USRE38430E1 - Solid phase chromatographic immunoassay - Google Patents

Solid phase chromatographic immunoassay Download PDF

Info

Publication number
USRE38430E1
USRE38430E1 US09/167,028 US16702898A USRE38430E US RE38430 E1 USRE38430 E1 US RE38430E1 US 16702898 A US16702898 A US 16702898A US RE38430 E USRE38430 E US RE38430E
Authority
US
United States
Prior art keywords
analyte
tracer
test strip
liquid sample
site
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US09/167,028
Inventor
Robert W. Rosenstein
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Becton Dickinson and Co
Original Assignee
Becton Dickinson and Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=31191918&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=USRE38430(E1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from US08/049,247 external-priority patent/US5591645A/en
Application filed by Becton Dickinson and Co filed Critical Becton Dickinson and Co
Priority to US09/167,028 priority Critical patent/USRE38430E1/en
Application granted granted Critical
Publication of USRE38430E1 publication Critical patent/USRE38430E1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54386—Analytical elements
    • G01N33/54387—Immunochromatographic test strips
    • G01N33/54388—Immunochromatographic test strips based on lateral flow
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/90—Plate chromatography, e.g. thin layer or paper chromatography

Definitions

  • This invention relates to an assay for an analyte, and more particularly to a solid phase assay.
  • Assays for various analytes have been accomplished by a so-called solid phase assay.
  • a binder specific for at least the ligand to be determined (analyte) is supported on a solid support, whereby, in the assay it is not necessary to employ an additional agent for separating the bound and free phases formed in the assay.
  • such solid supports have been in the form of tubes, solid particles, and in some cases, the solid phase has been in the form of a “dip-stick”.
  • a binder may be supported the dip-stick with the dip-stick, containing the binder, being dipped into an assay solution containing the analyte, and in general, such solution further contains a tracer.
  • the presence and/or amount of tracer on the dip-stick is then employed as a measure of analyte (either a qualitative or quantitative measure of analyte).
  • the present invention is directed to providing an improved solid phase assay for determining analyte, and more particularly to a solid phase assay.
  • a solid support having a first portion and a second portion with the first and second portions being in capillary flow communication with each other whereby material flows by capillarity.
  • the first and second portions are positioned on the solid support in a manner such that the first portion may be contacted with material, including any analyte, with material in said first portion being transported by capillarity from the first portion of the support to the second portion thereof.
  • the second portion of the solid support includes a binder which is a binder for at least the analyte, with the binder also being a binder for a tracer used in the assay, when the assay format is a so-called competitive assay format.
  • the solid support also includes a tracer, which is comprised of a ligand portion and a detectable label portion conjugated to the ligand portion of the tracer.
  • a tracer which is comprised of a ligand portion and a detectable label portion conjugated to the ligand portion of the tracer.
  • the assay format is a so-called competitive assay format
  • the ligand portion of the tracer is bound by the binder contained in the second portion of the solid support.
  • the assay format is a so-called sandwich assay format
  • the ligand portion of the tracer is bound by the analyte.
  • the tracer is supported on the solid support on a tracer portion of the solid support in a manner such that when wetted, the tracer is capable of being transported by capillarity to the second portion of the solid support, and thereafter, depending on the presence and/or absence of analyte and/or the amount of analyte, as hereinafter explained in more detail, to a third portion of the solid support.
  • the tracer portion of the solid support may be a separate portion of the solid support or may be the first portion of the solid support (the portion to which sample is added).
  • the binder which is supported on the second portion of the solid phase is supported in a manner such that the binder remains immobile and is not transported by capillarity to the third portion of the solid support.
  • the third portion of the solid support may be a portion for detecting tracer which has been transported by capillarity from the second portion to the third portion.
  • the third portion may or may not include a substance supported thereon for detecting tracer.
  • the third portion may function only to receive materials not bound in the second portion.
  • the amount of tracer which is immobilized in the second portion of the solid support by being bound either directly to the binder in the second portion (in a competitive assay format), or by being indirectly bound to the binder (tracer is bound to analyte which is bound to the binder in a sandwich assay format) is dependent upon the presence and/or amount of analyte in the sample.
  • the amount of tracer which is passed from the second portion to the third portion of the solid support by capillarity is indirectly proportional to the amount of analyte in the sample
  • the amount of tracer which passes from the second portion to the third portion of the solid support, by capillarity is directly proportional to the amount of analyte in the sample.
  • the solid support and the various components are produced and employed in a manner for determining analyte by a competitive assay format, with the tracer being supported on the first portion of the solid support.
  • the detectable label portion of the tracer is comprised of a sac or lipid vesicle (often referred to as a liposome), which includes a detectable label.
  • the tracer is supported on the solid support on the first portion thereof, and the first portion of the solid support is wetted with the sample containing analyte to be determined.
  • both sample and tracer flow by capillarity into the second portion of the solid support which contains a binder specific for both the analyte and tracer, with the binder being immobilized on the second portion of the solid support.
  • tracer becomes bound to the binder on the second portion of the solid support.
  • the tracer which is not bound by the binder on the second portion then flows by capillarity into the third portion of the solid support for detection and/or determination therein.
  • the assay format is to be a simple “yes or no” format (only determining whether or not analyte is present in the sample)
  • the binder supported on the second portion of the solid support is supported in an amount such that in the absence of a detectable amount of analyte in the sample, there is no detectable presence of tracer in the third portion of the solid support.
  • the amount of tracer which is not bound to the binder in the second portion of the solid support increases, thereby increasing the amount of tracer present in the third portion of the solid support.
  • a quantitative assay may be run by determining tracer which remains in the second portion of the solid support and/or which flows by capillarity into the third portion of the solid support, and comparing such detected amount of tracer in the second and/or third portion with a “standard curve” to determine the amount of analyte in the sample.
  • the determination of tracer and/or analyte may be either qualitative or quantitative.
  • tracer is preferably supported on a tracer portion of the solid support which is different from the first portion of the solid support.
  • the ligand portion of the tracer is bound by the analyte, with the binder in the second portion of the solid support being specific for the analyte.
  • the first portion of the solid support is contacted with the sample containing analyte, and the tracer portion of the solid support is wetted to cause both the tracer and analyte to flow by capillarity to the binder supported by the second portion of the support.
  • the amount of tracer which becomes bound to analyte is directly proportional to the amount of analyte in the sample, and tracer bound to analyte, as well as any unbound tracer, flow by capillarity to the second portion of the solid support.
  • analyte becomes bound to immobilized binder specific for the analyte, with the unbound tracer (tracer not bound to analyte which is bound to the immobilized binder) flows by capillarity to the third portion of the solid support.
  • the tracer on the third portion of the solid support may be detected as a measure of the presence and/or amount of analyte in the sample.
  • the amount of tracer which is employed on the first portion of the solid support as well as the amount of binder on the second portion of the solid support are such that in the presence of a detectable amount of analyte, essentially no detectable tracer flows into the third portion of the solid support.
  • the amount of binder which is employed on the second portion of the solid support is an amount such that essentially all of the analyte which is suspected of being present in the sample is bound by the binder on the second portion.
  • the solid support which is employed in the assay is one which is capable of absorbing analyte from the sample, and which, when wetted, provides for flow of analyte and tracer by capillary attraction from the first portion, and through the second portion into the third portion of the solid support.
  • the solid support is one which is capable of supporting tracer and the binder.
  • suitable solid supports there may be mentioned: glass fiber, cellulose, nylon, crosslinked dextran, various chromatographic papers, nitrocellulose, etc. A particularly preferred material is nitrocellulose.
  • the solid support is preferably shaped in the form of a strip, with the first, second and third portions being arranged on the strip in the same plane in a manner such that material can flow by capillary attraction from the first zone and through the second zone to the third zone.
  • the preferred shape is in the form of a strip, any other of a wide variety of shapes or forms may be employed as long as the shape and form permits separate portions for performing the various functions, as hereinabove described.
  • the tracer employed in the assay, as hereinabove indicated, is comprised of a ligand portion and a detectable label portion conjugated to the ligand portion.
  • the detectable label of the detectable label portion may be any one of a wide variety of detectable labels; however, in accordance with a preferred embodiment, the detectable label is one which provides a color change in the second and/or third portion of the solid support, which is either a visible color change, or one which requires an instrument to detect the change in color. In accordance with a preferred embodiment, the label which is employed provides a change in color in the second and/or third portion of the solid support which is visible without the use of an instrument.
  • such a change in color may be provided by employing an enzyme as the detectable label, and by providing a substrate for the enzyme in the third portion of the solid support, which substrate, when contacted with the enzyme, provides a visible detectable change in color.
  • the detectable label may be the substrate, and the third portion of the solid support may be provided with the enzyme, whereby there is a detectable change in color in the third portion by contacting of the enzyme with the substrate label.
  • various chromogens such as fluorescent materials, absorbing, dyes, and the like.
  • a preferred label portion is a vesicle, which includes a detectable marker, with the detectable marker being one which is visible.
  • the ligand portion of the tracer is dependent upon the assay format. If the assay is a competitive assay, then the ligand portion of the tracer is either the analyte or an appropriate analogue thereof. An appropriate analogue means that the analogue of the ligand is also specifically bound by the binder for the analyte. If the assay format is a sandwich type of assay, then the ligand portion of the tracer is a ligand which is specifically bound by the analyte or by an antibody which is specifically bound by the analyte.
  • the binder which is employed in the assay is one which at least binds the analyte. As hereinabove indicated, if the assay format is a competitive type of assay format, then the binder also binds the ligand portion of the tracer.
  • the binder may be either a naturally occuring binder or an antibody which is specific for the analyte (either a polyclonal and/or monoclonal antibody). If the analyte is an antibody, the binder may be either an antigen specific for the antibody or an antibody which specifically binds the antibody analyte.
  • the binder may be supported on the solid support in a manner which immobilizes the binder; e.g., adsorption, covalent coupling, etc.
  • the procedures for immobilizing binders on a solid support are generally known in the art.
  • the tracer when supported on the first portion of the solid support, is supported in a manner such that when the first portion is wetted the tracer flows by capillary action.
  • the tracer may be absorbed on the first portion of the support.
  • the tracer in a competitive assay, is comprised of a ligand conjugated to a vesicle, which vesicle contains a detectable marker, with the tracer being supported on the solid support.
  • a ligand conjugated to a vesicle which vesicle contains a detectable marker
  • the tracer being supported on the solid support.
  • Applicant has found that it is possible to support such a tracer on a solid support of the type hereinabove described, and that such tracer will flow by capillarity when the solid support is wetted with a sample containing or suspected of containing an analyte.
  • the lipid vesicles (liposomes) which are employed may be prepared from a wide variety of lipids, including phospholipids, glycol lipids, and as representative examples there may be mentioned lecithin, spingomyelin, dipalmitoyl lecithin, distearoylphosphatidylcholine, etc.
  • the amphiphilic lipids employed for producing liposomes generally have a hydrophilic group, such as a phosphato, carboxylic, sulfato, or amino group, and a hydrophobic group, such as saturated and unsaturated aliphatic hydrocarbons, and aliphatic hydrocarbon groups substituted by one or more aromatic or cycloaliphatic groups.
  • the wall forming compounds for producing the liposomes may further include a steroid component such as cholesterol, cholestanol, and the like.
  • a steroid component such as cholesterol, cholestanol, and the like.
  • the liposomes may be produced by procedures generally available in the art.
  • liposomes may be produced by a reverse phase evaporation technique wherein the compound or compounds used in producing liposomes are initially dissolved in an organic phase, followed by addition of an aqueous phase and forming of a homogeneous emulsion. After forming the emulsion, the organic solvent is evaporated to form a gel like material, and such gel may be converted to a liposome by agitation or dispersion in an aqueous media.
  • a material is to be encapsulated in the liposome, such material may be encapsulated in the liposome by including the material in the aqueous solution in which the liposome is formed. Alternatively, the material may be encapsulated into a previously formed empty liposome (without material to be encapsulated) by the procedure described in U.S. Pat. No. 4,539,376.
  • the liposomes may also be produced by the procedures disclosed in U.S. Pat. No. 4,522,803.
  • the material which is entrapped or encapsulated within the liposome is a detectable marker, such as dyes, radiolabels, fluorescent materials, chemiluminescent materials, electron spin resonance materials, and the like; substrates for detectable markers; and the like.
  • the liposome may be derivatized with a detectable marker, rather than entrapping a marker in the liposome.
  • the liposome is derivatized with a ligand for producing a tracer.
  • the liposome may be derivatized with a ligand by procedures known in the art, such as covalent coupling, derivatization or activation, etc.
  • a compound or compounds used in forming the liposome may be derivatized with the ligand, prior to forming the liposome, or alternatively, the liposome may be derivatized with the ligand, subsequent to forming of the liposome.
  • the assay may be accomplished as hereinabove described with general reference to a variety of tracers, except that the tracer includes a liposome as the detectable marker portion of the tracer.
  • the tracer used in the assay is a ligand conjugated to a particulate label which is visible.
  • the term “visible” as used herein means that the label can be seen without the use of instrumentation; i.e., with the naked eye.
  • the particulate label is may be a metal or alloy (e.g. colloidal gold) or a sac in particular a liposome containing a visible dye.
  • the marker preferably included in the sac is a dye or some other material which is visible, without lysing of the sacs.
  • the tracer comprising of ligand and particulate label may also be produced by labeling the ligand with an aqueous dispersion of a hydrophobic dye or pigment, or of polymer nuclei coated with such a dye or pigment.
  • a hydrophobic dye or pigment or of polymer nuclei coated with such a dye or pigment.
  • the colored organic compounds which are used as labels are in the form of a hydrophobic sol, which hydrophobic organic dyes or pigments are insoluble in water or soluble only to a very limited extent.
  • the visible particulate label may be visible polymer particles, such as colored polystyrene particles, preferably of spherical shape.
  • particulate labels which may be employed in producing a tracer for use in the assay of the present invention, in which the tracer would be visible, there may be mentioned; ferritin, phycoerythrins or other phycobili-proteins; precipitated or insoluble metals or alloys; fungal, algal, or bacterial pigments or derivatives such as bacterial chlorophylls; plant materials or derivative metal sols and the like.
  • at least the portion of the product which includes the binder is formed of a material having a surface area capable of supporting the binder thereon in an amount such that tracer bound in such portion is visible.
  • the surface area is capable of supporting the binder in a concentration of at least 1 ug/cm 2 , and most generally in a concentration of at least 10 ug/cm 2 .
  • a particularly preferred material is nitro-cellulose. Such materials and tracers are described in U.S. Pat. No. 4,703,017, which is hereby incorporated by reference.
  • FIG. 1 is a schematic representation of a chromatographic test strip wherein “A” represents the first portion of the test strip, “B” represents the second portion of the test strip and “C” and “D” represent a third portion of the test strip.
  • a strip 10 including a first portion A on which a tracer is supported; a second portion B on which a binder is supported and a third portion D in which tracer may be determined.
  • a portion C is between portions B and D to provide spacing between portions B and D, whereby the portion for determining tracer is separated by a distance from the portion containing binder.
  • portion A In a competitive assay format, employing an enzyme as a detectable label, portion A would contain ligand labeled with enzyme, with the ligand portion being the analyte or appropriate analogue thereof; portion B would contain a binder specific for the analyte and the ligand portion of the tracer; and portion D would contain a substrate for the enzyme which interacts with the enzyme to provide a change in color.
  • portion A of the strip 10 would be contacted with a sample containing analyte, whereby portion A would be wet with the sample.
  • the tracer in portion A, as well as, sample would be transported by capillarity to portion B, where tracer and analyte compete for binding sites on the binder. Unbound tracer and unbound analyte move by capillarity through portion C to portion D where any tracer interacts with the substrate in portion D to provide a change in color.
  • the assay may be a “yes-no” assay or a quantitative assay and detection of tracer in portion D is dependent upon the assay employed.
  • portion D would not require an additional substance, i.e., portion D would also be blank.
  • tracer may be determined without supporting an additional substance on portion D.
  • portion D could contain a suitable lysing agent, such as an enzyme or detergent which lyses liposomes to release label from the liposome in portion D for detection of tracer.
  • tracer in portion C it is also possible to determine tracer in portion C, with or without determining tracer in portion D.
  • a substrate could be added to portion C in the case where the label is an enzyme.
  • the product may be used as a dip stick. Alternatively, a sample may be applied to portion A. Accordingly, the product may be used in either a horizontal or vertical orientation.
  • the invention is applicable to detecting and/or measuring a wide variety of analytes, such as: drugs, including therapeutic drugs and drugs of abuse; hormones, vitamins, proteins, including antibodies of all classes, peptides; steroids; bacteria; fungi; viruses; parasites; components or products of bacteria, fungi, viruses, or parasites; allergens of all types; products or components of normal or malignant cells; etc.
  • drugs including therapeutic drugs and drugs of abuse
  • steroids bacteria
  • fungi viruses
  • parasites components or products of bacteria, fungi, viruses, or parasites
  • allergens of all types products or components of normal or malignant cells; etc.
  • T 4 T 3 ; digoxin; hCG; insulin; theophylline; leutinizing hormone; organisms causing or associated with various disease states, such as Streptococcus pyogenes (group A), Herpes Simplex I and II, cytomegalovirus, chlamydia, rubella antibody, etc.
  • group A Streptococcus pyogenes
  • Herpes Simplex I and II Herpes Simplex I and II
  • cytomegalovirus chlamydia
  • rubella antibody etc.
  • Zone B consisting of a 0.5 ⁇ 0.5 cm square of 5 um-pore nitrocellulose (S&S, Keene, N.H.) was spotted with 3 ul of affinity purified rabbit anti-Group A Streptococcus antigen and then blocked with 3% bovine serum albumin. After drying, it was applied to the taped side of the dipstick, approximately 1 cm from the bottom of the stick. A strip of filter paper 0.5 ⁇ 6.5 cm. (Whatman 3 mm) was applied just above and touching the nitrocellulose, at the positions indicated by zones C and D. Zone A, consisting of dry SEPHADEX G50 fine grade bead-formed gel of cross-linked dextran (Pharmacia) was then applied.
  • Detector liposomes packed with sulfo-rhodamine dye were prepared by the method outlined in O'Connell et al. (Clin. Chem. 31:1424 [1985]). They were covalently coupled to affinity purified rabbit anti-Group A Streptococcus antigen.
  • the detector liposomes were spotted (2 ul) onto Zone A, 0.5 cm from the bottom and air dried.
  • the liposomes are in a 0.05M Tris buffer, pH 6.8, containing 2% glycerol, 0.05% dimethyl sulfoxide, 20 mM EDTA.
  • Group A Streptococcus organisms were harvested from culture plates, washed with saline (0.9% NaCl), and adjusted to 1 ⁇ 10 9 organisms/ml. An aliquot (0.1 ml) containing 1 ⁇ 10 8 organisms was subjected to the micro nitrous acid extraction method for exposing the Group A carbohydrate antigen. This method consists of mixing 0.3 ml of 0.1M HCl with 40 ul of 4M NaNO 2 , adding this to the Streptococcus organisms and, after 3 minutes, neturalizing with 40 ul of 1M Tris base. To faciliate the extraction and the dipstick assay, the HCl and the subsequent diluting fluid contain 0.1% Tween-20 non-ionic detergent.
  • a dilution series were prepared ranging from 8 ⁇ 10 6 organisms/ml to 1.25 ⁇ 10 5 organisms/ml. Aliquots of these dilutions (0.5 ml) were placed in 12 ⁇ 75 mm test tubes and a dipstick placed into the fluid in each test tube. As the fluid containing extracted antigen wicks up the stick, it carries the liposome detector past the spot of capture antibody. In the presence of antigen, which binds to the capture antibody spot, some of the liposomes also bind, resulting in the appearance of a red spot in zone B. The remainder of the liposomes and antigen solution pass into zone D.
  • the assay can be “read” by observing the lowest concentration of organisms resulting in a red spot in zone B.
  • the results of this example are given in the following table and indicate the an end point of 5 ⁇ 10 5 organisms/ml, close to the sensitivity required for a direct throat swab diagnostic for Group A Streptococcus pharyngitis.
  • the present invention is advantageous in that there is provided a product and process which may be easily employed for accomplishing an assay.
  • the product and process do not require the addition of tracer in that tracer is included in the product.
  • the product and process are capable of providing for a rapid assay.

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

A chromatographic test strip comprising a solid support having at least a first portion and a second portion with said portions being in the same plane so as to permit capillary flow communication with each other. The sample is added to the first portion. The first portion also may comprise a tracer portion having a tracer movably supported therein. The tracer consists of a visible particulate marker. In the second portion, a binder is immobilized. The test strip is useful in a variety of immunoassays.

Description

This application is a continuation of U.S. Ser. No. 07/818,000, filed 30 Dec. 1991 (now abandoned) which is a continuation of U.S. Ser. No. 07/031,023, filed 27 Mar. 1987 (now abandoned).
BACKGROUND OF THE INVENTION
This invention relates to an assay for an analyte, and more particularly to a solid phase assay.
FIELD OF THE INVENTION
Assays for various analytes have been accomplished by a so-called solid phase assay. In a solid phase assay, a binder specific for at least the ligand to be determined (analyte) is supported on a solid support, whereby, in the assay it is not necessary to employ an additional agent for separating the bound and free phases formed in the assay.
In general, such solid supports have been in the form of tubes, solid particles, and in some cases, the solid phase has been in the form of a “dip-stick”.
In a dip-stick solid phase assay, a binder may be supported the dip-stick with the dip-stick, containing the binder, being dipped into an assay solution containing the analyte, and in general, such solution further contains a tracer. The presence and/or amount of tracer on the dip-stick is then employed as a measure of analyte (either a qualitative or quantitative measure of analyte).
The present invention is directed to providing an improved solid phase assay for determining analyte, and more particularly to a solid phase assay.
SUMMARY OF THE INVENTION
In accordance with one aspect of the present invention, there is provided a solid support having a first portion and a second portion with the first and second portions being in capillary flow communication with each other whereby material flows by capillarity. The first and second portions are positioned on the solid support in a manner such that the first portion may be contacted with material, including any analyte, with material in said first portion being transported by capillarity from the first portion of the support to the second portion thereof.
The second portion of the solid support includes a binder which is a binder for at least the analyte, with the binder also being a binder for a tracer used in the assay, when the assay format is a so-called competitive assay format.
The solid support also includes a tracer, which is comprised of a ligand portion and a detectable label portion conjugated to the ligand portion of the tracer. In the case where the assay format is a so-called competitive assay format, the ligand portion of the tracer is bound by the binder contained in the second portion of the solid support. In the case where the assay format is a so-called sandwich assay format, the ligand portion of the tracer is bound by the analyte.
The tracer is supported on the solid support on a tracer portion of the solid support in a manner such that when wetted, the tracer is capable of being transported by capillarity to the second portion of the solid support, and thereafter, depending on the presence and/or absence of analyte and/or the amount of analyte, as hereinafter explained in more detail, to a third portion of the solid support.
The tracer portion of the solid support may be a separate portion of the solid support or may be the first portion of the solid support (the portion to which sample is added).
The binder which is supported on the second portion of the solid phase is supported in a manner such that the binder remains immobile and is not transported by capillarity to the third portion of the solid support.
The third portion of the solid support may be a portion for detecting tracer which has been transported by capillarity from the second portion to the third portion. The third portion may or may not include a substance supported thereon for detecting tracer. Alternatively, the third portion may function only to receive materials not bound in the second portion.
In accordance with the present invention, the amount of tracer which is immobilized in the second portion of the solid support by being bound either directly to the binder in the second portion (in a competitive assay format), or by being indirectly bound to the binder (tracer is bound to analyte which is bound to the binder in a sandwich assay format) is dependent upon the presence and/or amount of analyte in the sample. In a so-called sandwich assay format, the amount of tracer which is passed from the second portion to the third portion of the solid support by capillarity is indirectly proportional to the amount of analyte in the sample, and in the so-called competitive assay format, the amount of tracer which passes from the second portion to the third portion of the solid support, by capillarity, is directly proportional to the amount of analyte in the sample.
In a preferred embodiment of the present invention, the solid support and the various components are produced and employed in a manner for determining analyte by a competitive assay format, with the tracer being supported on the first portion of the solid support.
In a particularly preferred embodiment, as hereinafter explained in more detail, the detectable label portion of the tracer is comprised of a sac or lipid vesicle (often referred to as a liposome), which includes a detectable label.
In employing a preferred embodiment wherein the assay is a competitive assay, the tracer is supported on the solid support on the first portion thereof, and the first portion of the solid support is wetted with the sample containing analyte to be determined. Upon wetting of the solid support with the sample, both sample and tracer flow by capillarity into the second portion of the solid support which contains a binder specific for both the analyte and tracer, with the binder being immobilized on the second portion of the solid support. Depending upon the presence and/or amount of analyte in the sample portion, tracer becomes bound to the binder on the second portion of the solid support. The tracer which is not bound by the binder on the second portion, then flows by capillarity into the third portion of the solid support for detection and/or determination therein. If the assay format is to be a simple “yes or no” format (only determining whether or not analyte is present in the sample), then the binder supported on the second portion of the solid support is supported in an amount such that in the absence of a detectable amount of analyte in the sample, there is no detectable presence of tracer in the third portion of the solid support. As should be apparent, as the amount of analyte in the sample increases, the amount of tracer which is not bound to the binder in the second portion of the solid support increases, thereby increasing the amount of tracer present in the third portion of the solid support. Accordingly, a quantitative assay may be run by determining tracer which remains in the second portion of the solid support and/or which flows by capillarity into the third portion of the solid support, and comparing such detected amount of tracer in the second and/or third portion with a “standard curve” to determine the amount of analyte in the sample. Thus, is an assay the determination of tracer and/or analyte may be either qualitative or quantitative.
In the sandwich assay format, tracer is preferably supported on a tracer portion of the solid support which is different from the first portion of the solid support. The ligand portion of the tracer is bound by the analyte, with the binder in the second portion of the solid support being specific for the analyte. The first portion of the solid support is contacted with the sample containing analyte, and the tracer portion of the solid support is wetted to cause both the tracer and analyte to flow by capillarity to the binder supported by the second portion of the support. The amount of tracer which becomes bound to analyte is directly proportional to the amount of analyte in the sample, and tracer bound to analyte, as well as any unbound tracer, flow by capillarity to the second portion of the solid support. In the second portion of the solid support, analyte becomes bound to immobilized binder specific for the analyte, with the unbound tracer (tracer not bound to analyte which is bound to the immobilized binder) flows by capillarity to the third portion of the solid support. The tracer on the third portion of the solid support may be detected as a measure of the presence and/or amount of analyte in the sample.
In a “yes or no” sandwich assay type format, the amount of tracer which is employed on the first portion of the solid support as well as the amount of binder on the second portion of the solid support are such that in the presence of a detectable amount of analyte, essentially no detectable tracer flows into the third portion of the solid support.
In a sandwich assay format, the amount of binder which is employed on the second portion of the solid support is an amount such that essentially all of the analyte which is suspected of being present in the sample is bound by the binder on the second portion.
The solid support which is employed in the assay is one which is capable of absorbing analyte from the sample, and which, when wetted, provides for flow of analyte and tracer by capillary attraction from the first portion, and through the second portion into the third portion of the solid support. In addition, the solid support is one which is capable of supporting tracer and the binder. As representative examples of suitable solid supports there may be mentioned: glass fiber, cellulose, nylon, crosslinked dextran, various chromatographic papers, nitrocellulose, etc. A particularly preferred material is nitrocellulose.
The solid support is preferably shaped in the form of a strip, with the first, second and third portions being arranged on the strip in the same plane in a manner such that material can flow by capillary attraction from the first zone and through the second zone to the third zone. Although the preferred shape is in the form of a strip, any other of a wide variety of shapes or forms may be employed as long as the shape and form permits separate portions for performing the various functions, as hereinabove described.
The tracer employed in the assay, as hereinabove indicated, is comprised of a ligand portion and a detectable label portion conjugated to the ligand portion. The detectable label of the detectable label portion may be any one of a wide variety of detectable labels; however, in accordance with a preferred embodiment, the detectable label is one which provides a color change in the second and/or third portion of the solid support, which is either a visible color change, or one which requires an instrument to detect the change in color. In accordance with a preferred embodiment, the label which is employed provides a change in color in the second and/or third portion of the solid support which is visible without the use of an instrument. For example, such a change in color may be provided by employing an enzyme as the detectable label, and by providing a substrate for the enzyme in the third portion of the solid support, which substrate, when contacted with the enzyme, provides a visible detectable change in color. Alternatively, the detectable label may be the substrate, and the third portion of the solid support may be provided with the enzyme, whereby there is a detectable change in color in the third portion by contacting of the enzyme with the substrate label. As representative examples of other detectable labels, which may or may not require an instrument for detecting a color change, there may be mentioned various chromogens, such as fluorescent materials, absorbing, dyes, and the like. As hereinafter indicated in a competitive assay, a preferred label portion is a vesicle, which includes a detectable marker, with the detectable marker being one which is visible.
The ligand portion of the tracer is dependent upon the assay format. If the assay is a competitive assay, then the ligand portion of the tracer is either the analyte or an appropriate analogue thereof. An appropriate analogue means that the analogue of the ligand is also specifically bound by the binder for the analyte. If the assay format is a sandwich type of assay, then the ligand portion of the tracer is a ligand which is specifically bound by the analyte or by an antibody which is specifically bound by the analyte.
The binder which is employed in the assay is one which at least binds the analyte. As hereinabove indicated, if the assay format is a competitive type of assay format, then the binder also binds the ligand portion of the tracer.
As generally known in the art, if the analyte is an antigen or a hapten, then the binder may be either a naturally occuring binder or an antibody which is specific for the analyte (either a polyclonal and/or monoclonal antibody). If the analyte is an antibody, the binder may be either an antigen specific for the antibody or an antibody which specifically binds the antibody analyte.
The binder may be supported on the solid support in a manner which immobilizes the binder; e.g., adsorption, covalent coupling, etc. The procedures for immobilizing binders on a solid support are generally known in the art.
The tracer, when supported on the first portion of the solid support, is supported in a manner such that when the first portion is wetted the tracer flows by capillary action. Thus, for example, the tracer may be absorbed on the first portion of the support.
In accordance with a particularly preferred embodiment of the present invention, in a competitive assay, the tracer is comprised of a ligand conjugated to a vesicle, which vesicle contains a detectable marker, with the tracer being supported on the solid support. Applicant has found that it is possible to support such a tracer on a solid support of the type hereinabove described, and that such tracer will flow by capillarity when the solid support is wetted with a sample containing or suspected of containing an analyte.
The lipid vesicles (liposomes) which are employed may be prepared from a wide variety of lipids, including phospholipids, glycol lipids, and as representative examples there may be mentioned lecithin, spingomyelin, dipalmitoyl lecithin, distearoylphosphatidylcholine, etc. The amphiphilic lipids employed for producing liposomes generally have a hydrophilic group, such as a phosphato, carboxylic, sulfato, or amino group, and a hydrophobic group, such as saturated and unsaturated aliphatic hydrocarbons, and aliphatic hydrocarbon groups substituted by one or more aromatic or cycloaliphatic groups. The wall forming compounds for producing the liposomes may further include a steroid component such as cholesterol, cholestanol, and the like. The compounds for producing liposomes are generally known in the art, and no further details in this respect are deemed necessary for a complete understanding of the present invention.
The liposomes may be produced by procedures generally available in the art. For example, liposomes may be produced by a reverse phase evaporation technique wherein the compound or compounds used in producing liposomes are initially dissolved in an organic phase, followed by addition of an aqueous phase and forming of a homogeneous emulsion. After forming the emulsion, the organic solvent is evaporated to form a gel like material, and such gel may be converted to a liposome by agitation or dispersion in an aqueous media.
Procedures for producing liposomes are described, for example, in U.S. Pat. No. 4,241,046; U.S. Pat. No. 4,342,828 and PCT International Publication No. WO 80-01515.
If a material is to be encapsulated in the liposome, such material may be encapsulated in the liposome by including the material in the aqueous solution in which the liposome is formed. Alternatively, the material may be encapsulated into a previously formed empty liposome (without material to be encapsulated) by the procedure described in U.S. Pat. No. 4,539,376.
The liposomes may also be produced by the procedures disclosed in U.S. Pat. No. 4,522,803.
The material which is entrapped or encapsulated within the liposome (the material is within the aqueous compartment or within the membrane bilayer of the liposome) is a detectable marker, such as dyes, radiolabels, fluorescent materials, chemiluminescent materials, electron spin resonance materials, and the like; substrates for detectable markers; and the like. Alternatively, the liposome may be derivatized with a detectable marker, rather than entrapping a marker in the liposome.
The liposome is derivatized with a ligand for producing a tracer. The liposome may be derivatized with a ligand by procedures known in the art, such as covalent coupling, derivatization or activation, etc. In derivatizing the liposomes with a ligand, a compound or compounds used in forming the liposome may be derivatized with the ligand, prior to forming the liposome, or alternatively, the liposome may be derivatized with the ligand, subsequent to forming of the liposome. Procedures for derivatizing liposomes with ligands, and suitable coupling agents, and the like for preparing derivatized liposomes are known in the art, and no further details in this respect are deemed necessary for a complete understanding of the present invention.
In employing a preferred tracer in which the detectable marker portion thereof is comprised of liposome including a detectable marker for use in a competitive assay, the assay may be accomplished as hereinabove described with general reference to a variety of tracers, except that the tracer includes a liposome as the detectable marker portion of the tracer.
In a particularly preferred embodiment, the tracer used in the assay is a ligand conjugated to a particulate label which is visible. The term “visible” as used herein means that the label can be seen without the use of instrumentation; i.e., with the naked eye. The particulate label is may be a metal or alloy (e.g. colloidal gold) or a sac in particular a liposome containing a visible dye. The marker preferably included in the sac is a dye or some other material which is visible, without lysing of the sacs.
The tracer comprising of ligand and particulate label may also be produced by labeling the ligand with an aqueous dispersion of a hydrophobic dye or pigment, or of polymer nuclei coated with such a dye or pigment. Such labels are described in more detail in U.S. Pat. No. 4,373,932, which issued on Feb. 15, 1983. The tracers produced in accordance with such patent may also be employed as tracers in the present invention.
As indicated in the aforesaid patent, the colored organic compounds which are used as labels are in the form of a hydrophobic sol, which hydrophobic organic dyes or pigments are insoluble in water or soluble only to a very limited extent.
The visible particulate label may be visible polymer particles, such as colored polystyrene particles, preferably of spherical shape.
As representative examples of other particulate labels which may be employed in producing a tracer for use in the assay of the present invention, in which the tracer would be visible, there may be mentioned; ferritin, phycoerythrins or other phycobili-proteins; precipitated or insoluble metals or alloys; fungal, algal, or bacterial pigments or derivatives such as bacterial chlorophylls; plant materials or derivative metal sols and the like. In such an embodiment, at least the portion of the product which includes the binder is formed of a material having a surface area capable of supporting the binder thereon in an amount such that tracer bound in such portion is visible. In general, the surface area is capable of supporting the binder in a concentration of at least 1 ug/cm2, and most generally in a concentration of at least 10 ug/cm2. A particularly preferred material is nitro-cellulose. Such materials and tracers are described in U.S. Pat. No. 4,703,017, which is hereby incorporated by reference.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a schematic representation of a chromatographic test strip wherein “A” represents the first portion of the test strip, “B” represents the second portion of the test strip and “C” and “D” represent a third portion of the test strip.
Referring to FIG. 1, there is shown a strip 10 including a first portion A on which a tracer is supported; a second portion B on which a binder is supported and a third portion D in which tracer may be determined. As particularly shown, a portion C is between portions B and D to provide spacing between portions B and D, whereby the portion for determining tracer is separated by a distance from the portion containing binder.
In a competitive assay format, employing an enzyme as a detectable label, portion A would contain ligand labeled with enzyme, with the ligand portion being the analyte or appropriate analogue thereof; portion B would contain a binder specific for the analyte and the ligand portion of the tracer; and portion D would contain a substrate for the enzyme which interacts with the enzyme to provide a change in color.
In use, portion A of the strip 10 would be contacted with a sample containing analyte, whereby portion A would be wet with the sample. The tracer in portion A, as well as, sample would be transported by capillarity to portion B, where tracer and analyte compete for binding sites on the binder. Unbound tracer and unbound analyte move by capillarity through portion C to portion D where any tracer interacts with the substrate in portion D to provide a change in color. As hereinabove indicated, the assay may be a “yes-no” assay or a quantitative assay and detection of tracer in portion D is dependent upon the assay employed.
In the case where the tracer has a detectable label which does not require an additional substance for determination thereof, the portion D would not require an additional substance, i.e., portion D would also be blank. Thus, for example if the tracer included a liposome having a dye as a detectable label, then tracer may be determined without supporting an additional substance on portion D. Alternatively, if for example, it was required to release detectable lable from the liposome, portion D could contain a suitable lysing agent, such as an enzyme or detergent which lyses liposomes to release label from the liposome in portion D for detection of tracer.
In addition, it is also possible to determine tracer in portion C, with or without determining tracer in portion D. For example, a substrate could be added to portion C in the case where the label is an enzyme.
The product may be used as a dip stick. Alternatively, a sample may be applied to portion A. Accordingly, the product may be used in either a horizontal or vertical orientation.
The invention is applicable to detecting and/or measuring a wide variety of analytes, such as: drugs, including therapeutic drugs and drugs of abuse; hormones, vitamins, proteins, including antibodies of all classes, peptides; steroids; bacteria; fungi; viruses; parasites; components or products of bacteria, fungi, viruses, or parasites; allergens of all types; products or components of normal or malignant cells; etc. As particular examples, there may be mentioned T4; T3; digoxin; hCG; insulin; theophylline; leutinizing hormone; organisms causing or associated with various disease states, such as Streptococcus pyogenes (group A), Herpes Simplex I and II, cytomegalovirus, chlamydia, rubella antibody, etc.
The invention will be further described with reference to the following example:
EXAMPLE
Dipsticks were constructed by first coating 0.5×8 cm strips of polystyrene with Scotch® #969 adhesive transfer tape (3M, St. Paul Minn. 55144). Zone B, consisting of a 0.5×0.5 cm square of 5 um-pore nitrocellulose (S&S, Keene, N.H.) was spotted with 3 ul of affinity purified rabbit anti-Group A Streptococcus antigen and then blocked with 3% bovine serum albumin. After drying, it was applied to the taped side of the dipstick, approximately 1 cm from the bottom of the stick. A strip of filter paper 0.5×6.5 cm. (Whatman 3 mm) was applied just above and touching the nitrocellulose, at the positions indicated by zones C and D. Zone A, consisting of dry SEPHADEX G50 fine grade bead-formed gel of cross-linked dextran (Pharmacia) was then applied.
DETAILED DESCRIPTION
Detector liposomes packed with sulfo-rhodamine dye were prepared by the method outlined in O'Connell et al. (Clin. Chem. 31:1424 [1985]). They were covalently coupled to affinity purified rabbit anti-Group A Streptococcus antigen.
The detector liposomes were spotted (2 ul) onto Zone A, 0.5 cm from the bottom and air dried. The liposomes are in a 0.05M Tris buffer, pH 6.8, containing 2% glycerol, 0.05% dimethyl sulfoxide, 20 mM EDTA.
Group A Streptococcus organisms were harvested from culture plates, washed with saline (0.9% NaCl), and adjusted to 1×109 organisms/ml. An aliquot (0.1 ml) containing 1×108 organisms was subjected to the micro nitrous acid extraction method for exposing the Group A carbohydrate antigen. This method consists of mixing 0.3 ml of 0.1M HCl with 40 ul of 4M NaNO2, adding this to the Streptococcus organisms and, after 3 minutes, neturalizing with 40 ul of 1M Tris base. To faciliate the extraction and the dipstick assay, the HCl and the subsequent diluting fluid contain 0.1% Tween-20 non-ionic detergent.
Using the extracted antigen, a dilution series were prepared ranging from 8×106 organisms/ml to 1.25×105 organisms/ml. Aliquots of these dilutions (0.5 ml) were placed in 12×75 mm test tubes and a dipstick placed into the fluid in each test tube. As the fluid containing extracted antigen wicks up the stick, it carries the liposome detector past the spot of capture antibody. In the presence of antigen, which binds to the capture antibody spot, some of the liposomes also bind, resulting in the appearance of a red spot in zone B. The remainder of the liposomes and antigen solution pass into zone D.
The assay can be “read” by observing the lowest concentration of organisms resulting in a red spot in zone B. The results of this example are given in the following table and indicate the an end point of 5×105 organisms/ml, close to the sensitivity required for a direct throat swab diagnostic for Group A Streptococcus pharyngitis.
Group A Strep Antigen (organisms/ml) × 10−5
80 40 20 10 5 2.5 1.25 0
+ + + + + − − −
(+) = positive indication of antigen (red spot)
(−) = negative indication of antigen (red spot)
The present invention is advantageous in that there is provided a product and process which may be easily employed for accomplishing an assay. The product and process do not require the addition of tracer in that tracer is included in the product. In addition, the product and process are capable of providing for a rapid assay.
These and other advantages should be apparent to those skilled in the art from the teachings herein.
Numerous modifications and variations of the present invention are possible in light of the above teachings; therefore, the invention may be practiced otherwise than as particularly described.

Claims (32)

What is claimed is:
1. A test strip for determining the presence of an analyte in a liquid sample comprising a solid support, said solid support comprising at least a first portion and a second portion, said portions being in the same plane so as to permit capillary flow communication with each other;
said first portion being the site for application of the liquid sample and further comprising a tracer site, said tracer site consisting of a tracer movably supported therein wherein said tracer comprises a ligand, which specifically binds to the analyte, conjugated to a visible particulate marker; and
said second portion being the site for visually determining the presence of the visible particulate marker, said second portion consisting of a binder immobilized therein which specifically binds to the analyte.
2. The test strip of claim 1 wherein the solid support comprises nitrocellulose.
3. The test strip of claim 1 wherein the visible particulate marker is selected from the group consisting of colloidal metals, colored liposomes, colored polymeric beads and polymerized dye molecules.
4. The test strip of claim 3 wherein the visible particulate marker is a colored liposome.
5. The test strip of claim 3 wherein the visible particulate marker is a colored polymeric bead.
6. The test strip of claim 1 wherein the analyte is an antigen and the ligand and the binder are antibodies thereto.
7. The test strip of claim 1 wherein the ligand and the binder are antigens or analogs thereof and the analyte is an antibody thereto.
8. The test strip of claim 1 wherein the first portion and the tracer portion are spatially separate from each other with the first portion being upstream of the tracer portion.
9. A no-wash, one-step method for determining the presence of an analyte in a liquid sample consisting of the steps of:
a) adding a liquid sample to the first portion of the test strip of claim 1;
b) allowing sufficient time for the liquid sample to flow to the second portion of the test strip; and
c) determining the presence of the analyte in the liquid sample by visual inspection of the second portion for the visible particulate marker wherein the presence of the analyte is indicated by the presence of the visible particulate marker.
10. The method of claim 9 wherein the liquid sample is added to the test strip by immersing the first portion into the liquid sample.
11. A test strip for determining the amount of an analyte in a liquid sample comprising a solid support, said solid support comprising at least a first portion and a second portion, said portions being in the same plane so as to permit capillary flow communication with each other;
said first portion being the site for application of the liquid sample and further comprising a tracer site, said tracer site consisting of a tracer movably supported therein wherein said tracer comprises a ligand, which is the analyte or an analog thereof, conjugated to a visible particulate marker; and
said second portion being the site for visually determining the amount of the visible particulate marker, said second portion consisting of a binder immobilized therein which specifically binds to the ligand.
12. The test strip of claim 11 which consists of a third portion in the same plane as the first and the second portions, all of said portions being in capillary flow communication with each other, and said third portion being an additional site for visually determining the amount of visible particulate marker bound therein.
13. The test strip of claim 11 wherein the visible particulate marker is selected from the group consisting of colloidal metals, colored liposomes, colored polymeric beads and polymerized dye molecules.
14. The test strip of claim 13 wherein the visible particulate marker is a colored liposome.
15. The test strip of claim 13 wherein the visible particulate marker is a colored polymeric bead.
16. The test strip of claim 11 wherein the analyte is an antigen.
17. The test strip of claim 11 wherein the analyte is an antibody.
18. The test strip of claim 11 wherein the first portion and the tracer portion are spatially separate from each other with the first portion being upstream of the tracer portion.
19. A no-wash, one-step method for determining the presence of an analyte in a liquid sample consisting of the steps of:
a) adding a liquid sample to the first portion of the test strip of claim 11;
b) allowing sufficient time for the liquid sample to flow to the second portion of the test strip; and
c) determining the presence of the analyte in the liquid sample by visual inspection of the second portion for the visible particulate marker wherein the presence of the analyte is indicated by the absence of the visible particulate marker.
20. A no-wash, one-step method for determining the amount of an analyte in a liquid sample consisting of the steps of:
a) adding a liquid sample to the first portion of the test strip of claim 12;
b) allowing sufficient time for the liquid sample to flow to the second portion and the third portions of the test strip; and
c) determining the amount of the analyte present in the liquid sample by visual inspection of the second portion and the third portion for the amount of the visible particulate marker bound in each portion wherein the presence of the analyte is indicated by the absence of the visible particulate marker.
21. The method of claim 19 wherein the liquid sample is added to the test strip by immersing the first portion into the liquid sample.
22. The method of claim 20 wherein the liquid sample is added to the test strip by immersing the first portion into the liquid sample.
23. The test strip of claim 11 wherein the solid support comprises nitrocellulose.
24. A method of detecting an analyte in a liquid sample, the method comprising the steps of:
(a) providing a solid support comprising:
sorbent material, in the form of a test strip having a first portion, a second portion and a third portion, and providing flow from said first portion to said second portion and to said third portion,
a sample application site in said first portion of said test strip,
a visual inspection site in said second portion immobilizing therein a binder comprising a protein capable of binding at least the analyte or analogue thereof,
an additional visual inspection site in said third portion, and,
a tracer site comprising a dried reagent, supported on said test strip upstream of said second portion, consisting essentially of a tracer comprising colored particulate material conjugated to a ligand capable of binding one of the analyte and binder;
(b) applying to said sample application site said liquid sample;
(c) transporting said liquid sample along said test strip by capillary action, wicking or wetting into contact with said tracer to produce an admixture of said liquid sample and said tracer, and thereafter transporting said admixture into contact with said visual inspection sites thereby to produce
at said visual inspection site in said second portion, when said analyte is present in said liquid sample, a specific binding reaction product comprising a concentration of said tracer to produce a color visible to the unaided eye indicative of the presence of said analyte, and
at said additional visual inspection site in said third portion, visual indication of the presence or absence of analyte in the liquid sample.
25. The method according to claim 24 wherein the colored particulate material is selected from the group consisting of colloidal metals, colored liposomes, colored polymeric beads and polymerized dye molecules.
26. The method according to claim 25 wherein the colored particulate material is a colloidal metal.
27. The method according to claim 25 wherein the colored particulate material is a colored liposome.
28. The method according to claim 25 wherein the colored particulate material is a colored polymeric bead.
29. The method according to claim 25 wherein the colored particulate material is a polymerized dye molecule.
30. The method according to claim 24 wherein the analyte is an antigen and the ligand and the binder are antibodies thereto.
31. The method according to claim 24 wherein the ligand and the binder are antigens or analogs thereof and the analyte is an antibody thereto.
32. The method according to claim 24 wherein the tracer site is spatially separate from the sample application site in the first portion.
US09/167,028 1987-03-27 1998-10-06 Solid phase chromatographic immunoassay Expired - Lifetime USRE38430E1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US09/167,028 USRE38430E1 (en) 1987-03-27 1998-10-06 Solid phase chromatographic immunoassay

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US3102387A 1987-03-27 1987-03-27
US81800091A 1991-12-30 1991-12-30
US08/049,247 US5591645A (en) 1987-03-27 1993-04-20 Solid phase chromatographic immunoassay
US09/167,028 USRE38430E1 (en) 1987-03-27 1998-10-06 Solid phase chromatographic immunoassay

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US08/049,247 Reissue US5591645A (en) 1987-03-27 1993-04-20 Solid phase chromatographic immunoassay

Publications (1)

Publication Number Publication Date
USRE38430E1 true USRE38430E1 (en) 2004-02-17

Family

ID=31191918

Family Applications (1)

Application Number Title Priority Date Filing Date
US09/167,028 Expired - Lifetime USRE38430E1 (en) 1987-03-27 1998-10-06 Solid phase chromatographic immunoassay

Country Status (1)

Country Link
US (1) USRE38430E1 (en)

Cited By (78)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030124739A1 (en) * 2001-12-24 2003-07-03 Kimberly-Clark Worldwide, Inc. Polyelectrolytic internal calibration system of a flow-through assay
US20040043512A1 (en) * 2002-08-27 2004-03-04 Kimberly-Clark Worldwide, Inc. Self-calibration system for a magnetic binding assay
US20040043511A1 (en) * 2002-08-27 2004-03-04 Kimberly-Clark Worldwide, Inc. Membrane-based assay devices
US20040121334A1 (en) * 2002-12-19 2004-06-24 Kimberly-Clark Worldwide, Inc. Self-calibrated flow-through assay devices
US20040126875A1 (en) * 2002-09-12 2004-07-01 Putnam Martin A. Assay stick
US20050175992A1 (en) * 2004-02-09 2005-08-11 Rapid Pathogen Screening Inc. Method for the rapid diagnosis of targets in human body fluids
US20050191704A1 (en) * 2004-03-01 2005-09-01 Kimberly-Clark Worldwide, Inc. Assay devices utilizing chemichromic dyes
US20050227371A1 (en) * 2004-03-23 2005-10-13 Quidel Corporation Hybrid phase lateral flow assay
US20050227252A1 (en) * 2002-08-20 2005-10-13 Moon John A Diffraction grating-based encoded articles for multiplexed experiments
US20050277163A1 (en) * 1997-07-25 2005-12-15 Shu-Ching Cheng Methods of use of one step immunochromatographic device for streptococcus a antigen
US20060057729A1 (en) * 2003-09-12 2006-03-16 Illumina, Inc. Diffraction grating-based encoded element having a substance disposed thereon
US20060063271A1 (en) * 2002-09-12 2006-03-23 Putnam Martin A Method and apparatus for aligning microbeads in order to interrogate the same
US20060071075A1 (en) * 2002-08-20 2006-04-06 Moon John A Optical reader for diffraction grating-based encoded optical identification elements
US20060072177A1 (en) * 2002-08-20 2006-04-06 Putnam Martin A Diffraction grating-based encoded microparticle assay stick
US20060121626A1 (en) * 2004-12-03 2006-06-08 Genzyme Corporation Diagnostic assay device
US20060118630A1 (en) * 2004-11-16 2006-06-08 Illumina, Inc. Holographically encoded elements for microarray and other tagging labeling applications, and method and apparatus for making and reading the same
US20060119913A1 (en) * 2003-08-20 2006-06-08 Illumina, Inc. Fourier scattering methods for encoding microbeads and methods and apparatus for reading the same
US20060188939A1 (en) * 2005-02-16 2006-08-24 Ping Gao Fecal sample test device and methods of use
US20060205059A1 (en) * 2005-03-11 2006-09-14 Javanbakhsh Esfandiari Dual path immunoassay device
US20060246600A1 (en) * 2005-04-29 2006-11-02 Kimberly-Clark Worldwide, Inc. Metering technique for lateral flow assay devices
US20060246597A1 (en) * 2005-04-29 2006-11-02 Kimberly-Clark Worldwide, Inc. Flow control technique for assay devices
US20060263907A1 (en) * 2005-04-29 2006-11-23 Zweig Stephen E Fluorescence lateral flow immunoassay
US20070048815A1 (en) * 2005-08-31 2007-03-01 Kimberly-Clark Worldwide, Inc. Enzyme detection technique
US20070048182A1 (en) * 2005-08-31 2007-03-01 Kimberly-Clark Worldwide, Inc. Nitrite detection technique
US20070048807A1 (en) * 2005-08-31 2007-03-01 Kimberly-Clark Worldwide, Inc. Diagnostic test kits with improved detection accuracy
US20070121181A1 (en) * 2005-11-22 2007-05-31 Cyvera Corporation Method and apparatus for labeling using optical identification elements characterized by X-ray diffraction
US20070134810A1 (en) * 2005-12-14 2007-06-14 Kimberly-Clark Worldwide, Inc. Metering strip and method for lateral flow assay devices
US20070134811A1 (en) * 2005-12-13 2007-06-14 Kimberly-Clark Worldwide, Inc. Metering technique for lateral flow assay devices
US20070184495A1 (en) * 2006-02-07 2007-08-09 Shaari Christopher M Rapid nasal assay kit
US20070236796A1 (en) * 2002-09-12 2007-10-11 Illumina, Inc. Method of manufacturing of a diffraction grating-based optical identification element
US20070236789A1 (en) * 2006-04-10 2007-10-11 Moon John A Optical scanner with improved scan time
US20070275475A1 (en) * 2006-01-23 2007-11-29 Greg Liang Rapid Test Apparatus
US20080081341A1 (en) * 2006-10-03 2008-04-03 Jonathan Scott Maher Immunoassay test device and method of use
US20080138842A1 (en) * 2006-12-11 2008-06-12 Hans Boehringer Indirect lateral flow sandwich assay
US7387890B2 (en) 2004-12-16 2008-06-17 Chembio Diagnostic Systems, Inc. Immunoassay devices and use thereof
US20080145947A1 (en) * 2006-12-14 2008-06-19 Kimberly-Clark Worldwide, Inc. Detection of formaldehyde in urine samples
US20080145272A1 (en) * 2006-12-15 2008-06-19 Feaster Shawn R Lateral flow assay device
US20080145949A1 (en) * 2006-12-15 2008-06-19 Xuedong Song Indicator immobilization on assay devices
US20080318341A1 (en) * 2005-03-11 2008-12-25 Javanbakhsh Esfandiari Dual Path Immunoassay Device
US20090004058A1 (en) * 2006-01-23 2009-01-01 Greg Liang Device for handling and analysis of a biological sample
US20090073520A1 (en) * 2004-11-17 2009-03-19 Illumina, Inc. Encoded microparticles and a method for fabricating
US20090194589A1 (en) * 2002-08-20 2009-08-06 Illumina, Inc. Optical reader system for substrates having an optically readable code
US20090208975A1 (en) * 2007-12-13 2009-08-20 Beckman Coulter, Inc. Device and methods for detecting a target cell
WO2009108224A1 (en) * 2007-11-16 2009-09-03 Eugene Tu Viral detection apparatus and method
US20090305231A1 (en) * 2008-04-09 2009-12-10 Becton, Dickinson And Company Sensitive Immunoassays Using Coated Nanoparticles
US7659983B2 (en) 2003-01-22 2010-02-09 Electronics And Telecommunications Resarch Institute Hybrid random bead/chip based microarray
US20100112725A1 (en) * 2005-02-09 2010-05-06 Rapid Pathogen Screening, Inc Method to increase specificity and/or accuracy of lateral flow immunoassays
US7713748B2 (en) 2003-11-21 2010-05-11 Kimberly-Clark Worldwide, Inc. Method of reducing the sensitivity of assay devices
US7781172B2 (en) 2003-11-21 2010-08-24 Kimberly-Clark Worldwide, Inc. Method for extending the dynamic detection range of assay devices
US7791802B2 (en) 2004-02-19 2010-09-07 Illumina, Inc. Optical identification element having a non-waveguide substrate
US20100246007A1 (en) * 2002-08-20 2010-09-30 Illumina Corporation composition including an item and an encoded optical substrate and a method for identifying an item
US20100246005A1 (en) * 2002-08-20 2010-09-30 Cyvera Corporation Encoded particle having a grating with variations in the refractive index
US20100285610A1 (en) * 2005-02-18 2010-11-11 Saul Steven J Lateral Flow Test Kit and Method for Detecting an Analyte
US20100290948A1 (en) * 2009-05-15 2010-11-18 Xuedong Song Absorbent articles capable of indicating the presence of urinary tract infections
US7923260B2 (en) 2002-08-20 2011-04-12 Illumina, Inc. Method of reading encoded particles
US7939342B2 (en) 2005-03-30 2011-05-10 Kimberly-Clark Worldwide, Inc. Diagnostic test kits employing an internal calibration system
US7943395B2 (en) 2003-11-21 2011-05-17 Kimberly-Clark Worldwide, Inc. Extension of the dynamic detection range of assay devices
US20110171754A1 (en) * 2007-09-14 2011-07-14 Gareth Redmond Analysis system
US8137985B2 (en) 2001-12-24 2012-03-20 Kimberly-Clark Worldwide, Inc. Polyelectrolytic internal calibration system of a flow-through assay
WO2012099897A1 (en) 2011-01-18 2012-07-26 Symbolics, Llc Lateral flow assays using two dimensional features
US8603835B2 (en) 2011-02-10 2013-12-10 Chembio Diagnostic Systems, Inc. Reduced step dual path immunoassay device and method
WO2014012077A1 (en) 2012-07-13 2014-01-16 Genisphere, Llc Lateral flow assays using dna dendrimers
WO2014015076A1 (en) 2012-07-18 2014-01-23 Symbolics, Llc Lateral flow assays using two dimensional features
WO2014043247A1 (en) 2012-09-12 2014-03-20 Force Diagnostics, Inc Rapid tests for insurance underwriting
WO2014134033A1 (en) 2013-02-26 2014-09-04 Astute Medical, Inc. Lateral flow assay with test strip retainer
WO2015038978A1 (en) 2013-09-13 2015-03-19 Symbolics, Llc Lateral flow assays using two dimensional test and control signal readout patterns
US9199232B2 (en) 2010-04-07 2015-12-01 Biosensia Patents Limited Flow control device for assays
US9234889B1 (en) 2008-12-18 2016-01-12 Charm Sciences, Inc. Method and test strip for detecting residues
US9414813B2 (en) 2009-02-16 2016-08-16 Express Diagnostics Int'l, Inc. Device for assaying analytes in bodily fluids
WO2016164365A1 (en) 2015-04-06 2016-10-13 Bludiagnostics, Inc. A test device for detecting an analyte in a saliva sample and method of use
US9885710B2 (en) 2014-04-02 2018-02-06 Chembio Diagnostic Systems, Inc. Immunoassay utilizing trapping conjugate
WO2018039047A1 (en) 2016-08-23 2018-03-01 Qoolabs, Inc. Lateral flow assay for assessing recombinant protein expression or reporter gene expression
US10094793B2 (en) 2015-09-19 2018-10-09 The Board Of Regents Of The University Of Texas System Nanomaterial-based photothermal immunosensing for quantitative detection of disease biomarkers
US10690667B2 (en) 2014-10-27 2020-06-23 Chembio Diagnostic Systems, Inc. Rapid screening assay for qualitative detection of multiple febrile illnesses
WO2022027037A1 (en) 2020-07-27 2022-02-03 Single Cell Technology, Inc. Anti-sars corona virus-2 spike protein antibodies
US11293839B2 (en) 2018-08-16 2022-04-05 Epitope Biotechnology Co., Ltd. Device for fecal sample collection and extraction
US11350913B2 (en) 2008-07-24 2022-06-07 Chembio Diagnostic Systems, Inc. Method and apparatus for collecting and preparing biological samples for testing
US12195531B2 (en) 2013-03-21 2025-01-14 Code Biotherapeutics, Inc. Cellular delivery of DNA intercalating agents

Citations (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4094647A (en) * 1976-07-02 1978-06-13 Thyroid Diagnostics, Inc. Test device
US4168146A (en) * 1975-01-27 1979-09-18 Ab Kabi Immunoassay with test strip having antibodies bound thereto
US4235601A (en) 1979-01-12 1980-11-25 Thyroid Diagnostics, Inc. Test device and method for its use
US4313734A (en) 1978-07-13 1982-02-02 Akzona Incorporated Metal sol particle immunoassay
US4361537A (en) 1979-01-12 1982-11-30 Thyroid Diagnostics, Inc. Test device and method for its use
US4373932A (en) 1980-01-11 1983-02-15 Akzona Incorporated Application of water-dispersible hydrophobic dyes or pigments as labels in immunoassays
US4435504A (en) * 1982-07-15 1984-03-06 Syva Company Immunochromatographic assay with support having bound "MIP" and second enzyme
US4446232A (en) * 1981-10-13 1984-05-01 Liotta Lance A Enzyme immunoassay with two-zoned device having bound antigens
US4461829A (en) * 1981-09-14 1984-07-24 Miles Laboratories, Inc. Homogeneous specific binding assay element and lyophilization production method
EP0158746A2 (en) 1983-11-25 1985-10-23 Janssen Pharmaceutica N.V. Visualization method for the direct or indirect detection of the reaction between a specific binding agent and the corresponding acceptor substance in blot overlay assays
US4552839A (en) * 1983-08-01 1985-11-12 Syntex (U.S.A.) Inc. Determination of analytes in particle-containing medium
EP0173375A1 (en) * 1984-07-23 1986-03-05 Polaroid Corporation Novel assay product and process
WO1986003839A1 (en) * 1984-12-20 1986-07-03 Cerny Erich H Solid phase diffusion assay
EP0191640A2 (en) 1985-02-14 1986-08-20 Abbott Laboratories Concentrating immunochemical test strip
EP0212599A2 (en) * 1985-08-28 1987-03-04 Miles Inc. Multizone analytical element for immunoassays having detectable signal concentrating zone
WO1987002774A1 (en) * 1985-10-30 1987-05-07 Boots-Celltech Diagnostics Limited Binding assay device
US4668619A (en) * 1980-10-30 1987-05-26 Miles Laboratories, Inc. Multilayer homogeneous specific binding assay device
US4690907A (en) * 1983-12-19 1987-09-01 Daiichi Pure Chemicals Co., Ltd. Capillary tube immunoassay
US4703017A (en) * 1984-02-14 1987-10-27 Becton Dickinson And Company Solid phase assay with visual readout
US4708933A (en) * 1984-06-12 1987-11-24 Leaf Huang Immunoliposome assay-methods and products
US4717676A (en) * 1986-03-03 1988-01-05 Becton Dickinson And Company Vesicles and use thereof in an assay
US4743560A (en) * 1984-03-26 1988-05-10 Becton Dickinson And Company Solid phase assay
EP0276152A2 (en) * 1987-01-23 1988-07-27 Synbiotics Corporation Orthographic flow immunoassays and devices
US4770853A (en) * 1986-12-03 1988-09-13 New Horizons Diagnostics Corporation Device for self contained solid phase immunodiffusion assay
WO1988008534A1 (en) 1987-04-27 1988-11-03 Unilever Plc Immunoassays and devices therefor
EP0306772A1 (en) * 1987-09-11 1989-03-15 Abbott Laboratories Lateral flow chromatographic binding assay device
US4855240A (en) * 1987-05-13 1989-08-08 Becton Dickinson And Company Solid phase assay employing capillary flow
US4859612A (en) 1987-10-07 1989-08-22 Hygeia Sciences, Inc. Metal sol capture immunoassay procedure, kit for use therewith and captured metal containing composite
US4861711A (en) 1984-12-15 1989-08-29 Behringwerke Aktiengesellschaft Sheet-like diagnostic device
US4920046A (en) 1987-02-20 1990-04-24 Becton, Dickinson And Company Process, test device, and test kit for a rapid assay having a visible readout
US4943522A (en) * 1987-06-01 1990-07-24 Quidel Lateral flow, non-bibulous membrane assay protocols
US4959307A (en) * 1986-09-05 1990-09-25 Syntex (U.S.A.) Inc. Immunoseparating strip
US4960691A (en) * 1986-09-29 1990-10-02 Abbott Laboratories Chromatographic test strip for determining ligands or receptors
US4999285A (en) * 1984-11-15 1991-03-12 Syntex (U.S.A.) Inc. Chromatographic cassette
US5006474A (en) * 1987-12-16 1991-04-09 Disease Detection International Inc. Bi-directional lateral chromatographic test device
EP0421294A2 (en) * 1989-10-05 1991-04-10 Abbott Laboratories Improved self-performing immunochromatographic device
US5030558A (en) * 1986-11-07 1991-07-09 Syntex (U.S.A.) Inc. Qualitative immunochromatographic method and device
US5037736A (en) * 1986-11-26 1991-08-06 Boehringer Mannheim Gmbh Process and test carrier for the determination of an analyte
US5039607A (en) * 1988-05-17 1991-08-13 Syntex (U.S.A.) Inc. Method for immunochromatographic analysis
US5081013A (en) * 1987-08-14 1992-01-14 Boehringer Biochemia Robin S.P.A. Immunodiagnostic device and method
US5120643A (en) 1987-07-13 1992-06-09 Abbott Laboratories Process for immunochromatography with colloidal particles
US5141850A (en) 1990-02-07 1992-08-25 Hygeia Sciences, Inc. Porous strip form assay device method
US5236826A (en) * 1985-12-10 1993-08-17 Murex Corporation Immunoassay for the detection or quantitation of an analyte

Patent Citations (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4168146A (en) * 1975-01-27 1979-09-18 Ab Kabi Immunoassay with test strip having antibodies bound thereto
US4094647A (en) * 1976-07-02 1978-06-13 Thyroid Diagnostics, Inc. Test device
US4313734A (en) 1978-07-13 1982-02-02 Akzona Incorporated Metal sol particle immunoassay
US4235601A (en) 1979-01-12 1980-11-25 Thyroid Diagnostics, Inc. Test device and method for its use
US4361537A (en) 1979-01-12 1982-11-30 Thyroid Diagnostics, Inc. Test device and method for its use
US4373932A (en) 1980-01-11 1983-02-15 Akzona Incorporated Application of water-dispersible hydrophobic dyes or pigments as labels in immunoassays
US4668619A (en) * 1980-10-30 1987-05-26 Miles Laboratories, Inc. Multilayer homogeneous specific binding assay device
US4461829A (en) * 1981-09-14 1984-07-24 Miles Laboratories, Inc. Homogeneous specific binding assay element and lyophilization production method
US4446232A (en) * 1981-10-13 1984-05-01 Liotta Lance A Enzyme immunoassay with two-zoned device having bound antigens
US4435504A (en) * 1982-07-15 1984-03-06 Syva Company Immunochromatographic assay with support having bound "MIP" and second enzyme
US4552839A (en) * 1983-08-01 1985-11-12 Syntex (U.S.A.) Inc. Determination of analytes in particle-containing medium
EP0158746A2 (en) 1983-11-25 1985-10-23 Janssen Pharmaceutica N.V. Visualization method for the direct or indirect detection of the reaction between a specific binding agent and the corresponding acceptor substance in blot overlay assays
US4690907A (en) * 1983-12-19 1987-09-01 Daiichi Pure Chemicals Co., Ltd. Capillary tube immunoassay
US4703017A (en) * 1984-02-14 1987-10-27 Becton Dickinson And Company Solid phase assay with visual readout
US4703017C1 (en) * 1984-02-14 2001-12-04 Becton Dickinson Co Solid phase assay with visual readout
US4743560A (en) * 1984-03-26 1988-05-10 Becton Dickinson And Company Solid phase assay
US4708933A (en) * 1984-06-12 1987-11-24 Leaf Huang Immunoliposome assay-methods and products
EP0173375A1 (en) * 1984-07-23 1986-03-05 Polaroid Corporation Novel assay product and process
US4999285A (en) * 1984-11-15 1991-03-12 Syntex (U.S.A.) Inc. Chromatographic cassette
US4861711A (en) 1984-12-15 1989-08-29 Behringwerke Aktiengesellschaft Sheet-like diagnostic device
WO1986003839A1 (en) * 1984-12-20 1986-07-03 Cerny Erich H Solid phase diffusion assay
EP0191640A2 (en) 1985-02-14 1986-08-20 Abbott Laboratories Concentrating immunochemical test strip
US4740468A (en) 1985-02-14 1988-04-26 Syntex (U.S.A.) Inc. Concentrating immunochemical test device and method
EP0212599A2 (en) * 1985-08-28 1987-03-04 Miles Inc. Multizone analytical element for immunoassays having detectable signal concentrating zone
US4806312A (en) * 1985-08-28 1989-02-21 Miles Inc. Multizone analytical element having detectable signal concentrating zone
EP0225054A1 (en) 1985-10-30 1987-06-10 Celltech Limited Binding assay device
WO1987002774A1 (en) * 1985-10-30 1987-05-07 Boots-Celltech Diagnostics Limited Binding assay device
US5236826A (en) * 1985-12-10 1993-08-17 Murex Corporation Immunoassay for the detection or quantitation of an analyte
US4717676A (en) * 1986-03-03 1988-01-05 Becton Dickinson And Company Vesicles and use thereof in an assay
US4959307A (en) * 1986-09-05 1990-09-25 Syntex (U.S.A.) Inc. Immunoseparating strip
US4960691A (en) * 1986-09-29 1990-10-02 Abbott Laboratories Chromatographic test strip for determining ligands or receptors
US5030558A (en) * 1986-11-07 1991-07-09 Syntex (U.S.A.) Inc. Qualitative immunochromatographic method and device
US5037736A (en) * 1986-11-26 1991-08-06 Boehringer Mannheim Gmbh Process and test carrier for the determination of an analyte
US4770853A (en) * 1986-12-03 1988-09-13 New Horizons Diagnostics Corporation Device for self contained solid phase immunodiffusion assay
EP0276152A2 (en) * 1987-01-23 1988-07-27 Synbiotics Corporation Orthographic flow immunoassays and devices
US4920046A (en) 1987-02-20 1990-04-24 Becton, Dickinson And Company Process, test device, and test kit for a rapid assay having a visible readout
GB2204398A (en) * 1987-04-27 1988-11-09 Unilever Plc Assays
WO1988008534A1 (en) 1987-04-27 1988-11-03 Unilever Plc Immunoassays and devices therefor
US4855240A (en) * 1987-05-13 1989-08-08 Becton Dickinson And Company Solid phase assay employing capillary flow
US4943522A (en) * 1987-06-01 1990-07-24 Quidel Lateral flow, non-bibulous membrane assay protocols
US5120643A (en) 1987-07-13 1992-06-09 Abbott Laboratories Process for immunochromatography with colloidal particles
US5081013A (en) * 1987-08-14 1992-01-14 Boehringer Biochemia Robin S.P.A. Immunodiagnostic device and method
EP0306772A1 (en) * 1987-09-11 1989-03-15 Abbott Laboratories Lateral flow chromatographic binding assay device
US4859612A (en) 1987-10-07 1989-08-22 Hygeia Sciences, Inc. Metal sol capture immunoassay procedure, kit for use therewith and captured metal containing composite
US5006474A (en) * 1987-12-16 1991-04-09 Disease Detection International Inc. Bi-directional lateral chromatographic test device
US5039607A (en) * 1988-05-17 1991-08-13 Syntex (U.S.A.) Inc. Method for immunochromatographic analysis
EP0421294A2 (en) * 1989-10-05 1991-04-10 Abbott Laboratories Improved self-performing immunochromatographic device
US5141850A (en) 1990-02-07 1992-08-25 Hygeia Sciences, Inc. Porous strip form assay device method

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
Analytical Biochemistry, vol. 85, 180-187 (1978).* *
Glad et al., Analytical Biochemistry, vol. 85, pp. 180-187 (1978).
Greenquist et al., Clinical Chemistry, vol. 27 No. 9, pp. 1614-1617 (1981).* *
Hsu, Immunogold for Detection of Antigen on Nitrocellulose Paper, Analytical Biochemistry, 142:221-225 (1984).
Ngo, Enzyme-Mediated Immunoassay, pp. 3-19 (1985).* *
Ostwald (ed.), Kolloid Chemische Beihefte (Colloid Chemistry Supplements), vol. II (1910-1911).
Surek et al., Visualization of Antigenic Proteins Blotted on Nitrocellulose Using the Immunogold Staining Method, Biochem. and Biophys. Res. Communic., 121(I):284-289 (1984).
Tyhach et al., Clinical Chemistry, vol. 27, No. 9, pp. 1499-1504 (1981).* *

Cited By (164)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7666614B2 (en) 1997-07-25 2010-02-23 Genzyme Corporation Method of use of one step immunochromatographic device for Streptococcus A antigen
US20060154315A1 (en) * 1997-07-25 2006-07-13 Shu-Ching Cheng Method of use of one step immunochromatographic device for streptococcus a antigen
US20050277163A1 (en) * 1997-07-25 2005-12-15 Shu-Ching Cheng Methods of use of one step immunochromatographic device for streptococcus a antigen
US7651841B2 (en) 2001-12-24 2010-01-26 Kimberly-Clark Worldwide, Inc. Polyelectrolytic internal calibration system of a flow-through assay
US20030124739A1 (en) * 2001-12-24 2003-07-03 Kimberly-Clark Worldwide, Inc. Polyelectrolytic internal calibration system of a flow-through assay
US8137985B2 (en) 2001-12-24 2012-03-20 Kimberly-Clark Worldwide, Inc. Polyelectrolytic internal calibration system of a flow-through assay
US7900836B2 (en) 2002-08-20 2011-03-08 Illumina, Inc. Optical reader system for substrates having an optically readable code
US8614852B2 (en) 2002-08-20 2013-12-24 Illumina, Inc. Elongated microparticles having an optically detectable code configured to at least one of reflect or filter light
US20050227252A1 (en) * 2002-08-20 2005-10-13 Moon John A Diffraction grating-based encoded articles for multiplexed experiments
US8333325B2 (en) 2002-08-20 2012-12-18 Illumina, Inc. Optical reader system for substrates having an optically readable code
US7872804B2 (en) 2002-08-20 2011-01-18 Illumina, Inc. Encoded particle having a grating with variations in the refractive index
US20090194589A1 (en) * 2002-08-20 2009-08-06 Illumina, Inc. Optical reader system for substrates having an optically readable code
US20060071075A1 (en) * 2002-08-20 2006-04-06 Moon John A Optical reader for diffraction grating-based encoded optical identification elements
US20060072177A1 (en) * 2002-08-20 2006-04-06 Putnam Martin A Diffraction grating-based encoded microparticle assay stick
US20100246005A1 (en) * 2002-08-20 2010-09-30 Cyvera Corporation Encoded particle having a grating with variations in the refractive index
US8498052B2 (en) 2002-08-20 2013-07-30 Illumina, Inc. Composition including an item and an encoded optical substrate and a method for identifying an item
US20100246007A1 (en) * 2002-08-20 2010-09-30 Illumina Corporation composition including an item and an encoded optical substrate and a method for identifying an item
US7923260B2 (en) 2002-08-20 2011-04-12 Illumina, Inc. Method of reading encoded particles
US20110114729A1 (en) * 2002-08-20 2011-05-19 Illumina, Inc. Optical reader system for substrates having an optically readable code
US7670786B2 (en) 2002-08-27 2010-03-02 Kimberly-Clark Worldwide, Inc. Membrane-based assay devices
US20040043511A1 (en) * 2002-08-27 2004-03-04 Kimberly-Clark Worldwide, Inc. Membrane-based assay devices
US20040043512A1 (en) * 2002-08-27 2004-03-04 Kimberly-Clark Worldwide, Inc. Self-calibration system for a magnetic binding assay
US20040126875A1 (en) * 2002-09-12 2004-07-01 Putnam Martin A. Assay stick
US7898735B2 (en) 2002-09-12 2011-03-01 Illumina, Inc. Methods and systems for writing an optical code within or on a fiber substrate
US8470605B2 (en) 2002-09-12 2013-06-25 Illumina, Inc. Optical reader for reading encoded microparticles
US20070236796A1 (en) * 2002-09-12 2007-10-11 Illumina, Inc. Method of manufacturing of a diffraction grating-based optical identification element
US20060063271A1 (en) * 2002-09-12 2006-03-23 Putnam Martin A Method and apparatus for aligning microbeads in order to interrogate the same
US20080165656A1 (en) * 2002-09-12 2008-07-10 Moon John A Method of Manufacturing of a Diffraction Grating-Based Optical Identification Element
US20100255603A9 (en) * 2002-09-12 2010-10-07 Putnam Martin A Method and apparatus for aligning microbeads in order to interrogate the same
US20040121334A1 (en) * 2002-12-19 2004-06-24 Kimberly-Clark Worldwide, Inc. Self-calibrated flow-through assay devices
US20110058172A1 (en) * 2003-01-22 2011-03-10 Illumina, Inc. Methods of identifying analytes and using encoded particles
US20100099574A1 (en) * 2003-01-22 2010-04-22 Cyvera Corporation Methods of identifying an analyte and nucleic acid analysis
US7843567B2 (en) 2003-01-22 2010-11-30 Illumina, Inc. Methods of identifying an analyte and nucleic acid analysis
US9268983B2 (en) 2003-01-22 2016-02-23 Illumina, Inc. Optical system and method for reading encoded microbeads
US8049893B2 (en) 2003-01-22 2011-11-01 Illumina, Inc. Methods of identifying analytes and using encoded particles
US7659983B2 (en) 2003-01-22 2010-02-09 Electronics And Telecommunications Resarch Institute Hybrid random bead/chip based microarray
US8081792B2 (en) 2003-08-20 2011-12-20 Illumina, Inc. Fourier scattering methods for encoding microbeads and methods and apparatus for reading the same
US8565475B2 (en) 2003-08-20 2013-10-22 Illumina, Inc. Optical system and method for reading encoded microbeads
US20060119913A1 (en) * 2003-08-20 2006-06-08 Illumina, Inc. Fourier scattering methods for encoding microbeads and methods and apparatus for reading the same
US20060057729A1 (en) * 2003-09-12 2006-03-16 Illumina, Inc. Diffraction grating-based encoded element having a substance disposed thereon
US7943395B2 (en) 2003-11-21 2011-05-17 Kimberly-Clark Worldwide, Inc. Extension of the dynamic detection range of assay devices
US7781172B2 (en) 2003-11-21 2010-08-24 Kimberly-Clark Worldwide, Inc. Method for extending the dynamic detection range of assay devices
US7713748B2 (en) 2003-11-21 2010-05-11 Kimberly-Clark Worldwide, Inc. Method of reducing the sensitivity of assay devices
US10001482B2 (en) 2004-02-09 2018-06-19 Quidel Corporation Device for the detection of an analyte in a fluid sample
US20050175992A1 (en) * 2004-02-09 2005-08-11 Rapid Pathogen Screening Inc. Method for the rapid diagnosis of targets in human body fluids
US7723124B2 (en) 2004-02-09 2010-05-25 Rapid Pathogen Screening, Inc. Method for the rapid diagnosis of targets in human body fluids
US8647890B2 (en) 2004-02-09 2014-02-11 Rapid Pathogen Screening, Inc. Method for the rapid diagnosis of targets in human body fluids using undiluted samples
US20100143891A1 (en) * 2004-02-09 2010-06-10 Rapid Pathogen Screening, Inc. Method for the Rapid Diagnosis of Targets in Human Body Fluids
US20070141564A1 (en) * 2004-02-09 2007-06-21 Rapid Pathogen Screening Inc. Method for the rapid diagnosis of targets in human body fluids
US7791802B2 (en) 2004-02-19 2010-09-07 Illumina, Inc. Optical identification element having a non-waveguide substrate
US20050191704A1 (en) * 2004-03-01 2005-09-01 Kimberly-Clark Worldwide, Inc. Assay devices utilizing chemichromic dyes
US20100068826A1 (en) * 2004-03-23 2010-03-18 Quidel Corporation Hybrid phase lateral flow assay
US20050227371A1 (en) * 2004-03-23 2005-10-13 Quidel Corporation Hybrid phase lateral flow assay
US7632687B2 (en) 2004-03-23 2009-12-15 Quidel Corporation Hybrid phase lateral flow assay
US20060118630A1 (en) * 2004-11-16 2006-06-08 Illumina, Inc. Holographically encoded elements for microarray and other tagging labeling applications, and method and apparatus for making and reading the same
US7796333B2 (en) 2004-11-17 2010-09-14 Illumina, Inc. Encoded microparticles and a method for fabricating
US20090073520A1 (en) * 2004-11-17 2009-03-19 Illumina, Inc. Encoded microparticles and a method for fabricating
US20060121626A1 (en) * 2004-12-03 2006-06-08 Genzyme Corporation Diagnostic assay device
US7465587B2 (en) 2004-12-03 2008-12-16 Genzyme Corporation Diagnostic assay device
US7569397B2 (en) 2004-12-16 2009-08-04 Chembio Diagnostic Systems, Inc. Immunoassay devices and use thereof
US7387890B2 (en) 2004-12-16 2008-06-17 Chembio Diagnostic Systems, Inc. Immunoassay devices and use thereof
US20080254444A1 (en) * 2004-12-16 2008-10-16 Javanbakhsh Esfandiari Immunoassay Devices and Use Thereof
US8445293B2 (en) 2005-02-09 2013-05-21 Rapid Pathogen Screening, Inc. Method to increase specificity and/or accuracy of lateral flow immunoassays
US20100112725A1 (en) * 2005-02-09 2010-05-06 Rapid Pathogen Screening, Inc Method to increase specificity and/or accuracy of lateral flow immunoassays
US9250236B2 (en) 2005-02-09 2016-02-02 Rapid Pathogen Screening, Inc. Method to increase specificity and/or accuracy of lateral flow immunoassays
US20060188939A1 (en) * 2005-02-16 2006-08-24 Ping Gao Fecal sample test device and methods of use
US7780915B2 (en) 2005-02-16 2010-08-24 Epitope Diagnostcs, Inc. Fecal sample test device and methods of use
US8709792B2 (en) 2005-02-18 2014-04-29 Charm Sciences, Inc. Lateral flow test kit and method for detecting an analyte
US20100285610A1 (en) * 2005-02-18 2010-11-11 Saul Steven J Lateral Flow Test Kit and Method for Detecting an Analyte
US9784734B2 (en) 2005-03-11 2017-10-10 Chembio Diagnostic Systems, Inc. Dual path immunoassay device
US20070148781A1 (en) * 2005-03-11 2007-06-28 Javanbakhsh Esfandiari Dual Path Immunoassay Device
US20080318341A1 (en) * 2005-03-11 2008-12-25 Javanbakhsh Esfandiari Dual Path Immunoassay Device
US7682801B2 (en) 2005-03-11 2010-03-23 Chembio Diagnostic Systems, Inc. Dual path immunoassay device
US8877450B2 (en) 2005-03-11 2014-11-04 Chembio Diagnostic Systems, Inc. Dual path immunoassay device
US7879597B2 (en) 2005-03-11 2011-02-01 Chembio Diagnostic Systems, Inc. Dual path immunoassay device
US20060205059A1 (en) * 2005-03-11 2006-09-14 Javanbakhsh Esfandiari Dual path immunoassay device
US20100173397A1 (en) * 2005-03-11 2010-07-08 Javanbakhsh Esfandiari Dual Path Immunoassay Device
US8507259B2 (en) 2005-03-11 2013-08-13 Chembio Diagnostics Systems, Inc. Dual path immunoassay device
US8932878B2 (en) 2005-03-30 2015-01-13 Kimberly-Clark Worldwide, Inc. Diagnostic test kits employing an internal calibration system
US7939342B2 (en) 2005-03-30 2011-05-10 Kimberly-Clark Worldwide, Inc. Diagnostic test kits employing an internal calibration system
US8173380B2 (en) 2005-04-29 2012-05-08 Kimberly-Clark Worldwide, Inc. Metering technique for lateral flow assay devices
US20110097734A1 (en) * 2005-04-29 2011-04-28 Kimberly-Clark Worldwide, Inc. Flow Control Technique for Assay Devices
US8124421B2 (en) 2005-04-29 2012-02-28 Kimberly-Clark Worldwide, Inc. Flow control technique for assay devices
US7803319B2 (en) 2005-04-29 2010-09-28 Kimberly-Clark Worldwide, Inc. Metering technique for lateral flow assay devices
US20060246600A1 (en) * 2005-04-29 2006-11-02 Kimberly-Clark Worldwide, Inc. Metering technique for lateral flow assay devices
US20100323392A1 (en) * 2005-04-29 2010-12-23 Kimberly-Clark Worldwide, Inc. Metering Technique for Lateral Flow Assay Devices
US7858384B2 (en) 2005-04-29 2010-12-28 Kimberly-Clark Worldwide, Inc. Flow control technique for assay devices
US20060246597A1 (en) * 2005-04-29 2006-11-02 Kimberly-Clark Worldwide, Inc. Flow control technique for assay devices
US20060263907A1 (en) * 2005-04-29 2006-11-23 Zweig Stephen E Fluorescence lateral flow immunoassay
US20090181416A1 (en) * 2005-08-31 2009-07-16 Kimberly-Clark Worldwide, Inc. Enzyme Detection Technique
US20070048815A1 (en) * 2005-08-31 2007-03-01 Kimberly-Clark Worldwide, Inc. Enzyme detection technique
US20070048182A1 (en) * 2005-08-31 2007-03-01 Kimberly-Clark Worldwide, Inc. Nitrite detection technique
US20070048807A1 (en) * 2005-08-31 2007-03-01 Kimberly-Clark Worldwide, Inc. Diagnostic test kits with improved detection accuracy
US7829347B2 (en) 2005-08-31 2010-11-09 Kimberly-Clark Worldwide, Inc. Diagnostic test kits with improved detection accuracy
US8003399B2 (en) 2005-08-31 2011-08-23 Kimberly-Clark Worldwide, Inc. Nitrite detection technique
US7504235B2 (en) 2005-08-31 2009-03-17 Kimberly-Clark Worldwide, Inc. Enzyme detection technique
US20070121181A1 (en) * 2005-11-22 2007-05-31 Cyvera Corporation Method and apparatus for labeling using optical identification elements characterized by X-ray diffraction
US20100025482A1 (en) * 2005-11-22 2010-02-04 Illumina Corporation Composition including an item and an encoded optical identification element that is physically associated with the item
US20070134811A1 (en) * 2005-12-13 2007-06-14 Kimberly-Clark Worldwide, Inc. Metering technique for lateral flow assay devices
US7838258B2 (en) 2005-12-14 2010-11-23 Kimberly-Clark Worldwide, Inc. Meter strip and method for lateral flow assay devices
US20100015658A1 (en) * 2005-12-14 2010-01-21 Kimberly-Clark Worldwide, Inc Meter Strip and Method for Lateral Flow Assay Devices
US20070134810A1 (en) * 2005-12-14 2007-06-14 Kimberly-Clark Worldwide, Inc. Metering strip and method for lateral flow assay devices
US7794656B2 (en) 2006-01-23 2010-09-14 Quidel Corporation Device for handling and analysis of a biological sample
US20070275475A1 (en) * 2006-01-23 2007-11-29 Greg Liang Rapid Test Apparatus
US20090004058A1 (en) * 2006-01-23 2009-01-01 Greg Liang Device for handling and analysis of a biological sample
US7871568B2 (en) 2006-01-23 2011-01-18 Quidel Corporation Rapid test apparatus
US8105794B2 (en) 2006-02-07 2012-01-31 Toxcure Llc Rapid nasal assay kit
US7888049B2 (en) 2006-02-07 2011-02-15 Toxcure. LLC Rapid nasal assay kit
US20110177529A1 (en) * 2006-02-07 2011-07-21 Toxcure, LLC Rapid nasal assay kit
US20070184495A1 (en) * 2006-02-07 2007-08-09 Shaari Christopher M Rapid nasal assay kit
US20070236789A1 (en) * 2006-04-10 2007-10-11 Moon John A Optical scanner with improved scan time
US7830575B2 (en) 2006-04-10 2010-11-09 Illumina, Inc. Optical scanner with improved scan time
US7749775B2 (en) 2006-10-03 2010-07-06 Jonathan Scott Maher Immunoassay test device and method of use
US20080081341A1 (en) * 2006-10-03 2008-04-03 Jonathan Scott Maher Immunoassay test device and method of use
US20080138842A1 (en) * 2006-12-11 2008-06-12 Hans Boehringer Indirect lateral flow sandwich assay
US8012761B2 (en) 2006-12-14 2011-09-06 Kimberly-Clark Worldwide, Inc. Detection of formaldehyde in urine samples
US20080145947A1 (en) * 2006-12-14 2008-06-19 Kimberly-Clark Worldwide, Inc. Detection of formaldehyde in urine samples
US20080145949A1 (en) * 2006-12-15 2008-06-19 Xuedong Song Indicator immobilization on assay devices
US7935538B2 (en) 2006-12-15 2011-05-03 Kimberly-Clark Worldwide, Inc. Indicator immobilization on assay devices
US20080145272A1 (en) * 2006-12-15 2008-06-19 Feaster Shawn R Lateral flow assay device
US8377379B2 (en) 2006-12-15 2013-02-19 Kimberly-Clark Worldwide, Inc. Lateral flow assay device
US8835184B2 (en) 2007-09-14 2014-09-16 Biosensia Patents Limited Analysis system
US20110171754A1 (en) * 2007-09-14 2011-07-14 Gareth Redmond Analysis system
WO2009108224A1 (en) * 2007-11-16 2009-09-03 Eugene Tu Viral detection apparatus and method
US20090208975A1 (en) * 2007-12-13 2009-08-20 Beckman Coulter, Inc. Device and methods for detecting a target cell
US20090305231A1 (en) * 2008-04-09 2009-12-10 Becton, Dickinson And Company Sensitive Immunoassays Using Coated Nanoparticles
EP2952897A1 (en) 2008-04-09 2015-12-09 Becton, Dickinson and Company Sensitive immunoassays using coated nanoparticles
US11350913B2 (en) 2008-07-24 2022-06-07 Chembio Diagnostic Systems, Inc. Method and apparatus for collecting and preparing biological samples for testing
US9234889B1 (en) 2008-12-18 2016-01-12 Charm Sciences, Inc. Method and test strip for detecting residues
US9414813B2 (en) 2009-02-16 2016-08-16 Express Diagnostics Int'l, Inc. Device for assaying analytes in bodily fluids
US9462998B2 (en) 2009-02-16 2016-10-11 Express Diagnostics Int'l, Inc. Device for assaying analytes in bodily fluids
US10076314B2 (en) 2009-02-16 2018-09-18 Express Diagnostics Int'l, Inc. Device for assaying analytes in bodily fluids
US20100290948A1 (en) * 2009-05-15 2010-11-18 Xuedong Song Absorbent articles capable of indicating the presence of urinary tract infections
US9199232B2 (en) 2010-04-07 2015-12-01 Biosensia Patents Limited Flow control device for assays
WO2012099897A1 (en) 2011-01-18 2012-07-26 Symbolics, Llc Lateral flow assays using two dimensional features
US11016090B2 (en) 2011-01-18 2021-05-25 Symbolics, Llc Lateral flow assays using two dimensional features
US9851366B2 (en) 2011-01-18 2017-12-26 Symbolics, Llc Lateral flow assays using two dimensional features
US9874576B2 (en) 2011-01-18 2018-01-23 Symbolics, Llc Lateral flow assays using two dimensional features
EP3187876A1 (en) 2011-01-18 2017-07-05 Symbolics, LLC Lateral flow assays using two dimensional features
US8486717B2 (en) 2011-01-18 2013-07-16 Symbolics, Llc Lateral flow assays using two dimensional features
US8603835B2 (en) 2011-02-10 2013-12-10 Chembio Diagnostic Systems, Inc. Reduced step dual path immunoassay device and method
WO2014012077A1 (en) 2012-07-13 2014-01-16 Genisphere, Llc Lateral flow assays using dna dendrimers
US9651549B2 (en) 2012-07-13 2017-05-16 Genisphere, Llc Lateral flow assays using DNA dendrimers
US9874556B2 (en) 2012-07-18 2018-01-23 Symbolics, Llc Lateral flow assays using two dimensional features
WO2014015076A1 (en) 2012-07-18 2014-01-23 Symbolics, Llc Lateral flow assays using two dimensional features
WO2014043247A1 (en) 2012-09-12 2014-03-20 Force Diagnostics, Inc Rapid tests for insurance underwriting
US10408828B2 (en) 2013-02-26 2019-09-10 Astute Medical, Inc. Lateral flow assay with test strip retainer
WO2014134033A1 (en) 2013-02-26 2014-09-04 Astute Medical, Inc. Lateral flow assay with test strip retainer
US10670596B2 (en) 2013-02-26 2020-06-02 Astute Medical, Inc. Lateral flow assay with test strip retainer
US9599615B2 (en) 2013-03-13 2017-03-21 Symbolics, Llc Lateral flow assays using two dimensional test and control signal readout patterns
US12195531B2 (en) 2013-03-21 2025-01-14 Code Biotherapeutics, Inc. Cellular delivery of DNA intercalating agents
WO2015038978A1 (en) 2013-09-13 2015-03-19 Symbolics, Llc Lateral flow assays using two dimensional test and control signal readout patterns
US10598657B2 (en) 2014-04-02 2020-03-24 Chembio Diagnostic Systems, Inc. Immunoassay utilizing trapping conjugate
US10473655B2 (en) 2014-04-02 2019-11-12 Chembio Diagnostic Systems, Inc. Immunoassay utilizing trapping conjugate
US10908158B2 (en) 2014-04-02 2021-02-02 Chembio Diagnostic Systems, Inc. Immunoassay methods utilizing trapping conjugate
US10976315B2 (en) 2014-04-02 2021-04-13 Chembio Diagnostic Systems, Inc. Immunoassay utilizing trapping conjugate
US9891216B2 (en) 2014-04-02 2018-02-13 Chembio Diagnostic Systems, Inc. Immunoassay methods utilizing trapping conjugate
US9885710B2 (en) 2014-04-02 2018-02-06 Chembio Diagnostic Systems, Inc. Immunoassay utilizing trapping conjugate
US10690667B2 (en) 2014-10-27 2020-06-23 Chembio Diagnostic Systems, Inc. Rapid screening assay for qualitative detection of multiple febrile illnesses
WO2016164365A1 (en) 2015-04-06 2016-10-13 Bludiagnostics, Inc. A test device for detecting an analyte in a saliva sample and method of use
US10094793B2 (en) 2015-09-19 2018-10-09 The Board Of Regents Of The University Of Texas System Nanomaterial-based photothermal immunosensing for quantitative detection of disease biomarkers
WO2018039047A1 (en) 2016-08-23 2018-03-01 Qoolabs, Inc. Lateral flow assay for assessing recombinant protein expression or reporter gene expression
US11293839B2 (en) 2018-08-16 2022-04-05 Epitope Biotechnology Co., Ltd. Device for fecal sample collection and extraction
WO2022027037A1 (en) 2020-07-27 2022-02-03 Single Cell Technology, Inc. Anti-sars corona virus-2 spike protein antibodies

Similar Documents

Publication Publication Date Title
USRE38430E1 (en) Solid phase chromatographic immunoassay
US5591645A (en) Solid phase chromatographic immunoassay
KR900005482B1 (en) Solid phase assay employing capillary flow
US6194220B1 (en) Non-instrumented assay with quantitative and qualitative results
US5998221A (en) Non-instrumented assay with quantitative and qualitative results
US6057165A (en) Quality control procedure for membrane flow-through diagnostic assay devices
EP0675361B1 (en) Method for storage of labile protein materials
EP0465266B1 (en) Complementary visual signal immunoassay
US5789154A (en) Liposome-enhanced immunoassay and test device
US5081013A (en) Immunodiagnostic device and method
US5073340A (en) Depositing a binder on a solid support
EP0154749A1 (en) Solid phase immunoassay with visual readout
EP0564494B1 (en) Test method and reagent kit therefor
WO1999064864A9 (en) Optimizing sensitivity in colloidal colorimetric flow through and lateral flow tests
US5567591A (en) Amplified assay for analyte
CA1318588C (en) Method and device for separating plasma from red cells
US5204061A (en) Depositing a binder on a solid support
EP0302673B1 (en) system and process for a visible assay for analyte
WO1999064863A1 (en) Colloidal colorimetric flow through and lateral flow assays utilizing soluble submicron particles
US5260025A (en) Depositing a binder on a solid support
CA1335321C (en) Process for immunochromatography with colloidal particles
JP2003262637A (en) Inspection piece and inspection method

Legal Events

Date Code Title Description
FPAY Fee payment

Year of fee payment: 8

SULP Surcharge for late payment

Year of fee payment: 7

FPAY Fee payment

Year of fee payment: 12