 shows the rigid exoskeleton 2915 affixed to the 2 layer 251 plus layer 265 assembly. This may be by 3 adhesive bonding or bjr incorporating protrusions in the 4 exoskeleton 2915. which will snap fit into corresponding apertures in the supporting layer 251. Where the Layer 6 265 adjoins an access port on the exoskeleton 2915, for 7 example, at cavity locations 3021, an adhesive layer, 8 preferably a commercial silicone rubber compound, will 9 ensure intimate local contact between Layer 265 and exoskeleton 2915.

12 Figure 31 shows a section 3100 through the assembly 3101 13 along the line "D" to "D". Depths are exaggerated in this 14 figure for clarity, but a typical overall height of the exoskeleton is lmm. This cross section shows that 16 cavities 266 are raised to the height of the exoskeleton, 17 cavities 269 are raised to a lesser extent (typically 18 0.5 mm) and the channel 267 has a low profile (typically 19 50 to 200um deep). A conductive strip 253 (typically 20 to 50um thick) is shown entering a cavity 256. Sealing 21 plugs 3124 are shown at the access port locations. These 22 sealing plugs will comprise compliant polymer, preferably 23 an elastomer such as polyurethane or silicone rubber.
24 These plugs will incorporate a feature allowing removal and replacement by a simple hand tool or, for continuous 26 unattended operation, allow automated removal and 27 replacement. Note also feature 3123 which is a tapered 28 section of cavity forming a smooth transition between the 29 cavity 266 and the channel 267.
31Figure 32 shows method of loading liquid electrolyte a 32(for example 2mM Tris, 2mM Acetate,0.5mM EDTA) by 33accessing a probe 3225 into an end cavity.Locations 3226 1 may be vented and sealed (plugs 3124) as part of the 2 filling process. Note that the micro-scale of the 3 penetration points will allow surface tension to prevent 9 unwarranted leakage while the sealing caps are applied.
6 Figure 33 shows a method of pre-loading a column of gel 7 3328.at the point of manufacture using a loading probe B 3327. The gel is loaded as a pre-determined dispensed 9 volume from the elution cavity end of the test segment.
The gel is preloaded with a fluorescing marker dye:

12 The test segment has now been pre-loaded ready for use, 13 and will be shipped in this condition to the point of 19 use. The only "wet chemistry" at the point of use is to load the test sample for analysis.

17 Figure 34 shows a loading probe 3429 penetrating through 18 the top loading port of the exoskeleton at the point of 19 use. The corresponding cap 3124-may be discarded or replaced depending on whether the tape is required to be.
21 archived after use. The test sample 3930 will be prepared 22 in a solution which is denser than the surrounding 23 electrolyte. in the tape cavity, for example, a solution 29 of sucrose will ensure that the test sample will flow under gravity into the tapered channel and gather right 26 at the top of the gel column.

28 The exoskeleton incorporates access ports which can be 29 oriented longitudinally (e.g. port no.3431) or perpendicularly (e. g. port no. 3932). Optionally port 31 3432 can be used to vent any unwanted build up of gas in 32 the lower cavity. .

1 These fabrication methods can create features which 2 provide a wide range of processing options at the point 3 of use.

With reference to Figure 35, the automated processing has 6 the steps of transporting the tape and selecting an area 7 for processing 3:51, piercing the apparatus with a probe B or probing the apparatus 352, and performing microfluidic 9 processing 353 at the selected area, then repeating 354 the.above steps until processing of the reel of,tape is 11 complete.

13 During these steps the fabricated apparatus with its 14 optional preloaded processing materials may be deformed in order to cause dynamic processing. The apparatus may 16 be deformed by bending, flexing, folding, twisting, 17 conforming to a rigid surface, mechanical deformation, 18 deformation by applying a sound pressure, deformation by 19 applying a liquid.pressure, and deformation by applying a gas pressure. Optionally the deformation can result in 21 the bringing of a part of the apparatus back into contact 22 with another part of itself or with another apparatus.
23 The deformation may move part of the apparatus into a 24 position for processing, including being in contact with a processing tool. The deformation of the apparatus 26 results in dynamic processing that includes pumping, 27 filling, pouring, pressurising, mixing, dispensing, 28 aspirating, separating, combining, heating and cooling.

Apparatuses that include impermeable membranes facilitate 31 further novel processing methods that involve the 32 impermeable membrane. The membrane may be pierced by one 33 or more probes. These probes may be pipettes.

1 Conducting probes that have pierced the membrane may 2 provide an electrical potential, and used for passing an 3 electric current through the conducting probe into a 4 conducting medium.
6 Optionally a grid of probes are mounted on a discrete 7 carrier or a continuous carrier that can be indexed or 8 replaced, such that another set of probes can be used 9 after the first set has worn out.
11 The grid of probes may be configured such that each probe 12 is separately addressable and each probe may have a 13 separate voltage applied in order to progressively move 14 the processing material through processing elements, such as indented troughs and permeation layers in the 16 apparatus; after the grid of probes has penetrated or 17 contacted a corresponding grid of impermeable membranes.
18 This arrangement can be used to move process materials 19 through permeation layers for molecular separation. The controlled and progressive switching of voltages on the 21 grid of probes can be used to split processing material 22 into more than one separate processing path through more 23 than one separate processing elements. These split 29 process materials may be further combined or different process materials may be combined at the junctions of 26 paths through the apparatus. In this way, the grid of 27 electrical probes can be configured to apply voltages 28 that cause a multi-dimensional separation of molecules, 29 e.g. polypeptide or protein molecules.
31 If the probes are pipettes, processing materials may be 32 introduced into the apparatus through the impermeable 33 membranes that have been penetrated or processing 1 materials removed from within the apparatus. An array of 2 pipettes compatible with 96, 192, 384, 1536 or 3456 well 3 assay plates can be matched to an array of commensurately 4 spaced impermeable membranes for penetration by the array 5 of pipettes. Probes that penetrate or touch the surface 6 of a membrane can cause processing to be performed, such 7 as pumping, filling, pouring, pressurising, mixing, 8 dispensing, aspirating, separating, combining, heating, 9 cooling, movement by electrokinesis, movement by, 10 electrokinesis, movement by the molecular entrapment 11 method of molecular tweezers, acoustic tweezers and bio-12 molecular motor principles.

14 An apparatus in the form of a.tape may be transported 15 through processing equipment and handling equipment by 16 friction of, for example, rollers in contact with the 17 apparatus or by pinions inserted into indents or 18 perforations in the apparatus in a similar manner to the 19 handling of photographic or cine film. Alternative 20 methods of moving the tape include sliding drawers and 21 walking beams. Moving the apparatus with electromagnetic 22 fields and induction within the apparatus or moving using 23 air or fluid pressure applied to the apparatus are also 24 possible.
26 The position of the apparatus in response to movement is 27 detected by measurement of indexing patterns. After 28 movement dynamic processing can be performed and then 29 further repeated movement and dynamic processing steps can be performed in a continuous fashion as the 31 continuous tape is indexed through the processing 32 equipment.

1 In conclusion, we present the advantages of the present 2 invention.

4 A significant and long-established traditional art for some of the kinds of bio-molecular separation described 6 herein is commonly referred to as "slab gel 7_ electrophoresis". The demands in material usage, process 8 time, operator time and workspace for this process are 9 recognised by those with even minor experience of this art. The procedure commonly employs manual preparation of 11 gels involving mixing, heating and casting steps.
12 Although the method can now employ pre-cast gels to 13 provide some degree of improvement, the overall process 19 remains manually intensive and inefficient.
16 In contrast, the present invention offers significant 17 advantages, by miniaturising all the elements of this 18 traditional process and eliminating many of the material 19 preparation and manual processing tasks.
21 While the traditional processes remain in common use, new 22 art is emerging which includes miniaturised bio-analysis 23 systems employing chip-scale technology, micro-fluidics, 24 and semiconductor fabrication techniques.
26 The present invention provides advantages over both 27 traditional and emerging techniques.

29 The present invention provides very significant savings in materials, time and workspace over traditional gel 31 electrophoresis methods.

1 The present invention provides an adaptable platform for 2 a very wide range of bio-analysis processes (not just gel 3 electrophoresis). and employs geometric patterning, 9 tooling methods and fabrication methods which are much less complex than other emerging micro-fluidic or chip 6 scale techniques. This allows rapid and cost effective 1 production of multiple versions of tape to match the 8 range of applications anticipated.

The present invention allows bio-sample processing in a 11 range from one single simple test up to highly parallel 12 and multiple complex tests in an uninterrupted continuous 13 serial or parallel mode_ The former is attractive to 19 small research laboratories, many quality control laboratories, and point of care clinics. The latter is 16 attractive to high throughput processing laboratories. A
1'1 combination of these processing methods is attractive to 18 public health hospitals and clinics whose demand can 19~ fluctuate significantly. This range of capability is provided in one single effective and efficient platform 21 regardless of usage patterns.

23 The present invention configures processing elements on a 29 highly flexible substrate and enables a versatile range of substrate indexing patterns and transport methods to 26 be utilised as described.

28 Additionally, these transport methods provide the 29 advantage of allowing the use of non complex, compact, low cost optical scanning means by the embodiment of a 31 fixed position transverse optical line-scanning system 32 whose focal plane is along a line across the width of the 1 substrate. The scanning function is provided by the 2 (already provided) indexing motion of the substrate.

9 This highly flexible substrate also enables the other described features and advantages which result from 6 bending, folding, twisting, flexing and deforming its 7 geometry.

9 The substrate flexibility also allows it to be penetrable by probes for the purposes~of processing material 11 delivery or removal,~electrical connection, and process 12 tooling introduction.
~3 Z4 Additionally this flexible substrate is suitable for 7.5 affixing a secondary impermeable membrane which is also 16 readily penetrable by suitable probes for the purposes of 17 processing material delivery or removal, electrical 18 connection, process tooling introduction.

The penetrable substrate and penetrable membrane provides 21 a processing system which can be fully enclosed and which 22 can provide some processing materials pre-loaded within 23 the system. This minimises preparation, avoids spillage, 29 avoids the need for cleaning or flushing procedures and simplifies waste disposal.

27 Alternatively, a stereo-lithographic method is described 28 to fabricate the substrate and the impermeable membrane 29 in one homogenous material with the advantage that this simplifies the means of construction.

32 Alternatively, a selective laser sintering method is 33 described to fabricate the substrate and the impermeable 1 membrane in a single fabrication process again with the 2 advantage that this simplifies the means of construction.

9 The present invention employs one generic material type in its construction (polymer) and avoids the significant 6 use of glass, silicon or metal in its fabrication. This 7 simplifies the waste disposal methods after bio-8 processing is complete.

The fabrication techniques described provide a wide range 11 of substrate geometries. These features can be created 12 by rapid and simple methods of tooling, thus avoiding the 13 long lead times and complexity of other miniaturised bio-19 processing systems.
16 The present invention has the advantage that these rapid 17 and simple fabrication techniques correspond to 18 processing elements whose dimensional accuracy is less 19 critical than those of chip scale devices. A
corresponding advantage is that this is achieved without 21 sacrifice to the overall device size because the device 22 size, in the current state of the art, is determined by 23 the practicalities of the size of the sample loading 29 wells and not by the processing element sizes.
26 The present invention can be enhanced by pre-printing 27 processing materials onto a planar plastic film substrate 28 using commercially available printing methods and then by 29 deforming that substrate in a non planar fashion such that the pre-printed material deforms into a desired 31 shape or position and such that, for example, a pre-32 printed permeation layer can subsequently (after forming 33 of the substrate) be hydrated into its gelatinous phase.

1 Related printing and forming methods are already 2 established in the field of foil manufacture for "in-3 mould decoration" of plastic injection moulded products .
9 (used for cosmetic effect mainly on consumer electronic 5 products), but the present invention provides the scope 6 for adapting these methods into this unconnected field of 7 application.

9 The flexible substrate is readily available in a range of 10 polymer materials whose optical properties can be matched 11 to available commercial optical systems for detection or 12 imaging of the bio-processing events during system 13 operation.

15 Further modifications and improvements may be added 16 without departing from the scope of the invention herein 17 described.

Claims (30)

Claims
1. An apparatus for microfluidic processing applications comprising an array of microfluidic processing areas disposed on a supporting layer of a non-rigid tape, each processing area comprising:
electrical terminal pads on the supporting layer; and a formed pattern layer on the supporting layer;
the formed pattern layer comprising formed cavities and a channel parallel to the plane of the tape adapted to be filled with gel and connecting the cavities channels adapted to be filled with gel;
wherein each processing area of the array additionally comprises rigid exoskeleton affixed to the assembly of the support layer and the formed pattern layer.
2. The apparatus as claimed in claim 1, wherein the supporting layer comprises a machine readable index mark.
3. The apparatus as claimed in claim 1 or 2, wherein the supporting layer comprises a thin flat optically clear film of either polycarbonate, polyester, polystyrene, polymethyl methacrylate, or other co-polymers of these materials.
4. The apparatus as claimed in claim 3, wherein the thin flat optically clear film is from 25 µm to 1000 µm thick.
5. The apparatus as claimed in claim 3, wherein the thin flat optically clear film is 125 µm thick.
6. The apparatus as claimed in any one of claims 1 to 5, wherein the electrical terminal pads have been applied to the supporting layer by screen printing, laser printing or ink jet printing.
7. The apparatus as claimed in any one of claims 1 to 6, wherein the formed patterned layer comprises primary access ports.
8. The apparatus as claimed in any one of claims 1 to 7, wherein the formed patterned layer comprises a thin film of either polycarbonate, polyester, polystyrene, polyethylene, polymethyl methacrylate, polypropylene or other co-polymers of these materials.
9. The apparatus as claimed in claim 8, wherein the thin film is from 10 µm to 200 µm thick.
10. The apparatus as claimed in claim 8, wherein the thin film is 50 µm thick.
11. The apparatus as claimed in any one of claims 1 to 10, wherein the formed patterned layer is translucent or opaque.
12. The apparatus as claimed in any one of claims 1 to 11, wherein the formed patterned layer comprises side channels.
13. The apparatus as claimed in any one of claims 1 to 12, wherein the formed patterned layer comprises secondary access ports.
14. The apparatus as claimed in any one of claims 1 to 13, wherein the formed patterned layer is made by high pressure thermoforming.
15. The apparatus as claimed in any one of claims 1 to 14, wherein the supporting layer and the formed pattern layer are assembled together by either heat sealing or an adhesive process or both.
16. The apparatus as claimed in claim 15, wherein, in the case of heat sealing, the surface of the formed pattern layer that contacts the supporting layer comprises a thin layer of a low-melting point polymer.
17. The apparatus as claimed in claim 16, wherein the low-melting point polymer is poly-ethylene.
18. The apparatus as claimed in claim 15, wherein the adhesive process uses commercial cyano-acrylate adhesives or a commercial silicone rubber compound.
19. The apparatus as claimed in any one of claims 1 to 18, wherein the exoskeleton comprises rigid access ports for loading and unloading the apparatus.
20. The apparatus as claimed in any one of claims 1 to 19, wherein the exoskeleton supports plugs for re-sealable access to the formed cavities.
21. The apparatus as claimed in claim 20, wherein the plugs comprise a compliant polymer.
22. The apparatus as claimed in claim 21, wherein the compliant polymer is an elastomer.
23. The apparatus as claimed in claim 22, wherein the elastomer is polyurethane or silicone rubber.
24. The apparatus as claimed in any one of claims 1 to 23, wherein the exoskeleton is made from a rigid polymer.
25. The apparatus as claimed in claim 24, wherein the rigid polymer is chosen from polycarbonate, ABS, polyester, polystyrene, polyethylene, polymethyl methacrylate, polypropylene and other co-polymers of these materials.
26. The apparatus as claimed in any one of claims 1 to 25, wherein the exoskeleton is from 0.5 mm to 3 mm thick.
27. The apparatus as claimed in any one of claims 1 to 25, wherein the exoskeleton is 1.0 mm thick.
28. The apparatus as claimed in any one of claims 1 to 27, wherein the exoskeleton comprises apertures to protect the cavities and an aperture to protect the channel.
29. The apparatus as claimed in claim 19, wherein the rigid access ports are penetrable by a sample loading probe.
30. The apparatus as claimed in any one of claims 1 to 29, wherein the exoskeleton is affixed to the supporting layer and the formed pattern layer by adhesive bonding or by incorporating protrusions in the exoskeleton which will snap fit into corresponding apertures in the supporting layer.
CA2468894A 2001-11-27 2002-11-27 Apparatus and methods for microfluidic applications Expired - Lifetime CA2468894C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0128350.6 2001-11-27
GBGB0128350.6A GB0128350D0 (en) 2001-11-27 2001-11-27 Non-rigid apparatus for microfluidic applications
PCT/GB2002/005339 WO2003046542A2 (en) 2001-11-27 2002-11-27 Apparatus and methods for microfluidic applications

Publications (2)

Publication Number Publication Date
CA2468894A1 CA2468894A1 (en) 2003-06-05
CA2468894C true CA2468894C (en) 2014-07-15

Family

ID=9926505

Family Applications (2)

Application Number Title Priority Date Filing Date
CA2468334A Expired - Lifetime CA2468334C (en) 2001-11-27 2002-11-27 Apparatus and methods for microfluidic applications
CA2468894A Expired - Lifetime CA2468894C (en) 2001-11-27 2002-11-27 Apparatus and methods for microfluidic applications

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CA2468334A Expired - Lifetime CA2468334C (en) 2001-11-27 2002-11-27 Apparatus and methods for microfluidic applications

Country Status (5)

Country Link
US (4) US20050079104A1 (en)
EP (2) EP1450955A2 (en)
CA (2) CA2468334C (en)
GB (3) GB0128350D0 (en)
WO (2) WO2003046542A2 (en)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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
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
GB0128350D0 (en) * 2001-11-27 2002-01-16 Lab901 Ltd Non-rigid apparatus for microfluidic applications
US8784335B2 (en) 2002-04-19 2014-07-22 Sanofi-Aventis Deutschland Gmbh Body fluid sampling device with a capacitive sensor
US7648468B2 (en) 2002-04-19 2010-01-19 Pelikon Technologies, Inc. Method and apparatus for penetrating tissue
US9314194B2 (en) 2002-04-19 2016-04-19 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8579831B2 (en) 2002-04-19 2013-11-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7547287B2 (en) 2002-04-19 2009-06-16 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7717863B2 (en) 2002-04-19 2010-05-18 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7708701B2 (en) 2002-04-19 2010-05-04 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device
US9795334B2 (en) 2002-04-19 2017-10-24 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
JP2006508790A (en) * 2002-12-04 2006-03-16 スピンクス インコーポレイテッド Apparatus and method for programmable microanalytical scale manipulation of fluids
US8574895B2 (en) 2002-12-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
WO2006001797A1 (en) 2004-06-14 2006-01-05 Pelikan Technologies, Inc. Low pain penetrating
EP1671096A4 (en) 2003-09-29 2009-09-16 Pelikan Technologies Inc 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
EP1706026B1 (en) 2003-12-31 2017-03-01 Sanofi-Aventis Deutschland GmbH Method and apparatus for improving fluidic flow and sample capture
US8828203B2 (en) 2004-05-20 2014-09-09 Sanofi-Aventis Deutschland Gmbh Printable hydrogels for biosensors
WO2005120365A1 (en) 2004-06-03 2005-12-22 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
US7402616B2 (en) 2004-09-30 2008-07-22 Lifescan, Inc. Fusible conductive ink for use in manufacturing microfluidic analytical systems
DE102004050062A1 (en) 2004-10-13 2006-04-27 Boehringer Ingelheim Microparts Gmbh Apparatus, meter and method for receiving and assaying or manipulating sample fluids in a microfluidic platform
GB0502556D0 (en) 2005-02-08 2005-03-16 Lab901 Ltd Analysis instrument
EP1707267A1 (en) * 2005-03-30 2006-10-04 F. Hoffman-la Roche AG Device having a self sealing fluid port
KR100738085B1 (en) * 2005-12-21 2007-07-12 삼성전자주식회사 A microfluidic device for electrochemically regulating the pH of a fluid therein and method for regulating the pH of a fluid in a microfuidic device using the same
US20080138248A1 (en) * 2006-12-11 2008-06-12 Institut Curie Method for improving the bonding properties of microstructured substrates, and devices prepared with this method
GB2445738A (en) * 2007-01-16 2008-07-23 Lab901 Ltd Microfluidic device
GB2445739A (en) * 2007-01-16 2008-07-23 Lab901 Ltd Polymeric laminates containing heat seals
KR20080080841A (en) * 2007-03-02 2008-09-05 주식회사 아이센스 Electrochemical biosensor
AU2012201370B2 (en) * 2007-03-02 2013-10-03 I-Sens, Inc. Electrochemical Biosensor Measuring System
KR100896234B1 (en) * 2007-08-10 2009-05-08 주식회사 아이센스 Electrochemical biosensor and measuring instrument thereof
WO2009023448A1 (en) 2007-08-13 2009-02-19 Polyone Corporation Electrically conductive polyolefin blends
GB0718012D0 (en) * 2007-09-14 2007-10-24 Lab901 Ltd Method for protein staining prior to electrophoresis
US7614202B2 (en) * 2007-11-27 2009-11-10 Atlas Vac Machine Co., Llc Sealer and interchangeable tooling therefor
KR101362905B1 (en) * 2007-11-30 2014-02-19 (주)바이오니아 The micro-chamber plate, manufacturing method thereof
WO2009126900A1 (en) 2008-04-11 2009-10-15 Pelikan Technologies, Inc. Method and apparatus for analyte detecting device
ES2352581T3 (en) * 2008-06-02 2011-02-21 Boehringer Ingelheim Microparts Gmbh STRUCTURE OF MICROFLUIDIC SHEET FOR DOSAGE OF LIQUIDS.
CN104043490A (en) * 2008-07-25 2014-09-17 弗卢丁公司 Method and system for manufacturing integrated fluidic chips
US8361299B2 (en) * 2008-10-08 2013-01-29 Sage Science, Inc. Multichannel preparative electrophoresis system
EP2208995A1 (en) * 2009-01-15 2010-07-21 Roche Diagnostics GmbH Folded carrier belt with consumption elements
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
WO2010108310A1 (en) * 2009-03-23 2010-09-30 红电医学科技股份有限公司 Fluid test chip and method to make it
JP5218443B2 (en) 2010-02-10 2013-06-26 ソニー株式会社 Microchip and manufacturing method of microchip
US8965476B2 (en) 2010-04-16 2015-02-24 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8709353B2 (en) * 2011-03-24 2014-04-29 Boehringer Ingelheim Microparts Gmbh Device and method for producing a fluidic connection between cavities
US9162226B2 (en) * 2011-05-12 2015-10-20 The United States Of America, As Represented By The Secretary Of Commerce Foldable microfluidic devices using double-sided tape
US8850895B2 (en) * 2011-09-03 2014-10-07 John Yan Unpowered, wireless pressure sensor for point-of-care glaucoma diagnosis
CA2887341C (en) 2012-10-12 2021-03-16 Sage Science, Inc. Side-eluting molecular fractionator
WO2015017591A1 (en) * 2013-07-30 2015-02-05 Express Diagnostics Int'l., Inc. Lateral flow devices and methods of manufacture and use
TWI526392B (en) 2014-01-21 2016-03-21 國立清華大學 Method for forming microfluidic structure
GB201416422D0 (en) * 2014-09-17 2014-10-29 Illumina Cambridge Ltd Flexible tape-based chemistry apparatus
WO2016061416A1 (en) 2014-10-15 2016-04-21 Sage Science, Inc. Apparatuses, methods and systems for automated processing of nucleic acids and electrophoretic sample preparation
US10214772B2 (en) 2015-06-22 2019-02-26 Fluxergy, Llc Test card for assay and method of manufacturing same
WO2016209735A1 (en) 2015-06-22 2016-12-29 Fluxergy, Llc Camera imaging system for a fluid sample assay and method of using same
US11371091B2 (en) 2015-06-22 2022-06-28 Fluxergy, Inc. Device for analyzing a fluid sample and use of test card with same
EP3414255B1 (en) 2015-11-20 2021-09-22 Washington University Preparative electrophoretic method for targeted purification of genomic dna fragments
WO2017100765A1 (en) 2015-12-11 2017-06-15 Trustees Of Boston University Detection device having capture region and detection region
JP2020515250A (en) 2017-04-07 2020-05-28 セージ サイエンス， インコーポレイテッド System and method for detecting genetic structural variation using integrated electrophoretic DNA purification
EP3676003A1 (en) * 2017-08-30 2020-07-08 The Charles Stark Draper Laboratory Inc. Systems and methods for fabricating microfluidic devices

Family Cites Families (59)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3689224A (en) * 1966-04-13 1972-09-05 Westinghouse Electric Corp Chemical contaminant detection sampler
US4049147A (en) 1974-01-14 1977-09-20 National Distillers And Chemical Corporation Plastic skin envelopes for glass bottles and the like
US4065263A (en) 1976-04-02 1977-12-27 Woodbridge Iii Richard G Analytical test strip apparatus
US4247591A (en) 1978-03-27 1981-01-27 Signode Corporation Fusible composite binding strap
US4472471A (en) 1982-01-27 1984-09-18 United Technical Products Inc. Chair mat
US4673657A (en) * 1983-08-26 1987-06-16 The Regents Of The University Of California Multiple assay card and system
DE58909087D1 (en) * 1988-12-01 1995-04-13 Bayer Ag Process for the production of deep-drawn molded plastic parts.
US5217563A (en) * 1988-12-01 1993-06-08 Bayer Aktiengesellschaft Apparatus for producing a deep-drawn formed plastic piece
US5284570A (en) 1991-06-26 1994-02-08 Ppg Industries, Inc. Fluid sample analyte collector and calibration assembly
US5288463A (en) 1992-10-23 1994-02-22 Eastman Kodak Company Positive flow control in an unvented container
US5342581A (en) * 1993-04-19 1994-08-30 Sanadi Ashok R Apparatus for preventing cross-contamination of multi-well test plates
WO1994026414A1 (en) 1993-05-17 1994-11-24 Syntex (U.S.A.) Inc. Reaction container for specific binding assays and method for its use
US6001229A (en) 1994-08-01 1999-12-14 Lockheed Martin Energy Systems, Inc. Apparatus and method for performing microfluidic manipulations for chemical analysis
US5500071A (en) 1994-10-19 1996-03-19 Hewlett-Packard Company Miniaturized planar columns in novel support media for liquid phase analysis
US5658413A (en) 1994-10-19 1997-08-19 Hewlett-Packard Company Miniaturized planar columns in novel support media for liquid phase analysis
DE4443458A1 (en) 1994-12-07 1996-06-13 Wolff Walsrode Ag Multilayer, stretched, heat-sealable polypropylene film
US5658647A (en) 1995-06-07 1997-08-19 Avery Dennison Corporation Garment labeling system, equipment and method and elastomeric label for use therewith
US20010055812A1 (en) * 1995-12-05 2001-12-27 Alec Mian Devices and method for using centripetal acceleration to drive fluid movement in a microfluidics system with on-board informatics
US20020090644A1 (en) * 1999-05-21 2002-07-11 Weigl Bernhard H. Microscale diffusion immunoassay
US6541213B1 (en) * 1996-03-29 2003-04-01 University Of Washington Microscale diffusion immunoassay
US5863801A (en) * 1996-06-14 1999-01-26 Sarnoff Corporation Automated nucleic acid isolation
US6054100A (en) * 1996-11-18 2000-04-25 Robbins Scientific Corporation Apparatus for multi-well microscale synthesis
AU7591998A (en) 1997-05-23 1998-12-11 Gamera Bioscience Corporation Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system
US5932799A (en) 1997-07-21 1999-08-03 Ysi Incorporated Microfluidic analyzer module
US6375871B1 (en) 1998-06-18 2002-04-23 3M Innovative Properties Company Methods of manufacturing microfluidic articles
US6426230B1 (en) * 1997-08-01 2002-07-30 Qualigen, Inc. Disposable diagnostic device and method
WO1999014368A2 (en) 1997-09-15 1999-03-25 Whitehead Institute For Biomedical Research Methods and apparatus for processing a sample of biomolecular analyte using a microfabricated device
JP2001517789A (en) * 1997-09-19 2001-10-09 アクレイラ バイオサイエンシズ，インコーポレイティド Liquid transfer device and liquid transfer method
AU1517999A (en) * 1997-10-15 1999-05-03 Aclara Biosciences, Inc. Laminate microstructure device and method for making same
US6632653B1 (en) * 1997-12-08 2003-10-14 Thomas W. Astle Continuous polymerase chain reaction apparatus with multiple temperature stations
JP3896435B2 (en) * 1997-12-17 2007-03-22 アークレイ株式会社 Sensor and sensor assembly
US6251343B1 (en) 1998-02-24 2001-06-26 Caliper Technologies Corp. Microfluidic devices and systems incorporating cover layers
US6123798A (en) * 1998-05-06 2000-09-26 Caliper Technologies Corp. Methods of fabricating polymeric structures incorporating microscale fluidic elements
US6274089B1 (en) 1998-06-08 2001-08-14 Caliper Technologies Corp. Microfluidic devices, systems and methods for performing integrated reactions and separations
US6106783A (en) * 1998-06-30 2000-08-22 Microliter Analytical Supplies, Inc. Microplate assembly and closure
US6787111B2 (en) 1998-07-02 2004-09-07 Amersham Biosciences (Sv) Corp. Apparatus and method for filling and cleaning channels and inlet ports in microchips used for biological analysis
US7155344B1 (en) 1998-07-27 2006-12-26 Caliper Life Sciences, Inc. Distributed database for analytical instruments
US6103199A (en) * 1998-09-15 2000-08-15 Aclara Biosciences, Inc. Capillary electroflow apparatus and method
WO2000074850A2 (en) * 1999-06-03 2000-12-14 University Of Washington Microfluidic devices for transverse electrophoresis and isoelectric focusing
US7601270B1 (en) * 1999-06-28 2009-10-13 California Institute Of Technology Microfabricated elastomeric valve and pump systems
WO2001007892A1 (en) 1999-07-27 2001-02-01 Esperion Therapeutics, Inc. Method and device for measurement of cholesterol efflux
US7108440B1 (en) * 1999-10-08 2006-09-19 The Procter & Gamble Company Applicator for distributing a substance onto a target surface
WO2001026812A1 (en) * 1999-10-14 2001-04-19 Ce Resources Pte Ltd Microfluidic structures and methods of fabrication
JP2004500233A (en) * 1999-10-22 2004-01-08 アクララ　バイオサイエンシーズ，　インコーポレイテッド Sealing for microfluidic devices
US6569674B1 (en) * 1999-12-15 2003-05-27 Amersham Biosciences Ab Method and apparatus for performing biological reactions on a substrate surface
US6361958B1 (en) * 1999-11-12 2002-03-26 Motorola, Inc. Biochannel assay for hybridization with biomaterial
US6451191B1 (en) * 1999-11-18 2002-09-17 3M Innovative Properties Company Film based addressable programmable electronic matrix articles and methods of manufacturing and using the same
US20030017467A1 (en) 2000-02-18 2003-01-23 Aclara Biosciences, Inc. Multiple-site sample-handling apparatus and method
US6627159B1 (en) * 2000-06-28 2003-09-30 3M Innovative Properties Company Centrifugal filling of sample processing devices
WO2002082057A2 (en) 2001-04-03 2002-10-17 Micronics, Inc. Split focusing cytometer
US7294478B1 (en) * 2001-06-06 2007-11-13 Rosetta Inpharmatics Llc Microarray reaction cartridge
US6863878B2 (en) * 2001-07-05 2005-03-08 Robert E. Klepper Method and apparatus for producing synthesis gas from carbonaceous materials
GB0128350D0 (en) * 2001-11-27 2002-01-16 Lab901 Ltd Non-rigid apparatus for microfluidic applications
US7241420B2 (en) 2002-08-05 2007-07-10 Palo Alto Research Center Incorporated Capillary-channel probes for liquid pickup, transportation and dispense using stressy metal
US7431888B2 (en) 2002-09-20 2008-10-07 The Regents Of The University Of California Photoinitiated grafting of porous polymer monoliths and thermoplastic polymers for microfluidic devices
WO2004080597A2 (en) 2003-02-05 2004-09-23 Iquum, Inc. Sample processing tubule
DE10307227A1 (en) 2003-02-14 2004-08-26 Cytocentrics Ccs Gmbh Introducing fluid into microfluidic structures for e.g. analysis or synthesis, locates elastic material above access opening and penetrates it using hollow needle
US7550267B2 (en) * 2004-09-23 2009-06-23 University Of Washington Microscale diffusion immunoassay utilizing multivalent reactants
US9238346B2 (en) * 2009-10-08 2016-01-19 National Research Council Of Canada Microfluidic device, composition and method of forming

Also Published As

Publication number Publication date
US20050089449A1 (en) 2005-04-28
US8790595B2 (en) 2014-07-29
WO2003046542A2 (en) 2003-06-05
AU2002352349A1 (en) 2003-06-10
CA2468334A1 (en) 2003-06-05
GB2397256B (en) 2006-06-28
US20120195809A1 (en) 2012-08-02
EP1450955A2 (en) 2004-09-01
EP1451568A2 (en) 2004-09-01
EP1451568B1 (en) 2013-04-03
GB0128350D0 (en) 2002-01-16
GB2397256A (en) 2004-07-21
GB2397384A (en) 2004-07-21
CA2468334C (en) 2012-02-21
GB0411088D0 (en) 2004-06-23
WO2003045557A2 (en) 2003-06-05
US8124029B2 (en) 2012-02-28
CA2468894A1 (en) 2003-06-05
US20050079104A1 (en) 2005-04-14
GB2397384B (en) 2006-06-07
GB0411087D0 (en) 2004-06-23
US20090022628A1 (en) 2009-01-22
AU2002347309A1 (en) 2003-06-10
WO2003046542A3 (en) 2003-12-18
WO2003045557A3 (en) 2003-12-31

Similar Documents

Publication Publication Date Title
CA2468894C (en) Apparatus and methods for microfluidic applications
US9539575B2 (en) Reaction plate
US7241421B2 (en) Miniaturized fluid delivery and analysis system
US9086371B2 (en) Fluidics devices
JP4885852B2 (en) Microfluidic devices for fluid manipulation and analysis
DE69634490T2 (en) APPARATUS AND METHOD FOR MOVING FLUIDS BY CENTRIFUGAL ACCELERATION IN AUTOMATIC LABORATORY TREATMENT
US20060113190A1 (en) Microfluidic device and method for improved sample handling
US20110120580A1 (en) Liquid channel device and production method therefor
US20030127327A1 (en) Microfluidic device and method for improved sample handling
WO2006098817A1 (en) Miniaturized fluid delivery and analysis system
AU2002352349B2 (en) Apparatus and methods for microfluidic applications
AU2002347309B2 (en) Apparatus and methods for microfluidic applications
US20230338954A1 (en) Multiplex Assays Using Separation Structure and Well Structure
US20130210070A1 (en) Microfluidic device and method for controlling interaction between liquids
Juncker et al. Microfluidic networks for patterning biomolecules and performing bioassays

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20221128