CN101678355A - Device for handling liquid samples - Google Patents

Device for handling liquid samples Download PDF

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Publication number
CN101678355A
CN101678355A CN200880012452.4A CN200880012452A CN101678355A CN 101678355 A CN101678355 A CN 101678355A CN 200880012452 A CN200880012452 A CN 200880012452A CN 101678355 A CN101678355 A CN 101678355A
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Prior art keywords
liquid
sample
different
reagent
projection
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CN200880012452.4A
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Chinese (zh)
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CN101678355B (en
Inventor
D·伯格曼
P·克鲁杰
D·朗霍尔姆
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J Remsen International Assets LLC
J&J JSC
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Amic AB
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    • 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
    • B01L3/502746—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 for controlling flow resistance, e.g. flow controllers, baffles
    • 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
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0017—Capillary or surface tension valves, e.g. using electro-wetting or electro-capillarity effects
    • 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
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • 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
    • B01L2300/0887—Laminated structure
    • 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
    • B01L2400/08—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
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K2099/0082—Microvalves adapted for a particular use
    • F16K2099/0084—Chemistry or biology, e.g. "lab-on-a-chip" technology

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

Abstract

There is disclosed a device for handling liquid samples, said device comprising: a) projections substantially perpendicular to the surface of said device, said projections having a height, diameter and a distance between the projections capable of generating capillary flow, lateral to said surface, of a fluid, b) at least one zone for receiving a sample, c) at least one sink with a capacity of receiving said liquid, said at least one sink exerting at least two different capillary forces on said liquid, d) at least two flow paths connecting said at least one zone for receiving a sample and saidat least one sink, said flow paths exerting at least two different capillary forces on said liquid, e) at least one connection between said at least two flow paths.

Description

The device of handling liquid samples
Technical field
[0001] the present invention relates to the field of the device of handling liquid samples.
Background technology
[0002] device of various handling liquid samples need be used for for example POCT (point ofcare) analysis.And this device can be used for analyzing various samples, and described sample comprises blood, blood plasma, serum, sweat, saliva, urine, tear, water sample, and the suspension of foodstuff samples or solution.
[0003] this determinator for example WO 2005/118139 (
Figure A20088001245200041
AB), WO2005/089082 (
Figure A20088001245200042
AB) and WO 03/103835 (
Figure A20088001245200043
AB) be described in.
[0004] other determinators are described among 852 (BIOSITE) and the EP1120164 (ROCHE DIAGNOSTICS GMBH) for example at US 5,458.
[0005] GB 2410086 (BRITISH BIOCELL INTERNAT LTD) discloses a kind of determinator, and it comprises that the flow barrier part is to determine the flow of liquid.
[0006] US 6,296,020 (BIOMICRO SYSTEMS, INC.) disclose a kind of by using passive valve or arresting stop to control method through the fluid stream of microchannel.
Summary of the invention
Technical problem
[0007] in some known determinators, added the sample that comprises analyte, this sample is along the flow path that is dissolved in reagent.The sample that comprises reagent now flows to analysis site, analyzes one or more character of this sample at this.Such technology has a lot of problems.
[0008] problem about above-mentioned technology is how to allow sample arrive analysis site before reagent.This needs in some applications.
[0009] another problem is how accurately to repeat to limit quantity of sample, described sample point by analysis before reagent arrives analysis site.
[0010] another problem is how to allow sample react for a long time at analysis site before reagent arrives analysis site.
[0011] another problem is to eliminate the influence that reagent can differently dissolve based on the degree of drying of for example Preservation of Reagent time and reagent.
[0012] measuring-signal during some are measured depends on amount of reagent and sample size.In a lot of mensuration, detect the particle of some kinds and/or the molecule of some kinds, therefore must limit sample size well.
Technical scheme
[0013] the objective of the invention is to alleviate at least some problems of the prior art.
[0014] this application of the invention realizes, the present invention provides a kind of device of handling liquid samples in first aspect, described device comprises: the projection that a) is substantially perpendicular to the surface of described device, described projection has height, distance between diameter and the projection, described projection can produce with described surface and become horizontal fluid capillary flow, b) at least one receives the zone of sample, c) at least one can receive the groove of described liquid, described at least one groove applies at least two different capillary forces to described liquid, d) connect the zone of described at least one reception sample and at least two streams of described at least one groove, described stream applies at least two different capillary forces to described liquid, e) at least one connecting portion between described at least two streams.
[0015] determinator has utilized the projection that is substantially perpendicular to described surface to produce capillary force so that liquid flow.The fact of described device utilization is: capillary force can be different for different runners based on distance, geometry, diameter and the height of projection.The difference of capillary force is used for guiding on required direction mobile.
[0016] the present invention also comprises a kind of method and external member of analytic sample.
Advantageous effects
[0017] advantage of the present invention comprises and can allow sample arrive analysis site before reagent.Another advantage is to limit quantity of sample, described sample point by analysis before reagent arrives analysis site.Further advantage is to eliminate or to alleviate the influence that reagent differently dissolves.
Description of drawings
[0018] Fig. 1 a-d shows each embodiment according to device of the present invention.
[0019] Fig. 2 a-d showed according to device of the present invention each stage in use.
[0020] Fig. 3 is the electron micrograph according to the part of analytical equipment of the present invention.The figure shows and be used for for example intersection of two runners of device shown in Figure 2.
[0021] Fig. 4 shows and comprises the cross section that can be used for according to the runner of the gate of determinator of the present invention.
The specific embodiment
Definition
[0022] in the present invention by before the disclosure and description at length, be understood that to the invention is not restricted to concrete structure disclosed herein, treatment step and material, because some changes can take place for such structure, treatment step, molecule and material.What will also be understood that is that the term that this paper adopts only is used to describe the purpose of specific embodiment, and is not used in qualification, because scope of the present invention is only limited by claims and equivalent thereof.
[0023] also must be noted that, as this specification and the employed singulative of claims " a kind of " and " as described in " comprise plural implication, except spelling out in the literary composition.Following term is used in the full text of specification and claims.
[0024] term used herein " analysis " expression sample is verified to obtain the process to the understanding of sample, for example about the qualitative and/or quantitative composition of sample.
[0025] point or the zone of measuring on term used herein " analysis site " the expression determinator.
[0026] analyzed material, chemical constituent or the biological components of term used herein " analyte " expression.
[0027] term used herein " reagent " expression participates in the chemistry or the biological components of analysis.
[0028] term used herein " sample " expression comprises the arbitrary substance of analyte.
Specifically describe
[0029] at least some of above-mentioned advantage realize by the determinator that uses particular design.The projection that the determinator utilization is substantially perpendicular to the surface produces capillary force so that liquid flow.The fact of the mensuration utilization of determinator is: capillary force can be different for different runners based on distance, geometry, diameter and the height of projection.The difference of capillary force is used for guiding on required direction mobile.
[0030] in an embodiment shown in Fig. 1 a, the device of handling liquid samples comprises a zone that receives sample, is shown as border circular areas.Be provided with two rectangular channels that separate that can receive described liquid, connect two streams of a groove respectively, and a connecting portion between described at least two streams.In the present embodiment, reactant mummification in the substrate in the zone that is labeled as " k ".Present embodiment further comprises gate, and it allows liquid flow when both direction contact liq at least, represent with " g " at gate described in Fig. 1.
[0031] must be noted that this gate only allows liquid flow more than a side contacts liquid time.Fig. 4 shows the example that can be used for gate of the present invention.Must be noted that can be used for gate of the present invention is not limited to gate shown in Figure 4.Can use the gate of any type, this gate barrier liquid when a side contacts liquid only flows and allow liquid flow more than a side contacts liquid time
[0032] flow to from a left side in stream shown in Figure 4 when right when liquid, flowing is blocked, and when liquid flows to a left side from the right side, and gate allows mobile on the both direction.Thereby flowing liquid will flow in the little stream on primary flow path next door and will allow liquid to converge together the permission liquid gate of flowing through from both sides from right to left.Position by regulating projection, distance, geometry, diameter and highly and the width of little stream and capillary force that the position makes gate when being suitable for estimating liquid, this can realize above-mentioned effect.
[0033] in one embodiment, gate comprise have adjusted positions, the projection of distance, geometry, diameter and height.
[0034] in alternative embodiment, there is not gate.The substitute is by making stream longer and/or reduce the capillary force be applied on the liquid, make at least one stream flow slower than flowing in other streams.
[0035] distance of projection, geometry, diameter and highly being adjusted makes capillary force at least a portion of stream and groove greater than the capillary force in the stream that leads to other grooves.
[0036] in one embodiment, at least a reagent is attracted at least one flow path surfaces.In another embodiment, reagent is attracted on the stream that applies minimum capillary force.
[0037] liquid is applied the stream of different capillary forces in one embodiment owing to different capillary forces has different liquid flow rates.
[0038] intersection of Fig. 2 stream embodiment is shown in Figure 3 and be made up of to produce different capillary forces the projection with different interval in this specific embodiment.
[0039] in an embodiment shown in Figure 1, has two different slots that liquid applied different capillary forces.In the alternative embodiment shown in Fig. 1 d, have a groove divided into two parts, it applies different capillary forces to liquid.Be represented by dotted lines the border between the described part among Fig. 1 d.When the part that applies maximum capillary force during by complete filling, liquid will begin to flow in the zone that liquid is applied littler capillary force, make this effect be similar to the effect shown in Fig. 1 a and the 1b.
[0040] in one embodiment, material is adsorbed and/or is bound to analysis site.In one embodiment, this material can fetter at least one analyte.This examples of substances comprises antibody.
[0041] in one embodiment, at least a reagent be adsorbed or mummification at least one runner.This reagent can be any chemistry or the biological entities that participates in the analysis.The example of reagent comprises antibody, and described antibody comprises can detect entity, but other detection molecules, and can be bound to molecule on the analyte.
[0042] in alternative embodiment, can carry out the multistep analysis, wherein for example two kinds, three kinds or plurality of reagents are added successively with the regular hour difference.This embodiment is shown in Fig. 1 c, and wherein two kinds of reagent k that separate and k ' are alternately added each other.In one embodiment, at least three different capillary forces are applied on the described liquid; First capillary force forms first groove, and second capillary force forms second groove, and the 3rd capillary force forms three-flute.In one embodiment, the groove that has the different size shown in Fig. 1 c.In another embodiment, projection is adjusted and makes that the capillary force that applies is different for different grooves and stream.
[0043] in another embodiment, can comprise the analysis in two steps or three steps.In one embodiment, comprise the global analysis in three steps.The specific example of this analysis is the device according to Fig. 1 c, and wherein the first antibody of direction analysis thing is bound to analysis site.In the first step, sample is put by analysis and analyte is bound on the sub-fraction of lip-deep first antibody.In second step, the SA of direction analysis thing is point by analysis, and described SA comprises general constraint unit.SA will be bound to analyte in second step, and described analyte is bound to first antibody at analysis site.In the 3rd step, but the detection molecules that can be bound to the general constraint unit on SA point by analysis.But detection molecules is bound to antibody in the 3rd step.The advantage that this three step is analyzed is that the 3rd step all was identical and therefore described the 3rd step can be used for a lot of different types of tests by a suboptimization for all types of tests.
[0044] in a second aspect of the present invention, a kind of method of analytic sample is provided, wherein use said apparatus analysis.In this method, sample preferably adds the zone that receives described sample to.Described method preferably includes the step that reads analysis result.
[0045] provides the external member that comprises said apparatus and at least a reagent in the third aspect.Randomly, external member comprises further determinator.The example of this determinator comprises the retainer of device, is used to insert the measurement device of described device, or helps other devices of analyzing.In one embodiment, this external member comprises at least one packing.In another embodiment, external member comprises explanatory note.In another embodiment, external member comprises the reader that can measure on described device.This reader can be measured on analysis site.
[0046] in one embodiment, when fluid sample is added to when receiving sample regional, liquid flows upward to gate and reagent by sample dissolution in a stream.This is shown in Fig. 2 a.Black rectangle characterizes reactant in Fig. 2.At another stream, liquid flows into the zone that receives sample.The analysis site of sample flow through measuring.Because bigger capillary force in a stream, liquid has the groove of bigger capillary force along flow path with maximum capillary force and filling.By complete filling, liquid just begins to flow into the zone with littler capillary force up to the groove with bigger capillary force.Time that sample is put by analysis in the first step and amount limit by the groove that filling has bigger capillary force.In Fig. 2 b, the groove with bigger capillary force is begun to flow in the zone that liquid is applied littler capillary force by complete filling and sample.
[0047] liquid will flow to gate then, and therefore when gate during at contact both sides liquid, the described liquid gate of can flowing through on both direction.The liquid of reactant with dissolving is with other grooves shown in the flow graph 2c.In Fig. 2 c, the reactant that shows the dissolving that characterizes with black rectangle is point by analysis.In Fig. 2 d, measurement finishes and all grooves are filled and/or no longer include available sample size fully.Therefore the time of gate before opening can be limited well and the described time is conditioned and makes and allow reagent fully to dissolve.

Claims (15)

1. the device of a handling liquid samples, described device comprises: the projection that a) is substantially perpendicular to the surface of described device, described projection has height, distance between diameter and the described projection, described projection can produce with described surface and become horizontal fluid capillary flow, b) at least one receives the zone of sample, c) at least one can receive the groove of described liquid, described at least one groove applies at least two different capillary forces to described liquid, d) connect the zone of described at least one reception sample and at least two streams of described at least one groove, described stream applies at least two different capillary forces to described liquid, and e) at least one connecting portion between described at least two streams.
2. device according to claim 1 is characterized in that, described at least one groove has two parts that described liquid applied different capillary forces.
3. device according to claim 1 comprises at least two different grooves, and each groove applies capillary force to described liquid, and described capillary force is different.
4. according to each described device of claim 1-3, it is characterized in that at least one of described stream comprises at least one gate, when described gate allows liquid flow during contact liq on both direction at least.
5. device according to claim 4 is characterized in that described gate further comprises the projection on the surface that is substantially perpendicular to described device.
6. according to each described device of claim 1-5, it is characterized in that at least a reagent is attracted at least one of described stream.
7. according to each described device of claim 1-6, it is characterized in that at least a reagent is attracted to described liquid is applied on the stream of minimum capillary force.
8. according to each described device of claim 1-7, it is characterized in that described at least two streams have the different flow rates of described liquid.
9. according to each described device of claim 1-8, it is characterized in that described device applies at least three different capillary forces to described liquid.
10. device according to claim 9 is characterized in that, described device further comprises at least two kinds of different reagent.
11. the method for an analytic sample is characterized in that, used each described device according to claim 1-10, and wherein said sample adds the zone that at least one receives described sample to.
12. method according to claim 11 is characterized in that, reads the result from described device.
13. an external member, it comprises according to each described device of claim 1-10 and at least a reagent.
14. external member according to claim 13 further comprises analytical equipment.
15., further comprise at least one reader that on described device, to measure according to each described external member of claim 13-14.
CN200880012452.4A 2007-04-16 2008-04-15 Device for handling liquid samples Active CN101678355B (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US92379807P 2007-04-16 2007-04-16
SE0700930-1 2007-04-16
SE07009301 2007-04-16
US60/923,798 2007-04-16
SE0700930A SE529978C2 (en) 2007-04-16 2007-04-16 Analysis device for liquid samples, e.g. patient samples, includes flow paths between sample receiving and holding areas capable of exerting different capillary forces
PCT/SE2008/050424 WO2008127191A1 (en) 2007-04-16 2008-04-15 Device for handling liquid samples

Publications (2)

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CN101678355A true CN101678355A (en) 2010-03-24
CN101678355B CN101678355B (en) 2012-11-14

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CA (1) CA2683920C (en)
SE (1) SE529978C2 (en)
WO (1) WO2008127191A1 (en)

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SE0700930L (en) 2008-01-22
JP5425757B2 (en) 2014-02-26
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CN101678355B (en) 2012-11-14
CA2683920C (en) 2016-05-31
EP2134472A4 (en) 2014-10-01
WO2008127191A1 (en) 2008-10-23
JP2010525319A (en) 2010-07-22
SE529978C2 (en) 2008-01-22
EP2134472A1 (en) 2009-12-23

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