EP3263217B1 - Microfluidic flow cell with a flowing reagent and/or sample material receiving storage space - Google Patents

Microfluidic flow cell with a flowing reagent and/or sample material receiving storage space Download PDF

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Publication number
EP3263217B1
EP3263217B1 EP16190102.0A EP16190102A EP3263217B1 EP 3263217 B1 EP3263217 B1 EP 3263217B1 EP 16190102 A EP16190102 A EP 16190102A EP 3263217 B1 EP3263217 B1 EP 3263217B1
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EP
European Patent Office
Prior art keywords
storage space
flow cell
cell according
section
cross
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EP16190102.0A
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German (de)
French (fr)
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EP3263217A1 (en
Inventor
Lutz Weber
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Thinxxs Microtechnology GmbH
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Thinxxs Microtechnology GmbH
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Priority to PCT/EP2017/062609 priority Critical patent/WO2018001648A1/en
Priority to US16/314,539 priority patent/US11045804B2/en
Priority to CN201780039510.1A priority patent/CN109414697B/en
Publication of EP3263217A1 publication Critical patent/EP3263217A1/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
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—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 for controlling flow resistance, e.g. flow controllers, baffles
    • 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
    • B01L3/52—Containers specially adapted for storing or dispensing a reagent
    • B01L3/523—Containers specially adapted for storing or dispensing a reagent with means for closing or opening
    • 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
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • 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
    • B01L2200/16—Reagents, handling or storing thereof
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/046—Function or devices integrated in the closure
    • B01L2300/047—Additional chamber, reservoir
    • 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
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • 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
    • B01L2300/0877—Flow chambers
    • 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
    • B01L2300/0883—Serpentine channels
    • 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
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic

Definitions

  • the invention relates to a microfluidic flow cell having a storage space containing liquid reagent and / or sample material and having an inflow channel for a fluid removing the reagent and / or sample material from the storage space and a drainage channel for the reagent and / or sample material and the fluid communicates, wherein the inflow channel and the outflow channel are connected by a bypass surrounding the storage space.
  • Microfluidic flow cells with these features are each out WO 2015/162060 A1 .
  • Microfluidic flow cells which are used primarily in the life sciences for diagnostics, analysis and synthesis, process increasingly smaller volumes of liquid samples and liquid reagents.
  • the invention has for its object to provide a new microfluidic flow cell of the type mentioned above with particular suitability for receiving and processing small amounts of reagent and / or sample material.
  • the problem solved microfluidic flow cell according to the invention is characterized in that the flow cross-section of the bypass for venting the inflow channel just sufficient to prevent the removal of reagent and / or sample material from the storage space by increasing in the inflow air pressure.
  • this invention solution allows a targeted removal and targeted mixing of stored in a storage space of the flow cell reagent and / or sample material by and with the transporting away fluid.
  • a sample or reagent quantity to be processed is provided in a channel section of a microfluidic network.
  • Typical volumes are in the range of 1 to 100 ⁇ l.
  • processing the sample or reagent amount is meant e.g. mixing with another sample or reagent or e.g. dilution in the ratio of typically 1: 1 to 1: 1000 or controlled onward transport.
  • the transport or processing or dilution liquid is typically at a different location of the sample from the position of the sample of the microfluidic network, e.g. a storage area or liquid blister. That is, between the two quantities of liquid is an empty, usually filled with gas or air channel-shaped inflow area.
  • the bypass branches off in the direction of flow immediately before the storage space from the inflow channel.
  • no air cushion can form between the front of the fluid flowing into the inflow channel and the reagent and / or sample material contained in the storage space, through which the reagent and / or sample material is transported out of the storage space before it reaches the front of the inflowing fluid ,
  • the storage space forms a flush with the inflow channel and the drainage channel section.
  • the cross section of the storage space perpendicular to the flow direction preferably coincides with the cross section of the inflow channel and / or the cross section of the outflow channel.
  • the vertical cross section of the storage space in the flow direction may be smaller or larger than the cross section of the inflow channel and / or the cross section of the outflow channel.
  • the flow cross-section of the bypass may in particular be dimensioned such that a desired proportion of the fluid flowing in through the inflow channel flows over the bypass, the proportion corresponding to a desired mixing ratio of reagent and / or sample material and fluid.
  • the bypass can be produced by deflection of a flexible, adjacent to the storage space cover.
  • the cover sheet may e.g. be pneumatically deflectable by the air pressure in the inflow channel or by a suction pressure generated from the outside by an operator device, alternatively mechanically.
  • the inflow channel, the outflow channel and possibly the storage space are formed by recesses in a substrate and the recesses are closed in a fluid-tight manner by a cover connected to the substrate.
  • the cover is preferably a covering film which is welded or / and glued to a plate surface of the substrate or else a preferably injection-molded covering substrate.
  • samples or reagents can be finally used in the otherwise completely completed flow cell.
  • Impairment in a storage space in the substrate introduced reagents by subsequent welding and / or bonding of the substrate, for example, with a cover omitted.
  • a receiving region of the carrier element for the reagent and / or sample material adjacent to the storage space is expediently formed in an end piece of a plug-like carrier element.
  • the bypass may suitably run between the end piece and the inner wall of the above-mentioned opening.
  • the microfluidic flow cell shown in detail comprises a plate-shaped substrate 1 and a cover foil 2 welded or bonded to the substrate 1.
  • the cover foil 2 closes cavity structures of the flow cell which are fluid-tightly formed in the substrate 1 and open towards the foil side.
  • Fig. 1 Visible are a storage space 3, an inflow channel 4 and an outflow channel 5.
  • the inflow channel 4 connects with the outflow channel 5 a bypass 6 branching off from the inflow channel 4 in the flow direction immediately before the storage space 3.
  • the storage space 3 has the same cross-section as the inflow and outflow channels in the flow direction, so that the storage space 3 only forms a section of a through-going channel.
  • the walls of the storage space 3 are at least partially hydrophilized, so that there liquid reagent 7 can be held in place and introduced in the course of manufacturing the flow cell in the flow cell.
  • the volume of the liquid reagent material 7 is preferably in the range of 1 to 100 ⁇ l, in particular in the range of 2 to 50 ⁇ l.
  • the storage area 3 can be separated from the inflow and outflow channel by means of local welding of the substrate with the cover film 2 acting as a predetermined breaking point (not shown).
  • the storage area 3 could additionally be connected to closable filling or venting channels for filling the reagent material 7 into the storage area (not shown).
  • another fluid introduced from the outside into the flow cell or fluid originating from a further storage region of the flow cell can flow via the inflow channel 4, flushing out the reagent material 7 from the storage space 3 and mixing it with the further fluid via the outflow channel 5 Reagent material 7 for further processing within the flow cell supplies.
  • the further fluid 8 may be e.g. a sample liquid to be assayed by the flow cell or another liquid reagent, e.g. a washing or dilution buffer, act.
  • a sample liquid to be assayed by the flow cell
  • another liquid reagent e.g. a washing or dilution buffer
  • mixtures of a sample liquid and a liquid reagent are also possible.
  • the flow cell itself or an operator device has a pressure source for the fluid transport through the inflow channel 4, the storage space 3 and the outflow channel 5 (not shown).
  • a pressure source could e.g. be formed by a blister memory for a washing and dilution buffer.
  • an area of the flow cell which can be elastically or plastically deformed from the outside by an operator device or manually by a user or an air pump which can be connected via an air or pneumatic connection of the flow cell to an operating device as a pressure source would be possible.
  • the fluid flowing in for the purpose of flushing out the reagent material 7 from the storage space 3 displaces the air contained in the inflow channel 4 in front of it. Without the bypass 6, an undesirable air cushion impeding the mixing of the reagent material and the fluid would arise between the reagent material 7 and the oncoming fluid.
  • the flow resistance of the bypass 6 for the Air is so low that the air pressure upstream of the storage space 3 in the direction of flow can not rise so high that the air can push out the reagent material 7 from the storage space 3 against the retention capacity of the storage space.
  • the front of the fluid 8 thereby reaches the reagent 7 and rinsing out the reagent 7 from the storage space 3 while mixing with the reagent 7.
  • the flow resistance of the bypass 6 for the fluid 8 is in the example of Fig. 1 on the other hand, so great that no appreciable portion of the oncoming fluid 8 flows past the bypass 6 past the storage space 3. It goes without saying that, when the flow resistance of the bypass 6 for the fluid 8 is reduced by enlarging the bypass cross section, the proportion of the fluid 8 flowing through the bypass increases. With a view to a faster mixing of reagent material 7 and fluid 8, a desired proportion of the fluid flowing through the bypass 6 can be set by selecting the flow source cross section.
  • FIGS. 2 to 7 show exemplary embodiments, which use a carrier element 9 for forming a storage space 3 for liquid reagent and / or sample material 7, which can be inserted into an opening 10 in the flow cell or its substrate 1 and can be connected in a fluid-tight manner to the flow cell.
  • a carrier element 9 for forming a storage space 3 for liquid reagent and / or sample material 7, which can be inserted into an opening 10 in the flow cell or its substrate 1 and can be connected in a fluid-tight manner to the flow cell.
  • With the memory space 3 are in the same manner as in the embodiment of Fig. 1 Channels connected.
  • the plug-like manner with a cylindrical end piece 11, a cone portion 12 and a collar 13 formed carrier element 9 has an open towards the end receiving groove for liquid reagent and / or sample material.
  • the opening 10 in the substrate 1 of the flow cell is approximately matched in shape to the carrier element 9.
  • the groove is hydrophilized so that the liquid reagent and / or sample material on the support member in the groove is held particularly tight.
  • the carrier element 9 with the end face of the cylindrical end piece 11 extends, if necessary, as far as the covering film 2, so that the carrier element 9 forms the storage space 3 together with the covering film 2.
  • the cross section of the storage space coincides with the cross section of an inflow channel which leads into the storage space (into the Fig. 2 to 7 not visible) and drainage channels match. Of the channels is in Fig. 2a the drainage channel 5 in cross section visible.
  • the storage space 3 is aligned with the channels. To secure the orientation of the storage space 3 to the Channels could be formed on the support member 9 and the substrate 1 per a stop.
  • a bypass 6 consisting of two flow channels is formed.
  • the storage space is closed to the outside fluid-tight.
  • the carrier element 9 could be welded to the substrate 1 in a fluid-tight manner and / or adhesively bonded.
  • Fig. 2 Compared to the embodiment of Fig. 1 have the embodiments of Fig. 2 to 7 the advantage that the reagent and / or sample material is not affected by final welding or / and bonding of the substrate 1 with the cover 2.
  • the embodiment of Fig. 3 differs from the embodiment of Fig. 2 in that the difference between the diameter of the end piece 11 and the end piece 11 receiving portion of the opening 10 is even greater than in the embodiment of Fig. 2 and thus the flow cross section of the formed bypass 6 is greater than the flow cross section of the bypass 6 of the embodiment of Fig. 2 is.
  • the bypass according to Fig. 3 Accordingly, a greater proportion of a fluid flowing through the inflow channel to flow through the bypass and, as already mentioned above, the mixing ratio of reagent and / or sample liquid with the oncoming fluid can be adjusted appropriately.
  • FIGS. 5 and 6 relate to embodiments in which a cover 2 in the region of a storage space 3 is deflected to form a bypass 6. According to Fig. 5 the deflection of the cover 2 is effected by the pressure of the air to be redirected.
  • Fig. 6 serves a negative pressure generating operator device 15 for deflecting the cover 2 by suction.
  • a cylindrical end piece 11 of a carrier element 9 does not have a groove open towards the end face of the end piece, but has a passageway.
  • the passage forms a storage space 3 whose cross section is smaller than the cross section of the channels opening into the storage space, of which in Fig. 7a the drainage channel 5 is visible in cross section.
  • the in Fig. 7a in its position indicated by dashed lines memory space 3 is aligned approximately at the center of the cross section of the opening channels.
  • Fluid flowing in via the bypass with a relatively large flow cross section through the inflow channel encloses the reagent and / or sample material in the outflow channel 5 in the flow, resulting in a type of centering of the reagent and / or sample material in the fluid flushing out the storage space 3.
  • This allows e.g. a sample with particles, e.g. the cells of a blood sample, centered in the drainage channel, to remove them e.g. individually to analyze according to the principle of a cytometer.
  • the substrate 1 and the carrier element 9 of the flow cells described above are preferably made of plastics such as PMMA, PC, COC, COP, PPE, PE and are produced by injection molding.
  • the materials of substrate 1 and carrier element 9 match.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
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  • Automatic Analysis And Handling Materials Therefor (AREA)
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Description

Die Erfindung betrifft eine mikrofluidische Flusszelle mit einem flüssiges Reagenz- oder/und Probenmaterial aufnehmenden Speicherraum, der mit einem Zuflusskanal für ein das Reagenz- oder/und Probenmaterial aus dem Speicherraum abtransportierenden Fluid und einem Abflusskanal für das Reagenz- oder/und Probenmaterial und das Fluid in Verbindung steht, wobei der Zuflusskanal und der Abflusskanal durch einen den Speicherraum umgebenden Bypass verbunden sind.The invention relates to a microfluidic flow cell having a storage space containing liquid reagent and / or sample material and having an inflow channel for a fluid removing the reagent and / or sample material from the storage space and a drainage channel for the reagent and / or sample material and the fluid communicates, wherein the inflow channel and the outflow channel are connected by a bypass surrounding the storage space.

Mikrofluidische Flusszellen mit diesen Merkmalen sind jeweils aus WO 2015/162060 A1 , WO 2012/056334 A1 und US 2013/149791 A1 bekannt.Microfluidic flow cells with these features are each out WO 2015/162060 A1 . WO 2012/056334 A1 and US 2013/149791 A1 known.

Mikrofluidische Flusszellen, wie sie vor allem in den Life Sciences zur Diagnostik, Analytik und Synthese zum Einsatz kommen, verarbeiten zunehmend kleinere Volumina von flüssigen Proben und flüssigen Reagenzien.Microfluidic flow cells, which are used primarily in the life sciences for diagnostics, analysis and synthesis, process increasingly smaller volumes of liquid samples and liquid reagents.

Der Erfindung liegt die Aufgabe zugrunde, eine neue mikrofluidische Flusszelle der eingangs genannten Art mit besonderer Eignung zur Aufnahme und Verarbeitung geringer Mengen von Reagenz- oder/und Probenmaterial zu schaffen.The invention has for its object to provide a new microfluidic flow cell of the type mentioned above with particular suitability for receiving and processing small amounts of reagent and / or sample material.

Die diese Aufgabe lösende mikrofluidische Flusszelle nach der Erfindung ist dadurch gekennzeichnet, dass der Strömungsquerschnitt des Bypass zur Entlüftung des Zuflusskanals gerade ausreicht, um einen Abtransport von Reagenz- oder/und Probenmaterial aus dem Speicherraum durch im Zuflusskanal ansteigenden Luftdruck zu verhindern.The problem solved microfluidic flow cell according to the invention is characterized in that the flow cross-section of the bypass for venting the inflow channel just sufficient to prevent the removal of reagent and / or sample material from the storage space by increasing in the inflow air pressure.

Vorteilhaft erlaubt diese Erfindungslösung einen gezielten Abtransport und eine gezielte Durchmischung des in einem Speicherraum der Flusszelle gespeicherten Reagenz- oder/und Probenmaterials durch das und mit dem abtransportierenden Fluid.Advantageously, this invention solution allows a targeted removal and targeted mixing of stored in a storage space of the flow cell reagent and / or sample material by and with the transporting away fluid.

Üblicherweise wird eine zu verarbeitende Proben- oder Reagenzmenge in einem Kanalabschnitt eines mikrofluidischen Netzwerks bereitgestellt. Typische Volumina liegen im Bereich von 1 - 100 µl. Unter Verarbeitung der Proben- oder Reagenzmenge versteht man z.B. das Mischen mit einer anderen Probe oder eines anderen Reagenz oder z.B. das Verdünnen im Verhältnis von typisch 1:1 bis 1:1000 oder einen kontrollierten Weitertransport. Dabei wird die Transport- oder Verarbeitungs- oder Verdünnungsflüssigkeit typischerweise an einer anderen zur Position der Probe beabstandeten Position des mikrofluidischen Netzwerks, z.B. einem Speicherbereich oder Flüssigkeitsblister, bereitgestellt. Das heißt, zwischen den beiden Flüssigkeitsmengen befindet sich ein leerer, in der Regel mit Gas oder Luft gefüllter kanalförmiger Zuflussbereich.Usually, a sample or reagent quantity to be processed is provided in a channel section of a microfluidic network. Typical volumes are in the range of 1 to 100 μl. By processing the sample or reagent amount is meant e.g. mixing with another sample or reagent or e.g. dilution in the ratio of typically 1: 1 to 1: 1000 or controlled onward transport. The transport or processing or dilution liquid is typically at a different location of the sample from the position of the sample of the microfluidic network, e.g. a storage area or liquid blister. That is, between the two quantities of liquid is an empty, usually filled with gas or air channel-shaped inflow area.

Vorzugsweise zweigt der Bypass in Strömungsrichtung gesehen unmittelbar vor dem Speicherraum von dem Zuflusskanal ab. Damit kann sich zwischen der Front des in dem Zuflusskanal anströmenden Fluids und des in dem Speicherraum enthaltenen Reagenz- oder/und Probenmaterials kein Luftpolster bilden, durch das das Reagenz- oder/und Probenmaterial vor Erreichen durch die Front des anströmenden Fluids aus dem Speicherraum abtransportiert wird.Preferably, the bypass branches off in the direction of flow immediately before the storage space from the inflow channel. Thus, no air cushion can form between the front of the fluid flowing into the inflow channel and the reagent and / or sample material contained in the storage space, through which the reagent and / or sample material is transported out of the storage space before it reaches the front of the inflowing fluid ,

In weiterer vorteilhafter Ausgestaltung der Erfindung bildet der Speicherraum einen mit dem Zuflusskanal und dem Abflusskanal fluchtenden Kanalabschnitt. Durch Angleichung der Strömungsrichtungen im Zu- und Abflusskanal sowie im Speicherraum kommt es schnell zu einer vollständigen Ausspülung des Reagenz- oder/und Probenmaterials aus dem Speicherraum.In a further advantageous embodiment of the invention, the storage space forms a flush with the inflow channel and the drainage channel section. By aligning the flow directions in the inflow and outflow channel and in the storage space, a complete rinsing of the reagent and / or sample material from the storage space quickly occurs.

Vorzugsweise stimmt der zur Strömungsrichtung senkrechte Querschnitt des Speicherraums mit dem Querschnitt des Zuflusskanals und/oder dem Querschnitt des Abflusskanals überein. Alternativ kann der in Strömungsrichtung senkrechte Querschnitt des Speicherraums kleiner oder größer als der Querschnitt des Zuflusskanals und/oder der Querschnitt des Abflusskanals sein.The cross section of the storage space perpendicular to the flow direction preferably coincides with the cross section of the inflow channel and / or the cross section of the outflow channel. Alternatively, the vertical cross section of the storage space in the flow direction may be smaller or larger than the cross section of the inflow channel and / or the cross section of the outflow channel.

Während es möglich wäre, dass sich der zur Strömungsrichtung senkrechte Querschnitt des Speicherraums in Strömungsrichtung ändert, ist er in einer bevorzugten Ausführungsform der Erfindung konstant.While it would be possible for the cross section of the storage space, which is perpendicular to the direction of flow, to change in the direction of flow, it is constant in a preferred embodiment of the invention.

Der Strömungsquerschnitt des Bypass kann insbesondere so bemessen sein, dass ein gewünschter Anteil des durch den Zuflusskanal heranströmenden Fluids über den Bypass strömt, wobei der Anteil einem gewünschten Mischungsverhältnis von Reagenz- oder/und Probenmaterial und Fluid entspricht.The flow cross-section of the bypass may in particular be dimensioned such that a desired proportion of the fluid flowing in through the inflow channel flows over the bypass, the proportion corresponding to a desired mixing ratio of reagent and / or sample material and fluid.

In einer Ausführungsform der Erfindung ist der Bypass durch Auslenkung eines flexiblen, an den Speicherraum grenzenden Abdeckfolie herstellbar.In one embodiment of the invention, the bypass can be produced by deflection of a flexible, adjacent to the storage space cover.

Die Abdeckfolie kann z.B. durch den Luftdruck in dem Zuflusskanal oder durch einen von außen durch ein Betreibergerät erzeugten Saugdruck pneumatisch auslenkbar sein, alternativ mechanisch.The cover sheet may e.g. be pneumatically deflectable by the air pressure in the inflow channel or by a suction pressure generated from the outside by an operator device, alternatively mechanically.

In einer besonders bevorzugten Ausführungsform der Erfindung sind der Zuflusskanal, der Abflusskanal und ggf. der Speicherraum durch Ausnehmungen in einem Substrat gebildet und die Ausnehmungen durch einen mit dem Substrat verbundene Abdeckung fluiddicht verschlossen. Bei der Abdeckung handelt es sich vorzugsweise um eine mit einer Plattenfläche des Substrats verschweißte oder/und verklebte Abdeckfolie oder auch ein bevorzugt spritzgegossenes Abdecksubstrat.In a particularly preferred embodiment of the invention, the inflow channel, the outflow channel and possibly the storage space are formed by recesses in a substrate and the recesses are closed in a fluid-tight manner by a cover connected to the substrate. The cover is preferably a covering film which is welded or / and glued to a plate surface of the substrate or else a preferably injection-molded covering substrate.

In einer weiteren besonders bevorzugten Ausführungsform der Erfindung grenzt an den Speicherraum ein das flüssige Reagenz- oder/und Probenmaterial aufnehmendes Trägerelement an, das unter fluiddichtem Abschluss des Speicherraums in eine Öffnung in dem Substrat einsetzbar und mit dem Substrat fluiddicht verbindbar ist.In a further particularly preferred embodiment of the invention adjacent to the storage space to the liquid reagent and / or sample material receiving carrier element, which is used under fluid-tight closure of the storage space in an opening in the substrate and fluid-tightly connected to the substrate.

Vorteilhaft können durch ein solches Trägerelement Proben oder Reagenzien in die im Übrigen vollständig fertiggestellte Flusszelle abschließend eingesetzt werden. Beeinträchtigung in einen Speicherraum im Substrat eingebrachter Reagenzien durch nachträgliches Verschweißen oder/und Verkleben des Substrats, z.B. mit einer Abdeckfolie, entfallen.Advantageously, by means of such a carrier element, samples or reagents can be finally used in the otherwise completely completed flow cell. Impairment in a storage space in the substrate introduced reagents by subsequent welding and / or bonding of the substrate, for example, with a cover omitted.

Ein an den Speicherraum grenzender Aufnahmebereich des Trägerelements für das Reagenz- oder/und Probenmaterial ist zweckmäßig in einem Endstück eines pfropfenartigen Trägerelements gebildet.A receiving region of the carrier element for the reagent and / or sample material adjacent to the storage space is expediently formed in an end piece of a plug-like carrier element.

Der Bypass kann zweckmäßig zwischen dem Endstück und der Innenwand der obengenannten Öffnung verlaufen.The bypass may suitably run between the end piece and the inner wall of the above-mentioned opening.

Die Erfindung wird nachfolgend anhand von Ausführungsbeispielen und der beiliegenden, sich auf diese Ausführungsbeispiele beziehenden Zeichnungen weiter erläutert. Es zeigen:

Fig. 1
ein Ausführungsbeispiel für eine Flusszelle nach der Erfindung mit einem durch ein Substrat und eine Abdeckfolie gegrenzten Speicherraum,
Fig. 2 bis 4
Flusszellen nach der Erfindung mit einem durch ein Trägerelement und eine Abdeckfolie begrenzten Speicherraum und zwischen dem Trägerelement und einem Substrat verlaufenden Bypasskanälen,
Fig. 5 und 6
Ausführungsbeispiele von Flusszellen nach der Erfindung mit Bypasskanälen, die durch ausgelenkte Abdeckfolien gebildet sind, und
Fig. 7
ein Ausführungsbeispiel einer erfindungsgemäßen Flusszelle mit einem durch ein Trägerelement gebildeten, gegenüber Spülkanälen verengten Speicherraum.
The invention will be explained below with reference to embodiments and the accompanying, relating to these embodiments drawings. Show it:
Fig. 1
An embodiment of a flow cell according to the invention with a limited by a substrate and a cover storage space,
Fig. 2 to 4
Flow cells according to the invention with a limited by a support member and a cover storage space and between the support member and a substrate extending bypass channels,
FIGS. 5 and 6
Embodiments of flow cells according to the invention with bypass channels, which are formed by deflected cover films, and
Fig. 7
An embodiment of a flow cell according to the invention with a formed by a support member, compared with scavenging channels narrowed storage space.

Eine in Fig. 1 ausschnittsweise gezeigte mikrofluidische Flusszelle umfasst ein plattenförmiges Substrat 1 und eine mit dem Substrat 1 verschweißte oder/und verklebte Abdeckfolie 2. Die Abdeckfolie 2 schließt fluiddicht im Substrat 1 gebildete, zur Folienseite hin offene Hohlraumstrukturen der Flusszelle ab.An in Fig. 1 The microfluidic flow cell shown in detail comprises a plate-shaped substrate 1 and a cover foil 2 welded or bonded to the substrate 1. The cover foil 2 closes cavity structures of the flow cell which are fluid-tightly formed in the substrate 1 and open towards the foil side.

Von diesen Hohlraumstrukturen in Fig. 1 sichtbar sind ein Speicherraum 3, ein Zuflusskanal 4 sowie ein Abflusskanal 5. Neben dem Speicherraum 3 verbindet den Zuflusskanal 4 mit dem Abflusskanal 5 ein in Strömungsrichtung unmittelbar vor dem Speicherraum 3 von dem Zuflusskanal 4 abzweigender Bypass 6.From these cavity structures in Fig. 1 Visible are a storage space 3, an inflow channel 4 and an outflow channel 5. In addition to the storage space 3, the inflow channel 4 connects with the outflow channel 5 a bypass 6 branching off from the inflow channel 4 in the flow direction immediately before the storage space 3.

Der Speicherraum 3 weist in dem gezeigten Beispiel in Strömungsrichtung den gleichen Querschnitt wie der Zufluss- und der Abflusskanal auf, so dass der Speicherraum 3 lediglich einen Abschnitt eines durchaehenden Kanals bildet. Im Unterschied zu den Kanalwänden sind jedoch die Wände des Speicherraums 3 zumindest teilweise hydrophilisiert, so dass dort flüssiges Reagenzmaterial 7 an Ort und Stelle festgehalten und im Zuge der Fertigung der Flusszelle in die Flusszelle eingebracht werden kann. Das Volumen des flüssigen Reagenzmaterials 7 liegt vorzugsweise im Bereich von 1 - 100 µl, insbesondere im Bereich von 2-50 µl. Der Speicherbereich 3 kann vom Zu- und Abflusskanal mittels als Sollbruchstelle wirkender lokaler Verschweißungen des Substrats mit der Deckfolie 2 getrennt sein (nicht gezeigt). Der Speicherbereich 3 könnte zusätzlich mit verschließbaren Füll- bzw. Entlüftungskanälen zum Einfüllen des Reagenzmaterials 7 in den Speicherbereich verbunden sein (nicht gezeigt).In the example shown, the storage space 3 has the same cross-section as the inflow and outflow channels in the flow direction, so that the storage space 3 only forms a section of a through-going channel. In difference However, to the channel walls, the walls of the storage space 3 are at least partially hydrophilized, so that there liquid reagent 7 can be held in place and introduced in the course of manufacturing the flow cell in the flow cell. The volume of the liquid reagent material 7 is preferably in the range of 1 to 100 μl, in particular in the range of 2 to 50 μl. The storage area 3 can be separated from the inflow and outflow channel by means of local welding of the substrate with the cover film 2 acting as a predetermined breaking point (not shown). The storage area 3 could additionally be connected to closable filling or venting channels for filling the reagent material 7 into the storage area (not shown).

Je nach Funktion der Flusszelle kann über den Zuflusskanal 4 ein weiteres, von außen in die Flusszelle eingegebenes Fluid oder aus einem weiteren Speicherbereich der Flusszelle stammendes Fluid heranströmen, das Reagenzmaterial 7 aus dem Speicherraum 3 herausspült und über den Abflusskanal 5 das mit dem weiteren Fluid vermischte Reagenzmaterial 7 einer Weiterverarbeitung innerhalb der Flusszelle zuführt.Depending on the function of the flow cell, another fluid introduced from the outside into the flow cell or fluid originating from a further storage region of the flow cell can flow via the inflow channel 4, flushing out the reagent material 7 from the storage space 3 and mixing it with the further fluid via the outflow channel 5 Reagent material 7 for further processing within the flow cell supplies.

Bei dem weiteren Fluid 8 kann es sich z.B. um eine durch die Flusszelle zu untersuchende Probenflüssigkeit oder um ein weiteres flüssiges Reagenz, z.B. einen Wasch- oder Verdünnungspuffer, handeln. Als weiteres Fluid 8 In Betracht kommen auch Mischungen aus einer Probenflüssigkeit und einem flüssigen Reagenz.The further fluid 8 may be e.g. a sample liquid to be assayed by the flow cell or another liquid reagent, e.g. a washing or dilution buffer, act. As further fluid 8, mixtures of a sample liquid and a liquid reagent are also possible.

Es versteht sich, dass die Flusszelle selbst oder ein Betreibergerät eine Druckquelle für den Fluidtransport durch den Zuflusskanal 4, den Speicherraum 3 und den Abflusskanal 5 aufweist (nicht gezeigt). Eine solche Druckquelle könnte z.B. durch einen Blisterspeicher für einen Wasch- und Verdünnungspuffer gebildet sein. Alternativ wäre ein von außen durch eine Betreibereinrichtung oder manuell durch einen Nutzer elastisch oder plastisch verformbarer Bereich der Flusszelle oder eine über einen Luft- bzw. Pneumatikanschluss der Flusszelle anschließbare Luftpumpe einer Betreibereinrichtung als Druckquelle möglich.It is understood that the flow cell itself or an operator device has a pressure source for the fluid transport through the inflow channel 4, the storage space 3 and the outflow channel 5 (not shown). Such a pressure source could e.g. be formed by a blister memory for a washing and dilution buffer. Alternatively, an area of the flow cell which can be elastically or plastically deformed from the outside by an operator device or manually by a user or an air pump which can be connected via an air or pneumatic connection of the flow cell to an operating device as a pressure source would be possible.

Das zwecks Ausspülung des Reagenzmaterial 7 aus dem Speicherraum 3 heranströmende Fluid verdrängt vor sich die in dem Zuflusskanal 4 enthaltene Luft. Ohne den Bypass 6 würde zwischen dem Reagenzmaterial 7 und dem heranströmenden Fluid ein unerwünschtes, die Vermischung von Reagenzmaterial und Fluid beeinträchtigendes Luftpolster entstehen. Der Strömungswiderstand des Bypass 6 für die Luft ist so gering, dass der Luftdruck in Strömungsrichtung vor dem Speicherraum 3 nicht so weit ansteigen kann, dass die Luft das Reagenzmaterial 7 gegen das Haltevermögen des Speicherraums aus dem Speicherraum 3 herausdrücken kann. Die Vorderfront des Fluids 8 erreicht dadurch das Reagenz 7 und spült unter Vermischung mit dem Reagenz 7 das Reagenz 7 aus dem Speicherraum 3 heraus.The fluid flowing in for the purpose of flushing out the reagent material 7 from the storage space 3 displaces the air contained in the inflow channel 4 in front of it. Without the bypass 6, an undesirable air cushion impeding the mixing of the reagent material and the fluid would arise between the reagent material 7 and the oncoming fluid. The flow resistance of the bypass 6 for the Air is so low that the air pressure upstream of the storage space 3 in the direction of flow can not rise so high that the air can push out the reagent material 7 from the storage space 3 against the retention capacity of the storage space. The front of the fluid 8 thereby reaches the reagent 7 and rinsing out the reagent 7 from the storage space 3 while mixing with the reagent 7.

Der Strömungswiderstand des Bypass 6 für das Fluid 8 ist in dem Beispiel von Fig. 1 hingegen so groß dass kein nennenswerter Anteil des heranströmenden Fluids 8 über den Bypass 6 vorbei an den Speicherraum 3 strömt. Es versteht sich, dass bei Verringerung des Strömungswiderstandes des Bypass 6 für das Fluid 8 durch Vergrößerung des Bypassquerschnitts der durch den Bypass strömende Anteil des Fluids 8 anwächst. Im Hinblick auf eine schnellere Durchmischung von Reagenzmaterial 7 und Fluid 8 kann ein gewünschter Anteil des durch den Bypass 6 strömenden Fluids durch Wahl des Strömungsquellenquerschnitts einstellbar sein.The flow resistance of the bypass 6 for the fluid 8 is in the example of Fig. 1 on the other hand, so great that no appreciable portion of the oncoming fluid 8 flows past the bypass 6 past the storage space 3. It goes without saying that, when the flow resistance of the bypass 6 for the fluid 8 is reduced by enlarging the bypass cross section, the proportion of the fluid 8 flowing through the bypass increases. With a view to a faster mixing of reagent material 7 and fluid 8, a desired proportion of the fluid flowing through the bypass 6 can be set by selecting the flow source cross section.

Die Figuren 2 bis 7 zeigen Ausführungsbeispiele, die zur Bildung eines Speicherraums 3 für flüssiges Reagenz- oder/und Probenmaterial 7 ein Trägerelement 9 verwenden, das in eine Öffnung 10 in der Flusszelle bzw. deren Substrat 1 einsetzbar und mit der Flusszelle fluiddicht verbindbar ist. Mit dem Speicherraum 3 sind in gleicher Weise wie bei dem Ausführungsbeispiel von Fig. 1 Kanäle verbunden.The FIGS. 2 to 7 show exemplary embodiments, which use a carrier element 9 for forming a storage space 3 for liquid reagent and / or sample material 7, which can be inserted into an opening 10 in the flow cell or its substrate 1 and can be connected in a fluid-tight manner to the flow cell. With the memory space 3 are in the same manner as in the embodiment of Fig. 1 Channels connected.

Das pfropfenartig mit einem zylindrischen Endstück 11, einem Konusabschnitt 12 und einem Kragen 13 ausgebildete Trägerelement 9 weist eine zur Stirnseite hin offene Aufnahmerille für flüssiges Reagenz- oder/und Probenmaterial auf. Die Öffnung 10 im Substrat 1 der Flusszelle ist in der Form etwa dem Trägerelement 9 angepasst. Die Rille ist hydrophilisiert, so dass das flüssige Reagenz- oder/und Probenmaterial an dem Trägerelement in der Rille besonders fest gehalten wird.The plug-like manner with a cylindrical end piece 11, a cone portion 12 and a collar 13 formed carrier element 9 has an open towards the end receiving groove for liquid reagent and / or sample material. The opening 10 in the substrate 1 of the flow cell is approximately matched in shape to the carrier element 9. The groove is hydrophilized so that the liquid reagent and / or sample material on the support member in the groove is held particularly tight.

In dem in die Flusszelle eingesetzten Zustand reicht das Trägerelement 9 mit der Stirnseite des zylindrischen Endstücks 11 ggf. bis an die Abdeckfolie 2 heran, so dass das Trägerelement 9 zusammen mit der Abdeckfolie 2 den Speicherraum 3 bildet. Der Querschnitt des Speicherraums stimmt mit dem Querschnitt eines in den Speicherraum einmündenden Zuflusskanals (in den Fig. 2 bis 7 nicht sichtbar) und Abflusskanals überein. Von den Kanälen ist in Fig. 2a der Abflusskanal 5 im Querschnitt sichtbar. In geeigneter Drehstellung des Trägerelements 9 ist der Speicherraum 3 zu den Kanälen ausgerichtet. Zur Sicherung der Ausrichtung des Speicherraums 3 zu den Kanälen könnte an dem Trägerelement 9 und dem Substrat 1 je ein Anschlag gebildet sein.In the state inserted into the flow cell, the carrier element 9 with the end face of the cylindrical end piece 11 extends, if necessary, as far as the covering film 2, so that the carrier element 9 forms the storage space 3 together with the covering film 2. The cross section of the storage space coincides with the cross section of an inflow channel which leads into the storage space (into the Fig. 2 to 7 not visible) and drainage channels match. Of the channels is in Fig. 2a the drainage channel 5 in cross section visible. In a suitable rotational position of the carrier element 9, the storage space 3 is aligned with the channels. To secure the orientation of the storage space 3 to the Channels could be formed on the support member 9 and the substrate 1 per a stop.

Indem der Durchmesser des Endstücks 11 geringer als der Durchmesser des das Endstück 11 aufnehmenden Abschnitts der Öffnung 10 in dem Substrat 1 ist, ist ein aus zwei Strömungskanälen bestehender Bypass 6 gebildet.By the diameter of the end piece 11 is smaller than the diameter of the portion 11 of the opening 10 receiving the end piece 11 in the substrate 1, a bypass 6 consisting of two flow channels is formed.

Durch den Konusabschnitt 12 des Trägerelements 9 ist der Speicherraum nach außen fluiddicht verschlossen. Zusätzlich zu dem Konusverschluss könnte das Trägerelement 9 mit dem Substrat 1 fluiddicht verschweißt oder/und verklebt sein.By the cone portion 12 of the support member 9, the storage space is closed to the outside fluid-tight. In addition to the cone closure, the carrier element 9 could be welded to the substrate 1 in a fluid-tight manner and / or adhesively bonded.

Gegenüber dem Ausführungsbeispiel von Fig. 1 haben die Ausführungsbeispiele von Fig. 2 bis 7 den Vorteil, dass das Reagenz- oder/und Probenmaterial nicht durch abschließende Verschweißung oder/und Verklebung des Substrats 1 mit der Abdeckfolie 2 beeinträchtigt wird.Compared to the embodiment of Fig. 1 have the embodiments of Fig. 2 to 7 the advantage that the reagent and / or sample material is not affected by final welding or / and bonding of the substrate 1 with the cover 2.

Das Ausführungsbeispiel von Fig. 3 unterscheidet sich von dem Ausführungsbeispiel von Fig. 2 dadurch, dass der Unterschied zwischen dem Durchmesser des Endstücks 11 und dem das Endstück 11 aufnehmenden Abschnitt der Öffnung 10 noch größer als bei dem Ausführungsbeispiel von Fig. 2 und damit der Strömungsquerschnitt des gebildeten Bypass 6 größer als der Strömungsquerschnitt des Bypass 6 des Ausführungsbeispiels von Fig. 2 ist. Durch den Bypass gemäß Fig. 3 kann dementsprechend ein größerer Anteil eines durch den Zuflusskanal zuströmenden Fluids über den Bypass fließen und, wie bereits oben erwähnt, das Mischungsverhältnis von Reagenz- oder/und Probenflüssigkeit mit dem heranströmenden Fluid geeignet eingestellt werden.The embodiment of Fig. 3 differs from the embodiment of Fig. 2 in that the difference between the diameter of the end piece 11 and the end piece 11 receiving portion of the opening 10 is even greater than in the embodiment of Fig. 2 and thus the flow cross section of the formed bypass 6 is greater than the flow cross section of the bypass 6 of the embodiment of Fig. 2 is. Through the bypass according to Fig. 3 Accordingly, a greater proportion of a fluid flowing through the inflow channel to flow through the bypass and, as already mentioned above, the mixing ratio of reagent and / or sample liquid with the oncoming fluid can be adjusted appropriately.

Es versteht sich, dass sowohl bei dem Ausführungsbeispiel von Fig. 2 als auch dem Ausführungsbeispiel von Fig. 3 ein sich nur über den halben Umfang des Endstücks 11 erstreckender Bypass möglich wäre.It is understood that both in the embodiment of Fig. 2 as well as the embodiment of Fig. 3 a bypass extending only over half the circumference of the end piece 11 would be possible.

Abweichend von den Ausführungsbeispielen von Fig. 2 und 3 ist gemäß Ausführungsbeispiel von Fig. 4 ein Bypass 6 dadurch gebildet, dass das konische Endstück 11 des Trägerelements 9 verkürzt ist und nicht bis an die Abdeckfolie 2 heranreicht.Notwithstanding the embodiments of Fig. 2 and 3 is according to embodiment of Fig. 4 a bypass 6 formed by the fact that the conical end portion 11 of the support member 9 is shortened and does not reach up to the cover sheet 2.

Fig. 5 und 6 betreffen Ausführungsbeispiele, bei denen eine Abdeckfolie 2 im Bereich eines Speicherraums 3 auslenkbar ist, um einen Bypass 6 zu bilden. Gemäß Fig. 5 erfolgt die Auslenkung der Abdeckfolie 2 durch den Druck der umzuleitenden Luft. FIGS. 5 and 6 relate to embodiments in which a cover 2 in the region of a storage space 3 is deflected to form a bypass 6. According to Fig. 5 the deflection of the cover 2 is effected by the pressure of the air to be redirected.

Gemäß Ausführungsbeispiel von Fig. 6 dient ein Unterdruck erzeugendes Betreibergerät 15 zur Auslenkung der Abdeckfolie 2 durch Saugwirkung.According to embodiment of Fig. 6 serves a negative pressure generating operator device 15 for deflecting the cover 2 by suction.

Bei einem in Fig. 7 gezeigten Ausführungsbeispiel weist ein zylindrisches Endstück 11 eines Trägerelements 9 keine zur Stirnseite des Endstücks hin offene Rille, sondern einen Durchgang auf. Der Durchgang bildet einen Speicherraum 3, dessen Querschnitt geringer als der Querschnitt der in den Speicherraum mündenden Kanäle ist, von denen in Fig. 7a der Abflusskanal 5 im Querschnitt sichtbar ist. Der in Fig. 7a in seiner Lage durch Strichlinien angedeutete Speicherraum 3 ist etwa auf die Mitte des Querschnitts der einmündenden Kanäle ausgerichtet.At an in Fig. 7 In the embodiment shown, a cylindrical end piece 11 of a carrier element 9 does not have a groove open towards the end face of the end piece, but has a passageway. The passage forms a storage space 3 whose cross section is smaller than the cross section of the channels opening into the storage space, of which in Fig. 7a the drainage channel 5 is visible in cross section. The in Fig. 7a in its position indicated by dashed lines memory space 3 is aligned approximately at the center of the cross section of the opening channels.

Über den Bypass mit verhältnismäßig großem Strömungsquerschnitt durch den Zuflusskanal zuströmendes Fluid schließt das Reagenz- oder/und Probenmaterial im Abflusskanal 5 in der Strömung ein, wobei es zu einer Art Zentrierung des Reagenz- oder/und Probenmaterials in dem den Speicherraum 3 ausspülenden Fluid kommt. Dadurch lässt sich z.B. eine Probe mit Partikeln, wie z.B. die Zellen einer Blutprobe, im Abflusskanal zentriert abführen, um sie z.B. einzeln nach dem Prinzip eines Cytometers zu analysieren.Fluid flowing in via the bypass with a relatively large flow cross section through the inflow channel encloses the reagent and / or sample material in the outflow channel 5 in the flow, resulting in a type of centering of the reagent and / or sample material in the fluid flushing out the storage space 3. This allows e.g. a sample with particles, e.g. the cells of a blood sample, centered in the drainage channel, to remove them e.g. individually to analyze according to the principle of a cytometer.

Das Substrat 1 und das Trägerelement 9 der vorangehend beschriebenen Flusszellen bestehen vorzugsweise aus Kunststoffen wie PMMA, PC, COC, COP, PPE, PE und sind durch Spritzgießen hergestellt. Vorzugsweise stimmen die Materialien von Substrat 1 und Trägerelement 9 überein.The substrate 1 and the carrier element 9 of the flow cells described above are preferably made of plastics such as PMMA, PC, COC, COP, PPE, PE and are produced by injection molding. Preferably, the materials of substrate 1 and carrier element 9 match.

Claims (12)

  1. Microfluidic flow cell having a storage space (3) which receives liquid reagent material and/or sample material (7) and which is connected to an inlet channel (4) for a fluid (8) which transports out of the storage space (3) the reagent material and/or sample material (7) and to an outlet channel (5) for the reagent material and/or sample material (7) and the fluid (8), wherein the inlet channel (4) and the outlet channel (8) are connected by a bypass (6) which bypasses the storage space (3),
    characterized
    in that, for the venting of the inlet channel (4), the flow cross section of the bypass (6) is just sufficient to prevent reagent material and/or sample material (7) from being transported, by way of air pressure increasing in the inlet channel (4), out of the storage space (3).
  2. Flow cell according to Claim 1,
    characterized
    in that the storage space (3) forms a channel portion which is aligned with the inlet channel (4) and with the outlet channel (5).
  3. Flow cell according to Claim 1 or 2,
    characterized
    in that the cross section of the storage space (3), which is perpendicular to the flow direction,
    corresponds to the cross section of the inlet channel (4) and/or the cross section of the outlet channel (5).
  4. Flow cell according to one of Claims 1 to 3,
    characterized
    in that the cross section of the storage space (3), which is perpendicular to the flow direction, is smaller or larger than the cross section of the inlet channel (4) and/or the cross section of the outlet channel (5).
  5. Flow cell according to one of Claims 1 to 4,
    characterized
    in that the cross section of the storage space (3), which is perpendicular to the flow direction, is constant in the flow direction.
  6. Flow cell according to one of Claims 1 to 5,
    characterized
    in that the bypass (6) is able to be produced by deflection of a flexible cover film (2) bordering the storage space (3).
  7. Flow cell according to Claim 6,
    characterized
    in that the cover film (2) is able to be deflected by way of the air pressure in the feed channel (4) or by way of a suction pressure generated externally by an operator device (15).
  8. Flow cell according to one of Claims 1 to 7,
    characterized
    in that the inlet channel (4), the outlet channel (5) and, if appropriate, the storage space (3) are formed by recesses in a substrate (1), and the recesses are closed off in a fluid-tight manner by a cover (2) which is connected to the substrate (1).
  9. Flow cell according to Claim 8,
    characterized
    in that the cover is a cover film (2) which is welded and/or adhesively bonded to a plate surface of the substrate (1).
  10. Flow cell according to one of Claims 1 to 9,
    characterized
    in that the storage space (3) is adjoined by a carrier element (9) which receives the liquid reagent material and/or sample material (7) and which, while closing off the storage space (3) in a fluid-tight manner, is able to be inserted into an opening (10) in the substrate (1) and is able to be connected to the substrate (1) in a fluid-tight manner.
  11. Flow cell according to Claim 10,
    characterized
    in that a receiving region (14), bordering the storage space (3), of the carrier element (9) for the reagent material and/or sample material (7) is formed in an end piece (11) of a plug-like carrier element (9).
  12. Flow cell according to Claim 11,
    characterized
    in that the bypass (6) extends between the end piece (11) and the inner wall of the opening (10).
EP16190102.0A 2016-06-30 2016-09-22 Microfluidic flow cell with a flowing reagent and/or sample material receiving storage space Active EP3263217B1 (en)

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US16/314,539 US11045804B2 (en) 2016-06-30 2017-05-24 Microfluidic flow cell having a storage space that holds liquid reagent material and/or sample material
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WO2018001647A1 (en) 2018-01-04
CN109328110A (en) 2019-02-12
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WO2018001648A1 (en) 2018-01-04
US20190321822A1 (en) 2019-10-24
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US20190262830A1 (en) 2019-08-29
CN109414697B (en) 2021-04-30
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US11045804B2 (en) 2021-06-29
CN109328110B (en) 2021-08-06

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