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EP1685900B1 - Utilisation d'un dispositif pour l'analyse d'un échantillon de liquide - Google Patents

Utilisation d'un dispositif pour l'analyse d'un échantillon de liquide Download PDF

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Publication number
EP1685900B1
EP1685900B1 EP06001069A EP06001069A EP1685900B1 EP 1685900 B1 EP1685900 B1 EP 1685900B1 EP 06001069 A EP06001069 A EP 06001069A EP 06001069 A EP06001069 A EP 06001069A EP 1685900 B1 EP1685900 B1 EP 1685900B1
Authority
EP
European Patent Office
Prior art keywords
sample liquid
reaction
channel
reagent
area
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP06001069A
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German (de)
English (en)
Other versions
EP1685900A1 (fr
Inventor
Gert Dr. Blankenstein
Ralf-Peter Dr. Peters
Thomas Willms
Claus Marquordt
Christian Schön
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim Microparts GmbH
Original Assignee
Boehringer Ingelheim Microparts GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE200510003961 external-priority patent/DE102005003961A1/de
Application filed by Boehringer Ingelheim Microparts GmbH filed Critical Boehringer Ingelheim Microparts GmbH
Publication of EP1685900A1 publication Critical patent/EP1685900A1/fr
Application granted granted Critical
Publication of EP1685900B1 publication Critical patent/EP1685900B1/fr
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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0605—Metering of fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0825—Test strips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions

Definitions

  • the present invention relates to an apparatus for assaying sample liquid such as blood, blood plasma, urine, saliva or the like.
  • 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.
  • 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.
  • test filter strips allow only a relatively inaccurate, qualitative detection of an analyte.
  • microcapillary systems are known for examining a sample fluid.
  • the EP 1 201 304 A2 discloses a microstructured platform for examining a sample fluid.
  • 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.
  • the known platform has delay structures along the edges of a broad, flat channel, in particular in the examination region.
  • 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.
  • the EP 1 201 304 A2 does not deal with as accurate a study as possible, in particular quantitative analysis, of a sample liquid.
  • the US2004 / 0077103 A1 describes a device and a method in which a sample first dissolves a reagent and transferred after a predetermined period of time in an examination area.
  • the older post-published WO2005 / 119211 A1 discloses a device with a side wall-free channel, wherein a channel portion may form a sample liquid sample area.
  • the design of the channel is chosen so that an optimal ventilation of the channel takes place when filling the channel with sample liquid W02005 / 119211 A1 also does not deal with a quantitative study of a sample liquid.
  • the present invention has for its object to provide a use of a device 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.
  • sample liquid such as blood, blood plasma, urine, saliva or the like.
  • a substantially more accurate examination of a sample liquid in particular a quantitative determination of at least one analyte in the sample footage, is made possible.
  • the reaction volume with the dissolved reagent or reaction products from the reaction area in the study area further promoted, 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, so 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 aforementioned sense, can take place.
  • 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 - for example optically - confirmed 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.
  • 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 shows in a schematic section a part of a first embodiment of a proposed device 1 for examining a sample liquid 2, in particular blood plasma o. 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.
  • the support 6 is excluded for the formation of the required microstructures and the cover 7 flat, preferably at least substantially ausappelungsoko formed.
  • this can be the other way around.
  • 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.
  • 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 one inlet immediately following, in the illustrated example in particular with a trench 8, a reaction area 9, an examination area 10 and / or a Collection area 11 on.
  • the device 1 preferably has only a single channel 3.
  • 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.
  • the sample liquid 2 preferably flows exclusively through capillary forces into or into the channel 3 in the flow direction S, as in FIG Fig. 1 indicated.
  • 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 distance of the channel 3 bounding, preferably parallel surfaces 4 and 5 - is at most 2000 microns, preferably at most 500 .mu.m, in particular 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 ⁇ l, particularly preferably not more than 10 ⁇ l.
  • the device 1 thus forms a microfluidic system.
  • 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.
  • 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.
  • the reagent is antibodies directed against the analyte of interest and bound to indicators (dyes, colorant particles, e.g., colloidal gold).
  • 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.
  • 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.
  • 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.
  • 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.
  • a particularly quantitative examination of the sample liquid 2 is made possible.
  • 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 stop by the sample liquid 2 itself, such as in the EP 1 441 131 Al described, or by a control fluid, not shown, or by a selective vent, such as in the EP 1419 818 Al described, fixed or can be canceled.
  • 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.
  • 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.
  • 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.
  • the liquid stop 14 is formed in particular by a groove-like or trench-like depression transverse to the flow direction S.
  • other constructive solutions are possible.
  • Fig. 3 shows in one too Fig. 2 corresponding plan view of 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.
  • 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.
  • a delay caused by the barriers 15 of the flow or reduction of the volume flow may be sufficient.
  • the device 1 further comprises a means 16 for preventing the lateral advancement of sample liquid 2 in the flow direction S and / or for generating an in Fig. 1 indicated, according to the plan view Fig. 2 little curved or rectilinear flow front F of the sample liquid 2 or to produce a homogeneous or laminar flow.
  • 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.
  • 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 connects sharp-edged to the channel 3, as in Fig. 1 . 3 and 4 indicated.
  • the recess 17 is formed only in the carrier 6, extends in the illustration according to Fig, 1 . 3 and 4 Thus, essentially only downwardly with respect to a lateral projection of the channel 3.
  • the recess 17 may, however, optionally also upwards or on both sides of the lateral projection of the channel 3, so in particular extend upwards and downwards.
  • 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.
  • 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 leadership of the sample liquid 2 in the channel 3 is also in the in Fig. 5 illustrated, third embodiment of the device 1 through the lateral recess 17 is possible.
  • 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.
  • 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.
  • Fig. 6 shows in a schematic section a fourth embodiment of the proposed device 1, wherein a side portion 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.
  • 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.
  • the channel 3 has at least one guide element for influencing, in particular equalizing, the filling with the sample liquid 2.
  • 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 in FIG Fig. 1, 2 and 4 to 6 shown. These are in particular arranged in rows transversely, preferably vertically, or longitudinally to the flow direction S, in particular alternately transversely offset.
  • the means 16 also includes, if necessary, said guide elements.
  • 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.
  • the Proben thoroughlylcezt 2 only after filling the channel 3 over the entire cross section fills the trench 8 and then the subsequent channel region.
  • 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.
  • the channel 3 can be formed partially or even at least substantially smoothly or even, that is to say in particular without guide elements, as in FIG Fig. 3 indicated.
  • 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.
  • the device 1 preferably has a vent 20 in communication with the recess 17, as in FIG Fig. 4 indicated. 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 sample liquid 2 is conducted into the reaction zone 9 by capillary forces in the channel 3.
  • 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.
  • 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.
  • the sample liquid 2 is temporarily stopped by the device 12 for a preferably predetermined time.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 ,
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 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.
  • the determination of the bound in the examination area 10 reagent or reaction product is preferably carried out optically, for example spectroscopically.
  • the Reagent or reaction product for example, as a conjugate of an antibody and a color complex, color particles or the like. is constructed.
  • 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.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Sampling And Sample Adjustment (AREA)

Claims (4)

  1. Utilisation d'un dispositif (1)
    avec un canal (3) qui reprend et transporte par des forces de capillarité un liquide d'échantillon (2) et qui présente un côté plat (4) par lequel le liquide d'échantillon (2) s'écoule latéralement et/ou laminairement,
    avec une zone de réaction (9) qui présente un réactif qui peut être dissous ou qui peut réagir sur le côté plat (4), la zone de réaction (9) pouvant être complètement remplie de liquide d'échantillon (2), ce qui permet de définir un volume de réaction de liquide d'échantillon (2),
    avec une zone d'examen (10) formée par le canal (3) en aval de la zone de réaction (9), la zone de réaction (9) et/ou la zone d'examen (10) étant configurées exactement à la même longueur ou à une longueur plus courte que la largeur du canal (3), la zone de réaction (9) et la zone d'examen (10) présentant au moins essentiellement la même taille et
    avec un moyen (16) qui forme un front d'écoulement (F) peu courbé ou rectiligne de liquide d'échantillon (2), le moyen (16) étant formé par le fait que le canal (3) est ouvert au moins dans le sens de sa longueur de manière à former un arrêt latéral pour le liquide d'échantillon (2) présent dans le canal (3) et que le liquide d'échantillon (2) soit guidé dans le canal (3) sans paroi latérale,
    pour étudier un liquide d'échantillon (2),
    le volume de réaction étant ralenti ou retenu temporairement dans la zone de réaction (9) et dans la zone d'examen (10) pour dissoudre et/ou faire réagir le réactif, par un dispositif (12, 15), et plus de 90 % du réactif étant dissous dans le volume de réaction défini par le liquide d'échantillon (2) et/ou réagissant avec ce dernier, et après sa retenue, plus de 90 % du réactif dissous et un produit de réaction du réactif s'écoulant dans la zone d'examen (10) en même temps que le volume de réaction.
  2. Utilisation d'un dispositif (1) selon la revendication 1, caractérisée en ce que le liquide d'échantillon (2) est guidé sur le côté plat (4) par des éléments de guidage, de préférence des saillies (19), pour obtenir un front de liquide (F) au moins essentiellement rectiligne et/ou empêcher un avancement latéral du liquide d'échantillon (2).
  3. Utilisation d'un dispositif (1) selon les revendications 1 ou 2, caractérisée en ce que le volume de réaction est retenu temporairement dans la zone d'examen (10), en particulier jusqu'à ce qu'au moins 95 % des complexes formés du réactif et d'un analyte présents dans le liquide d'échantillon (2), des composés ou des produits de réaction soient liés par un produit chimique de détection dans la zone d'examen (10).
  4. Utilisation d'un dispositif (1) selon l'une des revendications précédentes, caractérisée en ce que la zone d'examen (10) est rincée par du liquide d'échantillon (2) après le passage du volume de réaction et avant de réaliser un examen ou une détermination de préférence optiques, en particulier de produits de réaction liés à un produit chimique de détection, de complexes ou de composés constitués du réactif et d'un analyte à déterminer.
EP06001069A 2005-01-27 2006-01-19 Utilisation d'un dispositif pour l'analyse d'un échantillon de liquide Active EP1685900B1 (fr)

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DE200510003961 DE102005003961A1 (de) 2005-01-27 2005-01-27 Vorrichtung und Verfahren zur Untersuchung von Probenflüssigkeit

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JP (1) JP2006208388A (fr)
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ATE503578T1 (de) 2011-04-15
CN1811416A (zh) 2006-08-02
JP2006208388A (ja) 2006-08-10
ES2361169T3 (es) 2011-06-14
US20060216195A1 (en) 2006-09-28
DE502006009183D1 (de) 2011-05-12
EP1685900A1 (fr) 2006-08-02

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