Carrier Is Water Suspendible Particles Patents (Class 436/534)
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Patent number: 6352863Abstract: An assay device and method are provided which allow the determination of the presence or absence of at least one analyte in a test sample, while providing specific identification of the test subject. The assay device includes a reaction medium having at least one reaction zone and at least one control zone, which is capable of providing a pattern suitable for identifying the test subject. The pattern suitable for identifying the test subject is preferably a fingerprint. In a preferred embodiment of the invention, the reaction zone and the control zone include at least one member of a ligand/receptor pair.Type: GrantFiled: January 27, 1997Date of Patent: March 5, 2002Assignee: La Mina, Inc.Inventor: Raouf A. Guirguis
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Patent number: 6350620Abstract: The invention provides a method for producing a micro-carrier, which includes patterning pluralities of bar code on a mask; exposing the bar code to a substrate coated with photoresist; etching and removing residual photoresist and electroforming to a nickel plate; placing a bead coated with biotin or poly-L-lysine between two-nickel plates, and compressing the bar code on the surface of the bead to form a microcake-like particle with bar code; and combining the particle with the corresponding bio-molecule thereof to produce a micro-carrier with a label. The invention also provides a test method for identifying a bio-molecule, which includes mixing several micro-carriers with the labeled unknown bio-molecules; and identifying the bar code on the micro-carrier via image recognition system, wherein the numbers and types of the known micro-carrier can be flexibly adjusted.Type: GrantFiled: December 1, 2000Date of Patent: February 26, 2002Assignee: Genemaster Lifescience Co., LTDInventors: Rong-Seng Chang, Yu-Chan Chao
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Patent number: 6348322Abstract: A method for detecting the binding of a test compound to a probe molecule comprises providing a test compound, the test compound having a first fluorophore bound thereto, and providing a screening substrate. The screening substrate comprises a solid support, a probe molecule bound to the solid support, and a second fluorophore bound to the solid support adjacent the probe molecule. An advantage of the invention is that this obviates the need for binding the second fluorophore directly to the probe molecule. Preferably, the second fluorophore is bound to the solid support by a flexible linker group. This enables the second fluorophore to interogate different positions on the probe molecule, which is also bound to the solid support adjacent the linker group, enhancing the ability of the method of the invention to detect positive binding events (specific binding of the test compound to the probe molecule.Type: GrantFiled: October 17, 1997Date of Patent: February 19, 2002Assignee: Duke UniversityInventor: Warren J. Strittmatter
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Patent number: 6344336Abstract: The present invention relates to an assay apparatus for detecting a product in a sample. The assay apparatus comprises a fluid pathway with an input of the sample and an input for a reagent with a detectable moiety which transports the sample to a detecting means via a barrier arranged to prevent a product-reagent complex passage but allow passage of unbound reagent and sample. The apparatus also includes supply means for supplying a substance adapted to breakdown the complex into a detectable moiety which can flow through the barrier to the detecting means.Type: GrantFiled: October 21, 1999Date of Patent: February 5, 2002Assignee: Kalibrant LimitedInventors: Derek Adeyemi Palmer, Martin Thomas French
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Patent number: 6342396Abstract: The present invention relates to a method for at least one of detecting, quantifying or isolating at least one analyte from a liquid medium in which the analyte is distributed and comprises providing a reagent comprised of particles having a receptor for an analyte fixed to the particles distributed in the medium and a capturing means having an exposed surface defining an active zone. An intermediate reagent is formed by the complex of the reagent with the analyte. A second receptor is fixed in the active zone to capture either the analyte bound by the reagent or the receptor (capture partners). The active zone serves as a site of isolation and concentration of the capture partners.Type: GrantFiled: September 17, 1999Date of Patent: January 29, 2002Assignee: Bio MerieuxInventors: Agnés Perrin, Alain Theretz, Bernard Mandrand
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Patent number: 6340599Abstract: Compositions are disclosed comprising (a) a metal chelate wherein the metal is selected from the group consisting of europium, terbium, dysprosium, samarium osmium and ruthenium in at least a hexacoordinated state and (b) a compound having a double bond substituted with two aryl groups, an oxygen atom and an atom selected from the group consisting of oxygen, sulfur and nitrogen wherein one of the aryl groups is electron donating with respect to the other. Such composition is preferably incorporated in a latex particulate material. Methods and kits are also disclosed for determining an analyte in a medium suspected of containing the analyte. The methods and kits employ as one component a composition as described above.Type: GrantFiled: May 11, 1998Date of Patent: January 22, 2002Assignee: Dade Behring Marburg GmbHInventors: Sharat Singh, Edwin F. Ullman
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Patent number: 6319670Abstract: The present invention relates to methods, reagents and compositions, for conducting electrochemiluminescence binding assays which improve one or more characteristics of the assay or the instruments used to conduct the assay. The method is achieved using microparticles that include electrically conductive material. The electrically conductive material has one or more copies of an assay ligand immobilized an its outer surface and a plurality of electrochemiluminescent moieties immobilized an its outer surface. The assay ligand may be linked to the electrochemiluminescent moiety.Type: GrantFiled: December 23, 1997Date of Patent: November 20, 2001Assignee: Meso Scale Technology LLPInventors: George B. Sigal, Jacob N. Wohlstadter, Satyanarayana Gudibande, Mark T. Martin, James L. Wilbur
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Patent number: 6303325Abstract: The invention relates to methods of determining the presence or amount of an analyte in a sample suspected of containing the analyte, said method comprising the steps of: (a) bringing together in an aqueous medium to form a mixture: (i) the sample; (ii) at least one specific binder for the analyte; (iii) a first binding agent coupled to either (1) exogenous analyte or (2) the specific binder for the analyte; (iv) a support comprising a second binding agent; b) adding an activator to the mixture, wherein the activator binds the first binding agent and the second binding agent of the support to immobilize the first binding agent; c)determining the amount of the analyte in the sample by detecting the immobilized first binding agent, the presence or amount thereof being related to the presence or amount of the analyte in the sample.Type: GrantFiled: May 29, 1998Date of Patent: October 16, 2001Assignee: Dade Behring Inc.Inventors: Harshvardhan B. Mehta, Nurith Kurn
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Patent number: 6294342Abstract: Assay methods utilizing the response of a magnetically responsive reagent to the influence of a magnetic field to qualitatively or quantitatively measure binding between specific binding pair members. According to the invention, the presence of an analyte mediates whether or not the magnetically responsive reagent binds to a mobile solid phase reagent. The extent of binding will modulate the response of the magnetically responsive reagent or that of the mobile solid phase reagent, or both, to the influence of a magnetic field. Hence, by measuring the response to the magnetic field of the magnetically responsive reagent, or that of the mobile solid phase reagent, the presence or amount of analyte contained in a test sample can accurately be determined. The invention utilizes various devices to carry out the assay methods described.Type: GrantFiled: September 29, 1999Date of Patent: September 25, 2001Assignee: Abbott LaboratoriesInventors: Thomas E. Rohr, Tuan A. Elstrom, Lawrence V. Howard, Eric B. Shain
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Publication number: 20010021534Abstract: Materials and methods are provided for producing patterned multi-array, multi-specific surfaces for use in diagnostics. The invention provides for electrochemiluminescence methods for detecting or measuring an analyte of interest. It also provides for novel electrodes for ECL assays. Materials and methods are provided for the chemical and/or physical control of conducting domains and reagent deposition for use multiply specific testing procedures.Type: ApplicationFiled: January 29, 2001Publication date: September 13, 2001Applicant: Meso Scale Technologies, LLCInventors: Jacob N. Wohlstadter, James Wilbur, George Sigal, Mark Martin, Liang-Hong Guo, Alan Fischer, Jon Leland, Mark A. Billadeau
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Patent number: 6284459Abstract: Combinations, called matrices with memories, of matrix materials that are encoded with an optically readable code are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The matrix materials may additionally include fluophors or other luminescent moieties to produce luminescing matrices with memories. The memories include electronic and optical storage media and also include optical memories, such as bar codes and other machine-readable codes. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.Type: GrantFiled: September 5, 1996Date of Patent: September 4, 2001Assignee: Discovery Partners InternationalInventors: Michael P. Nova, Andrew E. Senyei, Xiao-Yi Xiao, Chanfeng Zhao, Hanan Potash
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Patent number: 6281021Abstract: The invention concerns methods for the detection of an analyte in a sample by chemiluminescence or electrochemiluminescence using derivatized test reagents. In addition new reagents and reagent kits for chemiluminescence and electrochemiluminescence detection methods are disclosed.Type: GrantFiled: June 18, 1999Date of Patent: August 28, 2001Assignee: Roche Diagnostics GmbHInventors: Martin Egger, Hans-Peter Josel, Gabriele Punzmann
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Patent number: 6268123Abstract: The present invention relates to processes for the direct detection of biochemically functional retroviruses in biological samples. The processes of the invention are characterized by the structure-specific extraction of retrovirus particles and a subsequent analysis and detection of retrovirus-specific enzymatic reactions. The processes of the invention have broad application in the diagnosis of retroviral infection and virological research.Type: GrantFiled: February 28, 1996Date of Patent: July 31, 2001Assignee: Retro-Tech GmbHInventor: Ortwin Faff
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Patent number: 6265169Abstract: The present invention refers to a method that allows the use of filamentous bacteriophages to detect the presence of molecules of interest in biological samples. It consists of a series of combined operations, which are drawn up and defined according to the characteristics of the phages employed. These have, exposed on the surfaces of the capsid, at least one molecule, generally but not exclusively of proteic nature, capable of binding at least one molecule of interest present in the biological sample. Detection of the presence of the molecule takes place, according to the method of the invention, using the association between the molecule exposed on the surfaces of the phage and the genome of the phage itself. The ability to form specific complexes typical of the molecule exposed on the capsid enables formation of phage-molecule of interest complexes, which can be detected by means of amplification of known sequences in the phage DNA.Type: GrantFiled: February 17, 2000Date of Patent: July 24, 2001Assignee: Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A.Inventors: Riccardo Cortese, Paolo Monaci
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Patent number: 6261848Abstract: A hand held, self-contained, automatic, low power and rapid sensor platform for detecting and quantifying a plurality of analytes. A sample solution potentially containing an unknown amount of an analyte is passed through an affinity column which contains antibodies to which the analyte binds thereby extracting the analyte. The affinity column is then rinsed to remove any other chemicals that may fluoresce. The rinsed affinity column is then eluted with a known volume of elution fluid causing the analyte to release from the antibody and dissolve in the fluid (eluant). The eluant is then placed in the quartz cuvette of a fluorometer. The analyte suspended in the eluant fluoresces at a waveband which is different than that of the light source that excites it. The amount of fluorescence is measured and the level of analyte determined.Type: GrantFiled: May 8, 1998Date of Patent: July 17, 2001Assignee: The Johns Hopkins UniversityInventors: Charles W. Anderson, C. Brent Bargeron, Richard C. Benson, Micah A. Carlson, Allan B. Fraser, John D. Groopman, Harvey W. Ko, David R. Kohler, Terry E. Phillips, Paul T. Strickland
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Publication number: 20010007775Abstract: A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.Type: ApplicationFiled: January 24, 2001Publication date: July 12, 2001Inventors: Michael Seul, Chiu Wo Chau
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Publication number: 20010007774Abstract: Disclosed herein is an immunoassay comprising reacting an immobilized antibody obtained by holding an antibody, which recognizes a part of an objective antigen of determination, on insoluble carrier particles with an antigen in a test specimen, then reacting a free antibody, which recognizes an antigen site different from that recognized by the immobilized antibody, with the antigen; or reacting a free antibody, which recognizes a part of an objective antigen of determination, with an antigen in a test specimen, then reacting an immobilized antibody obtained by holding an antibody, which recognizes an antigen site different from that recognized by the free antibody, on insoluble carrier particles with the antigen, and optically determining the degree of a change in agglutination occurred by the reaction.Type: ApplicationFiled: July 11, 1997Publication date: July 12, 2001Inventors: KAZUNORI SAITOH, MITSUHISA MANABE
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Patent number: 6258607Abstract: An indirect agglutination immunoassay includes the steps of providing, in a container, an immunoassay system comprising a test sample containing a desired analyte, and a reagent composed of magnetic particles or magnetic-material containing particles containing iron therein, wherein the magnetic particles or magnetic-material containing particles have been sensitized to allow specific binding to the desired analyte, and have a particle size in the range of 1 to 5 &mgr;m, with the content of the iron being in the range of 8 to 20 wt. %, precipitating the magnetic particles or magnetic-material containing particles by the application of magnetic force, allowing the container to stand at an inclination, and detecting the presence or absence of an immune reaction from the absence or presence of slippage observed of the precipitated magnetic particles or magnetic-material containing particles on the bottom of the container.Type: GrantFiled: June 28, 1993Date of Patent: July 10, 2001Assignee: Fujirebio Inc.Inventors: Tomo Saito, Mikio Ikeda
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Patent number: 6254830Abstract: A magnetic focusing immunosensor for the detection of pathogens comprising a laser, an exciting fiber and a collecting fiber, a fiber optic magnetic probe in communication with the collecting and exciting fibers and means for detecting, collecting and measuring fluorescent signals in communication with the collecting fiber. The probe and the collecting and exciting fibers are configured to focus paramagnetic microspheres attached to antigen/antibody/optically labeled complexes in a predetermined pattern in the field of view of the collecting fiber while blocking background interference.Type: GrantFiled: November 5, 1999Date of Patent: July 3, 2001Assignee: The Board of Governors for Higher Education, State of Rhode Island and Providence PlantationsInventors: Philip Pivarnik, He Cao, Stephen V. Letcher, A. Garth Rand
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Patent number: 6251581Abstract: Methods are disclosed for determining an analyte in a medium suspected of containing the analyte. One method comprises treating a medium suspected of containing an analyte under conditions such that the analyte, if present, causes a photosensitizer and a chemiluminescent compound to come into close proximity. The photosensitizer generates singlet oxygen and activates the chemiluminescent compound when it is in close proximity. The activated chemiluminescent compound subsequently produces light. The amount of light produced is related to the amount of analyte in the medium. Preferably, at least one of the photosensitizer and chemiluminescent compound is associated with a surface which is usually a suspendible particle, and a specific binding pair member is bound thereto. Compositions and kits are also disclosed.Type: GrantFiled: May 22, 1991Date of Patent: June 26, 2001Assignee: Dade Behring Marburg GmbHInventors: Edwin F. Ullman, Hrair Kirakossian, John S. Pease, Yuri Daniloff, Daniel B. Wagner
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Patent number: 6251691Abstract: A method and apparatus for the manipulation of colloidal particles and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.Type: GrantFiled: October 26, 1998Date of Patent: June 26, 2001Assignee: Bioarray Solutions, LLCInventor: Michael Seul
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Patent number: 6238931Abstract: Particles and methods for the detection or visualization of analytes using fluorescence energy transfer. Particles comprising an energy donor as a first component and a fluorescent dye as a second component positioned in said particles at an energy exchanging distance from one another, wherein the two components have a Stokes shift of greater than or equal to 50 nm, said particle having bound on its surface, a protein, polypeptide, nucleic acid, nucleotide or protein containing ligand analogue are disclosed and claimed.Type: GrantFiled: July 12, 1994Date of Patent: May 29, 2001Assignee: Biosite Diagnostics, Inc.Inventors: Kenneth F. Buechler, Joseph Barry Noar, Lema Tadesse
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Patent number: 6235536Abstract: Formed constituents of a quiescent anticoagulated whole blood sample are optically or visually analyzed in a sample chamber which has a varying through plane thickness due to convergent opposing sample chamber walls. At least one of the convergent walls of the chamber is transparent so that the blood sample constituents can be observed. The chamber's varying thickness produces a first lesser thickness region in the chamber wherein a quiescent monolayer of red blood cells in the sample will reside after the sample is introduced into and fills the chamber. Larger formed constituents such as white blood cells in the sample are unable to enter the aforesaid lesser thickness region of the chamber. The red cells which reside in the greater thickness regions will agglomerate to form rouleaux and lacunea. The exact thickness of the chamber at any particular location in the chamber can be predetermined, or can be determined in situ as the sample is being analyzed.Type: GrantFiled: February 12, 1999Date of Patent: May 22, 2001Assignees: Wardlaw Partners, LPInventor: Stephen C. Wardlaw
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Patent number: 6228660Abstract: An analytical test device useful for example in pregnancy testing, comprises a hollow casing (500) constructed of moisture-impervious solid material, such as plastics materials, containing a dry porous carrier (510) which communicates indirectly with the exterior of the casing via a bibulous sample receiving member (506) which protrudes from the casing such that a liquid test sample can be applied to the receiving member and permeate therefrom to the porous carrier, the carrier containing in a first zone a labelled specific binding reagent is freely mobile within the porous carrier when in the moist state, and in a second zone spatially distinct from the first zone unlabelled specific binding reagent for the same analyte which unlabelled reagent is permanently immobilized on the carrier material and is therefore not mobile in the moist state, the two zones being arranged such that liquid sample applied to the porous carrier can permeate via the first zone into the second zone, and the device incorporating meaType: GrantFiled: June 7, 1995Date of Patent: May 8, 2001Assignee: Conopco Inc.Inventors: Keith May, Michael Evans Prior, Ian Richards
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Patent number: 6210975Abstract: The invention involves methods for determining analytes, and reagents for use in these methods. The methods and reagents use one or both of a polyvinyl/pyrolidone with a molecular weight of at least 360,000, and a polyethylene glycol with molecular weight of at least 40,000. The assays are carried out nephelometrically, or turbidometrically. The reagents include at least one antibody which binds the analyte. The hook effect is reduced or avoided in the practice of the invention.Type: GrantFiled: October 4, 1991Date of Patent: April 3, 2001Assignee: Roche Diagnostics GmbHInventors: Johann Karl, Fridl Lang
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Patent number: 6210906Abstract: The present invention provides monoclonal antibodies specific for kringle 5 of apo(a) and hybridomas secreting such antibodies. The invention also relates to assay methods for directly measuring concentrations of lipoprotein(a) [Lp(a)] in a plasma sample. In one embodiment, the method involves the specific capture of Lp(a) from a plasma sample with a monoclonal antibody developed against kringle 5 of apo(a), which is non-cross-reactive with plasminogen and kringle 4 of apo(a). The quantity of the Lp(a) present in the sample is then measured by detecting the amount of Lp(a)-anti-kringle 5 complex that has formed in the reaction. Alternatively, the Lp(a) may be captured non-specifically and then detected with the monoclonal antibody specific for kringle 5 of apo(a). The invention also provides competitive assays using the above-mentioned kringle 5 specific monoclonal antibodies.Type: GrantFiled: January 20, 1999Date of Patent: April 3, 2001Assignee: Abbott LaboratoriesInventors: Samar K. Kundu, Robert N. Ziemann
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Patent number: 6207369Abstract: Materials and methods are provided for producing patterned multi-array, multi-specific surfaces for use in diagnostics. The invention provides for electrochemiluminescence methods for detecting or measuring an analyte of interest. It also provides for novel electrodes for ECL assays. Materials and methods are provided for the chemical and/or physical control of conducting domains and reagent deposition for use multiply specific testing procedures.Type: GrantFiled: September 17, 1996Date of Patent: March 27, 2001Assignee: Meso Scale Technologies, LLCInventors: Jacob N. Wohlstadter, James Wilbur, George Sigal, Mark Martin, Liang-Hong Guo, Alan Fischer, Jon Leland, Mark A. Billadeau
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Patent number: 6204068Abstract: This invention is thus related to a biospecific multiparameter assay employing single molecule detection. In particular, this invention is related to a new method for determination of several different biomolecules simultaneously in the same reaction solution. The method uses a fluorescent label for labelling biospecific primary probes and a combination of other labels, bound to secondary probes. Complexes are formed comprising primary probes, analyte molecules and secondary probes in the biospecific reaction. These single molecule complexes are counted selectively while discriminating the signals from other fluorescent molecules using confocal fluorometry or two-photon excitation fluorometry including an auto- and cross-correlator for the signals obtained from said fluorescent labels.Type: GrantFiled: May 13, 1997Date of Patent: March 20, 2001Inventors: Erkki Soini, Pekka Hänninen
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Patent number: 6200820Abstract: Disclosed are an optical flow particle apparatus and method for conducting a particle light scatter-based immunoassay for simultaneously measuring the presence or amount of one or more analytes in a fluid sample which involves the use of a reagent set for each analyte including first binding molecule-coated monodisperse microspheres and second binding molecule-coated colloidal particles in which at least one of the first or second binding molecules specifically binds a respective one of the analytes. In the case where more than one analytes are detected, each monodisperse microperse microsphere of a particular reagent set has a light scatter signal resolvable from that of microspheres of any other reagent set. Changes determined in the distributions of the measured light scatter signals for individual microspheres of each of the particular reagent sets are indicative of the presence or amount of the respective analyte(s) in the sample.Type: GrantFiled: June 7, 1995Date of Patent: March 13, 2001Assignee: Sienna Biotech, Inc.Inventors: W. Peter Hansen, Michael Cennerazzo, Carl Theodore Edens, Manish Kochar
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Patent number: 6194222Abstract: The invention relates in part to the use of independent assay controls (IACs) for the optical communication between an assay device and an instrument in monitoring and performing assays, preferably immunoassays.Type: GrantFiled: January 5, 1998Date of Patent: February 27, 2001Assignee: Biosite Diagnostics, Inc.Inventors: Kenneth F. Buechler, Joseph M Anderberg, Paul H. McPherson
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Patent number: 6187598Abstract: An analytical test device useful for example in pregnancy testing, comprises a hollow casing (500) constructed of moisture-impervious solid material, such as plastics materials, containing a dry porous carrier (510) which communicates indirectly with the exterior of the casing via a bibulous sample receiving member (506) which protrudes from the casing such that a liquid test sample can be applied to the receiving member and permeate therefrom to the porous carrier, the carrier containing in a first zone a labelled specific binding reagent is freely mobile within the porous carrier when in the moist state, and in a second zone spatially distinct from the first zone unlabelled specific binding reagent for the same analyte which unlabelled reagent is permanently immobilised on the carrier material and is therefore not mobile in the moist state, the two zones being arranged such that liquid sample applied to the porous carrier can permeate via the first zone into the second zone, and the device incorporating meaType: GrantFiled: June 7, 1995Date of Patent: February 13, 2001Assignee: Conopco Inc.Inventors: Keith May, Michael Evans Prior, Ian Richards
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Patent number: 6187268Abstract: Disclosed is a diagnostic device for the colorimetric detection of an analyte in a test fluid. The device is a dry reagent layer which is overcoated with a transparent, fluid permeable membrane. The membrane is made up of a combination of a water dispersible and a water soluble polymer. The membrane may contain a surfactant and a thickener.Type: GrantFiled: September 27, 1999Date of Patent: February 13, 2001Assignee: Bayer CorporationInventors: James P. Albarella, Karl-Heinz Hildenbrand, Spencer H. Lin, Michael J. Pugia, LLoyd S. Schulman
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Patent number: 6184043Abstract: The invention relates to a method for detecting specific target-cells in a simple and time saving way, using paramagnetic particles, antibodies recognizing the Fc portions of target-cell associating antibodies and target-cell associating antibodies directed to specific antigen determinants in the target-cell membranes. Incubation of the cell suspension with a mild detergent and/or second set of antibodies or antibody fragments, prelabeled or not with fluorescent agents, metallocolloids, radioisotopes, biotincomplexes or certain enzymes allowing visualization, with dramatically increase the specificity of the method. The method can further be used for isolation of the target-cells by magnetic field application and kit for performing the method according to the invention is described.Type: GrantFiled: June 24, 1997Date of Patent: February 6, 2001Inventors: Øystein Fodstad, Gunnar Kvalheim
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Patent number: 6180354Abstract: Compositions are disclosed comprising (a) a metal chelate wherein the metal is selected from the group consisting of europium, terbium, dysprosium, samarium osmium and ruthenium in at least a hexacoordinated state and (b) a compound having a double bond substituted with two aryl groups, an oxygen atom and an atom selected from the group consisting of oxygen, sulfur and nitrogen wherein one of the aryl groups is electron donating with respect to the other. Such composition is preferably incorporated in a latex particulate material. Methods and kits are also disclosed for determining an analyte in a medium suspected of containing the analyte. The methods and kits employ as one component a composition as described above.Type: GrantFiled: June 6, 1995Date of Patent: January 30, 2001Assignee: Dade Behring Marburg GmbHInventors: Sharat Singh, Edwin F. Ullman
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Patent number: 6177241Abstract: This invention provides a method, a reagent, and a kit for detecting herpesvirus-specific IgM antibodies indicative of recent infection while preventing detection of low levels of herpesvirus-specific IgM antibodies present in individuals of low risk. The invention also provides a reagent for use in detecting herpesvirus-specific IgM antibodies indicative of recent infection while preventing detection of low levels of herpesvirus-specific IgM antibodies present in individuals of low risk.Type: GrantFiled: September 22, 1997Date of Patent: January 23, 2001Assignee: Abbott LaboratoriesInventor: Gregory T. Maine
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Patent number: 6174734Abstract: The invention features a novel method of assaying glycated hemoglobin (GHb) in a sample using a capture molecule that binds GHb and hemoglobin (Hb), and detecting bound GHb with a molecule that distinguishes GHb from non-glycated hemoglobin (Hb). The molecule used to distinguish GHb from Hb may be an antibody. The assay and antibodies of the invention are useful for the evaluation of GHb in disease states such as diabetes.Type: GrantFiled: October 24, 1997Date of Patent: January 16, 2001Assignee: Abbott LaboratoriesInventors: Ralph K. Ito, Gordon Sanghera
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Patent number: 6159748Abstract: Immunoassay methods and apparatus are provided which utilize flow cytometry, coated latex microspheres, and labelled antibodies, to simultaneously detect the presence and amount of several antigens or antibodies in a sample. Microspheres can be sized by forward angle light scatter (FALS) or electronic volume. By combining FALS and fluorescence, it is practical to use beads of several different sizes, colors or shapes, each bead coated with a different protein or antibody, for the simultaneous detection of multiple analytes in a sample. Available auto-sampling systems make it even more appealing in this regard. In accordance with one embodiment, highly purified RNP. Sm, SS-A, SS-B and Scl-70 antigens are bound to 4, 5, 6, 7 and 10 .mu.m latex beads, respectively and stabilized for extended shelflife. Diluted patient serum is placed into test tubes containing a mixture of the five antigen coated beads and incubated. If an antibody is present for a specific antigen, it will bind to that specific bead.Type: GrantFiled: June 1, 1998Date of Patent: December 12, 2000Assignee: AffiniTech, LTDInventor: Mark K. Hechinger
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Patent number: 6159749Abstract: An apparatus and method for chemical and biological analysis, the apparatus having an optical trapping means to manipulate the reaction substrate, and a measurement means. The optical trapping means is essentially a laser source capable of emitting a beam of suitable wavelength (e.g., Nd:YAG laser). The beam impinges upon a dielectric microparticle (e.g., a 5 micron polystyrene bead which serves as a reaction substrate), and the bead is thus confined at the focus of the laser beam by a radial component of the gradient force. Once "trapped," the bead can be moved, either by moving the beam focus, or by moving the reaction chamber. In this manner, the bead can be transferred among separate reaction wells connected by microchannels to permit reactions with the reagent affixed to the bead, and the reagents contained in the individual wells.Type: GrantFiled: July 21, 1998Date of Patent: December 12, 2000Assignee: Beckman Coulter, Inc.Inventor: Yagang Liu
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Patent number: 6156524Abstract: Reagents and methods for the detection of Staphylococcus aureus are provided. The reagents contain an antibody that binds to a capsular polysaccharide of type 5 of Staphylococcus aureus, and can be used in methods for detection of oxacillin resistant Staphylococcus aureus that escapes detection by agglutination in the presence of fibrinogen and antibodies directed against protein A of Staphylococcus.Type: GrantFiled: May 30, 1995Date of Patent: December 5, 2000Assignee: Institut PasteurInventors: Jean-Michel Fournier, Alain Boutonnier
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Patent number: 6153442Abstract: The present invention relates to compounds that are bis-biotins. These compounds comprise two biotinyl radicals connected by a chain of atoms, usually at least 16 atoms in length. The bis-biotin is conjugated to a member of a specific binding pair ("sbp member") wherein the chain is not part of the sbp member. Also disclosed are compositions comprising a complex of avidin and a bis-biotin as described above. The compounds and compositions of the invention find use in an assay for an analyte wherein there is employed a reagent system comprising an avidin reagent and a biotin reagent. The improvement of the present invention comprises using as the biotin reagent a bis-biotin as described above. Also disclosed are kits comprising the present bis-biotins and methods of preparing a bis-biotinylated conjugate of a member of a specific binding pair ("sbp member") for use in a specific binding assay.Type: GrantFiled: May 20, 1998Date of Patent: November 28, 2000Assignee: Dade Behring Inc.Inventors: Marcel Rene Pirio, Dariush Davalian, Jacqueline Sadakan Ishkanian, Edwin F. Ullman
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Patent number: 6150182Abstract: A method for combining magnetic and centrifugal extraction techniques in a manner that improves wash efficiency and reduces the relative disadvantages of stand alone magnetic or centrifugal systems is provided. Centrifugation occurs about the rotational axis of a generally circular container with generally vertical sides featuring an inward protruding physical feature designed to retain material that exceeds the density of supernatent liquid and that is bound to magnetic particles during the centrifugation. During centrifugation, an external magnetic field is applied about the rotational axis of the container such that magnetic lines of force penetrate the container in any desired location. The magnetic and centrifugal forces may be independently modulated or modulated in relative unison to suit the hydrodynamic characteristics of a given complex.Type: GrantFiled: November 30, 1998Date of Patent: November 21, 2000Inventor: Michael M. Cassaday
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Patent number: 6150123Abstract: The present invention relates to a method for biotinylating a desired subset of a larger population of proteins, wherein the subset of proteins is first selectively bound to a solid phase, thereby separating it from undesired proteins of the population, and then, still bound to solid phase, it is biotinylated. Unreacted biotin may then be washed from the solid phase, and the biotinylated protein may be uncoupled from the solid phase.Type: GrantFiled: September 3, 1998Date of Patent: November 21, 2000Assignee: Centre Integre de Recherches Biocliniques sur le Sida (CIRBS)Inventor: Antonio Cosma
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Patent number: 6143577Abstract: A process for magnetic immunoseparation of cells, in particular bacteria, fetal cells, stock cells of bone marrow and circulating cancerous cells, of the type consisting in affixing the target cells on paramagnetic balls and in causing a magnetic field to act on a sample containing the affixed cells, the free cells and the surplus paramagnetic balls, in order to isolate the paramagnetic balls, in that the sample is caused to circulate in a tube the section of which is much less than the length over which the magnetic field is applied.Type: GrantFiled: May 15, 1998Date of Patent: November 7, 2000Assignee: Biocom S.A.Inventor: Jean-Claude Bisconte Sconte De Saint Julien
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Patent number: 6133048Abstract: A reagent useful in immunoassays, comprising a direct particulate level co-sensitized with a specific binding agent having specificity for an analyte or analyte analog and with a non-specific protein which can participate in a control reaction with another specific binding agent which does not bind to the first specific binding agent nor participate in the formation of a complex by means of which detection of the analyte or analyte analog is accomplished. Preferably the first specific binding agent is an antibody raised in a first species and the non-specific protein is an immunoglobulin from another species. Optionally, the reagent additionally comprises a second population of the direct particulate label sensitized solely with the non-specific protein.Type: GrantFiled: September 23, 1997Date of Patent: October 17, 2000Assignee: Unilever Patent Holdings BVInventors: Yvonne E. Penfold, David A. Percival
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Patent number: 6121008Abstract: A method and device are provided for the semi-quantitative and quantitative determination of an analyte in a sample. A non-competitive trap which can bind unreacted labelled receptor to analyte but has virtually no binding capabilities to receptor in the presence of analyte is used. Labelled receptor:analyte complex is trapped in a second trap. The relative amounts of unbound receptor in the non-competitive trap versus the amount of receptor:analyte complex in the second trap is a measure of the amount of analyte in the sample.Type: GrantFiled: March 20, 1997Date of Patent: September 19, 2000Assignee: Serex, Inc.Inventors: Judith Fitzpatrick, Regina B. Lenda
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Patent number: 6114179Abstract: A suspension of inert particles is prepared in an aqueous solution, to which an antibody or an antigen and a carrier-bound antigen or antibody, respectively, are added in any desired order. After centrifuging, the positive, weakly positive, or negative reaction can easily be recognized on the basis of a simple pattern.Type: GrantFiled: June 12, 1998Date of Patent: September 5, 2000Assignee: Stiftung fur Diagnostische ForschungInventors: Yves Lapierre, Dieter Josef, Jean Adam, Susanne Greber-Widmer
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Patent number: 6103538Abstract: Disclosed herein is a method for the detection of a target substance by a colloidal gold immunoassay, which comprises dissolving in an immunoreaction system a metal salt selected from the group consisting of sodium, potassium and lithium fluorides, sodium, potassium, lithium and magnesium iodides, sodium, potassium, lithium and magnesium bromides, lithium and magnesium chlorides, sodium, potassium, lithium and magnesium nitrates, sodium, potassium, lithium and magnesium sulfates, sodium, potassium, lithium and magnesium formates, sodium, potassium, lithium and magnesium acetates, and mixtures of at least two of these metal salts, whereby the metal salt is allowed to exist in a reaction mixture.Type: GrantFiled: December 22, 1997Date of Patent: August 15, 2000Assignee: SS Pharmaceutical Co., Ltd.Inventor: Takeshi Kotsugai
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Patent number: 6103478Abstract: The invention provides a method of assessment of carbohydrate-deficient transferrin in a transferrin containing body fluid, said method comprising the steps of:i) obtaining a transferrin containing liquid sample of or derived from a said fluid;ii) contacting said sample with a source of iron ions;iii) subsequently contacting said sample with an anionic ion exchange resin at a pH such as to cause carbohydrate-deficient transferrin to be retained by said resin;iv) subsequently contacting said resin with an eluant serving to release carbohydrate-deficient transferrin into the eluate from said resin;v) collecting a volume of said eluate substantially free from tetra- and penta-sialo transferrin; andvi) assessing the transferrin variant content in said volume of eluate.By including at least a proportion of the trisialotransferrin in the eluate, it is possible to use relatively simple assessment techniques such as turbidimetry in the assay.Type: GrantFiled: February 19, 1998Date of Patent: August 15, 2000Assignee: Axis-Shield ASAInventor: Erling Sundrehagen
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Patent number: 6093546Abstract: The invention relates to a process for making a test element, such as an analytical test element. Compositions of matter, such as analyte specific receptors, are treated to carry a charge. These are then applied to test carriers treated to carry a charge opposite that of the composition of matter. Interaction of charge fixes the composition of matter to the test element.Type: GrantFiled: September 3, 1992Date of Patent: July 25, 2000Assignee: Roche DiagnosticsInventors: David J. Ledden, David R. Moorman, Michael J. Kinch, Harvey B. Buck
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Patent number: 6086821Abstract: An ultrasonic energy source is used to provide a variable force for measuring the binding forces between molecular entities and for sensing the presence of an analyte in a test sample. The device includes a surface that has a first binding member attached thereto and one or more particles that have a second binding member attached thereto. A reaction vessel is provided for exposing the surface to the particles whereby, if the first binding member has a binding affinity for the second binding member, a complex is formed between individual first binding members and individual second binding members and the particles thereby become immobilized with respect to the surface. The ultrasonic energy source is positioned for applying a variable ultrasonic force onto the surface, and the position of the particles is monitored as the intensity of the ultrasonic force is varied.Type: GrantFiled: March 29, 1999Date of Patent: July 11, 2000Assignee: The United States of America as represented by the Secretary of the NavyInventor: Gil U Lee