EP3263215B1 - Device with a flow cell with reagent storage - Google Patents

Description

The invention relates to a device with at least one storage area containing a liquid reagent, the storage area being delimited by a carrier element introduced into an opening in a flow cell together with the reagent, the carrier element sealing off the storage area from the outside in a fluid-tight manner, the storage area connecting the liquid reagent the carrier element holding the vessel and / or capillary structure and wherein the storage area is connected to at least one transport channel located in the flow cell.

As is known, microfluidic flow cells are increasingly used in diagnostics, analysis and / or synthesis of substances, especially in the life sciences. It is known that such flow cells often process very small volumes of reagents which interact with the samples to be analyzed or processed and which are to be introduced into the flow cells in the course of the production or use of the flow cells.

Reagents can be stored within flow cells in storage spaces, transport channels or containers placed in the flow cells. For the storage of liquid reagents, in particular blisters closed by predetermined break barriers come into consideration, which are preferably made of aluminum laminates. The capacity of such blisters can neither be reduced nor reduced at will enlarge. Large blisters, in particular, require a cover housing that protects against inadvertent pressing out. The capacity is limited by manufacturing tolerances, with a lower limit of approx. 50 microliters. Such limitations do not exist in the case of storage spaces integrated in the flow cell, but complex connection channels are required for filling and venting which, after the reagent has been placed inside the flow cell, must then be sealed by welding or gluing in order to seal the storage space hermetically and in a stable manner. Liquid reagents can be, for example, fluorescent dyes, acids, bases, alcohols, bead solutions, lysis buffers, antibodies, enzymes, DNA fragments, PCR reagent mixtures or washing buffers.

Flow cells that have the features specified in the preamble of claim 1 are from US 2013/299041 A1 , EP 1285 628 A2 , US 2013/302842 A1 , EP1203959 A1 as EP 2 821 138 A1 known. In all of these known flow cells, the storage area is connected to a channel discharging the liquid reagent from the storage area.

The invention is based on the object of creating a new device of the type mentioned at the beginning with a storage area for small liquid reagent volumes, which can be produced with less effort than the prior art.

The device according to the invention which achieves this object is characterized in that the storage area is connected to a further transport channel of the flow cell and that a groove or a channel of the vessel and / or capillary structure is aligned with the transport channel and the further transport channel in such a way that a flushing flow can flow through the storage area.

The present invention advantageously allows a small volume of a liquid reagent to be introduced into the flow cell both in the course of production and use of a flow cell, preferably reagent volumes between 1 and 100 microliters, in particular between 5 and 50 microliters. Complex ventilation channels that have to be sealed can be avoided. The reagent to be stored can be conveniently applied in the vessel and / or capillary structure of the carrier element outside the flow cell by pipetting or dipping onto the carrier element.

In one embodiment of the invention, the storage area within a flow cell is hermetically sealed against internal cavities of the flow cell by at least one predetermined breaking barrier. In this way, the flow cell provided with the liquid reagent can be stored for a long time.

The carrier element can be connected to the flow cell solely by force and / or form fit, e.g. when the liquid reagent is introduced into the flow cell in the course of using the flow cell. As an alternative or in addition, the flow cell is welded and / or glued to the flow cell in a connection area arranged at a distance from the reagent. Due to the distance between the connection area and the reagent, adverse effects on the reagent due to welding heat or adhesive vapors can be avoided.

A predetermined breaking barrier hermetically enclosing the reagent can be formed in each of the channels.

The opening is preferably formed in a plate-shaped substrate of the flow cell and the flow cell comprises, in particular, a cover connected to the substrate, in particular a cover film, which covers the opening and possibly the at least one transport channel.

The storage area can be limited within the flow cell solely by the vessel and / or capillary structure of the carrier element or by the vessel and / or capillary structure and the cover.

Alternatively, the reagent with a free liquid surface adjoins an interior space of a chamber, in particular a mixing chamber, formed in the flow cell.

The carrier element is preferably designed in the manner of a plug which fills the opening with an end face having the vessel and / or capillary structure. In particular, the carrier element has a conical section which can ensure a tight closure of the storage area with sufficient ventilation of the storage area.

The carrier element is expediently provided with handling devices on an outside facing away from the storage area and comprises in particular a seat for connection to an assembly tool. The handling devices can be useful both when filling the vessel and / or capillary structure and when assembling the carrier element containing the reagent.

In a further embodiment, the carrier element has, on an outer side facing away from the storage area, a collar which forms the abovementioned connecting area and via which a welding and / or gluing to the flow cell can take place.

The groove or the channel is preferably open at at least one end to a lateral surface of the carrier element.

In a particularly preferred embodiment of the invention, devices are provided for detaching the liquid reagent from the vessel and / or capillary structure by means of an inertial force, in particular centrifugal force. To generate a centrifugal force, the flow cell can be set in rotation during use, e.g. by an operator device.

If the reagent with a free liquid surface adjoins an interior space of a mixing chamber formed in the flow cell, a fluid provided in the mixing chamber can wash off the liquid reagent, in particular by shaking the flow cell. Alternatively, the liquid reagent can be washed off in the mixing chamber by rinsing it over one or more times while moving a sample liquid or another mixed or rinsing liquid to and fro.

In a further preferred embodiment of the invention, the transport channel leading to the storage area and the transport channel leading away from the storage area are connected by a bypass bypassing the storage area. Air present between the liquid reagent and a flushing flow can thus flow past the storage area. If the flow cross-section of the bypass is smaller than that of the storage area, the reagent is completely washed out with the flushing fluid.

In a further embodiment, the flow cross-section of the storage area is smaller than the flow cross-section of a transport channel of the flow cell leading to the storage area and / or leading away from the storage area.

In addition, the flow cross-section of the bypass can also be larger than the flow cross-section of the storage area, so that any delayed or gradual flushing that may be desired takes place over a longer period of time.

The carrier element can be rotatably connected to the flow cell and, for example, have a stop, by means of which the aforementioned alignment of the storage area in relation to the channels is secured.

In a further embodiment of the invention, at least the vessel and / or capillary structure of the carrier element has a hydrophilic surface through which a desired reagent volume can be measured more precisely when wetted with the liquid reagent.

To further refine the dimensioning, the vessel and / or channel structure of the carrier element can also be adjoined by a hydrophobic surface of the carrier element in order to achieve a sharp contrast between wettability and non-wettability.

It goes without saying that a carrier element could also form several storage areas within a flow cell.

Fig. 1

eine erfindungsgemäße Vorrichtung mit einem in eine Flusszelle einsetzbaren Reagenzträgerelement in einer geschnittenen Teildarstellung,

Fig. 2

ein Ausführungsbeispiel für ein in einer Vorrichtung nach der Erfindung verwendbares Trägerelement,

Fig. 3 und 4

weitere Ausführungsformen für Vorrichtungen nach der Erfindung in geschnittener Teildarstellung,

Fig. 5 und 6

weitere Ausführungsbeispiele für Trägerelemente nach der Erfindung,

Fig. 7 bis 11

weitere Ausführungsbeispiele für Vorrichtung nach der Erfindung (Fig. 7 und 11a ausgenommen) in geschnittener Teildarstellung,

Fig. 12 bis 14

Schnittansichten weiterer Ausführungsbeispiele für erfindungsgemäße Trägerelemente, und

Fig. 15 und 16

weitere Ausführungsbeispiele für Vorrichtungen nach der Erfindung in geschnittener Teildarstellung.

The invention is explained in more detail below with the aid of exemplary embodiments and the accompanying drawings relating to these exemplary embodiments. Show it:

Fig. 1

a device according to the invention with a reagent carrier element that can be inserted into a flow cell in a sectional partial illustration,

Fig. 2

an embodiment of a carrier element that can be used in a device according to the invention,

Figures 3 and 4

further embodiments for devices according to the invention in a cut partial representation,

Figures 5 and 6

further embodiments for support elements according to the invention,

Figures 7-11

further embodiments for device according to the invention ( Fig. 7 and 11a except) in cut partial representation,

Figures 12-14

Sectional views of further exemplary embodiments for carrier elements according to the invention, and

Figures 15 and 16

further exemplary embodiments for devices according to the invention in a partial sectional view.

One in Fig. 1 The flow cell shown in detail comprises a plate-shaped substrate 1 which is glued or welded to a foil 2 on one side of the plate. Recesses in the substrate 1 that are open towards the film 2 form a structure of transport channels and chambers that is covered by the film 2 and is typical of flow cells, of which in FIG Fig. 1 a transport channel 3 is visible in cross section.

The transport channel 3 opens into a through opening 4 which is closed at one end by the film 2 and has a conical section 5. The latter is extended by an annular attachment 6 connected to the substrate 1. The mouth of the transport channel 3 is a mouth of another, in Fig. 1 not visible transport channel diametrically opposite.

A carrier element 7 for a liquid reagent 8 can be inserted into the through opening 4. The carrier element 7, which is rotationally symmetrical in the exemplary embodiment shown, has a lateral surface 9 corresponding to the through opening 4 and is provided on its outside with a circumferential collar 10. A recess 11 opening out towards the outer surface of the carrier element 7 serves as a seat for receiving a handling tool.

On its end face facing away from the outer surface, the carrier element 7 has a vessel and / or capillary structure in the form of a groove 12, as shown on the basis of FIG Fig. 2 , which shows a similar carrier element 7, can be seen. The groove 12 is open towards both the end face and the lateral surface 9 of the carrier element 7.

Before the assembly of the flow cell, the liquid reagent 8 is applied to the carrier element 7, for example by pipetting or immersing the carrier element in a reagent supply, where it is held in the groove 12 by capillary forces. Even after the carrier element 7 has been introduced into the through opening 4 and the collar 10 has been welded and / or glued to the ring attachment 6, the liquid remains Reagent 8 initially in the groove 12 covered by the film 2, which together with the film 2, to which the carrier element 7 reaches, forms a storage area 13 within the now completed flow cell.

The storable liquid volume of such a storage area 13 is between 1 and 100 microliters, preferably between 2 and 20 microliters.

The substrate 1 and the cover film 2 are preferably made of a plastic, in particular the same plastic, e.g. PMMA, PC, COC, COP, PP or PE. For the preferably injection-molded carrier element, in particular COC, PP, PET, PE, PMMA, PC, PEEK, TPE or silicone come into consideration as plastic. The carrier element 7 can also consist of the same plastic material as the substrate 1 and / or the cover film 2. The substrate preferably consists of a more brittle plastic, such as PC or COC, the carrier element 7 of a more ductile material, such as PE or PP, in order to make the conical press connection more pressure-resistant.

When the flow cell is in use, the liquid reagent 8 is removed from the storage area 13 if necessary, e.g. by means of a further fluid flowing in via the transport channel 3, e.g. a sample to be analyzed or another stored reagent, e.g. a washing or dilution buffer. The further fluid displaces the liquid reagent 8 from the storage area 13, which is aligned with the channel 3, into the mentioned, diametrically opposite transport channel and can mix there with the stored reagent.

If the liquid reagent 8 is flushed out and displaced from the storage area 13 itself by a liquid, the formation of an air cushion between the liquid reagent and the latter liquid must be avoided as far as possible. A bypass 14 can be used for this purpose, which according to FIG Fig. 3a can be formed by reducing the diameter of a cylindrical end piece 15 of the carrier element 7.

How Figure 3b shows, the formation of a bypass 14 'would also be possible by shortening the end piece 15. In the latter case, the carrier element 7 no longer extends as far as the cover film 2. It goes without saying that for ventilation according to FIG Fig. 3a a slot on only one side of the storage area 13 could also suffice.

Air flowing in front of a flushing liquid flows through the bypass 14 or 14 ′, while the liquid reagent initially continues through the storage area 13 Capillary forces is maintained. When the rinsing liquid reaches the storage area, the bypass 14, 14 'is also filled with rinsing liquid. Since the flow cross-section of the bypass 14, 14 'is smaller than the flow cross-section in the storage area 13, there is a lower flow resistance in the storage area 13 and the rinsing liquid transports the liquid reagent 8 out of the storage area.

The opening or opening channel is preferably aligned with the groove 12 forming the vessel and / or capillary structure, the cross-sections preferably having a width of 0.05 to 2 mm and a height of 0.1 to 3 mm.

Deviating from the examples shown, bypasses could also be formed in that the cover film 2 is not firmly connected to the substrate up to the edge of the through opening 4 and can be deflected by external means, e.g. by negative pressure, to form ventilation slots.

The flow cross-section of the side vents as shown in Fig. 3a shown, could also be larger than the corresponding cross section of the storage area 13, so that more rinsing liquid is transported through the ventilation slots and the reagent is dispensed over a longer period of time. In this way, the reagent and rinsing liquid can be intensively mixed.

In a further embodiment, the cross section of the storage area can be smaller than the cross section of the transport channels that are in fluid connection with the storage area, as shown in FIG Fig. 4 is indicated. As a result, the reagent is to a certain extent centered in the rinsing liquid, for example in the sense of hydrodynamic focusing. In the embodiment of Fig. 4 the storage area 13 forms exclusively a passage through the cylindrical end piece 15 of the carrier element.

Further embodiments for support elements go from Fig. 5 and 6th emerged.

Fig. 5 FIG. 7 shows a carrier element 7 which extends from the carrier element of FIG Fig. 2 differs in that two intersecting receiving grooves 12 and 12 'are provided to form a vessel and / or capillary structure.

In Fig. 6 For the sake of simplicity, only the ends of carrier elements with a vessel and / or capillary structure are shown. Figure 6a shows a carrier element with a central, pocket-shaped recess 50, which is centrally located in the end face of a plug-shaped support element is formed. The reagent wets the recess 50 and forms a reproducible drop shape. The recess is accessible from one side in order to rinse the reagent out of the recess; the exemplary embodiment is particularly suitable for use in connection with a mixing chamber, as will be explained below.

According to Figure 6b a microstructured surface is not formed, which has, for example, columns or grooves in a grid dimension between 10 and 500 micrometers, preferably 20 and 200 micrometers. The surface is preferably enlarged by hydrophilization and the wetting properties are improved, which means better control of the drop formation of the sample and thus better reproducibility of the dimensions of the reagent. The reagent can be rinsed out from one side.

Figure 6c shows a groove channel 16 which is open on three sides and has cross-sectional dimensions of typically 0.12 × 0.12 mm ² to 2 × 2 mm ² . The channel area is hydrophilically modified. Smaller channel dimensions allow better control of the wettability and thus reproducibility of the measured amounts of reagent. The beginning and end of the meandering meandering channel can be connected to a flushing channel.

Fig. 6d differs from the embodiment of FIG Figure 6c in that the meandering meandering channel 16 is covered by a film 17 made of plastic, which forms part of the two-part carrier element in this case. The foil 17 offers protection for the reagent before the mounting of the carrier element.

The surfaces delimiting the channel 16 can, as in the embodiment of FIG Figure 6c , be wholly or partially modified to be hydrophilic. Through the capillary-filling channel 16, reagent quantities can be measured precisely, in that the capillary action does not allow the channel 16 to be overfilled or underfilled. The channel 16 can also be integrated into a flushing channel for emptying.

Figure 6e shows a two-part reagent carrier element with a vessel and / or capillary structure, which is formed by an absorbent fleece 18 which absorbs the reagent in a capillary manner. The absorbed reagent can, for example, be released from the storage area within a mixing chamber by squeezing it out. Also a replacement by rinsing would be possible, for example, if a particularly slow release of the reagent is desired.

Fig. 7 shows a detail of a flow cell which is formed from a substrate 1 and a cover film 2 and in which a mixing chamber 19 is provided. A carrier element 7 with a liquid reagent 8 protrudes into the mixing chamber 19. The mixing chamber 19 is also connected to a transport channel 20, in which a predetermined breaking lock 21 is formed, which hermetically seals the mixing chamber 19. The predetermined breaking barrier 21 formed by welding a projection of the substrate 1 to the film 2 can be unlocked by pressure of the liquid in the mixing chamber 19 or by means that act on the flow cell from the outside. Liquid present in the mixing chamber 19 can wash out the reagent, which can be supported, for example, by shaking movements of the flow cell.

Fig. 8 shows a detail of a flow cell made of a substrate 1, a film 2 and a reagent carrier element 7. A storage area 13 for a liquid reagent 8 is formed within a transport channel 3 and aligned with the transport channel. In the example shown, the storage area 13 is hermetically sealed against the rest of the flow cell by a predetermined breaking block 21 'or 21''with a view to long-term storage of the flow cell before use. The storage element 7 has a stop element 22 for the precise alignment of the storage area 13 with the transport channel 3, for example by rotating the carrier element 7, which in this case is rotatably connected to the flow cell.

Fig. 9 shows a detail of a plan view of a flow cell with a channel area 23 in which a reagent carrier element 7 forms a storage area for a reagent 8. In order to improve the mixing of the reagent 8 with a transport fluid or a sample to be examined that is active as a transport fluid, the channel region 23 is designed in a meandering shape, with a widening 24 being formed downstream to further improve the mixing. The washing out can also be assisted by transporting the transport fluid back and forth.

A section of a flow cell with a channel region 23 and two mixing chambers 19 ′, 19 ″ shows Fig. 10 . In the mixing chambers, washable storage areas are formed by reagent carrier elements 7 ', 7 "and 7"'.

Fig. 11 shows excerpts of flow cells in the form of a round disk or a disk segment. The flow cells are designed to work with an operator device that rotates the flow cells. A mixing or reaction chamber 25 is located radially further outward than a storage area 13 formed by a carrier element.

Between the storage area 13 and the mixing chamber 25 of the flow cell of FIG Figure 11a there is a predetermined breaking lock 26. The mixing chamber 25 is also connected to a channel 27 for the supply of, for example, a sample and / or the discharge of the mixture from the mixing chamber, for example by pneumatic actuation. The transport of the reagent into the mixing chamber takes place through the centrifugal force generated during the rotation of the flow cell, whereby the predetermined breaking lock 26 is also opened through the pressure of the reagent. Alternatively, the breaking barrier could be unlocked by external means.

Figure 11b shows a flow cell provided for rotation with two storage chambers 28, for example for a washing buffer or other liquid reagents. The storage chambers 28 are each separated from a storage area 13 by a predetermined breaking barrier 29, the two storage areas 13 being connected to the mixing chamber 25, which is connected to a supply and discharge channel 27, via further predetermined breaking barriers 30. By rotating the flow cell, the washing buffer, for example, is transferred into the mixing chamber while rinsing out the storage areas, with the predetermined breaking barriers 29, 30 being able to be unlocked by the fluid pressure or other means.

One in Figure 11c The flow cell shown and provided for rotation also has a blister memory 31 for a wash buffer, which is arranged radially further out than a storage area 13 using the structural space of the flow cell. When the blister 31 is squeezed out, for example by mechanical actuation and squeezing, a predetermined breaking lock 32 opens. When the blister store 31 is squeezed out, the buffer is transferred into an antechamber 33 which is arranged radially further inward than the storage area 13. By rotating the flow cell, the washing buffer located in the storage space 33 is transported into the mixing chamber 25 while washing out the reagent in the storage area 13.

Fig. 12 shows a reagent carrier 7, in which not only the vessel and / or capillary structure is hydrophilized, but also the entire, the vessel and / or an end face having a capillary structure and a conical jacket surface 34. The hydrophilization is formed by a vitreous layer with a contact angle to water of less than 50 °.

Changes to the surface properties of the plastic forming the carrier element can be made wet-chemically by applying wetting agents or surfactants and then drying (hydrophilic or hydrophobic). In addition, surface activation by means of plasma, flame or corona treatment (hydrophilic) can be carried out. Surface coatings by plasma polymerisation, e.g. glass-like layers, hydrophilic or hydrophobic, or combinations thereof, can be applied locally over the entire area / completely or masked.

Instead of the in Fig. 12 Hydrophilization coating applied outside the vessel and / or capillary structure could be coated with a hydrophobic coating of the carrier element in this area, the typical contact angle being greater than 100 ° in order to emphasize the contrast of wettability and thus further refine the measurement of reagent quantities.

Fig. 13 shows a reagent carrier element 7 with a channel structure 35 which forms the storage area and which is formed by covering a groove open on three sides with a film 36. The channel walls of the channel structure 35, which is open on both sides, including the film 36, are hydrophilized, for example by wet chemical treatment.

Fig. 14 shows a two-part reagent carrier element made of a plastic injection-molded part 39 and a film 36, which has two conical sections 39, 39 'for insertion into two corresponding openings in a flow cell. A capillary channel 40 of one of the conical sections serves as a vessel and / or capillary structure for receiving a liquid reagent 8. The channel 40 is connected via a channel 41 to a channel 42 which is guided through the further conical section. The channel 40, which forms a storage area, can be integrated into a flushing channel of the flow cell via the channels 42 and 41.

One in Fig. 15 The flow cell shown in detail has a storage area 13 for a liquid reagent, as described above. The storage area 13 is connected to a supply channel 43 for a fluid for flushing out the liquid reagent from the storage area 13. The supply channel 43 is in Connection to a pressure source, not shown. A discharge channel 44 leading away from the storage area 13, which, like the supply channel 43, is partly meandering, leads into a mixing chamber 45. The mixing chamber 45 is either permanently closed or has a closure valve (not shown) that extends through an operator device for the flow cell can be operated.

The pressure source conveys the fluid with the rinsed off reagent into the mixing chamber 45, in which a counterpressure to the pressure source builds up through compression of the air contained therein. The pressure of the pressure source can be varied so that the counterpressure built up in the mixing chamber 45 reverses the movement of the fluid with the rinsed reagent and the fluid with the rinsed reagent can be moved back and forth with intensive mixing by varying the pressure of the pressure source .

One in Fig. 16 The flow cell shown in detail with a storage area 13 for a liquid reagent has a mechanically actuatable blister 46 as a pressure source, which is connected to the storage area 13 via a predetermined break lock 47 in a supply line 43. The blister 46 contains a fluid by means of which the liquid reagent can be flushed out of the storage area 13. A valve 48 which can be actuated by an operator device is provided in a discharge line 44. Between the storage area 13 and the valve 48, the discharge line 44 is in communication with a storage chamber 49.

By actuating the blister 46, the fluid presses against the predetermined breaking lock 47 and unlocks the predetermined breaking lock 47. When the valve 48 is closed, the fluid with the reagent that has been rinsed off is conveyed into the storage chamber 49, in which a counterpressure builds up. The counterpressure can be used to transport the fluid with the rinsed off reagent back into the blister 46, the wall of the blister expanding again. By operating the blister 46 several times, the fluid with the rinsed off reagent is moved back and forth with intensive mixing. The mixture can then be transported away via the opened valve 49 for further use within the flow cell.

In the above based on the Figures 3, 4 , 9 to 11 or 15 and 16 instead of carrier elements for a liquid reagent, carrier elements for a liquid sample to be analyzed could also be used. Especially for the Devices according to Figures 15 and 16 Carrier elements for a dry reagent would also come into consideration.

Subsequently, it should also be mentioned that a vessel and / or capillary structure can also be formed merely by a hydrophilized carrier surface, in particular a circular carrier surface, to which a hydrophobic surface is possibly adjacent.

Claims (13)

1. Apparatus having at least one reservoir region (13) which contains a liquid reagent (8), wherein the reservoir region (13) is delimited by a carrier element (7) which is introduced together with the reagent (8) into an opening in a flow cell, the carrier element (7) seals off the reservoir region (13) towards the outside in a fluid-tight manner, and the reservoir region (13) has a vessel and/or capillary structure (12) which holds the liquid reagent (8) against the carrier element (7), and wherein the reservoir region (13) is connected to at least one transport channel (3) situated in the flow cell,
   characterized
   in that the reservoir region (13) is connected to a further transport channel of the flow cell, and in that a groove (12) or a channel of the vessel and/or capillary structure (12) is oriented in relation to the transport channel (3) and the further transport channel in such a way that a flushing flow can flow through the reservoir region (13).
2. Apparatus according to Claim 1,
   characterized
   in that the reservoir region (13) is hermetically sealed with respect to a cavity within the flow cell by at least one predetermined breaking barrier (21, 29, 30, 32).
3. Apparatus according to Claim 1 or 2,
   characterized
   in that the carrier element (7) is connected to the flow cell solely by a force fit and/or form fit, and/or is welded and/or adhesively bonded to the flow cell in a connecting region (10) which is arranged at a distance from the reagent (8).
4. Apparatus according to one of Claims 1 to 3,
   characterized
   in that the carrier element (7) is formed in the manner of a plug which fills the opening (4) and which has a face side having the vessel and/or capillary structure (12), and has in particular a conical portion (5).
5. Apparatus according to one of Claims 1 to 4,
   characterized
   in that the carrier element (7) is provided with handling devices on an outer side facing away from the reservoir region (13) and comprises in particular a seat (11) for connection to a tool.
6. Apparatus according to one of Claims 1 to 5,
   characterized
   in that devices for releasing the liquid reagent (8) from the vessel and/or capillary structure by way of an inertial force, in particular centrifugal force, are provided.
7. Apparatus according to one of Claims 1 to 6,
   characterized
   in that, upstream of the reservoir region (13) in the flow direction of the fluid which flushes away the reagent (8), a reservoir region (28, 39, 46) is provided for the fluid which flushes away the reagent (8).
8. Apparatus according to one of Claims 1 to 7,
   characterized
   in that, downstream of the reservoir region (13) in the flow direction of the fluid which flushes away the reagent (8), a closed or closable mixing region (25, 45, 49) and a pressure source (46) which conveys the fluid with the flushed-away reagent (8) into the mixing region, with build-up of a counterpressure in the mixing region, are provided.
9. Apparatus according to Claim 8,
   characterized
   in that the pressure of the pressure source can be varied with back-and-forth movement of the fluid which has the flushed-away reagent (8) between the pressure source and the mixing region.
10. Apparatus according to one of Claims 1 to 9,
    characterized
    in that the transport channel (3) and the further transport channel are connected by a bypass (14) which bypasses the reservoir region (13).
11. Apparatus according to Claim 9 or 10,
    characterized
    in that the flow cross section of the reservoir region (13) is smaller than the flow cross section of a transport channel, conducting fluid to the reservoir region (13) and/or conducting fluid with reagent (8) away therefrom, of the flow cell.
12. Apparatus according to Claim 10 or 11,
    characterized
    in that the flow cross section of the bypass (14) is larger than the flow cross section of the reservoir region (13), and in particular the reagent (8) adjoins, with a free liquid surface, an interior space of a chamber (19), in particular mixing chamber, formed in the flow cell.
13. Apparatus according to one of Claims 1 to 12,
    characterized
    in that at least the vessel and/or capillary structure (12) of the carrier element (7) has, at least in part, a hydrophilized surface region.

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