EP1714698B1 - dispositif et procédé pour la manipulation d'un liquide - Google Patents

dispositif et procédé pour la manipulation d'un liquide Download PDF

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Publication number
EP1714698B1
EP1714698B1 EP06007697A EP06007697A EP1714698B1 EP 1714698 B1 EP1714698 B1 EP 1714698B1 EP 06007697 A EP06007697 A EP 06007697A EP 06007697 A EP06007697 A EP 06007697A EP 1714698 B1 EP1714698 B1 EP 1714698B1
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EP
European Patent Office
Prior art keywords
channel
liquid
portions
section
channel portion
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Not-in-force
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EP06007697A
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German (de)
English (en)
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EP1714698A3 (fr
EP1714698A2 (fr
Inventor
Thomas Willms
Gert Dr. Blankenstein
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Boehringer Ingelheim Microparts GmbH
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Boehringer Ingelheim Microparts GmbH
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Publication of EP1714698A3 publication Critical patent/EP1714698A3/fr
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Publication of EP1714698B1 publication Critical patent/EP1714698B1/fr
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    • 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
    • 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
    • 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
    • B01L3/502761—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 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • 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
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668—Trapping microscopic beads
    • 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
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0654—Lenses; Optical fibres
    • 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
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/0825—Test strips
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/089—Virtual walls for guiding liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • 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
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0424—Dielectrophoretic forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—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
    • 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
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/065—Valves, specific forms thereof with moving parts sliding 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
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break

Definitions

  • the present invention relates to a device for manipulating a liquid according to claim 1 and a method according to the preamble of claim 11.
  • the present invention is concerned with microfluidic systems.
  • the following statements relate to devices in which act capillary forces and are particularly crucial for the function.
  • capillary stops are known, for example as in US Pat EP 1 441 131 A1 disclosed.
  • the liquid in a channel or in a wide chamber is temporarily stopped due to a sudden increase in the capillary force.
  • the capillary stop may be formed by a transverse, in particular trench-like, control channel. If the control channel is flooded, for example by a control liquid or by the liquid itself, the liquid can overcome the capillary stop.
  • Critical here is the temporal and / or local accuracy. If there is no rejuvenation of the channel cross section in the area of the capillary stop, it is very difficult or impossible to achieve a time-defined starting of the liquid over the entire channel cross section.
  • the channel is tapered in the area of the capillary stop, in order to obtain a better timing or resolution, the previously wider liquid front is narrowed and then often widened again, whereby due to diffusion processes, the spatial resolution of the investigation can be significantly impaired.
  • Another difficulty is to flood the control channel quickly and precisely controlled.
  • the EP 0 075 605 A1 deals with reaction vessels for analysis, wherein adhesion surfaces are approximated perpendicular to their surface extension.
  • the EP 0 590 695 A2 deals with liquid transfer devices, for example, where a extending through the liquid connecting portion for bridging a capillary stop is provided.
  • the US 4,902,629 discloses apparatus and methods in which a capillary channel is introduced into a reservoir to receive a liquid from the reservoir by capillary action.
  • the WO 2004/007078 A1 deals with a test device with lateral flow.
  • a movement of liquid is made possible by a movement transversely to the surface extension of the device.
  • the WO 2004/050246 A1 apparently a device for flowing liquid on a surface.
  • a capillary stop can be overcome by moving perpendicular to the surface.
  • the US 5,766,962 relates to devices for collecting and analyzing body fluids.
  • the device comprises a body having a capillary channel and a receiving chamber connected to the channel.
  • a flexible sample holder with a sample to be examined can be inserted into a bore of a cover which leads to the inner capillary channel.
  • the sample is diluted and transported along the channel and analyzed.
  • the US 5,399,316 relates to a reaction chamber having a reaction zone for examining a biological material.
  • the chamber has a carrier with a capillary channel for receiving a sample.
  • the carrier with the capillary channel can be pressed against an absorbent material of the liquid intake chamber.
  • the present invention has for its object to provide an apparatus and a method for manipulating a liquid, which allow a temporary halting of the liquid in a particular wide channel, with a further flow is particularly possible with straight liquid front with relatively little effort and more precise timing.
  • a basic idea of the present invention is to bridge a capillary stop between a first channel section and a second channel section in that the two channel sections are moved relative to each other, in particular brought into contact with each other. This can be done, for example, that the two channel sections are pushed together.
  • the proposed solution allows even with large channel cross-sections a uniform starting of the liquid, so over the entire liquid front uniform transfer of the liquid from the first channel section into the second channel section.
  • the liquid can start simultaneously over the entire channel cross section. Accordingly, a timely control is possible.
  • an at least substantially rectilinear liquid front and in particular a uniform, laminar flow can preferably be maintained over the entire channel cross-section even when continuing from the first channel section into the second channel section, so that in addition to a temporal Auflö a good local resolution is also possible. This is desirable especially for analyzes, ie in particular when analyzing the liquid or for detecting analytes or reactants contained therein.
  • the channel sections and thus the channel formed therefrom preferably have a relatively large cross-section. These are wide or formed like a chamber. To simplify the description, only the channel or the channel sections will be discussed below.
  • Fig. 1 to 12 show devices according to the proposal 1 in not to scale representations to illustrate various aspects and ease of description.
  • Fig. 1 shows in a schematic longitudinal section a first embodiment of a proposed device 1 for manipulating a liquid 2, in particular a sample liquid, for example for chemical and / or biological investigations, in particular for the detection of an analyte by a reagent, an antibody or the like.
  • the device 1 has a first channel section 3 and a second channel section 4 for the liquid 2.
  • the liquid 2 is absorbed and / or conveyed in particular exclusively by capillary forces from the channel sections 3, 4.
  • other forces such as compressive forces, centrifugal forces or the like., Act.
  • the device 1 has a first carrier section 5 and a second carrier section 6, and preferably an associated cover 7.
  • the cover 7 is preferably continuous and formed, for example, by film or the like.
  • the channel formed by the channel sections 3, 4 is therefore preferably bounded or formed by only two opposing, substantially flat surfaces or flat sides, and designed free from side walls.
  • the channel sections 3, 4 are formed such that the liquid 2 in the flow direction S flows at least substantially laminar over the preferably flat, formed by the support sections 5, 6 flat sides and / or with at least substantially rectilinear liquid front transverse to the flow direction S.
  • the device 1 has a carrier 8 for forming and / or holding the required microstructures, in particular the carrier sections 5, 6.
  • the carrier 8 and the carrier sections 5, 6 are formed substantially flat or plate-like and optionally provided with necessary recesses, channels or the like.
  • the cover 7 is flat in the illustrated embodiment, and preferably formed at least substantially ausbloodungsoko. However, this can be the other way around. If necessary, both the carrier 8 and the recess 7 can be recessed and / or formed with projections for forming desired structures and, if necessary, for receiving chemicals, reagents, examination devices or the like, not shown.
  • the device 1 is a so-called microchip (platform with microstructure).
  • Fig. 2 shows the device 1 in a plan view without the cover.
  • Fig. 3 shows the device 1 in a section along line III-III of Fig. 1 ,
  • the cover 7 and the carrier 8 are not formed in one piece. Rather, the cover 7 is preferably placed, clamped, glued, welded or connected in any other suitable manner with the carrier 8. This facilitates, for example, the production, However, according to an embodiment, not shown, the cover 7 and the carrier 8 may also be integrally formed. In this case, then at least one support portion 5, 6 and in particular both support portions 5 and 6 are laterally inserted into the one-piece component. The device 1 is then correspondingly laterally open for receiving the first and / or second carrier section 5, 6.
  • the channel sections 3 and 4 - hereinafter sometimes also called only the "channel" - preferably have a flat and / or rectangular cross-section transverse to Fig. 1 and 3 indicated flow direction S of the liquid 2.
  • the height of the channel - ie the distance of the channel bounding, preferably parallel surfaces - is in the illustrated example a maximum of 2000 microns, preferably at most 500 microns, in particular about 50 to 200 microns.
  • the width of the channel is preferably about 100 to 5000 microns, more preferably about 200 to 4000 microns.
  • the height of the channel is significantly lower, in particular at least by a factor of 10 or 100, than the width of the channel.
  • the uptake volume of the channel is preferably less than 1 ml, in particular less than 100 ⁇ l, particularly preferably not more than 10 ⁇ l.
  • the device 1 thus forms a microfluidic system.
  • the device 1 is used for microfluidic diagnostics for medical or non-medical purposes or other examinations.
  • the channel and its main extension plane E extend in the position of use preferably at least substantially horizontally. Depending on the intended use or constructive solution, however, a different orientation is possible, especially since the inclusion or filling of the channel with the liquid 2 and / or the conveying of the liquid 2 in the channel is preferably determined or effected at least primarily by capillary forces.
  • the main extension planes of the channel sections 3, 4 are in the representation example at least substantially in the common plane E, as in Fig. 1 indicated.
  • the upper or flat side of the support sections 5, 6 run parallel to the plane E.
  • the device 1, according to the proposal, has a device for temporarily stopping the liquid 2.
  • This device is formed by a capillary stop 9.
  • the capillary stop 9 ensures at least temporary stopping of the liquid 2 before the passage from the first channel section 3 to the second channel section 4 and is preferably arranged at the end of the first channel section 3 or between the two channel sections 3, 4.
  • the capillary stop 9. This is achieved by a correspondingly sharp edge at the downstream end of the first channel section 3 or support section 5 in the flow direction S and / or another, in particular abrupt, cross-sectional enlargement, whereby the capillary forces a further flow of the liquid 2 in the second channel section 4 do not allow.
  • the capillary stop 9 is formed by a trench-like recess or a corresponding spacing of the two channel sections 3, 4 or carrier sections 5, 6.
  • the capillary stop 9 preferably extends across the entire width of at least one flat side delimiting the channel, preferably between the two carrier sections 5, 6.
  • the capillary stop 9 thus preferably extends transversely to the flow direction S of the liquid 2 and / or transversely in the longitudinal direction of the first or second Channel section 3, 4.
  • Fig. 1 to 3 show the device 1 in a state in which between the two channel sections 3 and 4 of the capillary stop 9 is formed, in particular in that the two support portions 5, 6 are spaced. As a result, the liquid 2 present in the first channel section 3 or on the first carrier section 5 is temporarily stopped.
  • the two channel sections 3, 4 for bridging or canceling the capillary stop 9 are movable relative to each other with each other in contact or conditioning can be brought.
  • the channel sections 3, 4 and in particular the support sections 5, 6 are translationally and / or rotationally movable relative to each other, relative to each other displaceable, preferably additionally deformable, hinged and / or bendable.
  • the two support sections 5, 6 are guided displaceably relative to each other, in particular by means of a in Fig. 1 and 3
  • the guide device 10 permits a displacement of at least one support section 5 or 6.
  • the corresponding support section 5, 6 or both support sections 5, 6 is or are formed, for example, carriage-like and in corresponding, preferably groove-like and / or formed in the support 8 guide sections the guide means 10 slidably guided.
  • the direction of movement of the two channel sections 3, 4 or carrier sections 5, 6 relative to one another preferably extends into or against the flow direction S of the liquid 2 and / or in the longitudinal extent or in the main extension plane E of the channel sections 3, 4 or carrier sections 5 ,. 6
  • the two channel sections 3, 4 or support sections 5, 6 are, if necessary, manually movable relative to each other, in particular brought into contact with each other. This allows a simple and inexpensive construction.
  • the device 1 has a suitable, not shown manipulation device or the like. On.
  • the device 1 preferably has an actuator or other drive, not shown, such as a motor, an electromagnet, a piezoelectric actuator or the like., To the channel sections 3, 4 and the support sections 5, 6 for canceling or bridging the capillary 9 to move relative to each other, in particular to bring into contact.
  • the drive can - as needed - purely mechanical or electrical, electromagnetic, magnetic, pneumatic and / or hydraulic work.
  • the two support sections 5 and 6 may be biased away from each other by means of a spring, not shown, or other biasing means such that an unwanted merging of the support sections 5 and 6 is excluded.
  • a spring not shown
  • other biasing means such that an unwanted merging of the support sections 5 and 6 is excluded.
  • the two carrier sections 5, 6 meet in the pushed together (not shown) state with their transverse sides or at least their channel facing transverse edges 11, 12, so that in this collapsed state at least substantially continuous surface of the two upper or Flat sides of the support sections 5, 6 is formed.
  • the capillary stop 9 is preferably simultaneously lifted or bridged over the entire channel cross section, and the liquid 2 can flow from the first channel section 3 formed by the first carrier section 5 into the second channel section 4 formed by the second carrier section 6.
  • the flow or conveyance of the liquid 2 is preferably carried out exclusively by capillary force.
  • the capillary force acting on the liquid 2 in the second channel section 4 is preferably greater in the first channel section 3.
  • This higher capillarity can be achieved by a corresponding modification of the second carrier section 6, for example by a corresponding coating, reducing the distance to the cover 7 and / or - as indicated in the illustration example - by corresponding microstructures 13, in particular elevations or the like
  • the microstructures 13 are arranged with a greater or increasing density on the second support portion 6 in contrast to the first support portion 5 to the desired increase in the capillary force to the second channel labites 4 or support section 6 to achieve.
  • the second channel section 4 represents an extension or continuation of the first channel section 3.
  • the channel sections 3 and 4 form a quasi-continuous, in particular rectilinear, channel, preferably of substantially constant cross-section.
  • the cross section of the first channel section 3 corresponds directly before the capillary stop 9 at least substantially the cross section of the second channel section 4 immediately after the capillary stop.
  • the channel formed by the channel sections 3, 4 preferably has a substantially constant cross-section.
  • the device 1 preferably has a means for preventing the lateral advancement of liquid 2 in the flow direction S and / or for generating a curved or rectilinear flow front which is as slightly curved or rectilinear as possible or for generating a homogeneous or laminar flow, which closes laterally to the channel sections 3, 4 a liquid stop, which is formed in particular by a groove or trench-like recess 14 in the carrier 8.
  • the lateral liquid stop for the liquid 2 constitutes a flow obstacle which can not be overcome by capillary forces, so that the liquid 2 is guided along the open longitudinal sides of the channel sections 3, 4 free of side walls.
  • the recess 14 forming the liquid stop preferably adjoins the channel sections 3, 4 with sharp edges and is formed in particular in the carrier 8, extends in the illustrations according to FIG Fig. 1 and 3 So essentially only down with respect to a lateral projection of the channel.
  • the recess may optionally also extend upwards or both sides of the lateral projection of the channel, ie in particular upwards and downwards.
  • the preferably rectangular cross-section recess 14 leads to such, in particular stepped or sudden cross-sectional enlargement, as is the case with the capillary stop 9, that reduce the capillary forces such that said liquid stop for the liquid 2 in the transition from the channel to the recess 14 is formed.
  • the height of the recess 14 at least twice as large as the height of the channel.
  • the recess 14 and the liquid stop formed therefrom preferably extend in the illustrated embodiment along the open longitudinal side of the channel, in particular around the channel sections 3, 4 or the carrier sections 5, 6 on all sides.
  • a corresponding side wallless leadership of the liquid 2 in the channel is also in the in Fig. 4a and 4b illustrated, second embodiment of the device 1 by the lateral recess 14 and the lateral liquid stop possible.
  • the liquid 2 is preferably only on a bottom or flat side - ie on the first support section 5 or the two support sections 5, 6 - out.
  • the liquid 2 is thus not in contact with the opposite, formed by the cover 7 flat side.
  • the cover 7 is arranged correspondingly higher or possibly except to obtain the desired distance.
  • Fig. 4a shows the device 1 with (still) separate channel sections 3 and 4, Fig. 4b with pushed channel sections 3 and 4.
  • the liquid 2 in the collapsed state - ie at connected channel sections 3, 4 - at least substantially evenly distributed over the channel sections 3 and 4, as in Fig. 4b indicated. This is the case in particular if at least substantially equal capillary forces act over the entire length of the channel and if there is no simultaneous guidance between the cover 7 and the support sections 5, 6.
  • the thickness of the liquid film formed by the liquid 2 depends in particular on the wetting behavior and on the amount of liquid 2 fed in, in particular metered in.
  • the illustrated second embodiment is otherwise formed substantially according to the first embodiment, so that there are corresponding advantages, aspects and characteristics.
  • Fig. 5 shows a third embodiment of the proposed device 1
  • a reaction region 15 and a collecting region 16 in the second channel section 4 and on the second support section 6 are formed.
  • a three-chamber system may be formed together with the first channel section 3, which may, if necessary, have the function of a so-called immunoassay.
  • the first carrier section 5 may be provided or coated with a preferably detachable reagent, which may be in one first phase after supplying the liquid 2 is dissolved by this or reacted with the reagent.
  • a second phase in particular after a certain period of time - the two channel sections 3, 4 or carrier sections 5, 6 are pushed together, this state is in Fig. 5 represented, so that the liquid 2 then flow into the reaction region 15 and finally into the collecting region 16 and in particular can collect there.
  • the liquid 2 or the reagent contained therein and / or an analyte contained therein - in particular a complex formed from the reagent, preferably an antibody, and the analyte - can react and in particular bind to immobilized antibodies or the like for detection.
  • a detection for example optically, take place in the reaction region 15.
  • the liquid 2 at least substantially completely from the first channel section 3 - in particular after expiry of a predetermined reaction time - in the subsequent reaction region 15 and then flows into the collection area 16 to allow a defined reaction.
  • a kind of block-wise movement of the liquid 2 results from the first channel section 3 to the end of the second channel section 4, this type of movement can in particular by accordingly rising Capillary forces - preferably by appropriate texturing or microstructuring and / or coating of the upper sides of the support sections 5, 6 - can be achieved.
  • the bridging or canceling of the capillary stop 9 can only be used to actually start a reaction or examination of the liquid 2.
  • the liquid 2 is initially supplied to the channel section 3 as a sample - in particular via a filling opening or the like, or possibly even with insertion of the first support section 5 into the support 8 - and so for a certain time stored or transported. Only after the moving together of the two support sections 5, 6 of the capillary stop 9 is bridged or canceled. The liquid 2 can then pass into the second channel section 4 and start the time-critical reaction or investigation.
  • the individual phases can then run one after the other in the second channel section 4.
  • the above-mentioned, preferably detachable reagent is not in the first channel section 3 or not on the first support section 5, but preferably at the beginning of the second channel section 4 or support section 6 - in particular in a release region, the Fig. 5 not shown separately - arranged.
  • reaction sequence or another sequence can also be controlled thereby - even more clearly in terms of time - by bringing several channel sections into contact with each other, depending on the desired progress of the reaction, with suspension or bridging of capillary stops 9 arranged therebetween.
  • Fig. 6a to 6c show in very schematic plan views a proposed device 1 without cover 7 according to a fourth embodiment, with the particular reactions or reaction sequences as in the second embodiment - as described above - realized are.
  • the device 1 has at least one further channel section 17, which is correspondingly formed by at least one further carrier section 18.
  • the further channel section 17 or support section 18 - hereinafter also referred to as another section 17/18 - allows, for example, that after the passage of the liquid 2 from the first channel section 3 or support section 5 into the second channel section 4 or support section 6, a further liquid , in particular a washing liquid, can be supplied, in which the further carrier section 18 is brought into contact with the further liquid with the first or second channel section 3, 4 or support section 5, 6.
  • FIG. 6a shows the still spaced apart support sections 5, 6, 18th
  • Fig. 6b shows the state in which the first support portion 5 has already been moved to the second support portion 6 and is in contact therewith.
  • Fig. 6c shows a further phase in which the further support portion 18 - in the illustrated embodiment with the first support portion 5 - was brought into contact, in particular to perform a washing step by a washing liquid or the like. Is supplied.
  • the reaction in the reaction region 15 can also be stopped very accurately again.
  • Fig. 7a to 7c show in a further abstracted plan view a fifth embodiment of the proposed device 1, in addition to the two first and second channel sections 3, 4 or carrier sections 5, 6 here several more sections 17/18 are provided, the demand successively and / or simultaneously and / or optionally moved to each other and in particular can be brought into contact with each other to the liquid 2 or possibly more liquids by canceling or bridging between the individual sections 3, 4, 17 and 5, 6, 18 existing Kapillarstops 9 in the desired manner manipulate and allow desired reaction (s) to run or allow investigations.
  • Fig. 7a shows the still separate channel sections 3, 4, 17 and support sections 5, 6, 18, wherein the arrow indicates that the first channel section 3 or support section 5 with an adjacent, here the second channel section 4 and support section 6 by sliding in contact is brought. Subsequently can the liquid 2 flow accordingly from the first channel section 3 into the second channel section 4,
  • Fig. 7b shows a state in which the first channel section 3 and the second channel section 4 or the first support section 5 and the second support section 6 are already in contact.
  • the arrows indicate the displacement of second further sections 17 and 18, respectively, in order to contact the second channel section 4 or support section 6, preferably from opposite sides and in particular simultaneously. Accordingly, then a forwarding or division of the liquid 2 to the other two channel sections 17 and carrier sections 18 is possible.
  • a further carrier element 18 serve to supply a further liquid, for example washing liquid.
  • further support portion 18 then serves, for example, a recording of the liquid 2 from the second channel section 4 and carrier section 6, which is displaced by the further liquid and in particular washed out.
  • a further carrier section 18 is in contact with the second channel section 4 or carrier section 6 and the liquid 2 has already flowed into this further carrier section 18 or the further channel section 17 formed therefrom.
  • the liquid 2 has completely overflowed. However, this depends in particular on the acting capillary forces.
  • the liquid 2 can also be distributed over a plurality of sections 3, 4, 17 or 5, 6, 18.
  • the two arrows indicate additional combination options with further sections 17/18.
  • the above statements on the constellation according to Fig. 7b corresponding.
  • Fig. 8 shows a schematic plan view of a sixth embodiment of the proposed device 1 without cover 7.
  • This embodiment preferably corresponds at least substantially to the third embodiment, wherein two second channel sections 4 and support sections 6 are arranged in parallel and can be applied in parallel with the liquid 2.
  • two parallel or independently running reactions can be started simultaneously.
  • the first channel section 3 or support section 5 with the liquid 2 on the one hand and the two second channel sections 4 and support sections 6 are movable relative to each other, in particular in Kotakt or plant brought. In the illustrated example, this takes place in that the first carrier section 5 is movable relative to the second carrier sections 6, in particular displaceable.
  • the arrangement shown is the first channel section 3 or support section 5 offset and / or centered with respect to the associated second channel sections 4 and 6 carrier sections arranged that the first support portion 5 - as indicated by the arrow - simultaneously with the two second support sections 6 in Contact is brought to allow simultaneous transfer of liquid 2 to the two second support sections 6.
  • the first support portion 5 have a correspondingly increased width and / or the second support portions 6 may have a reduced width, so that upon contact of the first support portion 5 to the two second support portions 6 Kapillarstops 9 between each preferably at least substantially over the entire width of the two second support portions 6 are canceled or bridged to a uniform as possible filling of the second support sections 6 defined second channel sections 4 with liquid 2 over the entire channel cross-section - in particular at least substantially perpendicular to the flow direction S extending Liquid front - to allow.
  • FIGS. 9 and 10 show a seventh embodiment of the proposed device in very schematic sectional views, which illustrate only the first and second support sections 5, 6.
  • Fig. 9 shows the spaced state, ie with not yet bridged or not raised Kapillarstop 9 between the first support section 5 and the second support section 6.
  • the connecting portion 19 is preferably flexible or elastically deformable and / or web-like. If necessary, the support portions 5, 6 and the connecting portion 19 are integrally formed.
  • the connecting portion 19 When moving relative, in particular pushing together, the connecting portion 19 is deformed such that the two support portions 5, 6 at least in the region of their transverse sides or transverse edges 11, 12 for canceling or bridging the capillary touch, as in Fig. 10 shown. Then, the liquid 2 can freely pass from the first support section 5 to the second support section 6 or continue to flow in the channel, not shown, as in Fig. 10 indicated.
  • the preferably elastic connecting portion 19 leads to the advantage that the two support portions 5, 6 in the manufacture and, for example, during storage and / or transport with already filled liquid can not be moved unintentionally relative to each other, so that an unintentional lifting or bridging the capillary stop can be excluded.
  • FIGS. 11 and 12 show an eighth embodiment of the proposed device 1 in schematic plan views without cover 7.
  • the two support sections 5,6 are here relative to each other rotatable or hinged to cancel the capillary stop 9 or at least to bridge, so that the liquid 2 from the first support section 5 on the second carrier section 6 can flow
  • Fig. 11 shows the state in the unfolded state, ie with temporarily stopped liquid.
  • Fig. 12 shows the folded state, ie with abolished Kapillarstop 9, wherein the liquid 2 from first carrier section 5 has already flowed onto the second carrier section 6.
  • the device 1 or the carrier 8 also to be disposed transversely to the flow direction at least substantially in the main extension plane E S buckling or bending axis to thereby adjacent channel sections or support sections to each other to move and bridging a capillary stop disposed therebetween or even cancel, so that then the liquid can continue to flow in the channel formed.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Fluid Mechanics (AREA)
  • Physics & Mathematics (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Micromachines (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)

Claims (13)

  1. Dispositif microfluide (1) dans lequel agissent des forces capillaires, pour la manipulation d'un liquide (2), comportant un premier segment de canal (3) et un deuxième segment de canal (4),
    le fluide (2) pouvant s'écouler du premier segment de canal (3) dans le deuxième segment de canal (4) et un arrêt capillaire (9) étant formé entre les segments de canal (3, 4), pour arrêter temporairement le fluide (2) avant un passage du premier segment de canal (3) dans le deuxième segment de canal (4),
    le dispositif (1) présentant des segments de support (5, 6) qui limitent les segments de canal (1, 4) et sont constitués en forme de plaque,
    les plans d'extension principaux des segments de canal (3, 4) se trouvant au moins substantiellement dans un plan commun (E) et les côtés plats des segments de support (5, 6) évoluant en parallèle à ce plan (E),
    le fluide (2) étant conduit indépendamment des parois latérales dans les segments de canal (3, 4),
    la hauteur des segments de canal (3, 4) étant substantiellement inférieure à la largeur des segments de canal (3, 4),
    le dispositif (1) étant conçu de telle sorte que les deux segments de canal (3, 4) puissent être mobiles l'un par rapport à l'autre pour contourner ou supprimer l'arrêt capillaire (9) et pouvant être mis en contact l'un avec l'autre au niveau frontal ; à cette fin, les segments de support (5, 6) pouvant être décalés l'un par rapport à l'autre dans leur plan d'extension principal.
  2. Dispositif selon la revendication 1, caractérisé en ce que les segments de canal (3, 4) ont une coupe transversale plane, rectangulaire et/ou au moins au niveau de l'ouverture, identique, et/ou en ce que les segments de canal (3, 4) ou les segments de support (5, 6) sont conçus de préférence de façon rigide sur toute leur longueur.
  3. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le deuxième segment de canal (4) forme un prolongement ou une continuation du premier segment de canal (3).
  4. Dispositif selon l'une des revendications précédentes, caractérisé en ce que les segments de canal (3, 4) sont formés des segments de support (5, 6) et d'un couvercle (7) commun, sur toute leur longueur.
  5. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le dispositif présente un dispositif de guidage (10) pour le guidage décalable d'au moins un segment de support (5, 6).
  6. Dispositif selon l'une des revendications précédentes, caractérisé en ce que, pour contourner ou supprimer l'arrêt capillaire (9), des côtés transversaux ou des bords transversaux (11, 12) des segments de support (5, 6) peuvent être mis en contact ou installés au niveau frontal, de préférence sur la longueur totale et/ou les segments de supports (5, 6).
  7. Dispositif selon l'une des revendications précédentes, caractérisé en ce que les segments de canal (3, 4) sont mobiles l'un par rapport à l'autre dans la direction de l'écoulement (S) du fluide (2) ou dans une direction opposée à celle-ci.
  8. Dispositif selon l'une des revendications précédentes, caractérisé en ce que la force capillaire agissant sur le fluide (2) est plus grande dans le deuxième segment de canal (4) que dans le premier segment de canal (3).
  9. Dispositif selon l'une des revendications précédentes, caractérisé en ce que la section du premier segment de canal (3) avant l'arrêt capillaire (9) correspond au moins substantiellement à la section du deuxième segment de canal (4) après l'arrêt capillaire (9).
  10. Dispositif selon l'une des revendications précédentes, caractérisé en ce que l'arrêt capillaire (9) s'étend sur au moins un côté ou une surface limitant le premier segment de canal (3), en particulier, la largeur totale, et/ou en ce que l'arrêt capillaire (9) s'étend perpendiculairement à la direction d'écoulement (S) du fluide (2) et/ou perpendiculairement à la direction longitudinale du premier ou du deuxième segment de canal (3, 4).
  11. Procédé de manipulation d'un fluide (2) au moyen d'un dispositif selon l'une des revendications précédentes, le fluide (2) du premier segment de canal (3) pouvant s'écouler dans le deuxième segment de canal (4) et étant arrêté temporairement au moyen de l'arrêt capillaire (9) avant un passage du premier segment de canal (3) dans le deuxième segment de canal (4), caractérisé en ce que
    pour contourner ou supprimer l'arrêt capillaire (9), les segments de canal (3, 4) limitant les segments de supports (5, 6) de section plane ou de type plat sont décalés l'un par rapport à l'autre dans un plan commun (E) de leur plan d'extension principal et sont installés au niveau frontal.
  12. Procédé selon la revendication 11, caractérisé en ce que plusieurs segments de canal (3, 4, 17) sont déplacés à volonté les uns par rapport aux autres, en particulier, sont mis en contact les uns avec les autres pour contourner ou supprimer l'arrêt capillaire (9) formé entre eux.
  13. Procédé selon la revendication 11 ou 12, caractérisé en ce que plusieurs segments de canal (3, 4, 17) sont déplacés les uns par rapport aux autres de façon concomitante ou consécutive, en particulier, sont mis en contact les uns avec les autres, pour contourner ou supprimer l'arrêt capillaire (9) formé entre eux.
EP06007697A 2005-04-15 2006-04-12 dispositif et procédé pour la manipulation d'un liquide Not-in-force EP1714698B1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE102005017653A DE102005017653A1 (de) 2005-04-15 2005-04-15 Vorrichtung und Verfahren zur Manipulation einer Flüssigkeit

Publications (3)

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EP1714698A2 EP1714698A2 (fr) 2006-10-25
EP1714698A3 EP1714698A3 (fr) 2008-07-16
EP1714698B1 true EP1714698B1 (fr) 2012-12-19

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US (1) US7655189B2 (fr)
EP (1) EP1714698B1 (fr)
JP (1) JP4813954B2 (fr)
CN (1) CN1865714B (fr)
DE (1) DE102005017653A1 (fr)

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US20040265171A1 (en) * 2003-06-27 2004-12-30 Pugia Michael J. Method for uniform application of fluid into a reactive reagent area
US20100062414A1 (en) * 2007-04-05 2010-03-11 Panasonic Corporation Sample liquid analytical chip
MX346456B (es) * 2008-02-27 2017-03-21 Boehringer Ingelheim Microparts Gmbh Dispositivo para la separación de plasma.
US20140000223A1 (en) * 2010-11-10 2014-01-02 Boehringer Ingelheim Microparts Gmbh Method for filling a blister packaging with liquid, and blister packaging with a cavity for filling with liquid
US20140227148A1 (en) * 2011-07-05 2014-08-14 Boehringer Ingelheim Microparts Gmbh Microfluidic Structure Having Recesses
AU2013318647B2 (en) * 2012-09-21 2017-10-26 Massachusetts Institute Of Technology Micro-fluidic device and uses thereof
US11441701B2 (en) 2017-07-14 2022-09-13 Hewlett-Packard Development Company, L.P. Microfluidic valve
CN108831819A (zh) * 2018-04-20 2018-11-16 中国药科大学 一种原态-变性转换离子源的设备及其应用
CA3148282A1 (fr) 2018-10-01 2020-04-09 Pierre-Alexandre GOYETTE Systeme et procede de distribution de fluide

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Also Published As

Publication number Publication date
US20060249387A1 (en) 2006-11-09
US7655189B2 (en) 2010-02-02
EP1714698A3 (fr) 2008-07-16
CN1865714B (zh) 2010-12-08
JP2006300944A (ja) 2006-11-02
EP1714698A2 (fr) 2006-10-25
JP4813954B2 (ja) 2011-11-09
DE102005017653A1 (de) 2006-10-19
CN1865714A (zh) 2006-11-22

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