CN101678355B - Device for handling liquid samples - Google Patents

Device for handling liquid samples Download PDF

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Publication number
CN101678355B
CN101678355B CN200880012452.4A CN200880012452A CN101678355B CN 101678355 B CN101678355 B CN 101678355B CN 200880012452 A CN200880012452 A CN 200880012452A CN 101678355 B CN101678355 B CN 101678355B
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fluid sample
sample
different
liquid
reagent
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CN101678355A (en
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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 said at 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
The present invention relates to the field of the device of handling liquid samples.
Background technology
The 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 said sample comprises blood, blood plasma, serum, sweat, saliva, urine, tear, water sample, and the suspension of foodstuff samples or solution.
This determinator is for example at WO 2005/118139 (
Figure G2008800124524D00011
MIC AB); Be described among WO2005/089082 (
Figure G2008800124524D00012
MIC AB) and the WO 03/103835 (
Figure G2008800124524D00013
MIC AB).
Other determinators are described among 852 (BIOSITE) and the EP1120164 (ROCHE DIAGNOSTICS GMBH) for example at US 5,458.
GB 2410086 (BRITISH BIOCELL INTERNAT LTD) discloses a kind of determinator, and it comprises that the flow barrier part is to confirm the flow of liquid.
US 6,296,020 (BIOMICRO SYSTEMS, INC.) disclose a kind of through using passive valve or arresting stop to control method through the fluid stream of microchannel.
Summary of the invention
Technical problem
In some known determinators, added the sample that comprises analyte, this sample is along the flow path of the dried reagent of dissolving.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.
A problem about above-mentioned technology is how to let sample before reagent, arrive analysis site.This needs in some applications.
Another problem is how accurately to repeat to limit quantity of sample, and said sample is the process analysis site before reagent arrives analysis site.
Another problem is how to let sample before reagent arrives analysis site, react for a long time at analysis site.
Another problem is to eliminate the influence that reagent can dissolve based on the degree of drying of for example Preservation of Reagent time and reagent differently.
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
The objective of the invention is to alleviate at least some problems of the prior art.
This application of the invention realizes; The present invention provides a kind of device of handling liquid samples in first aspect; Said device comprises: a) be substantially perpendicular to the projection on the surface of said device, said projection has the distance between height, diameter and the projection, and said projection can produce with said 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 said liquid, and said at least one groove applies at least two different capillary forces to said liquid, d) connects the zone of said at least one reception sample and at least two streams of said at least one groove; Said stream applies at least two different capillary forces to said liquid, e) at least one connecting portion between said at least two streams.
Determinator has utilized the projection that is substantially perpendicular to said surface to produce capillary force so that liquid flow.The fact of said 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 directing flow on required direction.
The present invention also comprises a kind of method and external member of analytic sample.
Advantageous effects
Advantage of the present invention comprises can let sample before reagent, arrive analysis site.Another advantage is to limit quantity of sample, and said sample is the process analysis site before reagent arrives analysis site.Further advantage is to eliminate or to alleviate the influence that reagent dissolves differently.
Description of drawings
Fig. 1 a-d shows each embodiment according to device of the present invention.
Fig. 2 a-d showed according to device of the present invention each stage in use.
Fig. 3 is the electron micrograph according to the part of analytical equipment of the present invention.The figure shows and be used for the for example intersection of two runners of device shown in Figure 2.
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
Before the present invention is at length disclosed and describes, be understood that to the invention is not restricted to the disclosed concrete structure of this paper, 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 accompanying claims and equivalent thereof.
Also must be noted that, comprise plural like this specification and the employed singulative of accompanying claims " a kind of " and " said ", except spelling out in the literary composition.Following term is used in the full text of specification and claims.
Term " analysiss " the expression sample that this paper uses is verified with the process of acquisition to the understanding of sample, for example about the qualitative and/or quantitative composition of sample.
Point or the zone measured on term " analysis site " the expression determinator that this paper uses.
Material, chemical constituent or biological components that term " analyte " expression that this paper uses is analyzed.
Chemistry or biological components that analysis is participated in term " reagent " expression that this paper uses.
Term " sample " expression that this paper uses comprises the arbitrary substance of analyte.
Specifically describe
At least some of above-mentioned advantage realize through 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 directing flow on required direction.
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 said liquid, connect two streams of a groove respectively, and a connecting portion between said 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.
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 more than a side contacts liquid time, allows liquid flow
When liquid flows to from a left side in stream shown in Figure 4 when right, mobile quilt stops, 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 from both sides and allows flow of liquid through gate together from right to left.Position through 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.
In one embodiment, gate comprise have adjusted positions, the projection of distance, geometry, diameter and height.
In alternative embodiment, there is not gate.The substitute is through making stream longer and/or reduce and to be applied to the capillary force on the liquid, make at least one stream flow slower than flowing in other streams.
The distance of projection, geometry, diameter and height are made capillary force at least a portion of stream and groove greater than the capillary force in the stream that leads to other grooves by adjustment.
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.
The stream that liquid is applied different capillary forces is in one embodiment owing to different capillary forces has the different liquid flow rate.
An embodiment of the intersection of Fig. 2 stream is being made up of to produce different capillary forces the projection with different interval shown in Fig. 3 and in this specific embodiment.
In an embodiment shown in Figure 1, have 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 said 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.
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.
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 said antibody comprises can detect entity, but other detection molecules, and can be bound to the molecule on the analyte.
In alternative embodiment, can carry out the multistep analysis, wherein for example two kinds, three kinds or plurality of reagents are added with the regular hour difference successively.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 said 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 is made that the capillary force that applies is different for different grooves and stream.
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 bound on the sub-fraction of lip-deep first antibody through analysis site and analyte.In second step, the SA of direction analysis thing is through analysis site, and said SA comprises general constraint unit.SA will be bound to analyte in second step, and said 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 the SA is through analysis site.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 said the 3rd step can be used for the number of different test by a suboptimization for all types of tests.
In 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 said sample to.Said method preferably includes the step that reads analysis result.
The external member that comprises said apparatus and at least a reagent is provided 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 said 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 on said device, measure.This reader can be measured on analysis site.
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.Sample flow is through carrying out the Analysis of measuring point.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.Sample limited through the groove that filling has bigger capillary force with amount through the time of analysis site in the first step.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.
Liquid will flow to gate then, and therefore when gate during at contact both sides liquid, the said liquid gate of can on both direction, flowing through.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 through analysis site.In Fig. 2 d, measure completion and all grooves and be filled and/or no longer include available sample size fully.Therefore the time of gate before opening can be limited well and the said time is conditioned and makes and allow reagent fully to dissolve.

Claims (15)

1. the device of a handling liquid samples; Said device comprises: the projection that a) is substantially perpendicular to the surface of said device; Said projection has the distance between height, diameter and the said projection; Said projection can produce with said surface and become horizontal fluid capillary flow, and b) at least one receives the zone of fluid sample, and c) at least one can receive the groove of said fluid sample; Said at least one groove applies at least two different capillary forces to said fluid sample; D) connect said at least one receive the zone of fluid sample and at least two streams of said at least one groove, said stream applies at least two different capillary forces to said fluid sample, and e) at least one connecting portion between said at least two streams.
2. device according to claim 1 is characterized in that, said at least one groove has two parts that said fluid sample applied different capillary forces.
3. device according to claim 1 comprises at least two different grooves, and each groove applies capillary force to said fluid sample, and said capillary force is different.
4. according to each described device of claim 1-3, it is characterized in that at least one of said stream comprises at least one gate, when said gate allows fluid sample to flow during the contact liq sample on both direction at least.
5. device according to claim 4 is characterized in that said gate further comprises the projection on the surface that is substantially perpendicular to said device.
6. device according to claim 1 is characterized in that at least a reagent is attracted at least one of said stream.
7. device according to claim 1 is characterized in that, at least a reagent is attracted to said fluid sample is applied on the stream of minimum capillary force.
8. device according to claim 1 is characterized in that, said at least two streams have the different flow rates of said fluid sample.
9. device according to claim 1 is characterized in that, said device applies at least three different capillary forces to said fluid sample.
10. device according to claim 9 is characterized in that, said device further comprises at least two kinds of different reagent.
11. the method for an analyzing liquid sample is characterized in that, used each described device according to claim 1-10, and wherein said fluid sample adds the zone that at least one receives said fluid sample to.
12. method according to claim 11 is characterized in that, reads the result from said 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 said 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

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CN101678355B true CN101678355B (en) 2012-11-14

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WO (1) WO2008127191A1 (en)

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CA2683920A1 (en) 2008-10-23
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
CN101678355A (en) 2010-03-24

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