WO2004087321A1 - Microfluidic device for the controlled directing of a fluid into a duct - Google Patents

Microfluidic device for the controlled directing of a fluid into a duct Download PDF

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Publication number
WO2004087321A1
WO2004087321A1 PCT/EP2004/003474 EP2004003474W WO2004087321A1 WO 2004087321 A1 WO2004087321 A1 WO 2004087321A1 EP 2004003474 W EP2004003474 W EP 2004003474W WO 2004087321 A1 WO2004087321 A1 WO 2004087321A1
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Prior art keywords
channel
fluid
duct
crossing
microfluidic device
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PCT/EP2004/003474
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German (de)
French (fr)
Inventor
Roland HERGENRÖDER
Peter Jacob
Markus Pfister
Oliver Vogt
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Siemens Aktiengesellschaft
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Publication of WO2004087321A1 publication Critical patent/WO2004087321A1/en

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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
    • B01L3/50273—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 the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0605—Metering of fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • 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
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal 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
    • 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
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • 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

Definitions

  • Microfluidic device for the controlled introduction of a fluid into a channel
  • EP 0 775 306 B1 discloses a microfluidic device for injecting a first fluid in the form of a dosing plug from a first channel into a second channel containing a second fluid and for electrokinetic delivery of the fluids through the second channel Channel crossing, the first channel opens straight into the second channel and a third channel containing the second fluid and a fourth channel open on the opposite side. Electrodes are arranged at locations of the four channels distant from the channel crossing, in particular in reservoirs for the fluids provided there, in order to convey the fluids electrokinetically through the channels by applying different electrical potentials.
  • the potentials are set in such a way that the second fluid is conveyed electrokinetically from the third channel both into the second and into the fourth channel, wherein it also pumps the electrokinetically from the first channel in the direction of the channel crossing keeps the first fluid away from the second channel and completely redirects it to the fourth channel.
  • the potential relationships are changed such that the second fluid is only conveyed from the third channel into the second channel, but not into the fourth channel, so that the first fluid from the first channel together with the second Fluid enters the second channel.
  • the device After a short time, the device is switched back to the first operating state, in which case the first fluid that entered the second channel during the second operating state is conveyed electrokinetically together with the second fluid through the second channel and is analyzed, for example, by capillary electrophoresis.
  • the known device requires two different voltage sources, one of which is connected to the first channel with a voltage pole and the other is connected to the third channel with a voltage pole. Furthermore, when the first fluid is injected into the second channel, it is mixed with the second fluid flowing simultaneously into the second channel, so that it cannot be injected into the second channel in the form of a sharply delimited dosing plug.
  • a microfluidic device for the controlled introduction of a first fluid from a first channel into a second channel containing a second fluid and for electrokinetic delivery of the fluids through the second channel, with a channel crossing into the the first channel, a third channel containing the second fluid, the second channel and a fourth channel open in this order in a clockwise or counter-clockwise direction, with a device which conveys the first fluid by means of pressure through the first channel in the direction of the channel crossing and with a single voltage source, one with a voltage pole to a point on the third channel distant from the channel crossing and with the other Voltage pole at points of both the second and the fourth channel distant from the channel crossing is switchable.
  • a pump is particularly suitable as a device for the pressure-driven delivery of the first fluid.
  • the device can have a fluid reservoir connected to the first channel at a location remote from the channel crossing, which is arranged higher than the channel crossing, so that the first fluid is directed towards the by the hydrostatic pressure resulting from the height difference Channel crossing is promoted.
  • the pressure for conveying the first fluid can also be generated in some other way, for example by centrifugal forces, capillary forces or electrolysis.
  • the microfluidic device manages with a single voltage source in order to electrokinetically convey the first fluid introduced into the second channel together with the second fluid located there through the second channel.
  • the second fluid is conveyed electrokinetically from the third channel into the fourth channel, so that the first fluid in the first channel is prevented from entering the second channel and is instead deflected by the flow of the second fluid into the fourth channel.
  • the voltage source of the third channel and / or the second and fourth channels is switched off, so that the first fluid is pressure-driven into the channel crossing and in
  • the second fluid is not simultaneously conveyed into the second channel, the two fluids are not mixed, so that the first fluid reaches the second channel as a sharply defined dosing plug.
  • the voltage source is only switched off by the fourth channel, so that here too the first fluid is driven by pressure into the channel crossing and further into the second channel, but in addition the second fluid is also conveyed electrokinetically from the third channel into the second channel , This is particularly advantageous if the first fluid is to be mixed with the second fluid when it is introduced into the second channel.
  • the voltage source is then connected again to the third, second and fourth channels, the first fluid which has entered the second channel is conveyed electrokinetically together with the second fluid through the second channel and at the same time the first fluid which is pressure-driven in the first channel when it enters the second channel prevented. Since only a single voltage is applied to the channels, the voltage can largely be freely selected and, for example, optimally set for an electrophoretic separation of the first fluid in the second channel.
  • FIG. 1 is a very simplified embodiment of the device according to the invention.
  • Figures 2, 3 and 4 exemplify the promotion of the fluids through the channel crossing and Figure 5 shows another simplified embodiment of the device according to the invention.
  • Figure 1 shows an arrangement, for example microstructured on a chip, for treating fluids with reservoirs 1, 2, 3, 4 for receiving the fluids before or after their treatment and with a channel system 5 which connects the reservoirs 1 to 4 to one another and in which the treatment of the fluids takes place.
  • the channel system 5 consists of a first one
  • Electrodes 11, 12 and 13 are arranged in the reservoirs 2, 3 and 4, of which the electrode 12 in the reservoir 3 is connected via a controllable switch 14 to a voltage pole 15 of a voltage source 16, the other voltage pole 17, here via a Earth connection, is connected to the electrodes 11 and 13 in the reservoirs 2 and 4, respectively.
  • the second fluid 20 is again electrokinetically conveyed from the third channel 8 into the second channel 7 and the fourth channel 9, which, as shown in FIG second channel 7, first fluid 18 passed through the second channel 7 together with the second fluid 20, while the pressure-driven fluid 18 is diverted from the first channel 6 by the corresponding partial flow of the second fluid 20 into the fourth channel 9.
  • the exemplary embodiment shown in FIG. 5 differs from that according to FIG. 1 in that the electrodes 11 and 12 are firmly connected to the voltage source 16 and only the electrode 13 can be selectively connected to the voltage source 16 via the controllable switch 14 or can be separated therefrom. If the switch 14 is opened to introduce the first fluid 18 from the first channel 6 into the second channel 7, only the electrokinetic delivery of the second one
  • Fluids 20 are switched off from the third channel 8 into the fourth channel 9, so that the first fluid 18 then penetrates pressure-driven from the first channel 6 into the second channel 7; the second fluid 20 is still conveyed kinetically from the third channel 8 into the second channel 7.
  • the channels 6 to 9 open into the channel crossing 10 at right angles.
  • the channels 6 to 9 can also open into the channel crossing 10 at different angles, the first channel 6 also not going straight into the second channel 7 and the third channel 8 must continue straight into the fourth channel 9.

Abstract

Disclosed is a microfluidic device for directing a first fluid in a controlled manner from a first duct into a second duct containing a second fluid and for electrokinetically conveying the fluids through the second duct. The first duct, a third duct containing the second fluid, the second duct, and a fourth duct extend clockwise or counterclockwise in said order into a duct intersection. According to the invention, only one voltage source (16) is provided, one pole (15) of which can be connected to a point of the third duct (8) located at a distance from the duct intersection (10) while the other pole (17) thereof can be connected to points of both the second duct (7) and the fourth duct (9) located at a distance from the duct intersection (10) when the first fluid (18) is conveyed in a pressure-driven manner through the first duct (6) in the direction of the duct intersection (10).

Description

Beschreibungdescription
Mikrofluidische Einrichtung zur gesteuerten Einleitung eines Fluids in einen KanalMicrofluidic device for the controlled introduction of a fluid into a channel
Zur Behandlung von Fluiden, insbesondere für deren Analyse, beispielsweise durch Kapillarelektrophorese, kann es notwendig sein, zwei Fluidströme derart miteinander zu koppeln, dass für eine bestimmte Zeit oder in einer vorgegebenen Menge eine Probe des einen Fluidstroms an einer Kreuzungs- oder Kontaktstelle in den anderen Fluidstrom eingefügt wird.For the treatment of fluids, in particular for their analysis, for example by capillary electrophoresis, it may be necessary to couple two fluid streams with one another in such a way that a sample of one fluid stream at a crossing or contact point in the other for a certain time or in a predetermined amount Fluid flow is inserted.
So ist aus der EP 0 775 306 Bl eine mikrofluidische Einrichtung zur Injektion eines ersten Fluids in Form eines Dosier- pfropfes aus einem ersten Kanal in einen ein zweites Fluid enthaltenden zweiten Kanal und zur elektrokinetischen Förderung der Fluide durch den zweiten Kanal bekannt, wobei an einer Kanalkreuzung der erste Kanal geradeaus in den zweiten Kanal mündet und auf einer Seite ein dritter, das zweite Fluid enthaltender Kanal und auf der gegenüberliegenden Seite ein vierter Kanal einmünden. An von der Kanalkreuzung entfernten Stellen der vier Kanäle, insbesondere in dort vorgesehenen Reservoirs für die Fluide, sind Elektroden angeordnet, um durch Anlegen von unterschiedlichen elektrischen Po- tenzialen die Fluide elektrokinetisch durch die Kanäle zu fördern.For example, EP 0 775 306 B1 discloses a microfluidic device for injecting a first fluid in the form of a dosing plug from a first channel into a second channel containing a second fluid and for electrokinetic delivery of the fluids through the second channel Channel crossing, the first channel opens straight into the second channel and a third channel containing the second fluid and a fourth channel open on the opposite side. Electrodes are arranged at locations of the four channels distant from the channel crossing, in particular in reservoirs for the fluids provided there, in order to convey the fluids electrokinetically through the channels by applying different electrical potentials.
In einem ersten Betriebszustand der bekannten Einrichtung sind die Potenziale derart eingestellt, dass das zweite Fluid elektrokinetisch aus dem dritten Kanal sowohl in den zweiten als auch in den vierten Kanal gefördert wird, wobei es das ebenfalls elektrokinetisch aus dem ersten Kanal in Richtung auf die Kanalkreuzung geförderte erste Fluid von dem zweiten Kanal fern hält und vollständig in den vierten Kanal umlei- tet. In einem zweiten Betriebszustand der bekannten Einrichtung werden die Potenzialverhältnisse derart geändert, dass das zweite Fluid aus dem dritten Kanal nur noch in den zweiten Kanal, nicht aber in den vierten Kanal gefördert wird, so dass das erste Fluid aus dem ersten Kanal zusammen mit dem zweiten Fluid in den zweiten Kanal gelangt.In a first operating state of the known device, the potentials are set in such a way that the second fluid is conveyed electrokinetically from the third channel both into the second and into the fourth channel, wherein it also pumps the electrokinetically from the first channel in the direction of the channel crossing keeps the first fluid away from the second channel and completely redirects it to the fourth channel. In a second operating state of the known device, the potential relationships are changed such that the second fluid is only conveyed from the third channel into the second channel, but not into the fourth channel, so that the first fluid from the first channel together with the second Fluid enters the second channel.
Nach einer kurzen Zeit wird die Einrichtung wieder in den ersten Betriebszustand umgeschaltet, wobei dann das während des zweiten Betriebszustandes in den zweiten Kanal gelangte erste Fluid zusammen mit dem zweiten Fluid durch den zweiten Kanal elektrokinetisch gefördert und beispielsweise durch Kapillarelektrophorese analysiert wird.After a short time, the device is switched back to the first operating state, in which case the first fluid that entered the second channel during the second operating state is conveyed electrokinetically together with the second fluid through the second channel and is analyzed, for example, by capillary electrophoresis.
Bei der bekannten Einrichtung werden zwei unterschiedliche Spannungsquellen benötigt, von denen eine mit einem Spannungspol an dem ersten Kanal und die andere mit einem Spannungspol an dem dritten Kanal angeschlossen ist. Weiterhin wird das erste Fluid bei seiner Injektion in den zweiten Ka- nal mit dem gleichzeitig in den zweiten Kanal einfließenden zweiten Fluid vermischt, so dass es nicht in Form eines scharf begrenzten Dosierpfropfes in den zweiten Kanal injizierbar ist.The known device requires two different voltage sources, one of which is connected to the first channel with a voltage pole and the other is connected to the third channel with a voltage pole. Furthermore, when the first fluid is injected into the second channel, it is mixed with the second fluid flowing simultaneously into the second channel, so that it cannot be injected into the second channel in the form of a sharply delimited dosing plug.
Gemäß der Erfindung werden die vorstehend genannten Nachteile vermieden durch eine mikrofluidische Einrichtung zur gesteuerten Einleitung eines ersten Fluids aus einem ersten Kanal in einen ein zweites Fluid enthaltenden zweiten Kanal und zur elektrokinetischen Förderung der Fluide durch den zweiten Ka- nal, mit einer Kanalkreuzung, in die der erste Kanal, ein das zweite Fluid enthaltender dritter Kanal, der zweite Kanal und ein vierter Kanal in dieser Reihenfolge im oder gegen den Uhrzeigersinn einmünden, mit einer das erste Fluid mittels Druck durch den ersten Kanal in Richtung auf die Kanalkreu- zung fördernden Vorrichtung und mit einer einzigen Spannungsquelle, die mit einem Spannungspol an eine von der Kanalkreuzung entfernte Stelle des dritten Kanals und mit dem anderen Spannungspol an von der Kanalkreuzung entfernte Stellen sowohl des zweiten als auch des vierten Kanals schaltbar ist.According to the invention, the above-mentioned disadvantages are avoided by a microfluidic device for the controlled introduction of a first fluid from a first channel into a second channel containing a second fluid and for electrokinetic delivery of the fluids through the second channel, with a channel crossing into the the first channel, a third channel containing the second fluid, the second channel and a fourth channel open in this order in a clockwise or counter-clockwise direction, with a device which conveys the first fluid by means of pressure through the first channel in the direction of the channel crossing and with a single voltage source, one with a voltage pole to a point on the third channel distant from the channel crossing and with the other Voltage pole at points of both the second and the fourth channel distant from the channel crossing is switchable.
Als Vorrichtung zur druckgetriebenen Förderung des ersten Fluids kommt insbesondere eine Pumpe in Betracht. Alternativ kann die Vorrichtung ein an einer von der Kanalkreuzung entfernten Stelle mit dem ersten Kanal verbundenes Fluidreser- voir aufweisen, das höher als die Kanalkreuzung angeordnet ist, so dass das erste Fluid durch den sich aus der Höhen- differenz ergebenden hydrostatischen Druck in Richtung auf die Kanalkreuzung gefördert wird. Darüber hinaus kann der Druck zur Förderung des ersten Fluids auch anderweitig, beispielsweise durch Zentrifugalkäfte, Kapillarkräfte oder Elektrolyse, erzeugt werden.A pump is particularly suitable as a device for the pressure-driven delivery of the first fluid. As an alternative, the device can have a fluid reservoir connected to the first channel at a location remote from the channel crossing, which is arranged higher than the channel crossing, so that the first fluid is directed towards the by the hydrostatic pressure resulting from the height difference Channel crossing is promoted. In addition, the pressure for conveying the first fluid can also be generated in some other way, for example by centrifugal forces, capillary forces or electrolysis.
Im Unterschied zu der bekannten Einrichtung kommt die erfindungsgemäße mikrofluidische Einrichtung mit einer einzigen Spannungsquelle aus, um das in den zweiten Kanal eingeleitete erste Fluid zusammen mit dem dort befindlichen zweiten Fluid elektrokinetisch durch den zweiten Kanal zu fördern. Gleichzeitig wird das zweite Fluid elektrokinetisch aus dem dritten Kanal in den vierten Kanal gefördert, so dass das erste Fluid in dem ersten Kanal daran gehindert ist, in den zweiten Kanal einzutreten und statt dessen von der Strömung des zweiten Fluids in den vierten Kanal umgelenkt wird.In contrast to the known device, the microfluidic device according to the invention manages with a single voltage source in order to electrokinetically convey the first fluid introduced into the second channel together with the second fluid located there through the second channel. At the same time, the second fluid is conveyed electrokinetically from the third channel into the fourth channel, so that the first fluid in the first channel is prevented from entering the second channel and is instead deflected by the flow of the second fluid into the fourth channel.
Zum Einleiten des ersten Fluids aus dem ersten Kanal in den zweiten Kanal wird die Spannungsquelle von dem dritten Kanal und/oder dem zweiten und vierten Kanal abgeschaltet, so dass das erste Fluid druckgetrieben in die Kanalkreuzung und imTo introduce the first fluid from the first channel into the second channel, the voltage source of the third channel and / or the second and fourth channels is switched off, so that the first fluid is pressure-driven into the channel crossing and in
Weiteren in den zweiten Kanal und in geringerem Maße auch in den dritten und vierten Kanal eindringt. Da im Unterschied zu der bekannten Einrichtung das zweite Fluid nicht gleichzeitig in den zweiten Kanal gefördert wird, kommt es auch zu keiner Mischung der beiden Fluide, so dass das erste Fluid als scharf begrenzter Dosierpfropf in den zweiten Kanal gelangt. Alternativ wird die Spannungsquelle nur von dem vierten Kanal abgeschaltet, so dass auch hier das erste Fluid druckgetrieben in die Kanalkreuzung und im Weiteren in den zweiten Kanal eindringt, zusätzlich aber auch das zweite Fluid elektrokine- tisch aus dem dritten Kanal in den zweiten Kanal gefördert wird. Dies ist insbesondere dann von Vorteil, wenn das erste Fluid bei seiner Einleitung in den zweiten Kanal mit dem zweiten Fluid gemischt werden soll.Further penetrates into the second channel and to a lesser extent into the third and fourth channels. Since, in contrast to the known device, the second fluid is not simultaneously conveyed into the second channel, the two fluids are not mixed, so that the first fluid reaches the second channel as a sharply defined dosing plug. Alternatively, the voltage source is only switched off by the fourth channel, so that here too the first fluid is driven by pressure into the channel crossing and further into the second channel, but in addition the second fluid is also conveyed electrokinetically from the third channel into the second channel , This is particularly advantageous if the first fluid is to be mixed with the second fluid when it is introduced into the second channel.
Da das des erste Fluid druckgetrieben und nicht elektrokinetisch in die Kanalkreuzung und im Weiteren in den zweiten Kanal eingeleitet wird, werden in vorteilhafter Weise auch Fehler (Bias) aufgrund unterschiedlicher elektrophoretischer/ elektrokinetischer Mobilitäten von unterschiedlichen Fluiden bzw. unterschiedlichen Fluidkomponenten vermieden.Since that of the first fluid is pressure-driven and not electrokinetically introduced into the channel crossing and further into the second channel, errors (bias) due to different electrophoretic / electrokinetic mobilities of different fluids or different fluid components are also advantageously avoided.
Wird anschließend die Spannungsquelle wieder an den dritten, zweiten und vierten Kanal geschaltet, so wird das in den zweiten Kanal gelangte erste Fluid zusammen mit dem zweiten Fluid elektrokinetisch durch den zweiten Kanal gefördert und zugleich das in dem ersten Kanal druckgetriebene erste Fluid am Eintreten in den zweiten Kanal gehindert. Da nur eine einzige Spannung an den Kanälen angelegt wird, kann die Spannung weitgehend frei gewählt und beispielsweise für eine elektro- phoretische Trennung des ersten Fluids in dem zweiten Kanal optimal eingestellt werden.If the voltage source is then connected again to the third, second and fourth channels, the first fluid which has entered the second channel is conveyed electrokinetically together with the second fluid through the second channel and at the same time the first fluid which is pressure-driven in the first channel when it enters the second channel prevented. Since only a single voltage is applied to the channels, the voltage can largely be freely selected and, for example, optimally set for an electrophoretic separation of the first fluid in the second channel.
Zur weiteren Erläuterung der Erfindung wird im Folgenden auf die Figuren der Zeichnung Bezug genommen; im Einzelnen zeigenTo further explain the invention, reference is made below to the figures of the drawing; show in detail
Figur 1 ein sehr vereinfachtes Ausführungsbeispiel der erfindungsgemäßen Einrichtung, dieFigure 1 is a very simplified embodiment of the device according to the invention, the
Figuren 2, 3 und 4 beispielhaft die Förderung der Fluide durch die Kanalkreuzung und Figur 5 ein weiteres vereinfachtes Ausführungsbeispiel der erfindungsgemäßen Einrichtung.Figures 2, 3 and 4 exemplify the promotion of the fluids through the channel crossing and Figure 5 shows another simplified embodiment of the device according to the invention.
Figur 1 zeigt eine, beispielsweise auf einem Chip mikrostrukturierte Anordnung zur Behandlung von Fluiden mit Reservoirs 1, 2, 3, 4 zur Aufnahme der Fluide vor bzw. nach ihrer Behandlung und mit einem Kanalsystem 5, das die Reservoirs 1 bis 4 untereinander verbindet und in dem die Behandlung der Fluide erfolgt. Das Kanalsystem 5 besteht aus einem erstenFigure 1 shows an arrangement, for example microstructured on a chip, for treating fluids with reservoirs 1, 2, 3, 4 for receiving the fluids before or after their treatment and with a channel system 5 which connects the reservoirs 1 to 4 to one another and in which the treatment of the fluids takes place. The channel system 5 consists of a first one
Kanal 6, einem zweiten Kanal 7, einem dritten Kanal 8 und einem vierten Kanal 9, die von jeweils einem der vier Reservoirs 1 bis 4 abzweigen und an einer Kanalkreuzung 10 miteinander verbunden sind. In den Reservoirs 2, 3 und 4 sind Elek- troden 11, 12 und 13 angeordnet, von denen die Elektrode 12 im Reservoir 3 über einen steuerbaren Schalter 14 mit einem Spannungspol 15 einer Spannungsquelle 16 verbunden ist, deren anderer Spannungspol 17, hier über eine Masseverbindung, mit den Elektroden 11 und 13 in den Reservoirs 2 bzw. 4 verbunden ist.Channel 6, a second channel 7, a third channel 8 and a fourth channel 9, each branching off from one of the four reservoirs 1 to 4 and connected to one another at a channel crossing 10. Electrodes 11, 12 and 13 are arranged in the reservoirs 2, 3 and 4, of which the electrode 12 in the reservoir 3 is connected via a controllable switch 14 to a voltage pole 15 of a voltage source 16, the other voltage pole 17, here via a Earth connection, is connected to the electrodes 11 and 13 in the reservoirs 2 and 4, respectively.
In dem Reservoir 1 ist ein erstes Fluid 18 enthalten, das mittels einer Pumpe 19 druckgetrieben durch den ersten Kanal 6 in Richtung auf die Kanalkreuzung 10 zu gefördert wird. Ist der steuerbare Schalter 14 geschlossen, so wird ein in dem Reservoir 3 enthaltenes zweites Fluid 20 elektrokinetisch durch den dritten Kanal 8 und die Kanalkreuzung 10 sowohl in den zweiten Kanal 7 als auch in den vierten Kanal 9 gefördert. Wie die vergrößerte Darstellung der Kanalkreuzung 10 in Figur 2 zeigt, wird dabei das in dem ersten Kanal 6 druckgetriebene erste Fluid 18 durch den elektrokinetisch von dem dritten Kanal 8 in den vierten Kanal 9 geförderten Anteil des zweiten Fluids 20 daran gehindert, in den zweiten Kanal 7 einzutreten.Contained in the reservoir 1 is a first fluid 18, which is pump-driven by a pump 19 through the first channel 6 in the direction of the channel crossing 10. If the controllable switch 14 is closed, a second fluid 20 contained in the reservoir 3 is conveyed electrokinetically through the third channel 8 and the channel crossing 10 into both the second channel 7 and the fourth channel 9. As the enlarged representation of the channel crossing 10 in FIG. 2 shows, the first fluid 18, which is pressure-driven in the first channel 6, is prevented in the second channel by the portion of the second fluid 20 that is electrokinetically conveyed from the third channel 8 into the fourth channel 9 7 to enter.
Zum Injizieren des ersten Fluids 18 aus dem ersten Kanal 6 in den zweiten Kanal 7 wird durch Öffnen des Schalters 14 die Spannungsquelle 16 von den Elektroden 11, 12, 13 weggeschaltet, so dass dann entsprechend der Darstellung in Figur 3 allein das erste Fluid 18 druckgetrieben aus dem ersten Kanal 6 geradeaus in den zweiten Kanal 7 eindringt. Eine Förderung des zweiten Fluids 20 findet zu diesem Zeitpunkt nicht statt.To inject the first fluid 18 from the first channel 6 into the second channel 7, the switch 14 is opened Voltage source 16 is disconnected from the electrodes 11, 12, 13, so that, as shown in FIG. 3, only the first fluid 18, driven by pressure, penetrates straight from the first channel 6 into the second channel 7. The second fluid 20 is not delivered at this time.
Wird anschließend der steuerbare Schalter 14 wieder geschlossen, so findet wieder eine elektrokinetische Förderung des zweiten Fluids 20 aus dem dritten Kanal 8 in den zweiten Kanal 7 und den vierten Kanal 9 statt, wobei entsprechend der Darstellung in Figur 4 das zuvor als Dosierpfropf 21 in den zweiten Kanal 7 gelangte erste Fluid 18 zusammen mit dem zweiten Fluid 20 durch den zweiten Kanal 7 gefördert wird, während aus dem ersten Kanal 6 das weiterhin druckgetriebene Fluid 18 von dem entsprechenden Teilstrom des zweiten Fluids 20 in den vierten Kanal 9 umgelenkt wird.If the controllable switch 14 is then closed again, the second fluid 20 is again electrokinetically conveyed from the third channel 8 into the second channel 7 and the fourth channel 9, which, as shown in FIG second channel 7, first fluid 18 passed through the second channel 7 together with the second fluid 20, while the pressure-driven fluid 18 is diverted from the first channel 6 by the corresponding partial flow of the second fluid 20 into the fourth channel 9.
Das in Figur 5 gezeigte Ausführungsbeispiel unterscheidet sich von dem nach Figur 1 dadurch, dass die Elektroden 11 und 12 fest mit der Spannungsquelle 16 verbunden sind und nur die Elektrode 13 über den steuerbaren Schalter 14 wahlweise mit der Spannungsquelle 16 verbindbar oder von dieser trennbar ist. Wenn zum Einleiten des ersten Fluids 18 aus dem ersten Kanal 6 in den zweiten Kanal 7 der Schalter 14 geöffnet wird, wird lediglich die elektrokinetische Förderung des zweitenThe exemplary embodiment shown in FIG. 5 differs from that according to FIG. 1 in that the electrodes 11 and 12 are firmly connected to the voltage source 16 and only the electrode 13 can be selectively connected to the voltage source 16 via the controllable switch 14 or can be separated therefrom. If the switch 14 is opened to introduce the first fluid 18 from the first channel 6 into the second channel 7, only the electrokinetic delivery of the second one
Fluids 20 aus dem dritten Kanal 8 in den vierten Kanal 9 abgeschaltet, so dass dann das erste Fluid 18 druckgetrieben aus dem ersten Kanal 6 in den zweiten Kanal 7 eindringt; das zweite Fluid 20 wird nach wie vor kinetisch aus dem dritten Kanal 8 in den zweiten Kanal 7 gefördert.Fluids 20 are switched off from the third channel 8 into the fourth channel 9, so that the first fluid 18 then penetrates pressure-driven from the first channel 6 into the second channel 7; the second fluid 20 is still conveyed kinetically from the third channel 8 into the second channel 7.
Bei den gezeigten Ausführungsbeispielen münden die Kanäle 6 bis 9 rechtwinklig in die Kanalkreuzung 10. Grundsätzlich können die Kanäle 6 bis 9 aber auch unter anderen Winkeln in die Kanalkreuzung 10 münden, wobei sich auch nicht der erste Kanal 6 geradeaus in den zweiten Kanal 7 und der dritte Kanal 8 geradeaus in den vierten Kanal 9 fortsetzen müssen. In the exemplary embodiments shown, the channels 6 to 9 open into the channel crossing 10 at right angles. In principle, the channels 6 to 9 can also open into the channel crossing 10 at different angles, the first channel 6 also not going straight into the second channel 7 and the third channel 8 must continue straight into the fourth channel 9.

Claims

Patentansprüche claims
1. Mikrofluidische Einrichtung zur gesteuerten Einleitung eines ersten Fluids (18) aus einem ersten Kanal (6) in einen ein zweites Fluid (20) enthaltenden zweiten Kanal (7) und zur elektrokinetischen Förderung der Fluide (18, 20) durch den zweiten Kanal (7), mit einer Kanalkreuzung (10), in die der erste Kanal (6), ein das zweite Fluid (20) enthaltender dritter Kanal (8), der zweite Kanal (7) und ein vierter Kanal (9) in dieser Reihenfolge im oder gegen den Uhrzeigersinn einmünden, mit einer das erste Fluid (18) mittels Druck durch den ersten Kanal (6) in Richtung auf die Kanalkreuzung (10) fördernden Vorrichtung und mit einer einzigen Spannungsquelle (16), die mit einem Spannungspol (15) an eine von der Kanal- kreuzung (10) entfernte Stelle des dritten Kanals (8) und mit dem anderen Spannungspol (17) an von der Kanalkreuzung (10) entfernte Stellen sowohl des zweiten Kanals (7) als auch des vierten Kanals (9) schaltbar ist.1. Microfluidic device for the controlled introduction of a first fluid (18) from a first channel (6) into a second channel (7) containing a second fluid (20) and for the electrokinetic delivery of the fluids (18, 20) through the second channel ( 7), with a channel crossing (10) into which the first channel (6), a third channel (8) containing the second fluid (20), the second channel (7) and a fourth channel (9) in this order in or open counter-clockwise, with a device which conveys the first fluid (18) by means of pressure through the first channel (6) in the direction of the channel crossing (10) and with a single voltage source (16) connected to a voltage pole (15) a point of the third channel (8) remote from the channel crossing (10) and switchable with the other voltage pole (17) to points of both the second channel (7) and the fourth channel (9) remote from the channel crossing (10) is.
2. Mikrofluidische Einrichtung nach Anspruch 1, d a d u r c h g e k e n n z e i c h n e t , dass die Spannungsquelle (16) in einem ersten Betriebszustand der Einrichtung an den dritten, zweiten und vierten Kanal (8, 7, 9) geschaltet ist und in einem zweiten Betriebszustand von dem dritten Kanal (8) und/oder dem zweiten und vierten Kanal (7, 9) abgeschaltet ist .2. Microfluidic device according to claim 1, characterized in that the voltage source (16) is connected to the third, second and fourth channels (8, 7, 9) in a first operating state of the device and in a second operating state of the third channel (8 ) and / or the second and fourth channels (7, 9) is switched off.
3. Mikrofluidische Einrichtung nach Anspruch 1, d a d u r c h g e k e n n z e i c h n e t , dass die Spannungsquelle (16) in einem ersten Betriebszustand der Einrichtung an den dritten, zweiten und vierten Kanal (8, 7, 9) geschaltet ist und in einem zweiten Betriebszustand nur von dem vierten Kanal (9) abgeschaltet ist.3. Microfluidic device according to claim 1, characterized in that the voltage source (16) is connected to the third, second and fourth channels (8, 7, 9) in a first operating state of the device and in a second operating state only from the fourth channel ( 9) is switched off.
4. Mikrofluidische Einrichtung nach einem der vorangehenden Ansprüche, d a d u r c h g e k e n n z e i c h n e t , dass die Vorrichtung eine Pumpe (19) aufweist. 4. Microfluidic device according to one of the preceding claims, characterized in that the device has a pump (19).
5. Mikrofluidische Einrichtung nach einem der vorangehenden Ansprüche, d a du r c h g e ke n n z e i c h n e t , dass die Vorrichtung ein an einer von der Kanalkreuzung (10) entfernten Stelle mit dem ersten Kanal (6) verbundenes Fluidre- servoir (1) aufweist, das höher als die Kanalkreuzung (10) angeordnet ist. 5. Microfluidic device according to one of the preceding claims, since you can see that the device has a fluid reservoir (1) which is connected to the first channel (6) at a location remote from the channel crossing (10) and which is higher than that Channel crossing (10) is arranged.
PCT/EP2004/003474 2003-04-04 2004-04-01 Microfluidic device for the controlled directing of a fluid into a duct WO2004087321A1 (en)

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EP3002489B1 (en) * 2008-05-16 2017-09-20 President and Fellows of Harvard College Valves and other flow control in fluidic systems including microfluidic systems

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US6001229A (en) * 1994-08-01 1999-12-14 Lockheed Martin Energy Systems, Inc. Apparatus and method for performing microfluidic manipulations for chemical analysis
US20020076806A1 (en) * 2000-09-21 2002-06-20 Dna Sciences, Inc. Sample injector system and method
US20030057092A1 (en) * 2000-10-31 2003-03-27 Caliper Technologies Corp. Microfluidic methods, devices and systems for in situ material concentration

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DE60140111D1 (en) * 2000-02-11 2009-11-19 Aclara Biosciences Inc MICROFLUIDIC DEVICE WITH A LIQUID SAMPLE INJECTION DEVICE AND USE METHOD

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US6001229A (en) * 1994-08-01 1999-12-14 Lockheed Martin Energy Systems, Inc. Apparatus and method for performing microfluidic manipulations for chemical analysis
US20020076806A1 (en) * 2000-09-21 2002-06-20 Dna Sciences, Inc. Sample injector system and method
US20030057092A1 (en) * 2000-10-31 2003-03-27 Caliper Technologies Corp. Microfluidic methods, devices and systems for in situ material concentration

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