CN203561636U

CN203561636U - Directional flow immunochromatography device

Info

Publication number: CN203561636U
Application number: CN201320537476.XU
Authority: CN
Inventors: 罗纳德·T·拉博德
Original assignee: Quantum Design Inc
Current assignee: Quantum Design Inc
Priority date: 2013-08-30
Filing date: 2013-08-30
Publication date: 2014-04-23
Anticipated expiration: 2023-08-30

Abstract

The utility model provides a directional flow immunochromatography device capable of guiding added samples to a directional flow box. The device is characterized in that a sample receiving opening defined by a plurality of layers of spliced materials is formed in one end of a test strip and is used for receiving the samples and specially guiding the samples to a film in a controlled manner. In addition, the device is characterized by comprising an approximately C-shaped shell structure, and the test strip crosses the opening of the C-shaped shell structure so as to facilitate the access of a reading device. By a preferable method, a target analyte is marked by superparamagnetic particles, and the electromagnetic reading device is used for detection and determination.

Description

Oriented flow device for immunochromatography

Technical field

The utility model relates generally to immunoassay, based on the analysis of acceptor, cell and molecule, and the liquid delivery device that comprises it.More specifically, the utility model relates to the analysis mensuration or the proving installation that comprise liquid delivery element, and can comprise the reagent for detection of paid close attention to analyte.

Background technology

There is a period of time in multiple chromatographic analysis and Microfluidic Immunoassay technology.For example, as far back as 1956, just utilize the latex agglutination test based on immune to detect the factor relevant with rheumatoid arthritis (Singer etc., Am.J.Med.22:888-892 (1956)).Can usually relate to immunoassay with the test that this chromatographic analysis and fluid system carry out, its specificity depending between antigen and corresponding antibodies interacts.Therefore, immunoassay is considered to test the existence of important molecule clinically or the important and method easily of the one of quantity or existence and quantity.

Chromatography and hydrometry system are for detection of analyte, especially a part for many analytic systems of those analytes that are biologically concerned.The analyte that usually utilizes these systems to measure has: (1) hormone, and for example hCG (hCG), it is usually as the signal of people's gestation and determined; (2) antigen, especially to bacterium, virus and protozoan pathogen antigen as special in streptococcus, hepatitis virus and giardia lamblia stiles; (3) antibody, especially because for example bacterium of pathogen or virus (as HTV) infect the antibody of inducing; (4) other oroteins, for example haemoglobin, determined in the mensuration ight soil occult blood process of being everlasting, be the early stage indicant of one of for example colon cancer of enterogastric diseases; (5) enzyme, for example aspartate transaminase, lactic dehydrogenase, alkaline phosphatase and glutamte dehydrogenase, they are often as the indicant of physiological function and tissue damage and determined; (6) medicine, had both comprised that curative drug was as microbiotic, and sedative and anticonvulsive drug comprise that again the illicit drug of abuse is as ***e, heroin and hemp; (7) vitamin; And (8) nucleic acid substances.

Doctor and medical skill personnel often use this chromatographic assay system to carry out in office, diagnosing fast.Therefore, they are commonly called " point of care " and (POC) install.These tests also can be used for various symptoms and disease to carry out therapeutic detection.They are also used for monitoring these symptoms and disease at home by patient more and more; By scientists, be used for genetically modified crops and environmental pollution to carry out field test; By soldier, be used for detection of biological weapon of war under battlefield surroundings; By animal doctor and first-aid personnel, in the situation that being badly in need of test fast, used.

Chromatographic analysis and the fluid technique of combining use with most of common immunoassays relate to immunochromatographiassays assays principle.In general, this technology adopts the label or the indicant that have been attached to the immune protein to molecular specific to be determined.This label is known as bond together with antibody/antigen, then it is mixed with sample.If there is the combination of this analyte molecule, cell or molecule in this sample, for example DNA, this bond will be combined with this molecule specifically.This label aspect provides and has existed the machine of this molecule to be determined or people can detect indication.The specific reaction adopting, changes with the characteristic of determined molecule and sample to be determined.These determine according to paid close attention to molecule, be easy to make.

According to the character of antigen-antibody complex to be detected and produce the required response hierarchy of this compound, immunochromatographiassays assays and fluid analysis can be divided into two main classifications: " sandwich " and " competitive mode ".In situation about detecting at antigen, sandwich immunochromatographiassays assays program requires the sample that comprises analyte to be determined to mix with the antibody of this analyte.These antibody are movably and are typically connected to a kind of label or a kind of reagent, for example latex, colloidal metal sol or the radioactive isotope of dyeing.Then this potpourri is applied in the chromatography media that comprises band or trapping region.This band or trapping region comprise the fixing antibody to paid close attention to analyte.This chromatography media can also be the strips of similar colloidal dye test strips (dipstick).When molecule to be determined with when the compound of labelled antibody/antigen has arrived the region of the capture protein being fixed on this stratographic analysis medium, combination occurs, and the mark capturing protein of this combination is positioned in this region.This shows the existence of molecule to be determined.Adopt this technology can obtain qualitative results.The example of the sandwich immunoassay carrying out in test-strips is at United States Patent (USP) the 4th, 168, No. 146 (Grubb etc.), the 4th, 366, No. 241 (Tom etc.), the 6th, 017,767 and 5,998, No. 220 (Chandler) and the 4th, in 305, No. 924 (Piasio etc.), describe to some extent.

In competitiveness or indirect immunoassays, this composition being fixed normally exists this removable composition with unknown quantity, to exist with in check amount.The removable composition of unknown quantity is to supplement by the identical component being labeled of known quantity, and this mark is that component measurable by adding, immuno-chemical reaction characteristic that do not disturb this composition realizes.This label can be by radioactive isotope, chromophore, particulate, fluorophor or enzyme composition.With immune chemical mode, be bonded to the amount of the mark substance of this solid-phase, will determine according to the amount of the unmarked composition of competing identical combination site in solution.The not principal component existing is more, in conjunction with the amount of marked member just fewer.Can carry out like this relative quantification.

Except immunochromatographiassays assays, the chromatographic analysis based on enzyme is also applied.These analyses based on enzyme relate to enzymic catalytic reaction, rather than antigen-antibody reaction.Enzymic catalytic reaction often produces detectable product.

Although the chromatographic technique of current available use test bar is useful, but there are many defects.Some sample, for example fecal specimens, comprises particle matter, and these particle matters can cover or make the hole of chromatography media painted, hinder to a great extent the detection of these labelled reagents.For example, blood obviously comprises cell and colored component, and these compositions have covered the color in test and produced, even therefore likely, is also difficult to identification.Haemocyte is also easy to the hole in blocking medium.Due to the mirror-reflection from chromatography media, moist chromatography media is also difficult to identification sometimes.Chromatographic technique also has many other defects, comprises the physical property of effluent (lateral flow), and fluid is along the reach of band, and generation intensity and the position of color.

For current adoptable Flow Control and device for immunochromatography and technology, it is the reason that causes other problems that sample preparation and refuse produce.The disease of propagating by blood and the blood constituent of infection, as the increased popularity of HIV and hepatitis B, can only be deepened these worries.These can utilize the lateral flow devices of form, and their a big chunk accessory, just for the machinery support of chromatographic film, is not what seal.Therefore processing is problem, rate of exchange costliness, and be biological harmful and may be dangerous owing to being considered to.Therefore, must prevent, can be not infected so that contact unintentionally workman or the personnel self of this refuse.

Known devices, particularly in lateral flow technology and microfluidic system, a total aspect is to read measurement result by vision, the line of getting by means of one or more optical readable in the test-strips remaining in carrier, or by " window " in this device, it can have multiple external form.As above summary, these known optics can detection assay exist several limitations or shortcoming.Because they by optics (by vision), can only detect that surface changes (normally dyeing).In addition, these tests are only suitable in the situation that sample solution is colourless.Further, target analytes may be present in sample solution, but there is very low concentration to such an extent as to measure trapping region in can only capture relatively little.This may provide fuzzy or even non-optical detectable reading, and may occur wrong negative reading.Quantitative evaluation is only the estimation of the color intensity based on detection line.Because the mensuration thing in prior art is optically read, they subject to the pollution causing due to the degraded exposing and photoconduction causes.Therefore, they have limited storage life.

Conventionally one end of test is exposed to sample, is usually certain fluid, for testing paid close attention to particular target analytes.This fluid moves by kapillary or chromatography media, and the analyte thus with its label is hunted down and fixes, and remaining fluid is adsorbed in a kind of medium in this mensuration thing far-end.The example of optically read lateral flow devices and method is in United States Patent (USP) 5,591,645; 5,798,273; 5,622,871; 5,602,040; 5,714,389; 5,879,951; 4,632,901; And describe to some extent in 5,958,790.

Many existing apparatus also have the fluid sample being communicated with the direct fluid of test-strips and apply element.This element is conventionally by being included in this device self, or the sorptive material that can stretch out from this device makes, and is introduced in this fluid sample being easier to.This adsorbability fluid sample applies element and attempts to control fluid by the flowing velocity of this device.If this be consider fluid sample be applied directly to test-strips, this test-strips be easily submerged and cause measuring invalid.And owing to expecting the relatively large amount of the liquid of processing, this applies element and is usually made by the material that is different from this test-strips itself.

Somebody attempts flowing to by utilizing capillary analysis form to control the fluid velocity of test-strips.The example of capillary analysis can be at United States Patent (USP) 4,883, finds in 760 and 5,474,902.But these are not suitable for situation about using in point of care.

The biosystem of non-sidestream immune analysis has adopted magnetic particle or microballon, and it is more specifically called as Superparamagnetic Iron Oxide impregnated polymer bead.Target analytes combination in these beads and sample, is then separated by magnetic action conventionally.Once separate, can further test, comprise directly by eyesight or with camera, observe the image of particulate.The example of these systems can be at United States Patent (USP) 3981776; 5395498; 5476796; 5817526; And find in 5922284.

Detect the another kind of apparatus of target molecule in liquid phase and describe to some extent in United States Patent (USP) 5981297, wherein adopted magnetizable particulate, and existence and the concentration of target molecule in sample has been indicated in the output of magnetic field sensor.The example that other applied physics power are carried out magnetic transducing is disclosed in United States Patent (USP) 5445970; 5981297; In 5925573.But in these devices, magnet need to have relatively high energy, because place the gap of mensuration thing, must reach enough wide to hold relatively thick determinator.

Therefore, it is useful having a kind of like this pick-up unit: in this device, the mode that fluid sample is applied in can be avoided the problem in prior art device, and it has the detection zone that standardized, reliable and reproducible result can be provided, and can preserve a period of time.The utility model meets these needs, and relevant advantage is provided simultaneously.

Utility model content

The utility model relates generally to immunoassay, based on the analysis of cell and molecule.More specifically, it relates to oriented flow determinator, and this determinator has sample reception port, and this port separates by microchannel and analyzing film.Oriented flow determinator of the present utility model can be for the quantitative measurment of biomarker, described biomarker indication diagnosis, to the medical science symptom that comprises whole diseases and illness, is monitored object medicinal treatment (be called and follow diagnosis (companion diagnostic)), hormonal readiness and biological chemistry level etc.In a preferred embodiment, these analytical equipments label of superparamagnetic particulate as test analyte.The compound of the combination of labeled microparticles and analyte is trapped in the preset range or region in test-strips, then by existence and the amount of magnetic means detectable label analyte.In some embodiments, also consider to detect these analytes by for example conventional optical means.The necessary particular agent of optical detection and bond have been used for many years and are well known.

In one embodiment, this device has and measures thing layer structure (it has first end and the second end) and contiguous this layer structure is installed and parallel porous analyzing film with it substantially.Each layer of layered structure is fixing by pressure sensitive adhesive (PSA).This porous analyzing film is preferably configured to contain capture antibody or antigen.This analyzing film has first end and the second end and at least one trapping region between this first end and the second end, and wherein at least one trapping region is provided for catching the labelled analyte that moves to the second end of this analyzing film from the first end of this analyzing film.In one embodiment, the analyzing film of described device is configured with two trapping regions that formed by capture antibody in column or antigen.Before shifting to the second end of this analyzing film from the first end of this analyzing film, described analyte and magnetic bond mix particles, simultaneously the analyte specific binding in antibody or antigen and trapping region.

Device herein also preferably has sample reception port, and this port is preferably connected with test-strips itself by passage or is communicated with its fluid.In these embodiments, do not use sample to apply element or sample pad.This sample reception port has suitable size and constructs to hold the fluid of specified quantitative, and is communicated with the direct fluid of this test-strips.This sample reception port is positioned at one end of this layer structure, is used for sample to be analyzed to introduce in described device.This sample reception port has fluid encapsulation material, and contiguous sealing material and the channel layer arranged.In this channel layer, there is opening, and passage, this opening is provided with the fluid of this passage and be communicated with, and this passage is provided with the fluid of this porous analyzing film be communicated with.In one embodiment, described passage preferably has open distal end wider compared with sample reception end.These features, that is, narrow front end and wide far-end and the violent transformation between two kinds of shapes, promote fluid to mix, and promote fluid to be transported on analyzing film in the process at fluid through sample port.Passage overlaps onto the even conveying that allows sample and bond on analyzing film.Hydrophilic material is arranged on this channel layer, and wherein has the opening corresponding with the opening of channel layer.Shim elements is arranged on this water wetted material, and wherein has opening to allow fluid to enter this port.This pad provides this mensuration thing and any sealing between housing around.

Other embodiment of the present utility model can have the diaphragm of the side in contrast to this layer structure that covers this analyzing film.This diaphragm can be opaque on optics.In other embodiment, diaphragm and perforated membrane monoblock type form, and alternatively, this diaphragm can be formed by the surface treatment of this perforated membrane.

Other embodiment of the present utility model can have control zone in perforated membrane, for collecting the magnetic bond of having been used to show this test-strips by trapping region.In other embodiment, on this diaphragm, can be printed at least one magnetic calibration area.This calibration areas may be the form of bar line, or or even single dot, etc.

Preferred implementation of the present utility model has lower casing portion for supporting this layer structure.This shell is preferably C shape, but also considers many other shapes here, as long as can allow reading device approach this test-strips.Housing department on also can existing in these embodiments.On this, shell quality award from the ministry choosing has complementary structure with lower casing portion, and is contained in the opening that makes this immunoassay test-strips stride across C shape in lower casing portion, or two arms.In other embodiments, the housing department of device of the present utility model is configured with the opening of other shapes, to be easy to that magnetic measurement is set, reads instrument (MAR).By after upper and lower enclosure closed, the utility model determinator is fixed to suitable position by the spot pressure in plastic casing, and the pressure sensitive adhesive in layer structure still exists but main power is not provided.

The utility model further provides and to have used the whole bag of tricks installing described in literary composition.For example, provide a kind of method quantitatively detecting for sample object being carried out to sidestream immune analysis.The method relates in conjunction with multiple superparamagnetic bond particulates (its target analytes that is designed to expect in sample is combined).Analyte and superparamagnetic particle complex are applied to one end of measuring thing the perforated membrane that is delivered to chromatography strip by sample reception port.The compound of analyte and superparamagnetic particulate moves through perforated membrane by capillary action.Then, in trapping region, the amount of labelled analyte is read by magnetometric analysis reading device.

To sum up, for realizing above-mentioned purpose of the present utility model, according to an aspect of the present utility model, provide a kind of for quantitatively detecting the oriented flow device for immunochromatography of sample target analytes, described device comprises:

Have the mensuration thing layer structure of first end and the second end, each layer of layered structure is fixed by pressure sensitive adhesive;

Be configured to contain that capture antibody or antigen and contiguous layered structure are installed and parallel porous analyzing film substantially with it, described analyzing film has first end and the second end and at least one trapping region between first end described in it and the second end, described at least one trapping region is configured to be formed by capture antibody in column or antigen, and is configured to catch the labelled analyte of shifting to described second end of described analyzing film from the described first end of described analyzing film; Before shifting to described second end of described analyzing film from the described first end of described analyzing film, described analyte and bond mix particles; Described analyte specific binding in described antibody or antigen and described trapping region, and

At the sample reception port at place, layered structure one end, for described sample to be analyzed is introduced to described device, described sample reception port comprises:

Be positioned at the channel layer above layered structure, described channel layer comprises opening and passage, and described opening provides with the fluid of described passage and is communicated with, and described passage provides and is communicated with the fluid of described porous analyzing film;

Be positioned at the water wetted material on described channel layer, in described water wetted material, there is the opening corresponding with described opening in described channel layer; And

Be positioned on described water wetted material and wherein have opening to allow fluid to enter the shim elements of described port, described pad provides Fluid Sealing for described determinator.

According to a kind of embodiment of the present utility model, described oriented flow device for immunochromatography further comprises the fluid encapsulation material between layered structure and described channel layer, and described fluid encapsulation material provides Fluid Sealing from bottom for described sample reception port.

According to another kind of embodiment of the present utility model, in described oriented flow device for immunochromatography, described analyzing film has two or more trapping regions.

According to another embodiment of the present utility model, in described oriented flow device for immunochromatography, described passage has the open distal end of the relatively described trapping region wider than the width of its contiguous described opening.

According to another embodiment of the present utility model, described oriented flow device for immunochromatography is further included in the diaphragm that covers described analyzing film on the opposite side with respect to layered structure, and described diaphragm is transparent or opaque.

According to another embodiment of the present utility model, in described oriented flow device for immunochromatography, described diaphragm and described perforated membrane are integrally formed.

According to another embodiment of the present utility model, described oriented flow device for immunochromatography is further included in a control trapping region in described perforated membrane, for collecting the bond to show that described test-strips has been used by described trapping region.

According to another embodiment of the present utility model, described oriented flow device for immunochromatography further comprises at least one magnetic calibration area being imprinted on described diaphragm.

According to another embodiment of the present utility model, described oriented flow device for immunochromatography further comprises that the lower casing portion with opening is for supporting layered structure, with have and the upper housing department of the structure of lower casing portion complementation, to be arranged on, in described lower casing portion, make the opening of described determinator across described crust of the device portion.

According to another embodiment of the present utility model, in described oriented flow device for immunochromatography, described open construction becomes the opening of C shape.

According to another embodiment of the present utility model, described oriented flow device for immunochromatography further comprises and is arranged in the upper housing department of described device and the strainer of lower casing.

The utility model has improved sensitivity on the basis of known lateral flow devices.It provides a kind of very fast (in minutes) analysis to measure method.Compared with coloured particulate well known in the prior art or other optical indicators (optical lindicator), adopt magnetic particle to have many advantages, and oriented flow can improve the test of these types.These comprise, for the quantitative linearity that exists the magnetic of amount of magnetic material of (reaching at least 4 orders of magnitude) to detect at wide region.Because magnetic particle is stable, time stability is also better, therefore allows that opened (developed) measured to thing and saves, and retest where necessary.In addition, magnetic particle is inertia to biosystem and environment conventionally.Therefore they not only can keep stable, and are also safe to environment and biology.Have, magnetic particle is widely used in diagnostics industry with other technologies again, and therefore they are easy to obtain.Other advantage of magnetic detection is that, because particulate is superparamagnetism, they only just have magnetic when being exposed to magnetic field.This allows them in solution, arbitrarily operated and do not condense.

Compared with optically read lateral flow devices of the prior art, another remarkable advantage is, adopts the utility model, and the total amount of the analyte in the trapping region of test-strips records as single quality in a volumetric measurement.It is all measured that the permeability in magnetic field can make to be included in any analyte in detecting device active region.Itself and optical sensing technology are completely different, in optical sensing technology, only on the surface of test-strips or the report thing (reporter) very contiguous with it-analyte interact and just can be detected.10 microns is can expect to send signal and expection measures the bounding depth of this signal.Common analyzing film thickness is 200 microns, and therefore optically read determination method only can detect 5% the signal being produced by colored particle or fluorescent particles.In the utility model, magnetic signal intensity directly increases along with the quality of comprised iron, with irrelevant to the degree of closeness on test-strips surface.This intrinsic linear relationship of magnetic detection contributes to increase sensitivity, accuracy and dynamics range.In addition, superparamagnetic particulate is physically similar to collaurum dimensionally, and may be easy to be applicable to the flow measurement mensuration of wide region.It should be noted, collaurum and fluorescent latex particulate, be applied in the optical sensing immunoassay of prior art conventionally, and as previously mentioned, pattern herein can greatly be improved these analytic approachs.

In most of lateral flow devices, in one end of perforated membrane, be Sample introduction district conventionally.This district consists of sample pad and pad routinely.In the prior art, pad is the source of the coloured particulate that can move freely aurosol, latex bead and the fluorescent particle of collaurum (normally from).In various embodiments of the present utility model, there is no sample pad or pad.These movably particulate be superparamagnetic particulate, the target analytes that its mark is imported into by fluid passage by sample.Here in a preferred embodiment, this sample mixes with superparamagnetic particulate before being applied to this device or meanwhile.This design brings several functions advantage.For example, the reaction kinetics of particulate in solution guaranteed that reaction velocity is faster, provides more completely and cultivated, and proceeded to.By contrast, when reaction is carried out forward with fluctuation form on perforated membrane, reaction trends towards slower, and existence can not reach as early as possible reaction end or can not reach the possibility of reaction end at all.

Together with the magnetic particle label and target analytes of sample and combination, by capillary action, along perforated membrane, move, and be hunted down in the precalculated position that is called trapping region or capture zone.Can there is more than one capture zone to can make to be multiplexed into into possibility.As used herein, term " multiplexed " refers to carry out the test more than the analyte of a type in same test-strips simultaneously.Excessive analyte and carrier fluid continue to be advanced through capture zone, to the other end of perforated membrane, sometimes form the control line separating with capture zone or control band.Another feature is, conventionally wicking pad (wicking pad) is mounted to the far-end at perforated membrane, with by driving the film that flows through whole length from the introducing of perforated membrane one end to strengthen capillary action.

Here, not using in the embodiment of optical detection, the end face of perforated membrane can be coated with another nontransparent protection thin slice or film.It can be completely opaque.On this, thin slice also may comprise preprinted standard, and when it makes to detect for alignment purpose at every turn, magnetic detector is all calibrated to guarantee entirely accurate.This protection thin slice can not be independent element in many cases, and can just after suitable processing, play the upper surface of the film of screening glass or protection surface action.

Disease is the unusual condition that affects biosome.Illness is the functional abnormal or disorderly of biosome inside.The hormone abnormality of internal system, or for example ovulation prediction thing, can be monitored.Validity and effect be measured and be evaluated to the therapy that relates to medicine interventional therapy need to by the level of evaluating drug labelling thing or metabolin.The example of these diseases comprises: cancer, endocrine disease, skin disease, illness in eye, enteron aisle disease, infectious disease, the human diseases relevant to infectious pathogen, the Ji Bing – (disease that should report to public health official) that must report, cardiovascular disease etc.

Except above-mentioned application, oriented flow determinator of the present utility model also can be used in the quantitative and qualitative analysis mensuration in following field:

-industry/operation

-military affairs/chemical, biological defense

-consumer diagnosis

-plant and animal health

-blood bank

-treatment monitoring

-environment

The test of-food security

This oriented flow diagnostic device and method can be used any fluid or material, comprise whole blood and component thereof, blood plasma and serum and but be not limited to: swab, ight soil in the mucomembranous surface of phlegm, saliva, seminal fluid, urine, cerebrospinal fluid (CSF), exchange, nose emission, nasopharynx aspirate, wound emission, cervix.

This oriented flow determinator is the new model of point of care (POC) application " Fast Measurement ", needs little or limited user's input, but is to provide superior sensitivity and the coefficient of variation (CV); And provide quantitative clinical data simultaneously.Hold and MICT from MagnaBioSciences ^tMthe disposable plastic casket of the oriented flow device of readout instrument combination provides that floor area is little, minimal maintenance and POC set sane cheap system.

Described oriented flow device is significantly different from whole other lateral flow devices in method for optimizing, the report thing that is not only predictive analysis thing is paramagnetic colloid, preferred size is between 100 and 300 nanometers, also be that sample and bond are marked to tubule mixes and with after through major path, import capillary-pipe film, described major path biased sample and bond are assembled and the mark sample being obtained are uniformly distributed to analyzing film to prevent magnetic bond/sample fluid.This test is called two step determination methods, because different from most of lateral flow devices, this bond is separation with test-strips.Because there is not sample pad or bond pad, thus many problems of standard lateral flow devices eliminated, and reduced the cost of these materials when determination method is set up.

Sample is above carried out to chromatography by the kapillary of film at analyzing film (being generally cellulose nitrate (NC)).Flow and the speed of the sample stream that kapillary control vertically moves along NC bar.On analysis bar, be capture antibody or antigen in column, wherein well known, described capture antibody or antigen are stripped on NC film with 90 degree with respect to expection stream in advance.Their form the trapping region of sample analytes and the magnetic mark thing that connects thereof.The width of these trapping regions is the 1mm order of magnitude, but extends to opposite side and vertically extend through this film from analyzing a side of bar.Can read magnetic signal at the whole internal volume of analysis area (from top to the thickness of the film of bottom with 2mm × 2mm area).

This oriented flow determination method use 100 microlitres pure or dilution sample fluid.After mixing with the bond of freeze-drying and sample fluid, fluid is applied to the input port of this device in tubule.Within 15 to 30 minutes consuming time, to launch, this depends on types of analytes and viscosity in this test.In MICT instrument reading result consuming time be approximately 20 seconds, this comprises that bar code identifies and the calculating of result.Quantitative result is presented on touch-screen and prints.

Accompanying drawing explanation

After the description related to the preferred embodiment of considering below in conjunction with accompanying drawing, these and other aspects of the present utility model, feature and advantage will become more obvious, in the accompanying drawings, and the parts of same Reference numeral TYP, in figure:

Fig. 1 is according to the decomposition diagram of oriented flow determinator of the present utility model;

Fig. 2 is the side sectional view of the test-strips of assembling in Fig. 1;

Fig. 3 is the skeleton view of the lower casing portion of Fig. 1 device;

Fig. 4 is the skeleton view of the inside of the upper housing department of Fig. 1 device; And

Fig. 5 is the skeleton view of completed assembled device of the present utility model.

Embodiment

Referring to accompanying drawing, preferred implementation of the present utility model is described, accompanying drawing forms a part of the present utility model, and it shows embodiment of the present utility model by way of example.Those of ordinary skill in the art should be understood that in the situation that not departing from the utility model scope, can adopt other embodiment, and can construct and program on change.

Referring now to Fig. 1 to 5, according to oriented flow determinator 10 of the present utility model, comprise immunoassay test-strips 12, its have contiguous layer structure 11 and with its porous analyzing film 14 of parallel installation substantially.Bonding coat 13 (Fig. 2) is fixed to layer structure 11 by analyzing film 14.This analyzing film has first end and the second end.

Superparamagnetic particulate (not shown) may be present in the sample preparation of this device outside.These particulates are provided for being combined with these target analytes in this sample.This film has the trapping region between a first end between this analyzing film and the second end.This trapping region has conventionally to be controlled and detection zone 28, as shown in Figure 1.This trapping region is provided for catching the analyte of the mark moving to its second end from the first end of this analyzing film.If needed, can there are other regions, for example, for calibration.For example, see the corrector strip 25 (Fig. 1 and Fig. 2) on diaphragm 24.This can be round dot equally, for example the round dot 27 in Fig. 5.As shown in Figure 2, it can be line or point.

An aspect of the present utility model is in one end of test-strips 12, to have sample reception port 30 for introducing the sample that will analyze.In existing apparatus, sample reception port is all almost to be formed by the housing of this device conventionally.In the utility model, sample reception port is usually located in test-strips, and is formed or formed by multiple coating material.

This sample reception port consists of the fluid encapsulation material 15 in bottom, and it is for soft polyethylene material and be positioned at layer structure top, and when plastics casket is closed, it provides sealing for determinator.Sealing is positioned at the bottom of upper outside shell.When plastics casket according to assembling mode of the present utility model in layer structure after closure, sample reception port bottom seals around opening.In addition, be present in thrust or " tooth " shape thing in sample reception port bottom, be pressed into the described polyethylene layer that sealing is finally provided.Fluid encapsulation material 15 is preferably hydrophilic.Layer 18 is arranged on fluid encapsulation material and layer 18 is formed with passage 16 and opening 19.Passage 16 is extending longitudinally along this test-strips, fluid is guided into the trapping region of this device.Conventionally this channels configuration becomes to have enough size and dimensions, and to allow sufficient liquid flow, and can there is not liquid, leak out from the side or there will not be and stop up or caking, otherwise, for the sample of viscosity more, may there is this situation as blood.Although Fig. 1 shows the passage 16 slightly narrower than opening 19,, also can consider here passage 16 with opening 19 with wide or even wider than opening 19.Alternatively, passage 16 can have the wider opening of width than its contiguous this sample reception port at the far-end of sample reception port.In the situation that needs consider that sample solidifies or lumps, this variant may be particularly useful.

Once after multilayer form assembling, this sample reception port has just formed.This port provides with the fluid of this passage and is communicated with, and this passage provides with the fluid of this analyzing film and is communicated with.Next water wetted material 20 is positioned on layer 18, and this water wetted material has the opening corresponding with opening 19, but covers passage 16.Shim elements 22 is positioned on water wetted material 20 and wherein has the opening corresponding with opening 19, to allow fluid to enter this port.This pad provides measures thing and any Fluid Sealing between housing around.

In the various embodiments of describing in the text, this housing is comprised of the lower casing portion 8 that supports layer structure 11.As shown in Figure 3, it also preferably has side butterfly sheet 6 for being appropriately placed on magnetic reader device.Lower casing portion 8 is usually designed to C shape, and open side is represented by Reference numeral 46.Fig. 4 shows the downside of housing department 42.It is conventionally in textural and lower casing portion complementation.Therefore, it is also C shape external form.Upper shell is contained in lower casing top and makes the opening 46 of test-strips 12 across C shape, as shown at the apparatus for assembling of Fig. 5.Therefore magnetic reader device can approach test-strips 12 from upper and lower surface simultaneously.Fig. 2 shows the side sectional view of the test-strips 12 of assembling.Wicking pad 26 is present in one end, and the diaphragm 24 of covering analyzing film 14.

Because test-strips 12 is across the opening 46 of assembled housing parts, and because it is arranged in the space of magnetic reader device, need to consider to allow this test-strips be fixed on rightly in this housing, to avoid the bending of test-strips or to move with respect to these two housing parts.The relative position that maintains control line, index line and result line is also very important.Therefore, embodiment of the present utility model comprises the clamping of these impacts and the factor of tensioning aspect controlled.

Refer again to Fig. 3, in the portion of lower casing shown in skeleton view 8.Although not shown in this Figure, test-strips 12 falls into groove 56.Preferably,, there is not in conjunction with or do not occur undesirable sideway movement in the width of the width adequate test-strips of this groove.Lateral trench 58 is present in the bottom of groove 56.Preferably at one end there are two such lateral trenchs of the layout of getting close to, and there is a lateral trench at the other end of groove.In addition, in one end of groove 46, have with domatic lateral trench 59.These grooves are designed to hold the character pair of upper housing department 42 downsides when assembling.Therefore, it is assembled into test-strips clamping and tensioning aspect is provided.

As shown in Figure 4, the downside of upper housing department 42 has multiple bolts 64, in one end of device, has two, and the other end has one.In the housing department of this device, preferably have strainer, this strainer is comprised of corresponding inclined-plane lateral trench 59 in the tensioning system 62 in upper housing department and lower casing portion.Tensioning system 62 is arranged on one end of this device and near single bolt 64 mentioned above.The tensioning system 62 illustrating has downward dip plane and crenation or carinate projecting edge.This edge contacts with test-strips, and the tension force of suitable degree is provided and does not cause the distortion of test-strips or tear.Design shown in this is only for example, and this tensioning system can have other equal effectively shapes.

The further feature of this device relates to avoids the movement of test-strips with respect to magnetic field.For example, lower casing portion 8 has fixed orifice 54, is used for receiving the fixed pin 65 on housing department 42.These are fixed together to avoid housing unit undesirable twisted or bending in assembled rear generation each parts than larger-diameter hole and pin.And as can be seen from Figure 3, the mounting hole 53 in lower casing portion is designed to receive the pin 67 in housing department.Pin in upper shell 67 has circular cross section, and the mating holes in lower casing has hexagonal cross-section 53, and when compressing, the two halves of housing weld together because of deformation and the cold flow of plastics.This has eliminated the bonding or ultrasonic soldering of any routine.

As mentioned above, Fig. 5 shows a kind of embodiment of the device of assembling completely.Show test-strips 12 across opening 46.The information that during barcode label area 47 on upper housing department 42 provides and measured, magnetic reader device is used, for example calibration and locating information.Also can provide about the character of fc-specific test FC or the information of sample aspect.

Should find out, although above, describe and relate generally to the quantitative detection of target analytes in oriented flow immunoassay, but the utility model can be equally for receptor determination, raji cell assay Raji or molecular assay.

Although in the above description the details aspect of many features of the present utility model and advantage and the utility model 26S Proteasome Structure and Function is described, but disclosed content is only exemplary, can in principle of the present utility model, carry out the variation in details, especially aspect the arrangement of shape, size and parts, the wide in range general sense of the term that the maximum magnitude of variation is explained by claims is represented.

Claims

1. for quantitatively detecting an oriented flow device for immunochromatography for sample target analytes, described device comprises:

2. device according to claim 1, further comprises the fluid encapsulation material between layered structure and described channel layer, and described fluid encapsulation material provides Fluid Sealing from bottom for described sample reception port.

3. device according to claim 1 and 2, wherein, described analyzing film has two or more trapping regions.

4. device according to claim 3, wherein, described passage has the open distal end of the relatively described trapping region wider than the width of its contiguous described opening.

5. device according to claim 4, is further included in the diaphragm that covers described analyzing film on the opposite side with respect to layered structure, and described diaphragm is transparent or opaque.

6. device according to claim 5, wherein, described diaphragm and described perforated membrane are integrally formed.

7. device according to claim 4, controls trapping region for one that is further included in described perforated membrane, for collecting the bond to show that test-strips has been used by described trapping region.

8. according to the device described in claim 5 or 6, further comprise at least one magnetic calibration area being imprinted on described diaphragm.

9. device according to claim 8, further comprise that the lower casing portion with opening is for supporting layered structure, with have and the upper housing department of the structure of lower casing portion complementation, to be arranged on, in described lower casing portion, make the opening of described determinator across described crust of the device portion.

10. device according to claim 9, wherein, described open construction becomes the opening of C shape.

11. according to the device described in claim 9 or 10, further comprises and is arranged in the upper housing department of described device and the strainer of lower casing.