EP1714698A2 - 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
EP1714698A2
EP1714698A2 EP06007697A EP06007697A EP1714698A2 EP 1714698 A2 EP1714698 A2 EP 1714698A2 EP 06007697 A EP06007697 A EP 06007697A EP 06007697 A EP06007697 A EP 06007697A EP 1714698 A2 EP1714698 A2 EP 1714698A2
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EP
European Patent Office
Prior art keywords
channel
section
sections
liquid
channel section
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.)
Granted
Application number
EP06007697A
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German (de)
English (en)
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EP1714698B1 (fr
EP1714698A3 (fr
Inventor
Thomas Willms
Gert Dr. Blankenstein
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim Microparts GmbH
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Boehringer Ingelheim Microparts GmbH
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Publication of EP1714698A2 publication Critical patent/EP1714698A2/fr
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 or 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 and a method for manipulating a liquid according to the preamble of claims 1 and 15, respectively.
  • 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 tapering 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, for better timing or resolution obtained, the previously wider liquid front is narrowed and then often widened again, which due to diffusion processes, the spatial resolution of the investigation can be significantly affected.
  • Another difficulty is to flood the control channel quickly and precisely controlled.
  • the present invention has for its object to provide a device and a method for manipulating a liquid, which allow a tezuporäres stopping the liquid in a particularly wide channel, with a further flow is particularly straight liquid front with relatively little effort and more precise timing possible.
  • 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 in particular start simultaneously over the entire channel cross-section. Accordingly, 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 as it continues to flow from the first channel section into the second channel section, so that in addition to a temporal resolution also a good local resolution is 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 formed wide or chamber-like. To simplify the description, only the channel or the channel sections will be discussed below.
  • Figures 1 to 12 show proposed devices 1 in not-to-scale representations to illustrate various aspects and Facilitation of the description.
  • FIG. 1 shows a schematic longitudinal section of 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 detecting 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 thus preferably limited or formed by only two opposite, in particular substantially planar surfaces or flat sides, in particular without 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 in particular the support sections 5, 6 are preferably formed substantially flat or plate-like and, if necessary, with required recesses, channels or dg1. Mistake.
  • 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 support 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 7.
  • 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 also referred to in part only as the "channel" - preferably have a flat and / or rectangular cross section transversely to the flow direction S of the liquid 2 indicated in FIGS. 1 and 3.
  • 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 preferably run parallel to the Ebeize 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 sudden 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 9 relatively movable, in particular with each other in contact or system can be brought.
  • the channel sections 3, 4 and in particular the support sections 5, 6 are translationally and / or rotationally movable relative to one another, preferably displaceable relative to one another, deformable, foldable and / or bendable.
  • the two support sections 5, 6 are guided displaceably relative to one another, in particular by means of a guide device 10 indicated in FIGS. 1 and 3.
  • the guide device 10 permits 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 for example formed like a slide and guided in corresponding, preferably groove-like and / or formed in the carrier 8 guide portions of the guide means 10 slidably.
  • 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, thus extending substantially only downwards with respect to a lateral projection of the channel in the illustrations according to FIGS. 1 and 3.
  • 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 guidance of the liquid 2 in the channel is also possible in the case of the second embodiment of the device 1 represented in FIGS. 4 a and 4 b by the lateral recess 14 or the lateral liquid stop.
  • 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. 4 a shows the device 1 with (still) separate channel sections 3 and 4, FIG. 4 b with channel sections 3 and 4 pushed together.
  • 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 indicated in Fig. 4b. 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 second embodiment shown in Fig. 4 is otherwise formed substantially in accordance with the first embodiment, so that there are corresponding advantages, aspects and properties.
  • FIG. 5 shows a third embodiment of the proposed device 1.
  • a reaction region 15 and a collecting region 16 are formed in the second channel section 4 and on the second carrier section 6, respectively.
  • 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.
  • 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, which is not separate in FIG is shown - 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.
  • 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.
  • a further liquid in particular a washing liquid
  • FIG. 6a shows the still spaced-apart support sections 5, 6, 18.
  • 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. 6 c shows a further phase in which the further carrier section 18 - in the illustrated example with the first carrier section 5 - has been brought into contact, in particular to perform a washing step by supplying a washing liquid or the like.
  • the reaction in the reaction region 15 can also be stopped very accurately again.
  • FIG. 7a to 7c show, in a further abstracted top view, a fifth embodiment of the proposed device 1.
  • a plurality of further sections 17/18 are provided here, which are arranged one after the other as required / or simultaneously and / or selectively moved to each other and in particular can be brought into contact with each other, the liquid 2 or possibly even more liquids by canceling or bridging between the individual sections 3, 4, 17 and 5, 6, 18 existing capillary stops 9 to manipulate in the desired manner and to have desired reaction (s) to perform or allow investigations.
  • Fig. 7a shows the still separate channel sections 3, 4, 17 and carrier sections 5, 6,18, wherein the arrow indicates that the first channel section 3 and carrier section 5 with an adjacent, here the second channel section 4 and carrier section 6 by Move is brought into contact. 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 carrier section 5 and the second carrier 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.
  • the two indicated in Fig. 7b further support portions 18 only alternatively - depending on the outcome of the previous reaction step or for optional variation of the reaction sequence - are brought into contact with the second channel section 4 and support section 6.
  • FIG. 7c the latter state is shown, in which 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 is.
  • 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 apply accordingly.
  • 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 are applied in parallel with the liquid 2 can.
  • 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 first channel section 3 or support section 5 is offset and / or centrally arranged with respect to the associated second channel sections 4 or support sections 6, that the first support section 5 - as indicated by the arrow - simultaneously the two second support portions 6 can be brought into contact to allow a simultaneous transfer of liquid 2 to the two second support portions 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.
  • 9 and 10 show a seventh embodiment of the proposed device in very schematic sectional views illustrating only the first and second support sections 5, 6.
  • 9 shows the spaced-apart state, that is, with the capillary stop 9 between the first carrier section 5 and the second carrier section 6 not yet bridged or raised.
  • the two carrier sections 5, 6 are in the seventh embodiment by a Connecting portion 19 connected to each other.
  • 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 shown in Fig. 10. Then, the liquid 2 can freely pass from the first support portion 5 to the second support portion 6 and continue to flow in the channel, not shown, as indicated in Fig. 10.
  • 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.
  • FIG. 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.
  • Fig. 11 shows the state in the unfolded state, ie with temporarily stopped liquid 2.
  • Fig. 12 shows the folded state, ie in abolished Kapillarstop 9, wherein the liquid 2 from the first support section 5 on the second support section 6 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)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Sampling And Sample Adjustment (AREA)
EP06007697A 2005-04-15 2006-04-12 dispositif et procédé pour la manipulation d'un liquide Expired - Lifetime EP1714698B1 (fr)

Applications Claiming Priority (1)

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DE102005017653A DE102005017653A1 (de) 2005-04-15 2005-04-15 Vorrichtung und Verfahren zur Manipulation einer Flüssigkeit

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

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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
JP2014503426A (ja) * 2010-11-10 2014-02-13 ベーリンガー インゲルハイム マイクロパーツ ゲゼルシャフト ミット ベシュレンクテル ハフツング ブリスタ包装材に液体を充填する方法及び液体を充填するためのキャビティを備えたブリスタ包装材
WO2013004673A1 (fr) * 2011-07-05 2013-01-10 Boehringer Ingelheim Microparts Gmbh Structure microfluidique comportant des creux
JP6265508B2 (ja) * 2012-09-21 2018-01-24 マサチューセッツ インスティテュート オブ テクノロジー マイクロ流体装置およびその使用
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
EP3861356A4 (fr) 2018-10-01 2022-07-06 Polyvalor, Limited Partnership Système et procédé de distribution de fluide

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EP1441131A1 (fr) 2003-01-23 2004-07-28 Steag MicroParts GmbH Commutateur microfluidique pour arrêter temporairement un courant de liquide

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WO2009106331A3 (fr) * 2008-02-27 2010-02-25 Boehringer Ingelheim Microparts Gmbh Dispositif de séparation de plasma
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Also Published As

Publication number Publication date
JP4813954B2 (ja) 2011-11-09
US20060249387A1 (en) 2006-11-09
CN1865714B (zh) 2010-12-08
DE102005017653A1 (de) 2006-10-19
CN1865714A (zh) 2006-11-22
EP1714698B1 (fr) 2012-12-19
EP1714698A3 (fr) 2008-07-16
US7655189B2 (en) 2010-02-02
JP2006300944A (ja) 2006-11-02

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