CN1936540A - Assay test strip with two or more markers, and reading method therefor - Google Patents
Assay test strip with two or more markers, and reading method therefor Download PDFInfo
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- CN1936540A CN1936540A CN 200610006621 CN200610006621A CN1936540A CN 1936540 A CN1936540 A CN 1936540A CN 200610006621 CN200610006621 CN 200610006621 CN 200610006621 A CN200610006621 A CN 200610006621A CN 1936540 A CN1936540 A CN 1936540A
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Abstract
In one aspect, the test strip has a test marker that especially binds to a target analyte and a monitoring marker that is free from a specific absorption affinity for a target analyte and exhibits different optical characteristics from the test marker. In the other aspect, the test strip has a test marker that especially binds to a target analyte and a unspecific bonding marker that is free from a specific absorption affinity for at least a target analyte. A system and method are described for reading the test strip.
Description
The cross reference of related application
Under 35U.S.C § 120, the rights and interests of common pending application below this application requires, these applications are incorporated herein by reference: the U.S. Patent application N0.11/112 that is entitled as " LATERAL FLOW ASSAY SYSTEMS AND METHODS " that is equaled submission on April 22nd, 2005 by Patrick T.Petruno, 807, equal the U.S. Patent application No.10/816 that is entitled as " OPTOELECTRONIC RAPID DIAGNOSTIC TESTSYSTEM " of submission on April 1st, 2004 by Patrick T.Petruno, 636, and equal the U.S. Patent application N0.11/044 that is entitled as " OPTOELECTRONIC RAPIDDIAGNOSTIC TEST SYSTEM " that submitted on January 26th, 2005,394 by Patrick T.Petruno.
This application also relates to Patrick T.Petruno and equals _ _ _ the U.S. Patent application No___[procurator file NO.10041360-1 that is entitled as " ASSAYTEST STRIPS AND READING SAME " that day submits to].
Background technology
The lateral flow assay test instrument is current can be widely used for testing multiple medical science and environmental baseline or compound, for example hormone, metabolic product, toxin or the cause of disease antigen of deriving.Fig. 1 shows a typical cross flow test piece (test strip) 10, and it comprises sample reception band 12 on the common substrate 22, indicia band 14, detect and be with 15 and absorption band 20.These bands 12-20 is generally made by such material (for example chemically treated nitrocellulose), and wherein this material allows to make fluid flow to absorption band 22 from sample reception band 12 by capillarity.Detection is with 15 to comprise pilot region 16 and control area 18, and pilot region 16 is used for the existence of target analytes in the test fluid sample, and control area 18 is used to refer to finishing of analytical test.
Fig. 2 A and 2B show the analysis by the exemplary realization of test piece 10.Fluid sample 24 (for example blood, urine or saliva) is applied to sample reception band 12.In the example shown in Fig. 2 A and the 2B, fluid sample 24 comprises target analytes 26 (being available molecule or the compound of analyzing by test piece 10).24 following currents of capillarity draw fluid sample are to indicia band 14, and this indicia band comprises the material 28 that is used for indirect labelling target analytes 26.In described example, mark substance 28 is made up of the immunoglobulin (Ig) 30 with reflection grain 32 (for example collaurum or silver-colored particle).The target analysis complex that immunoglobulin (Ig) 30 special combining target analytes 26 are labeled with formation.In some of the other embodiments, mark substance 28 is compounds of NIg mark, and the special combining target analyte 26 of this compound is to form the target analytes complex of mark.
The target analytes complex of mark and superfluous mark substance, transversely flow path is transported to pilot region 16, and this pilot region comprises the fixing compound 34 of combining target analyte 26 specially.In described example, fixing compound 34 is immunoglobulin (Ig)s of the analyte complex of special incorporation of markings, thus the target analytes complex of retention marker in pilot region 16.The existence of labelled analyte is generally proved by the observable variable color of the vision of pilot region 16 in the sample, and this variable color is the result of mark substance accumulation in the pilot region 16.
Control area 18 generally is designed to the indication analysis and is finished.Compound 35 combinations and retention marker material 28 in the control area 18.Behind accumulation capacity mark substance 28, as seen mark substance 28 generally becomes in control area 18.When in sample, not having target analytes 26, pilot region 16 nondiscolourings, and control area 18 is performed variable color with the indication analysis.Absorption band 20 is caught superfluous fluid sample 24.
In the lateral flow assay test piece design of the non-competing type shown in Fig. 2 A and the 2B, the increase of the concentration of analyte causes the increase of label concentration in the pilot region in the sample.In contrast, in the lateral flow assay test piece design of type of competition, the increase of analyte concentration causes the reduction of label concentration in the pilot region in the fluid sample.
Although the visual detection of the lateral flow assay device of the above-mentioned type can provide analysis result qualitatively, the method that reads this kind equipment can not provide quantitative analysis to measure, therefore is easy to occur the analysis result mistake.Researched and developed automated and semi-automatic lateral flow assay reader to overcome this defective.
Lateral flow assay test piece that required is and the system and method that reads this test piece are so that the detection of different capture regions improves, makes analytical test speed to improve and analysis to measure sensitivity is improved in the test piece.
Summary of the invention
On the one hand, the invention provides a kind of analysis test piece, the sample reception band that it comprises the flow path that is used for fluid sample and is coupled to this flow path.This analysis test piece comprises test mark and control mark in addition, the special combining target analyte of test mark, control mark to target analytes without any special affinity and have the optical properties that is different from test mark.Detect band and be coupled to the flow path in sample reception band downstream, and comprise the fixation test reagent and the special fixedly control reagent of special combining target analyte in conjunction with control mark.
On the other hand, the invention provides a kind of analysis test piece, it comprises the flow path that is used for fluid sample, the sample reception band that is coupled to this flow path and the detection band that is coupled to this sample reception band downstream flow path.This analysis test piece comprises the test mark of special combining target analyte in addition and at least one is to the non-special combination mark of target analytes without any special combination affinity.Detect first fixating reagent and special second fixating reagent in conjunction with test mark that band comprises special combining target analyte, wherein each non-special combination mark does not have any special combination affinity to any fixating reagent that detects in the band.
On the other hand, the invention provides a kind of diagnose testing system of analyzing test piece and reader that comprises.This analysis test piece comprises the flow path that detects band and cross over the fluid sample that detects band along the cross flow direction.This detection band comprises a capture region, and this capture region is by first size that crosses the cross flow direction and second characterization of size that is parallel to the cross flow direction.Reader comprises an illuminator, is used for focused beam to a zone detecting band, and this detection band has at least one surface size, and its maximum equals the first size of capture region and the minimum value of second size.
The present invention also provides a kind of diagnostic testing process, according to this method receiving and analyzing test piece.The lateral flow assay test piece comprises detecting is with and crosses over the flow path that be used for fluid sample of detection band along the cross flow direction.Detect band and comprise a capture region, it is by first size that crosses the cross flow direction and second characterization of size that is parallel to the cross flow direction.Light beam focuses on one or more zones of detecting band, and this detection band has at least one surface size, and its maximum equals the minimum value of first and second sizes of capture region.Luminous intensity measurement can obtain from the field of illumination of detecting band.
On the other hand, the invention provides a kind of diagnostic test system that comprises reader and data-analyzing machine.Reader is used for obtaining luminous intensity measurement from the exposure area that comprises the analysis test piece that detects band.Data-analyzing machine is used for carrying out following operation, comprising: confirmed test measured value from the luminous intensity measurement that test mark obtains, regional a combination of this test mark and the detection band that comprises first fixating reagent; Determine compensation measurement from the luminous intensity measurement that the compensation mark that is different from test mark obtains, this test mark is arranged in one or more zones of detecting band, and it is unspecial in compensation label fixed reagent that this detects band; And from test measurements and compensation measurement, determine a parameter value.
The present invention also provides a kind of diagnostic testing process, obtains from the exposure area that comprises the analysis test piece that detects band according to this method luminous intensity measurement.Test measurements is determined from the luminous intensity measurement that a zone of the test tape that comprises the test mark that combines with first fixating reagent obtains.Compensation measurement determines that this test mark is in not to be had in special one or more zones in conjunction with the detection band that compensates label fixed reagent from the luminous intensity measurement that the compensation mark that is different from test mark obtains.Can determine a parameter value from test measurements and compensation measurement.
Description of drawings
Fig. 1 is the synoptic diagram of the prior art of lateral flow assay test piece.
Fig. 2 A is the synoptic diagram of fluid sample that is applied to the sample reception band of the horizontal analysis test piece shown in Fig. 1.
Fig. 2 B is that fluid sample has passed the synoptic diagram that test piece flow to the lateral flow assay test piece shown in Fig. 2 A after the absorption band.
Fig. 3 is the block diagram that is loaded into the test piece among the embodiment of diagnostic test system.
Fig. 4 is the process flow diagram of an embodiment of diagnostic testing process.
Fig. 5 A is the schematic top view of an embodiment of test piece, and this test piece comprises the discoid test and the control capture region of separation.
Fig. 5 B is the schematic top view of an embodiment of test piece, and this test piece comprises the test and control capture region of three combinations, and each capture region has flat oval shape shape.
Fig. 6 is the schematic top view of an embodiment of test piece, and this test piece comprises a capture region, and this zone has test reagent subregion and control reagent subregion, and they and indicia band are equidistant.
Fig. 7 A is the synoptic diagram of an embodiment of the system of diagnostic test shown in Fig. 3, and this system comprises that focused beam arrives the illuminator of capture region and obtains the linear light detector array of luminous intensity measurement from test piece zone.
Fig. 7 B is the graphical representation of exemplary of total light intensity of the linear light detector array acquisition shown in Fig. 7 A as the function of time.
Fig. 8 is the schematic top view of a kind of embodiment of the diagnostic test system shown in Fig. 3, and this diagnostic test system is included in the light source of scanning light beam on the test piece zone.
Fig. 9 shows the schematic side elevational view of an embodiment of diagnostic test system shown in Figure 3.
Figure 10 shows the synoptic diagram of a kind of embodiment of diagnostic test system shown in Figure 3, and this diagnostic test system comprises first and second imaging devices, and they directly are placed on respectively on first and second capture regions of test piece.
Figure 11 shows the schematic side elevational view of a kind of embodiment of diagnostic test system shown in Figure 3, obtains to measure from test piece shown in Figure 6.
Figure 12 A shows the schematic top view of an embodiment of the test piece with indicia band, and this indicia band comprises test mark and non-special combination mark.
Figure 12 B is the schematic top view of embodiment after fluid sample has been flowed through this test piece of the test piece shown in Figure 12 A.
Figure 13 show a kind of can be by the process flow diagram of the embodiment of the performed method of embodiment of data-analyzing machine shown in Figure 3.
Embodiment
In the following description, similar Reference numeral is used to refer to similar element.And accompanying drawing is intended to the principal character of illustrated example embodiment in a schematic way.Accompanying drawing is not inclined to the relative size that each feature of describing practical embodiments also is not inclined to element shown in the description, and these sizes are not drawn in proportion.
I. introduce
The embodiment that describes in detail below provides lateral flow assay test piece that comprises a plurality of marks and the system and method that reads this test piece, and they make in the test piece detection of different capture regions improve, make analytical test speed to improve and analysis to measure sensitivity is improved.
Term " lateral flow assay test piece " comprises the lateral flow assay test piece of competition and non-competing type.The lateral flow assay test piece generally comprises the sample reception band and detects band, can have indicia band, also can not have indicia band.In some embodiments, the lateral flow assay test piece comprises the sample reception band that vertically is positioned on the indicia band, comprises the detection band that laterally is positioned at the indicia band downstream in addition.
Term " analyte " refers to the material that can be analyzed by this test piece.The example of dissimilar analytes includes organic compounds (for example protein and amino acid), hormone, metabolin, antibody, cause of disease derive antigen, medicine, toxin and microorganism (for example bacterium and virus).
Term used herein " mark " refers to material that analyte is had special affinity and has the characteristics of the detectable feature that can distinguish from other element of test piece.This mark can comprise the combination of mark substance and detecting material, and wherein mark substance (for example, the particle that fluoresces, for example quantum dot) provides detectable characteristic feature, and detecting material (for example immunoglobulin (Ig)) provides the special combination affinity to analyte.In some embodiments, mark has different optical properties, and for example luminous (for example fluorescing) or reflecting attribute, these optical properties allow to comprise the zone of the not test piece of isolabeling and distinguish mutually.
Term " reagent " refers to take place with target substance (for example mark or analyte) material of chemistry or biological respinse.
Term " capture region " refers to comprise a zone in the test piece of one or more fixating reagents.
Term " pilot region " refers to comprise the capture region that analyte is had the fixating reagent of special combination affinity.
Term " control area " refers to comprise the capture region that mark is had the fixating reagent of special combination affinity.
The general structure of II diagnostic test system
Fig. 3 shows an embodiment of diagnostic test system 40, and it comprises shell 42, reader 44, data-analyzing machine 46 and storer 47.Shell 42 comprises the port 48 that is used to receive test piece 50.When test piece 50 was placed on port 48 places, reader 44 obtained luminous intensity measurement from test piece 50.Generally speaking, luminous intensity measurement can not filter, or they filter in the mode of at least a wavelength and polarization.Data-analyzing machine 46 calculates at least one parameter from one or more luminous intensity measurements.Result indicator 52 provides the indication of the analysis result of one or more test pieces 50.In some embodiments, diagnostic test system 40 makes it can be used for any application of freely using or the application of single-use by relatively cheap parts preparation.
Shell 42 can be made by in the multiple material (comprising plastics and metal) any one.Shell 42 forms the protection periphery of other parts of reader 44, data-analyzing machine 46, power supply 54 and diagnostic analysis system 40.Shell 42 has also defined a container, and it mechanically deposits test piece 50 with respect to reader 44.This container can be designed to receive any one (comprising the test piece of type shown in Figure 1) of number of different types test piece 50.
In described embodiment, each test piece 50 is lateral flow assay test pieces of non-type of competition, it supports the transversely cross flow of flow direction 51 of fluid sample, and comprise indicia band and detect band, this indicia band comprises the mark substance that mark is attached to target analytes, detect band and comprise at least one pilot region, this pilot region comprises the fixed substance of combining target analyte.The one or more zones that comprise the detection band of test piece at least a portion are exposed to be used for the optical detection of reader 44.The exposed portion that detects band can be covered by the optical clear window, also can not covered by the optical clear window.
In other embodiments, test piece is the lateral flow assay test piece of type of competition, and wherein, the concentration of the mark of pilot region reduces along with the increasing of concentration of target analytes in the fluid sample.Some embodiment among these embodiment comprise indicia band, and other embodiments do not comprise indicia band.
Some embodiment among these state of conflict lateral flow assay test pieces embodiment comprise indicia band and pilot region, this indicia band comprises special mark in conjunction with target analytes in the fluid sample, pilot region comprises fixing target analytes, and this fixing target analytes is with special relative in conjunction with any non-binding label fixed test reagent (for example antibody) in the fluid sample.In operation, pilot region will be labeled when not having analyte to exist in the fluid sample.Yet, if target analytes exists in fluid sample, before mark flow to pilot region, the binding site of mark in the fluid sample analysis thing saturation flags band.Therefore, when marked flows overtesting zone, there is not binding site to be retained on the mark, so mark process and pilot region keep not being labeled.
In other state of conflict lateral flow assay test piece embodiment, indicia band only comprises preliminary making analyte (for example, the gold that combines with analyte), and pilot region comprises the fixation test reagent that analyte is had affinity.In these embodiments, if fluid sample comprises the concentration of the preliminary making analyte in the concentration greater than flag band of unlabelled analyte, then the label concentration of pilot region is with proportional minimizing.
Reader 44 comprises one or more optoelectronic components, is used for the exposure area of the detection band of optical detection test piece 50.In some embodiments, reader 44 comprises at least one light source and at least one photodetector.In some embodiments, light source can comprise semiconductor light-emitting-diode, and photodetector can comprise semiconductor photo diode.Depend on the attribute of the mark of test piece 50 uses, light source can be designed to launch the light of wavelength in the particular range of wavelengths or the light of particular polarization form.For example, if mark is a fluorescence labeling, quantum dot for example, light source will be designed so that to shine with the light in the wavelength coverage form of exposure area of the detection band of test piece 50, and the light guiding in this wavelength coverage is from the fluorescent emission of mark.Similarly, photodetector can be designed to optionally catch the form from the light of the exposure area of detecting band.For example, if mark is a fluorescence labeling, photodetector will be designed to the light in the capture of labels emitted fluorescence wavelength coverage optionally or have the form of the light of specific polarization.On the other hand, if mark is the mark of reflection type, photodetector will be designed to the form that selectivity is caught the light in the optical wavelength range of light emitted.For realizing these purposes, photodetector can comprise one or more light filters, and these light filters have defined capturing optical wavelength coverage or polarization axle.
Data-analyzing machine 46 is handled the luminous intensity measurement that is obtained by reader 44.Generally speaking, data-analyzing machine 46 can be carried out under any calculating or processing environment, is included in Fundamental Digital Circuit or carries out in computer hardware, firmware or software.In certain embodiments, data-analyzing machine 46 comprises processor (for example microcontroller, microprocessor or ASIC) and analogue-to-digital converters.In an illustrated embodiment, data-analyzing machine 46 is included in the shell 42 of diagnostic test system 40.Among other embodiment, data-analyzing machine 46 is arranged in for example computing machine of separation equipment, and this data-analyzing machine 46 can be connected communication by wired or wireless with diagnostic test system 40.
Generally speaking, result indicator 52 can comprise any of multiple different mechanisms, in order to indicate one or more analytical test results.In some embodiments, for example result indicator 52 comprises one or more light sources (for example light emitting diode), and they are activated to indicate finish (promptly working as capacity mark substance 28 accumulates) of positive test findings and analytical test in the control area.In other embodiments, result indicator 52 comprises that aplhanumeric visual display (for example two or three character light emitting diode matrixs) is used for the display analysis test findings.
Power supply 54 provides power to the active parts of diagnostic test system 40, comprises reader 44, data-analyzing machine 46 and result indicator 52.For example power supply 54 can be implemented by replaceable battery or rechargeable battery.In other embodiments, the diagnostic test system can be by outside main equipment (for example computing machine that links to each other by USB cable) power supply.
Fig. 4 shows a kind of embodiment of diagnostic testing process, and this method can be carried out by diagnostic test system 40, and is as described below.According to this method, when test piece 50 was placed in the port 48 of diagnostic test system 40, reader 44 obtained separable local luminous intensity measurement (square frame 60) from the zone of the exposure region of the detection band of test piece 50.Term used herein " separable local luminous intensity measurement " refers to that reader 44 is to allow the mode of data-analyzing machine 46 each luminous intensity measurement of independent analysis, from each regional area transmission of test piece or the ability of record luminous intensity measurement.
In this embodiment, the feature of each separable regional area (can obtain luminous intensity measurements by reader 44 by them) is characterized by at least one surface size less than the size of the exposure region of the detection band that crosses the cross flow direction.In some embodiments, each regional area all has a surface size, and it is approximately equal to or less than the minimum dimension that detects interesting areas (for example zone of pilot region, control area or fixation mark or unlabelled complex) in the band greatly.
Reader 44 is realized (square frame 60) after the luminous intensity measurement, luminous intensity measurement (square frame 62) that obtains from interesting areas of data-analyzing machine 46 identifications in these interested regional areas from detect band.In this process, data-analyzing machine 46 will be isolated with the measurement corresponding to area-of-interest corresponding to the measurement in other zone of test piece 50.With comprise area-of-interest outside the overall measurement of measurement in zone compare, the measurement of isolation has higher signal to noise ratio (S/N ratio).
Data-analyzing machine 46 calculates at least one parameter (square frame 64) from the luminous intensity measurement of an identification.Exemplary parameter comprises peak strength and total intensity value.Have higher signal to noise ratio (S/N ratio) because be used to calculate the measurement of these parameters, they are characterised in that interesting areas has higher accuracy, has improved the result of lateral flow assay thus.
III. the test piece and the read method thereof that have different tests and control mark
The embodiment that this part is described provides the lateral flow assay that comprises different tests and control mark test piece, and the system and method that reads these test pieces.The use of different tests and control mark makes test piece and diagnostic test system design with the detection degree that improves test and control signal, the mode improving analytical test speed and improve analysis to measure sensitivity.
A. the test piece that has different tests and control mark
Among these embodiment, indicia band 14 comprises test mark and the test badge that is used for each analyte to be analyzed.Usually, test mark has different separately detected characteristics or attribute with relevant control mark.In some embodiments, test mark fluoresces and control mark fluoresces at second characteristic wavelength that is different from first wavelengths characteristic at first characteristic wavelength.For example test mark can comprise the quantum dot of the first kind, and for example control mark can comprise the quantum dot of second type.In some embodiments, quantum dot is the semiconductor nanocrystal of nano-scale, and their fluorescence properties is by their size decision.Like this, the wavelength of fluorescence of quantum dot can be by changing the size adjustment of quantum dot.
Fixation test reagent combination in the tested measuring tape 15 of test mark, this reagent has special combination affinity to test mark.Fixedly control reagent combination in the tested measuring tape 15 of control mark, this reagent has special combination affinity to control mark.Different tests can be fixed on discrete capture region separately or be with 15 in identical test and the detection of controlling the test piece in the capture region with control mark.Usually, test and control area can be Any shape, comprise rectangle and non-rectangular shape.
For example, Fig. 5 A shows an embodiment of test piece 50, and this test piece has pilot region 70 and separation and different control areas 72, and pilot region 70 comprises fixation test reagent, and control area 72 comprises fixing control reagent.In the embodiment shown, each test and control area 70,72 have detection with the shape of discoid separately on the plane on 15 surfaces.This shape allows the reader 44 emissive lighting light beams of suitable configurations to the discoid zone of surveyed area 15, and this discoid zone corresponds essentially to test and control area 70,72 on size and dimension.Like this, can have higher signal to noise ratio (S/N ratio) level from the luminous intensity measurement of testing and control mark obtains, measure sensitivity and improve, analytes in low concentration error result probability reduces.
Fig. 5 B shows an exemplary embodiment of test piece 50, and it comprises the test and the control area 74,76,78 of three combinations.Each test comprises fixing separately test reagent and fixing separately control reagent with control area 74-78, and these reagent mix with 15 same area in detection.Each test reagent has special combination affinity for each target analytes that is labeled with 14 the special combination of each test mark, and each control reagent has special combination affinity for each control mark in the indicia band 14.In some embodiments, test mark and control mark among each capture region 74-78 fluoresce at the different characteristic wavelength, make their fluorescent emission can use wavelength separated technology (for example, diffractive optical device and light filter) to be distinguished.
Among the embodiment of the test piece shown in Fig. 5 B, each test has detection with the shape of flat oval separately (plano-elliptical) shape on the plane on 15 surfaces with control area 74-78.This shape allows the reader 44 emissive lighting light beams of suitable configurations to the flat oval shape zone of detecting with 15, and this zone corresponds essentially to test and control area 74-78 on size and dimension.Like this, the luminous intensity measurement from test and control mark acquisition can have higher signal to noise ratio (S/N ratio) level, measurement sensitivity raising, the error result probability minimizing of analytes in low concentration.
Fig. 6 shows an embodiment of test piece 50, and wherein test reagent and control immobilization of reagents are in the subregion separately 80,82 of test of making up and control area 84.Among the described embodiment, test reagent subregion 80 and control reagent subregion 82 and indicia band 14 equidistant (being DTBST=DCONTROL).Test reagent subregion 80 and control reagent subregion 82 are also equidistant with sample reception band 12.In this embodiment, in test and control before the result can determine, fluid sample only needs transversely the flow direction catch position of flowing through.Therefore, the analytical test speed of the embodiment that can be arranged in cross flow direction 51 diverse locations than the test that wherein separates and control area with respect to the analytical test speed of this test piece embodiment is fast.
B. different analyses and control mark throw light on
The light source that can make up and settle reader 44 with focus on or scanning light beam to a zone of the detection band of customization size and dimension, make to be easy to from detection with other zone differentiation of 15 from test and control mark reflection or fluorescigenic light.Among some embodiment, capture region (i.e. the test of test of Fen Liing and control area and combination and control area) can have non-rectangular shape, this allows to use relatively cheap optics to come projecting beam to the zone of detecting with 15, and this zone corresponds essentially to capture region on size and dimension.Like this, the resultant signal that is produced by the detection system of reader 44 is respectively greatly corresponding to capture region reflection or fluorescigenic light from illumination, therefore compare with the measurement of comparison that the illumination result in the basic corresponding zone of capture region shape of getting along well obtains, it has higher signal to noise ratio (S/N ratio).
Fig. 7 A shows embodiment of test piece 50 and of diagnostic test system 40
Embodiment.
Test piece comprises pilot region 90, and it separates and be different from control area 92 with control area 92.Pilot region 90 comprises the fixation test reagent of special combining target analyte, and control area 92 comprises label fixed control reagent, the wherein special combining target analyte of the mark in the indicia band 14 in the special incorporation of markings band 14.Each test and control capture region 90,92 are by the first size that crosses cross flow direction 51 (WT, WC) and be parallel to second size (LT, the LC) sign of cross flow direction 51.
In the embodiment that test and control mark can be for example distinguished by the different wave length of fluorescent emission, test and control area 90,92 can overlap.In these embodiments, a plurality of light filters or single tunable optical filter can be used for distinguishing the light from test and control mark reception.
During operation, when photodetector 104 moves with respect to test piece 50, the zone that light source 96 uses the exposed portion of light beam 106 irradiating and detecting bands 15.Irradiates light can be broadband or arrowband, can be polarization or unpolarized.Light source 96 is with on 15 to detection with definite shape focused beam 106, and this shape has the smaller of the characteristic dimension (WT, LT, WC, LC) that at least one surface size maximum equals to test and control capture region 90,92.In described embodiment, zone of light beam 106 irradiations, it corresponds essentially to each capture region on size and dimension.
Linear light detector array 98 from detection with obtaining separable local luminous intensity measurement the narrow part of 15 field of illumination.Usually, luminous intensity measurement can not filter, and perhaps they can filter in the mode of wavelength or polarization.Photodetector array 98 can be synchronous with light source 96.Usually, be with 15 illuminated or light sources 96 after the irradiating and detecting band 15 when detection, photodetector array 98 can be measured light intensity.Focus on each photodetector 100 of photodetector array 98 with 15 reflections or fluorescigenic smooth scioptics 102 from detection.Each photodetector 100 receives from the light of detection with each regional area of 15.That is each regional area that each detecting device 100 can resolved detection band 15 or make each regional area independence imaging.Photodetector 100 produces the signal of representative from the light quantity of each regional area reception.These signals are stored in the storer, and perhaps they can be transferred to data-analyzing machine 46 and handle.
When detection overlaps with one in 15 irradiation area and the capture region 90,92, the resultant signal that is produced by photodetector array 98 greatly reflects or fluorescigenic light corresponding to the capture region from illumination, therefore with from detection compare with 15 the big regional measurement of comparison that obtains, it has higher signal to noise ratio (S/N ratio).Test piece 50 can comprise position mark or comprise that the further feature that can be used by diagnostic test system 40 overlaps to determine when of detecting with in 15 field of illumination and the capture region 90,92.The description of the alignment characteristics of exemplary types can equal from PatrickT.Petruno _ _ _ the U.S. Patent application No.___[procurator file No.10041360-1 of " the LATERAL FLOW ASSAY TEST STRIPSAND READING SAME " by name that day submit to] acquisition.
Data-analyzing machine 46 (Fig. 3) is used for handling signal that each photodetector 100 of linear array 98 produces to discern a luminous intensity measurement that obtains from interesting areas (for example, pilot region 90 and control area 92).In some embodiments, detecting with 15 surface is basic homogeneous in the direction of crossing the cross flow direction.In these embodiments, can there be information loss ground to add up to substantially from the signal of the photodetector of linear array 98.
Fig. 7 B shows total luminous intensity measurement of being produced by linear light detector array 98 exemplary curve 108 as the function of time.In this example, in the time of on the photodetector in the array 98 100 is placed on pilot region 90 and control area 92, curve 108 comprises the total intensity 110,112 than hard intensity.According to this example, the threshold value by curve 108 is set is at intensity threshold level 114, and data-analyzing machine 46 can be discerned the luminous intensity measurement that obtains from pilot region 90 and control area 92.Being positioned at that luminous intensity measurement on the threshold level 114 is identified as is from pilot region 90 and control area 92.Extra information (for example obtaining the relative time of the luminous intensity measurement of an identification) can be used by data-analyzing machine 46, so that the luminous intensity measurement of identification is associated with pilot region 90 and control area 92.
Fig. 8 shows an embodiment of diagnostic test system 40, and this system comprises a light source 120, and it is used for passing detecting and comes scanning light beam 122 with 15 exposure area.Light source 120 is with on 15 to detection with definite shape focused beam 122, and this shape has characteristic dimension (WT, LT, WC, smaller value LC) that at least one surface size maximum equals to test and control capture region 90,92.Among the described embodiment, the surf zone that is thrown light on by light beam 122 has each characteristic dimension (WT, LT, WC, circular dimension LC) less than test and control area 90,92.Light beam 122 can be broadband or arrowband, can be polarization or unpolarized.
Usually, light source 120 can pass and detect with 15 exposure area along comprising any paths of pilot region 90 with control area 92 (comprising the direction of crossing the cross flow direction and the direction of parallel cross flow direction) scanning light beam 122.In described embodiment, light source 120 is along circuitous zig-zag path 124 scanning light beams 122 that cross over to detect with 15 exposure area.In some embodiments, light source 120 comprises optical transmitting set (for example light emitting diode or laser instrument), and one or more optics (for example one or more lens and rotating mirror) is used to be shaped or the light that scans emission to produce light beam 122.
In the embodiment shown in Fig. 8, use the unit piece or the multicomponent photodetector of any kind, diagnostic test system 40 can obtain separable local luminous intensity measurement, wherein photodetector has such visual field (field of view), this visual field comprises the path of cross over detecting with the light beam 122 of 15 exposure area, maybe follows the tracks of these zones when detecting when being shone by light beam 122 with 15 regional area this visual field.Luminous intensity measurement can not filter, or they filter with wavelength or polarization mode.Photodetector array can be synchronous with light source.Usually, illuminated or light source is after each separable regional area of irradiating and detecting band 15 with each separable regional area of 15 when detection, and photodetector array can be measured light intensity.Because only at the single regional area of a time irradiating and detecting band 15, the light that photodetector obtains is corresponding to regional area reflection or fluorescigenic light from irradiation for light beam 122.Therefore, each data point and each local zone association of the signal that is produced by photodetector have higher signal to noise ratio (S/N ratio) with comparing with the measurement of comparison of 15 big zone acquisition from detection.
Data-analyzing machine 46 (Fig. 3) can be handled the signal of photodetector generation to discern a luminous intensity measurement that obtains from interesting areas (for example pilot region 90 and control area 92).For example, in some embodiments, by giving the time dependent luminous intensity measurement signal sets threshold value that is produced by photodetector, data-analyzing machine 46 can be discerned from the luminous intensity measurement of pilot region 90 and control area 92 acquisitions.Being positioned at that luminous intensity measurement on the threshold level can be identified as is from pilot region 90 and control area 92.Extra information (for example obtaining the relative time of the luminous intensity measurement of an identification) can be used by data-analyzing machine 46, and the luminous intensity measurement of feasible identification and pilot region 90 and control area 92 are associated.
In the embodiment of the test piece 50 shown in Fig. 8, the position mark 126 of one group of regular spaces is placed along a limit of test piece 50.Position mark 126 comprises the feature that has with the surperficial different optical signature of test piece 50 (for example reflect or fluoresce).Therefore, near the measurement that obtains the edge of test piece 50 changes on intensity according to the shape of position mark 126.Like this, position mark is encoded along 50 pairs of positions of test piece in the cross flow direction.With each the Strength Changes cycle (for example peak value is to valley) the luminous intensity measurement of 15 edges acquisition, by the incremental positions counter, data-analyzing machine 46 can be determined the transversely coding site of flow direction from detection in use.In these embodiments, in data-analyzing machine 46 related luminous intensity measurements and the cross flow direction 51 along the position of test piece 50.Location association information can be stored in the question blank, and this is shown by location counter value index.Based on this information and predetermined information (this predetermined information makes the position of area-of-interest and the light intensity comparative pattern that produced by position mark 126 is associated), data-analyzing machine 46 can be discerned a luminous intensity measurement corresponding to area-of-interest.
C. detect light from different tests and control mark
In some embodiments, test mark fluoresces and control mark fluoresces at second characteristic wavelength that is different from first characteristic wavelength at first characteristic wavelength.The embodiment of reader 44 can comprise detection system, is used for mutually distinguishing from test and control mark reflection or fluorescigenic light and distinguishes detection with other regional light of 15.
Fig. 9 shows a kind of embodiment of reader 44, it can be used for separating from test mark and control mark emitted fluorescence, these tests and control mark be combined in the test that separates and the control area or combination (for example seeing Fig. 5 A) in identical test and control area (for example seeing Fig. 5 B and 6).Use photodetector array 160, reader 44 obtains separable local luminous intensity measurement, each detector element the 162, the 164th independently wherein, and diffracted lens 166 separate and the target of the special characteristic wavelength light handled.In the described example, different tests and control mark are fixed in the test and control area 168 of combination.The light 170 diffracted lens 166 of fixation test mark emission are manipulated to detector element 162, and are manipulated to detector element 164 from the fixing diffracted lens of light of control mark.In the embodiment depicted in fig. 9, the light filter that each detector element 162,164 additionally comprises separately, they have the narrow passband that preferably transmits respectively from the light of test and control mark.
In certain embodiments, reader 44 comprises first and second light filters, their light that first and second photodetectors (or first and second zones of the photodetector array of sharing) receive that is used for filtering.First light filter optionally transmits the light in first wavelength coverage.This first wavelength coverage comprises first characteristic wavelength but does not comprise second characteristic wavelength.Second light filter optionally transmits the light in second wavelength coverage, and this second wavelength coverage comprises second characteristic wavelength and do not comprise first characteristic wavelength.In some embodiments, first and second wavelength coverages correspond essentially to the main fluorescence emission spectrum of test and control mark.Like this, can reduce may be by noise element emission rather than that cause from the photoconduction that test and control mark are launched for first and second light filters.In some embodiments, light filter be polarization optionally to transmit from the polarized light of test and control mark reception.
According to this test piece embodiment, different tests and control mark are fixed on the discrete test and the control area of detecting with in 15 that separate.Test and control mark can be by the embodiment analyses of diagnostic test system 40, and wherein the position of detector member is associated with the position of test and control area, detect the test of test piece and the ability of control area with raising.
For example, Figure 10 shows an embodiment of test piece 50, and this test piece 50 comprises pilot region 90 and control area 92, and they comprise fixing test and control reagent respectively.Test and control reagent have special combination affinity to test in the indicia band 14 and control mark respectively.In some embodiments, test mark fluoresces at first characteristic wavelength, and control mark fluoresces at second characteristic wavelength that is different from first characteristic wavelength.For example test mark can comprise the quantum dot of the first kind, and for example control mark can comprise the quantum dot of second type.
Figure 10 also shows an embodiment of diagnostic test system 40, and this diagnostic test system comprises light source 180 and a pair of photodetector 182,184.Light source 180 can be realized that this diode produces the light beam of area-of-interest in the wide relatively irradiating and detecting band 15 by one or more light emitting diodes.Photodetector 182,184 can be realized by unit piece photodetector or multicomponent photodetector, when test piece 50 was loaded in the port 48 of diagnostic test system 40, these unit piece photodetectors or multicomponent photodetector directly were placed on pilot region 90 and the control area 92.Photodetector 182,184 comprises first and second light filters 186,188 respectively.First light filter 186 optionally transmits the light of first wavelength coverage, and this first wavelength coverage comprises first characteristic wavelength but do not comprise second characteristic wavelength.Second light filter 188 optionally transmits the light of second wavelength coverage, and this second wavelength coverage comprises second characteristic wavelength but do not comprise first characteristic wavelength.In some embodiments, first and second wavelength coverages correspond essentially to the main fluorescence emission spectrum of test and control mark.Like this, can reduce may be from the noise that light caused of element rather than test and control mark emission for light filter 186,188.In certain embodiments, light filter the 186, the 188th, polarization optionally to transmit the polarized light that receives from test and control mark.
When operation, light source 180 makes with light 190 exposure experiments zone 90 and control area 92.Irradiates light 190 can be broadband or arrowband, can be polarization or unpolarized.Photodetector 182,184 obtains separable local luminous intensity measurement from detection with 15 irradiation area.Photodetector 182,184 can be synchronous with light source 180.Usually, be with 15 illuminated or at light source 180 after the irradiating and detecting band 15, photodetector 182,184 can be measured light intensity when detection.92 reflections or fluorescigenic light are focused on photodetector 182,184 by lens 187,189 respectively from pilot region 90 and control area.Like this, photodetector 182,184 can be differentiated pilot region 90 and control area 92 or make pilot region 90 and control area 92 imagings respectively.Photodetector 182,184 produces the signal of representative from the light quantity of pilot region 90 and control area 92 receptions.If photodetector 182,184 is implemented by the unit piece detecting device, this signal representative is from the total quantity of the light of pilot region 90 or control area 92 receptions.If photodetector 182,184 is carried out by the multicomponent detecting device, this signal representative is from the quantity of the light of the regional area acquisition of pilot region 90 and control area 92.The signal that is produced by photodetector 182,184 can be stored in the storer or they can be transferred to data-analyzing machine 46 and handle.
In some embodiments, 92 reflections or fluorescigenic light preferably pass hole 192,194 transmission the aperture plate 196 from pilot region 90 and control area, and are stopped by aperture plate 196 substantially from other regional light of test piece 50.Therefore, the signal of photodetector 182,184 generations has higher signal to noise ratio (S/N ratio) with comparing with 15 the big regional measurement of comparison that obtains from detection.In addition, the light of photodetector 182,184 acquisitions corresponds essentially to respectively from pilot region 90 and control area 92 reflection or fluorescigenic light.Therefore, the signal that photodetector 182,184 produces is associated with pilot region 90 and control area 92 respectively, the luminous intensity measurement that data-analyzing machine 46 can Direct Recognition obtains from pilot region 90 and control area 92.That is, the luminous intensity measurement that photodetector 182 produces obtains from pilot region 90, and the luminous intensity measurement that photodetector 182 produces is 92 acquisitions from the control area.
Figure 11 shows a kind of embodiment of the diagnostic test system 40 that comprises illuminator 200, and this illuminator comprises first detecting device 202, second detecting device 204 and light source 206.Light source 200 can be implemented the interesting areas in these light beam 207 irradiating and detecting bands 15 by the one or more light emitting diodes that produce wide relatively light beam 207.Photodetector 202,204 can be realized by unit piece photodetector or multicomponent photodetector, when test piece 50 was loaded in the port 48 of diagnostic test system 40, these unit piece photodetectors or multicomponent photodetector directly were placed on test reagent subregion 80 and the control reagent subregion 82.Photodetector 202,204 comprises first and second light filters 208,210 respectively.First light filter 208 optionally transmits the light of first wavelength coverage, and this first wavelength coverage comprises first characteristic wavelength but do not comprise second characteristic wavelength.Second light filter 208 optionally transmits the light of second wavelength coverage, and this second wavelength coverage comprises second characteristic wavelength but do not comprise first characteristic wavelength.In some embodiments, first and second wavelength coverages correspond essentially to the main fluorescence emission spectrum of test and control mark.Like this, can reduce may be by the noise that light caused from element rather than test and control mark for light filter 208,210.In some embodiments, light filter the 208, the 210th, polarization optionally to transmit the polarized light that receives from test and control mark.
During operation, light source 200 usefulness light, 212 exposure experiment reagent subregions 80 and control reagent subregion 82.Irradiates light 207 can be broadband or arrowband, maybe can be polarization or unpolarized.Photodetector 202,204 obtains separable local luminous intensity measurement from detection with 15 irradiation area.Photodetector 202,204 can be synchronous with light source 200.Usually, be with 15 illuminated or at light source 200 after the irradiating and detecting band 15, photodetector 202,204 can be measured light intensity when detection.Focused on photodetector 202,204 by lens 214,216 respectively from test reagent subregion 80 and 82 reflections of control reagent subregion or fluorescigenic light.Like this, photodetector 202,204 can be differentiated test reagent subregion 80 and control reagent subregion 82 or make test reagent subregion 80 and 82 imagings respectively of control reagent subregion.Photodetector 202,204 produces the signal of representative from the quantity of the light of test reagent subregion 80 and 82 receptions of control reagent subregion.If photodetector 202,204 is implemented by the unit piece detecting device, then this signal representative is from the total quantity of the light of test reagent subregion 80 or 82 receptions of control reagent subregion.If photodetector 202,204 is implemented by the multicomponent detecting device, then this signal representative is from the quantity of the light of the regional area reception of test reagent subregion 80 and control reagent subregion 82.The signal that is produced by photodetector 202,204 can be stored in the storer or can be transferred to data-analyzing machine 46 to be handled.
IV. have the test piece of non-special combination mark and read this test piece
The embodiment of this part description provides the lateral flow assay that comprises one or more compensation marks test piece, and these one or more compensation marks are not therefrom compensated the special combination in zone of measurement.The compensation mark can non-exclusively be attached to detect with 15 catch or and non-capture region, perhaps it can be attached to specially detect with 15 some but be not Zone Full.These embodiment comprise the embodiment of diagnostic test system 40, this diagnostic test system is designed to the form of the influence of the non-special combination of compensation on parameter value, and these parameter values are to derive from the luminous intensity measurement of test and/or control mark from the basis of the luminous intensity measurement of compensation mark acquisition.These embodiment can implement with reference to the lateral flow assay test piece embodiment of competition or non-competing type.
Figure 12 A and 12B show an embodiment of test piece 50, and wherein indicia band 14 comprises test mark 230, control mark 232 and non-special combination compensation mark 234.Detection is with 15 to comprise pilot region 90 and control area 92, and pilot region 90 comprises the fixation test reagent of special combining target analyte, and control area 92 comprises special fixedly control reagent in conjunction with control mark.In some embodiments, the fluorescence of each mark 230-234 emission different characteristic wavelength.For example mark 230-234 can comprise dissimilar quantum dots.
Figure 12 A shows fluid sample and is applied to sample reception band 12 test piece 50 before.Figure 12 B show fluid sample (being applied to sample reception band 12) transversely the flow path in the flow direction 51 flow to the test piece 50 of absorption band 20 from sample reception band 12.In described example, the fluid sample that applies comprises target analytes, and this target analytes is by test mark and the special combination of test reagent.
Shown in Figure 12 B, although test mark 230 and control mark 232 all present non-special combination in detection in 15 non-capture region, mainly accumulation in pilot region 90 of test mark 230, mainly accumulation in control area 92 of control mark 232.On the other hand, because the non-special combination characteristic of non-special combination compensation mark, non-special combination compensation mark 234 is evenly distributed on to detect to be with on 15.
Usually, arbitrary embodiment of above-mentioned diagnostic test system can be used for obtaining luminous intensity measurement from the zones of different of the embodiment of test piece 50 (shown in Figure 12 B).In some embodiments, based on the luminous intensity measurement that obtains from non-special compensation mark 234, data-analyzing machine 46 (Fig. 3) compensation is to the influence of the non-special combination of the measurement of test in test and the control area 90,92 and control mark 230,232.
Figure 13 shows the process flow diagram of a kind of method embodiment, by the influence of this method data-analyzing machine 46 assessments to the non-special combination of the luminous intensity measurement that obtains from test mark.
According to this embodiment, data-analyzing machine 46 (Fig. 3) is the confirmed test measured value from the luminous intensity measurement that pilot region obtains, and this pilot region comprises the fixation test reagent (square frame 240) of special combining target analyte.In some embodiments, test measurements is corresponding to a statistical measurement (for example, peak strength value or average intensity value), and this statistical measurement is to calculate from the luminous intensity measurement that pilot region obtains.
Data-analyzing machine 46 can also be determined compensation measurement from detection with the luminous intensity measurement that obtains in the compensation mark one or more zones of 15, and it is unspecial in compensation label fixed reagent (square frame 242) that this detects band.
Usually, the compensation mark can be any mark that is not combined in specially in the zone of determining compensation measurement.For example, in some embodiments, the compensation mark can be non-special combination mark 234.In other embodiments, when determining on the basis of the luminous intensity measurement that compensating measure obtains in the zone (for example pilot region) in conjunction with the fixating reagent of control mark never specially, compensating mark can be control mark 232.In the compensation mark has the embodiment of the characteristic that is different from test mark and/or control mark or attribute the different wave length of fluorescent emission (for example by), determined in the luminous intensity measurement that compensating measure can obtain from test and/or control area.According to these embodiment, determine each compensating measure the luminous intensity measurement that data-analyzing machine 46 can obtain from the zone outside area-of-interest (for example test and control area) or the area-of-interest.Data-analyzing machine 46 can use these different compensating measures in determining the evaluate parameter value.
The statistical measurement (for example peak strength value or average intensity value) that these compensation measurement can be calculated corresponding to one or more zones of the detection band of fixating reagent never.In some embodiments, compensation measurement is determined from the luminous intensity measurement that the zone with the pilot region direct neighbor obtains.In other embodiments, compensation measurement is corresponding to an average intensity value, and this average intensity value is determined from crossing over to detect the luminous intensity measurement that obtains with 15 non-capture region.
Data-analyzing machine 46 (Fig. 3) is determined a parameter value (square frame 244) from test measurements and compensation measurement.For example this parameter value can be the relative populations of target analytes or the absolute quantity of target analytes.The relative populations of target analytes can be by relatively (for example poor or ratio operation) test measurements and compensation measurement are determined.Can determine the absolute quantity of target analytes, to revise test measurements and test measurements and correction chart of revising compared on the basis of compensation measurement, this correction chart is mapped to target analytes quantity with the test measurements of revising.Correction chart can be derived the luminous intensity measurement by one or more modification region acquisitions of data-analyzing machine 46 on being included in test piece.
In some embodiments, data-analyzing machine 46 (Fig. 3) can be determined an evaluate parameter value on the basis of test measurements of determining and the compensation measurement of determining.For example, this evaluate parameter can corresponding to indication analytical test result's value (for example, be/not, or just/negative).In some embodiments, data-analyzing machine 46 is with test measurements (M
T) and compensation measurement (M
C) ratio and threshold value (T1) compare to determine evaluate parameter value (EP1).For example
If (M
T)/(M
C)＞T1, EP1=1
Otherwise EP1=0
In another embodiment, data-analyzing machine 46 is with test measurements (M
T) and compensation measurement (M
C) difference and threshold value (T2) compare to determine evaluate parameter value (EP2).For example
If (M
T)-(M
C)＞T2, EP2=1,
Otherwise EP2=0
In certain embodiments, data-analyzing machine 46 (Fig. 3) can be determined two different analyte (A in the fluid sample on the basis of test measurements, B) relative populations, determined in the luminous intensity measurement that this test measurements obtains from each pilot region with fixation test reagent (for target analytes A, B has binding affinity separately).In these embodiments, relative populations (MR
A, MR
B) can be corresponding to by the compensation measurement (M that determines
C) test measurements (M that revises
A, M
B).For example,
MR
A＝M
A-M
C
MR
B＝M
B-M
C
In some embodiments, data-analyzing machine 46 (Fig. 3) is with the test measurements (M that revises
A-M
C, M
B-M
C) ratio and threshold value (T3) compare for example determining an evaluate parameter value (EP3),
If (M
A-M
C)/(M
B-M
C)＞T3, EP3=1
Otherwise, EP3=0.
V. conclusion
The foregoing description provides lateral flow assay test piece that comprises a plurality of marks and the system and method that reads this test piece, they make, and the detection of different capture regions improves in the test piece, analytical test speed improves, and analysis to measure sensitivity improves.
Other embodiment is in the scope of claims.
Claims (33)
1. analyze test piece for one kind, comprising:
The flow path that is used for fluid sample;
Be coupled to the sample reception band of flow path;
The test mark of special combining target analyte;
Control mark, to target analytes without any special combination affinity and have the optical characteristics that is different from test mark; And
Detect band, be coupled to the flow path in sample reception band downstream, described detection band comprises the fixation test reagent and the special fixedly control reagent in conjunction with control mark of special combining target analyte.
2. the described analysis test piece of claim 1, wherein test mark fluoresces at first characteristic wavelength, and control mark fluoresces at second characteristic wavelength that is different from first characteristic wavelength.
3. the described analysis test piece of claim 1 further comprises pilot region and control area, and pilot region comprises test reagent, and the control area comprises control reagent.
4. the described analysis test piece of claim 3, wherein the control area is positioned at the downstream of pilot region.
5. the described analysis test piece of claim 3, wherein control area and pilot region and sample reception band are equidistant.
6. the described analysis test piece of claim 1, wherein test mark comprises the quantum dot of the first kind, control mark comprises the quantum dot of second type.
7. the described analysis test piece of claim 1, wherein test reagent and control immobilization of reagents are in the test and the control area of the combination that detects band.
8. the described analysis test piece of claim 7, wherein test reagent and control reagent mix with the control area in test.
9. the described analysis test piece of claim 7, wherein test reagent and control reagent are arranged in the adjacent subarea territory that separates of testing with the control area.
10. the described analysis test piece of claim 7, wherein test has the flat oval shape with the control area.
11. the described analysis test piece of claim 1, wherein test has the discoid shape with the control area.
12. analyze test piece, comprising for one kind:
The flow path that is used for fluid sample;
Be coupled to the sample reception band of flow path;
The test mark of special combining target analyte;
At least one non-special combination mark, it to target analytes without any special combination affinity; And
Detect band, it is coupled to the flow path in sample reception band downstream, and comprise first fixating reagent of special combining target analyte and specially in conjunction with second fixating reagent of test mark, wherein each non-special combination mark is for detecting any fixating reagent in the band without any special combination affinity.
13. the described analysis test piece of claim 12, wherein test mark fluoresces at first characteristic wavelength, and non-special combination is marked at second characteristic wavelength that is different from first characteristic wavelength and fluoresces.
14. the described analysis test piece of claim 13, wherein test reagent and control immobilization of reagents are in the test and control area of the combination that detects band.
15. the described analysis test piece of claim 14, wherein test reagent and control reagent mix with the control area in test.
16. the described analysis test piece of claim 14, wherein test reagent and control reagent are arranged in the adjacent subarea territory that separates of testing with the control area.
17. a diagnostic test system comprises:
Analyze test piece, it comprise detect band and transversely flow direction cross over the flow path that is used for fluid sample that detects band, wherein detect band and comprise a capture region, this capture region is by first size that crosses the cross flow direction and second characterization of size that is parallel to the cross flow direction; And
Reader comprises illuminator, can focused beam to a zone detecting band, this detections is with has the minimum value that at least one surface size maximum equals first and second sizes of capture region.
18. the described system of claim 17, wherein capture region has the flat oval shape, and illuminator can arrive the flat oval shape zone of detecting band by focused beam, and this flat oval shape zone corresponds essentially to the size and the shape of capture region.
19. the described system of claim 17, wherein capture region has the discoid shape, and illuminator can arrive the discoid zone of detecting band by focused beam, and this flat oval shape zone corresponds essentially to the size and the shape of capture region.
20. the described system of claim 17, wherein test piece comprises special combining target analyte and at fluorescigenic first mark of first characteristic wavelength, with at fluorescigenic second mark of second characteristic wavelength that is different from first characteristic wavelength, detect first fixating reagent and second fixating reagent that band comprises special combining target analyte, this second fixating reagent specially in conjunction with second mark and second target analytes that combines with this second mark at least one of them.
21. the described system of claim 20, wherein reader comprises detection system, this detection system can obtain the luminous intensity measurement in first wavelength coverage from a zone corresponding to the detection band of first fixating reagent, can obtain the luminous intensity measurement in second wavelength coverage from a zone corresponding to the detection band of second fixating reagent, first wavelength coverage comprises first characteristic wavelength but does not comprise second characteristic wavelength that second wavelength coverage comprises second characteristic wavelength but do not comprise first characteristic wavelength.
22. the described system of claim 17, wherein first and second immobilization of reagents are in identical capture region.
23. the described system of claim 22, wherein first and second reagent mix in identical capture region.
24. the described system of claim 22, wherein first and second reagent are arranged in the adjacent subarea territory that separates of identical capture region.
25. the described system of claim 22, wherein detection system comprises an imaging subsystems, and this imaging subsystems can produce light intensity from light and detect; And an optical subsystem, the light of this optical subsystem self check in the future measuring tape is divided into different spectral components and guides the zones of different of this different spectral component to imaging subsystems.
26. the described system of claim 17, wherein capture region comprises first fixating reagent, detects band and comprises one or more extra capture regions, and these capture regions comprise fixating reagent separately.
27. the described system of claim 26, further comprise shell, it comprises a port and is used for receiving test piece, and wherein detection system comprises at least two imaging devices, and these at least two imaging devices directly are placed on each capture region when test piece is loaded in the port.
28. a diagnostic testing process comprises:
The receiving and analyzing test piece, this analysis test piece comprises the detection band and crosses over the flow path that is used for fluid sample that detects band along the cross flow direction that wherein the detection band comprises the capture region by second characterization of size of first size that crosses the cross flow direction and parallel cross flow direction.
Focused beam is to one or more zones of detecting band, and this detection band has the minimum value that at least one surface size maximum equals first and second sizes of capture region; With
Obtain luminous intensity measurement from the irradiation area that detects band.
29. a diagnostic test system comprises:
Reader obtains luminous intensity measurement from the exposure area that comprises the analysis test piece that detects band; And
Data-analyzing machine is carried out following operation, comprising: confirmed test measured value from the luminous intensity measurement that test mark obtains, regional a combination of this test mark and the detection band that comprises first fixating reagent; Determine compensation measurement from the luminous intensity measurement that the compensation mark that is different from test mark obtains, this test mark is arranged in one or more zones of detecting band, and it is unspecial in compensation label fixed reagent that this detects band; And from test measurements and compensation measurement, determine a parameter value.
30. the described system of claim 29, wherein data-analyzing machine is used for determining parameter value on the basis of the ratio of test measurements and compensation measurement.
31. the described system of claim 29, wherein data-analyzing machine is used for determining parameter value on the basis of the difference of test measurements and compensation measurement.
32. the described system of claim 29, wherein data-analyzing machine is used for determining parameter value with respect to threshold value and compensation measurement on respect to the basis of the comparison of threshold value in the analysis to measure value.
33. a diagnostic test system comprises:
From the exposure area that comprises the analysis test piece that detects band, obtain luminous intensity measurement;
Confirmed test measured value in the luminous intensity measurement that a zone from detect band obtains, this detection band comprises the test mark that combines with first fixating reagent;
Determine compensation measurement from the luminous intensity measurement that the compensation mark that is different from test mark obtains, this test mark is arranged in one or more zones of detecting band, and it is unspecial in compensation label fixed reagent that this detects band; And
From test measurements and compensation measurement, determine a parameter value.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/044394 | 2005-01-26 | ||
| US11/044,394 US20050221505A1 (en) | 2004-04-01 | 2005-01-26 | Optoelectronic rapid diagnostic test system |
| US11/112807 | 2005-04-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1936540A true CN1936540A (en) | 2007-03-28 |
Family
ID=37954166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610006621 Pending CN1936540A (en) | 2005-01-26 | 2006-01-25 | Assay test strip with two or more markers, and reading method therefor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1936540A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102007405A (en) * | 2008-03-04 | 2011-04-06 | 3M创新有限公司 | Methods and devices for monitoring of frying oil quality |
| CN102770751A (en) * | 2010-02-23 | 2012-11-07 | B.R.A.H.M.S有限公司 | A method for determining a marker in small volume of a sample of a bodily fluid |
| CN101836119B (en) * | 2007-10-26 | 2014-06-18 | 爱科来株式会社 | Sample detector and measurement device equipped with the same |
| US10036750B2 (en) | 2012-11-28 | 2018-07-31 | Furukawa Electric Co., Ltd. | Immunochromatography, and detection device and reagent for the same |
-
2006
- 2006-01-25 CN CN 200610006621 patent/CN1936540A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101836119B (en) * | 2007-10-26 | 2014-06-18 | 爱科来株式会社 | Sample detector and measurement device equipped with the same |
| CN102007405A (en) * | 2008-03-04 | 2011-04-06 | 3M创新有限公司 | Methods and devices for monitoring of frying oil quality |
| CN102007405B (en) * | 2008-03-04 | 2013-10-30 | 3M创新有限公司 | Methods and devices for monitoring of frying oil quality |
| CN102770751A (en) * | 2010-02-23 | 2012-11-07 | B.R.A.H.M.S有限公司 | A method for determining a marker in small volume of a sample of a bodily fluid |
| US10101326B2 (en) | 2010-02-23 | 2018-10-16 | B.R.A.H.M.S Gmbh | Method for determining a marker in small volume of a sample of a bodily fluid |
| US10036750B2 (en) | 2012-11-28 | 2018-07-31 | Furukawa Electric Co., Ltd. | Immunochromatography, and detection device and reagent for the same |
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