US20050112703A1 - Membrane-based lateral flow assay devices that utilize phosphorescent detection - Google Patents

Membrane-based lateral flow assay devices that utilize phosphorescent detection Download PDF

Info

Publication number
US20050112703A1
US20050112703A1 US10718989 US71898903A US2005112703A1 US 20050112703 A1 US20050112703 A1 US 20050112703A1 US 10718989 US10718989 US 10718989 US 71898903 A US71898903 A US 71898903A US 2005112703 A1 US2005112703 A1 US 2005112703A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
defined
method
detection
assay device
phosphorescent
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.)
Abandoned
Application number
US10718989
Inventor
Xuedong Song
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.)
Kimberly-Clark Worldwide Inc
Original Assignee
Kimberly-Clark Worldwide Inc
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

Links

Images

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/558Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6428Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302Apparatus specially adapted for immunological test procedures
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54393Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/585Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with a particulate label, e.g. coloured latex
    • G01N33/587Nanoparticles
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/805Test papers
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/81Packaged device or kit
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/97Test strip or test slide
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00Chemistry: analytical and immunological testing
    • Y10S436/805Optical property
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00Chemistry: analytical and immunological testing
    • Y10S436/807Apparatus included in process claim, e.g. physical support structures
    • Y10S436/81Tube, bottle, or dipstick

Abstract

A lateral flow, membrane-based assay device for detecting the presence or quantity of an analyte residing in a test sample is provided. The device utilizes phosphorescence to detect the signals generated by excited phosphorescent labels. The labels may have a long emission lifetime so that background interference from many sources, such as scattered light and autofluorescence, is practically eliminated during detection. In addition, the phosphorescent labels may be encapsulated within particles to shield the labels from quenchers, such as oxygen or water, which might disrupt the phosphorescent signal.

Description

    BACKGROUND OF THE INVENTION
  • Phosphorescence is the result of a three-stage process. In the first stage, energy is supplied by an external source, such as an incandescent lamp or a laser, and absorbed by the phosphorescent compound, creating excited electronic triplet states (as opposed to fluorescence, which only has a singlet excited state). In the second stage, the excited states exist for a finite time during which the phosphorescent compound undergoes conformational changes and is also subject to a multitude of possible interactions with its molecular environment. During this time, the energy of the excited states is partially dissipated, yielding relaxed states from which phosphorescence emission originates. The third stage is the phosphorescence emission stage wherein energy is emitted, returning the phosphorescence compound to its ground states. The emitted energy is lower than its excitation energy (light or laser) and thus of a longer wavelength. This shift or difference in energy or wavelength allows the emission energy to be detected and isolated from the excitation energy.
  • Various phosphorescent compounds, such as metalloporphyrins, have been proposed for use in immunoassays. Unfortunately, many of the proposed techniques fail to solve the problem of quenching. Specifically, oxygen and water are strong quenchers of triplet states and may cause decay of the phosphorescence signal, thereby limiting its use in most practical assay applications. In addition, many of the techniques that have been proposed are simply ill equipped for use in lateral flow, membrane-based devices. For example, in a lateral flow, membrane-based assay device, the concentration of the analyte is reduced because it is diluted by a liquid that may flow through the porous membrane. However, background interference becomes increasingly problematic at such low analyte concentrations because the phosphorescent intensity is relatively low. Because the structure of the membrane also tends to reflect the excited light, the ability of a detector to accurately measure the phosphorescent intensity of the labeled analyte is substantially reduced. In fact, the intensity of the emitted phosphorescence signal may be three to four orders of magnitude smaller than the excitation light reflected by the porous membrane. Many membranes, such as nitrocellulose membranes, also exhibit strong fluorescence when excited in the UV and visible regions. This fluorescence can interfere with the accuracy of phosphorescence measurements.
  • As such, a need currently exists for a simple, inexpensive, and effective system for using phosphorescence as a detection technique for membrane-based, lateral flow assay devices.
  • SUMMARY OF THE INVENTION
  • In accordance with one embodiment of the present invention, a method for detecting the presence or quantity of an analyte residing in a test sample is disclosed. The method comprises:
      • i) providing a lateral flow assay device that comprises a porous membrane in fluid communication with detection probes, the detection probes comprising a phosphorescent label encapsulated within a matrix, wherein the porous membrane defines a detection zone within which is immobilized a capture reagent that is configured to bind to the detection probes or complexes thereof;
      • ii) contacting the detection probes with the test sample;
      • iii) allowing the detection probes and the test sample to flow to the detection zone;
      • iv) exciting the phosphorescent label at the detection zone to generate an emitted detection signal; and
      • v) measuring the intensity of the detection signal, wherein the amount of the analyte within the test sample is proportional to the intensity of the detection signal.
  • In accordance with another embodiment of the present invention, a lateral flow assay device for detecting the presence or quantity of an analyte residing in a test sample is disclosed. The assay device comprises a porous membrane in fluid communication with detection probes. The detection probes comprise a phosphorescent metal complex encapsulated within a matrix. The porous membrane defines a detection zone within which a capture reagent is immobilized that is configured to bind to the detection probes or complexes thereof to generate a detection signal, wherein the amount of the analyte in the test sample is proportional to the intensity of the detection signal.
  • Other features and aspects of the present invention are discussed in greater detail below.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • A full and enabling disclosure of the present invention, including the best mode thereof, directed to one of ordinary skill in the art, is set forth more particularly in the remainder of the specification, which makes reference to the appended figures in which:
  • FIG. 1 is a perspective view of one embodiment of a lateral flow, membrane-based device of the present invention;
  • FIG. 2 is a schematic diagram of one embodiment of a phosphorescence reader that may be used in the present invention, including representative electronic components thereof;
  • FIG. 3 is a schematic diagram of another embodiment of a phosphorescence reader that may be used in the present invention, including representative electronic components thereof; and
  • FIG. 4 is a schematic diagram of still another embodiment of a phosphorescence reader that may be used in the present invention, including representative electronic components thereof.
  • Repeat use of reference characters in the present specification and drawings is intended to represent same or analogous features or elements of the invention.
  • DETAILED DESCRIPTION OF REPRESENTATIVE EMBODIMENTS Definitions
  • As used herein, the term “analyte” generally refers to a substance to be detected. For instance, analytes may include antigenic substances, haptens, antibodies, and combinations thereof. Analytes include, but are not limited to, toxins, organic compounds, proteins, peptides, microorganisms, amino acids, nucleic acids, hormones, steroids, vitamins, drugs (including those administered for therapeutic purposes as well as those administered for illicit purposes), drug intermediaries or byproducts, bacteria, virus particles and metabolites of or antibodies to any of the above substances. Specific examples of some analytes include ferritin; creatinine kinase MB (CK-MB); digoxin; phenyloin; phenobarbitol; carbamazepine; vancomycin; gentamycin; theophylline; valproic acid; quinidine; luteinizing hormone (LH); follicle stimulating hormone (FSH); estradiol, progesterone; C-reactive protein; lipocalins; IgE antibodies; cytokines; vitamin B2 micro-globulin; glycated hemoglobin (Gly. Hb); cortisol; digitoxin; N-acetylprocainamide (NAPA); procainamide; antibodies to rubella, such as rubella-IgG and rubella IgM; antibodies to toxoplasmosis, such as toxoplasmosis IgG (Toxo-IgG) and toxoplasmosis IgM (Toxo-IgM); testosterone; salicylates; acetaminophen; hepatitis B virus surface antigen (HBsAg); antibodies to hepatitis B core antigen, such as anti-hepatitis B core antigen IgG and IgM (Anti-HBC); human immune deficiency virus 1 and 2 (HIV 1 and 2); human T-cell leukemia virus 1 and 2 (HTLV); hepatitis B e antigen (HBeAg); antibodies to hepatitis B e antigen (Anti-HBe); influenza virus; thyroid stimulating hormone (TSH); thyroxine (T4); total triiodothyronine (Total T3); free triiodothyronine (Free T3); carcinoembryoic antigen (CEA); lipoproteins, cholesterol, and triglycerides; and alpha fetoprotein (AFP). Drugs of abuse and controlled substances include, but are not intended to be limited to, amphetamine; methamphetamine; barbiturates, such as amobarbital, secobarbital, pentobarbital, phenobarbital, and barbital; benzodiazepines, such as librium and valium; cannabinoids, such as hashish and marijuana; cocaine; fentanyl; LSD; methaqualone; opiates, such as heroin, morphine, codeine, hydromorphone, hydrocodone, methadone, oxycodone, oxymorphone and opium; phencyclidine; and propoxyhene. Other potential analytes may be described in U.S. Pat. No. 6,436,651 to Everhart, et al. and U.S. Pat. No. 4,366,241 to Tom et al.
  • As used herein, the term “test sample” generally refers to a material suspected of containing the analyte. The test sample may be used directly as obtained from the source or following a pretreatment to modify the character of the sample. The test sample may be derived from any biological source, such as a physiological fluid, including, blood, interstitial fluid, saliva, ocular lens fluid, cerebral spinal fluid, sweat, urine, milk, ascites fluid, mucous, synovial fluid, peritoneal fluid, vaginal fluid, amniotic fluid or the like. The test sample may be pretreated prior to use, such as preparing plasma from blood, diluting viscous fluids, and the like. Methods of treatment may involve filtration, precipitation, dilution, distillation, mixing, concentration, inactivation of interfering components, and the addition of reagents. Besides physiological fluids, other liquid samples may be used such as water, food products and the like for the performance of environmental or food production assays. In addition, a solid material suspected of containing the analyte may be used as the test sample. In some instances it may be beneficial to modify a solid test sample to form a liquid medium or to release the analyte.
  • DETAILED DESCRIPTION
  • Reference now will be made in detail to various embodiments of the invention, one or more examples of which are set forth below. Each example is provided by way of explanation of the invention, not limitation of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations may be made in the present invention without departing from the scope or spirit of the invention. For instance, features illustrated or described as part of one embodiment, may be used on another embodiment to yield a still further embodiment. Thus, it is intended that the present invention covers such modifications and variations as come within the scope of the appended claims and their equivalents.
  • In general, the present invention is directed to a lateral flow, membrane-based assay device for detecting the presence or quantity of an analyte residing in a test sample. The device utilizes phosphorescence to detect the signals generated by excited phosphorescent labels. The labels may have a long emission lifetime so that background interference from many sources, such as scattered light and autofluorescence, is practically eliminated during detection. In addition, the phosphorescent labels may be encapsulated within particles to shield the labels from quenchers, such as oxygen or water, which might disrupt the phosphorescent signal.
  • Referring to FIG. 1, for instance, one embodiment of a flow-through assay device 20 that may be formed according to the present invention will now be described in more detail. As shown, the device 20 contains a porous membrane 23 optionally supported by a rigid material 21. In general, the porous membrane 23 may be made from any of a variety of materials through which the test sample is capable of passing. For example, the materials used to form the porous membrane 23 may include, but are not limited to, natural, synthetic, or naturally occurring materials that are synthetically modified, such as polysaccharides (e.g., cellulose materials such as paper and cellulose derivatives, such as cellulose acetate and nitrocellulose); polyether sulfone; polyethylene; nylon; polyvinylidene fluoride (PVDF); polyester; polypropylene; silica; inorganic materials, such as deactivated alumina, diatomaceous earth, MgSO4, or other inorganic finely divided material uniformly dispersed in a porous polymer matrix, with polymers such as vinyl chloride, vinyl chloride-propylene copolymer, and vinyl chloride-vinyl acetate copolymer; cloth, both naturally occurring (e.g., cotton) and synthetic (e.g., nylon or rayon); porous gels, such as silica gel, agarose, dextran, and gelatin; polymeric films, such as polyacrylamide; and the like. In one particular embodiment, the porous membrane 23 is formed from nitrocellulose and/or polyether sulfone materials. It should be understood that the term “nitrocellulose” refers to nitric acid esters of cellulose, which may be nitrocellulose alone, or a mixed ester of nitric acid and other acids, such as aliphatic carboxylic acids having from 1 to 7 carbon atoms.
  • The device 20 may also contain a wicking pad 28. The wicking pad 28 generally receives fluid that has migrated through the entire porous membrane 23. As is well known in the art, the wicking pad 28 may assist in promoting capillary action and fluid flow through the membrane 23.
  • To initiate the detection of an analyte within the test sample, a user may directly apply the test sample to a portion of the porous membrane 23 through which it may then travel. Alternatively, the test sample may first be applied to a sampling pad (not shown) that is in fluid communication with the porous membrane 23. Some suitable materials that may be used to form the sampling pad include, but are not limited to, nitrocellulose, cellulose, porous polyethylene pads, and glass fiber filter paper. If desired, the sampling pad may also contain one or more assay pretreatment reagents, either diffusively or non-diffusively attached thereto.
  • In the illustrated embodiment, the test sample travels from the sampling pad (not shown) to a conjugate pad 22 that is placed in communication with one end of the sampling pad. The conjugate pad 22 is formed from a material through which the test sample is capable of passing. For example, in one embodiment, the conjugate pad 22 is formed from glass fibers. Although only one conjugate pad 22 is shown, it should be understood that other conjugate pads may also be used in the present invention.
  • To facilitate accurate detection of the presence or absence of an analyte within the test sample, labels are applied at various locations of the device 20. The labels may be used for both detection of the analyte and for calibration. Generally speaking, at least a portion of the labels used in the device 20 contain a phosphorescent compound. In general, such phosphorescent compounds may be phosphorescent molecules, polymers, dendrimers, particles, and so forth. In one particular embodiment, for example, the phosphorescent compound is a metal complex that includes one or more metals, such as ruthenium, osmium, rhenium, iridium, rhodium, platinum, indium, palladium, molybdenum, technetium, copper, iron, chromium, tungsten, zinc, and so forth. Especially preferred are ruthenium, rhenium, osmium, platinum, and palladium.
  • The metal complex may contain one or more ligands that facilitate the solubility of the complex in an aqueous or nonaqueous environments. For example, some suitable examples of ligands include, but are not limited to, pyridine; pyrazine; isonicotinamide; imidazole; bipyridine; terpyridine; phenanthroline; dipyridophenazine; porphyrin, porphine, and derivatives thereof. Such ligands may be, for instance, substituted with alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, carboxylate, carboxaldehyde, carboxamide, cyano, amino, hydroxy, imino, hydroxycarbonyl, aminocarbonyl, amidine, guanidinium, ureide, sulfur-containing groups, phosphorus containing groups, and the carboxylate ester of N-hydroxy-succinimide.
  • For example, porphyrins and porphine metal complexes possess pyrrole groups coupled together with methylene bridges to form cyclic structures with metal chelating inner cavities. Many of these molecules exhibit strong phosphorescence properties at room temperature in suitable solvents (e.g., water) and an oxygen-free environment. Some suitable porphyrin complexes that are capable of exhibiting phosphorescent properties include, but are not limited to, platinum(II)coproporphyrin-I and III, palladium(II)coproporphyrin, ruthenium coproporphyrin, zinc(II)-coproporphyrin-I, derivatives thereof, and so forth. Similarly, some suitable porphine complexes that are capable of exhibiting phosphorescent properties include, but not limited to, platinum(II)tetra-meso-fluorophenylporphine and palladium(II)tetra-meso-fluorophenylporphine. Still other suitable porphyrin and/or porphine complexes are described in U.S. Pat. No. 4,614,723 to Schmidt, et al.; U.S. Pat. No. 5,464,741 to Hendrix; U.S. Pat. No. 5,518,883 to Soini; U.S. Pat. No. 5,922,537 to Ewart, et al.; U.S. Pat. No. 6,004,530 to Sagner, et al.; and U.S. Pat. No. 6,582,930 to Ponomarev, et al., which are incorporated herein in their entirety by reference thereto for all purposes.
  • As indicated above, bipyridine metal complexes may also be utilized in the present invention. Some examples of suitable bipyridine complexes include, but are note limited to, bis[(4,4′-carbomethoxy)-2,2′-bipyridine]2-[3-(4-methyl-2,2′-bipyridine-4-yl)propyl]-1,3-dioxolane ruthenium(II); bis(2,2′bipyridine)[4-(butan-1-al)-4′-methyl-2,2′-bi-pyridine]ruthenium(II); bis(2,2′-bipyridine)[4-(4′-methyl-2,2′-bipyridine-4′-yl)-butyric acid]ruthenium(II); tris(2,2′bipyridine)ruthenium(II); (2,2′-bipyridine) [bis-bis(1,2-diphenylphosphino)ethylene]2-[3-(4-methyl-2,2′-bipyridine-4′-yl)propyl]-1,3-dioxolane osmium(II); bis(2,2′-bipyridine)[4-(4′-methyl-2,2′-bipyridine)-butylamine]ruthenium(II); bis(2,2′-bipyridine)[1-bromo-4(4′-methyl-2,2′-bipyridine-4-yl)butane]ruthenium(II); bis(2,2′-bipyridine)maleimidohexanoic acid, 4-methyl-2,2′-bipyridine-4′-butylamide ruthenium(II), and so forth. Still other suitable metal complexes that may exhibit phosphorescent properties may be described in U.S. Pat. No. 6,613,583 to Richter, et al.; U.S. Pat. No. 6,468,741 to Massey, et al.; U.S. Pat. No. 6,444,423 to Meade, et al.; U.S. Pat. No. 6,362,011 to Massey, et al.; U.S. Pat. No. 5,731,147 to Bard, et al.; and U.S. Pat. No. 5,591,581 to Massey, et al., which are incorporated herein in their entirety by reference thereto for all purposes.
  • Regardless of the type of phosphorescent label utilized, the exposure of the label to quenchers, such as oxygen or water, may result in a disruption of the phosphorescent signal. Thus, to ensure that the phosphorescent labels are capable of emitting the desired signal intensity, they are generally encapsulated within a matrix that acts as a barrier to the relevant quencher. For instance, in some embodiments, the matrix may have a low solubility in water and oxygen, and also be relatively impermeable to water and oxygen. In this manner, the phosphorescent label may be protected from emission decay that would otherwise result from exposure to oxygen or water. For example, the matrix may protect the label such that less than about 30%, in some embodiments less than about 20%, and in some embodiments, less than about 10% of the total phosphorescent signal is quenched when the detection probes are exposed to a particular quencher.
  • Various types of barrier matrices may be employed in the present invention to inhibit quenching of the phosphorescent compounds. For example, in some embodiments, the phosphorescent compound may be encapsulated within a particle. Some suitable particles that may be suitable for this purpose include, but not limited to, metal oxides (e.g., silica, alumina, etc.), polymer particles, and so forth. For example, latex polymer particles may be utilized, such as those formed from polystyrene, butadiene styrenes, styreneacrylic-vinyl terpolymer, polymethylmethacrylate, polyethylmethacrylate, styrene-maleic anhydride copolymer, polyvinyl acetate, polyvinylpyridine, polydivinylbenzene, polybutyleneterephthalate, acrylonitrile, vinylchloride-acrylates, derivatives thereof, etc. Other suitable particles may be described in U.S. Pat. No. 5,670,381 to Jou, et al. and U.S. Pat. No. 5,252,459 to Tarcha, et al., which are incorporated herein in their entirety by reference thereto for all purposes.
  • The phosphorescent compound may be encapsulated within the particulate matrix during and/or after particle formation. In one embodiment, encapsulated latex particles are formed through well-known precipitation techniques. For example, polymer particles may be co-dissolved with the phosphorescent compound in an organic solvent. Thereafter, another solvent may then be added to co-precipitate both the phosphorescent molecules and polymer particles. Some examples of suitable solvents that may be used in such a co-precipitation process include, but are not limited to, water, acetone, acetonitrile, tetrahydrofuran, methylene chloride, cyclohexane, chloroform, ethyl ether, propyl ether, methyl acetate, methyl alcohol, ethyl alcohol, propyl alcohol, pentane, pentene, hexane, methyl ethyl ketone, and other similar solvents.
  • Besides precipitation, other techniques for forming encapsulated phosphorescent particles may also be used in the present invention. In one embodiment, for example, latex-based phosphorescent particles are formed using swelling techniques. Specifically, a polymer particle is swelled with a swelling agent containing one or more volatile components and phosphorescent molecules. When swollen, the phosphorescent compound may permeate through the polymer particles and become encapsulated therein. Removal of the swelling solvent results in the encapsulated particles. Emulsion polymerization may also be used to form phosphorescent particles. For example, monomers covalently tagged with a phosphorescent moiety may be co-polymerized with other monomers to form phosphorescent particles.
  • Regardless of the technique by which they are formed, the shape of the encapsulated phosphorescent particles may generally vary. In one particular embodiment, for instance, the particles are spherical in shape. However, it should be understood that other shapes are also contemplated by the present invention, such as plates, rods, discs, bars, tubes, irregular shapes, etc. In addition, the size of the particles may also vary. For instance, the average size (e.g., diameter) of the particles may range from about 0.1 nanometers to about 1,000 microns, in some embodiments, from about 0.1 nanometers to about 100 microns, and in some embodiments, from about 1 nanometer to about 10 microns. For instance, “micron-scale” particles are often desired. When utilized, such “micron-scale” particles may have a average size of from about 1 micron to about 1,000 microns, in some embodiments from about 1 micron to about 100 microns, and in some embodiments, from about 1 micron to about 10 microns. Likewise, “nano-scale” particles may also be utilized. Such “nano-scale” particles may have an average size of from about 0.1 to about 10 nanometers, in some embodiments from about 0.1 to about 5 nanometers, and in some embodiments, from about 1 to about 5 nanometers.
  • In one embodiment of the present invention, the encapsulated phosphorescent particles form detection probes that are used to detect the presence or absence of an analyte within a test sample. In some instances, it is desired to modify the detection probes in some manner so that they are more readily able to bond to the analyte. In such instances, the detection probes may be modified with certain specific binding members to form conjugated detection probes. Specific binding members generally refer to a member of a specific binding pair, i.e., two different molecules where one of the molecules chemically and/or physically binds to the second molecule. For instance, immunoreactive specific binding members may include antigens, haptens, aptamers, antibodies, and complexes thereof, including those formed by recombinant DNA methods or peptide synthesis. An antibody may be a monoclonal or polyclonal antibody, a recombinant protein or a mixture(s) or fragment(s) thereof, as well as a mixture of an antibody and other specific binding members. The details of the preparation of such antibodies and their suitability for use as specific binding members are well known to those skilled in the art. Other common specific binding pairs include but are not limited to, biotin and avidin, biotin and streptavidin, antibody-binding proteins (such as protein A or G) and antibodies, carbohydrates and lectins, complementary nucleotide sequences (including label and capture nucleic acid sequences used in DNA hybridization assays to detect a target nucleic acid sequence), complementary peptide sequences including those formed by recombinant methods, effector and receptor molecules, hormone and hormone binding protein, enzyme cofactors and enzymes, enzyme inhibitors and enzymes, and so forth. Furthermore, specific binding pairs may include members that are analogs of the original specific binding member. For example, a derivative or fragment of the analyte, i.e., an analyte-analog, may be used so long as it has at least one epitope in common with the analyte.
  • The specific binding members may generally be attached to the detection probes using any of a variety of well-known techniques. For instance, covalent attachment of the specific binding members to the particles may be accomplished using carboxylic, amino, aldehyde, bromoacetyl, iodoacetyl, thiol, epoxy and other reactive or linking functional groups, as well as residual free radicals and radical cations, through which a protein coupling reaction may be accomplished. A surface functional group may also be incorporated as a functionalized co-monomer because the surface of the particle may contain a relatively high surface concentration of polar groups. In addition, although particles are often functionalized after synthesis, in certain cases, such as poly(thiophenol), the particles are capable of direct covalent linking with a protein without the need for further modification. For example, in one embodiment, the first step of conjugation is activation of carboxylic groups on the particle surface using carbodiimide. In the second step, the activated carboxylic acid groups are reacted with an amino group of an antibody to form an amide bond. The activation and/or antibody coupling may occur in a buffer, such as phosphate-buffered saline (PBS) (e.g., pH of 7.2) or 2-(N-morpholino)ethane sulfonic acid (MES) (e.g., pH of 5.3). As shown, the resulting particles may then be blocked with ethanolamine, for instance, to form the conjugated probe. Besides covalent bonding, other attachment techniques, such as physical adsorption, may also be utilized in the present invention.
  • In general, a variety of flow-through assay devices may be constructed according to the present invention for use in conjunction with a phosphorescence detection system. In this regard, various embodiments of the present invention will now be described in more detail. It should be understood, however, that the embodiments discussed below are only exemplary, and that other embodiments are also contemplated by the present invention. For instance, referring again to FIG. 1, one system for detecting the presence of an analyte within a test sample is schematically illustrated. Initially, a test sample containing an analyte is applied to the sampling pad (not shown). From the sampling pad, the test sample may then travel to the conjugate pad 22, where the analyte mixes with detection probes to form analyte complexes. In one embodiment, for example, the detection probes are formed from microparticles that encapsulate a porphyrin or porphine dye, such as described above, and bound to a specific binding member for the analyte of interest. Moreover, because the conjugate pad 22 is in fluid communication with the porous membrane 23, the complexes may migrate from the conjugate pad 22 to a detection zone 31 present on the porous membrane 23.
  • The detection zone 31 may contain an immobilized capture reagent that is generally capable of forming a chemical or physical bond with the detection probes. In some embodiments, the capture reagent may be a biological capture reagent. Such biological capture reagents are well known in the art and may include, but are not limited to, antigens, haptens, protein A or G, neutravidin, avidin, streptavidin, captavidin, antibodies (e.g., polyclonal, monoclonal, etc.), and complexes thereof. The immobilized capture reagents serve as stationary binding sites for probe conjugate/analyte complexes. In some instances, the analytes, such as antibodies, antigens, etc., have two binding sites. Upon reaching the detection zone 31, one of these binding sites is occupied by the specific binding member of the complexed detection probes. However, the free binding site of the analyte may bind to the immobilized capture reagent. Upon being bound to the immobilized capture reagent, the complexed detection probes form a new ternary sandwich complex.
  • The detection zone 31 may generally provide any number of distinct detection regions so that a user may better determine the concentration of a particular analyte within a test sample. Each region may contain the same capture reagents, or may contain different capture reagents for capturing multiple analytes. For example, the detection zone 31 may include two or more distinct detection regions (e.g., lines, dots, etc.). The detection regions may be disposed in the form of lines in a direction that is substantially perpendicular to the flow of the test sample through the assay device 20. Likewise, in some embodiments, the detection regions may be disposed in the form of lines in a direction that is substantially parallel to the flow of the test sample through the assay device.
  • Although the detection zone 31 may indicate the presence of an analyte, it is often difficult to determine the relative concentration of the analyte within the test sample using solely a detection zone 31. Thus, the assay device 20 may also include a calibration zone 32. In this embodiment, the calibration zone 32 is formed on the porous membrane 23 and is positioned downstream from the detection zone 31, although it may also be positioned upstream if desired. The calibration zone 32 is provided with a capture reagent that is capable of binding to probes, either uncaptured detection probes or separate calibration probes, which pass through the detection zone 31.
  • The capture reagents utilized in the calibration zone 32 may be the same or different than the capture reagents used in the detection zone 31. For example, biological capture reagents may be utilized. It may also be desired to utilize various non-biological reagents for the capture reagents. For instance, the capture reagents may include a polyelectrolyte that may bind to probes. The polyelectrolytes may have a net positive or negative charge, as well as a net charge that is generally neutral. For instance, some suitable examples of polyelectrolytes having a net positive charge include, but are not limited to, polylysine (commercially available from Sigma-Aldrich Chemical Co., Inc. of St. Louis, Mo.), polyethylenimine; epichlorohydrin-functionalized polyamines and/or polyamidoamines, such as poly(dimethylamine-co-epichlorohydrin); polydiallyldimethyl-ammonium chloride; cationic cellulose derivatives, such as cellulose copolymers or cellulose derivatives grafted with a quaternary ammonium water-soluble monomer; and so forth. In one particular embodiment, CelQuat® SC-230M or H-100 (available from National Starch & Chemical, Inc.), which are cellulosic derivatives containing a quaternary ammonium water-soluble monomer, may be utilized. Moreover, some suitable examples of polyelectrolytes having a net negative charge include, but are not limited to, polyacrylic acids, such as poly(ethylene-co-methacrylic acid, sodium salt), and so forth. It should also be understood that other polyelectrolytes may also be utilized in the present invention, such as amphiphilic polyelectrolytes (i.e., having polar and non-polar portions). For instance, some examples of suitable amphiphilic polyelectrolytes include, but are not limited to, poly(styryl-b-N-methyl 2-vinyl pyridinium iodide) and poly(styryl-b-acrylic acid), both of which are available from Polymer Source, Inc. of Dorval, Canada.
  • Similar to the detection zone 31, the calibration zone 32 may provide any number of distinct calibration regions in any direction so that a user may better determine the concentration of a particular analyte within a test sample. Each region may contain the same capture reagents, or may contain different capture reagents for capturing different phosphorescent labels. The calibration regions may be pre-loaded on the porous membrane 23 with different amounts of the capture reagent so that a different signal intensity is generated by each calibration region upon migration of the probes. The overall amount of capture reagent within each calibration region may be varied by utilizing calibration regions of different sizes and/or by varying the concentration or volume of the capture reagent in each calibration region. If desired, an excess of detection probes may be employed in the assay device 20 so that each calibration region reaches its full and predetermined potential for signal intensity. That is, the amount of uncaptured detection probes that are deposited upon calibration regions are predetermined because the amount of the capture reagent employed on the calibration regions is set at a predetermined and known level. In the alternative, a predetermined amount of separate calibration probes may be used that are configured to only bind to the capture reagent at the calibration zone 32.
  • Once captured, the phosphorescent signal of the probes at the detection zone 31 and/or calibration zone 32 may be measured using a phosphorescence reader 50. For example, in this embodiment, the phosphorescence reader 50 is constructed to emit pulsed light simultaneously onto the detection and calibration zones 31 and 32. The reader 50 may also simultaneously receive the phosphorescent signal from the excited labels at the detection and calibration zones 31 and 32. Alternatively, the phosphorescence reader 50 may be constructed to successively emit pulsed light onto the detection zone 31 and the calibration zone 32. In addition, a separate phosphorescence reader (not shown) may also be used to measure the phosphorescent signal at the calibration zone 32.
  • The construction of the phosphorescence reader 50 may generally vary depending on a variety of factors, such as cost, the level of accuracy required, the nature and concentration of the analyte of interest, and so forth. In one embodiment, for example, a “time-resolved” reader may be utilized. Time-resolved detection involves exciting the phosphorescent label with one or more short pulses of light, then typically waiting a certain time (e.g., between approximately 1 to 100 microseconds) after excitation before measuring the remaining the phosphorescent signal. In this manner, any short-lived phosphorescent or fluorescent background signals and scattered excitation radiation are eliminated. This ability to eliminate much of the background signals may result in sensitivities that are 2 to 4 orders greater than conventional fluorescence or phosphorescence. Thus, time-resolved phosphorescence detection is designed to reduce background signals from the emission source or from scattering processes (resulting from scattering of the excitation radiation) by taking advantage of the phosphorescence characteristics of certain phosphorescent materials.
  • To function effectively, time-resolved techniques generally require a relatively long emission lifetime for the phosphorescent labels. This is desired so that the label emits its signal well after any short-lived background signals dissipate. Furthermore, a long phosphorescence lifetime makes it possible to use low-cost circuitry for time-gated phosphorescence measurements. For example, phosphorescent labels used in the present invention may have a phosphorescence lifetime of greater than about 1 microsecond, in some embodiments greater than about 10 microseconds, in some embodiments greater than about 50 microseconds, and in some embodiments, from about 100 microseconds to about 1000 microseconds. For instance, platinum(II)coproporhpyrin-I and particles encapsulated with such compounds have an emission lifetime of approximately 50 microseconds, palladium(II)coproporphyrin and particles encapsulated with such compounds have an emission lifetime of approximately 500 microseconds, and ruthenium bipyridyl complexes and particles encapsulated with such compounds have an emission lifetime of from about 1 to about 10 microseconds.
  • In addition, the phosphorescent label may also have a relatively large “Stokes shift.” The term “Stokes shift” is generally defined as the displacement of spectral lines or bands of luminescent radiation to a longer emission wavelength than the excitation lines or bands. A relatively large Stokes shift allows the excitation wavelength of the phosphorescent label to remain far apart from its emission wavelengths and is desirable because a large difference between excitation and emission wavelengths makes it easier to eliminate the reflected excitation radiation from the emitted signal. Further, a large Stokes shift also minimizes interference from phosphorescent molecules in the sample and/or light scattering due to proteins or colloids, which are present with some body fluids (e.g., blood). In addition, a large Stokes shift also minimizes the requirement for expensive, high-precision filters to eliminate background interference. For example, in some embodiments, the phosphorescent labels have a Stokes shift of greater than about 50 nanometers, in some embodiments greater than about 100 nanometers, and in some embodiments, from about 100 to about 350 nanometers. For instance, platinum(II)coproporhpyrin-I has a Stokes shift of approximately 260 nanometers, palladium(II)coproporphyrin has a Stokes shift of approximately 270 nanometers, and ruthenium coproporphyrin has a Stokes shift of approximately 150 nanometers.
  • Referring again to FIG. 1, the phosphorescence reader 50 may thus utilize time-resolved detection techniques. In such instances, the reader 50 may include one or more pulsed excitation sources and photodetectors that are in communication with each other and other optional components, such as optical filters. The use of pulsed excitation and time-gated detection, optionally combined with optical filters, allows for specific detection of the phosphorescence from only the phosphorescent label, rejecting emission from other species present in the sample that are typically shorter-lived.
  • For instance, referring to FIG. 2, one embodiment of an exemplary phosphorescence reader 50 is shown that includes an excitation source 52 and a detector 54. Various excitation sources 52 may be used in the present invention, including, for example, light emitting diodes (LED), flashlamps, as well as other suitable sources. Excitation illumination may also be multiplexed and/or collimated; for example, beams of various discrete frequencies from multiple coherent sources (e.g., lasers) may be collimated and multiplexed using an array of dichroic mirrors. Further, illumination may be continuous or pulsed, or may combine continuous wave (CW) and pulsed illumination where multiple illumination beams are multiplexed (e.g., a pulsed beam is multiplexed with a CW beam), permitting signal discrimination between phosphorescence induced by the CW source and phosphorescence induced by the pulsed source. For example, gallium arsenide LED diodes (e.g., aluminum gallium arsenide red diodes, gallium phosphide green diodes, gallium arsenide phosphide green diodes, or indium gallium nitride violet/blue/ultraviolet (UV) diodes) may be used as an illumination source. One commercially available example of a suitable UV LED excitation diode suitable for use in the present invention is Model NSHU55OE (Nichia Corporation), which emits 750 to 1000 microwatts of optical power at a forward current of 10 milliamps (3.5-3.9 volts) into a beam with a full-width at half maximum of 10 degrees, a peak wavelength of 370-375 nanometers, and a spectral half-width of 12 nanometers.
  • Further, examples of suitable detectors 54 that may be used in the present invention include, but not limited to, photomultiplier devices; photodiodes, such as avalanche photodiodes, silicon photodiodes, etc.; high speed, linear charge-coupled devices (CCD), CID devices, or CMOS based imagers; and so forth. In one embodiment, the phosphorescent system utilizes a silicon photodiode for phosphorescent detection. Silicon photodiodes are advantageous in that they are inexpensive, sensitive, capable of high-speed operation (short risetime/high bandwidth), and easily integrated into most other semiconductor technology and monolithic circuitry. In addition, silicon photodiodes are physically small, which enables them to be readily incorporated into a system for use in membrane-based devices. If silicon photodiodes are used, then the wavelength range of the phosphorescent emission should be within their range of sensitivity, which is 400 to 1100 nanometers. Another detector option is a CdS (cadmium sulfide) photoconductive cell, which has the advantage of having a spectral sensitivity similar to that of human vision (photopic curve) that may make rejection of the reflected excitation radiation easier.
  • Optionally, optical filters (not shown) may be disposed adjacent to the excitation source 52 and the detector 54. The optical filters may have high transmissibility in the excitation wavelength range(s) and low transmissibility in one or more undesirable wavelength band(s) to filter out undesirable wavelengths from the excitation source. Undesirable wavelength ranges generally include those wavelengths that produce detectable sample autofluoresence and/or are within about 25 to about 100 nanometers of excitation maxima wavelengths and thus are potential sources of background noise from scattered excitation illumination. Several examples of optical filters that may be utilized in the present invention include, but are not limited to, dyed plastic resin or gelatin filters, dichroic filters, thin multi-layer film interference filters, plastic or glass filters, epoxy or cured transparent resin filters. In one embodiment, the detector and/or excitation source may be embedded or encapsulated within the filter. Although optical filters may be utilized, one beneficial aspect of the present invention is that such filters are often not required as a result of time-resolving. Specifically, due to the delay in phosphorescence emission, emission bandwidth filters may not be required to filter out any short-lived phosphorescence emitted by the excitation source.
  • Referring again to FIG. 2, various timing circuitry is also used to control the pulsed excitation of the excitation source 52 and the measurement of the emitted phosphorescence. For instance, in the illustrated embodiment, a clock source 56 (e.g., a crystal oscillator) is employed to provide a controlled frequency source to other electronic components in the phosphorescence reader 50. In this particular embodiment, for instance, the oscillator 56 may generate a 20 MHz signal, which is provided to an LED driver/pulse generator 55 and to an A/D converter 64. The clock signal from oscillator 56 to A/D converter 64 controls the operating speed of A/D converter 64. It should be appreciated that a frequency divider may be utilized in such respective signal paths if the operating frequency of A/D converter 64 or if the desired frequency of the clock input to LED driver/pulse generator 55 is different than 20 MHz. Thus, it should be appreciated that the signal from oscillator 56 may be modified appropriately to provide signals of a desired frequency. In some embodiments, a signal from oscillator 56 may also be provided to microprocessor 60 to control its operating speed. Additional frequency dividers may be utilized in other signal paths in accordance with the present invention.
  • Microprocessor 60 provides control input to pulse generator 55 such that the 20 MHz signal from oscillator 56 is programmably adjusted to provide a desired pulse duration and repetition rate (for example, a 1 kHz source with a 50% duty cycle). The signal from pulse generator 55 may then be provided to the excitation source 52, controlling its pulse repetition rate and duty cycle of illumination. In some embodiments, a transistor may be provided in the signal path to excitation source 52, thus providing a switching means for effecting a pulsed light signal at excitation source 52.
  • As described above, the pulsed light excites phosphorescent labels associated with the subject assay devices. After the desired response time (e.g., about 100 to about 200 microseconds), the detector 54 detects the phosphorescence signal emitted by the excited phosphorescent labels and generates an electric current representative thereof. This electric current may then be converted to a voltage level by a high-speed transimpedance preamplifier 78, which may be characterized by a relatively low settling time and fast recovery from saturation. The output of the preamplifier 78 may then be provided to the data input of A/D converter 64. Additional amplifier elements (such as a programmable gain amplifier) may be employed in the signal path after preamplifier 78 and before A/D converter 64 to yield a signal within an appropriate voltage range at the trailing edge of the excitation pulse for provision to the A/D converter 64. A/D converter 64 may be a high-speed converter that has a sample rate sufficient to acquire many points within the phosphorescence lifetime of the subject phosphorescent labels. The gain of the preamplifier 78 may be set such that data values drop below the maximum A/D count (e.g., 2047 for a 12-bit converter) on the trailing edge of the excitation pulse. Data within the dynamic range of A/D converter 64 would then be primarily representative of the desired phosphorescence signal. If the sample interval is short compared with the rise-time and fall-time of the excitation pulse, then the gain of preamplifier 78 may be set to ensure that signal values within the upper ½ or ¾ of the dynamic range of A/D converter 78 correspond to the trailing edge of the emission pulse.
  • A/D converter 64 samples the signal from preamplifier 78 and provides it to the microprocessor 60 where software instruction is configured for various processing of the digital signal. An output from the microprocessor 60 is provided to the A/D converter 64 to further control when the detected phosphorescence signal is sampled. Control signals to preamplifier 78 (not shown) and to A/D converter 64 may be continuously modified to achieve the most appropriate gain, sampling interval, and trigger offset. It should be appreciated that although the A/D converter 64 and the microprocessor 60 are depicted as distinct components, commercially available chips that include both such components in a single module may also be utilized in the present invention. After processing, the microprocessor 60 may provide at least one output indicative of the phosphorescence levels detected by the detector 54. One such exemplary output is provided to a display 86, thus providing a user with a visual indication of the phosphorescence signal generated by the label. Display 86 may provide additional interactive features, such as a control interface to which a user may provide programmable input to microprocessor 60.
  • Yet another embodiment of representative specific electronic components for use in a phosphorescence reader 50 is illustrated in FIG. 3. Many of the components in FIG. 3 are analogous to those of FIG. 2 and so the same reference characters are used in such instances. For example, one difference in the reader 50 of FIG. 3 as compared to that of FIG. 2 is the generation of a gate signal at phase delay module 57. A control signal from microprocessor 60 is provided to phase delay module 57 to program the effective phase shift of a clock signal provided thereto. This shifted clock signal (also referred to as a gate signal) is then provided to a mixer 58 where such signal is multiplied by the periodic detector signal received by the detector 54 and passed through preamplifier 78. The resulting output of mixer 58 is then sent through a low-pass filter 62 before being provided to A/D converter 64. A/D converter 64 may then measure the output of low-pass filter 62 to obtain a measurement of the phosphorescence during intervals defined by the gate signal.
  • Still further alternative features for an exemplary phosphorescence reader embodiment 50 are illustrated in FIG. 4. For instance, a sample/hold amplifier 88 (also sometimes referred to as a track-and-hold amplifier) is shown that captures and holds a voltage input signal at specific points in time under control of an external signal. A specific example of a sample/hold amplifier for use with the present technology is a SHC5320 chip, such as those sold by Burr-Brown Corporation. The sample/hold amplifier external control signal in the embodiment of FIG. 4 is received from a delay circuit 92, which may, for instance, be digital delay circuit that derives a predetermined delay from the clock using counters, basic logic gates, and a flip-flop circuit. Delay circuit 92 receives a clock signal from oscillator 56 and an enable signal from frequency divider 90, which simply provides a periodic signal at a reduced frequency level than that generated at oscillator 56. Delay circuit 92 may also receive a control input from microprocessor 60 to enable programmable aspects of a delay to ensure proper sampling at sample/hold amplifier 88. The delayed pulse control signal from delay circuit 92 to sample/hold amplifier 88 thus triggers acquisition of the phosphorescence signal from the detector 54 at preset time intervals after the excitation source 52 has turned off.
  • Regardless of the construction of the reader 50 utilized, the amount of the analyte may be ascertained by correlating the emitted phosphorescence signal, Is, of the labels captured at the detection zone 31 to a predetermined analyte concentration. In some embodiments, the intensity signal, Is, may also be compared with the emitted phosphorescence intensity signal, Ic, of labels captured at the calibration zone 32. The phosphorescence intensity signal Is, may be compared to the phosphorescence intensity signal Ic. In this embodiment, the total amount of the labels at the calibration zone 32 is predetermined, and known and thus may be used for calibration purposes. For example, in some embodiments (e.g., sandwich assays), the amount of analyte is directly proportional to the ratio of Is to Ic. In other embodiments (e.g., competitive assays), the amount of analyte is inversely proportional to the ratio of Is to Ic. Based upon the intensity range in which the detection zone 31 falls, the general concentration range for the analyte may be determined. As a result, calibration and sample testing may be conducted under approximately the same conditions at the same time, thus providing reliable quantitative or semi-quantitative results, with increased sensitivity.
  • If desired, the ratio of Is to Ic may be plotted versus the analyte concentration for a range of known analyte concentrations to generate a calibration curve. To determine the quantity of analyte in an unknown test sample, the signal ratio may then be converted to analyte concentration according to the calibration curve. It should be noted that alternative mathematical relationships between Is and Ic may be plotted versus the analyte concentration to generate the calibration curve. For example, in one embodiment, the value of Is/(Is+Ic) may be plotted versus analyte concentration to generate the calibration curve.
  • As indicated above, sandwich formats, competitive formats, and so forth, may be utilized for the device 20. Sandwich assay formats typically involve mixing the test sample with antibodies to the analyte. These antibodies are mobile and linked to the label. This mixture is then contacted with a chromatographic medium containing a band or zone of immobilized antibodies to the analyte. The chromatographic medium is often in the form of a strip resembling a dipstick. When the complex of the analyte and the labeled antibody reaches the zone of the immobilized antibodies on the chromatographic medium, binding occurs and the bound labeled antibodies are localized at the zone. This indicates the presence of the analyte. This technique may be used to obtain quantitative or semi-quantitative results. Some examples of such sandwich-type assays are described by U.S. Pat. No. 4,168,146 to Grubb, et al. and U.S. Pat. No. 4,366,241 to Tom, et al., which are incorporated herein in their entirety by reference thereto for all purposes.
  • In a competitive assay, the probe is generally a labeled analyte or analyte-analog that competes for binding of an antibody with any unlabeled analyte present in the sample. Competitive assays are typically used for detection of analytes such as haptens, each hapten being monovalent and capable of binding only one antibody molecule. Examples of competitive immunoassay devices are described in U.S. Pat. No. 4,235,601 to Deutsch, et al., U.S. Pat. No. 4,442,204 to Liotta, and U.S. Pat. No. 5,208,535 to Buechler, et al., which are incorporated herein in their entirety by reference thereto for all purposes. Various other device configurations and/or assay formats are also described in U.S. Pat. No. 5,395,754 to Lambotte, et al.; U.S. Pat. No. 5,670,381 to Jou, et al.; and U.S. Pat. No. 6,194,220 to Malick, et al., which are incorporated herein in their entirety by reference thereto for all purposes.
  • Although various embodiments of device configurations have been described above, it should be understood, that a device of the present invention may generally have any configuration desired, and need not contain all of the components described above.
  • The present invention may be better understood with reference to the following examples.
  • EXAMPLE 1
  • The ability to encapsulate platinum(II)tetra-meso-fluorophenylporphine (Pt(II)-MTPFP) in carboxylated latex particles was demonstrated. Initially, 8 milligrams of a carboxylated latex particle suspension (0.3-micrometer particle size, available from Bangs Laboratories, Inc) was washed twice with ethanol and then suspended in 100 microliters of ethanol. 100 micrograms of Pt(II)MTPFP in 55 microliters of methylene chloride and 45 microliters of ethanol was added to the particle suspension. The mixture was gently shaken for 20 minutes. Then, 100 microliters of water was added. The mixture was then shaken overnight. Approximately 50 vol. % of the solvent was then removed by air stream. 1 milliliter of ethanol was added and centrifuged, after which the supernatant was discarded. The particles were further washed twice with ethanol and then twice with water. The washed particles were suspended by bath sonication in 1.5 milliliter of water for storage. The particles exhibited very strong phosphorescence at an emission wavelength of 650 nanometers when excited at 390 nanometers at ambient conditions (without removing oxygen).
  • EXAMPLE 2
  • The encapsulation of platinum(II)tetra-meso-fluorophenylporphine in polyacrylonitrile particles was demonstrated. 118.5 milligrams of polyacrylonitrile and 1.19 milligrams of platinum(II)tetra-meso-fluorophenylporphine were dissolved in 25 milliliters of DMF. 125 milliliters of water was added to the mixture under vigorous stirring. Thereafter, 1 milliliter of a saturated sodium chloride aqueous solution was added to precipitate the dispersed particles. The mixture was centrifuged for 15 minutes and then washed twice with a sodium chloride solution (5 wt. %) and three times with 50 milliliters of water. The residue was then heated for 15 minutes at 70° C. and centrifuged in a phosphate buffer. This procedure is substantially identical to that described in Bioconjugated Chemistry, Kurner, 12, 883-89 (2001), with the exception that the ruthenium complexes were replaced with platinum(II)tetra-meso-fluorophenylporphine.
  • The resulting encapsulated particles exhibited very strong phosphorescence at an emission wavelength of 650 nanometers when excited at 390 nanometers under ambient conditions.
  • EXAMPLE 3
  • The ability to conjugate an antibody to phosphorescent particles was demonstrated. The particles were carboxylated latex phosphorescent particles having a particle size of 0.20 micrometers, 0.5% solids, and exhibiting phosphorescence at an emission wavelength of 650 nanometers when excited at a wavelength of 390 nanometers. The particles were obtained from Molecular Probes, Inc. under the name “FluoSpheres.”
  • Initially, 500 microliters of the particles were washed once with 1 milliliter of a carbonate buffer and twice with 2-[N-morpholino]ethanesulfonic acid (MES) buffer (pH: 6.1, 20 millimolar) using a centrifuge. The washed particles were re-suspended in 250 microliters of MES. Thereafter, 3 milligrams of carbodiimide (Polysciences, Inc.) was dissolved in 250 microliters of MES and added to the suspended particles. The mixture was allowed to react at room temperature for 30 minutes on a shaker. The activated particles were then washed twice with a borate buffer (Polysciences, Inc) and re-suspended in 250 microliters of borate buffer. 30 microliters of CRP monoclonal antibody (CRP Mab1) (3.4 milligrams per milliliter, A#5811 from Biodesign) was then added to the particle suspensions. The mixture was allowed to react at room temperature on an end-over-end shaker overnight. During the period of reaction, the suspensions were bath-sonicated twice. The particles were then collected and incubated in 250 microliters of 0.1 molar ethanolamine (Polysciences Inc.) under gentle shaking for 15 minutes. The particles were washed twice with a trizma acid/trizma base buffer (20 millimolar, pH: 7.2). The washed conjugates were suspended in 1 milliliter of the trizma acid/trizma base buffer and stored at 4° C.
  • EXAMPLE 4
  • The ability to conjugate an antibody to phosphorescent particles was demonstrated. The particles were carboxylated polyacrylonitrile phosphorescent particles having a particle size of 0.04 micrometers, 0.5% solids, and exhibiting phosphorescence at an emission wavelength of 650 nanometers when excited at a wavelength of 390 nanometers. The particles were obtained from Chromeon GmbH.
  • Initially, 500 microliters of the particles were suspended in 50 microliters of 2-[N-morpholino]ethanesulfonic acid (MES) buffer (0.1 molar). The particle suspension was bath-sonicated for 5 minutes. Thereafter, 6 milligrams of carbodiimide (Polysciences, Inc.) was dissolved in 50 microliters of MES and added to the suspended particles. The mixture was allowed to react at room temperature for 30 minutes on a shaker. The activated particles were then washed twice with a borate buffer (Polysciences, Inc) and re-suspended in 250 microliters of borate buffer. 30 microliters of CRP monoclonal antibody (CRP Mab1) (3.4 milligrams per milliliter, A#5811 from Biodesign) was then added to the particle suspensions. The mixture was allowed to react at room temperature on an end-over-end shaker overnight. During the period of reaction, the suspensions were bath-sonicated twice. The particles were then collected and incubated in 250 microliters of 0.1 molar ethanolamine (Polysciences, Inc.) under gentle shaking for 15 minutes. The particles were washed twice with a trizma acid/trizma base buffer (20 millimolar, pH: 7.2). The washed conjugates were suspended in 1 milliliter of the trizma acid/trizma base buffer and stored at 4° C.
  • EXAMPLE 5
  • The ability to form a lateral flow assay device with using phosphorescent particles was demonstrated. A nitrocellulose porous membrane (HF 120 from Millipore, Inc.) having a length of approximately 30 centimeters was laminated onto supporting cards. Goldline™ (a polylysine solution obtained from British Biocell International) was stripped onto the membrane to form a calibration line. In addition, monoclonal antibody for C-reactive protein (Mab2) (A#5804, available from Biodesign, concentration of 1 milligram per milliliter) was immobilized on the porous membrane to form a detection line. The membrane samples were then dried for 1 hour at a temperature of 37° C. A cellulosic fiber wicking pad (Millipore, Inc. Co.) was attached to one end of the membrane and cut into 4-millimeter half strips.
  • 200 microliters of the conjugated phosphorescent particles of Example 3 (concentration of 2.5 milligrams per milliliter in a trizma acid/trizma base buffer with 1 milligram per milliliter BSA) was applied with 200 microliters of Tween 20 (2%, available from Aldrich) and 200 microliters of sucrose in water (10%). The mixture was bath-sonicated for 20 minutes. The suspension was then loaded onto a 10-centimeter long glass fiber conjugate pad (Millipore Co.). The glass fiber pad was then dried at 37° C. for 2 hours. Thereafter, 600 microliters of Tween 20 (0.5%) was loaded onto a 10-centimeter long glass fiber sample pad (Millipore Co.) and dried at 37° C. for 2 hours. A cellulose wicking pad (Millipore Co.), the sample pad, and conjugate pad were then laminated onto the porous membrane. The laminated full card was then cut into a 4-millimeter wide lateral flow assay device.
  • EXAMPLE 6
  • The ability to form a lateral flow assay device with using phosphorescent particles was demonstrated. A nitrocellulose porous membrane (HF 120 from Millipore, Inc.) having a length of approximately 30 centimeters was laminated onto supporting cards. Goldline™ (a polylysine solution obtained from British Biocell International) was stripped onto the membrane to form a calibration line. In addition, monoclonal antibody for C-reactive protein (Mab2) (A#5804, available from Biodesign, concentration of 1 milligram per milliliter) was immobilized on the porous membrane to form a detection line. The membrane samples were then dried for 1 hour at a temperature of 37° C. A cellulosic fiber wicking pad (Millipore, Inc. Co.) was attached to one end of the membrane and cut into 4-millimeter half strips.
  • The half stick strips were put into a control and test microwell. The control microwell contained 200 microliters of the conjugated phosphorescent particles of Example 4 (concentration of 2.5 milligrams per milliliter in a trizma acid/trizma base buffer), 15 microliters of Tween 20 (2%, available from Aldrich), and 20 microliters of the trizma acid/trizma base buffer. The test microwell contained 200 microliters of the conjugated phosphorescent particles of Example 4 (concentration of 2.5 milligrams per milliliter in a trizma acid/trizma base buffer), 15 microliters of Tween 20 (2%, available from Aldrich), 15 microliters of the trizma acid/trizma base buffer, and C-reactive protein (2 micrograms per milliliter, available from Biodesign).
  • A half-stick was inserted into each microwell and allowed to develop for 20 minutes. When the assay was finished, the half stick was taken out mounted onto the sample holder of a Fluorolog III Spectrofluorometer (available from SA Instruments, Inc.) using tape. The detection line fit into a rectangular hole in the holder so that the excitation beam would shine directly on the detection line while the rest of the device was remained blocked from the excitation beam. Time-resolved phosphorescence techniques were used. Specifically, the following experiment parameters were used: (1) the angle of the excitation beam to the surface normal of the devices was 70° C.; the detection mode was front face; the slit width was 5 nanometer; (4) the number of scan was 1; (5) the excitation wavelength was 390 nanometers; (6) the emission wavelength was from 600 to 700 nanometers; (7) the sample window was 2 milliseconds (ms); (8) the initial delay was 0.02 ms; (9) the time-per-flash was 50 ms; and (10) the number of flashes was 10.
  • For the control, the measured phosphorescent intensity was 1.82K (K=1000), while the intensity for the test sample was 8.63K. The phosphorescent intensity was directly related to the quantity of the sandwich complex for the antigen, and therefore directly related to the concentration of the CRP antigen.
  • EXAMPLE 7
  • The ability to detect the presence of an analyte using a lateral flow assay device was demonstrated. A nitrocellulose porous membrane (HF 120 from Millipore, Inc.) having a length of approximately 30 centimeters was laminated onto supporting cards. Goldline™ (a polylysine solution obtained from British Biocell International) was stripped onto the membrane to form a calibration line. In addition, monoclonal antibody for C-reactive protein (Mab2) (A#5804, available from Biodesign, concentration of 1 milligram per milliliter) was immobilized on the porous membrane to form a detection line. The membrane samples were then dried for 1 hour at a temperature of 37° C. A cellulosic fiber wicking pad (Millipore, Inc. Co.) was attached to one end of the membrane and cut into 4-millimeter half strips. 200 microliters of the conjugated phosphorescent particles of Example 3 (concentration of 2.5 milligrams per milliliter in a trizma acid/trizma base buffer with 1 milligram per milliliter BSA) was applied with 200 microliters of Tween 20 (2%, available from Aldrich) and 200 microliters of sucrose in water (10%). The mixture was bath-sonicated for 20 minutes. The suspension was then loaded onto a 10-centimeter long glass fiber conjugate pad (Millipore Co.). The glass fiber pad was then dried at 37° C. for 2 hours. Thereafter, 600 microliters of Tween 20 (0.5%) was loaded onto a 10-centimeter long glass fiber sample pad (Millipore Co.) and dried at 37° C. for 2 hours. A cellulose wicking pad (Millipore Co.), the sample pad, and conjugate pad were then laminated onto the porous membrane. The laminated full card was then cut into a 4-millimeter wide lateral flow assay device.
  • Six (6) of the assay devices were tested. 50 microliters of a mixture of hepes buffer (N-[2-hydroxyethyl]piperazine-N′-(2-ethanesulfonic acid) from Sigma, pH: 7.4) and C-reactive protein were applied to the sample pad. Different concentrations of CRP were tested, i.e., 0, 20, 50, 100, 200 and 1000 nanograms per milliliter. The devices were allowed to develop for 30 minutes. The phosphorescent intensity was measured as described above in Example 6. The intensity at the detection line for CRP concentrations of 0, 20, 50, 100, 200 and 1000 nanograms per milliliter was determined to be 7.21 K, 6.03K, 9.31 K, 8.05K, 13.7K, 19.8K, respectively. Thus, as shown, the phosphorescent intensity was directly related to the CRP antigen.
  • While the invention has been described in detail with respect to the specific embodiments thereof, it will be appreciated that those skilled in the art, upon attaining an understanding of the foregoing, may readily conceive of alterations to, variations of, and equivalents to these embodiments. Accordingly, the scope of the present invention should be assessed as that of the appended claims and any equivalents thereto.

Claims (63)

  1. 1. A method for detecting the presence or quantity of an analyte residing in a test sample, said method comprising:
    i) providing a lateral flow assay device that comprises a porous membrane in fluid communication with detection probes, said detection probes comprising a phosphorescent label encapsulated within a matrix, wherein said porous membrane defines a detection zone within which is immobilized a capture reagent that is configured to bind to said detection probes or complexes thereof;
    ii) contacting said detection probes with the test sample;
    iii) allowing said detection probes and the test sample to flow to said detection zone;
    iv) exciting said phosphorescent label at said detection zone to generate an emitted detection signal; and
    v) measuring the intensity of the detection signal, wherein the amount of the analyte within the test sample is proportional to the intensity of the detection signal.
  2. 2. A method as defined in claim 1, wherein said phosphorescent label comprises a metal complex.
  3. 3. A method as defined in claim 2, wherein said metal complex comprises a metal selected from the group consisting of ruthenium, osmium, rhenium, iridium, rhodium, platinum, indium, palladium, molybdenum, technetium, copper, iron, chromium, tungsten, zinc, and combinations thereof.
  4. 4. A method as defined in claim 2, wherein said metal complex comprises a metal selected from the group consisting of ruthenium, osmium, rhenium, platinum, palladium, and combinations thereof.
  5. 5. A method as defined in claim 2, wherein said metal complex comprises a ligand selected from the group consisting of pyridine, pyrazine, isonicotinamide, imidazole, bipyridine, terpyridine, phenanthroline, dipyridophenazine, porphyrin, porphine, derivatives thereof, and combinations thereof.
  6. 6. A method as defined in claim 2, wherein said phosphorescent label comprises a porphyrin ligand, porphine ligand, derivatives thereof, or combinations thereof.
  7. 7. A method as defined in claim 6, wherein said phosphorescent label is selected from the group consisting of platinum(II)coproporphyrin-I and III, palladium(II)coproporphyrin, ruthenium coproporphyrin, zinc(II)-coproporphyrin-I, platinum(II)tetra-meso-fluorophenylporphine, palladium(II)tetra-meso-fluorophenylporphine, derivatives thereof, and combinations thereof.
  8. 8. A method as defined in claim 2, wherein said phosphorescent label comprises a bipyridine ligand or derivatives thereof.
  9. 9. A method as defined in claim 1, wherein said matrix comprises metal oxide particles, polymer particles, or combinations thereof.
  10. 10. A method as defined in claim 9, wherein said particles have an average size of from about 0.1 nanometers to about 1000 microns.
  11. 11. A method as defined in claim 9, wherein said particles have an average size of from about 0.1 nanometers to about 100 microns.
  12. 12. A method as defined in claim 9, wherein said particles have an average size of from about 1 nanometer to about 10 microns.
  13. 13. A method as defined in claim 1, wherein said matrix acts as a barrier to protect said phosphorescent label from quenching.
  14. 14. A method as defined in claim 13, wherein less than about 30% of the detection signal is quenched when said detection probes are exposed to a quencher.
  15. 15. A method as defined in claim 13, wherein less than about 20% of the detection signal is quenched when said detection probes exposed to a quencher.
  16. 16. A method as defined in claim 13, wherein less than about 10% of the detection signal is quenched when said detection probes are exposed to a quencher.
  17. 17. A method as defined in claim 1, wherein said phosphorescent label has a phosphorescence emission lifetime of greater than about 1 microsecond.
  18. 18. A method as defined in claim 1, wherein said phosphorescent label has an emission lifetime of greater than about 10 microseconds.
  19. 19. A method as defined in claim 1, wherein said phosphorescent label has an emission lifetime of from about 100 to about 1000 microseconds.
  20. 20. A method as defined in claim 1, wherein said capture reagent is selected from the group consisting of antigens, haptens, protein A or G, neutravidin, avidin, streptavidin, captavidin, primary or secondary antibodies, and complexes thereof.
  21. 21. A method as defined in claim 1, wherein said phosphorescent label is excited at said detection zone with a pulsed excitation source and said emitted detection signal is measured by a time-gated detector.
  22. 22. A method as defined in claim 1, wherein said porous membrane further defines a calibration zone within which a capture reagent is immobilized that is configured to bind to said detection probes or calibration probes that also comprise a phosphorescent label.
  23. 23. A method as defined in claim 22, further comprising exciting said phosphorescent label at said calibration zone to generate an emitted calibration signal, and measuring the intensity of the calibration signal, wherein the amount of the analyte within the test sample is proportional to the intensity of the detection signal calibrated by the intensity of the calibration signal.
  24. 24. A method as defined in claim 1, wherein said detection probes are conjugated with a specific binding member for the analyte.
  25. 25. A method as defined in claim 24, wherein said specific binding member is selected from the group consisting of antigens, haptens, aptamers, primary or secondary antibodies, biotin, and combinations thereof.
  26. 26. A method as defined in claim 1, wherein said assay device is a sandwich-type assay device.
  27. 27. A method as defined in claim 1, wherein said assay device is a competitive-type assay device.
  28. 28. A method for detecting the presence or quantity of an analyte residing in a test sample, said method comprising:
    i) providing a lateral flow assay device that comprises a porous membrane in fluid communication with detection probes, said detection probes comprising a phosphorescent metal complex encapsulated within a particle matrix, said phosphorescent metal complex comprising a ligand and a metal selected from the group consisting of ruthenium, rhenium, osmium, platinum, palladium, and combinations thereof, said phosphorescent metal complex having a phosphorescence emission lifetime of greater than about 1 microsecond, wherein said porous membrane defines a detection zone within which is immobilized a capture reagent configured to bind to complexes of said detection probes;
    ii) contacting said detection probes with the test sample;
    iii) allowing said detection probes and the test sample to flow to said detection zone;
    iv) exciting said phosphorescent metal complex at said detection zone to generate an emitted detection signal; and
    v) measuring the intensity of the detection signal, wherein the amount of the analyte within the test sample is proportional to the intensity of the detection signal.
  29. 29. A method as defined in claim 28, wherein said metal complex comprises a ligand selected from the group consisting of pyridine, pyrazine, isonicotinamide, imidazole, bipyridine, terpyridine, phenanthroline, dipyridophenazine, porphyrin, porphine, derivatives thereof, and combinations thereof.
  30. 30. A method as defined in claim 28, wherein said ligand comprises porphyrin, porphine, derivatives thereof, or combinations thereof.
  31. 31. A method as defined in claim 30, wherein said phosphorescent metal complex is selected from the group consisting of platinum(II)coproporphyrin-I and III, palladium(II)coproporphyrin, ruthenium coproporphyrin, platinum(II)tetra-meso-fluorophenylporphine, palladium(II)tetra-meso-fluorophenylporphine, derivatives thereof, and combinations thereof.
  32. 32. A method as defined in claim 28, wherein said ligand comprises bipyridine or derivatives thereof.
  33. 33. A method as defined in claim 28, wherein said particle matrix comprises metal oxide particles, polymer particles, or combinations thereof.
  34. 34. A method as defined in claim 33, wherein said particles have an average size of from about 0.1 nanometers to about 100 microns.
  35. 35. A method as defined in claim 28, wherein said particle matrix acts as a barrier to protect said phosphorescent metal complex from quenching.
  36. 36. A method as defined in claim 28, wherein less than about 30% of the detection signal is quenched when said detection probes are exposed to a quencher.
  37. 37. A method as defined in claim 28, wherein less than about 20% of the detection signal is quenched when said detection probes are exposed to a quencher.
  38. 38. A method as defined in claim 28, wherein less than about 10% of the detection signal is quenched when said detection probes are exposed to a quencher.
  39. 39. A method as defined in claim 28, wherein said phosphorescent metal complex has an emission lifetime of greater than about 10 microseconds.
  40. 40. A method as defined in claim 28, wherein said phosphorescent metal complex is excited at said detection zone with a pulsed excitation source and said emitted detection signal is measured by a time-gated detector.
  41. 41. A method as defined in claim 28, wherein said porous membrane further defines a calibration zone within which a capture reagent is immobilized that is configured to bind to said detection probes or calibration probes that also comprise a phosphorescent metal complex.
  42. 42. A method as defined in claim 41, further comprising exciting said phosphorescent metal complex at said calibration zone to generate an emitted calibration signal, and measuring the intensity of the calibration signal, wherein the amount of the analyte within the test sample is proportional to the intensity of the detection signal calibrated by the intensity of the calibration signal.
  43. 43. A method as defined in claim 28, wherein said detection probes are conjugated with a specific binding member for the analyte.
  44. 44. A lateral flow assay device for detecting the presence or quantity of an analyte residing in a test sample, said assay device comprising a porous membrane in fluid communication with detection probes, said detection probes comprising a phosphorescent metal complex encapsulated within a matrix, wherein said porous membrane defines a detection zone within which a capture reagent is immobilized that is configured to bind to said detection probes or complexes thereof to generate a detection signal, wherein the amount of the analyte in the test sample is proportional to the intensity of said detection signal.
  45. 45. A lateral flow assay device as defined in claim 44, wherein said metal complex comprises a metal selected from the group consisting of ruthenium, osmium, rhenium, platinum, palladium, and combinations thereof.
  46. 46. A lateral flow assay device as defined in claim 44, wherein said metal complex comprises a ligand selected from the group consisting of pyridine, pyrazine, isonicotinamide, imidazole, bipyridine, terpyridine, phenanthroline, dipyridophenazine, porphyrin, porphine, derivatives thereof, and combinations thereof.
  47. 47. A lateral flow assay device as defined in claim 46, wherein said ligand is porphyrin, porphine, derivatives thereof, or combinations thereof.
  48. 48. A lateral flow assay device as defined in claim 47, wherein said phosphorescent metal complex is selected from the group consisting of platinum(II)coproporphyrin-I and III, palladium(II)coproporphyrin, ruthenium coproporphyrin, zinc(II)-coproporphyrin-I, platinum(II)tetra-meso-fluorophenylporphine, palladium(II)tetra-meso-fluorophenylporphine, derivatives thereof, and combinations thereof.
  49. 49. A lateral flow assay device as defined in claim 46, wherein said ligand is bipyridine or derivatives thereof.
  50. 50. A lateral flow assay device as defined in claim 44, wherein said matrix comprises metal oxide particles, polymer particles, or combinations thereof.
  51. 51. A lateral flow assay device as defined in claim 50, wherein said particles have an average size of from about 0.1 nanometers to about 1000 microns.
  52. 52. A lateral flow assay device as defined in claim 50, wherein said particles have an average size of from about 0.1 nanometers to about 100 microns.
  53. 53. A lateral flow assay device as defined in claim 50, wherein said particles have an average size of from about 1 nanometer to about 10 microns.
  54. 54. A lateral flow assay device as defined in claim 44, wherein said matrix acts as a barrier to protect said phosphorescent metal complex from quenching.
  55. 55. A lateral flow assay device as defined in claim 54, wherein less than about 30% of the detection signal is quenched when said detection probes are exposed to a quencher.
  56. 56. A lateral flow assay device as defined in claim 54, wherein less than about 20% of the detection signal is quenched when said detection probes are exposed to a quencher.
  57. 57. A lateral flow assay device as defined in claim 54, wherein less than about 10% of the detection signal is quenched when said detection probes are exposed to a quencher.
  58. 58. A lateral flow assay device as defined in claim 44, wherein said phosphorescent metal complex has an emission lifetime of greater than about 10 microseconds.
  59. 59. A lateral flow assay device as defined in claim 44, wherein said capture reagent is selected from the group consisting of antigens, haptens, protein A or G, neutravidin, avidin, streptavidin, captavidin, primary or secondary antibodies, and complexes thereof.
  60. 60. A lateral flow assay device as defined in claim 44, wherein said detection probes are conjugated with a specific binding member for the analyte.
  61. 61. A lateral flow assay device as defined in claim 44, wherein said porous membrane further defines a calibration zone within which a capture reagent is immobilized that is configured to bind to said detection probes or calibration probes that also comprise a phosphorescent metal complex, wherein the amount of the analyte within the test sample is proportional to the intensity of the detection signal calibrated by the intensity of the calibration signal.
  62. 62. A lateral flow assay device as defined in claim 44, wherein said assay device is a sandwich-type assay device.
  63. 63. A lateral flow assay device as defined in claim 44, wherein said assay device is a competitive-type assay device.
US10718989 2003-11-21 2003-11-21 Membrane-based lateral flow assay devices that utilize phosphorescent detection Abandoned US20050112703A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US10718989 US20050112703A1 (en) 2003-11-21 2003-11-21 Membrane-based lateral flow assay devices that utilize phosphorescent detection

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US10718989 US20050112703A1 (en) 2003-11-21 2003-11-21 Membrane-based lateral flow assay devices that utilize phosphorescent detection
DE200460030615 DE602004030615D1 (en) 2003-11-21 2004-04-28 Lateral flow test devices on membrane-based using of phosphoreszenznachweises
PCT/US2004/013180 WO2005057215A1 (en) 2003-11-21 2004-04-28 Membrane-based lateral flow assay devices that utilize phosphorescent detection
EP20040820342 EP1692508B1 (en) 2003-11-21 2004-04-28 Membrane-based lateral flow assay devices that utilize phosphorescent detection
US11956397 US8557604B2 (en) 2003-11-21 2007-12-14 Membrane-based lateral flow assay devices that utilize phosphorescent detection
US14017342 US8703504B2 (en) 2003-11-21 2013-09-04 Membrane-based lateral flow assay devices that utilize phosphorescent detection

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11956397 Continuation US8557604B2 (en) 2003-11-21 2007-12-14 Membrane-based lateral flow assay devices that utilize phosphorescent detection

Publications (1)

Publication Number Publication Date
US20050112703A1 true true US20050112703A1 (en) 2005-05-26

Family

ID=34591211

Family Applications (3)

Application Number Title Priority Date Filing Date
US10718989 Abandoned US20050112703A1 (en) 2003-11-21 2003-11-21 Membrane-based lateral flow assay devices that utilize phosphorescent detection
US11956397 Active 2026-06-13 US8557604B2 (en) 2003-11-21 2007-12-14 Membrane-based lateral flow assay devices that utilize phosphorescent detection
US14017342 Active US8703504B2 (en) 2003-11-21 2013-09-04 Membrane-based lateral flow assay devices that utilize phosphorescent detection

Family Applications After (2)

Application Number Title Priority Date Filing Date
US11956397 Active 2026-06-13 US8557604B2 (en) 2003-11-21 2007-12-14 Membrane-based lateral flow assay devices that utilize phosphorescent detection
US14017342 Active US8703504B2 (en) 2003-11-21 2013-09-04 Membrane-based lateral flow assay devices that utilize phosphorescent detection

Country Status (4)

Country Link
US (3) US20050112703A1 (en)
EP (1) EP1692508B1 (en)
DE (1) DE602004030615D1 (en)
WO (1) WO2005057215A1 (en)

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060275920A1 (en) * 2005-06-01 2006-12-07 Petrilla John F Apparatus and method for discriminating among lateral flow assay test indicators
US20070048182A1 (en) * 2005-08-31 2007-03-01 Kimberly-Clark Worldwide, Inc. Nitrite detection technique
EP1908522A1 (en) 2006-10-03 2008-04-09 Meridian Bioscience, Inc. Immunoassay test device and method of use
EP1977242A2 (en) * 2006-01-27 2008-10-08 Oxonica Inc. Lateral flow immunoassay with encapsulated detection modality
US7575887B2 (en) 2005-08-31 2009-08-18 Kimberly-Clark, Worldwide, Inc. Detection of proteases secreted from pathogenic microorganisms
US20090298197A1 (en) * 2005-11-15 2009-12-03 Oxonica Materials Inc. Sers-based methods for detection of bioagents
US7662643B2 (en) 2002-12-19 2010-02-16 Kimberly-Clark Worldwide, Inc. Reduction of the hook effect in membrane-based assay devices
US7670786B2 (en) 2002-08-27 2010-03-02 Kimberly-Clark Worldwide, Inc. Membrane-based assay devices
US20100060893A1 (en) * 2006-07-24 2010-03-11 Norton Scott M Assay particle concentration and imaging apparatus and method
US7829347B2 (en) 2005-08-31 2010-11-09 Kimberly-Clark Worldwide, Inc. Diagnostic test kits with improved detection accuracy
US20110020541A1 (en) * 2003-04-03 2011-01-27 Kimberly-Clark Worldwide, Inc. Methods of Making Assay Devices Utilizing Hollow Particles
US7897360B2 (en) 2006-12-15 2011-03-01 Kimberly-Clark Worldwide, Inc. Enzyme detection techniques
CN102662065A (en) * 2012-04-28 2012-09-12 广州鸿琪光学仪器科技有限公司 Immunofluorescence dipstick component for quickly and quantitatively detecting protein of plurality of types and detection card component prepared from same and preparation method thereof
CN102662055A (en) * 2012-04-28 2012-09-12 广州鸿琪光学仪器科技有限公司 Immune fluorescent test strip component for quickly quantitatively detecting troponin I, detection card component comprising immune fluorescent test strip component and preparation methods for immune fluorescent test strip component and detection card component
CN102680704A (en) * 2012-04-28 2012-09-19 广州鸿琪光学仪器科技有限公司 immunofluorescence test strip module for rapidly and quantitatively testing microalbumin, test card module made of same and preparation method thereof
CN102680702A (en) * 2012-04-28 2012-09-19 广州鸿琪光学仪器科技有限公司 Immune-fluorescence test strip component for rapidly detecting C-reactive protein quantitatively, detection card component produced by same and method for preparing same
CN102680703A (en) * 2012-04-28 2012-09-19 广州鸿琪光学仪器科技有限公司 Immunofluorescence test strip component for quickly and quantitatively testing myoglobin, test card component using immunofluorescence test strip component, and preparation method for immunofluorescence test strip component
CN102692508A (en) * 2012-04-28 2012-09-26 广州鸿琪光学仪器科技有限公司 Immunofluorescence test strip component for quickly quantitatively testing troponin-T and test card component manufactured by same and production process of immunofluorescence test strip
CN102707056A (en) * 2012-04-28 2012-10-03 广州鸿琪光学仪器科技有限公司 Immunofluorescence test strip component for quickly and quantitatively detecting myocardial creatine kinase isozyme, detection card component comprising same and preparation method
CN102866252A (en) * 2012-08-09 2013-01-09 河南省农业科学院 Immunochromatography test strip marked by phosphorescent silica nano particles and used for quantitatively detecting cimaterol and preparation method for immunochromatography test strip
CN102866251A (en) * 2012-06-19 2013-01-09 深圳市艾瑞生物科技有限公司 Immunofluorescence test strip based on phosphorescent technology, and preparation method and application thereof
WO2013127144A1 (en) * 2012-03-01 2013-09-06 上海鑫谱生物科技有限公司 Fluorescence analysis method and device
US8758989B2 (en) 2006-04-06 2014-06-24 Kimberly-Clark Worldwide, Inc. Enzymatic detection techniques
JP2014521102A (en) * 2011-07-19 2014-08-25 ザ バイオ ナノ センター リミテッド Apparatus and method for lateral flow affinity assay
CN104278079A (en) * 2013-07-08 2015-01-14 嘉兴朝云帆生物科技有限公司 Test strip and method for detecting nucleic acid through nucleic acid chromatographic technique
CN104345148A (en) * 2013-07-28 2015-02-11 嘉兴朝云帆生物科技有限公司 Test strip and method for detecting protein by using immunochromatography
CN104345144A (en) * 2013-07-28 2015-02-11 嘉兴朝云帆生物科技有限公司 Test strip and method for detecting small-molecular organic compound by using immunochromatography
WO2015026663A1 (en) * 2013-08-19 2015-02-26 University Of Houston Phosphorescent reporters
US20150079608A1 (en) * 2012-04-06 2015-03-19 Adtec, Inc. Method for detecting or quantifying analyte, kit for detecting or quantifying analyte, and test strip for lateral flow type chromatography method for detecting or quantifying analyte
JP2015535341A (en) * 2012-10-23 2015-12-10 ロベルト・ボッシュ・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツングRobert Bosch Gmbh Sensor integration and its application in a lateral flow immunoassay
CN105929155A (en) * 2016-07-08 2016-09-07 同济大学 Immuno-chromatographic test paper and detection method thereof
US9739773B1 (en) 2010-08-13 2017-08-22 David Gordon Bermudes Compositions and methods for determining successful immunization by one or more vaccines

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006075678A1 (en) * 2005-01-14 2006-07-20 Hamamatsu Foundation For Science And Technology Promotion Photosensitive compound
DE102008019928A1 (en) * 2008-04-21 2009-12-31 Siemens Healthcare Diagnostics Gmbh Procedures for applying spots with capture molecules on substrate surface for chip, particularly optical sensor, involve washing substrate surface of chip by dipping in aqueous solution of cationic polyelectrolyte
US20110177962A1 (en) 2010-01-15 2011-07-21 Robert Bosch Gmbh Successive sampling device and associated method
GB201010768D0 (en) 2010-06-25 2010-08-11 Isis Innovation Analyte sensor
EP2786128A1 (en) * 2011-09-06 2014-10-08 Luxcel Biosciences Limited Dry laminated photoluminescent probe and methods of manufacture and use
CN104360085B (en) * 2014-12-05 2016-03-16 重庆乾德生物技术有限公司 One kind of detection kit afp
USD775738S1 (en) * 2015-01-05 2017-01-03 Ge Healthcare Bio-Sciences Ab Membrane card
WO2018185672A1 (en) 2017-04-06 2018-10-11 Magbiosense Inc. Bio-assay capture surfaces with bleached autofluorescence

Citations (99)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1366241A (en) * 1919-10-03 1921-01-18 Frederick W Burch Ratchet mechanism for camp-beds
US4006360A (en) * 1974-08-21 1977-02-01 Block Engineering, Inc. Method of discriminating between dyed particles and background fluorescence of the dye
US4094647A (en) * 1976-07-02 1978-06-13 Thyroid Diagnostics, Inc. Test device
US4110529A (en) * 1974-11-26 1978-08-29 Ceschoslovak Akademie Ved Method of manufacturing spherical polymer particles from polymer solutions
USRE30267E (en) * 1975-06-20 1980-05-06 Eastman Kodak Company Multilayer analytical element
US4210723A (en) * 1976-07-23 1980-07-01 The Dow Chemical Company Method of coupling a protein to an epoxylated latex
US4259574A (en) * 1979-11-06 1981-03-31 International Business Machines Corporation Microanalysis by pulse laser emission spectroscopy
US4275149A (en) * 1978-11-24 1981-06-23 Syva Company Macromolecular environment control in specific receptor assays
US4312228A (en) * 1979-07-30 1982-01-26 Henry Wohltjen Methods of detection with surface acoustic wave and apparati therefor
US4336459A (en) * 1980-06-11 1982-06-22 Union Carbide Corporation Method and apparatus for detecting fluorescence under ambient light conditions
US4341957A (en) * 1975-11-26 1982-07-27 Analytical Radiation Corporation Fluorescent antibody composition for immunofluorometric assay
US4374925A (en) * 1978-11-24 1983-02-22 Syva Company Macromolecular environment control in specific receptor assays
US4385126A (en) * 1980-11-19 1983-05-24 International Diagnostic Technology, Inc. Double tagged immunoassay
US4426451A (en) * 1981-01-28 1984-01-17 Eastman Kodak Company Multi-zoned reaction vessel having pressure-actuatable control means between zones
US4427836A (en) * 1980-06-12 1984-01-24 Rohm And Haas Company Sequential heteropolymer dispersion and a particulate material obtainable therefrom, useful in coating compositions as a thickening and/or opacifying agent
US4442204A (en) * 1981-04-10 1984-04-10 Miles Laboratories, Inc. Homogeneous specific binding assay device and preformed complex method
US4441373A (en) * 1979-02-21 1984-04-10 American Hospital Supply Corporation Collection tube for drawing samples of biological fluids
US4444592A (en) * 1981-06-02 1984-04-24 The Sherwin-Williams Company Pigment compositions and processes therefor
US4533629A (en) * 1981-04-17 1985-08-06 Syva Company Simultaneous calibration heterogeneous immunoassay
US4533499A (en) * 1980-02-14 1985-08-06 Ciba-Geigy Corporation Process for the production of triaryl methane compounds
US4534356A (en) * 1982-07-30 1985-08-13 Diamond Shamrock Chemicals Company Solid state transcutaneous blood gas sensors
US4537657A (en) * 1983-08-26 1985-08-27 Hercules Incorporated Wet strength resins
US4586695A (en) * 1984-06-22 1986-05-06 Miller Charlie D Continuous tube extractor
US4595661A (en) * 1983-11-18 1986-06-17 Beckman Instruments, Inc. Immunoassays and kits for use therein which include low affinity antibodies for reducing the hook effect
US4596697A (en) * 1984-09-04 1986-06-24 The United States Of America As Represented By The Secretary Of The Army Chemical sensor matrix
US4661235A (en) * 1984-08-03 1987-04-28 Krull Ulrich J Chemo-receptive lipid based membrane transducers
US4722889A (en) * 1985-04-02 1988-02-02 Leeco Diagnostics, Inc. Immunoassays using multiple monoclonal antibodies and scavenger antibodies
US4727019A (en) * 1984-05-11 1988-02-23 Hybritech Incorporated Method and apparatus for immunoassays
US4731337A (en) * 1984-07-26 1988-03-15 Labsystems Oy Fluorimetric immunological assay with magnetic particles
US4743542A (en) * 1985-04-11 1988-05-10 Ortho Diagnostic Method for forestalling the hook effect in a multi-ligand immunoassay system
US4818710A (en) * 1984-12-10 1989-04-04 Prutec Limited Method for optically ascertaining parameters of species in a liquid analyte
US4837168A (en) * 1985-12-23 1989-06-06 Janssen Pharmaceutica N.V. Immunoassay using colorable latex particles
US4843021A (en) * 1986-07-30 1989-06-27 Shino-Test Laboratory Inc. Immunological assay method
US4843000A (en) * 1979-12-26 1989-06-27 Syntex (U.S.A.) Inc. Simultaneous calibration heterogeneous immunoassay
US4842783A (en) * 1987-09-03 1989-06-27 Cordis Corporation Method of producing fiber optic chemical sensors incorporating photocrosslinked polymer gels
US4844613A (en) * 1986-11-03 1989-07-04 Stc Plc Optical surface plasmon sensor device
US4849338A (en) * 1982-07-16 1989-07-18 Syntex (U.S.A.) Inc. Simultaneous calibration heterogeneous immunoassay
US4895017A (en) * 1989-01-23 1990-01-23 The Boeing Company Apparatus and method for early detection and identification of dilute chemical vapors
US4916056A (en) * 1986-02-18 1990-04-10 Abbott Laboratories Solid-phase analytical device and method for using same
US4917503A (en) * 1985-12-02 1990-04-17 Lifelines Technology, Inc. Photoactivatable leuco base time-temperature indicator
US4940734A (en) * 1988-11-23 1990-07-10 American Cyanamid Process for the preparation of porous polymer beads
US4992385A (en) * 1986-07-24 1991-02-12 Ares-Serono Research And Development Limited Partnership Polymer-coated optical structures and methods of making and using the same
US5003178A (en) * 1988-11-14 1991-03-26 Electron Vision Corporation Large-area uniform electron source
US5023053A (en) * 1988-05-20 1991-06-11 Amersham International Plc Biological sensors
US5026653A (en) * 1985-04-02 1991-06-25 Leeco Diagnostic, Inc. Scavenger antibody mixture and its use for immunometric assay
US5035863A (en) * 1988-05-10 1991-07-30 Amersham International Plc Surface plasmon resonance sensors
US5096671A (en) * 1989-03-15 1992-03-17 Cordis Corporation Fiber optic chemical sensors incorporating electrostatic coupling
US5114676A (en) * 1988-08-04 1992-05-19 Avl Ag Optical sensor for determining at least one parameter in a liquid or gaseous sample
US5120662A (en) * 1989-05-09 1992-06-09 Abbott Laboratories Multilayer solid phase immunoassay support and method of use
US5124254A (en) * 1988-02-08 1992-06-23 University College Cardiff Consultants Limited Detection of diamines in biological fluids
US5134057A (en) * 1988-10-10 1992-07-28 501 Ppg Biomedical Systems, Inc. Method of providing a substrate with a layer comprising a polyvinyl based hydrogel and a biochemically active material
US5179288A (en) * 1991-09-30 1993-01-12 Ortho Pharmaceutical Corporation Apparatus and method for measuring a bodily constituent
US5182135A (en) * 1986-08-12 1993-01-26 Bayer Aktiengesellschaft Process for improving the adherency of metallic coatings deposited without current on plastic surfaces
US5196350A (en) * 1991-05-29 1993-03-23 Omnigene, Inc. Ligand assay using interference modulation
US5200084A (en) * 1990-09-26 1993-04-06 Immunicon Corporation Apparatus and methods for magnetic separation
US5208535A (en) * 1990-12-28 1993-05-04 Research Development Corporation Of Japan Mr position detecting device
US5221454A (en) * 1992-01-31 1993-06-22 Biometric Imaging Inc. Differential separation assay
US5225935A (en) * 1989-10-30 1993-07-06 Sharp Kabushiki Kaisha Optical device having a microlens and a process for making microlenses
US5314923A (en) * 1988-11-23 1994-05-24 Cytec Technology Corp. Porous polymer beads and process
US5316727A (en) * 1989-09-08 1994-05-31 Terumo Kabushiki Kaisha Measuring apparatus
US5321492A (en) * 1992-08-07 1994-06-14 Miles Inc. Dual function readhead for a reflectance instrument
US5320944A (en) * 1989-09-29 1994-06-14 Fujirebio Inc. Immunoassay using magnetic particle
US5327225A (en) * 1993-01-28 1994-07-05 The Center For Innovative Technology Surface plasmon resonance sensor
US5330898A (en) * 1991-02-20 1994-07-19 Diagnostic Markers, Inc. Method for the very rapid detection of polyamines
US5387503A (en) * 1990-06-06 1995-02-07 Novo Nordisk A/S Assay method using internal calibration to measure the amount of analyte in a sample
US5395754A (en) * 1992-07-31 1995-03-07 Hybritech Incorporated Membrane-based immunoassay method
US5415842A (en) * 1991-02-07 1995-05-16 Fisons Plc Surface plasmon resonance analytical device
US5418136A (en) * 1991-10-01 1995-05-23 Biostar, Inc. Devices for detection of an analyte based upon light interference
US5424841A (en) * 1993-05-28 1995-06-13 Molecular Dynamics Apparatus for measuring spatial distribution of fluorescence on a substrate
US5424219A (en) * 1991-10-25 1995-06-13 Cytech Biomedical, Inc. Method of performing assays for biomolecules and solid supports for use in such methods
US5432057A (en) * 1979-12-26 1995-07-11 Syva Company Simultaneous calibration heterogeneous immunoassay
US5436161A (en) * 1988-11-10 1995-07-25 Pharmacia Biosensor Ab Matrix coating for sensing surfaces capable of selective biomolecular interactions, to be used in biosensor systems
US5482830A (en) * 1986-02-25 1996-01-09 Biostar, Inc. Devices and methods for detection of an analyte based upon light interference
US5482867A (en) * 1989-11-13 1996-01-09 Affymax Technologies N.V. Spatially-addressable immobilization of anti-ligands on surfaces
US5484867A (en) * 1993-08-12 1996-01-16 The University Of Dayton Process for preparation of polyhedral oligomeric silsesquioxanes and systhesis of polymers containing polyhedral oligomeric silsesqioxane group segments
US5489988A (en) * 1995-01-03 1996-02-06 Motorola Environmental sensor and method therefor
US5489678A (en) * 1989-06-07 1996-02-06 Affymax Technologies N.V. Photolabile nucleoside and peptide protecting groups
US5492840A (en) * 1988-11-10 1996-02-20 Pharmacia Biosensor Ab Surface plasmon resonance sensor unit and its use in biosensor systems
US5496701A (en) * 1991-06-04 1996-03-05 Fisons Plc Optical biosensor method for determining an analyte
US5500350A (en) * 1985-10-30 1996-03-19 Celltech Limited Binding assay device
US5504013A (en) * 1993-11-12 1996-04-02 Unipath Limited Analytical devices and methods of use thereof
US5508171A (en) * 1989-12-15 1996-04-16 Boehringer Mannheim Corporation Assay method with enzyme electrode system
US5510481A (en) * 1990-11-26 1996-04-23 The Regents, University Of California Self-assembled molecular films incorporating a ligand
US5512131A (en) * 1993-10-04 1996-04-30 President And Fellows Of Harvard College Formation of microstamped patterns on surfaces and derivative articles
US5514785A (en) * 1990-05-11 1996-05-07 Becton Dickinson And Company Solid supports for nucleic acid hybridization assays
US5514559A (en) * 1993-03-29 1996-05-07 Boehringer Mannheim Gmbh Immunologically active conjugates and method for their preparation
US5516635A (en) * 1991-10-15 1996-05-14 Ekins; Roger P. Binding assay employing labelled reagent
US5518689A (en) * 1995-09-05 1996-05-21 Bayer Corporation Diffused light reflectance readhead
US5518883A (en) * 1992-07-02 1996-05-21 Soini; Erkki J. Biospecific multiparameter assay method
US5527711A (en) * 1993-12-13 1996-06-18 Hewlett Packard Company Method and reagents for binding chemical analytes to a substrate surface, and related analytical devices and diagnostic techniques
US5534132A (en) * 1995-05-04 1996-07-09 Vreeke; Mark Electrode and method for the detection of an affinity reaction
US5723294A (en) * 1996-03-05 1998-03-03 Gull Laboratories Methods for detection and discrimination of multiple analytes using fluorescent technology
US5876944A (en) * 1996-06-10 1999-03-02 Bayer Corporation Method for amplification of the response signal in a sandwich immunoassay
US20020004246A1 (en) * 2000-02-07 2002-01-10 Daniels Robert H. Immunochromatographic methods for detecting an analyte in a sample which employ semiconductor nanocrystals as detectable labels
US6387707B1 (en) * 1996-04-25 2002-05-14 Bioarray Solutions Array Cytometry
US6396053B1 (en) * 1998-11-02 2002-05-28 Olympus Optical Co. Scanning optical microscope apparatus capable of detecting a plurality of flourescent light beams
US6699722B2 (en) * 2000-04-14 2004-03-02 A-Fem Medical Corporation Positive detection lateral-flow apparatus and method for small and large analytes
US6720007B2 (en) * 2000-10-25 2004-04-13 Tufts University Polymeric microspheres
US6887851B2 (en) * 2001-09-18 2005-05-03 Bioexpertise, Llc IGF-binding protein-derived peptide

Family Cites Families (229)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3604927A (en) 1966-11-16 1971-09-14 Block Engineering Total reflection fluorescence spectroscopy
US3772076A (en) 1970-01-26 1973-11-13 Hercules Inc Reaction products of epihalohydrin and polymers of diallylamine and their use in paper
US3700623A (en) 1970-04-22 1972-10-24 Hercules Inc Reaction products of epihalohydrin and polymers of diallylamine and their use in paper
DE2222852A1 (en) 1971-05-11 1973-12-13 Image Analysing Computers Ltd Field illumination for the image analysis
US4299916A (en) 1979-12-26 1981-11-10 Syva Company Preferential signal production on a surface in immunoassays
US4540659A (en) 1981-04-17 1985-09-10 Syva Company Simultaneous calibration heterogeneous immunoassay
US5156953A (en) 1979-12-26 1992-10-20 Syntex (U.S.A.) Inc. Simultaneous calibration heterogeneous immunoassay
US4366241B1 (en) 1980-08-07 1988-10-18
US4357311A (en) 1980-10-03 1982-11-02 Warner-Lambert Company Substrate for immunoassay and means of preparing same
US4363874A (en) 1981-08-07 1982-12-14 Miles Laboratories, Inc. Multilayer analytical element having an impermeable radiation nondiffusing reflecting layer
US4480042A (en) 1981-10-28 1984-10-30 E. I. Du Pont De Nemours And Company Covalently bonded high refractive index particle reagents and their use in light scattering immunoassays
EP0073593A1 (en) 1981-09-01 1983-03-09 E.I. Du Pont De Nemours And Company Size-exclusion heterogeneous immunoassay
US4477635A (en) 1982-01-04 1984-10-16 Minnesota Mining And Manufacturing Company Polymeric triarylmethane dyes
US4435504A (en) 1982-07-15 1984-03-06 Syva Company Immunochromatographic assay with support having bound "MIP" and second enzyme
US4632559A (en) 1982-11-29 1986-12-30 Miles Laboratories, Inc. Optical readhead
US4537861A (en) 1983-02-03 1985-08-27 Elings Virgil B Apparatus and method for homogeneous immunoassay
GB8314523D0 (en) 1983-05-25 1983-06-29 Lowe C R Diagnostic device
EP0127797B1 (en) 1983-06-03 1987-06-16 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Labelled molecules for fluorescence immunoassays and processes and intermediates for their preparation
US4552458A (en) 1983-10-11 1985-11-12 Eastman Kodak Company Compact reflectometer
US4703017C1 (en) * 1984-02-14 2001-12-04 Becton Dickinson Co Solid phase assay with visual readout
US4698262A (en) 1984-04-27 1987-10-06 Becton, Dickinson And Company Fluorescently labeled microbeads
US5310687A (en) 1984-10-31 1994-05-10 Igen, Inc. Luminescent metal chelate labels and means for detection
US4680275A (en) * 1985-02-11 1987-07-14 Becton, Dickinson And Company Homogeneous fluorescence immunoassay using a light absorbing material
US5879881A (en) 1985-04-04 1999-03-09 Hybritech, Incorporated Solid phase system for use in ligand-receptor assays
GB8509492D0 (en) 1985-04-12 1985-05-15 Plessey Co Plc Optical assay
EP0335902B1 (en) * 1986-12-15 1993-12-01 British Technology Group Usa Inc. Monomeric phthalocyanine reagents
US4877965A (en) 1985-07-01 1989-10-31 Diatron Corporation Fluorometer
US4963498A (en) 1985-08-05 1990-10-16 Biotrack Capillary flow device
US5238815A (en) 1985-08-30 1993-08-24 Toyo Soda Manufacturing Co., Ltd. Enzymatic immunoassay involving detecting fluorescence while oscillating magnetic beads
US5585279A (en) 1986-01-23 1996-12-17 Davidson; Robert S. Time-resolved luminescence binding assays using a fluorescent transition metal label other than ruthenium
US4776944A (en) 1986-03-20 1988-10-11 Jiri Janata Chemical selective sensors utilizing admittance modulated membranes
US5591581A (en) 1986-04-30 1997-01-07 Igen, Inc. Electrochemiluminescent rhenium moieties and methods for their use
DE3789430T2 (en) 1986-06-17 1994-10-27 Baxter Diagnostics Inc Homogeneous fluorine-testing methods with repelling the fluorine producers, background.
US4935346A (en) 1986-08-13 1990-06-19 Lifescan, Inc. Minimum procedure system for the determination of analytes
US4791310A (en) 1986-10-02 1988-12-13 Syracuse University Fluorescence microscopy
US4857453A (en) 1987-04-07 1989-08-15 Syntex (U.S.A.) Inc. Immunoassay device
US4855240A (en) 1987-05-13 1989-08-08 Becton Dickinson And Company Solid phase assay employing capillary flow
US5670381A (en) 1988-01-29 1997-09-23 Abbott Laboratories Devices for performing ion-capture binding assays
US5268306A (en) 1988-02-29 1993-12-07 Boehringer Mannheim Gmbh Preparation of a solid phase matrix containing a bound specific binding pair
US5145784A (en) 1988-05-04 1992-09-08 Cambridge Biotech Corporation Double capture assay method employing a capillary flow device
DE68907519D1 (en) 1988-05-10 1993-08-19 Amersham Int Plc Biosensors.
GB8813307D0 (en) 1988-06-06 1988-07-13 Amersham Int Plc Biological sensors
US4877586A (en) 1988-07-27 1989-10-31 Eastman Kodak Company Sliding test device for assays
US5075077A (en) 1988-08-02 1991-12-24 Abbott Laboratories Test card for performing assays
US4973670A (en) 1988-08-12 1990-11-27 The Dow Chemical Company Method for preparing hollow latexes
US5252459A (en) 1988-09-23 1993-10-12 Abbott Laboratories Indicator reagents, diagnostic assays and test kits employing organic polymer latex particles
US6448091B1 (en) 1988-11-03 2002-09-10 Igen International, Inc. Method and apparatus for improved luminescence assays using particle concentration chemiluminescence detection
US5063081A (en) 1988-11-14 1991-11-05 I-Stat Corporation Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor
JP2853745B2 (en) 1989-04-12 1999-02-03 株式会社日立製作所 Light detection electrophoresis apparatus
US5234813A (en) 1989-05-17 1993-08-10 Actimed Laboratories, Inc. Method and device for metering of fluid samples and detection of analytes therein
US5770416A (en) 1989-05-26 1998-06-23 Upfront Chromatography A/S Permeable hollow particles having an outer shell of mechanically rigid porous material
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5166079A (en) 1989-07-19 1992-11-24 Pb Diagnostic Systems, Inc. Analytical assay method
JPH0366384A (en) 1989-08-04 1991-03-22 Senjiyu Seiyaku Kk System for controlling release of physiologically active material
US5235238A (en) 1989-08-10 1993-08-10 Dainabot Company, Limited Electrode-separated piezoelectric crystal oscillator and method for measurement using the electrode-separated piezoelectric crystal oscillator
US5468606A (en) 1989-09-18 1995-11-21 Biostar, Inc. Devices for detection of an analyte based upon light interference
CA2003942A1 (en) 1989-09-26 1991-03-26 Julie Lia Rudolph Solid assay support systems
GB8927503D0 (en) 1989-12-04 1990-02-07 Kronem Systems Inc Enzyme-amplified lanthanide chelate luminescence
GB9008261D0 (en) 1990-04-11 1990-06-13 Ares Serono Res & Dev Ltd Method of improving assay sensitivity
ES2092523T3 (en) 1990-05-09 1996-12-01 Abbott Lab Assays using links conjugate recovery.
DE4024476C1 (en) 1990-08-02 1992-02-27 Boehringer Mannheim Gmbh, 6800 Mannheim, De
GB9019123D0 (en) 1990-09-01 1990-10-17 Fisons Plc Analytical device
US5076094A (en) 1990-10-03 1991-12-31 The United States Of America As Represented By The United States Department Of Energy Dual output acoustic wave sensor for molecular identification
US5700636A (en) 1990-10-19 1997-12-23 Becton Dickinson And Company Methods for selectively detecting microorganisms associated with vaginal infections in complex biological samples
US6027944A (en) 1990-11-22 2000-02-22 Applied Research Systems Ars Holding Nv Capillary-fill biosensor device comprising a calibration zone
US5726064A (en) 1990-11-22 1998-03-10 Applied Research Systems Ars Holding Nv Method of assay having calibration within the assay
US6861264B2 (en) 1992-01-27 2005-03-01 Cis Bio International Method of measuring the luminescence emitted in a luminescent assay
US5834226A (en) 1991-01-31 1998-11-10 Xytronyx, Inc. One-step test for aspartate aminotransferase
US5489998A (en) * 1991-03-04 1996-02-06 Canon Kabushiki Kaisha Color image processing apparatus having transmitter and receiver which perform color correction in accordance with a common standard color image and method for same
US5795470A (en) 1991-03-25 1998-08-18 Immunivest Corporation Magnetic separation apparatus
US5466574A (en) 1991-03-25 1995-11-14 Immunivest Corporation Apparatus and methods for magnetic separation featuring external magnetic means
WO1993015230A1 (en) 1992-01-22 1993-08-05 Abbott Laboratories Calibration reagents for semi-quantitative binding assays and devices
US5137609A (en) 1992-01-31 1992-08-11 Biometric Imaging Inc. Differential separation assay
US5445971A (en) 1992-03-20 1995-08-29 Abbott Laboratories Magnetically assisted binding assays using magnetically labeled binding members
US5326692B1 (en) 1992-05-13 1996-04-30 Molecular Probes Inc Fluorescent microparticles with controllable enhanced stokes shift
US6156270A (en) 1992-05-21 2000-12-05 Biosite Diagnostics, Inc. Diagnostic devices and apparatus for the controlled movement of reagents without membranes
US6019944A (en) 1992-05-21 2000-02-01 Biosite Diagnostics, Inc. Diagnostic devices and apparatus for the controlled movement of reagents without membranes
GB9217864D0 (en) 1992-08-21 1992-10-07 Unilever Plc Monitoring method
US5356782A (en) 1992-09-03 1994-10-18 Boehringer Mannheim Corporation Analytical test apparatus with on board negative and positive control
US5674698A (en) 1992-09-14 1997-10-07 Sri International Up-converting reporters for biological and other assays using laser excitation techniques
EP0588153B1 (en) 1992-09-14 1996-12-27 Siemens Aktiengesellschaft Gas sensor
US6399397B1 (en) 1992-09-14 2002-06-04 Sri International Up-converting reporters for biological and other assays using laser excitation techniques
GB9221329D0 (en) 1992-10-10 1992-11-25 Delta Biotechnology Ltd Preparation of further diagnostic agents
US5358852A (en) 1992-12-21 1994-10-25 Eastman Kodak Company Use of calcium in immunoassay for measurement of C-reactive protein
US6200820B1 (en) 1992-12-22 2001-03-13 Sienna Biotech, Inc. Light scatter-based immunoassay
US5422726A (en) 1993-02-16 1995-06-06 Tyler; Jonathan M. Solid state spectrofluorimeter and method of using the same
DE4309393A1 (en) 1993-03-23 1994-09-29 Boehringer Mannheim Gmbh Reducing the hook effect in immunoassays with particulate carrier material
JP3479100B2 (en) 1993-06-02 2003-12-15 帝国臓器製薬株式会社 Immunochemical simple semi-quantitative method and apparatus
FI932866A0 (en) 1993-06-21 1993-06-21 Labsystems Oy Separeringsfoerfarande
US5658443A (en) 1993-07-23 1997-08-19 Matsushita Electric Industrial Co., Ltd. Biosensor and method for producing the same
FR2708348B1 (en) 1993-07-28 1995-10-06 Stago Diagnostica A method of assaying an immunological substance by means of magnetic latex particles and non-magnetic particles.
US5837546A (en) 1993-08-24 1998-11-17 Metrika, Inc. Electronic assay device and method
US5464741A (en) 1993-10-08 1995-11-07 Henwell, Inc. Palladium (II) octaethylporphine alpha-isothiocyanate as a phosphorescent label for immunoassays
JP2614707B2 (en) 1993-10-20 1997-05-28 株式会社エルジ化学 Method for producing an emulsion polymer having a hollow structure
US5352582A (en) 1993-10-28 1994-10-04 Hewlett-Packard Company Holographic based bio-assay
US5455475A (en) 1993-11-01 1995-10-03 Marquette University Piezoelectric resonant sensor using the acoustoelectric effect
ES2182836T3 (en) 1993-11-12 2003-03-16 Inverness Medical Switzerland Reading devices for test strips.
JP3504750B2 (en) 1993-12-22 2004-03-08 オルソ−クリニカル ダイアグノスティクス,インコーポレイティド Calibration equation re-calibration method and quantitative test kit
US5663213A (en) 1994-02-28 1997-09-02 Rohm And Haas Company Method of improving ultraviolet radiation absorption of a composition
GB9416002D0 (en) 1994-08-08 1994-09-28 Univ Cranfield Fluid transport device
US6117090A (en) 1994-08-25 2000-09-12 Caillouette; James C. Method and apparatus for detecting amine producing organisms in the vagina
US5599668A (en) 1994-09-22 1997-02-04 Abbott Laboratories Light scattering optical waveguide method for detecting specific binding events
US5620850A (en) 1994-09-26 1997-04-15 President And Fellows Of Harvard College Molecular recognition at surfaces derivatized with self-assembled monolayers
US5571684A (en) 1994-11-07 1996-11-05 Litmus Concepts, Inc. Assay for proline iminopeptidase and other hydrolytic activities
US5728352A (en) 1994-11-14 1998-03-17 Advanced Care Products Disposable electronic diagnostic instrument
US5866434A (en) 1994-12-08 1999-02-02 Meso Scale Technology Graphitic nanotubes in luminescence assays
KR0151203B1 (en) 1994-12-08 1998-12-01 이헌조 Multi-electrode type biosensor
US5569608A (en) 1995-01-30 1996-10-29 Bayer Corporation Quantitative detection of analytes on immunochromatographic strips
FR2730810B1 (en) 1995-02-21 1997-03-14 Thomson Csf highly selective chemical sensor
KR0156176B1 (en) 1995-06-01 1998-12-01 구자홍 Electrochemical immune biosensor
US6413410B1 (en) 1996-06-19 2002-07-02 Lifescan, Inc. Electrochemical cell
GB9602323D0 (en) 1996-02-06 1996-04-03 Boehringer Mannheim Gmbh Materials and methods relating to binding assays
US6287871B1 (en) 1996-03-19 2001-09-11 University Of Utah Research Foundation System for determining analyte concentration
US5753517A (en) 1996-03-29 1998-05-19 University Of British Columbia Quantitative immunochromatographic assays
EP0890104B1 (en) 1996-03-29 2001-08-01 The University Of British Columbia Platelet count assay using platelet granule proteins
ES2121565T6 (en) 1996-05-17 1998-11-16 Mercury Diagnostics Inc A disposable device for use in a sampling of body fluids.
US5951492A (en) 1996-05-17 1999-09-14 Mercury Diagnostics, Inc. Methods and apparatus for sampling and analyzing body fluid
DE19622458C2 (en) 1996-05-24 1998-03-26 Senslab Ges Zur Entwicklung Un Enzymatic-electrochemical single-step affinity sensor for the quantitative determination of analytes in aqueous media and affinity assay
DE19621133A1 (en) 1996-05-24 1997-11-27 Boehringer Mannheim Gmbh Determination method with oligomerized receptors
EP0901620B1 (en) 1996-05-28 2002-01-09 Zeptosens AG Optical detection apparatus for chemical analyses of small volumes of samples
US5852229A (en) 1996-05-29 1998-12-22 Kimberly-Clark Worldwide, Inc. Piezoelectric resonator chemical sensing device
US6004530A (en) 1996-06-04 1999-12-21 Roche Diagnostics Gmbh Use of metallo-porphyrin conjugates for the detection of biological substances
US6444423B1 (en) 1996-06-07 2002-09-03 Molecular Dynamics, Inc. Nucleosides comprising polydentate ligands
US5780251A (en) 1996-06-27 1998-07-14 Fci Fiberchem, Inc. Ultrasensitive single-step, solid-state competitive immunoassay sensor with interference modifier and/or gel layer
WO1998001744A1 (en) 1996-07-10 1998-01-15 Cambridge Imaging Limited Improved imaging system for fluorescence assays
US5660790A (en) 1996-08-13 1997-08-26 Litmus Concepts, Inc. PH and amine test elements
WO1998007022A1 (en) 1996-08-16 1998-02-19 Imaging Research, Inc. A digital imaging system for assays in well plates, gels and blots
US5832165A (en) 1996-08-28 1998-11-03 University Of Utah Research Foundation Composite waveguide for solid phase binding assays
US6020047A (en) 1996-09-04 2000-02-01 Kimberly-Clark Worldwide, Inc. Polymer films having a printed self-assembling monolayer
US5798273A (en) 1996-09-25 1998-08-25 Becton Dickinson And Company Direct read lateral flow assay for small analytes
US6194220B1 (en) * 1996-09-25 2001-02-27 Becton, Dickinson And Company Non-instrumented assay with quantitative and qualitative results
US5910940A (en) 1996-10-08 1999-06-08 Polaroid Corporation Storage medium having a layer of micro-optical lenses each lens generating an evanescent field
US6165798A (en) 1996-10-10 2000-12-26 University Of British Columbia Optical quantification of analytes in membranes
US5922537A (en) 1996-11-08 1999-07-13 N.o slashed.AB Immunoassay, Inc. Nanoparticles biosensor
US6048623A (en) 1996-12-18 2000-04-11 Kimberly-Clark Worldwide, Inc. Method of contact printing on gold coated films
US5922550A (en) 1996-12-18 1999-07-13 Kimberly-Clark Worldwide, Inc. Biosensing devices which produce diffraction images
US6407492B1 (en) 1997-01-02 2002-06-18 Advanced Electron Beams, Inc. Electron beam accelerator
US5962995A (en) 1997-01-02 1999-10-05 Applied Advanced Technologies, Inc. Electron beam accelerator
US5827748A (en) 1997-01-24 1998-10-27 The United States Of America As Represented By The Secretary Of The Navy Chemical sensor using two-dimensional lens array
US6391558B1 (en) 1997-03-18 2002-05-21 Andcare, Inc. Electrochemical detection of nucleic acid sequences
US6180288B1 (en) 1997-03-21 2001-01-30 Kimberly-Clark Worldwide, Inc. Gel sensors and method of use thereof
US6235471B1 (en) 1997-04-04 2001-05-22 Caliper Technologies Corp. Closed-loop biochemical analyzers
EP0872736A1 (en) 1997-04-18 1998-10-21 Byk Gulden Italia S.p.A. Assay utilizing magnetic particles
US6103536A (en) 1997-05-02 2000-08-15 Silver Lake Research Corporation Internally referenced competitive assays
US6008892A (en) 1997-05-23 1999-12-28 Molecular Dynamics, Inc. Optical substrate for enhanced detectability of fluorescence
US6171780B1 (en) 1997-06-02 2001-01-09 Aurora Biosciences Corporation Low fluorescence assay platforms and related methods for drug discovery
US6613583B1 (en) 1997-06-27 2003-09-02 Igen International, Inc. Electrochemiluminescent label based on multimetallic assemblies
US6136611A (en) 1997-07-31 2000-10-24 Research International, Inc. Assay methods and apparatus
US5943129A (en) 1997-08-07 1999-08-24 Cambridge Research & Instrumentation Inc. Fluorescence imaging system
EP0898169B1 (en) 1997-08-11 2002-02-06 F. Hoffmann-La Roche Ag Microparticle enhanced light scattering assay and microparticle reagents therefor
US20020166764A1 (en) 1997-08-12 2002-11-14 University Of Southern California Electrochemical sensor devices and methods for fast, reliable, and sensitive detection and quantitation of analytes
US6080391A (en) 1997-08-14 2000-06-27 Novo Nordisk A/S Reduction of malodour
US5906921A (en) 1997-09-29 1999-05-25 Matsushita Electric Industrial Co., Ltd. Biosensor and method for quantitative measurement of a substrate using the same
WO1999018438A1 (en) 1997-10-02 1999-04-15 Aclara Biosciences, Inc. Capillary assays involving separation of free and bound species
US6617488B1 (en) 1997-10-14 2003-09-09 Indicator Technologies, Inc. Method and apparatus for indicating the conditions in an absorbent article
US6174646B1 (en) 1997-10-21 2001-01-16 Konica Corporation Image forming method
US6087184A (en) 1997-11-10 2000-07-11 Beckman Coulter, Inc. Opposable-element chromatographic assay device for detection of analytes
US6030792A (en) 1997-11-13 2000-02-29 Pfizer Inc Assays for measurement of protein fragments in biological media
US5997817A (en) 1997-12-05 1999-12-07 Roche Diagnostics Corporation Electrochemical biosensor test strip
US6074725A (en) 1997-12-10 2000-06-13 Caliper Technologies Corp. Fabrication of microfluidic circuits by printing techniques
US6060256A (en) 1997-12-16 2000-05-09 Kimberly-Clark Worldwide, Inc. Optical diffraction biosensor
KR100593712B1 (en) 1998-01-22 2006-06-30 루미넥스 코포레이션 Microparticles having a plurality of fluorescent signal
DE19811622A1 (en) 1998-03-17 1999-09-23 Lre Technology Partner Gmbh Laboratory instrument incorporating split test card housing
DE69904307D1 (en) 1998-03-19 2003-01-16 Max Planck Gesellschaft Production of coated with more layers of particles and hollow shells by electrostatic self-organization of nanokompositmehrlagen on decomposable template
US6368873B1 (en) 1998-04-09 2002-04-09 Applied Biotech, Inc. Identification of human urine for drug testing
US6241863B1 (en) 1998-04-27 2001-06-05 Harold G. Monbouquette Amperometric biosensors based on redox enzymes
US6316466B1 (en) 1998-05-05 2001-11-13 Syntex (U.S.A.) Llc Pyrazole derivatives P-38 MAP kinase inhibitors
US6451607B1 (en) 1998-05-07 2002-09-17 Litmus Concepts, Inc. External dried-reagent control for analytical test devices
US6139961A (en) 1998-05-18 2000-10-31 Rohm And Haas Company Hollow sphere organic pigment for paper or paper coatings
JPH11326603A (en) 1998-05-19 1999-11-26 Seiko Epson Corp Microlens array and its production thereof, and display
WO1999064864A9 (en) * 1998-06-12 2000-03-23 New Horizons Diagnostics Inc Optimizing sensitivity in colloidal colorimetric flow through and lateral flow tests
US6030840A (en) 1998-06-15 2000-02-29 Nen Life Sciences, Inc. Neutral enhancement of lanthanides for time resolved fluorescence
US6183972B1 (en) 1998-07-27 2001-02-06 Bayer Corporation Method for the determination of analyte concentration in a lateral flow sandwich immunoassay exhibiting high-dose hook effect
US6171870B1 (en) 1998-08-06 2001-01-09 Spectral Diagnostics, Inc. Analytical test device and method for use in medical diagnoses
US6281006B1 (en) 1998-08-24 2001-08-28 Therasense, Inc. Electrochemical affinity assay
US20010036645A1 (en) 1998-09-29 2001-11-01 Mcneirney John C. Analyte detector and analyte detection method
GB9821526D0 (en) 1998-10-02 1998-11-25 Genosis Inc Capture assay
US6284472B1 (en) 1998-10-05 2001-09-04 Dade Behring Inc. Method for extending the range of an immunoassay
US6338790B1 (en) 1998-10-08 2002-01-15 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
DE19846928A1 (en) 1998-10-12 2000-04-13 Zeiss Carl Fa Imaging system, especially in a high throughput automatic analyzer useful for drug development or medical diagnosis, has a cylindrical lens array combined with or preceded by a prism array
FI982422A0 (en) * 1998-11-09 1998-11-09 Arctic Diagnostics Oy Porphyrin compounds, their conjugates, and methods of analysis based on the use of these conjugates
US6261779B1 (en) 1998-11-10 2001-07-17 Bio-Pixels Ltd. Nanocrystals having polynucleotide strands and their use to form dendrimers in a signal amplification system
CA2254223A1 (en) 1998-11-16 2000-05-16 Biophys, Inc. Device and method for analyzing a biologic sample
US6455861B1 (en) 1998-11-24 2002-09-24 Cambridge Research & Instrumentation, Inc. Fluorescence polarization assay system and method
US6221579B1 (en) 1998-12-11 2001-04-24 Kimberly-Clark Worldwide, Inc. Patterned binding of functionalized microspheres for optical diffraction-based biosensors
US6579673B2 (en) 1998-12-17 2003-06-17 Kimberly-Clark Worldwide, Inc. Patterned deposition of antibody binding protein for optical diffraction-based biosensors
US6660379B1 (en) 1999-02-05 2003-12-09 University Of Maryland, Baltimore Luminescence spectral properties of CdS nanoparticles
US6787368B1 (en) 1999-03-02 2004-09-07 Helix Biopharma Corporation Biosensor method for detecting analytes in a liquid
US6287783B1 (en) 1999-03-18 2001-09-11 Biostar, Inc. Optical assay device and method
US6511814B1 (en) 1999-03-26 2003-01-28 Idexx Laboratories, Inc. Method and device for detecting analytes in fluids
US6815218B1 (en) 1999-06-09 2004-11-09 Massachusetts Institute Of Technology Methods for manufacturing bioelectronic devices
DE19933104A1 (en) 1999-07-15 2001-01-18 Ingo Klimant Phosphorescent micro- and nanoparticles as a reference standard and Phosphoreszenzmarker
US6294392B1 (en) 1999-07-21 2001-09-25 The Regents Of The University Of California Spatially-encoded analyte detection
US6306665B1 (en) 1999-10-13 2001-10-23 A-Fem Medical Corporation Covalent bonding of molecules to an activated solid phase material
US6136549A (en) 1999-10-15 2000-10-24 Feistel; Christopher C. systems and methods for performing magnetic chromatography assays
USD450854S1 (en) 1999-11-04 2001-11-20 Therasense, Inc. Glucose strip
US6867851B2 (en) 1999-11-04 2005-03-15 Regents Of The University Of Minnesota Scanning of biological samples
WO2001038873A3 (en) 1999-11-24 2002-07-11 Biotronic Technologies Inc Devices and methods for detecting analytes using electrosensor having capture reagent
US6331438B1 (en) 1999-11-24 2001-12-18 Iowa State University Research Foundation, Inc. Optical sensors and multisensor arrays containing thin film electroluminescent devices
US6399295B1 (en) 1999-12-17 2002-06-04 Kimberly-Clark Worldwide, Inc. Use of wicking agent to eliminate wash steps for optical diffraction-based biosensors
US6509196B1 (en) 2000-01-04 2003-01-21 Response Biomedical Corp. Compensation for non-specific signals in quantitative immunoassays
US6255066B1 (en) 2000-02-08 2001-07-03 Allan L. Louderback Bacterial vaginosis screening technique and a diagnostic kit for use therein
US20010055776A1 (en) 2000-02-11 2001-12-27 Dale Greenwalt High throughput cell-based assay kits
WO2001063260A1 (en) 2000-02-25 2001-08-30 Cambridge Research & Instrumentation Inc. Instantaneous dual band fluorescence detection systems
DE60134219D1 (en) 2000-02-28 2008-07-10 Daiichi Pure Chemicals Co Ltd Measurement methods based on fluorescence energy transfer long with a donor fluorescence lifetime
US6607922B2 (en) 2000-03-17 2003-08-19 Quantum Design, Inc. Immunochromatographic assay method and apparatus
US6436722B1 (en) 2000-04-18 2002-08-20 Idexx Laboratories, Inc. Device and method for integrated diagnostics with multiple independent flow paths
DE10025145A1 (en) * 2000-05-20 2001-11-22 Presens Prec Sensing Gmbh Phosphorescent polyelectrolyte aggregate used e.g. for the labelling and detection of biomolecules, e.g. toxins or hormones, comprises a luminescent metal-ligand complex in a screening sheath of polyelectrolyte
WO2001098785B1 (en) 2000-06-19 2002-11-14 Univ Arizona Rapid flow-based immunoassay microchip
US7892854B2 (en) 2000-06-21 2011-02-22 Bioarray Solutions, Ltd. Multianalyte molecular analysis using application-specific random particle arrays
US6372895B1 (en) 2000-07-07 2002-04-16 3M Innovative Properties Company Fluorogenic compounds
DE10042023C2 (en) * 2000-08-08 2003-04-10 Biognostic Ag Capsules encapsulating solid particles of signal-generating organic substances, and their use in bioassays for detection of target molecules in a sample
DE10054426B4 (en) 2000-10-27 2006-03-09 Iom Innovative Optische Messtechnik Gmbh A method for multi-fluorescence detection
US20020164659A1 (en) 2000-11-30 2002-11-07 Rao Galla Chandra Analytical methods and compositions
DE10062062C1 (en) 2000-12-13 2002-02-28 Draegerwerk Ag Electrochemical sensor used e.g. in control technology has a microprocessor integrated on chip of an electronic device for receiving and further processing signals from the device
US20030162236A1 (en) 2001-03-26 2003-08-28 Response Biomedical Corporation Compensation for variability in specific binding in quantitative assays
JP2002303629A (en) 2001-04-06 2002-10-18 Matsushita Electric Ind Co Ltd Immune chromatography device and method for determining substance to be tested using the same
CA2383392A1 (en) * 2001-04-27 2002-10-27 Hirotaka Tanaka Bio-device, and quantitative measurement apparatus and method using the same
JP3741051B2 (en) 2001-05-10 2006-02-01 横河電機株式会社 Biochip reader
JP4834242B2 (en) 2001-05-30 2011-12-14 オリンパス株式会社 Fluorescence reader
CN100386627C (en) 2001-07-03 2008-05-07 包 刚;许扬清 Filtration-based microarray chip
US6818456B2 (en) 2001-07-20 2004-11-16 Varian, Inc. Color contrast system for lateral flow immunoassay tests
US8367013B2 (en) 2001-12-24 2013-02-05 Kimberly-Clark Worldwide, Inc. Reading device, method, and system for conducting lateral flow assays
US20030119203A1 (en) 2001-12-24 2003-06-26 Kimberly-Clark Worldwide, Inc. Lateral flow assay devices and methods for conducting assays
US7214427B2 (en) 2002-03-21 2007-05-08 Aviva Biosciences Corporation Composite beads comprising magnetizable substance and electro-conductive substance
US7314763B2 (en) 2002-08-27 2008-01-01 Kimberly-Clark Worldwide, Inc. Fluidics-based assay devices
US7432105B2 (en) 2002-08-27 2008-10-07 Kimberly-Clark Worldwide, Inc. Self-calibration system for a magnetic binding assay
US7285424B2 (en) 2002-08-27 2007-10-23 Kimberly-Clark Worldwide, Inc. Membrane-based assay devices
US20040106190A1 (en) 2002-12-03 2004-06-03 Kimberly-Clark Worldwide, Inc. Flow-through assay devices

Patent Citations (100)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1366241A (en) * 1919-10-03 1921-01-18 Frederick W Burch Ratchet mechanism for camp-beds
US4006360A (en) * 1974-08-21 1977-02-01 Block Engineering, Inc. Method of discriminating between dyed particles and background fluorescence of the dye
US4110529A (en) * 1974-11-26 1978-08-29 Ceschoslovak Akademie Ved Method of manufacturing spherical polymer particles from polymer solutions
USRE30267E (en) * 1975-06-20 1980-05-06 Eastman Kodak Company Multilayer analytical element
US4341957A (en) * 1975-11-26 1982-07-27 Analytical Radiation Corporation Fluorescent antibody composition for immunofluorometric assay
US4094647A (en) * 1976-07-02 1978-06-13 Thyroid Diagnostics, Inc. Test device
US4210723A (en) * 1976-07-23 1980-07-01 The Dow Chemical Company Method of coupling a protein to an epoxylated latex
US4275149A (en) * 1978-11-24 1981-06-23 Syva Company Macromolecular environment control in specific receptor assays
US4374925A (en) * 1978-11-24 1983-02-22 Syva Company Macromolecular environment control in specific receptor assays
US4441373A (en) * 1979-02-21 1984-04-10 American Hospital Supply Corporation Collection tube for drawing samples of biological fluids
US4312228A (en) * 1979-07-30 1982-01-26 Henry Wohltjen Methods of detection with surface acoustic wave and apparati therefor
US4259574A (en) * 1979-11-06 1981-03-31 International Business Machines Corporation Microanalysis by pulse laser emission spectroscopy
US5432057A (en) * 1979-12-26 1995-07-11 Syva Company Simultaneous calibration heterogeneous immunoassay
US4843000A (en) * 1979-12-26 1989-06-27 Syntex (U.S.A.) Inc. Simultaneous calibration heterogeneous immunoassay
US4533499A (en) * 1980-02-14 1985-08-06 Ciba-Geigy Corporation Process for the production of triaryl methane compounds
US4336459A (en) * 1980-06-11 1982-06-22 Union Carbide Corporation Method and apparatus for detecting fluorescence under ambient light conditions
US4427836A (en) * 1980-06-12 1984-01-24 Rohm And Haas Company Sequential heteropolymer dispersion and a particulate material obtainable therefrom, useful in coating compositions as a thickening and/or opacifying agent
US4385126A (en) * 1980-11-19 1983-05-24 International Diagnostic Technology, Inc. Double tagged immunoassay
US4426451A (en) * 1981-01-28 1984-01-17 Eastman Kodak Company Multi-zoned reaction vessel having pressure-actuatable control means between zones
US4442204A (en) * 1981-04-10 1984-04-10 Miles Laboratories, Inc. Homogeneous specific binding assay device and preformed complex method
US4533629A (en) * 1981-04-17 1985-08-06 Syva Company Simultaneous calibration heterogeneous immunoassay
US4444592A (en) * 1981-06-02 1984-04-24 The Sherwin-Williams Company Pigment compositions and processes therefor
US4849338A (en) * 1982-07-16 1989-07-18 Syntex (U.S.A.) Inc. Simultaneous calibration heterogeneous immunoassay
US4534356A (en) * 1982-07-30 1985-08-13 Diamond Shamrock Chemicals Company Solid state transcutaneous blood gas sensors
US4537657A (en) * 1983-08-26 1985-08-27 Hercules Incorporated Wet strength resins
US4595661A (en) * 1983-11-18 1986-06-17 Beckman Instruments, Inc. Immunoassays and kits for use therein which include low affinity antibodies for reducing the hook effect
US4727019A (en) * 1984-05-11 1988-02-23 Hybritech Incorporated Method and apparatus for immunoassays
US4586695A (en) * 1984-06-22 1986-05-06 Miller Charlie D Continuous tube extractor
US4731337A (en) * 1984-07-26 1988-03-15 Labsystems Oy Fluorimetric immunological assay with magnetic particles
US4661235A (en) * 1984-08-03 1987-04-28 Krull Ulrich J Chemo-receptive lipid based membrane transducers
US4596697A (en) * 1984-09-04 1986-06-24 The United States Of America As Represented By The Secretary Of The Army Chemical sensor matrix
US4818710A (en) * 1984-12-10 1989-04-04 Prutec Limited Method for optically ascertaining parameters of species in a liquid analyte
US5026653A (en) * 1985-04-02 1991-06-25 Leeco Diagnostic, Inc. Scavenger antibody mixture and its use for immunometric assay
US4722889A (en) * 1985-04-02 1988-02-02 Leeco Diagnostics, Inc. Immunoassays using multiple monoclonal antibodies and scavenger antibodies
US4743542A (en) * 1985-04-11 1988-05-10 Ortho Diagnostic Method for forestalling the hook effect in a multi-ligand immunoassay system
US5500350A (en) * 1985-10-30 1996-03-19 Celltech Limited Binding assay device
US4917503A (en) * 1985-12-02 1990-04-17 Lifelines Technology, Inc. Photoactivatable leuco base time-temperature indicator
US4837168A (en) * 1985-12-23 1989-06-06 Janssen Pharmaceutica N.V. Immunoassay using colorable latex particles
US4916056A (en) * 1986-02-18 1990-04-10 Abbott Laboratories Solid-phase analytical device and method for using same
US5482830A (en) * 1986-02-25 1996-01-09 Biostar, Inc. Devices and methods for detection of an analyte based upon light interference
US4992385A (en) * 1986-07-24 1991-02-12 Ares-Serono Research And Development Limited Partnership Polymer-coated optical structures and methods of making and using the same
US4843021A (en) * 1986-07-30 1989-06-27 Shino-Test Laboratory Inc. Immunological assay method
US5182135A (en) * 1986-08-12 1993-01-26 Bayer Aktiengesellschaft Process for improving the adherency of metallic coatings deposited without current on plastic surfaces
US4844613A (en) * 1986-11-03 1989-07-04 Stc Plc Optical surface plasmon sensor device
US4842783A (en) * 1987-09-03 1989-06-27 Cordis Corporation Method of producing fiber optic chemical sensors incorporating photocrosslinked polymer gels
US5124254A (en) * 1988-02-08 1992-06-23 University College Cardiff Consultants Limited Detection of diamines in biological fluids
US5035863A (en) * 1988-05-10 1991-07-30 Amersham International Plc Surface plasmon resonance sensors
US5023053A (en) * 1988-05-20 1991-06-11 Amersham International Plc Biological sensors
US5114676A (en) * 1988-08-04 1992-05-19 Avl Ag Optical sensor for determining at least one parameter in a liquid or gaseous sample
US5134057A (en) * 1988-10-10 1992-07-28 501 Ppg Biomedical Systems, Inc. Method of providing a substrate with a layer comprising a polyvinyl based hydrogel and a biochemically active material
US5492840A (en) * 1988-11-10 1996-02-20 Pharmacia Biosensor Ab Surface plasmon resonance sensor unit and its use in biosensor systems
US5436161A (en) * 1988-11-10 1995-07-25 Pharmacia Biosensor Ab Matrix coating for sensing surfaces capable of selective biomolecular interactions, to be used in biosensor systems
US5003178A (en) * 1988-11-14 1991-03-26 Electron Vision Corporation Large-area uniform electron source
US5314923A (en) * 1988-11-23 1994-05-24 Cytec Technology Corp. Porous polymer beads and process
US4940734A (en) * 1988-11-23 1990-07-10 American Cyanamid Process for the preparation of porous polymer beads
US4895017A (en) * 1989-01-23 1990-01-23 The Boeing Company Apparatus and method for early detection and identification of dilute chemical vapors
US5096671A (en) * 1989-03-15 1992-03-17 Cordis Corporation Fiber optic chemical sensors incorporating electrostatic coupling
US5120662A (en) * 1989-05-09 1992-06-09 Abbott Laboratories Multilayer solid phase immunoassay support and method of use
US5489678A (en) * 1989-06-07 1996-02-06 Affymax Technologies N.V. Photolabile nucleoside and peptide protecting groups
US5316727A (en) * 1989-09-08 1994-05-31 Terumo Kabushiki Kaisha Measuring apparatus
US5320944A (en) * 1989-09-29 1994-06-14 Fujirebio Inc. Immunoassay using magnetic particle
US5225935A (en) * 1989-10-30 1993-07-06 Sharp Kabushiki Kaisha Optical device having a microlens and a process for making microlenses
US5482867A (en) * 1989-11-13 1996-01-09 Affymax Technologies N.V. Spatially-addressable immobilization of anti-ligands on surfaces
US5508171A (en) * 1989-12-15 1996-04-16 Boehringer Mannheim Corporation Assay method with enzyme electrode system
US5514785A (en) * 1990-05-11 1996-05-07 Becton Dickinson And Company Solid supports for nucleic acid hybridization assays
US5387503A (en) * 1990-06-06 1995-02-07 Novo Nordisk A/S Assay method using internal calibration to measure the amount of analyte in a sample
US5200084A (en) * 1990-09-26 1993-04-06 Immunicon Corporation Apparatus and methods for magnetic separation
US5510481A (en) * 1990-11-26 1996-04-23 The Regents, University Of California Self-assembled molecular films incorporating a ligand
US5208535A (en) * 1990-12-28 1993-05-04 Research Development Corporation Of Japan Mr position detecting device
US5415842A (en) * 1991-02-07 1995-05-16 Fisons Plc Surface plasmon resonance analytical device
US5330898A (en) * 1991-02-20 1994-07-19 Diagnostic Markers, Inc. Method for the very rapid detection of polyamines
US5196350A (en) * 1991-05-29 1993-03-23 Omnigene, Inc. Ligand assay using interference modulation
US5496701A (en) * 1991-06-04 1996-03-05 Fisons Plc Optical biosensor method for determining an analyte
US5179288A (en) * 1991-09-30 1993-01-12 Ortho Pharmaceutical Corporation Apparatus and method for measuring a bodily constituent
US5418136A (en) * 1991-10-01 1995-05-23 Biostar, Inc. Devices for detection of an analyte based upon light interference
US5516635A (en) * 1991-10-15 1996-05-14 Ekins; Roger P. Binding assay employing labelled reagent
US5424219A (en) * 1991-10-25 1995-06-13 Cytech Biomedical, Inc. Method of performing assays for biomolecules and solid supports for use in such methods
US5221454A (en) * 1992-01-31 1993-06-22 Biometric Imaging Inc. Differential separation assay
US5518883A (en) * 1992-07-02 1996-05-21 Soini; Erkki J. Biospecific multiparameter assay method
US5395754A (en) * 1992-07-31 1995-03-07 Hybritech Incorporated Membrane-based immunoassay method
US5321492A (en) * 1992-08-07 1994-06-14 Miles Inc. Dual function readhead for a reflectance instrument
US5327225A (en) * 1993-01-28 1994-07-05 The Center For Innovative Technology Surface plasmon resonance sensor
US5514559A (en) * 1993-03-29 1996-05-07 Boehringer Mannheim Gmbh Immunologically active conjugates and method for their preparation
US5424841A (en) * 1993-05-28 1995-06-13 Molecular Dynamics Apparatus for measuring spatial distribution of fluorescence on a substrate
US5484867A (en) * 1993-08-12 1996-01-16 The University Of Dayton Process for preparation of polyhedral oligomeric silsesquioxanes and systhesis of polymers containing polyhedral oligomeric silsesqioxane group segments
US5512131A (en) * 1993-10-04 1996-04-30 President And Fellows Of Harvard College Formation of microstamped patterns on surfaces and derivative articles
US5504013A (en) * 1993-11-12 1996-04-02 Unipath Limited Analytical devices and methods of use thereof
US5504013B1 (en) * 1993-11-12 2000-03-14 Unipath Ltd Analytical devices and methods of use thereof
US5527711A (en) * 1993-12-13 1996-06-18 Hewlett Packard Company Method and reagents for binding chemical analytes to a substrate surface, and related analytical devices and diagnostic techniques
US5489988A (en) * 1995-01-03 1996-02-06 Motorola Environmental sensor and method therefor
US5534132A (en) * 1995-05-04 1996-07-09 Vreeke; Mark Electrode and method for the detection of an affinity reaction
US5518689A (en) * 1995-09-05 1996-05-21 Bayer Corporation Diffused light reflectance readhead
US5723294A (en) * 1996-03-05 1998-03-03 Gull Laboratories Methods for detection and discrimination of multiple analytes using fluorescent technology
US6387707B1 (en) * 1996-04-25 2002-05-14 Bioarray Solutions Array Cytometry
US5876944A (en) * 1996-06-10 1999-03-02 Bayer Corporation Method for amplification of the response signal in a sandwich immunoassay
US6396053B1 (en) * 1998-11-02 2002-05-28 Olympus Optical Co. Scanning optical microscope apparatus capable of detecting a plurality of flourescent light beams
US20020004246A1 (en) * 2000-02-07 2002-01-10 Daniels Robert H. Immunochromatographic methods for detecting an analyte in a sample which employ semiconductor nanocrystals as detectable labels
US6699722B2 (en) * 2000-04-14 2004-03-02 A-Fem Medical Corporation Positive detection lateral-flow apparatus and method for small and large analytes
US6720007B2 (en) * 2000-10-25 2004-04-13 Tufts University Polymeric microspheres
US6887851B2 (en) * 2001-09-18 2005-05-03 Bioexpertise, Llc IGF-binding protein-derived peptide

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7670786B2 (en) 2002-08-27 2010-03-02 Kimberly-Clark Worldwide, Inc. Membrane-based assay devices
US7662643B2 (en) 2002-12-19 2010-02-16 Kimberly-Clark Worldwide, Inc. Reduction of the hook effect in membrane-based assay devices
US8034397B2 (en) 2003-04-03 2011-10-11 Kimberly-Clark Worldwide, Inc. Methods of making assay devices utilizing hollow particles
US20110020541A1 (en) * 2003-04-03 2011-01-27 Kimberly-Clark Worldwide, Inc. Methods of Making Assay Devices Utilizing Hollow Particles
US20060275920A1 (en) * 2005-06-01 2006-12-07 Petrilla John F Apparatus and method for discriminating among lateral flow assay test indicators
US7829347B2 (en) 2005-08-31 2010-11-09 Kimberly-Clark Worldwide, Inc. Diagnostic test kits with improved detection accuracy
US7575887B2 (en) 2005-08-31 2009-08-18 Kimberly-Clark, Worldwide, Inc. Detection of proteases secreted from pathogenic microorganisms
US20070048182A1 (en) * 2005-08-31 2007-03-01 Kimberly-Clark Worldwide, Inc. Nitrite detection technique
US8003399B2 (en) * 2005-08-31 2011-08-23 Kimberly-Clark Worldwide, Inc. Nitrite detection technique
US8609401B2 (en) 2005-08-31 2013-12-17 Kimberly-Clark Worldwide, Inc. Detection of proteases secreted from a pathogenic microorganisms
US20090298197A1 (en) * 2005-11-15 2009-12-03 Oxonica Materials Inc. Sers-based methods for detection of bioagents
EP1977242A2 (en) * 2006-01-27 2008-10-08 Oxonica Inc. Lateral flow immunoassay with encapsulated detection modality
EP1977242A4 (en) * 2006-01-27 2009-03-25 Oxonica Inc Lateral flow immunoassay with encapsulated detection modality
US20090155811A1 (en) * 2006-01-27 2009-06-18 Oxonica, Inc. Lateral Flow Immunoassay With Encapsulated Detection Modality
US8758989B2 (en) 2006-04-06 2014-06-24 Kimberly-Clark Worldwide, Inc. Enzymatic detection techniques
US20100060893A1 (en) * 2006-07-24 2010-03-11 Norton Scott M Assay particle concentration and imaging apparatus and method
EP1908522A1 (en) 2006-10-03 2008-04-09 Meridian Bioscience, Inc. Immunoassay test device and method of use
US7897360B2 (en) 2006-12-15 2011-03-01 Kimberly-Clark Worldwide, Inc. Enzyme detection techniques
US9739773B1 (en) 2010-08-13 2017-08-22 David Gordon Bermudes Compositions and methods for determining successful immunization by one or more vaccines
JP2014521102A (en) * 2011-07-19 2014-08-25 ザ バイオ ナノ センター リミテッド Apparatus and method for lateral flow affinity assay
WO2013127144A1 (en) * 2012-03-01 2013-09-06 上海鑫谱生物科技有限公司 Fluorescence analysis method and device
US20150079608A1 (en) * 2012-04-06 2015-03-19 Adtec, Inc. Method for detecting or quantifying analyte, kit for detecting or quantifying analyte, and test strip for lateral flow type chromatography method for detecting or quantifying analyte
CN102680703A (en) * 2012-04-28 2012-09-19 广州鸿琪光学仪器科技有限公司 Immunofluorescence test strip component for quickly and quantitatively testing myoglobin, test card component using immunofluorescence test strip component, and preparation method for immunofluorescence test strip component
CN102692508A (en) * 2012-04-28 2012-09-26 广州鸿琪光学仪器科技有限公司 Immunofluorescence test strip component for quickly quantitatively testing troponin-T and test card component manufactured by same and production process of immunofluorescence test strip
CN102707056A (en) * 2012-04-28 2012-10-03 广州鸿琪光学仪器科技有限公司 Immunofluorescence test strip component for quickly and quantitatively detecting myocardial creatine kinase isozyme, detection card component comprising same and preparation method
CN102662065A (en) * 2012-04-28 2012-09-12 广州鸿琪光学仪器科技有限公司 Immunofluorescence dipstick component for quickly and quantitatively detecting protein of plurality of types and detection card component prepared from same and preparation method thereof
CN102662055A (en) * 2012-04-28 2012-09-12 广州鸿琪光学仪器科技有限公司 Immune fluorescent test strip component for quickly quantitatively detecting troponin I, detection card component comprising immune fluorescent test strip component and preparation methods for immune fluorescent test strip component and detection card component
CN102680702A (en) * 2012-04-28 2012-09-19 广州鸿琪光学仪器科技有限公司 Immune-fluorescence test strip component for rapidly detecting C-reactive protein quantitatively, detection card component produced by same and method for preparing same
CN102680704A (en) * 2012-04-28 2012-09-19 广州鸿琪光学仪器科技有限公司 immunofluorescence test strip module for rapidly and quantitatively testing microalbumin, test card module made of same and preparation method thereof
CN102866251A (en) * 2012-06-19 2013-01-09 深圳市艾瑞生物科技有限公司 Immunofluorescence test strip based on phosphorescent technology, and preparation method and application thereof
CN102866252A (en) * 2012-08-09 2013-01-09 河南省农业科学院 Immunochromatography test strip marked by phosphorescent silica nano particles and used for quantitatively detecting cimaterol and preparation method for immunochromatography test strip
JP2015535341A (en) * 2012-10-23 2015-12-10 ロベルト・ボッシュ・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツングRobert Bosch Gmbh Sensor integration and its application in a lateral flow immunoassay
CN104278079A (en) * 2013-07-08 2015-01-14 嘉兴朝云帆生物科技有限公司 Test strip and method for detecting nucleic acid through nucleic acid chromatographic technique
CN104345144A (en) * 2013-07-28 2015-02-11 嘉兴朝云帆生物科技有限公司 Test strip and method for detecting small-molecular organic compound by using immunochromatography
CN104345148A (en) * 2013-07-28 2015-02-11 嘉兴朝云帆生物科技有限公司 Test strip and method for detecting protein by using immunochromatography
WO2015026663A1 (en) * 2013-08-19 2015-02-26 University Of Houston Phosphorescent reporters
CN105929155A (en) * 2016-07-08 2016-09-07 同济大学 Immuno-chromatographic test paper and detection method thereof

Also Published As

Publication number Publication date Type
WO2005057215A1 (en) 2005-06-23 application
EP1692508B1 (en) 2010-12-15 grant
US8557604B2 (en) 2013-10-15 grant
US20140004506A1 (en) 2014-01-02 application
US8703504B2 (en) 2014-04-22 grant
EP1692508A1 (en) 2006-08-23 application
DE602004030615D1 (en) 2011-01-27 grant
US20080090253A1 (en) 2008-04-17 application

Similar Documents

Publication Publication Date Title
US4222744A (en) Assay for ligands
US5843680A (en) Differential separation assay methods and test kits
US4240751A (en) Method and apparatus for specific binding substances
Ge et al. 3D Origami-based multifunction-integrated immunodevice: low-cost and multiplexed sandwich chemiluminescence immunoassay on microfluidic paper-based analytical device
US5219763A (en) Agglutination method for the determination of multiple ligands
US4923819A (en) Time-resolved fluorescence immunoassay
US5618732A (en) Method of calibration with photoactivatable chemiluminescent matrices
Ullman et al. Luminescent oxygen channeling immunoassay: measurement of particle binding kinetics by chemiluminescence
US5942407A (en) Light-emitting immunoassay
US4421860A (en) Homogeneous fluoroimmunoassay involving autocorrelation processing of optically sensed signals
US4366241A (en) Concentrating zone method in heterogeneous immunoassays
US5631170A (en) Method for improving measurement precision in evanescent wave optical biosensor assays
US5968839A (en) Method and device producing a predetermined distribution of detectable change in assays
US4390343A (en) Multilayer analytical element having an impermeable radiation diffusing and blocking layer
US20110171754A1 (en) Analysis system
US20040151632A1 (en) Luminescence assays and assay readers
US5858648A (en) Assays using reference microparticles
US5236826A (en) Immunoassay for the detection or quantitation of an analyte
US5501949A (en) Particle bound binding component immunoassay
Hemmilä Fluoroimmunoassays and immunofluorometric assays.
US4407964A (en) Homogeneous fluoroimmunoassay involving sensing radiation for forward and back directions
EP0424634A2 (en) Method and apparatus for heterogeneous chemiluminescence assay
US4777128A (en) Fluorescence immunoassay involving energy transfer between two fluorophores
US20030119202A1 (en) Reading device, method, and system for conducting lateral flow assays
US20020137230A1 (en) Biosensor

Legal Events

Date Code Title Description
AS Assignment

Owner name: KIMBERLY-CLARK WORLDWIDE, INC., WISCONSIN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SONG, XUEDONG;REEL/FRAME:015231/0530

Effective date: 20040315