EP3108962A1 - Sample carrier - Google Patents

Abstract

The invention relates to a sample carrier (7) having a region (9) for receiving a sample (18) to be analyzed, whose volume is between 1 to 100 μl, and to a region (10) for handling the sample carrier. The sample carrier according to the invention is characterized by means for fluid-tight placement of the sample carrier (7) together with the sample (18) in an analysis device. The invention further relates to an analysis device, in particular a flow cell, with such a sample carrier.

Description

The invention relates to a sample carrier having a region for receiving a sample to be analyzed, in particular a biological sample whose volume is between 1 and 100 μl, and having an area for handling the sample carrier. The invention further relates to an analysis device, in particular a flow cell, with such a sample carrier.

From the WO 2005/094681 A1 a sample carrier is known for receiving a biological sample with a sample metered receiving capillary. The capillary is adjoined by a cylinder space in which a piston for ejecting the sample from the capillary can be moved via an air cushion. During sample taking through the capillary, an opening channel provides venting of the cylinder. With the displacement of the piston in the cylinder, this opening channel closes.

The WO 00/74853 A1 describes a sample carrier combined with a closure element for a container. When the container is closed by the closure element, for example, a biological sample passes into the container interior, where it is shielded from the outside environment and comes into contact with a diluting liquid. The diluted sample is then removed from the container and sent for analysis.

The present invention provides a new sample carrier of the type mentioned above, which is characterized by means for fluid-tight connection of the sample carrier containing the sample together with the sample in an analysis device.

Advantageously, a sample to be analyzed is supplied to the analysis process by the sample carrier according to the invention directly by the shortest route. The sample input, e.g. the input of a body fluid such as blood, urine and saliva, a food sample or an environmental sample, in particular water sample, in a flow cell is no longer an input port to close after entering, but the sample input in the analysis process is the fluid-tight placement of the sample amount possibly already metered carrying sample holder completed. Sample dosing within the flow cell can be omitted.

In a particularly preferred embodiment of the invention, the sample placed in the analysis device together with the sample carrier adjoins a cavity in the analysis device involved in the analysis, in particular in a flow cell, and the sample carrier closes the cavity outward in a fluid-tight manner. It is advantageous with the placement of the sample carrier, e.g. the flow cell is automatically closed by the sample carrier itself. It will be understood that the cavity may also be filled with a fluid-receiving material, such as e.g. a nonwoven or a porous membrane may be filled.

The above-mentioned cavity may be e.g. to act a transport channel or a chamber, in particular mixing chamber.

In a further preferred embodiment of the invention, the sample placed together with the sample carrier in the analysis device can be detached from the sample receiving region by a fluid flow. The fluid may be both a rinsing liquid and a gas, in particular compressed air.

The above-mentioned fluid flow may e.g. can be produced by emptying a reagent storage device integrated into the analyzer or fluid-tightly connected to the analyzer, e.g. a deformation of the storage space of the reagent storage is carried out by actuation.

In a further embodiment of the invention, the sample carrier itself may have means for removing the sample to be analyzed from the sample carrier, for example a rinsing channel extending through the sample carrier and carrying a rinsing liquid or a rinsing gas.

In a further particularly preferred embodiment of the invention, the sample carrier has facilities for preprocessing supplied sample material. In the course of preprocessing, the sample to be analyzed is formed from this.

The pre-processing devices preferably comprise means for metering the sample material, reagent or / and release agent, in particular for the separation of blood plasma.

Suitably, the sample carrier fluid-tight covers an opening into the cavity opening, in particular it can be inserted into the opening and preferably closes the opening in a plug-like manner.
In a particularly preferred embodiment of the invention, an interference fit for the sample carrier is formed through the opening, the sample carrier in particular having a cone corresponding to a Luer closure.

The sample holder which closes the opening in a plug-like manner can be rotatable in the opening under fluid-tight closure.

It is understood that the sample carrier, preferably in one piece, is produced as a plastic injection-molded part, with possibly several receiving regions for a sample being formed on a sample carrier.

Preferably, the receiving area itself has means for the metered recording of the sample, wherein in addition to geometric limitations of the sample receiving area especially surface coatings and / or locally used plastic materials for controlling the wettability of the receiving area into consideration, in particular such that the sample receiving area is selectively wetted with sample material ,

Preferably, the handling area allows manual handling of the sample carrier without touching the sample.

The handling region may be a handle which, after placement of the sample carrier in the analysis device, can be broken off from the remaining sample carrier at a predetermined breaking point.

In a further embodiment of the invention, the sample carrier may have a closure device preventing the removal of the placed sample carrier from the analysis device, such as e.g. a snap closure or the like.

In a further embodiment, the receiving area of the sample carrier comprises a dry reagent, optionally for a first reaction with the sample.

Fig. 1

eine erfindungsgemäße Flusszelle mit und ohne einen Probenträger in perspektivischer Ansicht,

Fig. 2

die Flusszelle von Fig. 1 perspektivisch in Ansicht von unten mit an der Flusszelle angebrachtem Probenträger,

Fig. 3

den in der Flusszelle von Fig. 1 und 2 verwendeten Probenträger in perspektivischer sowie axial geschnittener Ansicht,

Fig. 4 und Fig. 4a

die Aufnahme einer Probe durch den Probenträger von Fig. 1 bis 3 erläuternde Darstellungen,

Fig. 5

verschiedene Probenträger nach der Erfindung in geschnittenen Teilseitenansichten sowie in Draufsicht von unten,

Fig. 6

einen Probenträger nach der Erfindung mit einem Spülkanal und einem durch eine Kapillare gebildeten Probenaufnahmebereich,

Fig. 7

einen Probenträger nach der Erfindung mit einem Spülkanal und einem kegelförmigen Kapillaraufnahmebereich,

Fig. 8

einen Probenträger gemäß Fig. 6 mit einer Endverengung der Kapillare,

Fig. 9 und Fig. 9a

einen Probenträger nach der Erfindung mit einem jeweils an Enden eines Konus ausmündenden Spülkanal,

Fig. 10

Beispiele für die Verbindung eines Probenträgers nach der Erfindung mit unterschiedlichen Bereichen einer Flusszelle,

Fig. 11 und 12

die Probenträger von Fig. 6 und 9 in Verbindung mit einer Flusszelle,

Fig. 13

verschiedene Probenträger nach der Erfindung mit unterschiedlichen Probenaufnahmebereichen,

Fig. 14

Probenträger nach der Erfindung mit unterschiedlichen Handhabungsbereichen,

Fig. 15

einen weiteren Probenträger nach der Erfindung zur Vorverarbeitung einer Blutprobe unter Abtrennung von Blutplasma,

Fig. 16

einen Probenträger nach der Erfindung mit einem als Entlüftungsund Spülkanal dienenden Durchgang,

Fig. 17

den Probenträger von Fig. 16 in Verbindung mit einem Handhabungsgerät,

Fig. 18

den Probenträger von Fig. 16 in Verbindung mit einem gegenüber dem Handhabungsgerät von Fig. 17 modifizierten Handhabungsgerät,

Fig. 19

eine Teilansicht eines weiteren, durch das Handhabungsgerät von Fig. 18 manipulierbaren Probenträgers nach der Erfindung,

Fig. 20

ein drehbares Dosierelement,

Fig. 21

eine zur Zusammenarbeit mit dem Dosierelement von Fig. 20 vorgesehene Flusszelle, und

Fig. 22

eine Anordnung aus dem Dosierelement von Fig. 20 und der Flusszelle von Fig. 21 in verschiedenen Arbeitsstellungen des Dosierelements.

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 and without a sample carrier in perspective view,

Fig. 2

the flow cell of Fig. 1 in perspective view from below with attached to the flow cell sample carrier,

Fig. 3

in the flow cell of Fig. 1 and 2 used sample carriers in perspective as well as axially cut view,

Fig. 4 and Fig. 4a

the admission of a sample by the sample carrier of Fig. 1 to 3 explanatory illustrations,

Fig. 5

various sample carriers according to the invention in sectioned partial side views and in plan view from below,

Fig. 6

a sample carrier according to the invention with a flushing channel and a sample receiving region formed by a capillary,

Fig. 7

a sample carrier according to the invention with a flushing channel and a conical capillary receiving area,

Fig. 8

a sample carrier according to Fig. 6 with an end constriction of the capillary,

Fig. 9 and Fig. 9a

a sample carrier according to the invention with a flushing channel respectively opening at the ends of a cone,

Fig. 10

Examples of the connection of a sample carrier according to the invention with different regions of a flow cell,

FIGS. 11 and 12

the sample carriers of 6 and 9 in connection with a flow cell,

Fig. 13

various sample carriers according to the invention with different sample receiving areas,

Fig. 14

Sample carrier according to the invention with different handling areas,

Fig. 15

a further sample carrier according to the invention for preprocessing a blood sample with separation of blood plasma,

Fig. 16

a sample carrier according to the invention with a serving as vent and flushing passage,

Fig. 17

the sample carrier of Fig. 16 in connection with a handling device,

Fig. 18

the sample carrier of Fig. 16 in conjunction with a relative to the handling device of Fig. 17 modified handling device,

Fig. 19

a partial view of another, by the handling device of Fig. 18 manipulatable sample carrier according to the invention,

Fig. 20

a rotatable dosing element,

Fig. 21

one for cooperation with the dosing of Fig. 20 provided flow cell, and

Fig. 22

an arrangement of the metering of Fig. 20 and the flow cell of Fig. 21 in different working positions of the metering element.

A flow cell comprises a substrate 1 injection-molded from plastic, a laminate film 2 with layers of aluminum and plastic, and a cover film 3 on the side of the substrate 1 facing away from the laminate film 2.

In the substrate 1, chambers and channels are formed, e.g. the chamber 4 and the channel 5. bulges of the laminate film 2 form memory spaces. 6

As Fig. 1 a, a sample carrier 7 is arranged on a chamber wall 16 forming the chamber 4, which is screwed to a nozzle 12 projecting from the chamber wall 16, threaded projections 13 having.

The sample carrier 7 comprises a conical carrier element with a sample receiving region 9 at a free front end. The carrier element 8 protrudes from the bottom of a cup-shaped rotary handle part 10 with an internal thread 11 into which the thread projections 13 engage, and with rib projections 14. As Fig. 2 can be seen, the sample receiving portion 9 of the screwed with the nozzle 12 sample carrier 7 is in the chamber 4 inside. In order to introduce a sample to be analyzed into the flow cell, according to Fig. 4 Sample material 15 applied to the sample receiving area 9. In the example shown, the sample receiving region 9 comprises a groove 18 which is open on three sides and in which a sample quantity held by capillary forces remains. The user holding the sample carrier 7 on the rotary handle part 10 does not come into contact with the sample quantity if he introduces the sample quantity by screwing the sample carrier 7 with the nozzle 12 into the flow cell. When screwing the conical support member 8 forms with the conical inner surface of the nozzle 12 a fluid-tight press fit.

When feeding liquid sample material 15 to the receiving area 9 according to Fig. 4 it comes to the dimension of a defined, in the open on three sides groove 18 remaining sample amount. This is done, for example, by immersing the receiving region 9 in an open-access sample drop, which can be located eg at the exit of a syringe, in a container such as a microtiter plate or especially in the case of blood as a sample material, on the skin of a patient Fig. 4a on a fingertip 70. Alternatively, the sample material can also be pipetted or dropped. Decisive for the dimension of a defined amount of sample is on the one hand, the geometric shape of the groove 18, the groove walls form boundaries. The groove cross-section is approximately 2 x 2 mm ² in the example considered. On the other hand, a coating which determines the wettability of the groove walls in the receiving area 9 provides for the reproducible dimensioning of a sample volume. For example, blood or other aqueous samples as fluid sample material fill the groove capillary, whereby a certain blood sample quantity is measured on account of the hydrophilic wetting properties.

The amount of blood sample bound by capillary forces remains adhering to the receiving region 9 and is introduced into the chamber 4 with the aid of the sample carrier 7, as described above. In the course of an analysis to be carried out, a rinsing of the sample from the sample carrier.

A sample carrier 7 corresponding sample carrier is in Fig. 5a shown. The open on three sides groove 18 receives a defined amount of sample 17.

Other possibilities for the formation of receiving areas 9 of the sample carrier 7 described above go from the Fig. 5b to 5g out.

Fig. 5b shows a receiving area in the form of a pocket-shaped recess 19 in the end face of the conical carrier element 8. Through the recess 19, a sample quantity 20 is reproducibly formed in the form of drops.

Fig. 5c concerns how Fig. 5b a receiving area in the form of a round depression. However, the preferably hydrophilized depression has a wetting surface increasing microstructure, for example, from the bottom of the recess projecting columns 21. A grid of the column array is between 10 and 500 .mu.m, preferably between 20 and 200 microns. The microstructuring leads to improved wetting properties and better control of droplet formation and thus further improved reproducibility of the sample quantities.

Out Fig. 5d shows a receiving area, which is formed by a schlöngelten open at its ends groove channel 22 in the end wall of the conical support member. The cross section of this channel is in the example shown at 0.2 x 0.2 mm ² , preferably between 0.1 and 0.5 mm ² . The smaller cross-sectional dimensions of the optionally hydrophilically modified channel allow better control of the wettability and thus the reproducibility of the measured amount of sample.

An in Fig. 5e shown embodiment is similar to the example of Fig. 5d except for one arranged on the end face of the conical support member cover sheet 23, which forms part of the sample carrier constructed in two parts in this case. The closed by the cover 23 Nutenkanal 22 is capillary filled via an open end, which, in particular by partial or complete hydrophilic modification, a sample amount can be measured very accurately by the capillary filling ends at the other end of the channel by itself. For flushing the measured amount of sample, a targeted attacking purging device is preferably used in the analyzer.

Another sample carrier constructed in two parts with a through hole 24 as a receiving region has a through hole at one end occluding permeable membrane 25. The membrane has pores of such size that they are permeable to gas but not to liquid. The air permeability of the membrane 25 allows a capillary filling of the through hole 24. An embodiment of the same function but without permeable membrane 25 is also conceivable.

To empty this sample carrier in an analysis device, a pneumatic or hydraulic pressure is applied to the side covered by the membrane.

Another two-part sample carrier goes out Fig. 5g out. A sample receiving area is formed by an absorbent web 26 applied to the face of the conical support member. The fleece 26 absorbs sample liquid capillary.

In an analysis device, the sample can be released by squeezing the nonwoven fabric or rinsed out with the aid of a rinsing liquid. The sample can also be fed to the analysis process by being brought into contact with a lateral flow membrane, where it is sucked out of the fleece 26 of the sample carrier by the capillary action of the lateral flow membrane. This process can be assisted by a rinsing fluid that is transported through the lateral flow membrane.

It will be up now Fig. 6 Referring to FIG. 1, where a two-part sample carrier is shown comprising a conical support member 27 having a through hole 28. The capillary with sample material fillable through hole 28 terminates at a limited by a film 29 flushing channel 30. At the flushing channel 30 automatically ends the capillary filling of the through hole 28. The flushing channel 30 passes through another cone 31. About the conical support member 27 and the cone 31st For example, the sample carrier can be connected to a flow cell, where a measured amount of sample 32 can be flushed out of the through hole 28 hydraulically or pneumatically.

Fig. 7 shows an embodiment that differs from the embodiment of Fig. 6 differs in that instead of a through hole 28 having an approximately constant cross-section, a conically widening through hole 34 is formed. As a result, a larger amount of sample 33 can be recorded in a smaller space. Due to the smaller end opening of the through hole 34, the recorded sample amount is better reproducible. Typical diameters at the narrowest point are between 0.1 and 0.3 mm. At the furthest point of the

Diameter between 0.5 and 2 mm, wherein the length of the through hole 34 is typically 2 to 10 mm.

By varying the diameter or the volume of the sample receiving area, different sample volumes can be effectively introduced into a microfluidic flow cell simply by exchanging the sample carrier for the same external dimensions, and thus the measured quantities can be adapted to the requirements of different analyzes and / or samples.

An in Fig. 8 shown sample carrier resembles the sample carrier of Fig. 6 except for a constriction 35 of the through hole 28 at its end facing the flushing channel 30. The narrowing 35 of the sample carrier of Fig. 8 forms a capillary stop the capillary filling of the sample receiving area particularly precisely limiting capillary stop. The reproducibility of the design of samples is correspondingly high. Compared with the diameter of the through-hole 28, the dimensions of the constriction are typically reduced by 10 to 50%. The thickness of the constriction forming lip is typically 0.02 to 0.2 mm.

Fig. 9 relates to a sample carrier which faces the sample carrier of Fig. 8 is again extended by a cone 36 and has a flushing channel 37 with two inputs 38 and 39. At the sample carriers of Fig. 9 Advantageously, the formation of an air cushion in the flow direction before the rinsing liquid can be prevented by first filling the rinsing liquid from the inlet 38 to the inlet 39 and thus removing all air from the rinsing channel 37. The inlet for the sample is blocked by a valve (not shown). To flush out a sample amount 40, the valve is opened and at the entrance 39 a (not shown) valve is closed. The rinsing fluid flowing through the inlet 38 now transports the sample amount 40 out of the sample receiving area.

An in Fig. 9a shown, the sample carrier of Fig. 9 similar sample carrier has three conical plug-in elements, with which it can be plugged onto a flow cell. The middle plug element forms a sample receiving area with a widening receiving space 71 for receiving a blood sample. The hydrophilic coated walls having capillary fillable receiving space 71 is bounded at its end facing away from an opening by a plasma separation membrane 72, which limits the recorded blood sample amount.

The plasma separation membrane 72 adjoins a channel 74, which is coated on the inside with a hydrophilic film and covered by a film 73, whose ends communicate via a respective constriction 75 or 76 with a flushing channel 77 or 78 leading through an external plug-in element. In the example shown, the volume of the receiving space 71 is about 2½ times the volume of the channel 74.

In the plugged onto a flow cell state of in Fig. 9a shown sample carrier, the central conical element ends in a blind hole, so that the receiving space 71 is closed. Plasma of the blood sample received in the receiving space 71 passes through the plasma separation membrane 77 into the channel 74 which fills capillary, the constrictions 75, 76 each forming a capillary stop so that a precisely measured amount of plasma fills the channel 74. About the purge channels 77,78 this amount of plasma can be flushed out by a rinsing liquid or a purge gas and fed to the processing within the flow cell.
The in Fig. 9a In addition to the sample recording function, the sample carrier shown here also has the function of sample preprocessing.

Fig. 10 illustrates ways to connect a sample rack to different functional areas of a flow cell.

According to Fig. 10a the receiving area of a sample carrier with a conical carrier element protrudes into a mixing chamber 41 of a flow cell, wherein it is connected to the chamber wall via a conical interference fit. Via a channel 42, the mixing chamber can be partially or completely filled with rinsing liquid, for example from a reagent storage, whereby the sample is detached from the sample carrier and diluted. In this case, the flow cell is preferably in a vertical position, so that through a transparent cover 43 through the liquid level in the mixing chamber can be controlled and / or air in the mixing chamber can escape during the mixing process. For the return of the sample, it is advantageous to agitate the rinsing liquid, ie to pump back and forth. The diluted sample may be transported through channel 42 or another channel connected to the mixing chamber for further analysis or processing within the flow cell. The flow cell and the sample carrier may have structures, such as snap closures, undercuts or latching lugs, which engage in a single connection of the sample carrier with the flow cell and prevent removal of the sample carrier after the connection with the flow cell.

A the sample carrier of Fig. 5a corresponding sample carrier is according to Fig. 10b connected to a chamber 44 which is located near but outside a center of rotation of the flow cell. In the flow cell, the fluid transport takes place partially or completely by centrifugation. The sample is also transported almost completely by centrifugal force into a channel 44a connected to the transport chamber 44 for further analysis. In the manner described, an undiluted liquid sample can be removed.

According to Fig. 10c a sample receiving area of a sample carrier with conical carrier element projects into a transport channel 45 of a flow cell. The end of the conical sample holder reaches up to a cover foil 46 of the flow cell. In the example shown, the sample carrier and the flow cells have an alignment member 47 and 48, respectively, to ensure that a groove-shaped sample receiving area is aligned with the transport channel 45. The sample can be transported pneumatically or hydraulically from the sample receiving area in the transport channel 45 of the flow cell to further processing devices.

At an in Fig. 10d In the embodiment shown, alignment structures, such as a slot 49 or the like, are provided which indicate that a sample carrier is aligned with a groove-shaped sample receiving area transverse to the longitudinal direction of a transport channel. A sample carrier is still rotatable despite the press fit and can from such a position in the in Fig. 5d shown position where according to example of Fig. 10c the emptying of the sample receiving area can take place.

Out Fig. 11 is a connection of the sample of Fig. 5 with a flow cell. The rinsing channel 30 of the sample carrier is connected to a channel 50 of the flow cell, via which, according to arrow 51, compressed air or rinsing liquid is supplied, which presses the sample quantity 32 into a further channel 52 of the flow cell.

An example of a connection of the sample carrier of Fig. 9 with a flow cell pointing Fig. 12 , Via channels 53 to 55 of the flow cell, a rinsing of the stored sample amount while avoiding an air cushion, as is based on Fig. 9 is described.

Plastics generally have hydrophobic, for aqueous fluids, such as blood, poorly wettable surfaces. For the sample receiving area of sample carriers, hydrophilic surfaces are advantageous, also with regard to an exact dimensioning of sample quantities.
Changes (hydrophilic or hydrophobic) of the surface properties of plastics are known to be wet-chemically by applying wetting agents or surfactants and subsequent drying, by surface activation by plasma, flaming or corona treatment (hydrophilic), by surface coating by plasma polymerization, eg formation of glassy layers (hydrophilic or hydrophobic) or through combinations of these measures. Optionally, there is a local masking of treated surfaces.

Fig. 13a shows a sample carrier, the sample receiving region 57 and the conical sealing region is coated hydrophilic, for example with a glassy layer. The contact angle to water is <50 °. When dropping sample material in an amount that is greater than the amount of sample to be measured, the sample to be measured remains, for example, 10 mm ³ in the receiving area, while excess sample material, eg 30 to 40 mm ^{3 of} a blood drop, runs down on the conical support element and in the lower area of the sample rack. Suitable retention structures can prevent the collected sample material from entering a flow cell. Notwithstanding the example shown, the entire surface of the sample carrier could also be hydrophilized.

In the embodiment of Fig. 13b A surface treatment is limited to a groove-shaped receiving region 58, which may be hydrophilically modified, for example, by wet-chemical treatment or masked plasma coating. In this exemplary embodiment, the sample intake preferably takes place by dipping the sample carrier into a sample drop, for example blood on a fingertip. The amount of sample taken is defined by the geometry of the hydrophilically modified sample receiving area. In the adjacent areas with a hydrophobic surface, the sample hardly or not at all adheres.

The embodiment of Fig. 13c corresponds to the previous embodiment, but additionally has a hydrophobic coating 60 outside of the sample receiving area 59. The typical contact angle is> 90 ° in order to further increase the contrast of the wettability between the recording area and the adjacent area and thus to measure the sample quantities even more precisely.

Fig. 13d shows an embodiment of a sample carrier, which consists of two different wettable plastics. A core part 56 of a conical carrier element has a contact angle <70 °, for example PMMA, while an outer region of the conical carrier element, which consists for example of olefin plastic such as PP, has a contact angle> 90 °. The geometry of the core part 56 is cylindrical. The combination of materials is chosen so that both materials (eg PP and PMMA, PP and POM) do not bond firmly but rather movably in two-component injection molding. By means of such "assembly injection molding", in which the inner core remains movable, a sample receiving area which can be emptied by displacement of the inner core can be formed.

In the embodiment of Fig. 13e is compared to the embodiment of Fig. 13b formed a groove-shaped sample receiving area, which is closed on one side with a film 61, but open at the ends. The inner walls of this channel-shaped receiving area can be hydrophilic, for example wet-chemically or by plasma treatment.

In the embodiment of Fig. 13f For example, a sample receiving area is partially or completely coated with a dry reagent 62 and functionalized. In this way, a sample can be conditioned directly after the recording by the sample carrier before a connection of the sample carrier takes place with a flow cell or other processing device. For example, an anticoagulation reagent may be applied which, for example, prevents blood from clotting on the sample carrier, with materials such as heparin or citrate being suitable for this purpose. The dry reagent may also be a lysis buffer for lysing cells, eg a blood sample.

While in Fig. 14a again a sample carrier with a, as in the preceding embodiments, the conical carrier element is shown cup-shaped surrounding handling area, the embodiment of Fig. 14b a sample carrier with a conical handle 64 and a receiving area 63.

In the embodiment of Fig. 14c is a conical handle portion 65 at a predetermined breaking point 66 after connection of the sample carrier, eg with a flow cell, break off.

Fig. 14d shows a sample carrier with a recess 67, in which a after connection of the sample carrier, for example, with a flow cell, detachable handling pin 68 is used.

Another, a blood sample pre-processing sample carrier goes out Fig. 15 out.

At the sample carrier of Fig. 15 In a first plastic injection-molded part 81, a conically widening sample receiving space 79 is formed, which is delimited by a plasma separation membrane 80, which first stops the capillary filling of the sample receiving space 79 with a blood sample. A second, with the first molded part 81 glued or welded conical injection part 82 has a capillary fillable passage 83. Both the sample receiving space 79 and the passage 73 are hydrophilically coated on the inside. Via the conical injection part 82, the sample carrier can be connected to a flow cell.

After filling a blood sample into the receiving space 79, plasma enters the passageway 83 through the plasma separation membrane 80, the open end of which forms a capillary stop metering the plasma sample.

When attaching the sample carrier to a flow cell, the first injection molded part 81 can serve as a grip element, wherein expediently a cover cap is used to possibly prevent contamination of the environment by remaining in the receiving space 79 blood. The blood plasma to be analyzed by the flow cell can be sucked out of the passage by means of a fleece or a membrane adjoining the opening of the passage 83.

Fig. 16 shows a one-piece as a plastic injection molded sample carrier having a passage 86 with a constriction 85. Passage 86 forms a sample receiving capillary 84 as far as restriction 85. Passage 86 passes through a conical element and a handle portion integrally connected to the conical element. Between the handle part and the conical element an annular shoulder 87 is formed. When receiving a sample in the sample receiving capillary 84, the remaining passage 86 forms a vent passage. When the sample carrier is connected to a flow cell, the passage 86 may further form a flushing channel for flushing the sample into the flow cell.

Fig. 17 shows the sample carrier of Fig. 16 in conjunction with a pen-like handling device 88 which can be attached with one end to the annular shoulder 87 and with a conical inner wall 93 to a conical end of the sample carrier and can serve for attaching the sample carrier to a flow cell. The handling device has a core element 89 that can be moved in the axial direction in the manner of a ballpoint pen refill, in accordance with its movement Fig. 17c a detachment of the handling device 88 can be done by the plugged onto the flow cell sample carrier.

Like yourself Fig. 18 The core element 89 can also have a clamping projection 92 for engagement in the passage 86 of the sample carrier. The clamping is provided such that a venting of the sample channel is not disturbed thereby. To solve the clamping is in accordance with Fig. 18b the outer part of the handling device 88 advanced relative to the core member 89 under pressure against the annular shoulder 87.

Fig. 19 indicates that the sample carrier could also have a sample receiving region 90 in the manner of a groove or depression, as described above in connection with, for example, the sample carrier 7 of FIG Fig. 4 is described. The core element 89 of the handling device 88 could then clampingly engage in a longitudinal channel 91 of the sample carrier.

Fig. 20 shows a metering element with a conical plug neck 94, over which it has an in Fig. 21 illustrated flow cell can be plugged. The plug approach 94 has a groove channel 95 in an end wall at the free end and is connected to a comprehensive two-rotary knob 96, each with a stop 97 and 98 on the wings.

In the Fig. 21 illustrated flow cell has a conical plug-in opening 99 for receiving the plug neck 94. Via an input port 100, for example, a sample can be introduced into the flow cell with the aid of a pipette or syringe. The input port 100 communicates via a channel 101 and the plug-in opening 99 in conjunction with an overflow port 102. The flow cell consists of a plate 103 and a sheet 104 which is glued or welded to the plate and covers the channel 101.

The flow cell further has purge ports 105 and 106 communicating with each other via a passage 107. On the plate 103, stops 108 and 109 are formed on the side facing away from the channels 101,107 side.

For dimensioning a sample, the dosing element is inserted with the plug projection 94 first into the plug-in opening 99 of the flow cell, wherein the groove channel 95 is covered by the film 104. The dosing element is located in the in Fig. 22a shown rotational position in which the wings of the rotary handle 96 abut against the stops 108 and 109. In this position added according to Fig. 22b the groove channel 95 of the conical plug boss 94, the channel 101 between the input port 100 and the overflow port 102. A filled in the input port 100 sample material can flow into the overflow port 102.

To dose a certain amount of sample, the metering element is rotated by 90 °, according to Fig. 22c with its stops 97 and 98 against the input port 100 and overflow port 102 is present ( Fig. 22c ). The openings of the ports are sealed in this position by the wings of the rotary handle 96. By the rotation, a sample amount is measured, which corresponds to the internal volume of the groove channel 95. In this position, the groove channel 95 supplements the channel 107 between the flushing connections 105, 106.

The metering amount of a sample contained in the groove channel 95 can therefore be flushed out of the flow cell via the flushing connections 105 and 106 and sent for further processing.

Claims (15)

Sample carrier (7) having a region (9) for receiving a sample to be analyzed, whose volume is between 1 and 100 μl, and a region (10) for handling the sample carrier,
characterized by means for fluid-tight connection of the sample carrier (7) containing the sample with an analysis device. Sample carrier according to claim 1,
characterized,
in that the sample to be analyzed placed in the analysis device together with the sample carrier (7) adjoins a cavity in the analysis device, in particular to a cavity (4, 41, 44, 45, 46, 52, 54) in a flow cell, eg a cavity in the form of a transport channel (45, 46, 52), a chamber (4, 41, 44), in particular a mixing chamber (41) or / and a membrane expressing the sample. Sample carrier according to claim 1 or 2,
characterized,
in that the sample placed in the analysis device together with the sample carrier (7) can be detached from the receiving region (9) by a fluid flow, wherein the fluid flow can be generated, for example, by emptying a reagent reservoir integrated into the analysis device or fluid-tightly connected to the analysis device. Sample carrier according to one of claims 1 to 3,
characterized,
in that the sample carrier comprises means for preprocessing sample material supplied to the sample carrier to the sample to be analyzed, the preprocessing means preferably comprising means for metering, reagent (62) and / or separating means (72; 80), in particular for separating blood plasma. Sample carrier according to one of claims 1 to 4,
characterized,
in that the sample carrier has means for removing the sample to be analyzed from the sample carrier, in particular a flushing channel (77, 78, 86). Sample carrier according to one of claims 2 to 5,
characterized,
is used that the sample carrier (7) placeable in fluid-tight at one opening into the cavity opening, particularly in the opening (12). Sample carrier according to claim 6,
characterized,
in that the sample carrier (7) closes off the opening (12) in the manner of a plug, and in particular through the opening (12) an interference fit for preferably a conical carrier element (8) of the sample carrier (7) is formed in the manner of a LUER closure. Sample carrier according to one of claims 4 to 7,
characterized,
in that the receiving region (9) comprises means for the metered admission of the sample. Sample carrier according to claim 8,
characterized,
in that the means for metering in the sample comprise spatial boundaries of the sample receiving area (9). Sample carrier according to claim 8 or 9,
characterized,
in that the means for metering in the sample comprise at least one surface coating for controlling the wettability of the receiving area (9) or differently wettable plastic materials adjacent to the sample receiving area (9). Sample carrier according to one of claims 1 to 10,
characterized,
that the handle portion (10,64,65,68) has a manual handling of the sample carrier (7) without touching the sample allowed. Sample carrier according to one of claims 7 to 11,
characterized,
in that the sample holder which closes off the opening in a plug-like manner is rotatable under fluid-tight closure of the opening in the opening. Sample carrier according to one of claims 1 to 12,
characterized,
that a removal of the device connected to the analysis sample carrier (7) preventing closure device is provided. Sample carrier according to one of claims 4 to 13,
characterized,
in that the receiving area comprises a dry reagent (62) for a first sample material preprocessing reaction with the sample. Analysis device, in particular a flow cell provided as a disposable article, with a sample carrier according to one of claims 1 to 14.

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