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WO2003024597A1 - Systeme de manipulation de fluide a petite echelle - Google Patents

Systeme de manipulation de fluide a petite echelle Download PDF

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Publication number
WO2003024597A1
WO2003024597A1 PCT/SE2002/001698 SE0201698W WO03024597A1 WO 2003024597 A1 WO2003024597 A1 WO 2003024597A1 SE 0201698 W SE0201698 W SE 0201698W WO 03024597 A1 WO03024597 A1 WO 03024597A1
Authority
WO
WIPO (PCT)
Prior art keywords
microscale
fluid handling
multilayer
handling device
substrate
Prior art date
Application number
PCT/SE2002/001698
Other languages
English (en)
Inventor
Patrik Hollman
Ove ÖHMAN
Original Assignee
Åmic AB
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 Åmic AB filed Critical Åmic AB
Publication of WO2003024597A1 publication Critical patent/WO2003024597A1/fr

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Classifications

    • 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
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B01F33/301—Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions
    • B01F33/3017—Mixing chamber
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B01F33/304—Micromixers the mixing being performed in a mixing chamber where the products are brought into contact
    • 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
    • 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
    • B01J2219/00819—Materials of construction
    • B01J2219/00833—Plastic
    • 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
    • B01J2219/00851—Additional features
    • B01J2219/00869—Microreactors placed in parallel, on the same or on different 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
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00889—Mixing
    • 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
    • B01L2200/12—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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874—Three dimensional network
    • 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
    • B01L2300/0887—Laminated structure
    • 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
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves

Definitions

  • the present invention relates to microscale fluid handling devices and methods for manufacturing such. More specifically, the invention relates to a multilayer polymer microscale fluid handling device and a method of manufacturing the same.
  • Such systems are mainly produced by different replication techniques.
  • a master is formed on the surface of silicon wafer, mainly by different lithography and etching steps.
  • the master is then either used as a direct mold in the replication process, or it is used to create positive or negative master copies.
  • the step of replication may comprise techniques such as injection molding of a thermoplastic material, hot- embossing of a thermoplastic material, casting a thermoset polymer or elastomeric material.
  • a multilayer fluid handling system is described in US 5,961,932, in which a micro- ceramic chemical plant is disclosed.
  • the technique of forming a multilayer structure in the green ceramic-state, followed by sintering at high temperatures is a much more complicated manufacturing process, compared to replication of polymers. Therefore, this process is a low-volume process and the resulting ceramic fluid handling devices are expensive to produce and cannot be of single use type, whereby the risk for contamination is increased.
  • microscale fluid handling structures with well defined microscale communication holes between the microscale fluid handling structures on one surface and the opposite surface thereof. Furthermore, it is of great importance that such communication holes approximately have the same cross-sectional area as the microscale fluid handling structures that they are connected to. To achieve a uniform flow it is of great importance that all sections of the microscale fluidic system, except for reaction chambers and the like, have an essentially uniform cross sectional area.
  • WO 01/26812 Al disclose a microscale fluidic device having a cover laminated thereon and access holes that extend through the cover. These access-holes are solely intended for injection or withdrawal of fluid from the device and therefore they do not need to be microscale sized. Therefore the access-holes are punched or drilled out from the cover.
  • the method of punching holes has a number of disadvantages that limits the use of such holes to create well defined holes needed in a ulti layer microscale fluid handling device. Firstly, it is extremely difficult to punch holes with a size in the microscale region. Secondly, it is difficult to align the punched holes with the other microscale features in the device.
  • the object of the invention is to provide a multilayer microscale fluid handling system and a method for producing the same, which overcomes the drawbacks of the prior art multilayer microscale fluid handling systems and devices. This is achieved by the multilayer microscale fluid handling system as defined in claim 1, and the method as defined in claim 13.
  • One advantage with such a multilayer microscale fluid handling system is that it, due to low production costs, can be designed as a single use system, whereby contamination risks connected with reuse of fluid handling systems are avoided.
  • the system in a simple manner may comprise transparent substrates that permit in situ optical analysis of fluids in the system.
  • Another advantage is that the system may be of more complex nature compared to prior single layer microscale fluid handling systems.
  • Another advantage is that semi permeable membranes, filters and the like may be incorporated in the multilayer microscale fluid handling system in a simple manner.
  • Still another advantage is that microscale fluid handling systems comprising crossing microscale channels may be realized.
  • valves and pumps may be integrated in the microscale fluid handling system in a simple manner.
  • Fig. 1 is a cross-sectional view of a microscale fluid handling system according to the present invention comprising a lateral filter.
  • Fig. 2 shows a flow chart over the microscale fluid handling system in fig 1.
  • Fig 3 shows a flow chart over the microscale fluid handling system in fig 3.
  • Fig. 4 is a cross-sectional view of a microscale fluid handling system according to the invention comprising a crossing microscale channel.
  • Fig. 5 shows an example of a sample distribution on the surface of a substrate produced a 10 by 10 micro-array according to one embodiment of the present invention.
  • Figs. 6a and 6b show an example of a microscale valve in an open and closed state, respectively.
  • Fig. 7 shows an example of a microscale pump.
  • Fig. 8 shows an example of a silicon master for producing a layer in the multilayer microscale fluid handling system according to the present invention.
  • Fig. 9 shows a negative master copy of the silicon master of Fig 8.
  • Fig. 10 shows a resin layer applied on the negative master copy of fig 9.
  • Fig. 11 shows a lithography step in the method according to the present invention.
  • Fig. 12 shows the resulting polymer substrate from the method presented with reference to figs. 8 through 11.
  • a "through hole” is to be understood as a channel like structure through an essentially flat member.
  • the "through hole” has a first opening and a second opening on opposite sides of said member.
  • the geometries of said openings can be of optional shapes, and may be mutually different.
  • the present invention relates to microscale fluid handling systems with two or more fluid handling layers. By building up such systems from more than one layer a number of features can be provided that cannot be provided in a single layer. Furthermore, multi-layer systems offer the possibility to provide laterally extending structures or components in the fluidic system.
  • microscale fluidic structure refers to all types of microscale structures capable of handling fluid in a microscale device, and which may be produced on/ in the surface of a polymeric substrate.
  • microscale fluidic structure examples are microscale channels, ducts, different types of reaction or mixing chambers and the like.
  • fluid is intended to refer to fluids in all flowing states, i.e. gas, or liquid state.
  • the structure of the microscale fluid handling system according to the invention may be compared to multi layer circuit boards, wherein the conductors are substituted for microscale channels and inter-board connectors or vias by inter- laminar through holes.
  • the next layer is laminated on top of a layer with a microscale cannel, the channel is closed.
  • the individual "circuit board” type layers are piled on top of each other to create the desired fluid handling system.
  • the inter-laminar holes have to be aligned with the receiving structure in the next layer (microscale channel, another inter-laminar hole or the like).
  • the diameter of the holes is about 50-100 ⁇ m and the dimensions of the microscale channels are in the same order.
  • the alignment of different layers is may be done by optical techniques, of the type commonly used in the field of microelectronics. Alternatively, the alignment is performed by precision mechanical constructions of the type described in the Swedish patent application 0202092-3, whereby extremely fast and accurate alignment is achieved.
  • the individual polymer layers in the device according to the invention may be formed by replication in several ways, such as by, injection molding of a thermoplastic material, hot-embossing of a thermoplastic material, casting a thermoset polymer or elastomeric material.
  • the inter-laminar through holes are created directly in the replication process.
  • the inter-laminar through holes in the polymer layers may be formed in replicated polymer substrates, by micro machining techniques such as drilling, milling, laser or water ablation and the like. The individual layers are then glued together after being aligned.
  • the microscale fluid handling device may comprise microscale structures such as: fluid valves, filter structures, mixing or dilution chambers.
  • the device may further comprise one or more layers comprising a flow- cell which can, when pressed against an external substrate, allow fluid to flow over the external substrate.
  • the microscale fluid handling device may further comprise a number of independent fluid handling systems in the same device, such as numerous parallel systems for performing parallel experiments, or two or more flow-cells forming an array of flow-cells.
  • the microscale fluid handling device comprising a flow-cell or an array of flow-cells may also be used to direct fluids to sites on the surface of a substrate to produce a surface active substrate which in turn is used as an analytical device.
  • the principals of the present invention lies in a multilayer microscale fluid handling device that comprises at least one polymer substrate with a microscale fluidic structure formed in a first surface of the substrate, and a microscale trough-hole that extends from the microscale fluidic structure to an opposite surface of the substrate.
  • the overall method according to the invention comprises two main steps:
  • At least one polymer substrate with a microscale fluidic structure formed in a first surface of the substrate, and a microscale through-hole that extends from the microscale fluidic structure to an opposite surface of the substrate, and
  • a master 700 in the form of a silicon wafer 710 is produced.
  • Microscale channels 720 and other microscale surface structures 730 are formed in the surface 740 of the silicon wafer by methods known in the art, e.g. lithography followed by etching and the like.
  • the master comprises a large number of sections, each representing a layer in an independent microscale fluid handling system.
  • a negative master copy 750 (Fig. 9) of the structured silicon master 700 is created by electroplating in e.g. nickel, i.e. a copy with opposite polarity (containing convex structures) is created.
  • the process of making master copies by electroplating in nickel is well known in the art of micro replication and will therefore not be described in detail herein.
  • the negative master copy 750 is thereafter used as mold surface for the molding of polymer substrates for the inventive microscale fluid handling system.
  • the method of molding polymer substrates comprises the following steps:
  • an UV curing epoxy resin 760 (Fig. 10) (e.g. SU8 obtainable form Micro Chem. Corp.) of a desired thickness onto the mold surface of the nickel master copy 750 by spin-coating.
  • Other types of epoxy resins that are curable by electromagnetic radiation may also be used.
  • a mask 770 is placed above the epoxy resin 760 (Fig. 11).
  • the mask need not be in physical contact with the resin layer 760.
  • the mask 770 is preferably a glass plate on which a pattern of non-transparent areas 780 has been provided by a suitable technique. Mask making is an art well known to the skilled man and need not be further discussed herein. These areas 780 can take any desired shape to create holes of a suitable shape.
  • the mask 770 is placed such that the non-transparent spots 780 are aligned with microscale structures (see Fig. 11). Then, the disk is exposed to UV light in order to polymerize the non-shaded portions of the resin layer 760.
  • the resin is cured in the regions outside the shading areas 780.
  • the non-cured parts 790 of the resin layer 760 are dissolved in propylene glycol ether acetate, which opens up through holes 800, as shown in Fig. 12.
  • the molded resin layer is removed mechanically from the mold, and the polymer substrate 810 is finished, as shown in Fig 12.
  • the polymer substrate 810 is laminated with at least one additional layer to form a multilayer microscale fluid handling device according to the present invention.
  • the additional layers may be produced using the above molding method or any other applicable technique.
  • the microscale fluid handling device manufactured by the method according to the present invention is a low-cost polymeric disposable device that allows single-use, which eliminates the risk for contamination. Furthermore, the use of transparent polymeric materials permits that the device is formed such that optical analysis of samples in the device may be performed.
  • FIG. 1 shows a schematic embodiment according to the present invention comprising five individual layers 10 - 50 laminated on top of each other.
  • the first layer is referred to as top cover plate 10, the second as fluid delivery layer 20 the third as filter layer 30, the fourth as fluid receiving layer 40 and the fifth as bottom cover plate 50.
  • the top cover plate 10 is preferably a transparent polymer plate with at least one fluid inlet hole or well 60 into which the fluid to be filtered and analyzed is entered.
  • the inlet hole 60 in this plate may be of a relatively large diameter, compared to the underlying microscale structures.
  • the top cover plate 10 may be manufactured by microscale replication techniques such as molding and injection molding or simply by punching out inlet holes 60 from a polymer plate.
  • the top cover plate 10 further encloses a microscale channel 70 formed in the fluid delivery layer 20 for communication between the inlet hole 60 and an upper filter opening 80.
  • the fluid delivery layer 20 is formed by through-hole type microscale replication molding as is discussed in detail above, whereby extremely well defined microscale structures may be achieved.
  • the filter layer 30 provides a filter element 90 in the lateral region directly below upper filter opening 80. Fluid is directed to the filter element 90 by the opening 80, and collected from the filter element by a collecting microscale channel 100 in the fluid receiving layer 40.
  • the entire filter layer 30 is provided as a homogeneous unidirectional filter element 90, whereby fluid that is directed to the filter element by the opening 80 flows vertically though the filter element 90 without horizontal dispersion.
  • the fluid receiving layer 40 collects the filtered fluid from the filter element 90 and the collecting microscale channel 100 directs the fluid to a through hole 110 and eventually to an analyze-chamber 120 in the bottom cover plate 50.
  • the bottom cover plate 50 is preferably a transparent polymeric plate that allow optical characterization of the filtered fluid.
  • microscale fluid handling devices wherein two or more microscale channels cross.
  • To allow crossing of two microscale channels it is necessary to provide channels in more than one plane.
  • FIG. 3 shows a flowchart over a mixing-arrangement 200 comprising a number of mixing cells 205 each cell comprising one mixing chamber 210.
  • Each mixing chamber 210 is connected with one individual inlet 220, one individual outlet 230, and one common reagent inlet 240.
  • Each individual inlet 220 is connected to an inlet microscale channel 250, connecting them to an individual sample inlet 260, arranged a distance away from the reaction chamber and is used for injecting a sample into the mixing cell 205.
  • the individual outlet 230 of each cell 205 drains the mixing chamber 210.
  • the individual outlet 230 is connected to an outlet microscale channel 270 which ends at an individual sample outlet or at a sample analysis site 280.
  • the common reagent inlet 240 is connected to a reagent microscale channel 290. All reagent microscale channels 290 in the mixing arrangement 200 are in turn connected to a common feed microscale channel 300 for feeding the same reagent to all mixing chambers 210. At one end, the common feed microscale channel 300 is connected to a reagent inlet or well 310. As is shown in the figure, the common feed microscale channel 300 must cross the inlet microscale channels 250 (or the outlet microscale channels 270) to reach the individual mixing chambers 210.
  • Figure 4 shows a schematic example of the above mixing arrangement 200 that is possible according to another embodiment of the present invention.
  • a first layer 320 has a top surface 325 which comprises a number of mixing chambers 210, each having their individual inlet channels 250, individual outlet channels 270 and reagent microscale channels 290.
  • the reagent microscale channels 290 are provided with, a through-hole 330 that extends through the first layer 320 to the bottom surface 335.
  • the common feed microscale channel 300 is provided in a second layer 340 that is laminated to the bottom surface 335 of the first layer 320.
  • the common feed microscale channel 300 is aligned with the through holes 330, such that the common feed microscale channel 300 is in fluidic communication with all of the reagent microscale channels 290. Furthermore the first layer 320 is provided with a reagent supply through-hole 350, which is aligned with or otherwise arranged to be in fluidic communication with (side channel 355) the common feed microscale channel 300, and is used for feeding reagent to the common feed microscale channel 300.
  • the microscale fluid handling device comprises a number of individual flow-cells in an array that are individually addressed.
  • the microscale fluid handling device comprising a flow-cell or a micro-array of flow-cells is used to direct fluids to sites on the surface of a substrate for the purpose of in-situ analysis in real-time or ex-situ analysis. That is, the flow-cell is removed and the substrate analyzed using some form of external analytical method.
  • Figure 5 shows an example of the resulting sample distribution on the surface of a substrate from a 10 by 10 micro-array.
  • the polymeric microscale fluid handling device according to the invention may be formed such that micro-array systems of virtually any size and complexity can be produced at low cost, and with all benefits from the polymeric material.
  • active components such as valves and pumps are included in the fluid handling system. As is shown in figs. 6a, 6b and 7 the active components are based on the multi-layer design of the system.
  • Figs. 6a and 6b show a valve 500 that is used to close a microscale channel 510.
  • the valve 500 is basically comprised of a through-hole 520, at the upper end connected to a control channel (not shown) for controlling the valve, and at the end facing the microscale channel 510 closed by a flexible membrane 540.
  • the control channel 530 is at the other end connected to a pneumatic or fluidic control device (not shown) that controls the pressure in the control channel.
  • FIG. 7 shows one embodiment of a fluid pump 600 that may be incorporated in the microscale fluid system of the present invention.
  • the pump 600 is comprised of three independently controllable valves 610a-c. To achieve a pumping action, the three valves 610a-c are repeatedly actuated in a successive manner.

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

Abstract

La présente invention concerne un dispositif de manipulation de fluide multicouche à petite échelle qui comprend au moins un substrat (30) polymère avec une structure fluidique à petite échelle formée dans une première surface du substrat et un alésage à petite échelle qui s'étend de la structure fluidique à petite échelle à une surface opposée de ce substrat. Cette invention concerne aussi un procédé de fabrication de ce dispositif.
PCT/SE2002/001698 2001-09-18 2002-09-18 Systeme de manipulation de fluide a petite echelle WO2003024597A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0103110A SE0103110D0 (sv) 2001-09-18 2001-09-18 Microscale fluid handling system
SE0103110-3 2001-09-18

Publications (1)

Publication Number Publication Date
WO2003024597A1 true WO2003024597A1 (fr) 2003-03-27

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WO2006075966A1 (fr) 2005-01-17 2006-07-20 Gyros Patent Ab Parcours d'ecoulement polyvalent
WO2007041486A2 (fr) 2005-09-29 2007-04-12 Siemens Medical Solutions Usa, Inc. Puce microfluidique capable de synthetiser des molecules radiomarquees a une echelle adaptee a l'imagerie humaine par tomographie par emission de positrons
WO2007044938A3 (fr) * 2005-10-13 2007-12-21 Univ California Échantillonneurs microfluidiques et procédés pour les fabriquer et les utiliser
EP1992403A1 (fr) * 2007-05-15 2008-11-19 Corning Incorporated Mélangeurs et dispositifs oscillants microfluidiques autonomes et dispositifs et procédés les utilisant
US7829032B2 (en) 2007-01-23 2010-11-09 Siemens Medical Solutions Usa, Inc. Fully-automated microfluidic system for the synthesis of radiolabeled biomarkers for positron emission tomography
US8071035B2 (en) 2007-04-12 2011-12-06 Siemens Medical Solutions Usa, Inc. Microfluidic radiosynthesis system for positron emission tomography biomarkers
CN103055985A (zh) * 2012-12-31 2013-04-24 兰州大学 一种基于金属丝热压法的聚合物微流控芯片批量制造工艺
EP2806972A1 (fr) * 2012-01-24 2014-12-03 Koninklijke Philips N.V. Unité de filtre pour une cartouche

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US5962081A (en) * 1995-06-21 1999-10-05 Pharmacia Biotech Ab Method for the manufacture of a membrane-containing microstructure
WO2000060352A2 (fr) * 1999-04-01 2000-10-12 Whatman Plc Dispositifs fluidiques
WO2000072968A1 (fr) * 1999-05-27 2000-12-07 Orchid Biosciences, Inc. Processeur d'echantillons multiples et systeme
US6167910B1 (en) * 1998-01-20 2001-01-02 Caliper Technologies Corp. Multi-layer microfluidic devices
US6238538B1 (en) * 1996-04-16 2001-05-29 Caliper Technologies, Corp. Controlled fluid transport in microfabricated polymeric substrates

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US5882571A (en) * 1994-10-19 1999-03-16 Hewlett-Packard Company Method for making miniaturized planar columns in novel support media for liquid phase analysis
US5962081A (en) * 1995-06-21 1999-10-05 Pharmacia Biotech Ab Method for the manufacture of a membrane-containing microstructure
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WO2006075966A1 (fr) 2005-01-17 2006-07-20 Gyros Patent Ab Parcours d'ecoulement polyvalent
US8075851B2 (en) 2005-09-29 2011-12-13 Siemens Medical Solutions Usa, Inc. Microfluidic chip capable of synthesizing radioactively labeled molecules on a scale suitable for human imaging with positron emission tomography
WO2007041486A3 (fr) * 2005-09-29 2007-06-07 Siemens Medical Solutions Puce microfluidique capable de synthetiser des molecules radiomarquees a une echelle adaptee a l'imagerie humaine par tomographie par emission de positrons
JP2009510454A (ja) * 2005-09-29 2009-03-12 シーメンス メディカル ソリューションズ ユーエスエー インコーポレイテッド 陽電子放射断層撮影による人体撮像に適した規模で放射性物質で標識した分子を合成することが可能なマイクロ流体チップ
KR100984963B1 (ko) 2005-09-29 2010-10-05 지멘스 메디컬 솔루션즈 유에스에이, 인크. 양전자 방출 단층촬영에 의한 인체 영상화에 적합한 규모의방사성 표지 분자를 합성할 수 있는 마이크로유체 칩
WO2007041486A2 (fr) 2005-09-29 2007-04-12 Siemens Medical Solutions Usa, Inc. Puce microfluidique capable de synthetiser des molecules radiomarquees a une echelle adaptee a l'imagerie humaine par tomographie par emission de positrons
US8658112B2 (en) 2005-09-29 2014-02-25 Siemens Medical Solutions Usa, Inc. Microfluidic chip capable of synthesizing radioactively labeled molecules on a scale suitable for human imaging with positron emission tomography
WO2007044938A3 (fr) * 2005-10-13 2007-12-21 Univ California Échantillonneurs microfluidiques et procédés pour les fabriquer et les utiliser
US7829032B2 (en) 2007-01-23 2010-11-09 Siemens Medical Solutions Usa, Inc. Fully-automated microfluidic system for the synthesis of radiolabeled biomarkers for positron emission tomography
US8071035B2 (en) 2007-04-12 2011-12-06 Siemens Medical Solutions Usa, Inc. Microfluidic radiosynthesis system for positron emission tomography biomarkers
US8173073B2 (en) 2007-04-12 2012-05-08 Siemens Medical Solutions Usa, Inc. Portable microfluidic radiosynthesis system for positron emission tomography biomarkers and program code
EP1992403A1 (fr) * 2007-05-15 2008-11-19 Corning Incorporated Mélangeurs et dispositifs oscillants microfluidiques autonomes et dispositifs et procédés les utilisant
EP2806972A1 (fr) * 2012-01-24 2014-12-03 Koninklijke Philips N.V. Unité de filtre pour une cartouche
CN103055985A (zh) * 2012-12-31 2013-04-24 兰州大学 一种基于金属丝热压法的聚合物微流控芯片批量制造工艺

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