WO2004103564A1 - Dispositif et procede de positionnement et d'eclusage de compartiments de fluide encastres dans un milieu de separation - Google Patents

Dispositif et procede de positionnement et d'eclusage de compartiments de fluide encastres dans un milieu de separation

Info

Publication number
WO2004103564A1
WO2004103564A1 PCT/DE2004/001055 DE2004001055W WO2004103564A1 WO 2004103564 A1 WO2004103564 A1 WO 2004103564A1 DE 2004001055 W DE2004001055 W DE 2004001055W WO 2004103564 A1 WO2004103564 A1 WO 2004103564A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluid
positioning
fluid segment
discharging
segment
Prior art date
Application number
PCT/DE2004/001055
Other languages
German (de)
English (en)
Inventor
Gunter Gastrock
Andreas Grodrian
Thomas Henkel
Mark Kielpinski
Michael KÖHLER
Karen Lemke
Karin Martin
Josef Metze
Martin Roth
Thore Schön
Volker Baier
Original Assignee
Hans-Knöll-Institut für Naturstoff-Forschung e.V.
Institut für Physikalische Hochtechnologie e.V.
Institut für Bioprozeß- und Analysentechnik e.V.
Technische Universität Ilmenau
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hans-Knöll-Institut für Naturstoff-Forschung e.V., Institut für Physikalische Hochtechnologie e.V., Institut für Bioprozeß- und Analysentechnik e.V., Technische Universität Ilmenau filed Critical Hans-Knöll-Institut für Naturstoff-Forschung e.V.
Publication of WO2004103564A1 publication Critical patent/WO2004103564A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • 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
    • B01L3/502769—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 multiphase flow arrangements
    • B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • 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
    • 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
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • 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
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0418—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic electro-osmotic flow [EOF]
    • 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
    • B01L2400/0454—Moving fluids with specific forces or mechanical means specific forces radiation pressure, optical tweezers
    • 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
    • B01L2400/0457—Moving fluids with specific forces or mechanical means specific forces passive flow or gravitation
    • 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
    • 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
    • B01L3/502723—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 venting arrangements

Definitions

  • the invention relates to a device and a method for positioning and discharging fluid compartments embedded in a separation medium, in particular for microsystem technology.
  • microtiter plates are usually used to deposit the samples and are addressed using pipetting robotics.
  • Another approach consists in the generation of fluid compartments, in which a sample liquid and a liquid or a gas immiscible with it are generally combined using actuators in a suitable chip in such a way that the sample liquid is compartmentalized and the fluid segments generated (hereinafter referred to as compartments referred to) are embedded in the other liquid or gas (hereinafter also referred to as separation medium).
  • the deposit is then preferably carried out in a connected hose or capillary.
  • the compartment fluid can optionally be water or an aqueous solution.
  • the compartments can optionally contain educts for a chemical reaction, enzymes, substrates, cofactors or individual, several individual, an association or associations of pro- and / or eukaryotic cells or indicators, in particular pH indicators, or a combination of the contents mentioned.
  • the compartments can also contain individual, several individual, a bandage or groups of pro- and / or eukaryotic cells coupled to microcarriers.
  • the fluids metered in can contain, for example, reactants, substrates, gases or growth effectors.
  • the embedded compartments can have different fates in their depot, such as different product formation or different growth. At a given point in time, this requires a specific removal of certain compartments for further use.
  • At least the depots preferably contain at least one additional marker for identifying at least one compartment.
  • the marker preferably consists of at least one fluid segment, the at least one fluid segment leading to a detector signal that is significantly different from the detector signal of all fluid segments without a marker function and significantly different from the detector signal of the separation medium.
  • document DE 298 01 523.4 discloses a pipette or microreactor consisting of at least one capillary channel which is formed by a trench which is introduced into a substrate and can be covered by means of a microstructuring method and which is connected on one side to a pressure chamber, the pressure chamber being a controllable electrical heating medium
  • a thin-film heating resistor applied to an outer wall of a pressure chamber wall designed as a rigid membrane is assigned and an area of the connection between the capillary channel and the pressure chamber is provided with heat sink means and the capillary channel receives a liquid column or a plunger.
  • the document WO 98/16312 discloses a pipette which is provided in the pipette tip area with an integrated closure means and with at least one filter element.
  • a microdosing device for the defined delivery of small, self-contained liquid volumes is known from the document DE 100 10 208.5-52. It is also known that it is possible to structure liquids in channels or tubes by means of defined switching of valves or the like in the positively guided liquid flows.
  • the document DE 198 47 952.2-09 discloses a fluid flow switch for manipulating at least two liquid flows.
  • the document DE 100 55 318 AI discloses a method for the targeted and directed manipulation of small amounts of material on solid surfaces and from the document DE 100 62 246 Cl a person skilled in the art takes a method and a device for manipulating small amounts of liquid on a solid surface.
  • HPLC high pressure liquid chromatography
  • Carrier stream are miscible (for example. PCR solution in mineral oil).
  • the document DE 101 45 568.2 discloses a method for the parallel cultivation of microorganisms in microcapillaries in a liquid two-phase system, liquid segments serving as recreation rooms for microorganisms to be cultivated.
  • microchannels for guiding liquid streams have the disadvantage that it is not possible to specifically discharge certain liquid segments (compartments) from these systems (microchannels).
  • the invention is based on the object of specifying a device and a method for positioning and specifically discharging certain fluid segments from these systems, so that the selected segments can be supplied for further use.
  • Fig. 1 is a schematic representation of the device according to the invention.
  • the central component of the device is an arrangement, preferably a microchip (1), which contains at least two channels (2), which preferably have a round cross section with a diameter in the range of 0.1-2 mm, all of which have at least two Channels open into a common channel section (3) and all of these at least two channels are fluidly connected to one another.
  • the length of the common channel section (L) is at least the length of one fluid segment and at most the length of the distance between two successive fluid segments.
  • the inner surface of the channels has wetting properties for the separation medium and non-wetting properties for the compartment fluid.
  • Each of the fluid paths resulting from this arrangement can be separately addressed and controlled.
  • each of the at least two channels is connected to at least one valve (4) or at least one valve is integrated in each channel.
  • At least one of the channels is connected to a bidirectional actuator (5), preferably a controllable micropump, or this actuator is integrated in the channel.
  • a bidirectional actuator preferably a controllable micropump, or this actuator is integrated in the channel.
  • this actuator has a possibility of reversing the flow direction, so that both the flow speed and the flow direction of the fluid flow can be regulated with the same actuator.
  • fluid flows with or without fluid segments can be demanded from each channel via the common channel section into individual channels or each of the channels adjoining this channel section.
  • At least one of the channels is connected to a reservoir (6) for fluid segments embedded in the separation medium.
  • the device also includes at least one detection unit (7a) for the phase boundary between the fluid segment and the separation medium before, in or after the common channel section and at least one detection unit (7b) for the fluid segment content before, in or after the common channel section.
  • the detection of the phase boundary and the fluid segment content can be carried out both in the same detection unit and / or with the same detection method and in different detection units and / or with different detection methods.
  • the detection can advantageously be carried out by means of optical methods such as refraction, scattering, absorption, transmission, emission and fluorescence or by means of impedimetric methods such as electroimpedance spectroscopy, or by a combination of these methods.
  • a fluid segment to be discharged must first be positioned in the common channel section. This is done according to the invention by opening the valves for the corresponding fluid path and reducing the flow speed in the common channel section to almost zero by reducing the pressure pulse of the bidirectional actuator (5), the flow direction of the actuator being switched so that the fluid segment in question is in the direction of the common channel section and is transported into this.
  • the positioning process can both be carried out manually and automated by at least one control signal being sent to the corresponding valves and the actuator at a reproducible time after the detection has taken place, as a result of which a predetermined reduction in the pressure pulse of the actuator and a defined flow direction and Fluid path are specified, and by means of a retention time determined by the reproducible signal time and the instantaneous distance of the relevant fluid segment from the inner region of the common channel section, this fluid regime is processed until the fluid segment to be positioned is located in the inner region of the common channel section.
  • the positioning can be done by a Electrokinetic method take place, which electrokinetic method can be an electrophoretic, dielectrophoretic, electroosmotic method, a laser tweezer method or a method using field forces via quadrupoles or octopoles or a combination of these methods.
  • electrokinetic method can be an electrophoretic, dielectrophoretic, electroosmotic method, a laser tweezer method or a method using field forces via quadrupoles or octopoles or a combination of these methods.
  • the positioning can be carried out using a magnetic method or a method based on gravity or a combination of individual methods.
  • the device according to the invention contains at least one actuator (8) for generating a targeted pressure pulse build-up.
  • This is advantageously a pump or a gas-coupled pressure or suction connection.
  • the discharge process can be carried out manually, or it can be automated in that after the processing of the fluid regime for positioning, at least one control signal is sent to the corresponding valves and the at least one assembly to generate a targeted pressure pulse build-up, which leads to the fact that the targeted pressure pulse build-up is carried out in the common channel section.
  • the device according to the invention optionally contains a control computer (9) for processing the fluid control regimes.
  • the device optionally includes at least one depot device (10), the at least one depot device being fluidly connected to or integrated in at least one channel. LIST OF REFERENCE NUMBERS

Abstract

L'invention concerne un dispositif et un procédé de positionnement et d'éclusage de compartiments de fluide encastrés dans un milieu de séparation. En vue d'avoir un dispositif et un procédé d'éclusage ciblé de segments de fluide déterminés, à partir de ces systèmes, le dispositif selon l'invention est caractérisé en ce qu'il comprend au moins deux parcours de guidage de liquide, au moins l'un des parcours étant raccordé à un réservoir pour des segments de fluide encastrés dans le support de séparation, lesdits parcours de guidage de liquide débouchent dans une section commune de ces parcours, en ce que la longueur de ladite section commune s'étend au moins sur la longueur d'un segment de fluide et au plus, sur la distance de deux segments de fluide successifs, de façon qu'au moins un segment de fluide sélectionné puisse être positionné dans une section commune de guidage de liquide, en ce que chaque parcours de guidage de liquide présente au moins une vanne de commande de fluide et est raccordé, tout en permettant une circulation de fluide, avec un actionneur, chaque vanne et chaque actionneur pouvant être commandé individuellement, et en ce qu'il est prévu, dans la section de canal commune, ou en aval de celle-ci, au moins une unité de détection de limite de phase entre le segment de fluide et le milieu de séparation, ainsi qu'au moins une unité de détection desdits segments de fluide.
PCT/DE2004/001055 2003-05-19 2004-05-18 Dispositif et procede de positionnement et d'eclusage de compartiments de fluide encastres dans un milieu de separation WO2004103564A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2003122942 DE10322942A1 (de) 2003-05-19 2003-05-19 Vorrichtung zum Positionieren und Ausschleusen von in Separationsmedium eingebetteten Fluidkompartimenten
DE10322942.6 2003-05-19

Publications (1)

Publication Number Publication Date
WO2004103564A1 true WO2004103564A1 (fr) 2004-12-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2004/001055 WO2004103564A1 (fr) 2003-05-19 2004-05-18 Dispositif et procede de positionnement et d'eclusage de compartiments de fluide encastres dans un milieu de separation

Country Status (2)

Country Link
DE (1) DE10322942A1 (fr)
WO (1) WO2004103564A1 (fr)

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JP2011039051A (ja) * 2009-08-07 2011-02-24 F Hoffmann-La Roche Ag 液体試料の処理ユニットおよびその処理方法
US8940249B2 (en) 2009-08-07 2015-01-27 Roche Diagnostics Operations, Inc. System for the analysis of liquid samples

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DE102007032951B4 (de) 2007-07-14 2010-09-02 Karlsruher Institut für Technologie Vorrichtung und Verfahren zur Zuführung eines Flüssigkeitsstroms aus mindestens zwei Flüssigkeitsabschnitten in eine Messzelle
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