EP2308597B1 - Structure microfluidique et procédé de mesure et/ou de positionnement du volume d'un liquide - Google Patents

Structure microfluidique et procédé de mesure et/ou de positionnement du volume d'un liquide Download PDF

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Publication number
EP2308597B1
EP2308597B1 EP10186100.3A EP10186100A EP2308597B1 EP 2308597 B1 EP2308597 B1 EP 2308597B1 EP 10186100 A EP10186100 A EP 10186100A EP 2308597 B1 EP2308597 B1 EP 2308597B1
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EP
European Patent Office
Prior art keywords
liquid
measurement channel
wall portion
gas
valve
Prior art date
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Active
Application number
EP10186100.3A
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German (de)
English (en)
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EP2308597A3 (fr
EP2308597A2 (fr
Inventor
Rainer Gransee
Tina Röser
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Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
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Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
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Publication of EP2308597A3 publication Critical patent/EP2308597A3/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
    • B01L3/502—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
    • 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
    • B01L3/502738—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 integrated valves
    • 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
    • B01L2200/0605—Metering of fluids
    • 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
    • B01L2300/0883—Serpentine channels
    • 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
    • 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
    • B01L2400/0622—Valves, specific forms thereof distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
    • 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
    • B01L2400/0644—Valves, specific forms thereof with moving parts rotary valves
    • 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
    • B01L2400/0694—Valves, specific forms thereof vents used to stop and induce flow, backpressure valves
    • 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
    • Y10T137/00—Fluid handling
    • Y10T137/8593—Systems

Definitions

  • the invention relates to a Abmesskanal for use in a microfluidic system, a microfluidic structure in a substrate, in particular in a lab-on-chip system, with a plurality of fluid lines including a Abmesskanals and connected to the fluid lines valve for selectively connecting and / or disconnecting the fluid lines.
  • the invention further relates to a method for measuring and / or positioning a volume of a liquid in a microfluidic system, in particular in a lab-on-chip system.
  • the measuring and positioning or distribution of liquids in a microfluidic chip is known to be done with the help of so-called Abmessschleifen in combination with one or more rotary valves and filuidischen light barriers. Since virtually no more than two such Abmessschleifen can be connected via a valve, it requires the dimensioning and positioning of more than two liquids of several separate valve assemblies. The space required increases as a result, as well as the number of valve components and the optical components for the realization of the light barriers. Overall, this increases the cost of the system. Furthermore, through the combination of Abmessschleifen and rotary valves increased dead volumes and fluid losses are accepted.
  • the object of the present invention is to reduce the above disadvantages and to provide a cost-effective and efficient method for measuring and / or positioning a volume of a liquid in a microfluidic To provide system or a cost microfluidic structure for this purpose.
  • the inventive Abmesskanal for use in a microfluidic system in particular in a lab-on-chip system, has a first end, on which a first liquid-impermeable and gas-permeable wall portion is provided, which provides a gas connection, and a second end to which the Abmesskanal is connectable to at least one fluid line and to which a separation means is arranged, wherein in the Abmesskanal between the wall portion and the separating means a defined volume is included on.
  • the Abmesskanal which may for example be formed as a groove in a microfluidic chip and completed with a cover foil is limited by one or more the channel cross-section defining walls.
  • wall portion in the sense of this document is meant a limited, contiguous portion of one or more of these walls.
  • the channel is further limited by its two ends, which, however, do not require frontal walls, but initially only indicate positions and define the length or the volume of the Abmesskanals. The first end is thus the position of the first wall section along the Abmesskanals, the second end of the separation means.
  • the measuring takes place in the Abmesskanal (even without active optical monitoring) alone by filling the Abmesskanals up to the first wall section with a liquid and separating the volume of liquid trapped in the Abmesskanal between the wall portion and the separating means of a pending on the side of its second end in front of the separating means excess liquid residue.
  • the Abmesskanal is preferably closed or closed at a first end.
  • the following is also spoken of a dead channel.
  • This shape has the advantage, in particular in conjunction with the fact that the first liquid-impermeable and gas-permeable wall section is arranged at the closed or closable end of the Abmesskanals, that a small dead space and a very precise positioning of the metered liquid plug is ensured.
  • the separation means is advantageously designed as a second liquid-impermeable and gas-permeable wall section which provides a gas connection.
  • the separation or measuring takes place in the Abmesskanal (without active optical monitoring) alone by applying a pressure difference between an opening into the Abmesskanal filling opening and the gas connection over the first liquid-impermeable and gas-permeable wall section. Since pressure control for moving and positioning the so-called liquid plugs is necessary anyway in most microfluidic systems, the invention thus requires a smaller amount of equipment for measuring in comparison with measuring devices according to the prior art.
  • the separation means is advantageously designed as a valve alternatively.
  • the valve is again preferably at the same time separating means for measuring the volume of liquid and control valve for selectively connecting and / or separating the Abmesskanals with a desired fluid line (inlet or outlet). Also in this embodiment, the Abmesskanal comes without additional Fluid control or fluid control components.
  • Valve controls of different types are basically known in microfluidics. It will be an example of the writings US 2007/068573 A1 . US 2005/0056321 A1 or DE 102 28 767 A1 directed.
  • liquid-impermeable and gas-permeable wall sections are preferably designed in the form of a membrane and / or have a capillary structure passing through the channel wall, which presents an increased resistance to the passage of a liquid. It is crucial in both cases that the liquid through the wall section - if any - only by applying an increased limit differential pressure .DELTA.P G between the internal pressure P i in the Abmesskanal and the external pressure P a in the gas connection, starting from a for filling, emptying, or in general to overcome the normal differential pressure ⁇ P N used to convey the liquid.
  • a membrane as a liquid-impermeable and gas-permeable wall section, this preferably consists of a non-wettable material, preferably a polymer membrane and particularly preferably polytetrafluoroethylene.
  • a non-wettable material preferably a polymer membrane and particularly preferably polytetrafluoroethylene.
  • Such liquid-impermeable and gas-permeable membranes in a microfluidic system are known, for example, from the document US 2005/0266582 A1 known.
  • the gas connection is formed according to a preferred embodiment of the invention by an exhaust port beyond the liquid-impermeable and gas-permeable wall portion to the environment.
  • This construction is simple, as no pump connection is needed on the side of the gas connection.
  • the liquid transport in the metering channel is controlled on the inlet or outlet side, wherein the filling in this embodiment at the inlet requires an overpressure and the emptying at the outlet requires a negative pressure.
  • the microfluidic structure according to the invention in a substrate, in particular in a lab-on-chip system has a plurality of fluid conduits for receiving and / or conducting a fluid flow and a valve connected to the fluid conduits for selectively connecting and / or disconnecting the fluid conduits.
  • One of the fluid conduits is in the form of a metering channel as described above which is connected on the side of its second end via the valve to at least one other fluid conduit and closed or closable on the side of its first end.
  • "On the side of the first and second ends”, respectively, implies that the closure or valve forms the respective end of the metering channel, that is to say functionally associated with it, and that they lie at a distance from the ends outside the fluid channel.
  • a closure forming the first end which coincides with the first wall portion, allows filling and emptying with minimal fluid loss through dead spaces.
  • the filling, measuring and emptying can be realized in a simple manner.
  • the valve for selectively connecting and / or separating the fluid lines forms the separating means. It is also possible for a valve to be connected to a plurality of, and in particular more than two, of the metering channels according to the invention.
  • the gas connection and / or the at least one other fluid line is preferably connectable to a pump device which is set up to generate a pressure difference between the gas connection and the at least one other fluid line for supplying and / or discharging a fluid into the measurement channel.
  • a pump device which is set up to generate a pressure difference between the gas connection and the at least one other fluid line for supplying and / or discharging a fluid into the measurement channel.
  • the chip with the microfluidic structure according to the invention can be inserted into a so-called operator device, which provides a fluidic connection to the microfluidic chip via interfaces.
  • a pressure measuring device communicating with a fluid line in the microfluidic structure is provided, the signal of which can advantageously be used to control the pumping device according to one of the methods described below.
  • two or more of the above-described Abmesskanäle be arranged one behind the other, wherein the second end of a first Abmesskanals forms the first end of a second Abmesskanals.
  • step b) After filling in step b) is filled depending on the available amount of liquid, the entire Abmesskanal or only a part thereof. However, if the metering channel is in any case filled via the separating means, separation c) ensures that only exactly that between the first wall section and the defined, remaining liquid volume remains for further use.
  • step c If, as stated above, after the filling in step b), the metering channel is filled beyond the second wall section closer to the valve, it is ensured by the removal in step c ") that only the precisely defined liquid volume remaining between the wall sections in the metering channel remains remains for further use.
  • This variant represents the simpler case of a transverse filling, ie running in the direction of the channel.
  • the case is simpler insofar as the measuring has already taken place in one step.
  • the prerequisite is that the liquid is sucked through the inlet opening by a lower pressure at the gas connections than the pressure prevailing in the rest of the system.
  • the valve then serves to connect the metering channel to an outlet channel for emptying.
  • the second end of a first measuring channel forms the first end of a second measuring channel
  • the steps a) to c) or the step d) repeated.
  • the first filling of the Abmesskanals according to step b) takes place up to the first closer to the valve second wall portion which forms the starting point and the first wall portion during the second filling. Accordingly, the first removal takes place the excess liquid according to step d) of the first second wall portion and the second removal from a valve closer to the separation means.
  • the term "initially second” or “initially closer” refers to the wall section / separating means closer to the valve in the first filling / removal, and the indication “lying closer again” refers to the wall section / separating means closer to the valve in the second filling / removal.
  • supply line first derivative and second derivative is functional to understand and, so to speak, the same physical fluid line may be designated.
  • the filling is preferably carried out by continuously pumping the liquid into the metering channel by means of a pumping device.
  • Continuous pumping is one of two alternative pumping principles in addition to constant pressure pumping.
  • the pressure in the system is preferably monitored by means of a pressure measuring device communicating with the supply line or the metering channel.
  • the pressure at which the pumping device is switched off is higher than the system normal pressure P i and less than the limit differential pressure ⁇ P G between an increased internal pressure P ' i in the metering channel and the external pressure P a in the gas port the liquid breaks through the liquid-impermeable and gas-permeable wall section.
  • FIG. 1 the Abmesskanal 10 according to the invention is shown in a section through a microfluidic chip 12.
  • the microfluidic chip 12 typically has a substrate 14, in which the Abmesskanal 10 and any other fluid lines and / or other functional structures from its top 16 and / or its bottom 17 (this case is not shown here) are incorporated.
  • substrates with the fluid lines are produced by injection molding. Alternatively, they can also be milled into the surface of the substrate 14 or embossed in the injection-compression molding process.
  • the Abmesskanal 10 and the other, not shown here, fluid lines are closed to the environment by means of a cover film 18 on the top 16 (or bottom).
  • the cover sheet 18 is provided with two openings 20 and 22, of which an opening 20 opens flush with an end face 24 of the Abmesskanals 10 in the same. Due to the measuring surface 10 unilaterally limiting end face 24 of the Abmesskanal 10 for the liquid is a dead channel, but not for a gas which, as described below, can flow out of the channel 10 through the openings 20 and 22.
  • the liquid of Abmesskanal thus has only one access opening 25 through which it is fluidly connected or connected to the connected fluid lines. Nevertheless, it can be completely filled without dead spaces due to the flush with the opening 20 end surface 24.
  • the opening 20 Above the opening 20 is a liquid-impermeable and gas-permeable first wall section and above the opening 22 is a liquid-impermeable and gas-permeable second wall section.
  • the first wall portion and the second wall portion are each in the form of a membrane 26 and 28 is formed. Due to their gas permeability, these membranes provide a gas connection 27 or 29 for the metering channel 10.
  • For the supply or supply of gas is on the outside of the membranes 26 and 28 each have a gas line 30 and 32 flanged or mounted by the operator device.
  • the arrangement of the membranes as well as the gas lines is shown here only schematically simplified.
  • the membranes are preferably embedded in a membrane seat formed in the substrate and held, for example, by means of a pressing ring.
  • the pressing ring is preferably captively (ultrasonically) welded to the substrate and forms with the substrate a flush surface, which provides a sealing surface for the connection of a gas line.
  • This pressure increase can be detected by a suitable pressure measuring device (not shown) which is connected to a fluid line communicating with the metering channel 10. The corresponding signal is then supplied to a pump control, which shuts off the pump, to the increased internal pressure P ' i not so far increase so that the pressure difference between P ' j and P a exceeds the limit differential pressure .DELTA.P G , at which the liquid would escape through the membrane.
  • the liquid column is in front of the metering channel 10 beyond the second opening 22.
  • the measuring is now carried out in a second step by the second gas port 29 closer to the access opening 25 is acted upon by a higher external pressure P a than the internal pressure P i .
  • the resulting pressure difference causes the liquid present in front of the opening 22 in the direction of the access opening 25 to be pushed or sucked out of the channel in the opposite direction, so that only the volume V of liquid V between the two openings determined by the length of the measuring channel 10 remains 20 and 22 remains.
  • the second wall section thus forms the separating means.
  • This precisely metered volume of liquid can then be discharged from the metering channel 10 for further use by applying the gas port 27, which is further away from the opening 25, to a higher external pressure P a than the internal pressure P i .
  • FIG. 2 an exemplary microfluidic structure with a plurality of fluid lines on a microfluidic chip 100 is shown schematically simplified in plan view.
  • the plurality of fluid lines are: a supply line 102, a first, Abmesskanal 104, a merge channel or second, separate Abmesskanal 106, a meandering mixing section 108, a third Abmesskanal 110, which actually consists of two directly adjacent Abmesskanälen, and a discharge 112.
  • a rotary valve 114 is provided which selectively connects or disconnects the fluid lines.
  • the supply line 102 opens in the center of the rotary valve 114 and can via a first valve port 116 are selectively connected to each of the fluid lines 104, 106, 108, 112 directly.
  • the first metering channel 104 has at its end remote from the rotary valve 114 a liquid-impermeable and gas-permeable first wall section 118.
  • the first wall section 118 is formed by a membrane which fits into a membrane seat 120.
  • the merge passage 106 has two liquid-impermeable and gas-permeable first and second wall sections 122 and 124 spaced one behind the other, of which the first wall section 124 is at the opposite end of the rotary valve 114, and thus the second wall section 122 is approximately midway in the merge passage 106 and thus closer are arranged to the rotary valve 114. Between the two wall sections 122 and 124 opens a transverse filling opening 126 in the Georgia Events- or second Abmesskanal 106th
  • the mixing channel 108 is folded meander-shaped, so that two immediately consecutively introduced fluids due to the long distance and the multiple direction reversal at the output 128 of the meander arrived mixed.
  • the third Abmesskanal 110 connects, which has a total of three liquid-impermeable and gas-permeable wall sections 130, 132 and 134.
  • the wall portion 130 is the valve 114 nearest, the wall portion 134 of the valve 114 farmost wall portion.
  • the second Abmesskanal 106 between the distal first wall portion 124 and the closer second wall portion 122 through the filling opening 126 (for example by means of a syringe or by dropping a drop on the filling opening) with a liquid A (shown as a black bar) filled by a pressure difference is applied between the liquid flowing through the filling opening 126 on the one hand and the two gas ports on the wall portions 124 and 122 on the other hand.
  • the pressure difference causes the filling of the merge passage 106 to stop as soon as the fluid covers both wall sections 122 and 124.
  • the filling opening 126 can be closed, for example by means of an adhesive film or a plug.
  • the supply line 102 is connected to the first metering channel 104 and the metering channel 104 is subsequently filled with a liquid B (shown as a black bar) by applying a pressure difference between the supply line 102 and the first wall section 118 of the first metering channel.
  • a liquid B shown as a black bar
  • the gas connection can be switched to ambient pressure via the first wall section 118 and the supply line 102 can be operated with overpressure. If the wall section 118 is reached by the liquid B, a pressure rise can be registered with a pressure measuring device, not shown, which is for example in fluid communication with the supply line 102. A corresponding signal can then be supplied to the pressure source or pumping device or a valve and these automatically cause the fluid flow to be switched off or diverted.
  • the rotary valve 114 is adjusted so that the first Abmesskanal 104 is connected to the input of the second Abmesskanals 106. At the same time the supply line 102 of the first Abmesskanal 104 separated.
  • the valve 114 thus acts simultaneously as a release agent in the context of the invention.
  • a pressure difference between the wall portion 118 of the first Abmesskanals 104 and the valve 114 closer wall portion 122 of the second Abmesskanals 106 moves the previously located in the Abmesskanal 104, measured liquid B up to the wall portion 122 in the second Abmesskanal 106 inside.
  • a fourth step according to FIG. 6 the rotary valve 114 is further rotated by one step, so that it connects the second metering channel 106 with the meandering mixing channel 108.
  • a pressure difference between the rotary valve 114 further lying wall portion 124 of the second Abmesskanals 106 and at least the valve 114 distalmost wall portion 134 of the third Abmesskanals 110 are both liquids A and B initially successively through the meandering mixing channel 108 promoted, mixed therein and then in the third Abmesskanal 110 advanced to its distance from the mixing channel wall portion 134, see.
  • FIG. 7
  • the mixed liquid AB is then measured by the excess excess liquid located in front of the second wall section 130 closest to the valve 114 by applying a pressure difference between the gas connection over the second wall section 130 and the gas connection above the wall section 124 of the second dimensioning channel 106 remote from the valve derived the second Abmesskanal 106.
  • the second Abmesskanal 106 is used in the used state as a waste channel or waste.
  • the liquid AB located between the second wall portion 130 closest to the valve 114 and the nearest, middle (first) wall portion 132 is transported for further use inside or outside the microfluidic chip in the direction of the discharge line 112 by a pressure difference is applied between the gas port of the wall portion 132 and the internal pressure of the drain 112.
  • FIGS. 2 to 10 The basis of the FIGS. 2 to 10 For example, it is incumbent on the skilled person to generate the respectively necessary for the liquid transport pressure difference either by suction or pressure described sequence and the design of the microfluidic structure. It becomes apparent from the overall view of the present specification that it is not necessary to focus solely on the embodiment described in detail, but rather the underlying and in the patent claims specified method, the Abmesskanal and the microfluidic structure are relevant to the scope of protection.

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

Claims (12)

  1. Canal de mesure (10, 104, 106, 110) destiné à être utilisé dans un système microfluidique, en particulier dans un système de laboratoire sur puce, avec une première extrémité sur laquelle est disposée une première section de paroi (26, 118, 124, 132, 134), imperméable aux liquides et perméable aux gaz, réalisant un raccord de gaz (27), et une deuxième extrémité, sur laquelle le canal de mesure peut être raccordé à au moins une conduite de fluide et sur laquelle est disposé un moyen de séparation, un volume défini étant compris dans le canal de mesure (10, 104, 106, 110) entre la section de paroi (26, 118, 124, 132, 134) et le moyen de séparation, et le moyen de séparation étant réalisé sous forme d'une deuxième section de paroi (28, 122, 130, 132) imperméable aux liquides et perméable aux gaz, réalisant un raccord de gaz (29).
  2. Canal de mesure (10, 104, 106, 110) selon la revendication 1,
    caractérisé en ce que le canal de mesure (10, 104, 106, 110) est fermé ou peut être fermé sur sa première extrémité.
  3. Canal de mesure (10, 104, 106, 110) selon l'une des revendications précédentes,
    caractérisé en ce que la section de paroi (26, 28, 118, 122, 124, 130, 132, 134) imperméable aux liquides et perméable aux gaz est réalisée sous la forme d'une membrane.
  4. Structure microfluidique dans un substrat, en particulier dans un système de laboratoire sur puce, avec plusieurs conduites de fluide pour la collecte et/ou la conduction d'un flux fluidique et une vanne (114) raccordée aux conduites de fluide pour la liaison et/ou la séparations sélectives des conduites de fluide,
    caractérisée en ce qu'au moins une conduite de fluide est prévue sous la forme d'un canal de mesure (10, 104, 106, 110) selon l'une des revendications 1 à 3, lequel est sur le côté de sa deuxième extrémité raccordé par la vanne (114) à ladite au moins une autre conduite de fluide, et est fermé ou peut être fermé sur le côté de sa première extrémité.
  5. Structure microfluidique selon la revendication 4,
    caractérisée par un dispositif de mesure de pression communiquant avec une conduite de fluide dans la structure microfluidique.
  6. Procédé de mesure et/ou de positionnement d'un volume d'un liquide dans un système microfluidique, en particulier dans un système de laboratoire sur puce, avec un canal de mesure (10, 104, 106, 110) fermé ou pouvant être fermé sur le côté de sa première extrémité, et pouvant être raccordé par une vanne (114) à au moins une conduite de fluide sur le côté de sa deuxième extrémité, lequel présente sur sa première extrémité une première section de paroi (26, 118, 124, 132, 134) imperméable aux liquides et perméable aux gaz, réalisant un raccord de gaz (27), et présente un moyen de séparation sur sa deuxième extrémité, qui est réalisé comme deuxième section de paroi (28, 122, 130, 132) imperméable aux liquides et perméable aux gaz, réalisant un raccord de gaz (29), un volume défini étant compris entre la section de paroi (26, 118, 124, 132, 134) et le moyen de séparation, comprenant les étapes suivantes :
    a) raccordement du canal de mesure (10, 104, 106, 110) à une conduite d'amenée par l'intermédiaire de la vanne (114),
    b) remplissage du canal de mesure (10, 104, 106, 110) jusqu'à la première section de paroi (26, 118, 124, 132, 134) avec un liquide de la conduite d'amenée, un différentiel de pression étant appliqué entre la conduite d'amenée et le raccord de gaz (27) de la première section de paroi (26, 118, 132, 134),
    c) séparation du volume de liquide compris dans le canal de mesure entre la première section de paroi (26, 118, 124, 132, 134) et le moyen de séparation, d'un reste de liquide en excédent, présent devant le moyen de séparation sur le côté de sa deuxième extrémité.
  7. Procédé selon la revendication 6,
    caractérisé en ce que l'étape c) comprend :
    c') le raccordement du canal de mesure (10, 106, 110) à une première conduite d'évacuation par l'intermédiaire de la vanne (114),
    c") l'évacuation par la première conduite d'évacuation du liquide en excédent se trouvant entre la vanne (114) et la deuxième section de paroi (28, 122, 130, 132), un différentiel de pression étant appliqué entre le raccord de gaz (29) de la deuxième section de paroi (28, 122, 130, 132) et la première conduite d'évacuation.
  8. Procédé de mesure et/ou de positionnement d'un volume d'un liquide dans un système microfluidique, en particulier dans un système de laboratoire sur puce, avec un canal de mesure (106) fermé ou pouvant être fermé sur le côté de sa première extrémité, et pouvant être raccordé par une vanne (114) à au moins une conduite de fluide sur le côté de sa deuxième extrémité, lequel présente sur sa première extrémité une première section de paroi et sur sa deuxième extrémité une deuxième section de paroi (122, 124) imperméables aux liquides et perméables aux gaz, lesdites sections de paroi réalisant chacune un raccord de gaz, et entre lesquelles un volume défini est compris dans le canal de mesure (106), comprenant l'étape suivante :
    d) remplissage avec un liquide du canal de mesure (106) par une ouverture de remplissage (126) débouchant dans le canal de mesure (106) entre les sections de paroi (122, 124), un différentiel de pression étant appliqué entre l'ouverture de remplissage (126) d'un côté et les deux raccords de gaz de l'autre côté, suivi de la fermeture de l'ouverture de remplissage (126).
  9. Procédé selon l'une des revendications 6 à 8,
    caractérisé en ce que les étapes suivantes sont exécutées après l'étape c) ou après l'étape d) :
    e) raccordement du canal de mesure (10, 106, 110) à une deuxième conduite d'évacuation par l'intermédiaire de la vanne (114),
    f) évacuation par la deuxième conduite d'évacuation du liquide compris entre le moyen de séparation et la première section de paroi (26, 118, 124, 132, 134), un différentiel de pression étant appliqué entre le raccord de gaz (27) de la première section de paroi (26, 118, 124, 132, 134) et la deuxième conduite d'évacuation.
  10. Procédé selon l'une des revendications 6 à 9,
    caractérisé en ce que le remplissage est effectué par pompage continu du liquide dans le canal de mesure (10, 104, 106, 110) au moyen d'un dispositif de pompe.
  11. Procédé selon la revendication 10,
    caractérisé en ce que la pression est surveillée dans le système au moyen d'un dispositif de mesure de pression communiquant avec la conduite d'amenée ou le canal de mesure (10, 104, 106, 110).
  12. Procédé selon la revendication 11,
    caractérisé en ce que le dispositif de pompe est arrêté quand une élévation significative de pression est constatée dans la conduite d'amenée ou le canal de mesure (10, 104, 106, 110).
EP10186100.3A 2009-10-06 2010-10-01 Structure microfluidique et procédé de mesure et/ou de positionnement du volume d'un liquide Active EP2308597B1 (fr)

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Publication number Priority date Publication date Assignee Title
US9446403B2 (en) * 2011-10-24 2016-09-20 Xiamen Xinchuang Biological Technology Co., Ltd. Micro-channel chip
CA2886462C (fr) 2012-10-08 2021-06-15 General Electric Company Procede et appareil de test microfluidique de substances reactives au lal
US9440233B2 (en) 2013-08-09 2016-09-13 Shark Kabushiki Kaisha Microfluidic device for serial fluidic operations
DE102014105437A1 (de) 2014-04-16 2015-10-22 Amodia Bioservice Gmbh Mikrofluidik-Modul und Kassette für die immunologische und molekulare Diagnostik in einem Analyseautomaten
US20210008550A1 (en) * 2019-07-09 2021-01-14 Kryptos Biotechnologies, Inc. Microfluidic reaction vessel array with patterned films
CN111617812B (zh) * 2019-10-17 2021-12-03 北京京东方健康科技有限公司 微流控基板及其流体驱动方法、微流控装置
DE102020211697A1 (de) * 2020-09-18 2022-03-24 Robert Bosch Gesellschaft mit beschränkter Haftung Mikrofluidische Vorrichtung

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US56321A (en) * 1866-07-10 Improved shoe for stamping machinery
US266582A (en) * 1882-10-24 William demuth
US6899137B2 (en) * 1999-06-28 2005-05-31 California Institute Of Technology Microfabricated elastomeric valve and pump systems
US6536477B1 (en) * 2000-10-12 2003-03-25 Nanostream, Inc. Fluidic couplers and modular microfluidic systems
US6805841B2 (en) * 2001-05-09 2004-10-19 The Provost Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin Liquid pumping system
US6880576B2 (en) * 2001-06-07 2005-04-19 Nanostream, Inc. Microfluidic devices for methods development
US7077152B2 (en) * 2001-07-07 2006-07-18 Nanostream, Inc. Microfluidic metering systems and methods
US7128876B2 (en) * 2001-07-17 2006-10-31 Agilent Technologies, Inc. Microdevice and method for component separation in a fluid
US7244961B2 (en) * 2002-08-02 2007-07-17 Silicon Valley Scientific Integrated system with modular microfluidic components
US20050266582A1 (en) * 2002-12-16 2005-12-01 Modlin Douglas N Microfluidic system with integrated permeable membrane
US7296592B2 (en) * 2003-09-16 2007-11-20 Eksigent Technologies, Llc Composite polymer microfluidic control device
WO2007024798A2 (fr) * 2005-08-22 2007-03-01 Applera Corporation Dispositif, systeme et procede utilisant des volumes discrets de fluides non miscibles
EP1960306A4 (fr) * 2005-11-22 2014-04-02 Mycrolab Diagnostics Pty Ltd Structures microfluidiques
US20080035484A1 (en) * 2006-07-10 2008-02-14 Jiaqi Wu Method and apparatus for precise selection and extraction of a focused component in isoelectric focusing performed in micro-channels
EP2055384A1 (fr) * 2007-10-31 2009-05-06 Leukocare AG Dispositif de détection de composants dans un fluide

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DE102009045404A1 (de) 2011-04-07
EP2308597A2 (fr) 2011-04-13
DE102009045404B4 (de) 2012-04-19
US20110079094A1 (en) 2011-04-07
US8443835B2 (en) 2013-05-21

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