EP3263215A1 - Flow cell with reagent storage - Google Patents

Abstract

The invention relates to a flow cell with at least one storage area (13) containing a liquid reagent (8). According to the invention, the storage area (13) is delimited by a carrier element (7) introduced into an opening in the flow cell together with the reagent (8), the carrier element (7) sealing the storage area (13) to the outside in a fluid-tight manner and 8) on the carrier element (7) holding vascular and / or capillary structure (12).

Description

The invention relates to a flow cell having at least one storage area containing a reagent.

As is known, microfluidic flow cells are increasingly used in the diagnosis, analysis and / or synthesis of substances, especially in the life sciences. As is known, 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 during the manufacture 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 are in particular by predetermined breaking barriers sealed blisters into consideration, which are preferably made of aluminum laminates. The capacity of such blisters can not be arbitrarily reduced or enlarged. In particular, large blisters require protection against accidental expressions cover housing. At the bottom, the capacity is limited by manufacturing tolerances, with a lower limit of about 50 microliters.

Although there are no such limitations for storage spaces integrated into the flow cell, complicated connection channels for filling and venting are required, which are then carried out after placement of the reagent within the flow cell Welding or gluing are sealed to complete the storage space hermetically and storage stable. Liquid reagents may be, for example, fluorescent dyes, acids, bases, alcohols, bead solutions, lysis buffers, antibodies, enzymes, DNA fragments, PCR reagent mixtures or wash buffers.

The invention has for its object to provide a new flow cell with a storage area for small liquid reagent volumes, which can be produced with reduced complexity compared to the prior art.

The flow cell according to the invention that achieves this object is characterized in that the storage area is delimited by a carrier element introduced into an opening in the flow cell together with the reagent, the carrier element sealing off the storage area to the outside in a fluid-tight manner and holding the liquid reagent on the carrier element Vascular and / or capillary structure has.

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

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

The support member may be connected to the flow cell solely by force and / or positive engagement, for example, when the liquid reagent is introduced into the flow cell during use of the flow cell. Alternatively or additionally, the flow cell is welded or glued to the flow cell in a connection region arranged at a distance from the reagent. Due to the distance of the connection area to the reagent, impairments of the reagent due to welding heat or adhesive vapors can be avoided.

In a particularly preferred embodiment of the invention, the storage area is in fluid communication with at least one transport channel of the flow cell. In particular, a transport channel of the flow cell leads to the storage area and a transport channel of the flow cell away from the storage area, wherein in the channel or in each case the channels a reagent hermetically enclosing predetermined rupture barrier can be formed.

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 cover film, which covers the opening and possibly the at least one transport channel.

The storage area may 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 of a chamber formed in the flow cell, in particular a mixing chamber.

The carrier element is preferably designed in the manner of a plug filling the opening with an end face having the vessel or / and 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.

Suitably, the carrier element is provided on a side facing away from the storage area with means for handling and in particular comprises a seat for connection to a mounting tool. The handling devices may be useful both in filling the vessel and / or capillary structure and in mounting the carrier element having the reagent.

In a further embodiment, the carrier element on a side facing away from the storage area on a collar forming the above-mentioned connection region, via which a welding or / and gluing can be done with the flow cell.

In a further embodiment, the vascular and / or capillary structure has a groove receiving the reagent or a channel receiving the reagent, the groove or channel preferably being open at at least one end to a lateral surface of the support member.

In a particularly preferred embodiment of the invention, means for detaching the liquid reagent from the vessel or / and capillary structure are provided.

Such devices may be provided for detachment of the reagent by a fluid flushing the reagent or by an inertial force, in particular centrifugal force, detaching the reagent. To generate a centrifugal force, the flow cell can be used in use e.g. be rotated by an operator device in rotation.

When the reagent with a free liquid surface adjoins an interior space of a mixing chamber formed in the flow cell, in particular by shaking the flow cell, a fluid provided in the mixing chamber can wash off the liquid reagent. Alternatively, in the mixing chamber, the liquid reagent may be washed off by rinsing once or more while rocking a sample liquid or other mixing or rinsing liquid.

In a particularly preferred embodiment of the invention, the groove or the channel of the vessel and / or capillary structure is aligned with the transport channel leading to the storage area and away from the storage area, so that a flushing flow can flow through the storage area.

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 purge 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 the transport channel leading to the storage area and / or leading away.

In addition, the flow cross section of the bypass may be larger than the flow cross section of the storage area, so that a possibly desired delayed or gradual rinsing takes place over a longer period.

The support member may be rotatably connected to the flow cell, and e.g. have a stop, by which the above-mentioned alignment of the storage area is secured to the channels.

In a further embodiment of the invention, at least the vessel and / or capillary structure of the carrier element has a hydrophilic surface, by means of which a desired reagent volume can be measured more accurately during wetting with the liquid reagent.

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

It is understood that a carrier element could also form several storage areas within a flow cell.

Fig. 1

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

Fig. 2

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

Fig. 3 und 4

weitere Ausführungsformen für Flusszellen nach der Erfindung in geschnittener Teildarstellung,

Fig. 5 und 6

weitere Ausführungsbeispiele für Trägerelemente nach der Erfindung,

Fig. 7 bis 11

weitere Ausführungsbeispiele für Flusszellen nach der Erfindung in geschnittener Teildarstellung,

Fig. 12 bis 14

Schnittansichten weiterer Ausführungsbeispiele für erfindungsgemäße Trägerelemente, und

Fig. 15 und 16

weitere Ausführungsbeispiele für Flusszellen nach der Erfindung in geschnittener Teildarstellung.

The invention will be explained below with reference to embodiments and the accompanying, relating to these embodiments drawings. Show it:

Fig. 1

a flow cell according to the invention with a reagent carrier element which can be inserted into the flow cell in a partially cutaway view,

Fig. 2

an embodiment of a usable in a flow cell according to the invention carrier element,

3 and 4

further embodiments of flow cells according to the invention in a sectional partial representation,

FIGS. 5 and 6

Further embodiments of carrier elements according to the invention,

Fig. 7 to 11

further embodiments of flow cells according to the invention in a sectional partial representation,

Fig. 12 to 14

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

FIGS. 15 and 16

further embodiments of flow cells according to the invention in a sectional partial representation.

An in Fig. 1 Sectionally illustrated flow cell suitably comprises a plate-shaped substrate 1, which is glued or welded on a plate side with a film 2. Recesses which are open towards the film 2 in the substrate 1 form a structure of transport channels and chambers, which is covered by the film 2 and is typical for flow cells, of which Fig. 1 a transport channel 3 is visible in cross section.

The transport channel 3 opens into a closed through the film 2 at one end through opening 4 with a conical section 5. The latter is extended by a connected to the substrate 1 ring projection 6. The mouth of the transport channel 3 is an opening of another, in Fig. 1 invisible transport channel diametrically opposite.

In the through hole 4, a support member 7 for a liquid reagent 8 can be used. The rotationally symmetrical carrier element 7, which is rotationally symmetrical in the embodiment shown, has a lateral surface 9 corresponding to the passage opening 4 and is provided on its outside with a peripheral 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 vascular and / or capillary structure in the form of a groove 12, as described with reference to FIG Fig. 2 showing a similar carrier element 7, can be seen. The groove 12 is open both to the front side and to the lateral surface 9 of the support member 7.

Before the flow cell is mounted, 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 introduction of the support member 7 in the passage opening 4 and welding or / and bonding of the collar 10 with the annular shoulder 6 remains the liquid Reagent 8 first in the covered by the film 2 groove 12, which forms a storage area 13 within the now completed flow cell together with the film 2, to which the support member 7 extends.

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 sheet 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 as plastic into consideration. Also, the support member 7 may consist of the same plastic material as the substrate 1 and / or the cover 2. The substrate is preferably made of a brittle plastic, such as PC or COC, the carrier element 7 of a ductile material, such as PE or PP, to make the conical press connection more pressure-resistant.

In use of the flow cell, the liquid reagent 8 is removed from the storage area 13 as needed, e.g. by another fluid flowing over the transport channel 3, e.g. a sample to be analyzed or another stored reagent, e.g. a washing or dilution buffer. The additional fluid displaces the liquid reagent 8 from the storage area 13 oriented towards the channel 3 into the diametrically opposite transport channel mentioned above, where it can mix with the stored reagent.

If the rinsing and displacement of the liquid reagent 8 from the storage area 13 itself by a liquid, so the formation of an air cushion between the liquid reagent and the latter liquid must be avoided as possible. For this purpose, a bypass 14 serve, according to Fig. 3a can be formed by reducing the diameter of a cylindrical end piece 15 of the support member 7.
As Fig. 3b shows, the formation of a bypass 14 'by shortening the tail 15 would be possible. In the latter case, the carrier element 7 no longer extends to the cover sheet 2. It is understood that for ventilation according to Fig. 3a Also a slot on only one side of the memory area 13 could suffice.

A rinsing liquid advancing air flows through the bypass 14 or 14 ', while the liquid reagent initially continues in the storage area 13 by Copulatory forces is maintained. If the rinsing liquid reaches the storage area, the bypass 14, 14 'also fills with rinsing liquid. However, since the flow cross section of the bypass 14, 14 'is smaller than the flow cross section in the storage area 13, a lower flow resistance results in the storage area 13 and the rinsing liquid transports the liquid reagent 8 out of the storage area.

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

By way of derogation from the examples shown, bypasses could also be formed by the cover sheet 2 not being fixedly connected to the substrate as far as the edge of the through-hole 4 and by external means, e.g. by negative pressure, to the formation of ventilation slots can be deflected.

The flow cross-section of lateral vents, as in Fig. 3a may 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 discharged over a longer period. In this way, an intensive mixing of reagent and rinsing liquid can take place.

In another embodiment, the storage area may be smaller in cross section than the cross section of the transport channels in fluid communication with the storage area, as shown in FIG Fig. 4 is indicated. As a result, the reagent is effectively centered in the rinsing fluid, 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 of carrier elements go from the Fig. 5 and 6 out.

Fig. 5 shows a carrier element 7, extending from the carrier element of 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 ends of carrier elements with a vessel or / and capillary structure are shown. Fig. 6a shows a support member having a central, pocket-shaped recess 50 which centrally in the end face of a plug-shaped carrier element is formed. The reagent wets the recess 50 and forms a reproducible drop shape. The well is accessible from one side to flush the reagent out of the well, the embodiment is particularly suitable for use in conjunction with a mixing chamber, as discussed below.

According to Fig. 6b is not a continuous recess but a microstructured surface formed, for example, has columns or grooves in a grid between 10 and 500 microns, preferably 20 and 200 microns. Preferably, the surface is increased by hydrophilization and the wetting properties are improved, which brings about a better control of the drop formation of the sample and thus better reproducibility of the dimension of the reagent. The reagent is accessible from one side for rinsing.

Fig. 6c shows a three sides open towards the groove passage 16 with cross-sectional dimensions of typically 0.12 x 0.12 mm ² to 2 x 2 mm ^2. The channel region is hydrophilic modified. Smaller channel dimensions allow better control of the wettability and thus reproducibility of the measured reagent quantities. The beginning and end of the meandering meandering channel may communicate with a flushing channel.

Fig. 6d differs from the embodiment of Fig. 6c in that the meandering meandering channel 16 is covered by a film 17 made of plastic, which forms a part of the two-part carrier element in this case. The film 17 provides protection for the reagent prior to assembly of the support member.

The surfaces 16 delimiting the channel can, as in the embodiment of Fig. 6c , wholly or partially hydrophilically modified. Due to the capillary-filling channel 16 reagent amounts can be measured accurately by the capillary action allows neither an over-nor a sub-filling of the channel 16. Also, the channel 16 may be integrated for emptying into a flushing channel.

Fig. 6e shows a two-part reagent carrier element with a vascular and / or capillary structure, which is formed by an absorbent fleece 18, which receives the reagent capillary. For example, the sucked-up reagent can be released within a mixing chamber by expressing it from the storage area. Also a replacement by rinsing would be possible, for example, if a particularly slow release of the reagent is desired.

Fig. 7 shows a section of a flow cell, which consists of a substrate 1 and a cover 2 and formed in which a mixing chamber 19 is provided. Into the mixing chamber 19 projects a carrier element 7 with a liquid reagent 8 in. The mixing chamber 19 is also in communication with a transport channel 20, in which a hermetically occluding the predetermined breaking barrier 21 is formed. 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 acting on the flow cell from the outside. In the mixing chamber 19 existing liquid can wash out the reagent, which can be supported for example by shaking the flow cell.

Fig. 8 shows a section of a flow cell 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 by a predetermined rupture barrier 21 'or 21 "against the remaining flow cell with a view to long-term storage of the flow cell prior to use to the transport channel 3, for example by rotation of the rotatably connected in this case with the flow cell support member. 7

Fig. 9 shows a detail of a plan view of a flow cell with a channel region 23, in which a reagent carrier element 7 a storage area for a reagent 8 is formed. To improve the mixing of the reagent 8 with a transport fluid or a sample to be examined as a transport fluid, the channel region 23 is meander-shaped, with a widening 24 being formed downstream for further improvement of the mixing. The washing 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 , Washable storage areas are formed in the mixing chambers by reagent carrier elements 7 ', 7 "and 7'".

Fig. 11 shows fragmentary flow cells in the form of a round disk or a disk segment. The flow cells are provided for cooperation with an operator device that rotates the flow cells. A mixing or reaction chamber 25 is located radially further outside 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. 11a there is a predetermined breaking barrier 26. The mixing chamber 25 is also in communication with a channel 27 for the supply of eg 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 by means of the centrifugal force generated during the rotation of the flow cell, whereby the predetermined rupture barrier 26 is opened by the pressure of the reagent. Alternatively, the disruption of the predetermined breaking barrier by external means could take place.

Fig. 11b shows a provided for rotation flow cell with two storage chambers 28, for example for a washing buffer or other liquid reagents. The storage chambers 28 are each separated by a predetermined breaking barrier 29 from a storage area 13, wherein the two storage areas 13 via further predetermined breaking barriers 30 in conjunction with the mixing chamber 25, which is connected to an inlet and outlet channel 27, stand. By rotation of the flow cell, for example, the washing buffer is transferred while flushing the storage areas in the mixing chamber, wherein the predetermined breaking barriers 29,30 can be digested by the fluid pressure or other means.

An in Fig. 11c shown, provided for rotation flow cell additionally has a blister store 31 for a wash buffer, which is arranged using the space of the flow cell radially further outward than a storage area 13. When pressing out the blister 31 by, for example, mechanical actuation and pressing, a predetermined breaking barrier 32 opens. When the blister accumulator 31 is pressed 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 its vascular and / or capillary structure is hydrophilized, but also the whole, the vascular or / and capillary having end face and a conical surface 34. The hydrophilization is formed by a glassy layer with a contact angle to water less than 50 °.

Changes in the surface properties of the plastic forming the carrier element can be carried out wet-chemically by applying wetting agents or surfactants and subsequent drying (hydrophilic or hydrophobic). In addition, a surface activation by means of plasma, flaming or corona treatment (hydrophilic) can be performed. Surface coatings by plasma polymerization, e.g. glassy layers, hydrophilic or hydrophobic, or combinations thereof may be applied over the entire area / completely or masked locally.

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

Fig. 13 shows a Reagenzträgerelement 7 with a memory region forming channel structure 35, which is formed by covering a three-sided open groove with a film 36. The channel walls of the two-sided open channel structure 35 are hydrophilized including the film 36, for example by wet chemical treatment.

Fig. 14 shows a two-piece reagent carrier element of a plastic injection molded part 39 and a film 36, the 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 or / and capillary structure for receiving a liquid reagent 8. The channel 40 communicates via a channel 41 in communication with a channel 42 which is passed through the further conical section. Via the channels 42 and 41, the channel 40 forming a memory area can be integrated into a flushing channel of the flow cell.

An in Fig. 15 The flow cell shown in section has a liquid reagent storage area 13 as described above. The storage area 13 is in communication with a supply channel 43 for a fluid for purging the liquid reagent from the storage area 13. The supply channel 43 is in Connection with a pressure source, not shown. A discharge channel 44 which leads away from the storage area 13 and which, like the supply channel 43, is partially meandered, leads into a mixing chamber 45. The mixing chamber 45 is either permanently closed or has a closure valve (not shown) which extends through an operating device for the flow cell let operate.

The pressure source conveys the fluid with the rinsed reagent into the mixing chamber 45 in which a back pressure to the pressure source builds up by compression of air contained therein. The pressure of the pressure source is variable, so that achieved by the back pressure built up in the mixing chamber 45, a reversal of the movement of the fluid with the rinsed reagent and the fluid with the rinsed reagent with intensive mixing by varying the pressure of the pressure source to move back and forth ,

An in Fig. 16 A flow cell with a storage area 13 for a liquid reagent has a mechanically actuable blister 46 which is connected to the storage area 13 via a predetermined breakage barrier 47 in a feed line 43. The blister 46 contains a fluid through which the liquid reagent can be rinsed out of the storage area 13. In a discharge line 44, an operable by an operating device valve 48 is provided. Between the storage area 13 and the valve 48, the discharge line 44 is in communication with a storage chamber 49th

By actuation of the blister 46, the fluid presses against the predetermined breaking barrier 47 and closes the predetermined breaking barrier 47. When the valve 48 is closed, the fluid is transported with the rinsed reagent in the storage chamber 49, in which builds up a back pressure. The back pressure can be used for a return transport of the fluid with the rinsed reagent in the blister 46, wherein the wall of the blister inflates again. By repeatedly pressing the blister 46, the fluid with the rinsed reagent with intensive mixing is moved back and forth. Via the opened valve 49, the mixture can then be transported away for further use within the flow cell.

In the above based on the FIGS. 3, 4 . 9 to 11 or 15 and 16 flow cells described could also be used instead of carrier elements for a liquid reagent and carrier elements for a liquid sample to be analyzed. Especially for the According to flow cells FIGS. 15 and 16 Carrier elements for a dry reagent would also be considered.

It should also be mentioned later that a vessel and / or capillary structure can also be formed only by a hydrophilized carrier surface, in particular a circular carrier surface to which, if appropriate, a hydrophobic surface adjoins.

Claims (15)

Flow cell with at least one storage area (13) containing a liquid reagent (8),
characterized,
in that the storage area (13) is delimited by a carrier element (7) introduced into an opening in the flow cell together with the reagent (8), the carrier element (7) sealing the storage area (13) to the outside in a fluid-tight manner and a liquid reagent ( 8) on the carrier element (7) holding vascular and / or capillary structure (12). Flow cell according to claim 1,
characterized,
in that the storage area (13) is hermetically sealed against a cavity within the flow cell by at least one predetermined rupture stop (21, 29, 30, 32). Flow cell according to claim 1 or 2,
characterized,
that the support element (7) connected to the flow cell only by force and / or form closure and / or arranged in a to the reagent (8) at a distance from the connecting region (10) welded to the flow cell and / or is glued. Flow cell according to one of claims 1 to 3,
characterized,
in that the storage area (13) is in fluid communication with at least one transport channel (3) of the flow cell and in particular a transport channel of the flow cell leads to the storage area (13) and leads away a transport channel of the flow cell from the storage area (13). Flow cell according to one of claims 1 to 4,
characterized,
that the support element (7) in the manner of the opening (4) filling with a plug the vascular and / or capillary structure (12) having end face is formed, and in particular a conical portion (5). Flow cell according to one of claims 1 to 5,
characterized,
in that the carrier element (7) is provided on a side facing away from the storage area (13) with handling means and in particular comprises a seat (11) for connection to a tool. Flow cell according to one of claims 1 to 6,
characterized,
in that devices for detaching the liquid reagent (8) from the vessel or / and capillary structure are provided, the detachment devices in particular for detaching the reagent (8) by a fluid flushing off the reagent (8) or by detaching the reagent (8) Inertia, in particular centrifugal force, are provided. Flow cell according to one of claims 1 to 7,
characterized,
in that a storage area (28, 39, 46) for the fluid rinsing off the reagent (8) is provided upstream of the storage area (13) in the direction of flow of a fluid flushing the reagent (8). Flow cell according to one of claims 1 to 8,
characterized,
that in the flow direction of the reagent abspülendes (8) fluid downstream of the storage area (13) is a closed or closable mixing region (25,45,49) and the fluid with the rinsed reagent (8) in the mixing section under construction of a back pressure in the mixing region conveying pressure source (46) are provided. Flow cell according to claim 9,
characterized,
in that the pressure of the pressure source can be varied by reciprocating the fluid having the flushed reagent (8) between the pressure source and the mixing area. Flow cell according to one of claims 4 to 10,
characterized,
that a groove (12) or a channel of the vascular and / or to the capillary structure to the storage area afferent and leading away from the storage area transport channel (3) is aligned. Flow cell according to claim 11,
characterized,
in that the transport channel leading to the storage area (13) and the transport channel leading away from the storage area are connected by a bypass (14) bypassing the storage area (13). Flow cell according to claim 11 or 12,
characterized,
is that the flow cross-section of the storage area (13) smaller than the flow cross-section of to the storage area (13) afferent and / or leading away transport channel. Flow cell according to claim 12 or 13,
characterized,
that the flow cross section of the bypass (14) is greater than the flow cross section of the storage area (13) and, in particular, the reagent (8) having a free liquid surface at an interior of a chamber formed in the flow cell (19), in particular mixing chamber adjacent. Flow cell according to one of claims 1 to 14,
characterized,
that at least the vessel and / or capillary structure (12) of the carrier element (7) at least partially has a hydrophilized surface area.

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