CN102680680B - Detecting device containing non-protein capturing substance on control region - Google Patents
Detecting device containing non-protein capturing substance on control region Download PDFInfo
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Abstract
The invention provides a detection device to detect if an analyte exists in a sample. The detecting device includes a reagent strip for supporting the liquid sample to flow; the reagent strip includes a detection region including a special binding molecule and a control region including one or more non-protein captures. In some embodiments, one or more non-protein flocculating regents or coagulations are included on the control region or the masculine control region. The production cost of the dection device provided by the invnetion is low without changing the detecting result.
Description
The application is Chinese invention patent application, application number 2006100503082, and the applying date is the divisional application on April 12nd, 2006.
Technical field
The invention belongs to diagnostics classes device, specifically, be about a kind of novel diagnostic reagent srip, the control area of reagent strip comprise one or more non-protein a certain amount of and catches material.
Background technology
The dry chemical scrip utilizing immunology principle to react is used in clinical diagnosis in a large number, and such as very early pregnancy reagent strip detects HCG.This kind of test strips and being used in a lot of patent documentation of they have description, such as China authorized utility model patent 01239923.X and 02202021.7, and application publication 02122907.4 and 02139704.X, 01131834.1 etc. disclose such.Such as, the most common test strips utilizing the single stage method of sandwich principle to detect, sample application zone in test strip adds the sample that will detect, because capillary layer suction effect is along test paper longitudinal flow forward in this sample, through marked region, if there is analyte in sample, on this analyte and marked region, another material specific bond forms compound; This compound continues flow forward along with liquid, through including the surveyed area of catching analyte region, then with the catches specific bond of catching on analyte region, thus compound is captured, and makes to accumulate at surveyed area.Another material-specific on marked region can be labeled mass signatures; This mark substance can be the band colored particle of the known non-aqueous solution of prior art, such as gold grain colloid and latex particle, also can be fluorescence labeling, can also be the marking particle of water-soluble, such as, be polymerized marking particle formed etc. by dextran.When on marked region containing band colored particle, then on surveyed area, occur a colored symbol, this symbol both directly with the naked eye just can read result, also can by the reading result of instrument quantitative and qualitative analysis more accurately.This analyte and catching the pairing between the catches specific bond on analyte region, and the combination between analyte and the markd material of band is the known material of prior art, these combine can the direct specific bond between them also can be both indirectly specific bond, common as double-antibody sandwich, double antigens sandwich or its indirect method, also have competition law etc.These pairings have a lot of mode, such as antigen and its antibody conjugates, antibody and antiantibody pairing, antibody and haptens pairing, pairing between biotin and the antibody of antibiotin, biotin and antibody conjugates, and the multiple combinations of pairs of formation between them etc., antibody also comprises the antibody of antibody fragment, the antibody in such as anti-Fc site etc.
Simultaneously, the downstream of catching analyte region on these reagent strips also has a testing result control area, also be fixed with a certain amount of antibody or Special Proteins material on the area, these antibody or Special Proteins material (albumin A or protein B) can be caught labeled complex matter unnecessary in solution and accumulate in testing result control area.Generally, in testing result control area, occur that color then represents that the testing result on surveyed area is effective, otherwise be invalid, such as US Patent No. 5,541,059 and European patent EP 0 560 411 disclose such.In addition, disclose in some patent documentations and antibody is fixed on positive control area, no matter whether there is analyte in sample, positive control area all occurs colored line, these lines and specific bond analyte region intersect to form special can the symbol of Direct Recognition, such as US Patent No. 4,916,056, US 5,160,701 and US 5,075,078 disclose such.From the prior art, testing result control area or positive control area are fixed special antibody or other similar differential protein material is the method be commonly used as catching material, therefore, in producing in a large number, can greatly improve because of the specific antibody of use high price or albuminoid material the cost producing product on the one hand on control area; Also can cause in a large number with the waste of the specific binding molecule of mark substance on the other hand, because want formation control lines, the specific binding molecule with mark substance generally in reagent areas is excessive.
Openly apply for a patent in 2004/0161859 in the U.S. and disclose another kind of testing result control area, before reagent strip is not by use, just there are blue lines in the testing result control area on reagent strip, when reaction is carried out time, these blue lines will become red and represent that reaction has terminated or testing result is effective.Although this reagent strip reduces production cost, but this reagent strip is just present in obvious lines before not using on testing result control area, is easy to like this allow user produce illusion, thinks that this reagent strip has been previously used.
At United States Patent (USP) 6,855,561 disclose and utilize the pick-up unit of a kind of fixing of dye on positive control area.In a specific embodiment, before this device does not participate in reaction, itself is hidden in below nitrocellulose membrane with this dyestuff of a kind of color; In time detecting, because nitrocellulose filter is wet by water and become transparent, thus the dyestuff under making to be hidden in film displays and region in conjunction with analyte forms certain discernible shape.In actual production, special equipment be used and need complicated loaded down with trivial details technique just can produce actual meet business demand as this patent the product that discloses.
Apply for a patent in China, application number for disclose in 200510049177.1 on positive control area, comprise one or more be a kind of color in dry is the material of another kind of color wet time, this positive control area and analyte calmodulin binding domain CaM can form certain discernible symbol.In actual production, this material showing different colours under dry and wet two kinds of different situations directly be processed on nitrocellulose filter is more difficult thing, that this material can make the efficiency of process greatly reduce by free diffusing on film because the solution containing this material is directly processed on film.
In order to overcome these defects of the prior art and deficiency, our control area of very surprised discovery in this kind of pick-up unit processes flocculation agent or coagulum can well reach coml requirement.This kind of flocculation agent or coagulum are the reagent that wastewater treatment is often used, their low prices, and easily obtain.So both can save in a large number because buying the cost that expensive antibody or albumen spend, on the other hand, in a concrete embodiment, do not need special equipment and complicated technique just this flocculation agent or coagulum directly can be fixed on nitrocellulose filter and form positive control area.
Summary of the invention
The invention provides a kind of pick-up unit detected in sample whether containing analyte, pick-up unit comprises the reagent strip supporting liquid sample flow; This reagent strip comprises surveyed area and control area; Comprise a kind of molecule of specific bond at surveyed area, comprise the catches of one or more non-protein compositions in control area.
In one embodiment, water absorptivity reagent strip only has surveyed area and testing result control area, surveyed area comprises a specific binding molecule, testing result control area comprises flocculation agent or the coagulum of one or more non-protein compositions.When detection, can first the molecular mixing of another specific bond of the sample that will detect and tape label material, if containing the material that will detect in sample, on surveyed area, then there will be color change show in sample whether there is analyte, whether effectively testing result control area occurs color change shows this testing result.Usually, testing result control area there is color occur representing that this testing result is effective, otherwise be invalid testing result.
In another embodiment, the reagent strip of support liquid flow is cellulose nitrate reagent strip, surveyed area is fixed with the molecule of specific bond analyte, complete the molecule that the necessary reagent areas of reaction comprises another specific bond analyte with mark substance, testing result control area is fixed with a certain amount of non-protein flocculation agent or coagulum.
In another embodiment, reagent strip also comprises reagent areas, reagent areas comprises two regions, one is the region with dyestuff, another region is marked region, and marked region comprises another specific binding molecule with mark substance; Surveyed area comprises the molecule of a specific bond, comprises a certain amount of one or more non-protein flocculation agent or coagulums in testing result control area.In a concrete embodiment, specific binding molecule with mark substance can be antibody, antibody fragment, one of biotin or nucleic acid (DNA, RNA) fragment, the specific binding molecule on surveyed area can be one of antibody of another antibody, antibody fragment, anti-biotin antibodies or anti-nucleic acid.
In another embodiment, this reagent strip is made up of water-absorbing material, it comprises sample application zone, complete the necessary reagent areas of reaction, surveyed area, testing result control area and suction zone, containing a certain amount of non-protein flocculation agent or coagulum on testing result control area, molecule containing specific bond on surveyed area, reagent areas comprises marked region and dye area, containing another molecule with mark substance specific bond on marked region.
In another embodiment, reagent strip is nitrocellulose assay strip, reagent areas comprises specific binding molecule with mark substance and a certain amount of dyestuff, surveyed area comprises specific bond analyte region and positive control area, positive control area comprises a certain amount of non-protein flocculation agent or coagulum, and region and the positive control area of specific bond analyte intersect to form certain shape mutually.In the present embodiment, testing result control area and suction zone can also be comprised in the downstream of surveyed area, testing result control area comprises a certain amount of non-protein flocculation agent or coagulum.Simultaneously, in another embodiment, some protide catches can be fixed in positive control area, antibody of such as antibody, antibody fragment, albumin A, Protein G or anti-albumin A etc., testing result control area is fixed flocculation agent or the coagulum of some non-protein compositions, and the region of specific bond analyte and positive control area intersect to form the shape that +/-, Y, X etc. easily identify mutually.In the present embodiment in another specific embodiment, reagent strip comprises and is from upstream to downstream along liquid flow direction and is followed successively by sample receiving pad, label pad, nitrocellulose filter containing surveyed area and testing result control area and adsorptive pads, and these parts are connected and liquid can be allowed to flow to the other end from one end by capillary absorption power; In sample receiving pad, process has some reagent to regulate the pH value of reaction, in label pad, process has the specific binding molecule with mark substance, on nitrocellulose filter, process has the molecule of specific bond analyte and positive control area, on positive control area, process has a certain amount of non-protein flocculation agent or coagulum, and the region of positive control area and specific bond analyte intersects to form certain shape mutually.These non-protein flocculation agent or coagulum can be some inorganic polymer flocculation agent or organic polymer flocculation agent.Mark substance on reaction reagent region can be colored colloidal solid, as gold grain colloid, latex particle; Can also be as Chinese invention apply for a patent 99809129.4 water-soluble marker's material of disclosing.
On the other hand, the invention provides the method detecting analyte in sample.In one embodiment, to pick-up unit dropping liquid sample body, make sample from the sample application zone of reagent strip sequentially through marked region, surveyed area and testing result control area, when liquid flows through testing result control area, the catches of one or more non-protein compositions that the mark substance that on the detected region of a dissolving part in a liquid, specific binding molecule is caught is fixed on testing result control area caught, and testing result control area occurs color change represents that this testing result is effective.In another particular embodiment of the invention, non-protein molecule is flocculation agent or the coagulum that organic or inorganic is dissolved in water.
In another embodiment, to detection reagent strip sample application zone dropping liquid sample body, this liquid sample relies on capillary absorption power to flow through marked region, dye area, surveyed area and testing result control area successively.When liquid by dye area time, this dyestuff can by liquid sample dissolve and flow detection output control region, in testing result control area, this dyestuff is caught by the coagulum of non-protein composition or flocculation agent.In another particular embodiment of the invention, surveyed area comprises the region of specific bond analyte and positive control area, positive control area and specific bond analyte region intersect to form certain shape mutually, and on positive control area, process has flocculation agent or the coagulum of a certain amount of non-protein composition.When the liquid being dissolved with dyestuff flows through positive control area, the flocculation agent on positive control area or coagulum can be caught the dyestuff in liquid and demonstrate color change.If there is no analyte in sample, just on surveyed area, only there is a colored line negative sign (-), represent that testing result is negative; If there is analyte, then on specific bond analyte region, occur colored line, the lines on these lines and positive control area intersect to form positive sign (+), and expression result is positive findings.The flocculation agent of the non-protein composition on testing result control area or coagulum also can catch dyestuff in liquid and on testing result control area Show Color, represent that this testing result is effective result, otherwise this testing result is invalid.
In another embodiment, water absorptivity reagent strip only has surveyed area and testing result control area and sample application zone, surveyed area comprises a specific binding molecule, testing result control area comprises flocculation agent or the coagulum of one or more non-protein compositions.When detection, can first the molecular mixing of another specific bond of the sample that will detect and tape label material, then the sample application zone of reagent strip is inserted in liquid sample and goes, if containing wanting analyte in sample, on surveyed area, then there will be color change show in sample whether there is analyte, whether effectively testing result control area occurs color change shows this testing result.Usually, testing result control area there is color occur representing that this testing result is effective, otherwise be invalid testing result.
Accompanying drawing explanation
Fig. 1 is for the invention provides an embodiment.Reagent strip 1 comprises sample application zone 25, reagent areas 115, surveyed area 95, testing result control area 85 and suction zone 65, arrow express liquid flow direction, testing result control area 85 includes a certain amount of non-protein components condense thing or flocculation agent.
Fig. 2 is for the invention provides another embodiment.Compared to Figure 1, difference is, the reagent areas 115 on reagent strip 2 comprises the band marked region 15 of colored particle and the dye area 35 with dyestuff, testing result control area 85 comprises flocculation agent or the coagulum of non-protein composition.
Fig. 3 is for the invention provides another embodiment.Compared with Fig. 2, surveyed area 95 comprises a positive control area 55 and analyte calmodulin binding domain CaM 45, testing result control area 85, wherein on testing result control area 85 and positive control area 55, all processed a certain amount of coagulum or flocculation agent, positive control area 55 and analyte calmodulin binding domain CaM intersect to form ten subrack shapes (+) simultaneously.
Fig. 4 is for the invention provides the embodiment of shown in Fig. 3.Reagent strip 4 is connected with water absorbent sheet 465 by sample blank film 425, marker slip 4115, nitrocellulose filter 475, liquid can flow to absorbing sheet 465 from sample blank film 425, and wherein surveyed area 495 and testing result control area 485 are positioned on nitrocellulose filter 475.On on marker slip 415, process has specific binding molecule with color mark material and dyestuff, in conjunction with molecule analyte region 445 comprising specific bond analyte.On positive control area 455 and testing result control area 485, process has a certain amount of coagulum or flocculation agent.
Fig. 5 is for the invention provides another embodiment, compared with Fig. 3, reagent areas 115 only includes a marked region 15, there is no testing result control area 85 and dye area 35 simultaneously, positive control area 55 comprises a certain amount of coagulum or flocculation agent.
Fig. 6 is for the invention provides the embodiment of shown in Fig. 5, compared with Fig. 4, without testing result control area 485 on this reagent strip 6, marker slip 4115 only includes the specific binding molecule of band colored particle, positive control area 455 comprises a certain amount of non-protein coagulum or flocculation agent.
Fig. 7 the invention provides a concrete embodiment, and the embodiment difference shown with Fig. 2 is, on marked region 15, process has the specific binding molecule with color water-soluble dye.
Fig. 8 is for the invention provides another embodiment, and the embodiment difference shown with Fig. 7 is reagent strip 8 does not have testing result control area, and on positive control area, process has a certain amount of coagulum or flocculation agent.
description of reference numerals
Reagent strip 1, 2, 3, 4, 5, 6, 7, 8, sample application zone 25, reagent areas 115, marked region 15, dye area 35, surveyed area 95, analyte calmodulin binding domain CaM 45, testing result control area 85, positive control area 55, suction zone 65, sample blank film 425, marker slip 4115, nitrocellulose filter 475, surveyed area 495 on nitrocellulose filter, testing result control area 485 on nitrocellulose filter, analyte calmodulin binding domain CaM 445 on nitrocellulose filter, positive control area 455 on nitrocellulose filter.
Embodiment
In the following detailed description, the subsidiary reference word of legend is a part here, and it is to illustrate that the present invention can the mode of actable specific concrete scheme illustrate.We do not get rid of the present invention can also carry out other concrete scheme and when without prejudice to changing structure of the present invention when right of the present invention.
surveyed area
Surveyed area mentioned here refers to and can carry out reaction on the area to detect in sample whether there is interested analyte.Reaction mentioned here can be immune response, as single stage method immunoreagent bar etc.As shown in Figure 1, Figure 2 and Figure 7, containing a surveyed area 95 on reagent strip, surveyed area 95 secures some specific binding molecule, whether detect on the area in sample containing analyte.
In one embodiment, surveyed area 95 is fixed the molecule of a specific bond analyte, reagent areas 115 comprises another molecule of the specific bond analyte with mark substance.In time containing analyte in sample, another specific binding molecule of a part in analyte and reagent areas forms compound substance, this compound is on surveyed area, another specific binding molecule be fixed on surveyed area is caught and is gathered on surveyed area, due on compound with color, show analyte whether be present in sample so also there will be color change on surveyed area.In a specific embodiment, another specific binding molecule of tape label material can be antibody or antibody fragment, and another specific binding molecule be fixed on surveyed area also can be antibody or antibody fragment.Be generally double antibody sandwich method or dual-antigen sandwich method detects.
In another embodiment, not containing another molecule with the specific bond analyte of mark substance on reagent strip, but before the reaction, first form aqueous solution sample with another molecular mixing of mark substance, and then reagent strip is inserted in this mixed solution goes or mixed solution is added drop-wise on reagent strip, also there will be color change at the surveyed area of reagent strip like this and show in sample whether there is analyte.
In another embodiment, be the analog of analyte with markd specific binding molecule, surveyed area is fixed with the molecule of specific bond analyte.In time containing analyte in sample, the similar substance of analyte and tape label can be vied each other in conjunction with the specific binding molecule on surveyed area, like this on surveyed area can because analyte number and occur different depth color to show analyte number, if analyte is more, the color relation that surveyed area occurs is more shallow, otherwise darker.Such as the common competition law that utilizes carries out illicit drugs inspection reagent strip.
As shown in Fig. 3-6,8.In other embodiments, this surveyed area 95 comprises positive control area 55 and analyte calmodulin binding domain CaM 45, positive control area can be fixed with the protein ingredient such as antibody, antibody fragment and catch material, that also can fix some non-protein compositions catches material, such as inorganic coagulum or flocculation agent catches, analyte calmodulin binding domain CaM comprises the molecule of specific bond analyte.This positive control area and the certain identifiable design symbol of the interlaced formation of analyte calmodulin binding domain CaM directly show the result of detection.Such as form positive sign (+) or negative sign (-) etc. (Fig. 5 and Fig. 3).In the present embodiment, no matter whether there is color to occur in conjunction with analyte region, this positive control area has color to occur.Specifically, if there is analyte in sample, on surveyed area 95, just occur the symbol (+) being expressed as positive findings, if there is no then there is the symbol (-) representing negative findings in analyte.
Surveyed area fixed the technology of a certain amount of specific binding molecule and utilize this technology whether to there is analyte be that persons skilled in the art can be known to detect in sample, these technology are detailed description and elaboration all in the prior art, such as U.S. Patent number 5,075,078; It is such that 5,541,059 and European patent EP 0 560 411 etc. are disclosed.
control area
There is the effect of several aspect control area mentioned here.Whether one is whether the testing result that can control to be presented on surveyed area as testing result control area is effective, or be presented at the process that surveyed area reacts and how long complete or completed.Can also as positive findings control area, another is exactly form certain shape to carry out reaction detection result directly perceived with another analyte calmodulin binding domain CaM on surveyed area, time in sample containing analyte, just intuitively show positive findings, time as there is not analyte in sample, just intuitively show negative findings.Give explanation in detail below.
testing result control area.in the prior art, the antibody of some protein ingredients or antibody fragment are fixed on the testing result control area in surveyed area downstream, and the excessive specific binding molecule with mark substance is processed at the upstream region of surveyed area.When detecting, these specific binding molecule with mark substance these protein ingredients that can be detected on output control region that another specific binding molecule on detected region is caught are caught material and caught, thus to show this testing result be effective.On the contrary, if do not have color to change on testing result control area, represent that this testing result is invalid, so this detection must from new detection.On the other hand, the indicative function of reaction process on surveyed area can also be served as in testing result control area, such as on testing result control area, occurred color change, can think that the reaction on surveyed area finishes, the result that surveyed area shows is the net result detected.The distance of testing result control area and surveyed area also can require to regulate arbitrarily according to difference, such as testing result control area can be distant apart from surveyed area, and approximately distance liquid flows to from surveyed area the distance that testing result control area needs 5 minutes to 10 minutes.The setting of this distance freely can design according in the cellulosic speed of liquid stream pernitric acid.Like this, when testing result control area occurs that color changes time, represent that the reaction that surveyed area carries out continue for about 5-10 minute.Control area on reagent strip can be one or more, in order to control the process of detection reaction more accurately, first testing result control area can be set up at distance about 5 minutes places, surveyed area downstream, in distance, 10 minutes places set up second testing result control area, when color appears in first testing result control area time, represent that the reaction on surveyed area continue for about 5 minutes, when second surveyed area 2 has occurred that color change represents that the reaction on surveyed area continue for 10 minutes, or think that the result in 10 minutes on surveyed area is effective, spend 10 minutes and represented that the result on surveyed area is invalid.
The present invention said " upstream " or " downstream " refer to upstream on liquid flow direction or downstream.Under normal circumstances, liquid flow to downstream area from upstream region.Such as liquid flows from sample application zone, successively through surveyed area and testing result control area flow further downstream, then sample application zone is positioned at the upstream of surveyed area, surveyed area is positioned at the upstream of testing result control area, and testing result control area is positioned at the downstream of sample application zone and surveyed area.
positive control area.meanwhile, in the prior art, the antibody of a large amount of protein ingredients or antibody fragment are fixed on the positive control area on surveyed area, regardless of testing result, positive control area all can occur color changes.Another analyte calmodulin binding domain CaM on surveyed area and positive control area form certain shape and carry out reaction detection result directly perceived.These are fixed on antibody on positive control area or antibody fragment and are also used to catch the superfluous markd specific binding molecule of band.Like this, in a large amount of production, need antibody or the antibody fragment of a large amount of protein ingredient, meanwhile, also need a large amount of specific binding molecule with color mark material.The cost of the reagent strip product produced like this can significantly improve, because produce or buy protein antibodies or antibody fragment and be very high with the cost of the specific binding molecule of mark substance.In addition, in prior art some chemical substance treatment on positive control area, such as United States Patent (USP) 6,855,561 and U.S. Patent Application Publication 2006/0029924 in describe utilization process on positive control area some chemical dyes or some utilize chemical reaction come Show Color change, thus and analyte calmodulin binding domain CaM combination visual display detecting result.But in real process, it is very difficult that these chemical substances are directly processed on nitrocellulose filter, process superincumbent chemical substance easily to spread, simultaneously because chemical reaction also can affect testing result, the cost producing this product is in addition also very high.
Utilize reagent strip provided by the invention, control area processes certain non-protein and catches material the reagent strip of production can be made with low cost, easily produce and can not affect the quality of reagent strip.In an embodiment as shown in Figure 1, reagent strip 1 comprises a testing result control area 85, testing result control area is fixed with coagulum or the flocculation agent catches of a certain amount of non-protein composition.In reagent areas 115, process has movably with the specific binding molecule of mark substance.When these specific binding molecule with mark substance are taken to testing result control area 85 place by liquid, be fixed on the molecule that coagulum on testing result control area or flocculation agent catch these tape label materials.On testing result control area, so just occur that color change display testing result is effective, otherwise testing result is invalid.In another particular embodiment of the invention, being positioned at the surveyed area downstream distance of about 10 minutes with the coagulum of a certain amount of non-protein composition or the testing result control area of flocculation agent, then representing that when occurring that color changes on testing result control area reaction has been carried out 10 minutes.
In another embodiment as shown in Figure 2, testing result control area 85 is fixed with a certain amount of coagulum or flocculation agent, on the dye area 35 of surveyed area 95 upstream, process has a certain amount of dyestuff, without any specific binding molecule on this dyestuff, on the marked region 15 of upstream, dye area, process the specific binding molecule with colored particle simultaneously.When detecting, dyestuff by liquid to take on testing result control area 85 by coagulum or flocculation agent catch and accumulate, thus on testing result control area, occurred that color change represents that testing result is effective, if do not have color to change, represent that testing result is invalid.Meanwhile, the specific binding molecule on surveyed area 95 and the molecule with mark substance on marked region 15 carry out immune response to detect in sample whether there is analyte.In an embodiment, the mark substance on marked region is granular metallic colloid or latex colloid, and the specific binding molecule on mark substance can be antibody or antibody fragment, also can be antigen or antigen fragment etc.In another embodiment, the embodiment difference shown with Fig. 2 is, on marked region 15, process has the specific binding molecule (Fig. 7) with water-soluble dye.
In another embodiment as shown in the figure, region 45 containing specific bond analyte on surveyed area 95 and positive control area 55, a testing result control area 85 is had in the downstream of surveyed area 95, there is reagent areas 115 in surveyed area upstream, reagent areas comprises marked region 15 and dye area 35.Wherein, positive control area 55 and testing result control area 85 are fixed with coagulum or flocculation agent catches respectively, the region 45 of specific bond analyte and positive control area 55 intersect to form ten subrack shapes mutually.When detecting, the dyestuff on dye area is caught by the coagulum of positive control area or flocculation agent and is formed positive control lines, and the coagulum on detected output control region 85 or flocculation agent are caught and formed output control lines.Meanwhile, the specific binding molecule with color mark material on marked region just participates in and the reaction of specific bond analyte carrys out testing result, and need not process excessive mark substance to participate in the positive control line of formation or testing result control line.The binding molecule with mark substance that such part is expensive has just well been saved.
In another particular embodiment of the invention, positive control area 55 also can process antibody or the antibody fragment of some protein ingredients, or other albumen of capture of labels material can catch material, are fixed with coagulum or flocculation agent on testing result control area simultaneously.
In another embodiment shown in Fig. 5, surveyed area comprises region containing specific bond analyte molecule and and positive findings control area 55, on Positive Structures control area, process has a certain amount of coagulum or flocculation agent to catch.Meanwhile, in reagent areas, only process has the transportable specific binding molecule with color mark material.Like this, when detecting, the coagulum on positive control area or flocculation agent catch unnecessary mark substance and formation control lines.This positive controls lines can form the symbol that can identify to show testing result with specific bond analyte region.
non-protein catches
Antibody on prior art control area or antibody fragment or some protein ingredients are caught the catches that material replaces to non-protein composition, greatly reduces the cost of reagent strip like this and don't change the sensitivity and specificity that reagent strip detects.The pollutant adopting flocculation agent or coagulum to be separated and to remove the colloidal state in waste water is used in a large number in field of waste water treatment.The present invention utilizes flocculation agent or coagulum to have this character of particle in condensation and precipitating liquid sample and forms color change in control area.The absorption that this flocculation agent or coagulum cause and precipitation are nonspecific absorption and precipitation.Here non-specific be in solution with particulate material can be flocculated reagent or coagulum precipitation and absorb.Non-protein mentioned here is the relative material of antibody, antibody fragment or albumin A, the protein B commonly used with prior art; do not refer to these flocculation agent or coagulum not containing any protein substance; but these flocculation agent or coagulum are not substantially in specific bond mode to catch other specific binding molecule in solution, but they carry out non-selectivity in the mode of non-specific binding catch particles in solution or particle matter.
In a concrete embodiment, as shown in Figure 1, a certain amount of flocculation agent or coagulum are fixed in testing result control area 85, the special molecular of a certain amount of band color colloidal solid of 115 process in the reagent areas of surveyed area 95 upstream.In time detecting, the liquid from sample application zone 25 flows through reagent areas 115 successively, surveyed area 95 and testing result control area 85.When flowing through testing result control area 85, the band color colloidal solid be comprised in liquid can be fixed on flocculation agent on surveyed area or coagulum precipitated.As shown in Figure 2, in another particular embodiment of the invention, in order to save the specific binding molecule of band color mark material, reagent areas 115 can also process some colored dyestuffs (35), when detecting, dyestuff in dye area is taken to by liquid and testing result control area is flocculated reagent or coagulum precipitates, and so just on testing result control area, Show Color represents that testing result is effective.
As Fig. 3-6; with in other embodiments shown in Fig. 8; positive control area 55,455 can process some flocculation agent or coagulum; these flocculation agent or coagulum can colloidal solid in precipitating liquid or dye granules; whether contain analyte regardless of in sample, positive control area all can have color occur.
The flocculation agent of indication of the present invention or coagulum comprise the reagent commonly used in wastewater treatment.Such as inorganic polymer flocculation agent (IPF) and organic polymer flocculation agent.Wherein inorganic polymer flocculation agent is mainly many derivants prepared by base stock with aluminium polychloride, as polymeric ferric aluminum, polymeric aluminium-silica and organic composite type flocculation agent.
The most conventional is organic polymer flocculation agent, and organic polymer flocculation agent has Prof. Du Yucang and natural two kinds.These flocculation agent can molecular cation type, nonionic and anionic by the difference of functional group.Water-solublely by whether can be divided into water-soluble and water-insoluble flocculation agent.The polyacrylamide (PAM) of such as nonionic, polyoxyethylene, anionic polypropylene acid (PAA), poly-methacrylate hydrolysis polyacrylamide (HPAM), poly-sulfostyrene; Cationic is butyl bromide ethene pyrrole, poly-propyl-dimethyl amine (PDADMA).Organic polymer flocculation agent has form larger flco and consequent huge adsorption effect between particle.Containing many active groups can worked with glue particle and some site, fine particle suspended particle surface in the water soluble organic polymer polymkeric substance of those high polymerization degrees or the molecule of multipolymer, molecular weight hundreds thousand of to millions of.The nonionic functional group of flocculating polymer reagent is hydroxyl (-OH), (-CN) and acid amides (-CONH2); Cationic functional group is that primary amine (-NH2), secondary amine (NH-R), tertiary amine (NH-RR) and quaternary amine (R-N-RR), anionic functional group are as carboxylic acid (-COOH), sulfonic acid (-SO3H) and sulfuric acid ester (-OSO3H) etc.
These flocculation agent or coagulum in China's application publication 200510023481,200410024480,200310122818,00130879 and 01129968, and are all described later in detail in Chinese patent 99116150,98116440 and 86104833.These organic or inorganic flocculation agent can by buying to Wuxi Lan Bo Chemical Company.Of the present invention one preferred embodiment in, the flocculation agent of use is water-soluble high analyte organic-flocculation reagent.
The known method of prior art can be used in flocculation agent process to control area.The reagent of these commercial uses can directly use, and after general inorganic flocculation agent can regulate suitable pH value, result of use is better; To flocculating polymer reagent, in order to obtain better disperse state, ordinary priority should select can dispersed in water, dissolve, there is macromolecular compound matter or the water-soluble high-molecular compound matter of adsorption activity group.In a concrete embodiment, the flocculation agent that commercial wastewater treatment is commonly used first can be diluted to certain concentration with pure water or soft water, then Membrane jetter device is regulated to be sprayed directly on on nitrocellulose filter with the trace that a micro-processing machines controls, then dry, in addition, be also fine with on liquid-transfering gun manual process flocculation agent to nitrocellulose filter.The flocculation agent of these industrial wastewater treatments is processed on film after also can dilute certain concentration with some buffer solution again.To the not special requirement of handled film, as long as the film can fixing some albumen is all feasible, such as nitrocellulose filter, nylon membrane, cellulose acetate membrane, filter paper etc.The membrane material that any persons skilled in the art can be expected in conjunction with the present invention.In one preferred embodiment, some surface-active agents can also be added in flocculation agent dilute solution.
reagent areas and specific binding molecule
Reagent areas comprises the marked region of the specific binding molecule with mark substance, surveyed area is fixed with another specific binding molecule, specific binding molecule and another specific binding molecule with mark substance specific bond can form a signal on surveyed area.Producing signal can be based on three sandwich method of showing one's high ideals or competition laws, or their derivative and other methods that is that go out.The specific binding molecule of analyte refer to combine with analyte and can not with the binding molecule of other any molecule strong bonded in sample.The specific binding molecule of analyte also can combine with the existence showing analyte in sample or the molecule be associated with the existence of analyte.Strong bonded refers to that combination reaches and changes test findings or make the unconspicuous degree of test findings.In some concrete schemes, specific binding molecule may be a kind of antibody or a kind of antibody fragment (such as, a kind of Fab district of antibody), a kind of antigen, the acceptor of binding partner or a fragment for acceptor, or biotin-streptavidin is in conjunction with the combination pair of right composition or other type.Such reagent area just can provide mark, and when sample flows through reagent area time, analyte combines the mark that can produce detectable signal." label pad " refers to the position of the material containing the analyte that may exist in mark sample in matrix.Therefore a reagent area is exactly a label pad." mark " can be any suitable mark producing detectable signal.Such as, mark can be sol particle, fluorescent grain, chemiluminescent molecule, and metal or alloy (such as, collaurum), or capsule, particularly comprise the liposome of visible dyes.Hydrophobic sol is also that useful, hydrophobic organic dyestuff or pigment are soluble or only have very limited sub-fraction solvable in water.Mark can also be polymer particles, such as coloured granules of polystyrene (such as, spherical).Other useful granular mark comprises ferritin, phycoerythrin, phycobilin-albumen, precipitation or the metal of solubility or alloy, fungi, marine alga, or the pigment of bacterium or derivant, the chlorophyll of such as bacterium or other plant material.In some concrete scheme, mark is coloured particle, such as dextran bead.In other concrete scheme, the color that the mark as positive control is identical with dye selection, to strengthen the interaction of two kinds of signals in matrix or when Medium Culture produces single obvious symbol.
In other concrete scheme, mark may be a kind of specific binding molecules (such as, a kind of antibody) be labeled of analyte.Such as, in a concrete scheme, target analyte is human chorionic gonadotrophin (hCG), and the mark in conjunction with hCG is the Anti-hCG antisera of aurosol mark.When sample arrives reagent area (or label pad), the hCG in sample is combined by the Anti-hCG antisera that aurosol marks.Labelled antibody does not disturb the capture molecules of analyte land and the hCG of mark to combine.Such as, mark can in conjunction with of an analyte part, and capture molecules can in conjunction with another part of analyte or incorporation of markings.HCG-Anti-hCG antisera-Au composite moves to the downstream of matrix.Combine with capture molecules when the complex reaches the analyte binding area and form the anti-hCG-Anti-hCG antisera of gold-anti-hCG.Capture molecules may be the another kind of specific binding molecules of hCG, or the specific binding molecules of halfbody in conjunction with hCG analyte.When gold-anti-hCG specific binding molecules-hCG-anti-hCG specific binding molecules compound is attached to analyte land, analyte land is by the golden marker coloring on compound and to become naked eyes at analyte land gold mark visible.In a concrete scheme, specific binding molecule is antibody or antibody fragment.Mark and catch binding molecule can in conjunction with epitopes different on analyte, in a concrete scheme, the specific binding molecules of mark combines β-hCG, and catches binding molecule and combine α-hCG.
" antibody " refers to immunoglobulin (Ig), is no matter natural or some or all of synthesis.This term also comprises the derivant of the antibody wherein keeping binding ability, also comprise any containing with the binding domain homologue of immunoglobulin (Ig) or the protein of the binding domain of homology to a great extent.These protein may be derived from natural materials, also may be some or all of synthesis.A kind of antibody may be monoclonal or polyclonal.Antibody may be a member in any immunoglobulin class, comprises the immunoglobulin class of any mankind: IgG, IgM, IgA, IgD, IgG and IgE." antibody fragment " is the derivant of antibody or the part being less than total length of antibody.Antibody fragment can remain to the remarkable site of the binding ability of a few full length antibody.The example of antibody fragment comprises Fab, Fab', F (ab')
2, scFv, Fv, dsFv dimer, and Fd fragment, but not only comprise above these.
Antibody fragment can be generated by any mode.Such as, antibody fragment can be generated by enzymolysis or the complete antibody of chemical cracking one, or also can by the genetic recombination from coded portion antibody sequence.In other words, antibody fragment can be recombinated generation partially or entirely.Antibody fragment can be arbitrary single chain antibody fragments.In other words, antibody fragment can comprise many peptide chains interconnected, and such as, passes through disulfide linkages.Antibody fragment also can be arbitrary a kind of multi-molecular complex.One has the antibody fragment of function usually to comprise at least about 50 amino acid, and more antibody fragment comprises at least about 200 amino acid usually.
ScFv s (scFvs) is the antibody fragment of restructuring, and it is only by variable light (V
l) and variable heavy chain (V
h) mutually with polypeptied chain covalent bond.V
land V
hin a side there is amido end regions.Polypeptied chain length and composition are variable, and its length can make two mutual bridgings of variable domain and not have a strong impact on the arrangement of atom.Polypeptied chain extends formation primarily of glycocoll and serine residue usually, wherein has some glutamic acid and lysine residue to be dispersed in distribution to increase its solubleness." dimer " refers to the dipolymer of scFv s.Short usually than most of scFv s of the peptide chain that dimeric monomer comprises, and they demonstrate the tendency forming dipolymer.
" Fv " fragment is by a V
hwith a V
lterritory is interconnected composition with non-covalent.Term " dsFv " here refers to and comprises a stable V
h-V
lthe Fv of right intermolecular disulfide bond." F (ab')
2" fragment is a fragment of antibody, identical with by the pepsin fragment that digestion immunoglobulin (Ig) (normally IgG) obtains when pH 4.0-4.5 in essence.This fragment also can be re-combined into." Fab' " fragment is a kind of antibody fragment, in essence and by reduce F (ab')
2the fragment that two interconnective cystine linkages of heavy chain in fragment obtain is identical.Fab' fragment also can be re-combined into.“Fab”
Fragment is the antibody fragment that one is identical with the fragment obtained with papain digestion immunoglobulin (Ig) (usual IgG) in essence.Fab fragment also can be re-combined into.Heavy chain fragment in Fab fragment is Fd fragment.
The said reagent areas of the present invention can comprise one or several reagent areas, and these reagent areas differ to establish a capital and exist on reagent strip certainly.In one embodiment, reagent areas 115 is positioned at the upstream (as Fig. 1-8) of surveyed area 95.In a concrete embodiment, reagent areas 115 can comprise a marked region 15 and dye area 35, on marked region, process has the specific binding molecule of band color mark material, on dye area, process has colored dyestuff, this dyestuff does not have specific binding molecule (Fig. 2).In other embodiments, in reagent areas, also process has the chemical reagent regulating reaction conditions, these chemical reagent can to offer the best condition for the specific binding molecule on surveyed area and the reaction between band colored particle mark substance molecule, such as regulate the pH value of reaction, reduce the interfering material of other disturbance reponse in sample.These chemical reagent can process in sample application zone, also can process between dye area and surveyed area.
In another embodiment, reaction reagent first and sample mixing, and then can be inserted into the reagent strip containing surveyed area and control area in solution and goes to react.
In another embodiment, reagent areas comprises marked region 15, on marked region, process has the excessive specific binding molecule with mark substance, like this when liquid flows through positive control area 55, a part of mark substance in solution is flocculated reagent or nonspecific the catching of coagulum and produces color change; On specific bond analyte region, specific binding molecule and the specific binding molecule with mark substance produce specific bond (Fig. 5).
the specific binding molecule of tape label material and mark substance
The specific binding molecule of tape label material mentioned here refers to that this molecule and another specific binding molecule be fixed on surveyed area are man-to-man combinations.So-called specific binding be a molecule by physics or another molecule of chemical mode specific bond, be combineding with each other between these two molecules can distinguish with other combination.Specific bond between this two molecules is except comprising the antibody of antigen and antigen, also comprise another antibody of antibody and this antibody anti-, the albumen of biotin and antibiotin, between polypeptide fragment, DNA and DNA, RNA and RNA, and the specific binding pair molecule obtained by recombinant technique etc.This combination can be direct combination, can also be to be closed by the intermolecular access node of its special pairing.Specifically, the combination be fixed between specific binding molecule on surveyed area and the molecule of tape label material can carry out detectable antigens by double antibody sandwich method, dual-antigen sandwich method detect antibody or by them derive other directly and indirect method.These specific bond are that those skilled in the art combine point invention easily to arriving.
Mark substance mentioned here refers to the material that a class can be read by direct visual perception or machine.The mark substance of many types can produce the signal that can identify by physics or chemical mode.Such as enzyme, fluorescent material, chemiluminescent substance, radiomaterial, other material comprises its own band colored particle shape material, and this particulate material can be metallic colloid or latex colloid etc., can also be water-soluble dye.
the type of sample and analyte
The sample of any type can both be tested with device of the present invention, comprises body fluid (such as, urine and other body fluid, and clinical sample).Fluid sample may be derived from solid or semisolid sample, comprises excrement, biological tissue and foodstuff samples.These solids can be transformed into fluid sample by any applicable method with semisolid sample, such as mix in a kind of suitable liquid, stamp broken, macerate, hatch, dissolving or enzymolysis solid sample are (such as, water, phosphate buffer or other damping fluid)." biological sample " comprises the sample being derived from animal alive, plant and food, also urine, saliva, blood and blood constituent, cerebrospinal fluid, vaginal swab is comprised, the culture of seminal fluid, ight soil, sweat, secretion, tissue, organ, tumour, tissue and organ, no matter the conditioned media of cell culture and there is people or animal.Foodstuff samples comprises finished composition of food and last product, meat, cheese, wine, milk and potable water.Plant sample comprises the sample of conditioned media being derived from any plant, plant tissue, plant cell cultures and there." environmental sample " is that those are derived from the sample (such as, the sample of lake water sample or other water body, sewage sample, pedotheque, groundwater sample, seawater sample, the sample of refuse water) of environment.Sewage and relevant refuse also can be included in environmental sample.
Any analyte can be analyzed with the present invention.The example of the analyte that can detect with the present invention comprises (but not only comprising) human chorionic gonadotrophin (hCG), lutropin (LH), ovarian stimulation element (FSH), hepatitis C virus (HCV), hepatitis B (HBV), hepatitis B surface antigen, the medicine of AIDS virus and any abuse.Analyte can detect in any liquid or liquefied sample, such as urine, saliva, saliva, blood, blood plasma, or serum.The example of other analyte also has the acid of flesh ammonia acid anhydride, cholerythrin, nitrite, protein (nonspecific), blood, leucocyte, blood sugar, heavy metal and toxin, bacterial component is (such as, the special protein and sugar of the bacterium of particular type divides, such as colon bacillus 0157: H7, staphylococcus aureus, salmonella, C.perfringens, campylobacter, listeria monocytogenes, V. parahaemolyticus, or wax bacillus).Other analyte of applicable lateral flow test format any can detect with this device.
reagent strip and the device with reagent strip
What reagent strip mentioned here referred to can allow liquid at the reagent strip of upper flowing, and reagent strip at least comprises surveyed area and control area.This reagent strip can be made by a lot of material, such as cellulose, filter paper, nitrocellulose filter or nylon membrane etc., anyway just passable as long as liquid can be allowed from one end of reagent strip to flow to the material of the other end.
In a concrete embodiment, this reagent strip is nitrocellulose assay strip.Specifically, as shown in Figure 6, this reagent strip 6 is made up of four parts, comprises sample absorbance sheet 425, marker slip 4115 and cellulose nitrate sheet 475 and water absorbent sheet 465.This few part is interconnected and liquid can be allowed from sample blank film 425 to arrive water absorbent sheet 465 through marker slip 4115, nitrocellulose filter 475.Wherein, the specific binding molecule with colored particle is had in mark chip processing, nitrocellulose filter 475 comprises surveyed area 495, surveyed area 495 comprises region 445 containing specific bond analyte and positive control area 455, and positive control area is fixed with a certain amount of flocculation agent or coagulum.The material forming these sheets can some common absorbent materials, as plain in glass fibre element, polyester fiber, filter paper etc.In a preferred embodiment, sample blank film is that glass fibre element sheet, marker slip are polyester diaphragm, water absorbent sheet is filter paper.In another embodiment, be to also have a testing result control area 485 in the downstream of surveyed area with the embodiment difference shown in Fig. 6, surveyed area is fixed with a certain amount of flocculation agent or coagulum (Fig. 4).In any one embodiment above-described, the part of composition reagent strip can be fixed on a hydrophobic backing plate.In another embodiment, this reagent strip can be placed in the device containing upper plate and lower plate and go, the upper plate of this device has the sample application zone on a liquid through-hole and reagent strip communicate, the result reading window of upper plate and surveyed area and testing result control area corresponding.The material of these reagent strips and device are that those skilled in the art easily expect in conjunction with the present invention, and they are not emphasis of the present invention, the material forming reagent strip various piece and the device holding reagent strip all at United States Patent (USP) 5,602,040; 5,989,921; 6,352,862; 6,319,676,5,824,268; 6,184,040; 6,472,160; 6,267,722; 6,649,418; 6,537,828; 5,739, there is detailed announcement in 041.
in order to better the beneficial effect of the invention is described, now give description of test
the detector bar of experiment 1 with flocculation agent detects HCG (HCG)
This example describes the concrete scheme using reagent strip of the present invention to detect the HCG in urine
the preparation of reagent.flocculation agent process: dilute BWD-Q1 decolorization flocculation reagent (Wuxi Lan Bo Chemical Company) with distilled water and add the Surfactant preparations of S-10.The ratio of dilution is followed successively by (flocculation agent: water) (volume ratio): 1:50,1:100,1:200,1:400,1:800,1:1600.
Dyestuff process: be PBS buffering liquid dilution Eosin Dye Y (reagent company limited is thought carefully in Shanghai) of 7 with pH.The final concentration of dilution is: 0.2%, 0.1%, 0.055%, 0.025%, 0.0125%, 0.006255%.
reagent strip of the present invention prepares.reagent strip is according to commonsense method manufacture in this area.With reference to Fig. 6, on marker slip 4115, process contains little mouse-anti β hCG IgG and the Eosin Dye Y of aurosol mark, the analyte calmodulin binding domain CaM 445 of nitrocellulose filter 475 processes goat-anti α HCG IgG(4.0mg/ml), treatments B WD-Q1 decolorization flocculation reagent on the positive control area 455 of nitrocellulose filter 475.These agent treated can be sprayed at arbitrarily on film with the micro-flusher of a Microprocessor S3C44B0X on nitrocellulose filter.Then these with the sheet material handled well (4115,475) drying.After dried, sample blank film 425, marker slip 4115, nitrocellulose filter 475 and water absorbent sheet 465 are connected in turn according to shown in Fig. 6.The concentration of the BWD-Q1 decolorization flocculation reagent on the mark dye strength of chip processing and positive control area carrys out reagent treatment bar according to the combination shown in table 1.
the preparation of contrast agents bar.with the difference of reagent strip of the present invention be exactly contrast agents bar positive control area on process anti-human igg (1.3mg/ml), reagent areas does not have dyestuff.Other all the same
.
detect negative and positive urine liquid.detect feminine gender (10) and positive urine liquid (10) respectively according to the reagent strip of above process, do control experiment simultaneously.
experimental result 1:
Table 1: the control lines experimental result of the different B WD-Q1 decolorization flocculation reagent concentration on control area
experimental result 2:
Table 2: the flocculation agent that control area processes and the specific antibody of process are on the impact of testing result
conclusion
From the result shown in table 1, the flocculation agent that positive control area processes can reach the result of G8-G9, when detecting, positive control area occurs very bright-coloured red lines.Time dye reagent concentration is 0.0125%-0.00625%, the background of this reagent strip is fine, bright-colored.
Meanwhile, as can be seen from Table 2, we detect positive urine fluid samples with these reagent strips, and detection control region all shows the result of positive sign "+", and negative sample all demonstrates negative sign "-" result, consistent with the testing result of the reagent strip of contrast.Then illustrate, the BWD-Q1 decolorization flocculation reagent on this positive control area to the specific binding reaction on analyte calmodulin binding domain CaM be do not have influential.
Here G8, G9 are the internal control standards weighing shade, and be generally that color deepens gradually from colourless from G0 to G12, generally on control area, color is that more than G7 just can reach require that of commercial product.The depth of background is also a control of product standard, the reason of production background be these colored particles (dyestuff and mark substance) on nitrocellulose filter because capillary layer inhales flow forward, these particles due to be subject to the micropore on nitrocellulose filter resistance and in showing color belt on film, along with the flowing of liquid, these colors can disappearance gradually.General coml requires bright-colored for what control area occurred, and the speed that background shoals in certain hour is faster, then the quality of product is better.
The invention described of illustrating herein just can use when each part possesses, and being limited in of it does not just specify here.It is not uniquely constant for being used for the term of tracing device and expression way herein, and we use these terms and expression way to get rid of the expression way describing the structure of this device or any same meaning of feature without any intention, the various different expression way of our approvals in the scope of the claims in the present invention.Therefore, although we think that the present invention in this article clearly displays with various concrete scheme and arbitrary feature interpretation, but the expression way changing the design disclosed herein also will seek help from those experienced professional technique personages, and the claim that these changes will be subsidiary with the present invention is consistent.
The content of the application of article, patent, patent and other documents all and mention herein and the useful digitized information quoted as proof combine, reference must be carried out as a complete content, deliver wherein any one part and all will specialize this point.Applicant has the right these any and whole articles, patent, patent application or the information of other document and material being integrated with the application.
Claims (8)
1. one kind is detected the pick-up unit whether containing analyte in sample, comprise: the reagent strip supporting liquid sample flowing, reagent strip comprises reagent areas, surveyed area and positive control area, reagent areas there is mark substance, surveyed area comprises a species specific binding molecule, it is characterized in that, described positive control area comprises non-protein flocculation agent.
2. pick-up unit as claimed in claim 1, is characterized in that, the analyte calmodulin binding domain CaM on this positive control area and described surveyed area intersects to form a symbol that can identify.
3. pick-up unit as claimed in claim 2, it is characterized in that, described positive control area and described surveyed area intersect to form a crux.
4. pick-up unit as claimed in claim 3, it is characterized in that, described reagent areas also comprises marked region, and described mark substance is positioned at marked region.
5. pick-up unit as claimed in claim 4, it is characterized in that, described reagent areas also comprises a dye area, and dye area comprises the coloured dyestuff of band.
6. pick-up unit as claimed in claim 5, it is characterized in that, this dye area is positioned at the downstream of marked region, the upstream of surveyed area.
7. the pick-up unit as described in one of claim 1-6, it is characterized in that, described reagent strip is nitrocellulose assay strip, reagent strip comprises sample reception region, is wherein followed successively by sample reception region, reagent areas and surveyed area along liquid flow direction being from upstream to downstream.
8. pick-up unit as claimed in claim 1, it is characterized in that, described non-protein flocculation agent is water soluble organic polymer flocculation agent.
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|---|---|---|---|---|
| US4916056A (en) * | 1986-02-18 | 1990-04-10 | Abbott Laboratories | Solid-phase analytical device and method for using same |
| CN1455242A (en) * | 2003-06-04 | 2003-11-12 | 苏向东 | Quantitative measuring apparatus and method of gold colloid immuno chromatography |
| CN1682114A (en) * | 2002-06-27 | 2005-10-12 | 因韦尔尼斯医药瑞士股份有限公司 | Assay device for liquid sample |
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| US6855561B2 (en) * | 2001-09-10 | 2005-02-15 | Quidel Corporation | Method for adding an apparent non-signal line to a lateral flow assay |
| US7459314B2 (en) * | 2003-02-13 | 2008-12-02 | Inverness Medical Switzerland Gmbh | Lateral flow immunoassay controls |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4916056A (en) * | 1986-02-18 | 1990-04-10 | Abbott Laboratories | Solid-phase analytical device and method for using same |
| CN1682114A (en) * | 2002-06-27 | 2005-10-12 | 因韦尔尼斯医药瑞士股份有限公司 | Assay device for liquid sample |
| CN1455242A (en) * | 2003-06-04 | 2003-11-12 | 苏向东 | Quantitative measuring apparatus and method of gold colloid immuno chromatography |
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