WO2001030490A1 - Obturation de dispositifs microfluidiques - Google Patents

Obturation de dispositifs microfluidiques Download PDF

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Publication number
WO2001030490A1
WO2001030490A1 PCT/US2000/041275 US0041275W WO0130490A1 WO 2001030490 A1 WO2001030490 A1 WO 2001030490A1 US 0041275 W US0041275 W US 0041275W WO 0130490 A1 WO0130490 A1 WO 0130490A1
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WO
WIPO (PCT)
Prior art keywords
collar
microfluidic device
reservoirs
lid
substrate
Prior art date
Application number
PCT/US2000/041275
Other languages
English (en)
Inventor
Sam Schaevitz
Travis Boone
Torlief Ove Bjornson
Original Assignee
Aclara Biosciences, 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 Aclara Biosciences, Inc. filed Critical Aclara Biosciences, Inc.
Priority to JP2001532896A priority Critical patent/JP2004500233A/ja
Priority to AU19701/01A priority patent/AU1970101A/en
Priority to CA002387064A priority patent/CA2387064A1/fr
Priority to EP00982707A priority patent/EP1225977A1/fr
Publication of WO2001030490A1 publication Critical patent/WO2001030490A1/fr

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Classifications

    • 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
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
    • 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
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
    • 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
    • B01L3/502715—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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00331—Details of the reactor vessels
    • B01J2219/00333—Closures attached to the reactor vessels
    • B01J2219/00335—Septa
    • 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
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00783—Laminate assemblies, i.e. the reactor comprising a stack of plates
    • 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
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00891—Feeding or evacuation
    • 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
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • 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
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • 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
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0421—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic electrophoretic flow
    • 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
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements
    • 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
    • B01L2400/0442—Moving fluids with specific forces or mechanical means specific forces thermal energy, e.g. vaporisation, bubble jet
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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

Definitions

  • the field of this invention is microfluidic devices.
  • Microfluidic devices offer great promise for the accurate manipulation of very small volumes, the rapid execution of a wide variety of operations, the minimal use of reagents, as well as many other benefits. As with all situations, the benefits come with challenges. For many purposes, one wishes to have a number of independent electrokinetic units in a single substrate. Since each unit will frequently comprise a plurality of reservoirs and channels, it is important that the individual units do not communicate except as required by the design of the device. Also importantly, is the problem of the very small volumes, which are frequently involved with the operations, due to evaporation. Where there is an interest in doing a quantitative analysis of an operation involving kinetics, it is important that the solvent volume remain substantially constant, so that the concentrations of the reactants are not changing due to decreasing volume.
  • lids have been used to seal the ports of microfluidic devices. Lids may provide sealing through the pressure of their weight, by providing adhesion, using various forms of latches or clasps, or by fitting snugly around a part and held by friction. There is an interest in developing devices and methods to substantially diminish the injurious events that may occur due to open ports of a microfluidic device, where the devices are effective and can be readily fabricated and methods readily performed. Relevant Art
  • U.S. Patent no. 5,4443, 890 and references cited therein describe leakage-proof sealing of microfluidic devices.
  • WO99/43432 describes microfluidic devices and systems incorporating cover layers.
  • U.S. Patent no. 5,545,280 describes applying adhesive to protrusions on a substrate.
  • Improved microfluidic devices are provided for use in performing operations involving the manipulation of small volumes.
  • Substrates are formed comprising channels and reservoirs, where the channels communicate with the reservoirs and the channels are otherwise enclosed, and the reservoirs have an aligned collar in relief, extending beyond the planar surface of the substrate and outwardly from the border of the reservoir.
  • the reservoirs are more efficiently sealed with an appropriate cover which contacts the crown of the collar.
  • the substrates may be formed by plastic molding or other means.
  • devices employing electrokinesis for movement of solutions from one site to another in the device, where the substrate comprises a plurality of individual electrokinetic units and the volumes involved generally are below about 5 ⁇ l.
  • Fig. 1 is a plan view of a device with collars around microstructures
  • Fig. 1 a is a cross- sectional view of the device of Fig. 1 along lines la- la
  • Fig. 2 is a plan view of the device of Fig. 1, with the collars removed to provide details of the individual units
  • Fig. 2a is a diagrammatic exploded view of the units of Fig. 2;
  • Fig. 3 is a side elevation cross-sectional view of a reservoir microstructure of a unit with a cover. DESCRIPTION OF THE SPECIFIC EMBODIMENTS
  • Microfluidic devices are provided for manipulation of small volumes, where the devices comprise a substrate, usually an organic substrate in which are channels and reservoirs, where the reservoirs have a raised collar above the planar surface of the substrate.
  • a bottom film including a rigid substrate, is adhered to and encloses the channels and the bottoms of the reservoirs.
  • the reservoirs can be sealed on the top sideusing a film, which seals to the upper surface of the collar.
  • the microfluidic devices will be characterized by having one or more operational units present in the substrate, where the number of units may vary from 16 to 1536 units, more usually not more than about 384 units, the number of units frequently being related to the number of wells in a microtiter well plate.
  • Each unit will have at least one channel and at least two reservoirs, usually having at least two channels and at least four reservoirs.
  • the total number of reservoirs for a device will generally be in the range of about 4 to 1600, more usually in the range of about 64 to 1500.
  • the sealing cover or lid will be a film, which forms a seal about the collar, so as to at least substantially inhibit fluid flow from the reservoir.
  • the cover will provide for sealing interaction with the collar upper surface, as a result of a compliant surface contacting the collar or an adhesive surface adhering to the upper surface of the collar, particularly an adhesive surface, which is removable. Contact will usually be minimal or not at all between the sealing cover or lid and the planar surface.
  • the forces providing the sealing may be gravity, adhesive forces, or mechanical forces.
  • compliant surfaces such as elastomeric films, skin-surface (closed-cell) foams, soft films
  • pressure would be applied, as a result of a weighted backing, latching or gripping devices for holding the film against the collars, a vacuum chuck which holds the film in position and can release the film, as appropriate, etc.
  • the film may be stretched across the collars, held in position by clasps at the periphery of the substrate, a sealing pliable band around the periphery, a vacuum chuck, etc.
  • a continuous sealing film may be used, which may be unrolled from a reel as the devices are moved in a continuous manner, for example, on a wheel or moving belt.
  • the films may be natural rubber, polyisoprene, ethylene-propylene elastomers, polyurethane foams, polydimethylsiloxane, etc.
  • the films may be thin or thick, so long as they have a minimum dimension, which provides for their sealing of the collars. Generally, the films will be at least about 50 ⁇ in thickness.
  • films may be used, which have a thin adherent layer, which will adhere to the surface of the collar and after the film has fulfilled its function, the adhesive may be removed.
  • Useful adhesives include pressure sensitive adhesives, such as ethylene-containing polymers, urethane polymers, butyl rubber, butadiene-acrylonitrile polymers, butadiene-acrylonitrile-isoprene polymers, and the like. See, for example, U.S. Patent no. 5,908,695 and references cited therein.
  • the substrate will generally have a thickness of at least about 20 ⁇ m, more usually at least about 40 ⁇ m, and not more than about 0.5cm, usually not more than about 0.25cm.
  • the width of the substrate will be determined by the number of units to be accommodated and may be as small as about 2mm and up to about 6cm or more.
  • the dimension in the other direction will generally be at least about 0.5cm and not more than about 20cm, usually not more than about 10cm.
  • the substrate may be a flexible film or relatively inflexible solid, where the microstructures, such as reservoirs and channels, may be provided by embossing, molding, machining, etc.
  • the collars may be formed at the same time using the same process, although more expensive processes maybe used, such as photolithography or laser ablation.
  • the channel dimensions will generally be in the range of about 0.1 ⁇ m to 1mm deep and about 0.5 ⁇ m to 500 ⁇ m wide, where the cross-section will generally be 0.1 ⁇ m 2 to about 0.25mm 2 .
  • the channel lengths will vary widely depending on the operation for which the channel is to be used, generally being in the range of about 0.05mm to 10cm, more usually in the range of about 0.5mm to 1cm.
  • the reservoirs will generally have volumes in the range of about 1 Onl to 1 O ⁇ l, more usually have volumes in the range of about 20nl to l ⁇ l.
  • the reservoirs may be cylindrically shaped or conically shaped, particularly inverted cones, where the diameter of the port will be from about 1.5 to 25 times, usually 1.5 to 15 times, the diameter of the bottom of the reservoir, where the reservoir connects to the channel.
  • the supporting film will generally be at least about 40 ⁇ m and not more than about 5mm thick.
  • the film used to enclose the channels and the bottom of the reservoirs will generally have a thickness in the range of about lO ⁇ m to 2mm, more usually in the range of about 20 ⁇ m to 1mm. The selected thickness is primarily one of convenience and assurance of good sealing and the manner in which the devices will be used to accommodate instrumentation. Therefore, the ranges are not critical.
  • the collars surrounding the reservoir ports will generally have a height from the planar surface of the substrate in the range of about 0.1 to 1mm, more usually about 0.2 to 1mm, and preferably about 0.25 to 0.75mm.
  • the crown will be thick enough to provide a good seal between the sealing film or lid and the crown, so that usually it will be about 0.05 to 1mm thick, more usually about 0.1 to about 0.5mm thick.
  • the collars may be considered extensions of the inner walls of the microstructures, having an inner wall aligned with the inner wall of the microstructure, where the collars then extend outwardly from the inner wall, much like the structure of a volcano.
  • the collar inner wall may be displaced from the reservoir inner wall, generally displaced less than about 1mm, usually less than about 0.5mm and may be less than about 0.1mm. In this way the inner wall is offset from the edge of the reservoir, serving as a fence around the reservoir.
  • the area occupied by a single unit will vary widely, depending on the number of units of the device, the function of the units, and the like. As illustrative, for the most part, where the devices are designed to be compatible with 96 to 384 microtiter well plates, the units will have from about 4.5 to 9mm spacings.
  • the substrate may be a flexible film or inflexible solid, so the method of fabrication will vary with the nature of the substrate.
  • embossing at least two films will be used, where the films may be drawn from rolls, one film embossed and the other film adhered to the embossed film to provide a physical support.
  • the individual units may be scored, so as to be capable of being used separately, or the roll of devices retained intact. See, for example, application serial no. PCT/98/21869. Where the devices are fabricated individually, they will usually be molded, using conventional molding techniques.
  • the substrates and accompanying film will generally be plastic, particularly organic polymers, where the polymers include addition polymers, such as acrylates, methacrylates, polyolefins, polystyrene, etc. or condensation polymers, such as polyethers, polyesters, polyamides, polyimides, etc. Desirably, the polymers will have low fluorescence inherently or can be made so by additives or bleaching.
  • the underlying enclosing film will then be adhered to a substrate by any convenient means, such as thermal bonding, adhesives, etc.
  • the literature has many examples of adhering such films, see, for example, U.S. Patent nos. 4,558,333; and 5,500,071.
  • Liquids may be moved through the units by any convenient means, including electrokinesis, pneumatics, sonics, thermal, etc.
  • Electrokinetic devices will usually have two or more reservoirs connected by microchannels, where the microchannels may cross, providing for injection of a plug from one microchannel into another microchannel.
  • the devices may find use in sequencing of nucleic acids, detection of binding between two entities, e.g. proteins with proteins, small molecules or cells, or various assays for the determination of drugs, single nucleotide polymorphisms, etc.
  • the methods employing the subject devices may be associated with the transfer to the microstructures of the devices of volumes ranging from about lOnl to 500 ⁇ l, with reaction volumes ranging from about 20nl to 0.5ml, usually 50nl to 0.1ml.
  • the volumes may be transferred by any efficient means, including pins, ink-jet dispensers, other piezoelectric devices, pipettes, etc.
  • the applicable seal may be applied. Instead of dispensing liquid into the microstructure, the process may involve withdrawing liquid from the microstructure. Where the seal is in place, the seal would be removed, the liquid withdrawn from the microstructure and the seal replaced. In this way the integrity of the concentration of the solution in the microstructure may be maintained. Alternatively, one may have a self-sealing film, where the seal would be pierced for the transfer of liquid.
  • FIG. 1 is depicted a plan view of a microfluidic device having 96 units with the spacing appropriate to a 96 well microtiter plate, where the spacing of the collars is shown.
  • the device 100 has a substrate 102 with collars 104 associated with the reservoirs 106.
  • Fig. la a cross-sectional view is shown of the device 100.
  • the device 100 is shown with reservoirs 106, only two reservoirs being shown for clarity.
  • Above the reservoirs 106 on the upper planar surface 108 of the device are collars 104.
  • An enclosing film 110 provides the bottom of the device, serving to enclose the reservoirs 106 and channels 1 12.
  • FIG. 2 the device 150 is shown with the sealing film removed to provide the detail of the individual microfluidic units 152.
  • An expanded version of the microfluidic units 152 is depicted in a diagrammatic plan view in Fig. 2a. This unit is for illustration purposes only and demonstrates a unit for performing a reaction with incubation, followed by separating the components of the reaction mixture using electrophoresis and identifying the product with a detector, not shown.
  • the unit 152 has a separation channel 154, beginning with electrophoresis buffer reservoir 156 and terminating in waste reservoir 158.
  • the assay channel 160 begins with a reagent incubation reservoir 162 and ends with a second waste reservoir 164.
  • the reagent incubation reservoir 162 receives the various components of the reaction where the reagents may react. Some of the liquid in the reagent incubation reservoir 162 may wick by capillary action through the separation channel to a stop-junction reservoir 168 provided in assay channel 160 to stop the movement of the reaction solution. After sufficient time for incubation liquid remaining in the reagent incubation reservoir 162 is moved by pressure to the stop-junction reservoir 168 and the electrophoretic process begun by introducing electrodes into the waste reservoirs 158 and 164, the stop-junction reservoir 168 and the buffer reservoir 156. By activating the electrodes in the stop-junction reservoir 168 and the waste reservoir 164, the reaction components may be moved to cross-section 166 for injection into separation channel 154. The electrodes in the reservoirs 164 and 168 may then be allowed to float, while the electrodes in buffer reservoir 156 and waste reservoir 158 are activated for electrophoretic transport and separation in separation channel 154 for detection of product.
  • Fig. 3 is shown a cross-section of a reservoir with the collar on a substrate.
  • the substrate 200 has an upper planar surface 202. Extending upward from upper planar surface 202 is the external wall of collar 204. As shown in the Figure, the collar 204 meets with the upper opening 206 of reservoir 208.
  • the wall 210 of reservoir 208 is shown as conical having a linearly even surface, but could be vertical or irregular, as needed.
  • the reservoir wall 210 is aligned with the collar wall 204, having a smooth transition, being a single feature when molding the substrate. As already indicated, the collar inner wall may be offset from the port edge.
  • the reservoir 208 terminates at the bottom into channel 212.
  • the channel 212 is enclosed by film 214, which adheres to the bottom surface 216 of the substrate.
  • the reservoir 208 is enclosed by a conformable cover film 218, backed by a weighted backing 220, to hold the film 218 in sealing relationship with the top surface 222 of collar 204.
  • the subject invention provides many advantages in enclosing, usually reversibly, small reservoirs or other microstructure.
  • the subject collar structure has a small contact area, which serves to concentrate the force produced by whatever means of application of the lid onto a much smaller area, as compared to a cover which bonds to the entire surface of the device.
  • a reduction in differential pressures created during application of the lid is achieved.
  • the upper surface is flat, without areas in relief, a conformal lid comes down in such a way that it will usually first make contact with a large ring around the area to be sealed. The air trapped within this ring is pressurized into the volume to be sealed.
  • the lid makes contact before it reaches the device main surface, avoiding trapping large volumes of air.
  • the subject method increases the local pressure with which the lid is attached to the part.
  • This increased pressure generally improves the seal and improves the proximity of conformal lids.
  • This improved seal can enable the use of a weighted lid to produce an airtight seal without requiring a large mass or an extremely conformable lid material.
  • the lid will act to resist or prevent fluid flow. Capillary stop junctions may be prone to failure by condensation or other mechanism, in which case the sealed lid provides a backup mechanism.
  • the sealed lid can easily counteract relatively strong fluidic forces, such as surface tension.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Dispersion Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

Obturation améliorée de microstructures situées dans des dispositifs(100, 150) microfluidiques possédant une pluralité d'unités (152), ce qui consiste à mettre en application des colliers (104, 204) entourant les ouvertures (206) de ces microstructures, telles que des réservoirs (208). Ces colliers (104, 204) consistent en des saillies s'étendant depuis la surface (108, 202) des dispositifs (100, 150) et les parois internes (210) de ces colliers (104, 204) sont généralement alignées sur les parois (210) internes de la microstructure. On utilise des couvercles (218, 220) adaptables et/ou adhésifs afin de fermer hermétiquement ces microstructures.
PCT/US2000/041275 1999-10-22 2000-10-18 Obturation de dispositifs microfluidiques WO2001030490A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2001532896A JP2004500233A (ja) 1999-10-22 2000-10-18 微小流体デバイスのためのシーリング
AU19701/01A AU1970101A (en) 1999-10-22 2000-10-18 Sealing for microfluidic devices
CA002387064A CA2387064A1 (fr) 1999-10-22 2000-10-18 Obturation de dispositifs microfluidiques
EP00982707A EP1225977A1 (fr) 1999-10-22 2000-10-18 Obturation de dispositifs microfluidiques

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16120399P 1999-10-22 1999-10-22
US60/161,203 1999-10-22

Publications (1)

Publication Number Publication Date
WO2001030490A1 true WO2001030490A1 (fr) 2001-05-03

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WO2003055790A1 (fr) * 2001-12-31 2003-07-10 Gyros Ab Dispositif microfluidique et son procede de fabrication
WO2003072251A2 (fr) * 2002-02-28 2003-09-04 Ibidi Gmbh Systeme microfluidique
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US6936167B2 (en) 2002-10-31 2005-08-30 Nanostream, Inc. System and method for performing multiple parallel chromatographic separations
WO2006085071A3 (fr) * 2005-02-08 2006-12-21 Lab901 Ltd Instrument d'analyse
US7238255B2 (en) 2001-12-31 2007-07-03 Gyros Patent Ab Microfluidic device and its manufacture
WO2008000276A2 (fr) * 2006-06-28 2008-01-03 Microlytic Aps Dispositif et procédé pour favoriser une cristallisation
US8501305B2 (en) 2007-01-16 2013-08-06 Agilent Technologies, Inc. Laminate
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CN103201633B (zh) 2010-11-08 2014-10-08 株式会社日立高新技术 反应板组件、反应板及核酸分析装置
JP2012103019A (ja) * 2010-11-08 2012-05-31 Hitachi High-Technologies Corp 反応プレートアセンブリ、反応プレート及び核酸分析装置

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EP1302243A1 (fr) * 2001-09-25 2003-04-16 Becton Dickinson and Company Microplaques fermes
WO2003045557A3 (fr) * 2001-11-27 2003-12-31 Lab901 Ltd Appareil et procedes d'application microfluidiques
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WO2004071660A1 (fr) * 2003-02-14 2004-08-26 Cytocentrics Ccs Gmbh Procede et dispositif pour etablir un contact avec une structure microfluidique
WO2006085071A3 (fr) * 2005-02-08 2006-12-21 Lab901 Ltd Instrument d'analyse
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