CN102012421B - Detection device for analyzing analyte in liquid sample - Google Patents

Detection device for analyzing analyte in liquid sample Download PDF

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Publication number
CN102012421B
CN102012421B CN200910152616.XA CN200910152616A CN102012421B CN 102012421 B CN102012421 B CN 102012421B CN 200910152616 A CN200910152616 A CN 200910152616A CN 102012421 B CN102012421 B CN 102012421B
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China
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chamber
liquid sample
aperture
piston
film
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CN102012421A (en
Inventor
金忠其
余双
黄富强
邹健
刘威
吴银飞
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ABON Biopharm Hangzhou Co Ltd
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ABON Biopharm Hangzhou Co Ltd
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Priority to CN200910152616.XA priority Critical patent/CN102012421B/en
Priority to EP10796658.2A priority patent/EP2451576B1/en
Priority to US13/394,759 priority patent/US9327283B2/en
Priority to PCT/CN2010/001020 priority patent/WO2011003281A1/en
Publication of CN102012421A publication Critical patent/CN102012421A/en
Application granted granted Critical
Publication of CN102012421B publication Critical patent/CN102012421B/en
Priority to US15/135,418 priority patent/US20160310938A1/en
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Abstract

The invention relates to a device for analyzing analyte in a liquid sample, which comprises a detection cavity (716, 202, 601, 171) used for accommodating a detection element, a liquid sample transfer cavity (208, 502, 172) and a hydrophobic micropore film (170) arranged between the detection cavity and the liquid sample transfer cavity, wherein when the detection device is inserted into a liquid sample collecting cavity 101, the liquid sample in the collecting cavity enters the liquid sample transfer cavity, the liquid sample can not enter the detection cavity through the film; and when a piston 102 is inserted into the liquid sample transfer cavity, the piton forces part of liquid samples in the transfer cavity to enter the detection cavity through the micropore film. Quantitative sampling can be carried out and the detection can be completed once by using the device.

Description

The pick-up unit of analyte in analytic liquid sample body
Technical field
The invention belongs to liquid sample collection field, belong to especially the field of collecting liquid sample and detecting analyte in sample, especially detect in sample, whether to contain the metabolin of drug abuse material or the detection of the quick diagnosis of forepart pregnant women aspect.
Background technology
In recent years, pick-up unit is made in a large number for detecting people's body fluid, urine for example, the analyte in saliva or blood, for example indicator substance of drug abuse or disease.Traditional like this pick-up unit need to be collected in liquid sample to container conventionally, then testing element is inserted in liquid and then takes out the test result reading on (with the naked eye see or read with machine) testing element.So likely allow operator be contaminated by the sample.Use this pick-up unit except being used by professional testing staff, do not had the people of professional experiences to use gradually by some, for example, use in the family, this just need to provide a kind of operation simpler, and testing result is pick-up unit more accurately.
Summary of the invention
On the one hand, the present invention relates to the pick-up unit of analyte in a kind of analytic liquid sample body, this device can quantitative sampling and is detected in sample, whether there is analyte.Pick-up unit comprises, for accommodating the test chamber of detecting element; A liquid sample transfer chamber; An and aperture film being arranged between test chamber and liquid sample transfer chamber, wherein, when this pick-up unit is inserted in a liquid sample collection chamber, the liquid sample in collecting chamber enters in liquid sample transfer chamber, but this liquid can not enter in test chamber by this film; And wherein, when a piston is inserted in liquid sample transfer chamber, piston forces the partially liq sample in transfer chamber to enter into test chamber by this porous membrane.
In some preferred modes, aperture can be set to have surface tension of liquid, when the pressure differential of described transfer chamber and test chamber is less than or equal to the set surface tension of liquid of this aperture, the liquid sample in transfer chamber can not enter test chamber by the aperture on this hydrophobic film; When the pressure differential of described transfer chamber and test chamber is greater than the set surface tension of liquid of this aperture, the liquid in transfer chamber enters in test chamber by described aperture.Preferred, allowing piston relatively move in transfer chamber increases the pressure in transfer chamber, and allows it be greater than the set surface tension of liquid of described aperture.In other preferred modes, between liquid sample transfer chamber and collecting chamber, can also comprise a fluid passage, the partially liq sample in collecting chamber flow into after transfer chamber by this passage, and described first passage is by this piston seal.Preferably, in the time of piston seal first passage, the pressure in described transfer chamber is less than or equal to the set surface tension of liquid of second channel.
In the preferred mode of other, piston has primary importance and the second place in transfer chamber; When piston is positioned at primary importance, now, the fluid passage between piston seal collecting chamber and transfer chamber allows holding portion liquid sample in plunger shaft simultaneously; Liquid sample can not enter in test chamber by being arranged on the aperture on hydrophobic film between test chamber and transfer chamber; When piston moves to the second place from primary importance, piston forces the liquid sample of transfer chamber to enter into test chamber by the aperture on hydrophobic film.
On the other hand, the present invention also provides a kind of detection box, comprising: a kind of pick-up unit, comprise liquid sample transfer chamber, and test chamber wherein arranges one deck aperture film between transfer chamber and test chamber; A liquid sample collection chamber, comprises that one for being inserted into the piston of transfer chamber; When in use, this pick-up unit is inserted in collecting chamber, and the liquid sample in collecting chamber flow in transfer chamber, but can not by the aperture on film, enter in test chamber; And wherein, when piston is inserted in transfer chamber, thereby force the partially liq sample in transfer chamber to enter in test chamber and contact with testing element by film.
In a preferred mode, aperture can be set to have surface tension of liquid, when the pressure differential of described transfer chamber and test chamber is less than or equal to the set surface tension of liquid of this aperture, the liquid sample in transfer chamber can not enter test chamber by this aperture; When the pressure differential of described transfer chamber and test chamber is greater than the set surface tension of liquid of this aperture, the liquid in transfer chamber can enter in test chamber by described aperture.More preferably, liquid sample transfer chamber can also comprise a passage, and the partially liq sample in collecting chamber flow into after transfer chamber by this passage, and described passage is by this piston seal.More excellent, in the time of piston seal passage, the pressure in described transfer chamber is less than or equal to the set surface tension of liquid of second channel.
Other preferred embodiment in, piston has primary importance and the second place in transfer chamber; When piston is positioned at primary importance, piston seal fluid passage, allows holding portion liquid sample in plunger shaft, and meanwhile, the pressure in plunger shaft is less than or equal to the set surface tension of liquid of aperture; When piston moves to the second place from primary importance, piston increases the pressure in plunger shaft and allows it be greater than the surface tension of liquid of set aperture.
On the other hand, the invention provides the method for analyte in a kind of analytic liquid sample body, comprising: pick-up unit is inserted in a liquid sample collection chamber; Allow the liquid sample in collecting chamber enter in the liquid sample transfer chamber of pick-up unit by fluid passage, but allow liquid not enter in test chamber by the hydrophobicity aperture film being arranged between test chamber and transfer chamber; Allow piston be inserted in liquid sample transfer chamber, force the liquid sample in transfer chamber to enter in test chamber by the aperture film being arranged between test chamber and transfer chamber.At one, specifically more preferably in mode, can allow the liquid sample in test chamber contact with detecting element.In another one embodiment, piston can be positioned at collecting chamber.
In addition, can allow piston in transfer chamber, there are the first and second positions; When piston is positioned at primary importance, liquid sample can not enter in test chamber by this hydrophobicity aperture film, piston seal fluid passage; Allow piston move to the second place from primary importance, thereby force the partially liq sample in transfer chamber to enter in test chamber by the hydrophobicity aperture film being arranged between test chamber and transfer chamber.
In other embodiment, liquid sample transfer chamber, test chamber and aperture film can be connected as a single entity; Collecting chamber and piston can be connected as a single entity.
In other mode, can allow aperture be set to there is surface tension of liquid, allow the pressure differential of transfer chamber and test chamber be less than or equal to the set surface tension of liquid of this aperture, thereby make the liquid sample in transfer chamber not enter test chamber by this aperture; Allow the pressure differential of transfer chamber and test chamber be greater than the set surface tension of liquid of this aperture, thereby the liquid in transfer chamber can be entered in test chamber by described aperture.In a mode, allowing piston relatively move in transfer chamber increases the pressure in transfer chamber.
In above all embodiments, in more concrete preferred embodiment, can also be: piston is positioned at the bottom of collecting chamber and to upper process; Piston can be arranged in liquid sample collection chamber and be connected as a single entity with liquid sample collection chamber; Transfer chamber can also be connected as a single entity with test chamber.In addition, aperture film can be hydrophobicity aperture film.Also have, the quantity of aperture can be 2 for one or more, 3, and 4,5 or more; Aperture diameter can be 1-100 micron; 1-10 millimeter can be 0.1,0.2,0.3,0.4,0.5,0.8,0.9,1,2,3,4,5 or 6 millimeter; The shape of aperture can be cylindrical or taper or other shapes.These devices, the detecting element detecting in box or method can be cross flow reagent strips, can also comprise a fetch equipment that reads test result on detecting element.
Beneficial effect
The present invention makes to detect sample and settles at one go, and can be to environment, and simple operation can realize quick diagnosis and detect family's use.In addition, this device can quantitatively detect, and can improve accuracy and the sensitivity of detection.
Accompanying drawing explanation
Fig. 1 is that some specific embodiment principle of work in the situation that of liquid sample abundance of device of the present invention is not intended to;
Fig. 2 is the profile schematic diagram of the sub-shown device principle of work of other specific embodiment;
Fig. 3 is principle of work schematic diagram in other embodiments of device of the present invention;
Fig. 4 detects box schematic appearance in specific embodiment of the present invention;
Fig. 5 is the structure exploded perspective view that Fig. 4 detects box;
Fig. 6 is the perspective view of the gathering-device shown in Fig. 4;
Fig. 7 is the perspective view of the pick-up unit shown in Fig. 4;
Fig. 8 is the cross-sectional view of pick-up unit shown in Fig. 7;
Fig. 9 is another cross-sectional view of detection part shown in Fig. 7;
Figure 10 is small structure enlarged diagram in examples of implementation;
Figure 11 is small structure enlarged diagram in another examples of implementation;
Figure 12 is the medium and small pore passage structure enlarged diagrams of another examples of implementation;
Figure 13 is that the pick-up unit shown in Fig. 4 is inserted in collecting chamber but piston is not also inserted into the cross-sectional view in transfer chamber;
Figure 14 is the enlarged diagram of A part-structure shown in Figure 13;
Figure 15 is that the fluid passage of the transfer chamber shown in Figure 14 is moved and forces liquid sample by aperture 713, to enter the Operation Profile structural representation of test chamber in transfer chamber by piston seal back piston;
Figure 16 is the enlarged diagram of B part-structure shown in Figure 15;
Figure 17 is in embodiment of the present invention, test chamber and transfer chamber part-structure enlarged diagram in pick-up unit;
Figure 18 is the array mode of hydrophobicity aperture film in the different embodiments of the present invention.
Description of reference numerals:
Pick- up unit 20,60,71; Detect box 70,90,56; Detecting element 40,717; Lid 711; Test chamber 202,601,716,171; Aperture film 209,7111; Aperture 203,205,713,714; Aperture inside surface 2003, tapered openings 713, back taper aperture 714, transfer chamber 208,172, plunger shaft 201,501,712; Fluid passage or plunger shaft opening 503,204,715; One end 604 of test chamber, result display window 710, piston 102,722, collecting chamber opening 723, collecting chamber 721,101, bottom 724,104, fetch equipment 718, O-ring seal 105,726; Barrier element 719, screw thread 727; Hydrophobicity aperture film 170, perforate 173.
Embodiment
In the following detailed description, accompanying drawing and corresponding explanatory note are only the modes that illustrates that by way of example the present invention can actable specific concrete scheme.We do not get rid of the present invention can also be in any other embodiment within the scope of the claims in the present invention.
On the one hand, the invention provides the pick-up unit of analyte in a kind of tracer liquid sample.This device can detect chemical examination and not pollute other remaining liquid samples liquid sample.And this detection is that a step completes, and does not need complicated operation steps.This pick-up unit 20 comprises: for accommodating the test chamber 202 of detecting element; A liquid sample transfer chamber 208; With one test chamber and the separated aperture film 209 of liquid sample transfer chamber; Wherein, when this pick-up unit being inserted in a liquid sample collection chamber 101, in the liquid sample 30 influent sample transfer chamber 208 in collecting chamber 101, but can not enter in test chamber by this film 209; And wherein, when a piston 102 is inserted in liquid sample transfer chamber 208, piston 102 forces the partially liq sample 301 in transfer chamber 208 to enter into test chamber 202 by this porous membrane 209.
As Figure 1A-1D has shown a specific embodiment of the present invention.Now describe in detail.As Figure 1A, shown the liquid-sample collection device 10 in one embodiment of the present invention, comprise a chamber 101 of collecting liquid sample, encircled a city by sidewall and bottom 104 in this chamber and an end opening is used for receiving or accommodating liquid sample, and the other end is closed.One piston 102 is positioned at the bottom 104 of collecting chamber and to upper process.As Figure 1B, shown that a pick-up unit 20 in embodiment of the present invention comprises a test chamber 202, this test chamber can be used for holding detecting element 40 and accept the liquid sample from transfer chamber, with a liquid sample transfer chamber 208, between test chamber 202 and liquid sample transfer chamber 208, one deck hole film 209 is set, this film is separated test chamber 202 and liquid sample transfer chamber 201.In Figure 1B, transfer chamber can be specially plunger shaft 201, this plunger shaft one end opening provides and allows liquid enter the fluid passage 204 of plunger shaft, the other end, by the narrow meshed diaphragm seal of one deck, is specially two apertures 203 and 204 in Figure 1B, and these two apertures connect plunger shaft and test chamber.When in use, pick-up unit is inserted in the collecting chamber 101 in gathering-device, the liquid sample in collecting chamber enters in transfer chamber by passage 204, but liquid can not enter in test chamber 202 by film 209; Piston 102 in collecting chamber is inserted in transfer chamber 208, is specially in plunger shaft 201 in Fig. 1, and piston forces partially liq sample to enter in test chamber 202 by the aperture 203,205 on film 209, as shown in Figure 1 C.In a preferred mode, if comprise a detecting element 40 in test chamber, enter liquid sample in test chamber and contact with detecting element and chemically examine detection, as Fig. 1 D.
In other concrete optimal ways, size or shape that aperture can be set allow aperture have certain surface tension of liquid, for example, allow the interior diameter of aperture be 0.5 millimeter.In collecting chamber, collected after a certain amount of liquid sample, as shown in Figure 1A, a large amount of liquid samples is collected in collecting chamber, then pick-up unit 20 is inserted in collecting chamber 101, in insertion with near in the process of piston 102, partially liq sample in collecting chamber enters in plunger shaft 201 by passage 204, air in plunger shaft is by aperture 203 or 205 simultaneously, be rejected to outside plunger shaft, because test chamber and atmosphere communicate, the pressure of plunger shaft interior 201 and test chamber 202 equates, pressure differential is almost nil, be less than the surface tension of liquid of predefined aperture.Along with plunger shaft continue move down, air in plunger shaft is by drained gradually, and liquid sample 30 is full of whole plunger shaft 201, and now liquid contacts with air at aperture place, due to the existence of aperture, liquid just descends under the effect in hole and produces certain surface tension of liquid; Along with plunger shaft 201 continue move down, the liquid level in plunger shaft gradually lower than the liquid level of collecting chamber 101 (when liquid sample is more sufficient or a large amount of time).Along with plunger shaft continues to move down, the opening of plunger shaft, passage 204, with piston 102 cooperations and by piston seal, due to piston seal passage 204, stoped in collecting chamber more liquid sample to enter in plunger shaft, this in time piston be positioned at the primary importance in plunger shaft.In this time, because two liquid surfaces have a height difference H, as Fig. 1 C, thereby make way for the subsurface pressure of aperture 203 or 205, increase.But owing to being provided with size or the shape of aperture, between liquid and air, effect produces a surface tension of liquid, and this tension force can be set to larger than the pressure producing due to the poor H of liquid level, this time, liquid sample in transfer chamber can not enter in test chamber from aperture 203,205.Along with plunger shaft 201 continues to move down, from primary importance, move to the second place, the piston 102 that is arranged in collecting chamber is done further movement in plunger shaft, liquid in piston compressing plunger shaft 201 increases by the pressure of aperture lower surface, thereby broken the set surface tension of liquid of aperture, allow the liquid sample in plunger shaft pass through aperture 203 or 205, enter in test chamber and react with testing element 202, now piston is positioned at the second place of plunger shaft.
In some other specific embodiment, in plunger shaft, hold after a part of liquid sample, can allow piston 101 in the process of seal fluid passage 204 movement in plunger shaft, still allow piston and plunger shaft keep sealing state, can stop like this liquid sample in collecting chamber to enter in plunger shaft, reach the object of quantitative sampling, in order to reach better sealing effectiveness, outside surface at piston arranges one or several plastics, rubber or silica gel sealing ring, for example " 0 " shape circle 105, as Figure 1A.Can certainly not allow piston seal passage 204, but along with plunger shaft with piston than relative motion faster, allow the liquid in piston compressing plunger shaft produce the pressure of moment, this instantaneous pressure can be broken the intrinsic surface tension of liquid that aperture is set up and allow the liquid in plunger shaft enter test chamber.
Except above concrete mode, the aperture film with this character can be selected arbitrarily, for example, select those films with micro hole, cellulose nitrate film for example, nylon film or filter paper, glass fibre etc.Certainly can also be the plastic sheet with micro-aperture.
In other some, more preferably in embodiment, aperture film is hydrophobicity aperture film.Here said " hydrophobicity aperture film " can be originally hydrophobic material as hydrophobic material or essence for the material of formation or composition aperture film; Or the material that forms aperture film is water wettability, but hydrophilic film has formed hydrophobic film after hydrophobic agents is processed.Hydrophilic material can be cellulose nitrate film, nylon film or filter paper, and process and formation hydrophobicity through some hydrophobic agents on the surface of the materials such as glass fibre.Hydrophilic material usually, mostly with the molecule of polar group, has large affinity to water, can attract hydrone, or be dissolved in water.The surface of the solid material that this quasi-molecule forms, easily moistening by water institute.Hydrophobic molecule is partial to nonpolar, and therefore can be dissolved in neutral and non-polar solution (as organic solvent).Hydrophobic molecule is conventionally converged to one in water, and water can form a very large contact angle and form drops when hydroholic solution surperficial.This film can be at least 20% hydrophobicity; Be at least 30% or 50% hydrophobicity; 60% or 70% hydrophobicity more preferably; Be preferably 80% or 90% hydrophobicity.Aperture on film can also can freely design at film forming while self-assembling formation in processing or production run, the size of aperture can for 0.1-100 micron not etc., it can be 3-80 micron, 4-50 micron, also can be 8-15 micron etc., the size of aperture can be even size, can be also to change within the specific limits, for example, can be that size is the aperture of the even size of 20,30,8 or 25 microns; Also can be the size of 30% aperture on those films between 20-15 micron, other 70% micropore size is between 2-13 micron.These hydrophobic films can be hydrophobicity cellulose nitrate films, hydrophobicity nylon film or hydrophobicity filter paper, hydrophobic glass fiber or hydrophobicity mylar etc.These aperture films also can directly be bought from existing market, for example, from Ao Silong filtration company, buy (AHLSTROM FILTRATION LLC), station address: www.ahlstrom.com; CompanyAddress: the Kentucky State, Kentucky State 42431-0030, the U.S. (270) 821-0140, (270) 326-3290 fax; Post-office box(P.O.B.) 1410.
In a concrete embodiment, as shown in FIG. 17 and 18; Figure 17 is the part-structure enlarged diagram of the pick-up unit of the object lesson in one embodiment of the present invention.The public face 177 of test chamber 171 and transfer chamber 172 is opened an aperture 173 on this face 177, and diameter is approximately 6-8 millimeter; Then at the sticky one deck hydrophobicity aperture film 170 in the place of aperture, by this hydrophobicity aperture film, test chamber 171 and transfer chamber 172 are kept apart.Optionally, for convenient for production; Can be when injection moulding be produced and to be touched tool, disposable hydrophobicity aperture film is injection-moulded between test chamber and transfer chamber.For example, when producing pick-up unit shown in Figure 17, place a slice hydrophobicity aperture film touching on tool, then liquid plastics are filled into and are touched in chamber, hydrophobicity aperture film is just injection-moulded between two chambeies 171 and 172 by disposable like this.This film can be one deck hydrophobicity aperture film, and thickness is approximately 10-50 micron, and pulling strengrth is 30-100 pound/inch; Gas permeability is 1-800 cubic inch/minute/square inch (CFM) (Cubic feet per minute per square meter); Preferably, gas permeability is 10-600 cubic inch/minute/square inch; Also can be 150-400 cubic inch/minute/square inch, can also be 150-400CFM, can be also 200-300CFM.Also can be double-layer films, near transfer chamber be one deck hydrophobicity aperture film 170, near test chamber be one deck hydrophilic film 174, Figure 18 B; Also can be two-layer be all the little empty film of hydrophobicity 170,175, Figure 18 C that sticks together, can also be on aperture film 170, to process one deck hydrophobic agents 176, Figure 18 D.
Utilize hydrophobicity aperture film allow to enter the liquid sample volume of test chamber to keep relatively constant, in the fixing situation of the shape of test chamber, the height of liquid in test chamber is relatively constant; Be used for like this detecting the degree of depth that the detecting element that contains analyte in sample is dipped into liquid sample in test chamber and just remain on a relatively constant height, like this, the accuracy detecting can be improved greatly, and reduces the error of the testing result between product.Because it is different that the liquid sample absorption site of detecting element is dipped into height or the degree of depth of liquid, within a certain period of time, the amount of liquid that detecting element absorbs is also just different, so just may affect the testing result of whole detecting element.Especially, when reading the result on detecting element with some electronic components, when wishing to obtain accurately testing result, more wish that detecting element is relatively stable and be disturbed less.In addition, the detection accuracy impact that volume change causes the variation of liquid height in test chamber to detect index to some is larger, for example, detects the tetrahydrocannabinol (THC) in urine specimen, if the volume entering in test chamber is not relatively constant; And it is large to change fluctuation range, to same sample, may there are two contrary testing results.Utilize porous membrane to reach and allow the liquid volume that enters test chamber a relatively constant scope, may be because comprise a lot of tiny micropores on this film, they are in 0.1-100 micron left and right, when detection part is put in gathering-device, because the opening of transfer chamber enters in transfer chamber by liquid sample, along with entering of liquid, gas in transfer chamber is discharged to outside transfer chamber by these micropores on film, can allow like this liquid sample be full of whole transfer chamber completely, but the hydrophobicity due to film contact liq one side, liquid can not enter in test chamber by these apertures, when piston is inserted in transfer chamber, liquid sample in transfer chamber is oppressed and enter in test chamber by these apertures, and due to the existence of these a plurality of apertures, liquid sample also easily enters in test chamber.When selecting film, the gas permeability of film, pulling strengrth can be used as a reference index and selects, and gas permeability can be with reference to determining venting capability, and pulling strengrth can be with reference to the pressure that determines to bear.
In the preferred embodiment of other, the public face of test chamber 202 and transfer chamber 201,209 on Figure 1B for example, this face is separated test chamber and transfer chamber, on this face 209, some apertures 203 or 205 are set, these aperture communication with detection chamber and transfer chamber.In a preferred mode, pick-up unit is once injection moulding, and public isolation surface 209 is plastic sheet, and thickness is approximately 1.5 millimeters, and some apertures are set on plastic sheet.In other examples of implementation, the surface tension of liquid that the aperture on film has is set, liquid surface can come to arrange arbitrarily as required, for example, change the internal diameter size of aperture, the perforate degree of depth of aperture, the shape of aperture or the combination of these features.The quantity of aperture can be 2 for one or more, 3, and 4,5 or more; The diameter of aperture can be 1-5 millimeter, can be 0.1,0.2,0.3,0.4,0.5,0.8,0.9,1,2,3,4,5 or 6 millimeter; The shape of aperture can be cylindrical or taper or other shapes; The thickness of aperture is 0.1-10 millimeter, can be 0.1,0.2,0.5,1.0,1,3,5,7,9,2,4 or 6 millimeters etc.In specific embodiment, as shown in Figure 10-12, aperture is tubular 203, and the interior diameter of aperture is 0.5 millimeter, is 1.5 millimeters deeply, can be also tapered aperture 713, Figure 11, or back taper aperture 714, Figure 12.Change the size of these apertures, the mode of shape or the degree of depth has a variety of, can be by selecting the film, filter paper, glass fibre etc. of the micro-aperture of different materials.Test chamber and the separated mode of transfer chamber are also had a variety of, for example passed through before this once injection moulding hollow circular cylinder, his both ends open, then the position in the middle of right cylinder arranges one deck with the film of micro hole, for example a layer thickness is the filter paper of 1.5 millimeters, this layer film is separated into two chambeies this right cylinder, test chamber 202 and transfer chamber 201.
Fig. 2 A-2D has shown another concrete embodiment of the present invention.Now describe in detail.As Fig. 2 A, shown the liquid-sample collection device 10 in embodiment of the present invention, comprise a chamber 101 of collecting liquid sample, this chamber by sidewall and bottom, surrounded and an end opening for receiving or accommodating liquid sample, the other end is closed.One piston 102 is positioned at the bottom of collecting chamber and to upper process.As Figure 1B, shown that a pick-up unit 20 in embodiment of the present invention comprises a test chamber 202, this test chamber can be used for holding detecting element 20 and accept the liquid sample from transfer chamber, with a plunger shaft 201, between test chamber 202 and plunger shaft 201, one deck filter paper 209 is set, this filter paper is separated test chamber and liquid sample transfer chamber.Liquid sample in collecting chamber 101 is less, when detection part 20 is inserted in collecting chamber, because liquid sample is less, plunger shaft 201 is partially filled liquid sample, air in piston is discharged to outside chamber by the intrinsic micro hole of filter paper, and the liquid surface in plunger shaft and the liquid level of collecting chamber are contour, and now the air pressure of the air pressure in plunger shaft and test chamber equates, pressure differential is zero, Fig. 2 C.Along with pick-up unit continues to move down, piston seal fluid passage 204, allows the liquid volume in plunger shaft 201 no longer increase.Plunger shaft further moves down, and piston impels the liquid in plunger shaft relatively to move up, and exists the surplus air in plunger shaft to pass through filter paper 209, is discharged from outside chamber.When piston, do further and move in plunger shaft, impel the liquid in plunger shaft to enter in test chamber 202 by the micro hole on filter paper.
Fig. 4-16 are some examples of implementation more specifically of the present invention.In an object lesson, detect box 70 and comprise gathering-device 72 and pick-up unit 71.Gathering-device 72 comprises the collecting chamber 721 of an end opening 723 and the other end 724 sealings, in sealing one end 724 of collecting chamber, i.e. and bottom, the piston 722 of a projection is set, it is upper that this piston is fixed on collecting chamber bottom, and Fig. 6, arranges an O-ring seal 726 in the top of piston extension.Pick-up unit 71 comprises test chamber 716 and plunger shaft 712, and test chamber and plunger shaft share a bottom 7111, and two apertures 714,713 are set on 7111, allows aperture communication with detection chamber and plunger shaft, Fig. 5 and Fig. 7; Make being shaped as of aperture cylindrical, Figure 10, the diameter of two apertures is respectively 0.5 millimeter, and the degree of depth is 1 millimeter.The position of piston and plunger shaft is set, when piston is inserted into collecting chamber, can allows piston over against plunger shaft; The height of piston and the degree of depth of plunger shaft are set, piston can be all inserted in plunger shaft; The diameter of piston and plunger shaft is set simultaneously, piston 722 can be just inserted in plunger shaft 712 can allow the opening 715 that piston can well packed-piston chamber simultaneously.In the present embodiment, test chamber 716, plunger shaft 712 and the bottom 7111 that they are public are plastic material disposable tool injection mo(u)lding; Collecting chamber 721, the piston 722 of bottom and projection is plastic material disposable tool injection mo(u)lding.Certainly, in other specific embodiment, piston and collecting chamber can be connected as a single entity or disposable tool injection mo(u)lding; Also can be to manufacture then and bond together by glue respectively.Test chamber and plunger shaft can be also moulding respectively, and then between arranges one deck aperture film, and aperture film is separated test chamber and transfer chamber like this.When in use, pick-up unit 71 is inserted into after collecting chamber 721, the liquid that is arranged in collecting chamber enters into plunger shaft by plunger shaft opening 715, now piston is not also inserted in plunger shaft, gas in plunger shaft is excluded by aperture, and because aperture has surface tension of liquid, the liquid in plunger shaft can not enter in test chamber by aperture, Figure 13,14.When piston is inserted in plunger shaft, piston increases by the pressure in plunger shaft, has broken the surface tension that aperture place forms, and forces liquid sample to enter test chamber, Figure 15 and 16.In test chamber, can also comprise a testing element 717, can also comprise the fetch equipment 718 of testing result on a read test element, fetch equipment is directly presented at the result reading on a LCD screen 710, Fig. 8.When liquid sample enters after test chamber, testing element contact liq sample reaction detection obtain testing result, by fetch equipment, testing result are directly presented in lcd screen.As Chinese invention patent application, application number 200410045273.4, in 200410045275.3,200410063910.0, disclosed all embodiments about testing element and fetch equipment can be used to the analyte that comes in the present invention in tracer liquid sample and the result of laboratory test on read test element.
In a more excellent embodiment, the lid 711 that test chamber 716, plunger shaft 712 and being used for covers collecting chamber opening is integrally connected, and as Fig. 8, shown in Figure 13-16, collecting chamber and lid are provided with respectively screw thread 727.In the time of on the opening that lid is covered to collecting chamber, rotation lid moves to low level by lid from a high position, drive the test chamber be connected as a single entity with lid together with plunger shaft from moving down, thereby complete sampling and the transfer of liquid sample.For example, shown in Figure 13-16, when cover cap is incorporated on gathering-device collecting chamber opening time, the plunger shaft being connected as a single entity with lid is inserted in collecting chamber, now, liquid sample in collecting chamber enters in plunger shaft 712 by plunger shaft opening 715, and the gas in plunger shaft is rejected in test chamber.Along with lid further rotates, Figure 15, allows distance that lid moves and the height of piston equate, like this, in the time of lid sealing collecting chamber opening, piston is full of whole plunger shaft, and piston forces the liquid in plunger shaft almost all by aperture, to enter in test chamber.
In some cases, due to continuity and the transience of sampling operation, from aperture liquid sample out, be sometimes " injection " shape and enter in test chamber.In order to prevent that these liquid samples are ejected on other elements that are positioned at test chamber, a protecting component is set above aperture, this element can be ejected on other elements by barrier liquid, does not affect again liquid sample and contacts with testing element simultaneously.Figure 14 institute for example arranges one and falls " U " shape or " ⊥ " structure of falling above aperture, and this structure can allow the liquid sample that is " injection " shape slowly enter in test chamber and contact and can not be ejected on other element with testing element.When particularly containing electronic component in test chamber, utilize protecting component can allow electronic component can not destroy some functions because of contact liq sample more safely.
In the preferred mode of other, when utilization arranges the size of aperture, shape or the degree of depth arrange capillary time, before preferably pick-up unit being inserted into collecting chamber, allow the inside surface 2003 of aperture, 7113, keep dry, can obtain desirable surface tension like this, because show by experiment, when having adhered to one deck hydrone on little internal surface of hole, may reduce the surface tension producing at aperture place between liquid and air.Meanwhile, in order to obtain better effect, allow pick-up unit be arranged to disposable and can not reuse.
As Fig. 3 has shown other specific embodiments of the present invention.In specific embodiment, gathering-device 50 provided by the invention comprises a liquid sample collection chamber 101 and is positioned at the plunger shaft 501 of collecting chamber bottom, Fig. 3 A.Pick-up unit 60 comprises a test chamber 601, an end opening of test chamber, and the other end is sealed by the foraminate film 209 of one deck band.In a concrete mode, test chamber bottom end 604, comprise two apertures 602,603, whole test chamber can be for cylindrical, comprise that one end 604 of aperture and the opening of plunger shaft 503 coordinates and can packed-piston chamber 501, Fig. 3 B, whole test chamber and narrow meshed heterodoxy are all plastic material injection moulding disposal molding.Plunger shaft 501 and the foraminate one end of test chamber band form transfer chamber jointly.In use, in collecting chamber, collect when having liquid sample, liquid sample can pass through opening one end 503 of piston, and the fluid passage of transfer chamber, enters in plunger shaft 501.When test chamber is inserted in collecting chamber, first 604 one end, bottom of test chamber contact with liquid sample.Although one end of test chamber bottom has two apertures, owing to being provided with shape or the size of aperture, for example allow the interior diameter of each aperture be 0.3 millimeter, allow these apertures produce surface tension under the effect of liquid, this surface tension is enough to stop the liquid sample in collecting chamber to enter in test chamber, even under the liquid level in test chamber bottom end 604 lower than collecting chamber, there is difference in height, surface tension of liquid on aperture still can stop the liquid sample in collecting chamber to enter in test chamber, Fig. 3 C.Along with test chamber further moves, the opening 503 in 604 packed-piston chambeies, the foraminate one end of test chamber band, thereby stop the liquid in collecting chamber 101 to enter in plunger shaft 501, allow the liquid sample volume in plunger shaft no longer increase, can reach the object of quantitative sampling.In this time, still can allow the liquid sample in plunger shaft not enter in test chamber by aperture, and now piston is in primary importance.When piston moves to the process of the second place from primary importance, be that piston continues to move down, effect due to external force, thereby allow the pressure increase at aperture place break the surface tension that is arranged on aperture place, allow the liquid sample in plunger shaft pass through aperture 602,603 enter 601 li of test chamber, Fig. 3 C.In test chamber, sample and the testing element being positioned in test chamber react.
On the other hand, the invention provides a kind of method that whether contains analyte in tracer liquid sample.The method is inserted into pick-up unit in a liquid sample collection chamber; Allow the liquid sample in collecting chamber enter in the liquid sample transfer chamber of pick-up unit by fluid passage, but allow liquid not enter in test chamber by the aperture film being arranged between test chamber and transfer chamber; Allow piston be inserted in liquid sample transfer chamber, force the liquid sample in transfer chamber to enter in test chamber by the aperture film being arranged between test chamber and transfer chamber.More specifically, as shown in Figure 1, pick-up unit 20 is inserted in liquid sample collection chamber 101, liquid sample in collecting chamber 101 enters into liquid sample transfer chamber 201, now, liquid sample can not enter in test chamber by being arranged on the aperture film 209 arranging between test chamber 202 and transfer chamber 201; Allow piston 102 be inserted in transfer chamber 201, piston forces partially liq sample to enter into test chamber by aperture film 209.In a concrete embodiment shown in Fig. 4-16, detection method comprises provides a pick-up unit 71, comprise test chamber 716 and transfer chamber 712, between test chamber and transfer chamber, arrange one with the plastic sheeting 7111 of aperture 713,714, it is 0.5 millimeter that described aperture interior diameter is set, height is 1.5 millimeters, as Figure 10.Provide a gathering-device 702 to comprise collecting chamber 721 and be positioned at the piston 722 in collecting chamber, this piston by the bottom 724 of collecting chamber to upper process; Pick-up unit is inserted in collecting chamber, allow liquid in collecting chamber enter in transfer chamber 712 by fluid passage 715, then allow the fluid passage of piston seal transfer chamber and collecting chamber, piston is arranged in the primary importance of transfer chamber, and now liquid sample can not enter test chamber from transfer chamber by the film of aperture; Allow piston be inserted in transfer chamber, from primary importance, move to the second place, force liquid sample from transfer chamber, to enter test chamber by the film of aperture, till allowing piston move to can not to move, all liq sample in transfer chamber is whole oppressed entering in test chamber almost always.
In other specific embodiment, when piston is inserted into transfer chamber and forces liquid sample to enter after test chamber by aperture, no longer allow the relative transfer chamber of piston move back.For example, when rotating by clockwise lid, allow plunger shaft move up with respect to piston and force the liquid sample in plunger shaft to enter after test chamber by aperture, inhour is rotated lid again, can not allow like this liquid sample backflow that enters test chamber enter in transfer chamber, thereby may pollute the liquid sample in collecting chamber.
" sample " that the present invention refers to refers to any material whether needs chemical examination existed and (or) analyzed analyte concentration, maybe need to determine whether one or more samples exist and (or) the material of the analyte of quantity, maybe need to carry out the material of qualitative evaluation.Sample can be liquid sample, for example liquid sample.Liquid sample comprises body fluid, such as blood, serum, blood plasma, saliva, urine, tears, seminal fluid and marrow; Liquid sample can be also water sample, such as seawater, river, river etc., or from domestic water, municipal water use or service water resource, runoff water or sewage; Sample can be food sample, such as milk and wine.Mucus, semisolid or solid sample can be used for making liquid, eluate, suspending liquid or leachate equal samples.For example, throat or genitals sample may be dipped in and in liquid, make sample.Sample can comprise potpourri or any relevant potpourri of liquid, solid and gas, such as the cell suspending liquid in dilution or solution.Sample comprises biological substance, such as cell, microorganism, organelle and biochemical complexes.Liquid sample can be produced from solid, semisolid or high-viscosity materials such as soil, ight soil, tissue, organ, biological fluid or other occurring in nature non-liquid samples.For example, the solution that these solids or semi-solid samples can be suitable with dilution one class mixes.Sample can be macerated, freezing and thaw, or other extracting method form liquid samples.Remaining particulate material can be used the method that filtration or precipitation etc. are traditional to remove.
The analyte that the present invention refers to can be " drug abuse " (DOA) or other there is interested material in sample." drug abuse " (DOA) refers to that non-medical destination used medicine (conventionally plaing a part to benumb neural).Abuse these medicines and can cause body & mind to suffer damage, produce dependence, addicted and/or dead.The example of drug abuse comprises cocaine; Amphetamine (for example, black beauty, white amphetamine tablet, dextroamphetamine, dexie, Beans); Crystal methamphetamine (crank, meth, crystal, speed); Barbiturate (as Valium, RochePharmaceuticals, Nutley, New Jersey); Sedative (paramedicines of sleeping); Lysergic acid diethylamide (LSD); Inhibitor (downers, goofballs, barbs, blue devils, yellow jackets, methaqualone); The anti-antidepressant of tricyclic antidepressants (TCA, i.e. imipramine, amitriptyline and doxepin); Hog (PCP); Tetrahydrocannabinol (THC, pot, dope, hash, weed, etc.), opiate (being morphine, opium, codeine, heroin, hydroxyl dihydrocodeinone), anxiolytic and hypnotic sedative agent, anxiolytic is that a class is mainly used in anxiety reduction, nervous, frightened, set the mind at rest, have the medicine of hypnosis sedation concurrently, comprise Benzodiazepines (benzodiazepines, BZ), atypia BZ class, merge phenodiazine NB23C class, the tall and erect class of benzene nitrogen, the part class of BZ acceptor, open loop BZ class, diphenylmethane derivatives, piperazine carboxylic acid salt, piperidine carboxylic acid salt, Kui azoles quinoline ketone, thiazine and thiazole, other heterocyclic, imidazole type calmness/anodyne, propanediol derivative one carbamates, fatty compound, anthracene derivative etc.Use this device also can be for detection of belonging to medical usage but the easily detection of overdose, as tricyclic antidepressant (imipramine or analog) and Paracetamol etc.After these medicines are absorbed by the body, can resolve into different small-molecule substances, these small-molecule substances are present in the body fluid such as blood, urine, saliva, sweat or part body fluid exists above-mentioned small-molecule substance.
Experiment
For a better understanding of the present invention, now give description of test.This experiment is only done specific description to effect of the present invention and embodiment, not the explanation to limiting property of the present invention.
test the sample collection quantitative changeization experiment of 1 pick-up unit.
4-7 by reference to the accompanying drawings, 17,13-16 illustrates this experiment.The structure of the pick-up unit that this experiment adopts is as shown in Fig. 4-7, between the test chamber 716 shown in Fig. 7 and transfer chamber 712, it not plastic tab, on thin slice, open 2 apertures, but open a diameter on plastic tab, it is the hole of 7 millimeters, on aperture, paste the hydrophobic porous film of one deck, the diameter of film is the thin rounded flakes of 10 millimeters, and sectional drawing as shown in figure 17.This film is bought from Ao Silong and is filtered company (AHLSTROM FILTRATION LLC), station address: www.ahlstrom.com; CompanyAddress: the Kentucky State, Kentucky State 42431-0030, the U.S. http:// www.ahlstrom.comphone (270) 821-0140 fax, (270) 326-3290; Post-office box(P.O.B.) 1410.Use is as follows at the specifying information of the porous membrane of this experiment: batch number 0256; Thickness is 16.5 microns, and transverse tensile strength is 86.0 pounds/inch, and pulling strengrth is 78.0 pounds/inch longitudinally; Gas permeability (CFM) is 256.0 cubic inches/minute/square inches; Material is mylar (Polyestermembrane), and the size in hole is about 8 microns of left and right.
Then in collecting chamber, collect respectively 55,70,80,90, the amount of urine of 105 milliliters, represents with A; .Then allow different people operate according to the process shown in Figure 13-16, repeat respectively 41 times, 40 times, 41 times, 30 times and 29 times.Each operation steps repeating is as follows: 1, collection cups 72 on surface level; 2, the mark line (not shown) of alignment transparent cup edge and lid also inserts detection part 71 in transparent cup 72 gently, and the lid that then turns clockwise is until screw; 3, measure and enter the volume of urine in test chamber.Attention: lid inserts after transparent cup, does not pick up lid again.
The last interior different volume of urine of statistics collection cup 72 enters the variation of the volume of urine (representing with B) in test chamber.Experimental result is as following table.As can be seen from the table, adopt device of the present invention, the volume of urine variation of collecting in cup can not make a significant impact the liquid volume amount entering in test chamber; In carrying out 181 operations, 177 operations allow volume of urine in test chamber between 1.5-2.9 milliliter, only have 4 operations to make volume between dead volume.Because the experiment by us shows, as fruit volume is less than 1.5 milliliters or be greater than 3.0 milliliters of testing results that all can not correctly obtain THC.This is the conclusion as single factor, THC testing result being drawn investigating liquid volume variation.
Certainly, if detecting analyte is not THC, but other material, can be by selecting the aperture film of different parameters regulate the liquid volume that enters test chamber, for example can be constant between 4-5 milliliter, between 6-7 milliliter or between 1-2.5 milliliter etc.
In table 1 collecting chamber, different volume of urine are on entering the impact of test chamber volume.
A B A B A B A B A B
55ml 2.2 70ml 2.2 80ml 2.3 90ml 2.3 105ml 2.2
55ml 2.3 70ml 2.2 80ml 2.3 90ml 2.2 105ml 2.2
55ml 2.2 70ml 2.2 80ml 2.2 90ml 2.3 105ml 2.4
55ml 2.3 70ml 3.0 80ml 2.3 90ml 2.3 105ml 2.2
55ml 2.3 70ml 2.0 80ml 2.1 90ml 2.4 105ml 2.3
Figure G200910152616XD00161

Claims (18)

1. a pick-up unit for analyte in analytic liquid sample body, comprising: one for accommodating the test chamber of detecting element; A liquid sample transfer chamber; An and aperture film being arranged between test chamber and liquid sample transfer chamber; Wherein, when this pick-up unit is inserted in a liquid sample collection chamber, the liquid sample in collecting chamber enters in liquid sample transfer chamber, but this liquid sample can not enter by described film in test chamber; And wherein, when a piston is inserted in liquid sample transfer chamber, this piston forces the partially liq sample in transfer chamber to enter into test chamber by this porous membrane; Wherein, the size of aperture is between 0.1-80 micron.
2. device as claimed in claim 1, wherein, described aperture film is hydrophobic film.
3. pick-up unit as claimed in claim 2, wherein, described hydrophobicity aperture film comprises hydrophilic film, wherein on hydrophilic film, processes and has hydrophobic agents.
4. pick-up unit as claimed in claim 2, wherein, described hydrophobicity aperture film comprises glass fibre, mylar, acetate film.
5. device as claimed in claim 1, wherein, described aperture film is two-layer.
6. device as claimed in claim 5, wherein, near transfer chamber be one deck hydrophobicity aperture film, near test chamber is one deck hydrophilic film.
7. device as claimed in claim 5, wherein, two-layer aperture film is hydrophobic film.
8. the pick-up unit as described in one of claim 1-7, wherein, between described liquid sample transfer chamber and collecting chamber, comprise a fluid passage, the partially liq sample in collecting chamber flow into after transfer chamber by this passage, and described first passage is by this piston seal.
9. device as claimed in claim 8, wherein, transfer chamber, test chamber and aperture film are integrated injection mo(u)lding.
10. device as claimed in claim 2, wherein, this device also comprises a detecting element that is arranged in test chamber.
11. devices as claimed in claim 2, wherein, this device also comprises a fetch equipment that reads test result on detecting element.
12. devices as claimed in claim 11, wherein, testing element is cross flow reagent strip.
13. 1 kinds are detected box, comprising: a pick-up unit, comprise liquid sample transfer chamber, and test chamber wherein arranges one deck hydrophobicity aperture film between transfer chamber and test chamber; A liquid sample collection chamber, this collecting chamber comprises that one for being inserted into the piston of transfer chamber; When in use, this transfer chamber is inserted in collecting chamber, and the liquid sample in collecting chamber flow in transfer chamber, but this liquid sample can not enter in test chamber by aperture film; And wherein, when piston is inserted in transfer chamber, piston forces the partially liq sample in transfer chamber to enter in test chamber by aperture film; Wherein, the size of described aperture is between 0.1-80 micron.
14. detection box as claimed in claim 13, wherein, described liquid sample transfer chamber also comprises a fluid passage, and the partially liq sample in collecting chamber flow into after transfer chamber by this passage, and described passage is by this piston seal.
15. detection boxes as claimed in claim 14, wherein, in the time of piston seal first passage, the pressure in described transfer chamber is less than or equal to the set surface tension of liquid of aperture.
16. detection boxes as claimed in claim 15, wherein, piston has primary importance and the second place in transfer chamber; When piston is positioned at primary importance, piston seal fluid passage, allows in plunger shaft and holds the partially liq sample from collecting chamber, and meanwhile, liquid sample can not enter in test chamber by aperture film; When piston moves to the second place from primary importance, piston forces liquid to enter in test chamber by aperture film.
17. detection boxes as claimed in claim 13, wherein, piston is positioned at the bottom of collecting chamber and to upper process.
18. pick-up units as claimed in claim 2, wherein, the gas permeability of hydrophobicity aperture film is 10-800 cubic inch/minute/square inch.
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EP10796658.2A EP2451576B1 (en) 2009-07-09 2010-07-09 Device and method for analyzing analyte in liquid sample
US13/394,759 US9327283B2 (en) 2009-07-09 2010-07-09 Device and method for analyzing analyte in liquid samples
PCT/CN2010/001020 WO2011003281A1 (en) 2009-07-09 2010-07-09 Device and method for analyzing analyte in liquid sample
US15/135,418 US20160310938A1 (en) 2009-07-09 2016-04-21 Device and method for analyzing analyte in liquid sample

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