Digestion Or Removing Interfering Materials Patents (Class 436/175)
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Patent number: 5972717Abstract: A method of detecting heparin-induced antibodies to complete a diagnosis of heparin-induced thrombocytopenia (HITP) is disclosed. This method comprises the first step of attaching a glycosaminoglycan to a solid support, wherein the glycosaminoglycan is attached to the solid support only at the reducing end of the molecule (unidirectionally). Platelet factor 4 is then bound to the glycosaminoglycan forming a complex having an epitope recognizable by antibodies generated in an HITP immune response. Human blood plasma or serum from a patient suspected of having HITP is exposed to the complex and the complex is analyzed to determine if HITP-related antibodies are present. A device and kit used in performing the diagnostic assay are also disclosed.Type: GrantFiled: November 19, 1997Date of Patent: October 26, 1999Assignee: The Blood Center Research Foundation, Inc.Inventors: Richard H. Aster, Gian Visentin
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Patent number: 5968832Abstract: A reagent for measurement of leukocytes and hemoglobin concentration in the blood includes a cationic surfactant in an amount sufficient to lyse erythrocytes and denature hemoglobin, at least one of the following hemoglobin stabilizers:(a) sulfosalicylic acid, or its salt, in an amount effective for promoting the conversion of hemoglobin into methemoglobin,(b) 0.2 to 10.0 g/L of a water-soluble chelating agent having a nitrogen atom and a carboxyl group, and(c) piperazine, or its salt, in an amount effective for promoting the conversion of hemoglobin into methemoglobin, anda buffer for maintaining pH at 4 to 6.Type: GrantFiled: April 8, 1998Date of Patent: October 19, 1999Assignee: Sysmex CorporationInventors: Kinya Uchihashi, Yoshiro Ikeuchi, Atsushi Shirakami, Yukio Hamaguchi
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Automated histo-cytochemistry apparatus and encapsulation system for processing biological materials
Patent number: 5965454Abstract: There is disclosed an automated apparatus, reagents and process for immunocytochemical staining of biological materials using ligand pairing. The present invention provides a method for storing a ligand in a macroscopic solid support and releasing the ligand into contact with a biological sample mounted on a surface of a substrate. The process includes providing a macroscopic solid support formed of a solidified matrix material encapsulating a ligand therein with the macroscopic solid support being disintegratable to release the ligand therefrom. The solid support is placed in a first chamber which is in flow communication with a second chamber containing the substrate with the biological sample affixed thereto. The step of disintegrating the macroscopic solid support may include heating the macroscopic solid support to liquefy it when the matrix material is gelatin or a wax.Type: GrantFiled: May 5, 1997Date of Patent: October 12, 1999Assignee: Histaggen IncorporatedInventors: A. James Farmilo, Ronald H. Stead -
Patent number: 5962310Abstract: The present invention relates to a vehicle for delivery of particles to a sample of cells. The vehicle includes a barrier to retain the particles, which barrier is a dissolvable material Once released into the sample, the particles are useful in methods to lyse or disrupt cells or in methods to separate cellular components from one another if the cells in the sample are already lysed or disrupted.Type: GrantFiled: July 23, 1998Date of Patent: October 5, 1999Assignee: Becton Dickinson and CompanyInventors: Matthew P. Collis, Stephen H. Szczepanik
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Patent number: 5962239Abstract: An improved method for detecting even low titer HLA antibodies in proposed organ transplant recipients employs flow cytometry crossmatching (FCXM) on pronase-treated B-cells and T-cells of the donor. Two-color FCXM is preferably employed. The peripheral blood lymphocytes, after pronase digestion, are maintained under conditions to suppress Fcy R receptor regeneration, combined with sera of the proposed transplant recipient, and tested against control sera, using fluorescent reporting complexing agents. Use of pronase digested lymphocytes permits the assay to distinguish between normal or irrelevant IgG B cell binding and immunologically important HLA antibody binding.Type: GrantFiled: May 6, 1997Date of Patent: October 5, 1999Assignee: The University of Virginia Patent FoundationInventor: Peter I. Lobo
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Patent number: 5958781Abstract: Cyanide-free reagents for the determination of hemoglobin and leukocytes present in a blood sample contain an aqueous solution of at least one quaternary ammonium salt, preferably selected from the group of alkyltrimethylammonium salts, alkyldimethylbenzylammonium salts or alkylpyridium salts consisting of tetradecyltrimethyl ammonium bromide (TTAB), dodecyltrimethyl ammonium chloride, cetyltrimethyl ammonium bromide, hexadecyltrimethyl ammonium bromide and benzalkonium chlorides, and hydroxylamine salts, especially hydrochloride, sulfate and phosphates and other acid salts. The method involves mixing the reagent with a diluent- diluted blood sample, presenting it to an absorbance spectrophotometer and measuring the resulting optical density as an indicator of hemoglobin concentration. This cyanide-free reagent could be used solely for hemoglobin determinations, or , it can also be used in leukocyte counting and sizing using hematology instrumentation.Type: GrantFiled: May 27, 1997Date of Patent: September 28, 1999Assignee: Abbott LaboratoriesInventors: Show-Chu Wong, Sylvia Khoo
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Patent number: 5948278Abstract: A method for enriching rare cell populations from a whole blood sample by separating rare cell fractions from whole blood sample according to the relative charge density and/or the relative binding affinity for a leukocyte depletion solid phase matrix is described. The enrichment method may be operated stand alone, or as a pre or post-processing step in conjunction with a charge-flow separation method.Type: GrantFiled: October 10, 1997Date of Patent: September 7, 1999Assignee: BioSeparations, Inc.Inventors: David W. Sammons, Michael Manley, Joseph G. Utermohlen, Garland E. Twitty
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Patent number: 5945342Abstract: The present invention relates to methods for digesting diphosphonic acid substituted cation exchange resins that have become loaded with actinides, rare earth metals, or heavy metals, in a way that allows for downstream chromatographic analysis of the adsorbed species without damage to or inadequate elution from the downstream chromatographic resins. The methods of the present invention involve contacting the loaded diphosphonic acid resin with concentrated oxidizing acid in a closed vessel, and irradiating this mixture with microwave radiation. This efficiently increases the temperature of the mixture to a level suitable for digestion of the resin without the use of dehydrating acids that can damage downstream analytical resins. In order to ensure more complete digestion, the irradiated mixture can be mixed with hydrogen peroxide or other oxidant, and reirradiated with microwave radiation.Type: GrantFiled: May 18, 1998Date of Patent: August 31, 1999Assignee: Westinghouse Savannah River CompanyInventors: Sherrod L. Maxwell, III, Sheldon T. Nichols
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Patent number: 5939328Abstract: A method for the determination of iodide in aqueous solutions, preferably in urine. The process is characterized in that the sample solution is admixed with a chromogen and a peracid solution and the color reaction is evaluated visually or photometrically. In the determination of iodide in urine, the sample is pretreated by means of a purified activated carbon.Type: GrantFiled: September 3, 1997Date of Patent: August 17, 1999Assignee: Merck Patent Gesellschaft Mit Beschrankter HaftungInventors: Wolfgang Fischer, Thomas Groh, Stefanie Beil
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Patent number: 5939326Abstract: A device for analyzing a whole blood sample is provided. The device comprises a conventionl hematology analyzer integrated with a fluorescence cyometry analyzer. A controller is provided for controlling the analyzers, obtaining and utilizing data from both and reporting a quantitative result. Methods are also provided for analyzing a whole blood sample. One such method comprises the steps of performing on a single instrument an analysis of impedance associated with the blood sample, an analysis of light scatter associated with the blood sample, and an analysis of fluorescence associated with the blood sample. Data is collected and utilized. A result is reported.Type: GrantFiled: March 13, 1997Date of Patent: August 17, 1999Assignee: Abbott LaboratoriesInventors: Vernon L. Chupp, Peter E. Lobban, Young Ran Kim, Roderick Walton Larue, John Paul Stuart
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Patent number: 5932481Abstract: A method for the rapid estimation of hyperplastic and hypertrophic changes in animal airways is an assay which specifically measures acidic and neutral mucoproteins in a linear fashion from 0.5 to at least 10 .mu.g. The assay comprises exposure of a test animal to a suspected metaplastic inducer, removal of the lungs, homogenization in an appropriately buffered solution containing reducing agents and protease inhibitors; removal of particulate matter; and size-fractionation of the SDS treated soluble extract. The high molecular weight material is immobilized and stained for either acidic or neutral mucosubstances and the specific staining is quantitated. The changes observed are consistent with those seen in histological sections of the exposed tissues.Type: GrantFiled: March 23, 1998Date of Patent: August 3, 1999Assignee: Merck Frosst Canada & Co.Inventors: Douglas J. Pon, Louise Boulet, Carlo J. van Staden, Rejean Fortin
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Patent number: 5932174Abstract: A method of pretreating aqueous chemical oxygen demand (COD) samples to remove the risk of potential chloride ion interference. The method comprises acidifying an aqueous COD test sample, and thereafter passing the acidified sample through a source of pentavalent bismuth (Bi.sup.5+) such as sodium bismuthate.Type: GrantFiled: May 30, 1997Date of Patent: August 3, 1999Assignee: Hach CompanyInventors: Scott Vance Brayton, Donald Gene Miller
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Patent number: 5919708Abstract: A method of assessing glycated blood protein in a sample which comprises separating glycated and non-glycated protein using a liquid phase precipitation reagent, contacting the sample with a signal forming agent capable of binding preferentially to the glycated protein, and assessing the signal forming agents.Type: GrantFiled: December 11, 1995Date of Patent: July 6, 1999Assignee: Axis Biochemicals ASInventor: Erling Sundrehagen
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Patent number: 5912180Abstract: A method for detecting a substance in a liquid sample involves precipitating a substance from the liquid sample and filtering it from the liquid sample. The precipitate is then tested for the substance of interest by contacting the precipitate with a dye that forms a visible reaction when exposed to the substance. A releasing agent may be used after filtering the precipitate and prior to testing the precipitate with a dye. In another embodiment, the sample is filtered without the prior use of a precipitating agent.Type: GrantFiled: January 9, 1997Date of Patent: June 15, 1999Assignee: HybriVet Systems, Inc.Inventor: Marcia J. Stone
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Patent number: 5898002Abstract: A method for removing ferric-ferrous oxides from a liquid containing ferric-ferrous oxides and ferrous ions and to a method for determining the amount of ferrous ion in a liquid. The invention has particular utility for use in a method to accurately determine the corrosion rates of ferrometals in contact with aqueous liquids by filtering ferric-ferrous oxides from the aqueous liquid prior to determining the ferrous ion content of the aqueous liquid.Type: GrantFiled: August 22, 1997Date of Patent: April 27, 1999Assignee: BetzDearborn Inc.Inventor: Terence P. Small
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Patent number: 5895749Abstract: Kits and assays, incorporating antibodies specific for glutathione peroxidase, for determining the fertilizing ability of a male at home or in a clinical laboratory are disclosed.Type: GrantFiled: October 31, 1994Date of Patent: April 20, 1999Assignee: Beth Israel Deaconess Medical CenterInventor: Juan G. Alvarez
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Patent number: 5891735Abstract: Nitrosyl (FeII) hemoglobin can be detected in biological samples, using a method which involves injections of samples into a photolysis cell, prior to detection of chemiluminescence generated by the reaction between nitric oxide and ozone. This method is useful for monitoring the levels of nitric oxide bioactivity in both normal physiological states, and disease states, such as septic shock, atherosclerosis, thrombosis, hyperhomocysteinemia, pulmonary hypertension, malignancy, infections and central nervous system disorders.Type: GrantFiled: March 15, 1996Date of Patent: April 6, 1999Assignee: Duke University Medical CenterInventor: Jonathan S. Stamler
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Patent number: 5891734Abstract: Provided are automated methods for distinguishing and differentiating cells in a whole blood sample. In one of the methods, a whole blood sample is provided. One or more tests to be performed on the whole blood sample is selected. The tests to be performed on the whole blood sample are correlated. A volume of the whole blood sample is aspirated into an automated instrument system which automatically performs conventional hematology analysis and fluorescent cytometry analysis on the whole blood sample. A first aliquot of the whole blood sample is dispensed into at least one sample receiving vessel. The first aliquot of the whole blood sample is mixed with a fluorescent reagent. The first aliquot of the whole blood sample mixed with fluorescent reagent is diluted and transported through a flow transducer system.Type: GrantFiled: July 17, 1996Date of Patent: April 6, 1999Assignee: Abbott LaboratoriesInventors: James E. Gill, Vernon L. Chupp, Luc Van Hove
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Patent number: 5882934Abstract: A cyanide-free lytic reagent composition and method for measuring the total hemoglobin concentration in a blood sample, for counting the number of leukocytes and for deferential counting of leukocyte subpopulations are described. The cyanide-free lytic reagent composition cotains a quaternary ammonium salt or a pyridinium salt to lyse erythrocytes and release hemoglobin, and an organic ligand including triazole and its derivatives, tetrazole and its derivatives, alkaline metal salts of oxonic acid, melamine, aniline-2-sulfonic acid, quinaldic acid, 2-amino-1,3,4-thiadiazole, triazine and its derivatives, urazole, DL-pipecolinic acid, isonicotinamide, anthranilonitrile, 6-aza-2-thiothymine, 3-(2-thienyl)acrylic acid, benzoic acid and alkali metal and ammonium salts of benzoic acid, and pyrazine and its derivatives to form a stable chromogen with hemoglobin, and a salt to adjust conductivity of the reagent for impedance measurement.Type: GrantFiled: March 24, 1998Date of Patent: March 16, 1999Assignee: Coulter International Corp.Inventors: Yi Li, Carole Young
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Patent number: 5882943Abstract: A multi-filter apparatus for processing ova and parasites from human and animal specimens. The filtration apparatus includes a specimen receptacle, a filter holder section and a collection receptacle. The filter holder section contains two filters, a coarse filter and a fine filter. The method for using the apparatus includes mixing a specimen with a preservation solution to form a mixture, transferring the solution to the specimen receptacle and then fractionating the mixture. After fractionation, the specimen receptacle, filter holder section and supernatant are conveniently discarded. The resulting concentrated parasite sample may be analyzed using conventional analytic techniques. The invention further includes a kit including a filtration apparatus and a preservation fluid dispenser.Type: GrantFiled: July 31, 1996Date of Patent: March 16, 1999Inventor: William Erick Aldeen
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Patent number: 5882937Abstract: Ammonia monitor and method of use are disclosed. A continuous, real-time determination of the concentration of ammonia in an aqueous process stream is possible over a wide dynamic range of concentrations. No reagents are required because pH is controlled by an in-line solid-phase base. Ammonia is selectively transported across a membrane from the process stream to an analytical stream under pH control. The specific electrical conductance of the analytical stream is measured and used to determine the concentration of ammonia.Type: GrantFiled: July 9, 1997Date of Patent: March 16, 1999Assignee: The United States of America as represented by the Administrator of the National Aeronautics and Space AdministrationInventors: Richard L. Sauer, James R. Akse, John O. Thompson, James E. Atwater
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Patent number: 5882933Abstract: A method is provided for differentiating leukocyte subpopulations, immunophenotyping of lymphocytes and counting white blood cells. The method preserves leukocyte morphology and surface markers without using fixatives. In addition, the method finds utility in determination of hemoglobin concentration without using cyanide. The stable hemoglobin chromogen formed is measured at approximately 540 nm.Type: GrantFiled: July 25, 1997Date of Patent: March 16, 1999Assignee: Coulter International Corp.Inventors: Yi Li, Carole Young, Robert H. Raynor
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Patent number: 5879950Abstract: Disclosed are improvements for enzyme-catalyzed reactions involving DNA or RNA, including restriction digests, which are based on conducting such reactions in the presence of lipids.Type: GrantFiled: June 7, 1995Date of Patent: March 9, 1999Inventors: Paavo Kai Johannes Kinnunen, Pekka Kristian Mustonen, Juha Kalervo Kere
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Patent number: 5879945Abstract: In a flue gas desulfurization process based on the wet lime-gypsum method, the controlled oxidation of sulfites, by comparison of the redox potential of an absorbing fluid in a sample tank and the redox potential of the absorbing fluid in a completely oxidized state in a reference tank, and adjustment of the rate of air flow through the absorbing fluid, is improved by removing peroxides from the absorbing fluid in the reference tank before passing air therethrough to effect oxidization to a completely oxidized state. The method avoids instability due to the presence of peroxides in the absorbing fluid.Type: GrantFiled: August 22, 1997Date of Patent: March 9, 1999Assignee: Mitsubishi Heavy Industries, Ltd.Inventors: Susumu Okino, Hiroshi Tanaka, Koosoo Tao
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Patent number: 5877149Abstract: A deepithelialized skin cell diffusion system which can be used to select topical gel and cream formulations containing human other wound healing promoters such as plasma fibronectin. The formulations provide slow release and increased contact time of fibronectin or other wound healing promoters to the wound site leading to its effective absorption.Type: GrantFiled: June 19, 1997Date of Patent: March 2, 1999Inventor: Andre Beaulieu
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Patent number: 5877027Abstract: An analytical method for the quantitative determination of the impurities in silicon dioxide by which trace amounts of hardly soluble impurities contained in silicon dioxide can be reliably decomposed and converted into a solution so that the contents of all of the impurities contained in silicon dioxide or, in particular, zirconium in a natural quartz powder can be accurately determined. Silicon dioxide is decomposed with hydrofluoric acid or an acid mixture of hydrofluoric acid and another inorganic acid to give a decomposition solution which is, as such or after admixture with another inorganic acid, subjected to evaporation to dryness and the residue is heated to cause fusion with addition of a salt or hydroxide of an alkali metal followed by dissolution of the salt or hydroxide of an alkali metal with pure water or with an aqueous solution of an inorganic acid to give an aqueous solution which is subjected to quantitative analysis of the impurities therein.Type: GrantFiled: August 27, 1997Date of Patent: March 2, 1999Assignee: Shin-Etsu Quartz Products Co., Ltd.Inventors: Katsuhiko Kemmochi, Kiyotaka Maekawa, Chuzaemon Tsuji, Manabu Saitou, Hiroyuki Miyazawa, Hiroyuki Watanabe
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Patent number: 5874310Abstract: A method is provided for differentiation of nucleated red blood cells. In addition, the method provides for a concurrent differentiation of leukocytes in a blood cell sample by suitable electronic and optical measurements. The method includes exposing a blood cell sample to a reagent system to lyse mature red blood cells and subsequently analyzing nucleated red blood cells in a flow cell by optical analysis. A concurrent differentiation of nucleated blood cells and leukocytes can be performed using electronic and optical analysis. The electronic and optical analysis includes light scatter and impedance measurements. This method eliminates the use of nuclear stain for identification of nucleated red blood cells. The method of the present invention, for the first time, reports differentiation and enumeration of nucleated red blood cells without using fluorescence.Type: GrantFiled: November 21, 1997Date of Patent: February 23, 1999Assignee: Coulter International Corp.Inventors: Yi Li, Jing Li, Carole Young
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Patent number: 5874311Abstract: A method is provided for differentiation of reticulocytes. In addition, the method provides for a concurrent differentiation of leukocyte subpopulations in a blood cell sample by suitable electronic and optical measurements. The method includes exposing a blood cell sample to a reagent system to lyse mature red blood cells and subsequently analyzing reticulocytes in a flow cell by optical analysis. A concurrent differentiation of reticulocytes and leukocytes can be performed using electronic and optical analysis. The electronic and optical analysis includes light scatter and impedance measurements. This method does not require the use of nuclear stain for differentiation of reticulocytes.Type: GrantFiled: November 21, 1997Date of Patent: February 23, 1999Assignee: Coulter International Corp.Inventors: Yi Li, Jing Li, Carole Young
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Patent number: 5872009Abstract: Total bilirubin or direct bilirubin is measured by allowing nitrous acid as an oxidizing agent to act on a sample of living body fluid, and measuring optical changes of the sample. For measuring the direct bilirubin, nitrous acid is allowed to act on the sample in the presence of thiourea as a reaction inhibitor for indirect bilirubin. For measuring the total bilirubin, nitrous acid is allowed to act on the sample in the presence of cetyltrimethylammonium bromide as a reaction accelerator. Or, direct bilirubin is measured by allowing an oxidizing agent to act on a sample of living body fluid in the presence of a specific non-ionic surfactant. These methods have a good correlation to the conventional enzymatic method and a good reagent stability and provide safe methods for measuring bilirubin with less danger to environmental pollution.Type: GrantFiled: June 30, 1997Date of Patent: February 16, 1999Assignee: Nitto Boseki Co., Ltd.Inventors: Ryo Kojima, Katsuhiro Katayama, Yoshikiyo Sasagawa
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Patent number: 5872010Abstract: A microscale fluid handling system that permits the efficient transfer of nanoliter to picoliter quantities of a fluid sample from the spatially concentrated environment of a microfabricated chip to "off-chip" analytical or collection devices for further off-chip sample manipulation and analysis is disclosed. The fluid handling system is fabricated in the form of one or more channels, in any suitable format, provided in a microchip body or substrate of silica, polymer or other suitable non-conductive material, or of stainless steel, noble metal, silicon or other suitable conductive or semi-conductive material. The microchip fluid handling system includes one or more exit ports integral with the end of one or more of the channels for consecutive or simultaneous off-chip analysis or collection of the sample. The exit port or ports may be configured, for example, as an electrospray interface for transfer of a fluid sample to a mass spectrometer.Type: GrantFiled: July 3, 1996Date of Patent: February 16, 1999Assignee: Northeastern UniversityInventors: Barry L. Karger, Frantisek Foret, Paul M. Zavracky, E. Nicol McGruer, Qifeng Xue, Yuriy M. Dunayevskiy
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Patent number: 5869273Abstract: The subject invention provides methods and kits for detecting increased bone resorption in patients. These methods and kits use chondroitin sulfate, a glycosaminoglycan, as a marker for bone resorption. Levels of chondroitin sulfate are detected in samples of urine or serum taken from patients. Measurements of chondroitin sulfate levels are made by methods such as fluorophore-assisted carbohydrate electrophoresis (FACE). Knowledge of increased bone resorption rates is useful in diagnosis of bone disorders such as osteoporosis.Type: GrantFiled: September 13, 1996Date of Patent: February 9, 1999Assignee: Glyko, Inc.Inventor: John C. Klock
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Patent number: 5866352Abstract: A kit of two liquid reagent components for determining the fructosamine content of a blood sample measured by color change, and methods of determining fructosamine content of a blood sample using these two liquid reagents are disclosed.Type: GrantFiled: July 2, 1997Date of Patent: February 2, 1999Assignee: Roche Diagnostic Systems, Inc.Inventor: Ewald Vorberg
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Patent number: 5863740Abstract: The invention concerns interference-eliminating agents for avoiding unspecific interactions in immunoassays in which avidin or streptavidin or a derivative thereof are used as the interference-eliminating agents.Type: GrantFiled: September 5, 1996Date of Patent: January 26, 1999Assignee: Boehringer Mannheim GmbHInventors: Rosemarie Kientsch-Engel, Frederic Donie, Michael Wiedmann
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Patent number: 5858790Abstract: Hematology reference control cells and method of manufacture. The invention relates to the methods of preparing stable white blood cell ("WBC") and nucleated red blood cell ("NRBC") fractions and the hematology control reagents containing such stablized cells for primary use on a multi-angle light scatter based hematology instrument.Type: GrantFiled: June 26, 1996Date of Patent: January 12, 1999Assignee: Abbott LaboratoriesInventors: Young Ran Kim, Jean Emiko Kihara
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Patent number: 5858789Abstract: A pre-determined concentration of stabilized, maturation-arrested porcine reticulocytes in a red blood cell base, useful as a reticulocyte control composition. The composition can be provided in the form of a concentrated reticulocyte composition, to be diluted to a desired final reticulocyte concentration at the time of use. The composition can also be provided in the form of a diluted, ready-to-use control composition. Also included is a method of preparing such a composition, the method involving sequential steps of forming and sedimenting Rouleaux bodies.Type: GrantFiled: April 6, 1998Date of Patent: January 12, 1999Assignee: Research & Diagnostic Systems, inc.Inventors: Ralph T. Francis, Alan M. Johnson
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Patent number: 5858794Abstract: The invention describes an improved stable reagent composition and method for the determination of hemoglobin (Hb) using whole blood samples and automated hematology analyzers. The Hb reagent contains an inorganic cyanide salt, at least one surfactant and a base and has a final pH of about 10.0 to about 11.2, preferably about 10.4 to about 11.2 or less and more preferably about 10.8 to about 11.2 or less. This reagent is intended for use as a universal Hb determination reagent for all of the instruments in the aforementioned series and will provide accurate and precise results without accompanying interference from elevated numbers of white blood cells, especially as found in abnormal blood specimens, and without system-to-system variation in the results obtained.Type: GrantFiled: May 13, 1997Date of Patent: January 12, 1999Assignee: Bayer CorporationInventor: Michael J. Malin
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Patent number: 5851834Abstract: Impurity distributions in microelectronic structures formed from an aluminum-containing material are determined. A passivation layer, e.g., a titanium/titanium nitride layer or a borphosphosilicate glass (BPSG) layer, is formed on a substrate. A layer of the aluminum-containing material is formed on the passivation layer. The layer of the aluminum-containing material is then exposed to a phosphoric acid solution to remove aluminum from the layer of the aluminum-containing material and leave a precipitate on the passivation layer. The precipitate is then analyzed using scanning electron microscope (SEM) photomicrograms and/or Auger analysis to determine a distribution of impurities in the layer of the aluminum-containing material.Type: GrantFiled: September 19, 1997Date of Patent: December 22, 1998Assignee: Samsung Electronics Co., Ltd.Inventors: Sung-teak Moon, Sung-pil Choi, Dong-jun Lee
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Patent number: 5849597Abstract: A treatment apparatus for analyzing the impurities in silicic material with high precision, includes a container having an inner space in which at least one analysis sample container and a sample decomposing solution are accommodated. The container is divided into a lid body and a lower body, each of the lid body and the lower body being opened at the division surface side thereof to form an open end and being closed at the surface side opposite to the division surface side to form a close end thereof. The inner peripheral surface of the open end of the lower body is formed in a stepwise shape so that the analysis sample container is disposed to be spaced from the surface of the decomposing solution which is stocked in the lower body, and the inner peripheral surfaces of the lid body and the lower body are smoothly continuously threadily engaged with each other through abutment faces thereof to keep the container in an appropriate hermetic level.Type: GrantFiled: December 18, 1996Date of Patent: December 15, 1998Assignee: Toshiba Ceramics Co., Ltd.Inventors: Fumio Tokuoka, Kazuhiko Shimanuki
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Patent number: 5843794Abstract: A novel technique is disclosed for the prevention of false positive reactions in immunological testing which are caused by interference of C.sub.1 and C.sub.1q. The method is based on heating a sample of a body fluid at a temperature of 59.degree.-64.degree. C. in the presence of a particular neutral salt. A method for screening for rheumatoid factor is also disclosed.Type: GrantFiled: November 29, 1995Date of Patent: December 1, 1998Assignee: Montefiore Medical CenterInventor: Jacques Singer
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Patent number: 5843657Abstract: A method of microdissection which involves: forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes an activatable adhesive layer which provides chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated the transfer surface and tissue sample are separated. During separation the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample.Type: GrantFiled: October 10, 1995Date of Patent: December 1, 1998Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Lance A. Liotta, Michael E. Buck, Rhonda Weiss, Zhongping Zhuang
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Patent number: 5840583Abstract: A method for microwave assisted chemical processes is disclosed that comprises applying sufficient microwave radiation to a temperature-monitored mixture of reagents, with at least one of the reagents being thermally responsive to electromagnetic radiation in the microwave range, and based on the monitored temperature, to maintain the added reagents at or closely about a predetermined temperature while substantially avoiding thermal dilution (or before substantial thermal dilution can occur) that otherwise would have been caused by the addition of the reagents to one another.Type: GrantFiled: September 5, 1997Date of Patent: November 24, 1998Assignee: CEM CorporationInventors: David A. Barclay, William Edward Jennings, Edward E. King
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Patent number: 5827478Abstract: Method and apparatus for transportation and processing of multiple protocol assays within an automated immunoassay analyzer instrument. The apparatus includes a cuvette ring movably coupled to a magnet ring. In one embodiment, the magnet ring and cuvette ring are provided having circular shapes. A temperature controlled housing is disposed about the cuvette and magnet rings to provide a rotary incubation and particle separation chamber. The cuvette ring holds a plurality of cuvettes each of which may have a different assay disposed therein. The cuvette ring advances the cuvettes around the circumference of the incubation chamber. A plurality of discrete processing centers for aspiration and dispensing fluid samples, reagents and wash fluids are disposed at predetermined positions about the incubation chamber.Type: GrantFiled: October 31, 1996Date of Patent: October 27, 1998Assignee: Chiron Diagnostics CorporationInventors: Glen A. Carey, Michael L. Malek
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Patent number: 5821128Abstract: A method for differentiating and isolating sub-populations of leucocytes in a blood sample involved treating the sample with polyoxyethylene 9-lauryl ether. This method is suitable for isolating basophil granulocytes when it is conducted in an acid medium.Type: GrantFiled: June 13, 1996Date of Patent: October 13, 1998Assignee: Hycel DiagnosticsInventor: Rene Provost
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Patent number: 5817518Abstract: This invention relates to a lytic reagent and a method of using the lytic reagent for automatically determining leukocyte subpopulations in blood. More specifically, the new lytic reagent lyses red blood cells and affects the eosinophils which enables the differentiation of at least one subpopulation of leukocytes. The lytic reagent is an acidic, hypertonic aqueous solution containing alkali metal salt of alkyl sulfite, an eosinolytic agent, a nonionic surfactant and a physiological salt. When used in combination with a second lytic reagent system, one is able to obtain at least a five part differential of leukocytes using DC and RF measurements.Type: GrantFiled: December 18, 1995Date of Patent: October 6, 1998Assignee: Coulter International Corp.Inventors: Yi Li, Carole Young, Sergio C. Veulens
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Patent number: 5811307Abstract: The novel dicationic dye N,N'-bis?3,3'-(dimethylamino)propylamine!-3,4,9,10-perylenetetracarboxylic diimide (DAPER) is prepared by reacting 3,4,9,10-perylenetetracarboxylic dianhydride with N,N-dimethylaminopropylamine. The dye DAPER is particularly useful in a rapid, sensitive method for the precipitation, recovery and quantitation of DNA from solutions containing DNA, which method involves the steps of (a) adding the dye DAPER to a solution containing DNA and allowing the resulting mixture to equilibrate; (b) collecting the resulting precipitate; (c) removing weakly bound DAPER from the precipitate; (d) extracting DAPER therefrom by the addition of a solvent therefor; and (e) determining the amount of DNA precipitated by measuring either the absorbance or fluorescence of DAPER in the solvent extract from step (d).Type: GrantFiled: June 11, 1997Date of Patent: September 22, 1998Assignee: Florida State UniversityInventors: Randolph L. Rill, Zhi-Ren Liu
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Patent number: 5804389Abstract: A method for detecting abnormal cell shedding rates of mature epithelial cells of a warm-blooded animal, such as the epithelial cells of the gastric or colonic glands. A labeling composition containing, e.g., a cyanine dye is applied to epithelial cells, following which the site is observed over time. Abnormal cell shedding rates are indicative of disease states such as carcinoma.Type: GrantFiled: December 29, 1995Date of Patent: September 8, 1998Assignee: Phanos Technologies, Inc.Inventor: Masahiro Tada
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Patent number: 5798217Abstract: The invention provides a method for enriching a sample in tumor cells and determining the DNA ploidy and proliferative index of the tumor cells present in the sample. The method uses a pan-leukocyte monoclonal antibody conjugated to a separable substrate such as magnetic microspheres to conjugate and remove leukocytes from the sample. A fluorescently labelled monoclonal antibody specific to a tumor associated antigen or an antigen arising from the presence of the tumor and a DNA staining reagent are added to the leukocyte depleted sample. The sample is then analyzed by dual color flow cytometry to determine cells having an abnormal DNA content by gating on fluorescently labelled cells.Type: GrantFiled: June 12, 1995Date of Patent: August 25, 1998Assignee: Coulter CorporationInventors: Wade E. Bolton, Norma Sue Kenyon, Olavi Siiman, Robert J. Schmittling
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Patent number: 5795786Abstract: A process and a reagent for the specific and direct determination of the LDL-fraction in the presence of other serum lipoproteins by adding a polymeric LDL-aggregating agent, followed by direct turbidimetric measurement of the LDL aggregate. Preferred are polymers which have a comb or brush type structure with the side groups having acid character, such as branched alkane sulfonic acids.Type: GrantFiled: August 6, 1996Date of Patent: August 18, 1998Assignee: Boehringer Mannheim GmbHInventors: Karl-Siegfried Boos, Dietrich Seidel, Wolf-Dieter Engel, Angelika Kurrle-Weittenhiller
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Patent number: 5786224Abstract: A lytic reagent composition is provided which selectively stromatolyses red blood cells in a blood sample. In addition, a lytic reagent system is provided which enables the differentiation of at least three subpopulations of leukocytes. A method for using the lytic reagent system is also provided. Still further, the lytic reagent system finds use in the determination of the hemoglobin in the blood. The lytic reagent system utilizes an alkyl sulfate, polyoxyethylene based surfactant and acid with a hypertonic, alkaline, stabilizing reagent. The system and analysis method maintains the cellular morphology of the leukocytes and can be used to analyze normal and abnormal blood samples, fresh and aged blood, human and non-human animal blood samples.Type: GrantFiled: June 29, 1995Date of Patent: July 28, 1998Assignee: Coulter CorporationInventors: Yi Li, Carole Young, Timothy J. Fischer
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Patent number: 5783400Abstract: A method is provided for preparing lipoprotein (a) from a volume of biological fluid that is substantially free of lipoproteins of another class. The method involves an ultracentrifugation step in which at least one fraction is recovered that contains Lp(a). This material is then reacted with immobilized ligand to remove non-Lp(a) interfering substances from the fraction, the Lp(a) remaining unbound. The non-reacted Lp(a) is subsequently obtained in a form that is suitable for use in the analysis of any of protein concentration, protein isoform determination or cholesterol assays. A method of identifying and measuring an amount of one or more isoforms of Lp(a) is further provided.Type: GrantFiled: June 7, 1995Date of Patent: July 21, 1998Assignee: Genzyme CorporationInventors: Christine P. Gebski, C. William Christopher, James F. Ollington