EP1685900A1 - Device and method for analysing a liquid sample - Google Patents

Abstract

A device for testing sample liquids (2) with a reaction zone (9) with a reagent (R) on the flat side, a test zone (10) and a device for holding (2) in zone (9) for the dissolution and/or reaction of (R), in which there is a means of producing a straight flow front in (2), and at least 90% of (R) reacts with (2) and is transferrable with it to zone (10), or the concentration of (R) or reaction product in (10) varies by not more than 10%. A device (1) for testing sample liquids (2), with: (a) a channel (3) for taking up and transporting the liquid (2) by means of capillary forces, which has a flat side (4) over which the liquid (2) passes with lateral and/or laminar flow; (b) a reaction zone (9) with a soluble and/or reactive reagent (R) on the flat side (4), which can be completely filled with (2) to define a reaction volume (V) of liquid (2); (c) a test zone (10) formed by the channel (3) and following zone (9); and (d) a device (12) for keeping (2) in the reaction zone (9) temporarily for the dissolution and/or reaction of (R). The device (1) also has a means (16) of producing a minimally curved or straight flow front (F) in the liquid (2); the reagent (R) is soluble in and/or reacts with the defined volume (V) of (2) to the extent of at least 90%, and at least 90% of the dissolved (R) or a reaction product of (R) is transferrable to zone (10) together with (V), or the concentration of dissolved (R) or reaction product within (V) in zone (10) varies by not more than 10%. An independent claim is also included for a method for testing sample liquids (2) with the above device, in which the liquid (2) flows from zone (9) into zone (10) with an at least substantially straight flow front (F) and/or at least without any substantial change in flow cross-section.

Description

The present invention relates to a device for the examination of sample fluid, such as blood, blood plasma, urine, saliva or the like, according to the preamble of claim 1 or 4 and such a method according to the preamble of claim 26.

The present invention is concerned with microfluidic systems. The following statements relate to devices in which act capillary forces and are particularly crucial for the function.

For the examination of a sample liquid, in particular for the determination of blood sugar, blood fat, enzymes or other values, so-called test filter strips are frequently used which consist of paper, foils, filters, membranes or the like. consist. Such a test filter strip is designed for sample application and also assumes transport functions. For example, the sample liquid is transported in the test filter strip due to capillary forces in a non-woven material. The sample liquid can react with previously introduced reagents and, for example, cause a color change upon detection of an analyte in the sample liquid. However, such test filter strips allow only a relatively inaccurate, qualitative detection of an analyte.

Alternatively, microcapillary systems are known for examining a sample fluid. EP 1 201 304 A2, for example, discloses a microstructured platform for the examination of a sample liquid. The platform has a filling area, an examination area and a channel system. The sample liquid can be absorbed and promoted solely by capillary forces. In order to achieve the least possible curved flow front and a homogeneous flow velocity, the known platform has delay structures along the edges of a broad, flat channel, in particular in the examination region. Further, the sample liquid can be stopped in the known platform, if necessary, at a predetermined location for a predetermined period, for example, a chemical reaction or physical process such as heating or cooling. However, EP 1 201 304 A2 does not deal with the most precise possible examination, in particular quantitative examination, of a sample liquid.

The present invention has for its object to provide an apparatus and a method for examining sample liquid, such as blood, blood plasma, urine, saliva or the like., Which at low cost, preferably a quantitative examination, in particular determination of blood sugar, blood fat, enzymes or other values.

The above object is achieved by a device according to claim 1 or 4 or by a method according to claim 26. Advantageous developments are the subject of the dependent claims.

By means of the combination of measures according to the preamble, a substantially more accurate examination of a sample liquid, in particular a quantitative determination of at least one analyte in the sample consistency, is made possible. The defined stopping of the sample liquid in the reaction region defines a reaction volume in which a reagent can be dissolved in the reaction region or with which the reagent can react. Subsequently, the reaction volume with the dissolved reagent or reaction products from the reaction area in the investigation area further promoted, wherein the lateral, at least substantially laminar flow and / or the at least substantially rectilinear flow front of the sample liquid leads to a low dispersion, ie an at least substantially uniform Concentration profile of the dissolved reagent or reaction products can be reached in the further funded in the study area reaction volume. Accordingly, within a defined time, a much more precise investigation, in particular determination of values in the sense mentioned, can take place.

For the purpose of investigation or determination, for example, complexes or compounds formed by the dissolved reagent and an analyte to be determined can be bound in the examination area by means of an immobilized detection chemical and subsequently detected, for example optically or measured. From this, it is then possible to determine, for example, the concentration of the analyte in the sample liquid.

A further, independently realizable aspect of the present invention is to provide the reaction area, the examination area and / or the channel with an at least substantially constant cross-section and / or the height of the channel at least by a factor of 10 smaller than the width of the channel form and / or the reaction area and / or the examination area maximum as long as wide or shorter form.

The above measures are conducive to quantitative analysis or biochemical investigations. In particular, a defined examination of the defined reaction volume is made possible or an undesirable dispersion of the reaction volume is avoided. Further advantages include short examination times, fast reactions, short diffusion paths and / or short flow paths.

Fig. 1

einen schematischen Längsschnitt eines Teils einer vorschlagsgemäßen, teilweise mit Probenflüssigkeit gefüllten Vorrichtung gemäß einer ersten Ausführungsform;

Fig. 2

eine schematische Draufsicht eines Trägers der ungefüllten Vorrichtung gemäß Fig.1;

Fig. 3

eine zu Fig. 2 korrespondierende Draufsicht eines Trägers einer ungefüllten Vorrichtung gemäß einer zweiten Ausführungsform;

Fig. 4

einen schematischen Querschnitt der Vorrichtung gemäß der ersten Ausführungsform entlang Linie IV-IV gemäß Fig. 1;

Fig. 5

einen Fig. 4 entsprechenden, schematischen Querschnitt der Vorrichtung gemäß einer dritten Ausführungsform; und

Fig. 6

einen Fig. 3 entsprechenden, schematischen Querschnitt der Vorrichtung gemäß einer vierten Ausführungsform.

Further advantages, features, characteristics and aspects of the present invention will become apparent from the claims and the following description of preferred embodiments with reference to the drawing. It shows:

Fig. 1

a schematic longitudinal section of a portion of a proposed, partially filled with sample liquid device according to a first embodiment;

Fig. 2

a schematic plan view of a carrier of the unfilled device according to Fig.1;

Fig. 3

a corresponding to Fig. 2 top view of a carrier of an unfilled device according to a second embodiment;

Fig. 4

a schematic cross-section of the device according to the first embodiment along line IV-IV of FIG. 1;

Fig. 5

a corresponding to Fig. 4, a schematic cross section of the device according to a third embodiment; and

Fig. 6

a corresponding to Fig. 3, a schematic cross section of the device according to a fourth embodiment.

In the figures, the same reference numerals are used for the same or similar parts, and corresponding or comparable properties and advantages are achieved, even if a repeated description is omitted.

1 shows in a schematic section a part of a first embodiment of a proposed device 1 for the examination of a sample liquid 2, in particular blood plasma or the like.

The device 1 has a channel 3 receiving the pump fluid 2 by capillary forces. The channel 3 is preferably bounded or formed by only two opposite, in particular substantially flat surfaces or flat sides 4 and 5.

The device 1 has a preferably plate-shaped support 6 and an associated cover 7, between which the channel 3 is formed. In the illustrated embodiment, only the support 6 is excluded for the formation of the required microstructures and the cover 7 flat, preferably at least substantially ausnehmungsfrei formed. However, this can be the other way around. If necessary, however, both the carrier 6 and the cover 7 can be excluded and / or formed with projections for forming the desired structures and, if necessary, for holding chemicals, reagents, examination devices or the like, not shown. In particular, the device is thus a so-called microchip (platform with microstructure).

Fig. 2 shows in a schematic plan view of the carrier 6 of the device 1, but without cover 7 and without sample liquid 2. The channel 3 preferably has an inlet immediately after one another, in the representation example in particular with a trench 8, a reaction area 9, an examination area 10 and / or a collection area 11.

If necessary, a dosage of the sample liquid 2, not shown, in the channel 3 or in the channel 3, in particular in front of the inlet, take place, as described for example in EP 1440 732 Al.

The device 1 preferably has only a single channel 3. Here, the channel 3 is to be understood in terms of a single capillary. If necessary, however, the channel 3 can lead in different directions or to different areas or branch. In the illustrated example, the sample liquid 2 preferably flows exclusively through capillary forces into or into the channel 3 in the flow direction S, as indicated in FIG. 1. However, the sample liquid 2 may additionally or alternatively also be conveyed, for example, by pressure through the channel 3.

The channel 3 preferably has a substantially rectangular and / or flat cross section transverse to the flow direction S of the sample liquid 2.

The indicated in Fig. 1 and 4 height H of the channel 3 - ie the distance of the channel 3 bounding, preferably parallel surfaces 4 and 5 - is at most 2000 microns, preferably at most 500 microns, especially about 50 to 200 microns. The width of the channel 3 is preferably about 100 to 5000 microns, in particular about 200 to 4000 microns. The height H of the channel 3 is substantially smaller, in particular at least by a factor of 10 or 100, than the width of the channel 3. The absorption volume of the channel 3 is preferably less than 1 ml, in particular less than 100 μl, particularly preferably not more than 10 μl.

The device 1 thus forms a microfluidic system. In particular, the device 1 is used for microfluidic diagnostics for medical or non-medical purposes or other examinations.

The channel 3 and its main extension plane preferably extend at least substantially horizontally in the position of use. Depending on the intended use or constructive solution, however, a different orientation is possible, especially since the reception or filling of the channel 3 with sample liquid 2 is preferably determined or effected at least primarily by capillary forces.

The reaction region 9 with a reagent which can be dissolved and / or reacted with the sample liquid 2 and the preferably immediately adjoining examination region 10 are formed in the channel 3, preferably successively on the same flat side 4 of the channel 3.

The reaction region 9 has a reagent, which is preferably detachable from the sample liquid 2, for an analyte to be determined in the sample liquid 2. In particular, the reagent is antibodies directed against the analyte of interest and bound to indicators (dyes, colorant particles, e.g., colloidal gold). In the reaction area 9, the reagent is dissolved when filled with the sample liquid 2. The analyte, when contained in the sample fluid 2, then reacts with the antibody bound to the dye, and in particular forms a compound or complex.

Alternatively or additionally, the reagent reacts with the analyte and in particular forms a reaction product, even if the reagent is not dissolved if necessary. The following statements with regard to the (dissolved) reagent therefore apply correspondingly to the reaction product.

In the case of the illustration, the examination region 10 is provided with a preferably immobilized detection chemical, which in particular binds compounds or complexes of analyte and reagent or the reaction product. Unbound reagent and other ingredients then flow with the sample fluid 2 further into the collection area 11, where they are taken up, thereby preventing backflow. In the examination region 10, for example, the bound reagent can be determined optically and from this the presence and in particular the concentration of the analyte in the sample liquid 2 can be determined. Thus, a particularly quantitative examination of the sample liquid 2 is made possible.

According to the proposal, the device 1 has a device 12 for temporary stopping of the sample foot 2 in the reaction area 9 for dissolving and / or reacting the reagent and / or in the examination area 10

The device 12 is preferably designed such that the temporary stopping by the sample liquid 2 itself, as described for example in EP 1 441 131 Al, or by a control fluid, not shown, or by a selective venting, as described for example in EP 1419 818 Al , fixable or can be canceled. Preferably, the device 12 holds the sample liquid 2 for a predetermined period of time, possibly only after the complete filling of the reaction zone 9, and / or until the reaction zone 9 has been completely filled.

In the illustrated example, the device 12 has, in particular, a control channel 13 which supplies sample liquid 2 to a liquid stop 14 arranged between the reaction zone 9 and the examination zone 10 within a defined time, so that then the sample liquid 2 or reaction volume located in the reaction zone 9 on sample liquid 2 overcome the liquid stop 14 and can flow into the examination area 10.

If necessary, the device 1 has a further device 12 for temporary stopping of the sample liquid 2 - in particular the reaction volume of sample liquid 2 which has previously flowed from the reaction region 9 into the examination region 10 and contains dissolved reagent or the reaction product - in the examination region 10 in order to obtain the most accurate possible or to permit quantitative determination, in particular in order to enable an at least substantially complete reaction or binding of the compounds or complexes of reagent and analyte or of the reaction product to the detection chemical in the examination area 10.

The further device 12 is designed in particular according to the aforementioned device 12. Accordingly, in turn, a control channel 13 is provided, the sample liquid 2 after or in a defined time to a arranged between the examination area 10 and the downstream collection area 11 liquid stop 14 supplies, so that then the sample liquid 2 or located in the examination area 10 reaction volume of sample liquid. 2 overcome the liquid stop 14 and continue to flow into the collection area 11 and the inflowing sample liquid. 2 then a washing out of unbound reagent or reaction product in the examination area 10 can cause.

In the illustrated example, the liquid stop 14 is formed in particular by a groove-like or trench-like depression transverse to the flow direction S. However, other constructive solutions are possible. In particular, from US 5,458,852 further constructive solutions for the realization of the device (s) 16 are known, which can be used alternatively or additionally.

FIG. 3 shows, in a plan view corresponding to FIG. 2, the unfilled carrier 6 of a device 1 according to a second embodiment. The devices 12 each have here, instead of a preferably groove-like or trench-like liquid stop 14, at least one preferably web-like barrier 15, in particular two or more barriers 15 arranged one behind the other. Thus, if necessary, a corresponding temporary stopping of the sample liquid 2 can be achieved.

In the second embodiment, the channel 3 does not have a substantially constant cross-section, in contrast to the first embodiment. Instead, the cross section of the channel 3 at the transition from the reaction region 9 to the examination region 10 and / or during the transition from the examination region 10 into the collection region 11 is reduced. This reduction in cross-section is preferably achieved by uniform tapering of the liquid stream and subsequent spreading of the liquid stream. The device 12 or barrier 15 is then preferably arranged in the region of the reduced cross section.

Said cross-sectional reduction already leads to a reduction in the volume flow through the channel 3, so that, if necessary, no complete temporary stop is required. In particular, a delay caused by the barriers 15 of the flow or reduction of the volume flow may be sufficient.

The device 1 according to the first or second embodiment further comprises a means 16 for preventing the lateral advancement of sample liquid 2 in the flow direction S and / or for generating a in Fig. 1 indicated, with respect to the plan view of FIG. 2 little curved or rectilinear flow front F of the sample liquid 2 or to produce a homogeneous or laminar flow.

In the illustrated example, the means 15 is formed in that the channel 3 is formed open at least on the long side. The side of the channel 3 is followed by a recess 17, which is formed in particular nut- or trench-like. Thus, a lateral liquid stop for the sample liquid 2 - that is, a flow impediment that can not be overcome by capillary forces - is formed and the sample liquid 2 is guided along the open longitudinal sides in the channel 3 without sidewalls.

The recess 17 preferably adjoins the channel 3 in a sharp-edged manner, as indicated in FIGS. 1, 3 and 4. In the illustrated embodiment, the recess 17 is formed only in the carrier 6, that extends in the representation according to FIGS. 1, 3 and 4 essentially only downwardly with respect to a lateral projection of the channel 3. The recess 17 may however also be up or extend on both sides of the lateral projection of the channel 3, so in particular up and down.

The preferably rectangular cross-section recess 17 leads to such, in particular stepped or sudden cross-sectional enlargement that reduce the capillary forces such that said liquid stop for the sample liquid 2 is formed in the transition from channel 3 to the recess 17 out. In particular, the height of the recess 17 is at least twice as large as the height H of the channel 3.

The recess 17 extends in the representation example along the open side of the channel 3, in particular, it is formed circumferentially around the channel 3 open on all sides.

A corresponding side wallless guidance of the sample liquid 2 in the channel 3 is also possible in the third embodiment of the device 1 through the lateral recess 17 shown in FIG. 5. However, the sample liquid 2 is guided here only on a bottom or flat side 4. The sample liquid 2 is thus not in contact with an opposite flat side 5 as in the first embodiment. Instead, in the illustrated embodiment, the cover 7 is excluded accordingly or the surface 4 is arranged correspondingly deep in the carrier 6 in order to maintain a sufficient distance to the then possibly flat cover 7 can. The thickness of the liquid film formed by the sample liquid 2 on the surface 4 depends in particular on the wetting behavior and on the quantity of sample liquid 2 fed in, in particular metered in. The corresponding dimensions then apply to the liquid film, as explained for the channel 3 in the first embodiment.

6 shows in a schematic section a fourth embodiment of the device 1 according to the invention, wherein a side region of the channel 3 is shown enlarged for clarity.

The means 16 for preventing the lateral advancement of sample liquid 2, for producing a slightly curved or rectilinear flow front F and / or for generating a homogeneous or laminar flow may alternatively or additionally also have a side wall 18 which delimits the channel 3 on the long side or on all sides by forming corresponding guide elements or delay structures, in particular projections or elevations 19 or the like., The flow or filling speed along the side wall 18 in the flow direction S reduces the filling speed, in particular so that the filling rate of the sample liquid 2 at the edge that in the central region of Channel 3 does not exceed, but this at least substantially corresponds. As an alternative or in addition to the guide elements or delay structures, the wetting of the side wall 18 can also be modified, in particular reduced, in such a way that the undesirable advancing of sample liquid 2 along the side wall 18 is avoided.

In addition, with regard to possible embodiments, in order to avoid a pre-shooting of the sample liquid 2 along the side, reference is made to the possibilities described in this respect in EP 1201304 A2.

In the illustration examples, the channel 3 has at least one guide element for influencing, in particular equalizing, the filling with the sample liquid 2. In particular, the channel 3 preferably has regularly distributed elevations 19 as guide elements on the flat side 4 or possibly both flat sides 4, 5, as shown in FIGS. 1, 2 and 4 to 6. These are in particular arranged in rows transversely, preferably vertically, or longitudinally to the flow direction S, in particular alternately transversely offset. Thus, it can be achieved that the sample liquid 2 fills the channel 3 in rows, ie row by row, and thereby advances with a substantially straight-line liquid front F in the flow direction S. The means 16 also includes, if necessary, said guide elements.

If necessary, the area density, the distance and / or the size of the elevations 19 vary, in particular as a function of the respective distance to the inlet, in order to achieve a desired course of the capillary forces or possibly a compensation of flow resistances.

The elevations 19 are preferably web-like, hump-shaped or column-like, in particular with a round or polygonal base surface. Alternatively or additionally, however, it is also possible to provide depressions, such as the trench 8, or the barriers 15 or other guide elements, which extend transversely or longitudinally to the flow direction S of the channel 3.

The preferably provided groove-like, in cross-section in particular rectangular or semicircular trench 8 has a much smaller depth than the liquid stop 14 and the recess 17 and therefore forms only a temporary liquid stop to equalize the liquid front F. Thus, it can be achieved that the Probenflüssiglcezt 2 only after filling the channel 3 over the entire cross section fills the trench 8 and then the subsequent channel region.

It should be emphasized that a highly uniform filling of the channel 3 in particular by capillary forces with at least substantially straight-line or perpendicular to the flow direction S extending liquid front F can be achieved by the combination of side wallless guidance of the sample liquid 2 and the guide elements.

Alternatively, the channel 3 in regions or in total also at least substantially smooth or even, ie in particular without guide elements, be formed, as indicated in Fig. 3.

The structuring or texturing of the reaction area 9 and / or the examination area 10, in particular by guide elements, such as the elevations 19 or the like, facilitates the preferably uniform application of a chemical or the like, which subsequently dries and thereby, for example, a dry chemical or immobilized Chemical forms.

In addition, it should be noted that the device 1 preferably has a vent 20 in communication with the recess 17, as indicated in Fig. 4. This allows in a very simple way effective ventilation. This is conducive to a uniform, bubble-free filling of the channel 3 with the sample liquid 2.

The interaction of the proposed measures will be explained in more detail below, reference being made in particular to the first embodiment and the representation according to FIGS. 1 and 2.

After filling, the sample liquid 2 is conducted into the reaction zone 9 by capillary forces in the channel 3. In this case, the sample liquid 2 flows in the channel 3 - at least in the reaction region 9 and examination region 10 - laterally over the flat side 4 and preferably at least substantially laminar or with homogeneous flow velocity or slightly curved or rectilinear flow front F. This is in particular by said means 16 - In particular in combination with the preferably at least in the reaction region 9 and / or examination area 10 provided guide elements - achieved.

In the reaction region 9, the sample liquid 2 is temporarily stopped by the device 12 for a preferably predetermined time. In the reaction area 9, the sample liquid 2 can dissolve or react with the reagent, which is preferably present as a dry chemical, for determining an analyte in the sample liquid 2. The reagent is, for example a conjugate composed of an antibody binding to the analyte and a dye particle or the like. is formed. The dissolved reagent or conjugate then binds to the analyte.

Due to the temporary stopping of the sample liquid 2, the reaction area 9 is filled with a defined reaction volume of the sample foot 2, so that the reagent dissolves at least substantially only in this reaction volume or only reacts with it. As a result of the temporary stop, an undesired dispersion or extensive distribution of the reagent or a reaction product of the reagent in the sample liquid 2 can thus already be avoided.

Furthermore, the time for the temporary stop is preferably chosen such that the reagent is dissolved to at least 90%, in particular at least 95% or substantially more in particular in the reaction volume of sample liquid 2 or reacts with it. If necessary, the dissolution or reaction by heat or other measures, such as applying a voltage or the like, Can be supported.

The reagent is preferably applied uniformly or in a predetermined concentration distribution on the flat side 4 in the reaction region 9. Thus, it can be achieved that - if necessary, taking into account the filling process by the sample liquid 2 - as fast and uniform distribution of the dissolved reagent or the Reaktionsprodulcts is achieved in said reaction volume.

The most even distribution in the reaction volume is also beneficial that the reagent on the flat side 4 of the channel 3 is arranged and that due to the relatively low channel height H accordingly a fast diffusion and thus uniform distribution of the dissolved reagent or the reaction product in the reaction volume can be achieved ,

After the defined release or reaction, the device 12 releases the sample liquid 2, so that the sample liquid 2 - in particular the defined reaction volume - from the reaction region 9 in the study area 10 can continue to flow. Due to the measures mentioned, and in particular the means 16, a particularly small dispersion of the dissolved reagent as well as the compounds or complexes formed from the reagent and the analyte can in turn be prevented from the reaction volume. In particular, it is achieved that the reagent or the reaction product to at least 90%, preferably 95% or more flows together with the reaction volume in the examination area 10 or is promoted.

In the examination area 10, the sample liquid 2 or the reaction volume is again temporarily stopped, if necessary, for the respectively desired examination, in particular the binding or compounds formed from the reagent and the analyte in the examination area 10, preferably on the flat side 4 immobilized detection chemical support. However, such a temporary stop in the examination area 10 is not absolutely necessary, so that the further, the examination area 10 associated device 12 may possibly be omitted.

The intended detection chemical is, in particular, an immobilized dry chemical, for example a capture antibody, which captures and binds the compounds or complexes of reagent and analyte.

In addition, further examination steps can be carried out by means of other further chemicals in the examination area 10 or in a plurality of examination areas 10 arranged one after the other. For example, an investigation can also be made as to whether the analyte to be determined is contained in the sample liquid 2 at all.

The examination region 10 preferably directly adjoins the reaction region 9, so that undesired dispersion of the reagent or of compounds or complexes formed by the reagent with the analyte or of other reaction products from the reaction volume into other regions of the sample liquid 2 is at least substantially prevented or minimized. Due to the fact that the examination area 10 preferably immediately adjacent to the reaction region 9, namely the dead volume and thus the dispersion are minimized.

Due to the flat cross section of the channel 3, the reaction area 9 and / or the examination area 10 can be formed relatively short in the flow direction S, so that a total of very short flow paths and thus a low dispersion can be achieved. In particular, the reaction area 9 and / or the examination area 10 is formed only as long as or shorter than the width of the channel 3.

In particular, the dispersion which can be achieved according to the proposal in the examination zone 10 is so small that the concentration of the reagent or reaction product in the reaction volume in the examination zone 10 varies by a maximum of 10%, preferably less than 5%, very preferably at most 3%.

The relatively low height H of the channel 3 and the preferably provided arrangement of Nachweischikalie on a flat side, in particular the flat side 4, cause the complexes contained in the reaction volume or, compounds of reagent and analyte or other reaction products very quickly or with a very high efficiency of the detection chemical or the like. can be tied.

In a subsequent washing step, the sample liquid 2 flows further into the collecting area 11, which may optionally be provided with an absorbent material and / or guide elements, such as the elevations 19, to absorb the sample liquid 2 and to prevent a reflux, the volume of Collection area 11 is preferably greater than the reaction volume by at least a factor of 2 or 5 in order to achieve efficient washing out of unbound reagent, unbound reaction products and / or other possibly interfering particles or substances from examination area 10.

Subsequently, the determination of the bound in the examination area 10 reagent or reaction product is preferably carried out optically, for example spectroscopically. This is particularly possible because the Reagent or reaction product, for example, as a conjugate of an antibody and a color complex, color particles or the like. is constructed. In particular, the concentration of the analyte in the sample liquid 2 can then be determined from the number or concentration of bound complexes or compounds. Consequently, the proposed device 1 and the method described above allow a comparison with conventional test filter strips or the like. much more accurate examination of the sample liquid 2, in particular quantitative determination of an analyte or optionally also several analytes in the sample liquid 2.

Claims (30)

Device (1) for examining a sample liquid (2),
with a channel (3) receiving and conveying the sample liquid (2) by capillary forces, which has a flat side (4) over which the sample liquid (2) flows laterally and / or laminarly,
with a reaction region (9) with a detachable and / or reacting reagent on the flat side (4), wherein the reaction region (9) can be completely filled with sample liquid (2) and thereby a reaction volume of sample liquid (2) can be defined,
with an examination region (10) arranged downstream of the reaction region (9) and formed by the channel (3), and
with a device (12) for temporarily stopping the sample liquid (2) in the reaction region (9) for dissolving and / or reacting the reagent,
characterized,
in that the device (1) has a means (16) for producing a slightly curved or rectilinear flow front (F) of the sample liquid (2), wherein the reagent is at least 90% soluble in the defined reaction volume of sample liquid (2) and / or reacts with and wherein the dissolved reagent or a reaction product of the reagent to at least 90% together with the reaction volume in the examination area (10) is conveyed or the concentration of the dissolved reagent or the reaction product within the reaction volume in the examination area (10) varies by a maximum of 10% , Apparatus according to claim 1, characterized in that the channel (3) has an at least substantially constant cross-section - at least from the reaction area (9) to the examination area (10) - or forms for the sample liquid (2). Apparatus according to claim 1 or 2, characterized in that the height (H) of the channel (3), in particular by at least a factor of 10, preferably 100, smaller than the width of the channel (3). Device (1) for examining a sample liquid (2), in particular according to one of the preceding claims,
with a channel (3) receiving and conveying the sample liquid (2) by capillary forces, which has a flat side (4) over which the sample liquid (2) flows laterally and / or laminarly,
with a reaction region (9) with a detachable and / or reacting reagent on the flat side (4),
with an examination region (10) arranged downstream of the reaction region (9) and formed by the channel (3),
characterized,
that comprises the reaction region (9) of the examination zone (10) and / or the channel (3) has an at least substantially constant cross-section or have,
that the height (H) of the channel (3) is at least a factor of 10 smaller than the width of the channel (3), and / or
that the reaction zone (9) and / or the examination zone (10) is as long as wide or shorter maximum or are. Apparatus according to claim 4, characterized in that the device (1) comprises means (12) for temporarily stopping the sample liquid (2) in the reaction region (9) for dissolving and / or reacting the reagent. Apparatus according to claim 4 or 5, characterized in that the device (1) comprises means (16) for preventing the lateral advancement of sample liquid (2) in the flow direction (S) and / or for producing a slightly curved or rectilinear flow front (F). the sample liquid (2). Device according to one of claims 4 to 6, characterized in that the reaction region (9) with sample liquid (2) is completely fillable and thereby a reaction volume of sample liquid (2) is definable, wherein the reagent is at least 90% in the defined reaction volume of sample liquid (2) solvable and / or reacts with the dissolved reagent or a reaction product of the reagent is at least 90% together with the reaction volume in the examination area (10) is conveyed or the concentration of the dissolved reagent or of the reaction product within the reaction volume in the examination area (10) varies by a maximum of 10%. Device according to one of the preceding claims, characterized in that the sample liquid (2) can be received and / or conveyed exclusively by capillary forces in the channel (3) and / or that the device is designed such that at least 95% of the reagent can be dissolved in the reaction volume and with this in the study area (10) are eligible. Device according to one of the preceding claims, characterized in that the channel (3) has a substantially rectangular and / or flat cross-section, and / or extends in a straight line and / or extends at least substantially horizontally in the position of use. Device according to one of the preceding claims, characterized in that the channel (3) is preferably limited only by two opposite flat sides (4, 5), between which the sample liquid (2) can be guided and with which the sample liquid (2) is in contact , Device according to one of the preceding claims, characterized in that the reagent is present as a dry chemical and is detachable from the sample liquid (2) and / or that the reaction region (9) and the examination region (10) have at least substantially the same size. Device according to one of the preceding claims, characterized in that the examination region (10) directly adjoins the reaction region (9), in particular wherein the device (12) or a liquid stop (14) or a barrier (15) of the device (12) between the reaction region (9) and the examination area (10) is arranged. Device according to one of the preceding claims, characterized in that the examination region (10) has a preferably immobilized detection chemical, in particular for the detection of compounds or complexes formed from the reagent and an analyte in the sample liquid (2). Device according to one of the preceding claims, characterized in that the channel (3) has a collecting region (11) downstream of the examination region (10) for the sample liquid (2), in particular wherein the volume of the collecting region (11) is at least a factor of 2 or 5 is greater than the reaction volume. Device according to one of the preceding claims, characterized in that the device (12) is designed such that the temporary stopping by the sample liquid (2) itself or a control liquid or by a selective venting can be fixed or canceled Device according to one of the preceding claims, characterized in that the device (12) has a control channel (13) which supplies sample liquid (2) to a liquid stop (14) at the end of the reaction zone (9) so that the sample liquid (2) then overcome the liquid stop (14) and the reaction volume from the reaction region (9) in the study area (10) can continue to flow. Device according to one of the preceding claims, characterized in that the device (12) stops the sample liquid (2) for a predetermined period of time and / or after the reaction zone (9) has been completely filled. Device according to one of the preceding claims, characterized in that the sample liquid (2), in particular the reaction volume, can be temporarily stopped in the examination area (10) by means of the or a further device (12). Device according to one of the preceding claims, characterized in that the means (16) is formed in that the channel (3) is open at least on the longitudinal side, so that a lateral liquid stop for the sample liquid (2) in the channel (3) formed and the sample liquid (2) can be guided without side walls in the channel (3). Device according to one of the preceding claims, characterized in that the means (16) has a recess (17), which preferably adjoins the channel (3) laterally in order to form a liquid stop. Apparatus according to claim 19, characterized in that the recess (17) is formed circumferentially, in particular laterally surrounds or limits the channel (3) on all sides. Device according to one of the preceding claims, characterized in that the channel (3) is formed circumferentially laterally open. Device according to one of the preceding claims, characterized in that the means (16) has a side wall (18) inhibiting the advancing of the sample liquid (2), in particular wherein the side wall (18) is curved or rounded in cross-section and / or guide elements, in particular Surveys (19). Device according to one of the preceding claims, characterized in that the device (1) is designed such that a certain volume of sample liquid (2) in the channel (3) can be metered Device according to one of the preceding claims, characterized in that the device (1) is designed as a platform provided with at least one microstructure for forming the channel (3). Method for examining a sample liquid (2),
wherein the sample liquid (2) flows by capillary forces laterally and / or laminarly over a flat side (4) of a channel (3),
wherein the sample liquid (2) completely fills a reaction area (9) with a detachable and / or reacting reagent on the flat side (4) and thereby defines a reaction volume of sample liquid (2),
the reaction volume being slowed or temporarily stopped in the reaction zone (9) for dissolving and / or reacting the reagent,
characterized,
in that the sample liquid (2) flows from the reaction zone (9) into the examination zone (10) with an at least substantially straight liquid front (F) and / or at least substantially without a flow cross section change. A method according to claim 26, characterized in that the reagent is at least 90% dissolved in the defined reaction volume of sample liquid (2) and / or reacts with it and wherein after stopping the dissolved reagent or a reaction product of the reagent to at least 90% together with the reaction volume in a reaction region (9) downstream of the channel (3) formed examination area (10) flows or the concentration of the dissolved reagent or the reaction product within the reaction volume in the examination area (10) varies by a maximum of 10%. Method according to Claim 26 or 27, characterized in that the sample liquid (2) is guided on the flat side (4) in the channel (3) and / or via guide elements, preferably elevations (19), about an at least substantially straight liquid front (F) to reach and / or prevent a lateral Vorschießen the sample liquid (2). Method according to one of claims 26 to 28, characterized in that the reaction volume in the examination area (10) is temporarily stopped, in particular up to at least 95% of complex formed from the reagent and an analyte in the sample liquid (2) or compounds or reaction products of a detection chemical in the study area (10) are bound. Method according to one of claims 26 to 29, characterized in that the examination region (10) is flushed after passing through the reaction volume with sample liquid (2) before a preferably optical examination or determination, in particular of bound to a detection chemical reaction products, complexes or compounds from the reagent and an analyte to be determined takes place,

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