Antigen Or Antibody Entrapped Within The Carrier (e.g., Gel, Hollow Fiber, Etc.) Patents (Class 436/535)
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Patent number: 5094962Abstract: A water-insoluble microporous article comprises a microporous substrate having first and second outer surfaces. Affixed to at least one of those surfaces is a stabilized specific binding reagent admixed with certain hydrophilic, neutral or positively-charged binder materials. Particularly useful binder materials include certain quaternary polymers, vinylpyrrolidone polymers and acrylamide polymers. In this mixture, the reagent exhibits improved keeping stability compared to similar reagents used without binder materials. The reagent comprises water-insoluble particles to which are attached receptor molecules to a target ligand. Substantially none of the reagent is entrapped within the microporous substrate. This article is useful for the detection of a target ligand in an assay involving the specific binding reaction of the ligand with corresponding receptor molecules, and can be included in a diagnostic test kit.Type: GrantFiled: June 13, 1988Date of Patent: March 10, 1992Assignee: Eastman Kodak CompanyInventors: Brian A. Snyder, Elizabeth A. Grogan, Richard C. Sutton
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Patent number: 5084398Abstract: Disclosed is a method and a family of materials useful for removing immune complexes from blood preferentially to soluble antibodies. The material comprises analogs of proteins which bind to the Fc region of immunoglobulin. The analogs are produced by truncating or otherwise altering the amino acid sequence of the binding protein to reduce their affinity for Fc. An array of such analogs disposed about the surface of an insoluble matrix has the ability to form multiple points of attachment to the multiple Fc's in a complex so as to bind complex strongly, whereas only weak associations are developed between the Fc region of soluble IgG and inidivdual analogs. The preferred analogs are truncated proteins homologous to a portion of the domains of Protein A or Protein G which bind with Fc. Complex may be removed from whole blood or serum using the material and conventional plasmapheresis techniques.Type: GrantFiled: October 23, 1990Date of Patent: January 28, 1992Assignee: Creative BioMoleculesInventors: James S. Huston, Lynn Baird, Charles Cohen, Hermann Oppermann
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Patent number: 5073344Abstract: In a diagnostic apparatus system, a one piece porous substrate is located in a container. The substrate serves both to extract an antigen in or on a top layer with the remainder of the substrate serving as a reservoir. The pores in the top surface of the substrate are microscopic for entrapment of microspheres carrying antibodies. A target antigen in a test sample attaches to the antibodies when the test sample is poured through the top layer. The pores in all but the top layer of the substrate have a much greater pore size to define the reservoir portion of the substrate. The invention also includes a method of casting a microporous matrix in surfaces of a plurality of macroporous slugs.Type: GrantFiled: July 21, 1988Date of Patent: December 17, 1991Assignee: Porex Technologies Corp.Inventors: Michael W. Smith, Robert S. Pierce
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Patent number: 5071746Abstract: The present invention provides a test carrier for the analytical determination of a component of a sample liquid with the help of immunological reagents having a conjugate layer (2, 12), which contains a soluble conjugate of a first immunological binding partner with a labelling, a porous fixing layer (3, 13), which contains a second binding partner in carrier-fixed form binding specifically with the first binding partner, and an optical detection layer (8, 18), wherein the fixing layer (3, 13) is constructed in such a manner that the suction speed with which the liquid is transported in it is so high that the time needed for the spreading out of the liquid in the fixing layer is considerably shorter than the incubation time which is needed for the completion of the specific binding reaction between the first binding partner and the second binding partner and the optical detection layer (8, 18) is so fixed on the test carrier (1, 11) that, in a first position, it is not in contact with the fixing layer (3, 13Type: GrantFiled: April 13, 1989Date of Patent: December 10, 1991Assignee: Boehringer Mannheim GmbHInventors: Hans-Erich Wilk, Karin Munter, Rolf Lerch
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Patent number: 5068198Abstract: Assay methods and compositions are provided for determining an analyte in a sample suspected of containing the analyte. The composition comprises in a novel single liquid reagent at least one specific binding pair (sbp) member and its complementary member wherein at least one sbp member is reversibly confined in a material that temporarily renders the confined sbp member incapable of binding with its complementary sbp member. At least one of the sbp members is bound to a member of a signal producing system capable of producing a detectable signal in relation to the amount of analyte in the sample. The confinement is reversed, any remaining members of the signal producing system are added, and the signal produced in relation to the amount of analyte is measured. Examples of the confining material are lipid bilayers, cells and gels.Type: GrantFiled: January 13, 1989Date of Patent: November 26, 1991Assignee: Syntex (U.S.A.) Inc.Inventors: Ian Gibbons, Edwin F. Ullman, Philip L. Felgner
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Patent number: 5066372Abstract: A unitary multiple electrode sensor for detecting analytes in test samples and devices for using them. The unitary multiple electrode sensor includes a sensor support member and at least one electrode array being deposited on the sensor support member, the electrode array having sensor-activating chemical(s) attached to an embodient thereof. A test sample is applied to the electrode array to begin the test; and a sensor apparatus measures the test reaction which is occurring on the electrode array.Type: GrantFiled: June 21, 1990Date of Patent: November 19, 1991Assignee: Ciba Corning Diagnostics Corp.Inventor: Howard H. Weetall
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Patent number: 5063151Abstract: A method of binding an antibody with protein A cells is provided which includes a sequence of incubation and dilution steps to produce a preselected amount and concentration of antibody with a preselected distribution of antibody among the protein A cells. In addition, a method is provided for preparing an antibody entrapped porous matrix and apparatus which includes a specific porous matrix with a preselected position of antibody bound bacterium cells therein along with means for drawing fluids through the porous medium and means for facilitating the deposition of fluids onto the surface of the porous matrix. The apparatus and method is useful for testing for the level of progesterone in animal body fluids, such as milk, plasma, serum, whole blood and saliva.Type: GrantFiled: September 20, 1985Date of Patent: November 5, 1991Assignee: Biometallics, Inc.Inventors: Christa G. Kuehn, Debra J. Rossi, Stephan S. Isied
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Patent number: 5055415Abstract: A method for immunoassay for an antigen involves the following steps: reacting a sample possibly containing an antigen to be determined, a definite amount of a conjugate of the antigen and a charged substance and a definite amount of labeled antibody specific for antigen; allowing the reaction products to electrophoretically migrate towards a carrier bearing an attached antibody specific for the charged substance, so that when the reaction products contact the carrier any reaction product of labeled antibody and antigen passes through the carrier and any reaction product of the labeled antibody and conjugate binds to the carrier attached antibody specific for the charged substance; determining the amount of labeled antibody thereby bound to the carrier and relating the determined amount of labeled antibody to the amount of antigen in the sample.Type: GrantFiled: April 1, 1988Date of Patent: October 8, 1991Assignee: Hitachi, Ltd.Inventors: Kyoko Imai, Yasushi Nomura
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Patent number: 5055395Abstract: An agglutination method for the detection of antibodies against streptococcal deoxyribonuclease B is described, in which carrier-bound antibodies against streptococcal DNase B are mixed with a solution of streptococcal DNase which contains a protease inhibitor, and the sample in which the antibodies are to be detected, as well as an agent suitable for this method.Type: GrantFiled: October 30, 1987Date of Patent: October 8, 1991Assignee: Behringwerke AktiengesellschaftInventor: Tibor Toth
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Patent number: 5055390Abstract: A process for the chemical manipulation of liquid and gel microdroplets is disclosed. The process involves providing first microdroplets having aqueous interiors, such that the first microdroplets are surrounded by a non-aqueous fluid. The aqueous interior chemical composition of the first microdroplets is then manipulated by exposure to compounds soluble in both the non-aqueous and aqueous phases, or by exposure to emulsions or suspensions of second microdroplets such that contact between the first and second microdroplets is made. This allows chemical manipulation to be accomplished without removing the first microdroplets from a non-aqueous fluid environment.Type: GrantFiled: April 22, 1988Date of Patent: October 8, 1991Assignee: Massachusetts Institute of TechnologyInventors: James C. Weaver, Gregory B. Williams, Jonathan G. Bliss
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Patent number: 5047318Abstract: A dye-providing composition is useful in various diagnostic assays wherein a peroxidase-labeled specific binding species is used. This composition is substantially free of peroxidase and such labeled species, and comprises an imidazole leuco dye and 4'-hydroxyacetanilide present in an amount up to about 2.5 mmolar. This composition can be included as part of a diagnostic test kit.Type: GrantFiled: June 13, 1988Date of Patent: September 10, 1991Assignee: Eastman Kodak CompanyInventors: Brian A. Snyder, Harold C. Warren, III, Gregory J. McClune
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Patent number: 5045480Abstract: An immobilized hapten reagent for use in a specific binding assay for the determination of a hapten or binding analog thereof in a liquid test sample and methods for preparing and using the immobilized hapten reagent. The immobilized hapten reagent comprises a hapten moiety covalenty linked substantially only to the external surface of a gel particle. The immobilized hapten reagent is prepared by forming a reaction mixture comprising the hapten moiety and the carrier material in a nonswelling solvent wherein the gel particle is substantially impervious to the hapten moiety and wherein an analytically insignificant amount of the hapten moiety is nonspecifically bound to the gel particle. The immobilized hapten reagent is characterized by being substantially stable in aqueous solutions and exhibits an insignificant amount of leakage of the hapten moiety into a liquid test medium.Type: GrantFiled: February 9, 1989Date of Patent: September 3, 1991Assignee: Miles Inc.Inventors: Richard D. Johnson, H.-Volker Runzheimer, Ronald G. Sommer, Kin F. Yip
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Patent number: 5041266Abstract: A microtiter plate containing a plurality of reaction wells for conducting immunogenic reactions wherein the bottom wall of the reaction well has an inner surface which is substantially hydrophilic, and the side wall of the reaction well has an inner surface which is substantially hydrophobic and a process for producing said trays.Type: GrantFiled: December 21, 1989Date of Patent: August 20, 1991Assignee: Hoffmann-La Roche Inc.Inventor: William A. Fox
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Patent number: 5030555Abstract: For the serodiagnosis of a fluid sample, it is particularly advantageous to use a device comprising (A) a supported, porous membrane wherein a first immunoreagent is bound so as to be capable of binding a foreign analyte and forming a complex when the foreign analyte is brought into contact therewith; and (B) a matrix which presents a first surface and an opposing second surface and which contains a second, labeled immunoreagent that is capable of binding the foreign analyte to form a labeled complex when the foreign analyte is sandwiched between the first immunoreagent and the second immunoreagent. In such a device, the first surface of the matrix is adjacent to a surface of the membrane, (ii) the matrix is wettable by or soluble in an aqueous fluid, and (iii) the second immunoreagent is mobilized when the matrix is wetted.Type: GrantFiled: September 12, 1988Date of Patent: July 9, 1991Assignee: University of FloridaInventor: Roger M. Clemmons
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Patent number: 5013669Abstract: A solid phase binding member for the detection of an analyte in a test sample is described. The binding member comprises: (1) a solid support having micropores; (2) a polymer reversibly water-soluble before its application to the solid support; and (3) a ligand covalently attached to the polymer, the ligand interacting specifically with the analyte. The solid support can have micropores throughout or on its surface, and can be rayon, paper, fabric, plastic, agarose or polyacrylamide beads, glass, microcrystalline cellulose, or acid-treated plastic. The polymer can be carrageenan or sodium alginate. The ligand can be an antibody, a univalent antigen-binding fragment of an antibody, an antigen, a hapten, an enzyme, a hormone, or a single-stranded nucleic acid. Methods of use of the binding member are also described involving incorporation into a test device. The test device can be a dip stick, a hollow vessel, a slide, or a porous bead.Type: GrantFiled: June 1, 1988Date of Patent: May 7, 1991Assignee: SmithKline Diagnostics, Inc.Inventors: Donald F. Peters, Jr., Lawrence C. Dumont
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Patent number: 5011771Abstract: The invention relates to an immunometric assay for a multivalent antigen in a sample which comprises forming a complex of the antigen together with multiple immobilized monoclonal antibodies against different epitopes of the antigen and with a detectably labeled soluble monoclonal antibody which is identical to one of the multiple immobilized antibodies. The labeled antibody associated with the complex is separated from the remaining soluble antibody and the detectably labeled antibody associated with the complex or unassociated with the complex is detected. Any one of the multiple immobilized monoclonal antibodies shows, by itself, substantially less binding towards the antigen in the immunometric assay, when used with itself or another monocolonal antibody in soluble labeled form, than when used with the multiple immobilized antibodies in combination.Type: GrantFiled: September 24, 1987Date of Patent: April 30, 1991Assignee: The General Hospital CorporationInventors: Dominique Bellet, Jack R. Wands
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Patent number: 5008080Abstract: A novel material and device useful in solid-phase binding assays to determine the presence or amount of an analyte in a test sample, particularly antigens, antibodies, or other ligands or DNA segments. The material and device comprises a reaction site having procedural controls and an analyte binding area capable of being simultaneously contacted by the sample and reagent used in the performance of the assay. The procedural controls and analyte binding areas operate to provide readable results as to the presence or absence of analyte and simultaneously verify the assay procedure and therefore the assay result.Type: GrantFiled: February 6, 1990Date of Patent: April 16, 1991Assignee: Abbott LaboratoriesInventors: William E. Brown, III, Sarah E. Safford, John M. Clemens
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Patent number: 4981961Abstract: A novel class of compounds, methods for the preparation thereof and the use thereof in chromatographic methods for binding various biologically active materials non-covalently are disclosed. The class of compounds comprises the reaction product of a polymeric gel with a pyridine base, such as 4-dimethylaminopyridine (DMAP), and a halogen-substituted pyridine, such as 3,5-dichloro-2,4,6-trifluoropyridine (DCTFP), which reaction product may in turn be optionally reacted with hydroxyl ions or specified low-molecular-weight compounds. These compounds are capable of selectively and efficiently binding proteins and other organic materials of interest non-covalently to a degree comparable or superior to the heretofore preferred natural affinity ligands, such as Protein A gels. The novel compounds find particular utility in purification and recovery of proteins such as serum albumin and immunoglobulins of various classes from crude sources, such as diluted serum samples from various species.Type: GrantFiled: September 8, 1989Date of Patent: January 1, 1991Assignee: BioProbe International, Inc.Inventor: That T. Ngo
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Patent number: 4973394Abstract: The present invention provides a stabilized potassium ion-selective membrane comprising lysine-substituted valinomycin covalently bound to a polymeric substrate. The membrane of the invention exhibits improved stability and is used either on ISEs or on solid-state coated wire or semiconductor devices.Type: GrantFiled: September 2, 1988Date of Patent: November 27, 1990Assignee: SRI InternationalInventors: Pepi Ross, Allan J. Johnston, Amrit K. Judd
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Patent number: 4963245Abstract: A unitary multiple electrode sensor for detecting analytes in blood or blood component samples and devices for using them. The unitary multiple electrode sensor includes a sensor support member and at least one electrode array being deposited on the sensor support member, the electrode array having sensor-activating chemical(s) attached to an embodiment thereof. A test sample is applied to the electrode array to begin the test; and a sensor apparatus measures the test reaction which is occurring on the electrode array.Type: GrantFiled: March 9, 1990Date of Patent: October 16, 1990Assignee: Ciba Corning Diagnostics Corp.Inventor: Howard H. Weetall
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Patent number: 4960716Abstract: A substantially pure antigen found on normal and benign breast epithelial cell membranes and in breast cancer cells, fused cell hybrids which produce antibodies specific for such antigen, the monoclonal antibodies produced by such fused cell hybrids, a method for detecting the presence of breast cancer in a patient which is based on measuring the concentrations of one or more determinants of such antigen in a patient sample, and a method for either identifying those breast cancer patients whose tumors would respond to estrogen manipulation or determining prognosis based on the degree of differentiation, which method is based on measuring the concentration of an estrogen-modulated determinant of such antigen.Type: GrantFiled: December 28, 1988Date of Patent: October 2, 1990Assignee: Ciba Corning Diagnostics Corp.Inventors: Michael A. Harvey, Brenda D. Manning, Mary L. Nicholson, Karen L. Travis, Albert A. Luderer
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Patent number: 4952517Abstract: An assay procedure that is particularly valuable for detecting and/or determining the presence of threshold levels of analyte ligands in biological fluids. In one particularized and specialized aspect the disclosure is directed to procedures for detecting and/or determining threshold levels of hormone metabolites such as pregnanediol-3-glucuronide (P.sub.3 G) and estrone-3-glucuronide (E.sub.1 3G) in human urine. The assay consists of contacting a sample containing the analyte with a known amount of an antibody thereto and with a calibrated amount of the analyte itself that is conjugated to said solid support. When the level of the analyte in the sample exceeds a threshold level, such as 5 ug/ml for P.sub.3 G, the antibody will be insufficient to block all of the corresponding analyte on the solid support.Type: GrantFiled: February 8, 1988Date of Patent: August 28, 1990Assignee: Hygeia Sciences, Inc.Inventor: Izak Bahar
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Patent number: 4943522Abstract: A method and apparatus for conducting specific binding pair assays, such as immunoassays, is described. A porous membrane capable of non-bibulous lateral flow is used as assay substrate; a member of the binding pair is affixed in an indicator zone defined in the substrate. The sample is applied at a position distant from the indicator zone and permitted to flow laterally through the zone; any analyte in the sample is complexed by the affixed specific binding member, and detected. A novel method of detection employs entrapment of observable particle in the complex. Blood is a particularly preferred sample as the red blood cells can be used as the observable particles for detection of the complex.Type: GrantFiled: August 10, 1988Date of Patent: July 24, 1990Assignee: QuidelInventors: Robert W. Eisinger, Mohammed H. Khalil, David H. Katz, Robert B. Sargeant
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Patent number: 4925787Abstract: A monoclonal anti-idiotypic antibody specific to a human IgG.sub.1 type monoclonal antibody possessing specificity to nicotinic acetylcholine receptor; a method for the production of the aforementioned monoclonal anti-idiotypic antibody by the steps of immunizing an animal with a human IgG.sub.1 type monoclonal antibody specific to nicotinic acetylcholine receptor, collecting antibody-producing cells from the animal, fusing the collected cells with neoplastic cells, selecting from the product of fusion a hybridoma capable of producing a monoclonal anti-idiotypic antibody specific to the human IgG.sub.1 type monoclonal antibody possessing specificity to nicotinic acetylcholine receptor, propagating the selected hybridoma thereby giving rise to said monoclonal anti-idiotypic antibody, and collecting the produced monoclonal anti-idiotypic antibody; and use of the monoclonal anti-idiotypic antibody as a reagent and as an adsorbent.Type: GrantFiled: March 30, 1988Date of Patent: May 15, 1990Assignees: Agency of Industrial Science and Technology, Ministry of International Trade and IndustryInventors: Masao Tanihara, Hideaki Yamada, Toshihide Nakashima, Yoshiaki Omura, Koichi Takakura
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Patent number: 4916056Abstract: A novel material and device useful in solid-phase binding assays to determine the presence or amount of an analyte in a test sample, particularly antigens, antibodies, or other ligands or DNA segments. The material and device comprises a reaction site having procedural controls and an analyte binding area capable of being simultaneously contacted by the sample and reagent used in the performance of the assay. The procedural controls and analyte binding areas operate to provide readable results as to the presence or absence of analyte and simultaneously verify the assay procedure and therefore the assay result.Type: GrantFiled: March 28, 1988Date of Patent: April 10, 1990Assignee: Abbott LaboratoriesInventors: William E. Brown, III, Sarah E. Safford, John M. Clemens
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Patent number: 4891324Abstract: Assay methods are provided for determining an analyte in a sample suspected of containing the analyte. The method is carried out using a composition that includes a conjugate of a first sbp member with a particle. A luminescer is reversibly associated with a nonaqueous phase of the particle. Where the first sbp member is not complementary to the analyte, a second sbp member that is capable of binding to the first sbp member is employed. Unbound conjugate is separated from conjugate that is bound to the analyte or to the second sbp member. A reagent for enhancing the detectability of the luminescer is added and the light emission of the luminescer acted on by the reagent is measured.Type: GrantFiled: January 7, 1987Date of Patent: January 2, 1990Assignee: Syntex (U.S.A.) Inc.Inventors: John Pease, Litai Weng, Hrair Kirakossian, Edwin F. Ullman
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Patent number: 4874691Abstract: Improved, economical devices for immunoassays employ a reusable syringe or vacuum manifold to withdraw samples through a membrane containing an affinity partner for analyte. The devices can also be adapted to direct blood sampling and to automated assays.Type: GrantFiled: October 16, 1987Date of Patent: October 17, 1989Assignee: Quadra Logic Technologies Inc.Inventor: Howard Chandler
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Patent number: 4874692Abstract: An analytical element has a peroxidase-labeled ligand analog distributed within a layer comprising from 0.1 to 10.0 g/m.sup.2 of poly(vinyl-alcohol) and from 0.2 to 20.0 g/m.sup.2 of glycerol. The concentration of the glycerol must be greater than 1 times the concentration of poly(vinylalcohol) in the layer. As a result, the peroxidase retains more of its stability prior to use. Such elements can be used to determine a number of different immunologically reactive analytes, such as digoxin.Type: GrantFiled: July 20, 1987Date of Patent: October 17, 1989Assignee: Eastman Kodak CompanyInventor: Jon N. Eikenberry
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Patent number: 4868158Abstract: The invention relates to a method for the preparation of a carrier loaded with lipophilic biologically active substance based on reconstituted LDL (Low Density Lipoprotein), wherein (1) LDL is lyophilized in the presence of a protective agent; (2) the lyophilized LDL is extracted with an organic solvent; (3) the biologically active substance solubilized in a solvent is incubated with extracted LDL; the solvent is evaporated and the reconstituted LDL solubilized in an aqueous buffer; the non-incorporated biologically active substance is separated from the LDL-complex, characterized in that in step (1) the protective agent is a monosaccharide, a disaccharide, a water-soluble polysaccharide, a sugar alcohol or a mixture of these and in step (3) optionally the extract obtained during the extraction of the lyophilized LDL is mixed with the lipophilic biologically active substance solubilized in an organic solvent and this mixture is then incubated with the LDL.Type: GrantFiled: February 12, 1987Date of Patent: September 19, 1989Assignee: Oncholab ABInventors: Michele Masquelier, Mikael Ros, Curt Peterson, Mats Rudling, Sigurd Vitols
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Patent number: 4868108Abstract: An assay employing two antibodies. A microporous carrier supports a plurality of layers, in which conjugates form between test antigens and antibodies. Quantitative results are obtained from an immobilized antibody within an indicating substrate.Type: GrantFiled: December 12, 1985Date of Patent: September 19, 1989Assignee: Hygeia Sciences, IncorporatedInventors: Izak Bahar, Francis Cole
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Patent number: 4863729Abstract: Macromolecular monoclonal antibody compositions are provided which are capable of selectively forming stable bonds to cells having a predetermined concentration of at least one surface antigen, such concentration being greater in such cells than in other cells in the cell population, wherein the composition comprises a substrate and a plurality of monoclonal antibodies specific to said surface antigen or antigens, which antibodies are covalently bonded to the substrate.Type: GrantFiled: October 10, 1986Date of Patent: September 5, 1989Assignee: Linus Pauling Institute of Science and MedicineInventor: Emile Zuckerkandl
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Patent number: 4855240Abstract: Test device and assay for determining analyte wherein tracer and sample may be simultaneously applied to different absorbent material portions both in capillary flow communication with an absorbent material portion having a binder supported thereon in a manner whereby sample contacts binder, prior to any substantial contact between sample and tracer or tracer and binder.Type: GrantFiled: May 13, 1987Date of Patent: August 8, 1989Assignee: Becton Dickinson and CompanyInventors: Robert W. Rosenstein, Timothy G. Bloomster
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Patent number: 4853335Abstract: A sandwich immunoassay method is disclosed that is useful for the identification of an antigen in biological specimens. The method is comprised of a colloidal gold labeled binder specific for epitopes or receptors of a ligand, nonporous particulate solid phase which have antiligand covalently attached, and which said reagents are combined with the biological specimen or an extract of the biological specimen, and after an appropriate incubation, the said reactant mixture is contacted to a porous film having an exposed surface area of contact no greater than 30 mm.sup.2 to separate and concentrate the particle bound colloidal gold labeled binder from the unbound. The identification of an antigen is determined by the presence of color on the surface of the solid phase particles captured on the surface of the film. A competitive inhibition assay can be also used to identify the presence of a hapten or antigen, in which case the presence of the analyte is determined by the absence of color.Type: GrantFiled: September 28, 1987Date of Patent: August 1, 1989Inventors: Duane A. Olsen, David Bernstein
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Patent number: 4844869Abstract: An assay apparatus employing total internal reflection of excitation radiation at the interface between an optically conductive rod or fiber and a surrounding liquid phase of lower index of refraction. Immobilized on the surface of the fiber is a component of a complex formed in an immunochemical-type reaction; a fluorophore that can be excited into fluorescence by the excitation radiation is attached to another component of the complex. The fiber is coaxially mounted in cantelivered position within a length of tubing, so that the excitation radiation can be launched into the unsupported end of the fiber and the fluorescent radiation tunneling back into the fiber may be observed at the same fiber end.Type: GrantFiled: September 9, 1985Date of Patent: July 4, 1989Assignee: ORD, Inc.Inventor: Thomas R. Glass
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Patent number: 4831118Abstract: The present invention is a protein purification column comprising an organic substrate matrix having low reactivity to proteins, said matrix being capable of maintaining monoclonal antibodies attached thereto in an external configuration and preventing interaction with the protein to be bound to the antibody, and a monoclonal antibody attached to the substrate, the monoclonal antibody having a specific affinity for the protein to be isolated.The present invention also is a method for isolating and purifying specific protein from a solution, wherein1. Protein-specific monoclonal antibody is attached to the organic substrate matrix described above to form an antibody-substrate conjugate; and2. Protein to be isolated, in an appropriate buffer solution, is contacted with the antibody-substrate conjugate.An appropriate buffer may be applied to remove non-antibody bound contaminants, followed by an appropriate eluting agent to remove the protein from the monoclonal antibody.Type: GrantFiled: August 7, 1987Date of Patent: May 16, 1989Assignee: Scripps Clinic and Research FoundationInventors: Theodore S. Zimmerman, Carol A. Fulcher
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Patent number: 4822747Abstract: An immobilized hapten reagent for use in a specific binding assay for the determination of a hapten or binding analog thereof in a liquid test sample and methods for preparing and using the immobilized hapten reagent. The immobilized hapten reagent comprises a hapten moiety covalently linked substantially only to the external surface of a polyacrylamide gel particle. The immobilized hapten reagent is prepared by forming a reaction mixture comprising the hapten moiety and the carrier material in a nonswelling solvent wherein the gel particle is substantially impervious to the hapten moiety and wherein an analytically insignificant amount of the hapten moiety is nonspecifically bound to the gel particle. The immobilized hapten reagent is characterized by being substantially stable in aqueous solutions and exhibits an insignificant amount of leakage of the hapten moiety into a liquid test medium.Type: GrantFiled: December 9, 1986Date of Patent: April 18, 1989Assignee: Miles Inc.Inventors: Richard D. Johnson, H. Volker Runzheimer, Ronald G. Sommer, Kin F. Yip
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Patent number: 4791069Abstract: Methods for attaching one component of a ligand-anti-ligand pair onto a solid phase surface. The component may be attached to a photoactivatable cross-linker capable of coupling the component to a colloidal medium coating the surface or alternatively, the component may be coupled to a bead and held in place against the surface by an overlay of the colloidal media having voids and spaces smaller than the diameter of the particle but large enough to permit diffusion of the other of the ligand-anti-ligand pair to be detected.Type: GrantFiled: May 8, 1987Date of Patent: December 13, 1988Assignee: Ortho Diagnostic Systems Inc.Inventors: George Hovorka, W. Peter Hansen
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Patent number: 4783400Abstract: A liposome assay reagent for determination of an analyte in a homogeneous immunoassay. The reagent includes a suspension of oligolamellar lipid vesicles containing encapsulated glucose-6-phosphate dehydrogenase (G6PD), at a specific activity of between about 1-15 units/.mu.mole vesicle lipid, and glucose-6-phosphate (G6P) at a concentration of at least about 5 mM. The encapsulated G6P protects the enzyme against inactivation on preparation, by reverse phase evaporation in the presence of organic solvent, and on storage as an aqueous suspension.Type: GrantFiled: August 20, 1986Date of Patent: November 8, 1988Assignee: Cooper LipotechInventors: Eleanor Canova-Davis, Viola T. Kung, Carl T. Redemann
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Patent number: 4780285Abstract: Device for the carrying out of an immunochemical determination comprising at least one holder which is provided with an opening at the top and to the inside of which an immunochemically active substance has been applied. The device is closed at the top by a removable closure means and the holder contains at least a second immunochemically active substance which, in the absence of test medium, in the form in which the second immunochemically active substance is contained in the closed holder, during storage and transport under normal conditions exhibits no interaction with the inside of the holder and is inert with respect to the immunochemically active substance applied thereto. The holder contains a solid, more or less spherical, freeze-dried particle which contains the second immunochemically active substance.Type: GrantFiled: August 5, 1986Date of Patent: October 25, 1988Assignee: Akzo N.V.Inventors: Leonardus P. C. Kuypers, Gerrit Wolters
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Patent number: 4752562Abstract: Disclosed is a method for detection for serum antibody and/or microbial surface antigen by radial partition immunoassay. The method of this invention is applicable to (a) the evaluation of a clinical specimen for identification of a microorganism; (b) antimicrobial sensitivity assays for determination of an efficacious antibiotic for use against a specific microorganism; (c) a semi-quantitative determination of viral surface antigen; and, (d) a quantitative method for the determination of the presence of serum antibodies to microbial antigens. In each of the foregoing applications, the analyte of interest can be immobilized within a porous matrix (solid phase) by simple pipetting of the sample onto the prepared matrix. Appropriate reagents are subsequently applied to the matrix to effect immunochemical interaction of a labeled binding material to the surface antigen (or antibody) of the analyte of interest. The portion of the matrix within which such interaction takes place is termed the "reaction zone".Type: GrantFiled: October 17, 1984Date of Patent: June 21, 1988Assignee: Baxter Travenol Laboratories, Inc.Inventors: Mark I. Sheiman, Joseph L. Giegel, Mary Brotherton
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Patent number: 4752638Abstract: Conjugate monomers, polymers, and methods for the de novo synthesis of the polymers are provided. Conjugate organic monomers contain binding-pair members which upon polymerization become integrally associated with the resultant polymer. Specifically, antigens, antibodies, receptors, and ligands may be bound to organic monomers either directly by chemical reaction or indirectly by chemical spacer arms, and these conjugates may be polymerized or copolymerized with nonderivatized monomers to form polymers containing variable amounts of the binding-pair members. Such conjugate monomers and polymers find a wide variety of uses in binding to their binding-pair-member cognate which include selective removal of complementary binding-pair members from solution as well as in immunoassay procedures and in immunization regimes.Type: GrantFiled: June 30, 1986Date of Patent: June 21, 1988Assignee: Genetic Systems CorporationInventors: Robert C. Nowinski, Allan S. Hoffman, Raymond L. Houghton, John H. Priest, Nobuo Monji
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Patent number: 4727023Abstract: A reagent for use in solid phase immunoassay diagnostics comprises a matrix of non-active hybridoma cells embedded with its self-produced, covalently bound, actively presented monoclonal antibodies.The solid phase reagent according to the invention is prepared by incubating in vitro a culture medium containing active hybridoma cells capable of producing monoclonal antibodies, allowing the formation of antibodies to proceed, separating and washing said cells, resuspending the cells in a buffer solution, adding to the resulting suspension an inactivator substance capable of converting active hybridoma cells into the non-active state.Type: GrantFiled: September 9, 1985Date of Patent: February 23, 1988Assignee: I.D.L. International Diagnostic Laboratories LimitedInventors: Lynn Wang, Michael Inbar
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Patent number: 4708932Abstract: An improved process of performing analysis methods based upon biospecific affinity reactions in heterogeneous systems, wherein a ligand dissolved in a liquid is reacted with a receptor immobilized on a carrier, characterized by utilizing as the carrier a porous matrix in the form of a material body having an open capillary pore system capable of absorbing and retaining liquid phase and having such limited void dimensions that the total reaction rate of the biospecific reaction or reactions within the pore system between ligand and immobilized receptor will be at least substantially independent of the diffusion of the ligand in the liquid phase. A porous matrix for use in said process has the characteristics mentioned above.Type: GrantFiled: September 28, 1984Date of Patent: November 24, 1987Assignee: Pharmacia ABInventors: Rolf E. Axen, Goran L. Kaj, Rune Bjorkman
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Patent number: 4703002Abstract: A method for preparing a blush polymer coating composition containing an immunologically reative species comprises milling the species and the other materials used in the composition to uniformly disperse the species therein. This coating composition can be used to prepare analytical elements for determining analytes (e.g. creating kinase-MB) whereby the effects of potential interferents are immunochemically removed. By milling the immunologically reactive species, e.g. antisera, into the coating composition, the resulting element has improved stability resulting in improved keeping in high humidity environments.Type: GrantFiled: May 1, 1985Date of Patent: October 27, 1987Assignee: Eastman Kodak CompanyInventors: John B. Findlay, Annie L. Wu
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Patent number: 4695548Abstract: Gel inserts comprising a solidified liquid such as agarose suitable for use in an electrophoretic method, lysed cells entrapped within a matrix formed by the solidified liquid and macromolecules such as DNA or intact chromosomes derived from the lysed cells may be advantageously used in electrophoretic separations. The gel inserts are placed directly in a suitable support medium and subjected to one or more electric fields to separate the macromolecules.Type: GrantFiled: September 25, 1984Date of Patent: September 22, 1987Assignee: The Trustees of Columbia University in the City of New YorkInventors: Charles R. Cantor, David C. Schwartz
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Patent number: 4689310Abstract: Methods for attaching one component of a ligand-anti-ligand pair onto a solid phase surface. The component may be attached to a photoactivatable cross-linker capable of coupling the component to a colloidal medium coating the surface or alternatively, the component may be coupled to a bead and held in place against the surface by an overlay of the colloidal media having voids and spaces smaller than the diameter of the particle but large enough to permit diffusion of the other of the ligand-anti-ligand pair to be detected.Type: GrantFiled: September 21, 1984Date of Patent: August 25, 1987Assignee: Ortho Diagnostic Systems Inc.Inventors: Peter B. Kramer, W. Peter Hansen
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Patent number: 4677055Abstract: A process for the immunobacteriological detection of pathogenic germs possessing specific antigenic determinants, and a kit for carrying out the process, with the aid of a magnetic gel to which are coupled anti-specific antigenic determinant antibodies, characterized by the following steps:(a) a biological medium supposedly contaminated by a pathogenic germ possessing a specific antigenic determinant is brought into contact with particles of the magnetic gel,(b) the particles of magnetic gel are then removed by magnetic means and(c) are inoculated onto a nutrient agar medium,(d) the agar medium is incubated to develop culture colonies of the pathogenic germs;(e) areas containing serum containing antibodies specific to the pathogenic germ to be detected are formed in the agar,(f) the germs are lysed by means of lysing agents,(g) the lysate is incubated with the serum for a time enabling the serological antibody-antigen reaction to take place by immunodiffusion on the agar, and(h) the quantity of germs containeType: GrantFiled: December 7, 1983Date of Patent: June 30, 1987Assignee: Institut PasteurInventors: Andre Dodin, Eustrate Avrameas, Bruno Goud, Michel Guillou, Renee Nicolas
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Patent number: 4671938Abstract: An assay apparatus employing total internal reflection of excitation radiation at the interface between an optically conductive rod or fiber and a surrounding liquid phase of lower index of refraction. Immobilized on the surface of the fiber is a component of a complex formed in an immunochemical-type reaction; a fluorophore that can be excited into fluorescence by the excitation radiation is attached to another component of the complex. The fiber is coaxially disposed in cantilevered manner within a length of tubing, so that the excitation radiation can be launched into the unsupported end of the fiber and the fluorescent radiation tunneling back into the fiber may be observed at the same fiber end, thereby preventing that portion of the fiber surface between the unsupported fiber end and the mounted end being in contact with other than the surrounding liquid phase.Type: GrantFiled: September 9, 1985Date of Patent: June 9, 1987Assignee: Ciba-Corning Diagnostics, Corp.Inventor: Thomas A. Cook
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Patent number: 4668619Abstract: A homogeneous specific binding assay device, a method for its preparation, and a method for its use in determining a ligand, such as antigen, hapten, or antibody, in, or the ligand binding capacity of, a liquid sample. The test device comprises a solid carrier member, such as a fibrous web matrix, e.g., paper, or a polymeric film or gel, incorporated with reagents for a homogeneous specific binding assay system which produces a detectable response, usually an electromagnetic radiation signal, that is a function of the presence or amount of the ligand in or the ligand binding capacity of the sample. Useful homogeneous specific binding assay systems include those involving enzyme substrate labels, enzyme prosthetic group labels, and enzyme labels. The detectable response preferably is a luminescent, fluorescent, spectrophotometric, or colorimetric response, which is measurable by visual observation or instrument means.Type: GrantFiled: July 20, 1984Date of Patent: May 26, 1987Assignee: Miles Laboratories, Inc.Inventors: Alfred C. Greenquist, Thomas M. Li, Patricia A. Rupchock, Richard J. Tyhach, Bert Walter
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Patent number: 4665034Abstract: The invention relates to a device and method for performing qualitative enzyme immunoassays. The device comprises at least one tube having antibody, antigen or hapten attached to an internal surface thereof. A first syringe is connectable to a first end of the tube or tubes and supplies a flow of test liquid therethrough. A second syringe having a two piston arrangement is connected to the tube so as to allow a first wash solution followed by an enzyme conjugate solution to be flowed therethrough. Finally a third syringe, also having a two piston configuration, is connected to the tube so as to allow a second wash solution followed by an enzyme substrate and metabolite indicator solution to be flowed therethrough.Type: GrantFiled: November 15, 1983Date of Patent: May 12, 1987Assignee: Allelix Inc.Inventor: Howard M. Chandler