WO2004103564A1 - Device and method for positioning and removing fluid compartments that are embedded in a separation medium - Google Patents

Device and method for positioning and removing fluid compartments that are embedded in a separation medium

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)
French (fr)
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/en

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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

The invention relates to a device and a method for positioning and removing fluid compartments that are embedded in a separation medium The aim of the invention is to provide a device and a method for removing defined fluid segments from these systems in a targeted manner. For this purpose, the device comprises at least two fluid routes. At least one of these fluid routes is linked with a reservoir for fluid segments that are embedded in separation media. The fluid routes run into one common fluid route section, the length of the common fluid route section having at least the length of a fluid segment and not more than the length of the distance between two subsequent fluid segments so that at least one selected fluid segment can be positioned in the common fluid route section. Every fluid route comprises at least one valve for controlling the fluid and is fluidically connected to at least one actuator. Every valve and every actuator can be individually controlled. Upstream, inside or downstream of the common channel section at least one detection unit for the phase boundary between the fluid segment and the separation medium and at least one detection unit for the fluid segments is provided.

Description

Vorrichtung und Verfahren zum Positionieren und Ausschleusen von in Separationsmedium eingebetteten FluidkompartimentenDevice and method for positioning and discharging fluid compartments embedded in the separation medium
Die Erfindung betrifft eine Vorrichtung und ein Verfahren zum Positionieren und Ausschleusen von in einem Separationsmedium eingebetteten Fluidkompartimenten, insbesondere für die Mikrosystemtechnik.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.
Im Rahmen von mikrotechnischen Hochdurchsatzverfahren werden durch verschiedene Techniken große Probenzahlen mit kleinen Probenvolumina erzeugt, die in geeigneter Weise deponiert, gezielt adressiert und weiterverwendet werden sollen. Für die Deponierung der Proben werden üblicherweise Mikrotiterplatten verwendet, die mittels Pipettier-Robotik adressiert werden. Ein weiterer Ansatz besteht in der Erzeugung von Fluidkompartimenten, wobei im allgemeinen eine Probenflüssigkeit und eine mit ihr nichtmischbare Flüssigkeit oder ein Gas mittels Aktuatoren in einem geeigneten Chip auf die Weise zusammengeführt werden, dass die Probenflüssigkeit kompartimentiert wird und die erzeugten Fluidsegmente (im Folgenden als Kompartimente bezeichnet) in der anderen Flüssigkeit oder dem Gas (im Folgenden auch als Separationsmedium bezeichnet) eingebettet sind. Die Deponierung erfolgt dann vorzugsweise in einem angeschlossenen Schlauch oder einer Kapillare. Mit Hilfe geeigneter Chips besteht anschließend die Möglichkeit, ausgewählten oder allen Kompartimenten im Durchfluss weitere Fluide zuzudosieren. Bei dem Kompartiment-Fluid kann es sich gegebenenfalls um Wasser oder eine wässrige Lösung handeln. Die Kompartimente können dabei gegebenenfalls Edukte für eine chemische Reaktion, Enzyme, Substrate, Cofaktoren oder einzelne, mehrere einzelne, einen Verband oder Verbände von pro- und/oder eukaryotischen Zellen oder Indikatoren, insbesondere pH-Indikatoren, oder eine Kombination der genannten Inhalte enthalten. Auch können die Kompartimente an Mikrocarrier gekoppelte einzelne, mehrere einzelne, einen Verband oder Verbände von pro- und/oder eukaryotischen Zellen enthalten. Die zudosierten Fluide können beispielsweise Reaktanden, Substrate, Gase oder Wachstumseffektoren beinhalten. Auf diese Weise können die eingebetteten Kompartimente in ihrem Depot verschiedene Schicksale, wie unterschiedliche Produktbildung oder unterschiedliches Wachstum, haben. Dies erfordert zu einem gegebenen Zeitpunkt eine gezielte Ausschleusung bestimmter Kompartimente für eine weitere Verwendung. Vorzugsweise enthalten mindestens die Depots mindestens einen zusätzlichen Marker zur Identifikation mindestens eines Kompartimentes. Der Marker besteht vorzugsweise aus mindestens einem Fluidsegment, wobei das mindestens eine Fluidsegment zu einem Detektorsignal führt, das signifikant verschieden vom Detektorsignal aller Fluidsegmente ohne Markerfunktion und signifikant verschieden vom Detektorsignal des Separationsmediums ist.Within the framework of microtechnical high-throughput processes, large numbers of samples with small sample volumes are generated using various techniques, which should be deposited in a suitable manner, specifically addressed and used. 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. With the help of suitable chips it is then possible to add further fluids to selected or all compartments in the flow. 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. In this way, 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.
Das Strukturieren von Flüssigkeiten durch definiertes Dosieren von Flüssigkeitssegmenten, bspw. vermittels Pipetten, ist seit langem bekannt.The structuring of liquids by defined dosing of liquid segments, for example by means of pipettes, has been known for a long time.
So offenbart die Schrift DE 298 01 523.4 eine Pipette oder Mikroreaktor bestehend aus wenigstens einem Kapillarkanal, der durch einen mittels Mikrostrakturierungsverfahren in ein Substrat eingebrachten und abdeckbaren Graben gebildet ist, der einseitig mit einer Druckkammer in Verbindung gebracht ist, der Druckkammer ein ansteuerbares elektrisches Heizmittel in Form eines auf eine Außenwandung einer als steife Membran ausgebildeten Druckkammerwandung aufgebrachten Dünnschichtheizwiderstandes zugeordnet ist und ein Bereich der Verbindung zwischen dem Kapillarkanal und der Druckkammer mit Wärmesenkenmitteln versehen ist und der Kapillarkanal eine Flüssigkeitssäule oder einen Stößel aufnimmt.For example, 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 Form of 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.
Die Schrift WO 98/16312 offenbart eine Pipette, die im Pipettenspitzenbereich mit einem integrierten Verschlussmittel und mit wenigstens einem Filterelement versehen ist. Aus der Schrift DE 100 10 208.5-52 ist eine Mikrodosiervorrichtung zur definierten Abgabe kleiner in sich geschlossener Flüssigkeitsvolumina bekannt. Auch ist bekannt, dass ein Strukturieren von Flüssigkeiten in Kanälen oder Röhren durch definiertes Schalten von Ventilen o.a. in den zwangsgeführten Flüssigkeitsströmen möglich ist.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.
So offenbart bspw. die Schrift DE 198 47 952.2-09 einen Fluid- Stromschalter zum Manipulieren von mindestens zwei Flüssigkeitsströmen.For example, the document DE 198 47 952.2-09 discloses a fluid flow switch for manipulating at least two liquid flows.
Weiterhin ist bekannt, dass ein Strukturieren von Flüssigkeiten auf Oberflächen vermittels Ultraschall möglich ist.It is also known that it is possible to structure liquids on surfaces by means of ultrasound.
Die Schrift DE 100 55 318 AI offenbart ein Verfahren zur gezielten und gerichteten Manipulation kleiner Materialmengen auf Festkörperoberflächen und aus der Schrift DE 100 62 246 Cl entnimmt der Fachmann ein Verfahren und eine Vorrichtung zur Manipulation kleiner Flüssigkeitsmengen auf einer Festkörperoberfläche. Auf der Festkörperoberfläche gemäß DE 100 62 246 Cl ist mindestens ein Aufenthaltsbereich vorgesehen, der andere Benetzungseigenschaften aufweist als die umgebende Oberfläche, so dass Flussigkeitsleitwege vorgegeben sind, auf denen kleine Flüssigkeitsmengen bewegbar sind.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. On the solid surface according to DE 100 62 246 Cl at least one area is provided, which has different wetting properties than the surrounding surface, so that liquid flow paths are specified, on which small amounts of liquid can be moved.
Von der Methode der Hochdruckflüssigkeitschromatographie (HPLC) ist bekannt, dass in einen permanenten Flüssigkeitsstrom (Träger) kleine Volumina von Flüssigkeiten (Proben) sequenziell über ein Ventil zu Analysezwecken eingesteuert werden.It is known from the high pressure liquid chromatography (HPLC) method that small volumes of liquids (samples) are sequentially introduced into a permanent liquid flow (carrier) via a valve for analysis purposes.
Aus der Publikation von Burns u.a. ist ein in Mikrokapillaren geführtes flüssiges System bekannt, bei dem zwei flüssige Proben zusammengeführt werden und bei dem es durch in die flüssigkeitsführenden Mikrokapillaren einmündende gasführende Mikrokapillaren möglich ist, die Flüssigkeiten durch Gaseinleitung zu segmentieren. (M. A. Burns, B. N. Johnson, S. N. Brahmasandra, K. Handique, J. R. Webster, M. Krishnan, T. S. Sammarco, P. M. Man, D. Jones, D. Heldsinger, C. H. Mastrangelo and D. Burke,; An Integrated Nanoliter DNA Analysis Device; Sience, Vol. 282, 18.10.1998; Seiten 484-487)From the publication by Burns et al. a liquid system guided in microcapillaries is known in which two liquid samples are brought together and in which gas-conducting microcapillaries flowing into the liquid-carrying microcapillaries make it possible to segment the liquids by introducing gas. (MA Burns, BN Johnson, SN Brahmasandra, K. Handique, JR Webster, M. Krishnan, TS Sammarco, PM Man, D. Jones, D. Heldsinger, CH Mastrangelo and D. Burke ,; An Integrated Nanoliter DNA Analysis Device; Sience, vol. 282, October 18, 1998; pages 484-487)
Aus der Publikation von Schneegass und Köhler ist bekannt, dass eine Segmentierung von Flüssigkeiten in Mikrokanälen durch gezieltes Einbringen von Luftblasen zu erreichen ist (I. Schneegass, J. M. Köhler; Flow-through polymerase chain reactions in chip thermocyclers; Reviews in Molecular Biotechnology 82; 2001; 1001-121).From the publication by Schneegass and Köhler it is known that a segmentation of liquids in microchannels by targeted Air bubbles can be introduced (I. Schneegass, JM Köhler; Flow-through polymerase chain reactions in chip thermocyclers; Reviews in Molecular Biotechnology 82; 2001; 1001-121).
Weiterhin ist aus den Veröffentlichungen von Köhler, J. M., Dillner, U., Mokansky, A., Poser, S. and Schulz, T. ["Micro Channel reactors for fast thermocycling". In: 2nd International Conference on MicroreactionFurthermore, from the publications by Koehler, J.M., Dillner, U., Mokansky, A., Poser, S. and Schulz, T. ["Micro Channel reactors for fast thermocycling". In: 2nd International Conference on Microreaction
Technology (ed. Ehrfeld, W.) p. 241-247 (Springer, New Orleans, LA,Technology (ed. Ehrfeld, W.) p. 241-247 (Springer, New Orleans, LA,
USA, 1998)], Poser, S., Ehricht, R., Schulz, T., Uebel, S., Dillner, U., and Köhler, J. M. ["Rapid PCR in flow-through Si chip thermocyclers." 3th International Conference on Microreaction Technology, Frankfurt a.M., 294-301 (1999)] und Schneegaß, L, Bräutigam R., Köhler J.M.USA, 1998)], Poser, S., Ehricht, R., Schulz, T., Uebel, S., Dillner, U., and Köhler, J. M. ["Rapid PCR in flow-through Si chip thermocyclers." 3rd International Conference on Microreaction Technology, Frankfurt a.M., 294-301 (1999)] and Schneegaß, L, Bräüttam R., Köhler J.M.
["Miniaturized flow-through PCR with different template types in aMiniaturized flow-through PCR with different template types in a
Silicon chip thermocycler." Lab-on-a-chip 1: 42-49 (2001)] bekannt, dass Mineralöl als Trägermedium für den seriellen Fluß von Flüssigkeitströpfchen in einem Flüssigkeitsträgerstrom Verwendung finden kann, da die Flüssigkeitströpfchen nicht mit der Flüssigkeit desSilicon chip thermocycler. "Lab-on-a-chip 1: 42-49 (2001)] discloses that mineral oil can be used as a carrier medium for the serial flow of liquid droplets in a liquid carrier stream, since the liquid droplets are not in contact with the liquid of the
Trägerstroms mischbar sind (bspw. PCR-Lösung in Mineralöl).Carrier stream are miscible (for example. PCR solution in mineral oil).
Die Schrift DE 101 45 568.2 offenbart ein Verfahren zur Parallelkultivierung von Mikroorganismen in Mikrokapillaren in einem flüssigen Zweiphasensystem, wobei Flüssigkeitssegmente als Aufenthaltsräume für zu kultivierende Mikroorganismen dienen.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.
Alle bisher bekannten Mikrosyteme (Mikrokanäle) zum Führen von Flüssigkeitsströmen haben den Nachteil, dass ein gezieltes Ausschleusen bestimmter Flüssigkeitssegmente (Kompartimente) aus diesen Systemen (Mikrokanälen) nicht möglich ist.All previously known microsystems (microchannels) for guiding liquid streams have the disadvantage that it is not possible to specifically discharge certain liquid segments (compartments) from these systems (microchannels).
Der Erfindung liegt die Aufgabe zugrunde, eine Vorrichtung und ein Verfahren zum Positionieren und gezielten Ausschleusen bestimmter Fluidsegmente aus diesen Systemen anzugeben, so dass die ausgewählten Segmente einer weiteren Verwendung zuführbar sind.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.
Erfindungsgemäß wird die Aufgabe durch eine Vorrichtung gemäß Anspruch 1 und ein Verfahren gemäß Anspruch 8 gelöst. Vorteilhafte Ausgestaltungen sind in den untergeordneten Ansprüchen 2 bis 7 sowie 9 bis 20 angegeben. Die Erfindung wird nachstehend an Hand der schematischen Zeichnung näher erläutert. Es zeigt:According to the invention the object is achieved by a device according to claim 1 and a method according to claim 8. Advantageous embodiments are specified in the subordinate claims 2 to 7 and 9 to 20. The invention is explained below with reference to the schematic drawing. It shows:
Fig. 1 eine schematische Darstellung der erfindungsgemäßen Vorrichtung.Fig. 1 is a schematic representation of the device according to the invention.
Das zentrale Bauteil der Vorrichtung ist eine Anordnung, vorzugsweise ein Mikrochip (1), der mindestens zwei Kanäle (2), die vorzugsweise einen runden Querschnitt mit einem Durchmesser im Bereich von 0,1 - 2 mm aufweisen, enthält, wobei alle dieser mindestens zwei Kanäle in einen gemeinsamen Kanalabschnitt (3) einmünden und wobei alle dieser mindestens zwei Kanäle fluidisch miteinander verbunden sind. Die Länge des gemeinsamen Kanalabschαittes (L) beträgt dabei mindestens die Länge eines Fluidsegmentes und höchstens die Länge des Abstandes zwischen zwei aufeinanderfolgenden Fluidsegmenten. Die innere Oberfläche der Kanäle weist dabei für das Separationsmedium benetzende und für das Kompartimentfluid nichtbenetzende Eigenschaften auf. Jede der aus dieser Anordnung resultierenden Fluidstrecken ist getrennt adressierbar und ansteuerbar. Dazu ist jeder der mindestens zwei Kanäle mit mindestens einem Ventil (4) verbunden bzw. ist mindestens ein Ventil in jeden Kanal integriert. Durch die Schaltung der Ventile werden ausgewählte Fluidstrecken für eine Passage geöffnet und die für den augenblicklichen Prozessschritt nicht benötigten Fluidstrecken sind geschlossen. Mindestens einer der Kanäle ist mit einem bidirektionalen Aktuator (5), vorzugsweise einer regelbaren Mikropumpe verbunden bzw. ist dieser Aktuator in den Kanal integriert. Mit Hilfe dieses bidirektionalen Aktuators wird die Strömungsgeschwindigkeit des Fluides reguliert. Darüberhinaus verfügt dieser Aktuator über eine Möglichkeit der Flussrichtungsumkehr, so dass sowohl die Strömungsgeschwindigkeit, als auch die Strömungsrichtung des Fluidstromes mit demselben Aktuator regulierbar sind. Mit Hilfe dieser Vorrichtung können aus jedem Kanal Fluidströme mit oder ohne Fluidsegmente über den gemeinsamen Kanalabschnitt in einzelne oder jeden der sich an diesen Kanalabschnitt anschließenden Kanäle gefordert werden. Mindestens einer der Kanäle ist mit einem Reservoir (6) für in Separationsmedium eingebettete Fluidsegmente verbunden. Bei dem Reservoir handelt es sich vorzugsweise um einen Schlauch oder eine Kapillare. Die Vorrichtung beinhaltet zudem mindestens vor, im oder nach dem gemeinsamen Kanalabschnitt mindestens eine Detektionseinheit (7a) für die Phasengrenze zwischen Fluidsegment und Separationsmedium und mindestens vor, im oder nach dem gemeinsamen Kanalabschnitt mindestens eine Detektionseinheit (7b) für den Fluidsegmentinhalt. Dabei können die Detektion der Phasengrenze und des Fluidsegmentinhaltes sowohl in der gleichen Detektionseinheit und/oder mit dem gleichen Detektionsverfahren als auch in verschiedenen Detektionseinheiten und/oder mit verschiedenen Detektionsverfahren ausgeführt werden. Die Detektion kann vorteilhaft mittels optischen Verfahren, wie Brechung, Streuung, Absorption, Transmission, Emission und Fluoreszenz oder mittels impedimetrischen Verfahren, wie Elektroimpedanzspektroskopie, oder durch eine Kombination dieser Verfahren erfolgen. Nach der erfolgten Detektion muss ein auszuschleusendes Fluidsegment zunächst im gemeinsamen Kanalabschnitt positioniert werden. Dies geschieht erfindungsgemäß durch Öffnung der Ventile für die entsprechende Fluidstrecke und die Verringerung der Strömungsgeschwindigkeit im gemeinsamen Kanalabschnitt auf nahezu Null durch eine Minderung des Druckimpulses des bidirektionalen Aktuators (5), wobei die Flussrichtung des Aktuators so geschaltet ist, dass das betreffende Fluidsegment in Richtung des gemeinsamen Kanalabschnittes und in diesen hinein transportiert wird. Der Vorgang der Positionierung kann sowohl manuell ausgeführt werden, als auch dadurch automatisiert werden, dass nach erfolgter Detektion zu einem reproduzierbaren Zeitpunkt mindestens ein Steuersignal an die entsprechenden Ventile und den Aktuator gegeben wird, wodurch eine vorgegebene Minderung des Druckimpulses des Aktuators und eine definierte Flussrichtung und Fluidstrecke vorgegeben werden, und mittels einer über den reproduzierbaren Signalzeitpunkt und dem momentanen Abstand des betreffenden Fluidsegmentes vom inneren Bereich des gemeinsamen Kanalabschnittes festgelegten Vorhaltezeit dieses Fluidregime solange abgearbeitet wird, bis sich das zu positionierende Fluidsegment im inneren Bereich des gemeinsamen Kanalabschnittes befindet. Neben der Positionierung auf fluidischem Wege kann die Positionierung durch ein elektrokinetisches Verfahren erfolgen, wobei dieses elektrokinetische Verfahren ein elektrophoretisches, dielektrophoretisches, elektroosmotisches Verfahren, ein Lasertweezer-Verfahren oder ein Verfahren mittels Feldkräften über Quadrupole oder Oktopole oder eine Kombination dieser Verfahren sein kann. Ferner kann die Positionierung über ein magnetisches oder ein auf Schwerkraft basierendes Verfahren oder eine Kombination einzelner der genannten Verfahren erfolgen.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. For this purpose, 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. By switching the valves, selected fluid paths are opened for a passage and the fluid paths that are not required for the current process step are closed. 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. With the help of this bidirectional actuator, the flow velocity of the fluid is regulated. In addition, 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. With the aid of this device, 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. In which The reservoir is preferably a tube or a capillary. 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. After the detection has taken place, 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. In addition to the positioning in a fluidic way, 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. Furthermore, the positioning can be carried out using a magnetic method or a method based on gravity or a combination of individual methods.
Die Ausschleusung des positionierten Fluidsegmentes in einen der angeschlossenen Kanäle erfolgt dann erfindungsgemäß durch Öffnung der Ventile für die entsprechende Fluidstrecke und durch einen gezielten Druckimpulsaufbau in dem gemeinsamen Kanalabschnitt. Dazu ist in der erfindungsgemäßen Vorrichtung mindestens ein Aktuator (8) zur Erzeugung eines gezielten Druckimpulsaufbaus enthalten. Dabei handelt es sich vorteilhaft um eine Pumpe oder einen gasgekoppelten Druck- oder Sauganschluss. Der Vorgang der Ausschleusung kann sowohl manuell ausgeführt werden, als auch dadurch automatisiert werden, dass nach Abarbeitung des Fluidregimes für die Positionierung mindestens ein Steuersignal an die entsprechenden Ventile und die mindestens eine Baugruppe zur Erzeugung eines gezielten Druckimpulsaufbaus gegeben wird, das dazu führt, dass der gezielte Druckimpulsaufbau in dem gemeinsamen Kanalabschnitt ausgeführt wird. Die erfindungsgemäße Vorrichtung enthält optional einen Steuerrechner (9) zur Abarbeitung der Fluidsteuerungsregime. Zur Aufnahme des ausgeschleusten Fluidsegmentes beinhaltet die Vorrichtung optional mindestens eine Depotvorrichtung (10), wobei die mindestens eine Depotvorrichtung fluidisch mit mindestens einem Kanal verbunden ist oder in diesen integriert ist. BezugszeichenlisteThe discharge of the positioned fluid segment into one of the connected channels then takes place according to the invention by opening the valves for the corresponding fluid path and by a specific pressure pulse build-up in the common channel section. For this purpose, 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. To accommodate the discharged fluid segment, 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
1 Mikrochip1 microchip
2 Kanäle2 channels
3 gemeinsamer Kanalabschnitt3 common channel section
4 Ventil4 valve
5 bidirektionaler Aktuator5 bidirectional actuator
6 Reservoir6 reservoir
7 Detektionseinheit7 detection unit
8 Aktuator8 actuator
9 Steuerrechner9 control computer
10 - Depotvorrichtung10 - deposit device
L Länge des gemeinsamen Kanalabschnitts L length of the common channel section

Claims

Patentansprüche claims
1. Vorrichtung zum Positionieren und Ausschleusen von mindestens einem in einem Separationsmedium eingebetteten Fluidsegment umfassend mindestens zwei Flussigkeitsleitwege, wobei mindestens einer der Flussigkeitsleitwege mit einem Reservoir für in Separationsmedium eingebettete Fluidsegmente verbunden ist, die Flussigkeitsleitwege in einen gemeinsamen Leitwegabschnitt einmünden, die Länge des gemeinsamen Leitwegabschnittes mindestens die1.Device for positioning and discharging at least one fluid segment embedded in a separation medium, comprising at least two liquid guide paths, at least one of the liquid guide paths being connected to a reservoir for fluid segments embedded in the separation medium, the liquid guide paths opening into a common route section, the length of the common route section at least the
Länge eines Fluidsegments und höchstens die Länge des Abstandes zweier aufeinanderfolgender Fluidsegmente ausweist, so dass mindestens ein ausgewähltes Fluidsegment im gemeinsamen Leitwegabschnitt positionierbar ist, jeder Leitweg mindestens ein Ventil besitzt und mit mindestens einem Aktuator fluidisch verbunden ist, jedes Ventil und jeder Aktuator einzeln ansteuerbar ist, sich vor, im oder nach dem gemeinsamen Leitwegabschnitt mindestens eine Detektionseinheit für die Phasengrenze zwischen Fluidsegment und Separationsmedium befindet, sich vor, im oder nach dem gemeinsamen Leitwegabschnitt mindestens eine Detektionseinheit für die Fluidsegmente befindet.Shows the length of a fluid segment and at most the length of the distance between two successive fluid segments, so that at least one selected fluid segment can be positioned in the common route section, each route has at least one valve and is fluidly connected to at least one actuator, each valve and each actuator can be controlled individually, there is at least one detection unit for the phase boundary between the fluid segment and the separation medium before, in or after the common route section, at least one detection unit for the fluid segments is located before, in or after the common route section.
2. Vorrichtung nach Anspruch 1, dadurch gekennzeichnet, dass die Flussigkeitsleitwege vorzugsweise durch einen Kanal mit rundem2. Device according to claim 1, characterized in that the liquid routes preferably through a channel with a round
Querschnitt und mit einem Durchmesser von 0,1 mm bis 2 mm gebildet sind.Cross section and with a diameter of 0.1 mm to 2 mm are formed.
3. Vorrichtung nach Anspruch 1, dadurch gekennzeichnet, dass die innere Oberfläche der Flussigkeitsleitwege für das3. Apparatus according to claim 1, characterized in that the inner surface of the liquid routes for
Separationsmedium benetzende und für die Fluidsegmente nicht benetzende Eigenschaften aufweist.Has separation medium wetting and non-wetting properties for the fluid segments.
4. Vorrichtung nach Anspruch 1, dadurch gekennzeichnet, dass das Reservoir vorzugsweise ein Schlauch oder eine Kapillare ist. 4. The device according to claim 1, characterized in that the reservoir is preferably a tube or a capillary.
5. Vorrichtung nach Anspruch 1, dadurch gekennzeichnet, dass der Aktuator bidirektional ist.5. The device according to claim 1, characterized in that the actuator is bidirectional.
6. Vorrichtung nach Anspruch 5, dadurch gekennzeichnet, dass der Aktuator mit einer regelbaren Mikropumpe verbunden ist.6. The device according to claim 5, characterized in that the actuator is connected to a controllable micropump.
7. Vorrichtung nach Anspruch 1, dadurch gekennzeichnet, dass der Aktuator manuell oder automatisch ansteuerbar ist.7. The device according to claim 1, characterized in that the actuator can be controlled manually or automatically.
8. Verfahren zum Positionieren und Ausschleusen mindestens eines Fluidsegments unter Verwendung einer Vorrichtung nach einem oder mehreren der voranstehenden Ansprüche, dadurch gekennzeichnet, dass das Positionieren durch eine definierte Steuerung der Fluidströmung in mindestens einem Kanal realisiert wird, indem die Verringerung der Fluidstromgeschwindigkeit im gemeinsamen Kanalabschnitt auf nahezu Null durch eine Minderung des Druckimpulses des bidirektionalen Aktuators erzielt wird und dabei das zu positionierende Fluidsegment in Richtung des gemeinsamen Kanalabschnittes transportiert wird, wobei der Vorgang der Positionierung manuell ausgeführt oder durch ein8. A method for positioning and discharging at least one fluid segment using a device according to one or more of the preceding claims, characterized in that the positioning is realized by a defined control of the fluid flow in at least one channel by reducing the fluid flow velocity in the common channel section almost zero is achieved by a reduction in the pressure pulse of the bidirectional actuator and the fluid segment to be positioned is transported in the direction of the common channel section, the positioning process being carried out manually or by a
Steuersignal, das zu einem reproduzierbaren Zeitpunkt nach erfolgter Detektion erfolgt, automatisch gestartet werden kann und dass das Fluidsegment zu einem Detektorsignal führt, das signifikant verschieden vom Detektorsignal des Separationsmediums ist und somit eine Identifikation eines jedenControl signal that occurs at a reproducible point in time after detection, can be started automatically and that the fluid segment leads to a detector signal that is significantly different from the detector signal of the separation medium and thus an identification of each
Fluidsegments in dem Kanalabschnitt möglich ist und das Ausschleusen mindestens eines im gemeinsamen Kanalabschnitt positionierten Fluidsegments durch einen gezielten Druckimpulsaufbau in dem gemeinsamen Kanalabschnitt mittels des Aktuators eines Kanals erfolgt, wobei der Vorgang desFluid segment is possible in the channel section and the discharge of at least one fluid segment positioned in the common channel section takes place by means of a targeted pressure pulse build-up in the common channel section by means of the actuator of a channel, the process of
Ausschleusens manuell ausführbar oder mittels eines Steuersignals automatisierbar ist.Discharge can be carried out manually or can be automated by means of a control signal.
9. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass nach dem Ausschleusen das ausgeschleuste Fluidsegment einer Depotvorrichtung zur Weiterverarbeitung zugeführt wird.9. A method for positioning and discharging a fluid segment according to claim 8, characterized in that after the discharge, the discharged fluid segment is fed to a depot device for further processing.
10. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass die10. The method for positioning and discharging a fluid segment according to claim 8, characterized in that the
Fluidströme mit oder ohne Fluidsegmente aus jedem Kanal über den gemeinsamen Kanalabschnitt in jeden sich an diesenFluid flows with or without fluid segments from each channel through the common channel section into each itself
Kanalabschnitt anschließenden Kanal gefordert werden können.Channel section connecting channel can be requested.
11. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass die Positionierung mindestens eines ausgewählten Fluidsegments im gemeinsamen Kanalabschnitt durch ein elektrokinetisches Verfahren erfolgt, wobei dieses ein elektrophoretiscb.es, dielektrophoretisches, elektroosmotisches oder Lasertweezer-11. The method for positioning and discharging a fluid segment according to claim 8, characterized in that the positioning of at least one selected fluid segment in the common channel section is carried out by an electrokinetic method, this being an electrophoretic, dielectrophoretic, electroosmotic or laser tweezer.
Verfahren, oder eine Kombination mindestens zweier dieser Verfahren sein kann.Process, or a combination of at least two of these processes.
12. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass die12. The method for positioning and discharging a fluid segment according to claim 8, characterized in that the
Positionierung mindestens eines ausgewählten Fluidsegments im gemeinsamen Kanalabschnitt durch ein auf Schwerkraft basierendes Verfahren erfolgt.Positioning of at least one selected fluid segment in the common channel section is carried out by a method based on gravity.
13. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass die Positionierung mindestens eines ausgewählten Fluidsegments im gemeinsamen Kanalabschnitt durch ein magnetisches Verfahren erfolgt.13. A method for positioning and discharging a fluid segment according to claim 8, characterized in that the positioning of at least one selected fluid segment in the common channel section is carried out by a magnetic method.
14. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass die Detektion des Fluidsegments mittels eines optischen Verfahrens erfolgt. 14. A method for positioning and discharging a fluid segment according to claim 8, characterized in that the detection of the fluid segment is carried out by means of an optical method.
15. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass die Detektion des Fluidsegments mittels eines impedimetrischen Verfahrens erfolgt.15. A method for positioning and discharging a fluid segment according to claim 8, characterized in that the detection of the fluid segment is carried out by means of an impedimetric method.
16. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Ansprach 8, dadurch gekennzeichnet, dass die Detektion der Phasengrenze zwischen Separationsmedium und Fluidsegment mittels eines optischen Verfahrens erfolgt.16. A method for positioning and discharging a fluid segment according to spoke 8, characterized in that the phase boundary between the separation medium and the fluid segment is detected by means of an optical method.
17. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass die Detektion der Phasengrenze zwischen Separationsmedium und Fluidsegment mittels eines impedimetrischen Verfahrens erfolgt.17. A method for positioning and discharging a fluid segment according to claim 8, characterized in that the phase boundary between the separation medium and the fluid segment is detected by means of an impedimetric method.
18. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass die die Detektion der Phasengrenze zwischen Separationsmedium und Fluidsegment und die Detektion des Fluidsegments mit der gleichen Detektionseinheit und/oder durch das gleiche18. The method for positioning and discharging a fluid segment according to claim 8, characterized in that the detection of the phase boundary between the separation medium and the fluid segment and the detection of the fluid segment with the same detection unit and / or by the same
Detektionsverfahren ausgeführt werden.Detection methods are carried out.
19. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass das Separationsmedium eine Flüssigkeit ist.19. A method for positioning and discharging a fluid segment according to claim 8, characterized in that the separation medium is a liquid.
20. Verfahren zum Positionieren und Ausschleusen eines Fluidsegments nach Anspruch 8, dadurch gekennzeichnet, dass das Separationsmedium ein Gas ist. 20. A method for positioning and discharging a fluid segment according to claim 8, characterized in that the separation medium is a gas.
PCT/DE2004/001055 2003-05-19 2004-05-18 Device and method for positioning and removing fluid compartments that are embedded in a separation medium WO2004103564A1 (en)

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