Electron Dense Compounds (e.g., Ferritin, Etc.) Patents (Class 436/801)
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Patent number: 7695972Abstract: Method for the in vitro diagnostic or for the monitoring of a disease involving an inflammatory reaction within a patient, which comprises the steps of: a) providing a biological sample from the patient; b) measuring the amount of selenoprotein P which is contained in the biological sample; c) comparing the amount of selenoprotein P measured at step b) i) with the amount of selenoprotein P which is contained in a biological sample from an individual which is not affected with the disease; or ii) with the amount of selenoprotein P which was contained in a biological sample from the same patient.Type: GrantFiled: May 15, 2002Date of Patent: April 13, 2010Inventor: Xavier Forceville
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Patent number: 7419833Abstract: A method for determining the sequence of at least a portion of a single-stranded nucleic acid molecule by base-specifically labeling the exposed bases of the nucleic acid molecule using heavy element-substituted nucleotide bases which form Watson-Crick type base-pairs with the exposed bases of the nucleic acid molecule and then imaging the labeled single-stranded nucleic acid molecule using electron microscopy, e.g., transmission electron microscopy (TEM), or some other method that permits discrimination of the heavy element substituted nucleotide bases is described. The image is analyzed to determine the base sequence of at least a portion of the nucleic acid molecule.Type: GrantFiled: April 28, 2003Date of Patent: September 2, 2008Assignee: Nagayama IP Holdings LLCInventor: Kuniaki Nagayama
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Patent number: 7354733Abstract: We disclose methods of sorting or separating mixtures of living cells (e.g., eukaryotic, prokaryotic, mammalian, pathogenic, bacterial, viral, etc.). We perform our methods by activating cell-selective photophoric labels, which photosensitize and chemically reduce a photosensitive metal compound to form metal grains, particles or crystals. The metal adheres to the cells and forms the basis for sorting or separating different cell types. Photophoric labels may include chemiluminescent agents such as peroxidase enzymes activated with peroxidase substrates capable of luminescence. Photosensitive metal compounds may be present in a light-sensitive matrix or emulsion containing photosensitizable metal compounds, which form metal grains, particles or crystals upon exposure to a developer solution. Developer solutions are formulated to substantially allow living cells to remain viable after exposure to the developing solution.Type: GrantFiled: March 26, 2002Date of Patent: April 8, 2008Assignee: Cellect Technologies Corp.Inventors: Shmuel Bukshpan, Gleb Zilberstein
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Patent number: 7176036Abstract: Methods and devices for electrochemical detection of a specific binding pair member utilizing a microsphere with an incorporated electroactive marker, wherein a member of the specific binding pair to be detected is bound, directly or through one or more intermediates, to the microsphere. Multiple specific binding pair members may be detected by use of electrochemically distinguishable electroactive markers. Microspheres with incorporated electroactive markers may include one or more functional groups for binding members of specific binding pairs, and are preferably insoluble in aqueous solvents but soluble in selected organic solvents.Type: GrantFiled: September 18, 2003Date of Patent: February 13, 2007Assignee: Arrowhead Center, Inc.Inventors: Joseph Wang, Ronen Polsky, Kathryn L. Turner
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Patent number: 6750065Abstract: Immunoassay displacement methods for detecting (preferably identifying) the presence or amount of a target analyte (e.g. drug) in a sample comprising the steps of: (a) exposing the sample to a complex comprising an immobilized antibody capable of specifically binding the analyte, said antibody being specifically bound to a displacement agent, wherein said agent comprises: (I) an analyte analog capable of specifically binding the antibody, (ii) a surface enhanced resonance raman scattering (SERRS) or a surface enhanced raman scattering (SERS) active label, (iii) a SERRS or SERS surface-seeking group (e.g. benztriazole), whereby any analyte present in the sample causes the displacement of agent from the antibody; (b) exposing any displaced agent to a SERRS or SERS surface; and, (c) detecting any displaced agent associated with said surface using SERRS or SERS. In preferred forms of the invention several target analytes are detected from a single source or sample simultaneously.Type: GrantFiled: November 20, 2000Date of Patent: June 15, 2004Assignee: University of StrathclydeInventors: Peter Cyril White, Salah Athmani, William Ewen Smith, Daran Antony Sadler
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Patent number: 6387614Abstract: The present invention provides methods and compositions for detecting the presence of biologically-important analytes by using redox liposome biosensors. In particular, the present invention provides liposome/sol-gel electrodes suitable for the detection of a wide variety of organic molecules, including but not limited to bacterial toxins.Type: GrantFiled: June 30, 2000Date of Patent: May 14, 2002Assignee: The Regents of the University of CaliforniaInventors: Quan Cheng, Raymond C. Stevens
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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: 6284475Abstract: The present invention provides methods for diagnosing and/or monitoring thrombophilic disease in a patient that can result from the antiphospholipid antibody syndrome (aPL syndrome). The methods of the invention are premised on the inhibition of binding of an anticoagulant protein, annexin, preferably annexin-V, to phospholipids by antiphospholipid (aPL) antibodies in a patient blood sample.Type: GrantFiled: July 10, 1998Date of Patent: September 4, 2001Assignee: Mount Sinai School of Medicine of the City of New YorkInventor: Jacob H. Rand
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Patent number: 6219137Abstract: A probe for a surface-enhanced Raman scattering spectrometer is provided for injection into a cell in order to detect trace amounts of a compound within that cell. The probe has a spherical shape with a diameter less than one micrometer and preferably in the 10-500 nanometer range. The nanoprobes can have a receptor coating related to the specific compound to be detected by the probe. A process for producing, injecting and utilizing the nanoprobes are described.Type: GrantFiled: December 3, 1998Date of Patent: April 17, 2001Assignee: Lockheed Martin Energy Research CorporationInventor: Tuan Vo-Dinh
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Patent number: 5872013Abstract: An aggregate for qualitatively or quantitatively determining bindable substances. Said aggregate comprises an ultra small colloidal particle and a specific binding agent characterized in that the mean diameter of the colloidal particle is below 2 nm. Preferably the size of the metal particle is selected so that the aggregate is capable of penetrating in standard biological specimens. The invention further provides a universally applicable detection system for determining bindable substances in particular in living material. Further there is provided a process for preparing said aggregate.Type: GrantFiled: October 4, 1995Date of Patent: February 16, 1999Assignee: Janssen Pharmaceutica N.V.Inventors: Johannes Leonardus Maria Leunissen, Marc Joris De Brabander, Petrus Franciscus Elisabeth Maria Van de Plas
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Patent number: 5792622Abstract: A microbiological assay for chemicals, which uses a cell and a reducing dye to quantitatively measure inhibition of electron transport in the cell membrane as a function of chemicals in the substance being tested, is disclosed. This assay and method is reliable, simple, fast, and inexpensive, requires a minimum amount of durable equipment, and avoids the need for the use of live animals as the indicator organisms. The assay is particularly useful for testing for toxicity in food products, environmental, medical and industrial processes, sewage treatment, effluent, agricultural wastes, and chemical dumps.Type: GrantFiled: November 16, 1995Date of Patent: August 11, 1998Assignee: New Mexico State University Technology Transfer CorporationInventor: James L. Botsford
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Patent number: 5710011Abstract: Half-sandwich complexes of transition metals having a single .pi.-ligand with delocalised .pi. bonding are of use in mediating electron transfer between an electrode and a redox protein, for example an oxidoreductase enzyme such as in an amperometric enzyme sensor. Suitable compounds include complexes of the general formula:(.pi.-ligand)M(not-.pi.-ligand).sub.nwherein the complex is charged or neutral, .pi.-ligand represents the single .pi.-bonded ligand, M represents the transition metal atom, n is the number of ligands which are not .pi.-ligands, and the n not-.pi.-ligands are the same or different, are univalent or multivalent, and serve to satisfy the valency of the transitional metal M.Type: GrantFiled: March 6, 1995Date of Patent: January 20, 1998Assignee: Medisense, Inc.Inventors: Nigel Forrow, Stephen Walters
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Patent number: 5686244Abstract: This invention relates to a new electrochemiluminescent (ECL) label for oligonucleotides using phosphoramidite chemistry.Type: GrantFiled: June 5, 1995Date of Patent: November 11, 1997Assignee: IGEN IncorporatedInventors: Satyanarayana R. Gudibande, John H. Kenten
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Patent number: 5627036Abstract: Detectably labelled annexines and compositions thereof are disclosed. Also disclosed are methods for diagnosing a disruption or activation of the hemostatic system or a prothrombotic state in an individual suspected of having a hemostatic disorder, by contacting the blood of said individual with an annexine, and detecting whether an annexine-platelet complex is formed.Type: GrantFiled: January 21, 1994Date of Patent: May 6, 1997Assignee: Boehringer Ingelheim International GmbHInventor: Christiaan Reutelingsperger
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Patent number: 5597910Abstract: This invention relates to a new electrochemiluminescent (ECL) label for oligonucleotides using phosphoramidite chemistry.Type: GrantFiled: June 7, 1995Date of Patent: January 28, 1997Assignee: Igen, Inc.Inventors: Satyanarayana R. Gudibande, John H. Kenten
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Patent number: 5587292Abstract: A novel method for detecting chitin, and for diagnosing fungal infections (including yeast infections), with a chitinase or other chitin-specific binding protein. This method should allow the convenient, broad spectrum diagnosis of fungal infections in tissue samples or in body fluids. Fungal infections are a particular problem in immunocompromised hosts such as AIDS patients, where they can cause opportunistic infections. This invention overcomes difficulties experienced by prior methods of diagnosing fungal infections.Type: GrantFiled: March 9, 1995Date of Patent: December 24, 1996Assignee: Board of Supervisors of Louisiana State University and Agricultural and Mechanical CollegeInventors: Roger A. Laine, Wai C. J. Lo
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Patent number: 5567628Abstract: A method, composition, device, apparatus, and kit for the determination of the presence or amount of an analyte by monitoring an analyte-mediated ligand binding event in a test mixture which contains the analyte to be assayed, a specific binding member, a Raman-active label, and a particulate having a surface capable of inducing a surface-enhanced Raman light scattering. The test mixture is illuminated with a radiation sufficient to cause the Raman-active label in the test mixture to emit a detectable Raman spectrum. The differences in the detected surface-enhanced Raman scattering spectra are dependent upon the amount of the analyte present in the test mixture. Thus, by monitoring these differences, the presence or amount of the analyte are determined.Type: GrantFiled: June 30, 1994Date of Patent: October 22, 1996Assignee: Abbott LaboratoriesInventors: Peter J. Tarcha, Thomas E. Rohr, James J. Markese, Therese Cotton, Bernard N. Rospendowski
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Patent number: 5516697Abstract: A simple, cost effective assay of iron is accomplished by using lactoferrin as part of a biosensor to detect iron in a sample. The lactoferrin releases protons when the iron is sequestered by the lactoferrin and the change in potential caused by the release of protons is measured by a potentiometer or pH sensing device. The sensing devices include the ion-selective or ion sensitive field effect transistors (ISFET), a potentiometric device or the pH indicator papers.Type: GrantFiled: August 9, 1995Date of Patent: May 14, 1996Assignee: Ferrosensor, Inc.Inventor: Marian L. Kruzel
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Patent number: 5501983Abstract: According to the method of the invention, immunoassays are applied to measure free PSA as well as a proteinase inhibitor complex. Free PSA and PSA complex are according to the invention measured by a non-competitive immunoassay employing at least two different antibodies. The invention is further characterized in that the PSA proteinase inhibitor complex of interest is formed with .alpha..sub.1 -antichymotrypsin. Moreover, the invention is characterized in that free PSA, the PSA-proteinase inhibitor complex and their ratio are applied in the diagnosis of patients with prostate cancer.Type: GrantFiled: March 19, 1993Date of Patent: March 26, 1996Inventors: Hans Lilja, Ulf-Hakan Stenman
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Patent number: 5272061Abstract: A dry analytical element for the determination of serum cholinesterase (CHE) activity is disclosed. The element analyses undiluted body fluids and employs butyrylthiocholine as the substrate for CHE. Butyrylthiocholine is hydrolyzed by serum cholinesterase and liberates butyric acid and thiocholine. The thiocholine liberated then reduces ferricyanide to ferrocyanide and the rate of change is measured by reflectance densitometry.Type: GrantFiled: September 20, 1991Date of Patent: December 21, 1993Assignee: Eastman Kodak CompanyInventor: Stephen C. Hasselberg
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Patent number: 5266498Abstract: An assay for an analyte in a test sample that uses a ligand binding reaction between the analyte and a specific binding member or a binding member pair that includes one binding member having a Raman active reporter. The analyte can be assayed by measurement of the Raman scattering signal of the Raman-active reporter. The Raman scattering signal can be either a noon-enhanced Raman scattering signal or a Raman scattering signal that is enhanced by a surface capable of enhancing that Raman scattering signal.Type: GrantFiled: November 7, 1991Date of Patent: November 30, 1993Assignee: Abbott LaboratoriesInventors: Peter J. Tarcha, Thomas E. Rohr, Therese Cotton
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Patent number: 5248589Abstract: An Fc receptor protein conjugated with Ferritin binds to an exposed Fc region of an antibody to form a cell/Ferritin complex. Magnetic particles are added to the medium and bind to the complex. The magnetic particles when bound to the complex significantly enhance the magnetic field gradient of the complex such that it may be separated magnetically from the medium.Type: GrantFiled: January 16, 1992Date of Patent: September 28, 1993Assignee: Board of Governors for Higher Education, State of Rhode Island and Providence PlantationsInventors: Arijit Bose, Srinivas V. Sonti
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Patent number: 5120643Abstract: The present invention relates to improved specific binding assay methods, kits and devices utilizing chromatographically mobile specific binding reagents labelled with colloidal particles. Specific binding reagents labelled with colloidal particles such as gold and selenium may be subjected to rapid chromatographic solvent transport on chromatographic media by means of selected solvents and chromatographic transport facilitating agents. Further, impregnation of solid substrate materials with labile protein materials including colloidal particle and enzyme labelled reagents in the presence of meta-soluble proteins provides for the rapid resolubilization of such materials which have been dried onto such substrate materials.Type: GrantFiled: July 13, 1987Date of Patent: June 9, 1992Assignee: Abbott LaboratoriesInventors: Shanfun Ching, Patricia Billing, Julian Gordon
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Patent number: 5079172Abstract: A method and test kit for detecting a first antibody using a gold particle labeled secondary antibody is described. Microspheres coated with an antigen reactive with the first antibody is reacted with the first antibody from serum or other sources. The gold-labeled antibody is reacted with the first antibody antigen complex on the microsphere and detected. Preferably the gold particles are detected using an electron microscope.Type: GrantFiled: November 4, 1988Date of Patent: January 7, 1992Assignee: Board of Trustees operating Michigan State UniversityInventors: V. Hari, David A. Baunoch, Pritam Das
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Patent number: 5068178Abstract: A method of identifying and enumerating specific cell types in a heterogeneous population of cells by enhancing the specific staining of desired cells, comprising contacting a sample from the heterogeneous population of cells with a labeled primary antibody which recognizes and binds to a desired cell surface antigen and an unlabeled cross-linking agent which recognizes and binds to the primary antibody is disclosed.Type: GrantFiled: April 27, 1990Date of Patent: November 26, 1991Assignee: Genetic Systems CorporationInventor: Robert C. Nowinski
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Patent number: 4962023Abstract: An immunoassay method for one-step detection of specific antibodies which includes incubation of a solid phase support or matrix having a spot of the antigen bound thereto with a sample of the clinical fluid to be tested in the presence of a signal developing reagent, including a detector substance, which is preferably a colloidal metal sol, and a ligand, such as protein A or other antibody binding ligand. A diagnostic field kit containing the test antigens and signal developing reagent is also described.Type: GrantFiled: June 22, 1987Date of Patent: October 9, 1990Assignee: Louisiana State University, Agricultural and Mechanical CollegeInventors: William J. Todd, Paul A. Barstad
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Patent number: 4900660Abstract: Proteinaceous, antigenic factor derived from a group C Streptococcus which is receptor for the Fc region of IgG, a method for its preparation and immunoassay and antigen detection methods employing the receptor.Type: GrantFiled: November 25, 1985Date of Patent: February 13, 1990Assignee: University of FloridaInventors: Michael D. P. Boyle, Kathleen J. Reis, Elia M. Ayoub
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Patent number: 4882270Abstract: There are provided monoclonal antibodies which react with human oncofetal ferritin and which do not react with human spleen ferritin or with liver ferritin; there are also provided monoclonal antibodies which react both with human placenta oncofetal ferritin and with human adult spleen ferritin. There is provided a process for producing clones producing such antibodies and such clones, and an assay for the detection of human breast cancer based on the determination of oncofetal ferritin, which assay is based on such monoclonal antibodies.Type: GrantFiled: January 22, 1988Date of Patent: November 21, 1989Inventor: Chaya Moroz
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Patent number: 4855226Abstract: A novel competitive assay for theophylline wherein caffeine-like (7-substituted) labeled conjugates are used to detect the presence and/or amount of theophylline present in a test sample. The use of such conjugates in a competitive assay for theophylline results in improved sensitivity of the assay method. Where the assay method is a nephelometric or turbidimetric inhibition immunoassay procedure, the assay was found to be less temperature dependent than prior art immunoassays.Type: GrantFiled: June 7, 1985Date of Patent: August 8, 1989Assignee: Beckman Instruments, Inc.Inventors: Alan J. Polito, Anthony K. Cheng
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Patent number: 4788138Abstract: A method for obtaining an actual linear standard curve in a sandwich type of immunoassay where a first antibody bound to an insoluble support and a second unbound labelled antibody complex with the antigen contained in a test sample to form an insoluble antibody:antigen:labelled antibody complex which is then detected. Unbound unlabelled first antibody and/or unbound unlabelled second antibody are added to the reaction mixture to divert excess antigen away from the desired end-product complex, thus rendering the antigen of interest the rate-limiting factor in the overall immunoreaction. This results in a pseudo first-order reaction which produces an actual linear standard curve.Type: GrantFiled: April 30, 1987Date of Patent: November 29, 1988Assignee: Beckman Instruments, Inc.Inventors: Ker-Kong Tung, Linda K. Cragle, Frederick W. Rood, Jr., Shih-Yun Lee
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Patent number: 4742000Abstract: Methods and procedures are described for the isolation of human progestin receptors and for the use of human progestin receptors as immunogens in producing both monoclonal and polyclonal antibodies. These antibodies are used for the detection of progestin receptors, such as the progesterone receptor both normal and cancerous tissues.Type: GrantFiled: May 2, 1986Date of Patent: May 3, 1988Assignee: University of ChicagoInventor: Geoffrey L. Greene
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Patent number: 4687732Abstract: A method for detecting a minute quantity of an inorganic or organic target molecule by combining it with a composition of a detecting agent for the target molecule which carries, by direct or indirect means, a visualization polymer. The visualization polymer is composed of multiple units of a visualization monomer which are covalently linked together directly or indirectly covalently linked together by coupling agents which bond to chemical groups of the monomer. The monomer may be an enzyme, a tagged polypeptide, a tagged polyol, a tagged polyolefin or a tagged carbohydrate. The detecting agent may be an antibody, an enzyme, a lectin, strand of a DNA receptor protein, avidin, streptavidin and the like. The visualization polymer produces a high degree of amplification for the detection of the target molecule.Type: GrantFiled: June 10, 1983Date of Patent: August 18, 1987Assignee: Yale UniversityInventors: David C. Ward, Jeffry J. Leary, David J. Brigati
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Patent number: 4668620Abstract: Background interference which disrupts the measurement of an analyte in enzyme immunoassays with samples is substantially diminished. In accordance with one embodiment of the invention, the serum sample is treated with a sufficient amount of a peracid compound, either organic or inorganic, for a time and under conditions sufficient to reduce or eliminate background interference contributed by serum components other than analyte. The peracid compound is readily quenched, without adversely affecting the assay compositions. In another embodiment of the invention a liqand for the interfering component of the sample, such as unconjugated enzyme which is inactive but antigenic, is mixed with the sample to be analyzed. The presence of the liqand substantially reduces or eliminates background interference from components of the sample other than analyte.Type: GrantFiled: February 22, 1984Date of Patent: May 26, 1987Assignee: Syntex (U.S.A.) Inc.Inventors: Richard Armenta, Ian Gibbons, John Olson
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Patent number: 4578350Abstract: An improved immunoassay for determining the presence of an analyte in a serum sample and conjugates therefor are described. The known method comprises combining the sample with a conjugate of the analyte and an enzyme and with a receptor for analyte, and determining the presence of analyte in the sample from the effect that the sample has on the enzymatic activity when compared to the enzymatic activity in the absence of analyte or in the presence of known amounts of analyte. The present invention resides in the conjugation to the enzyme label of a label protectant which allows modulation of the enzymatic activity to occur and minimizes background interference between the enzyme label and the sample, which would alter the enzymatic activity.Type: GrantFiled: September 23, 1983Date of Patent: March 25, 1986Assignee: Syntex (U.S.A.) Inc.Inventors: Richard D. Armenta, Ian Gibbons
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Patent number: 4560648Abstract: Composition and method are provided for enzyme immunoassays for high molecular weight proteins, such as ferritin. An enzyme is conjugated to the high molecular weight protein through a specific linking group. Usually, on the average, about 2 to 10 enzyme molecules are bonded to each protein molecule. In an assay, the conjugate competes with an unknown sample for receptor and the resulting enzymatic activity is compared to a standard for a determination of the presence and amount of protein in the unknown.Type: GrantFiled: September 23, 1983Date of Patent: December 24, 1985Assignee: Syntex (U.S.A.) Inc.Inventor: Richard Armenta
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Patent number: 4469787Abstract: A method and kit for determining the presence of a polyvalent ligand in an aqueous fluid. The method involves incubating the fluid with an immobilized antibody to the ligand to form an immobilized ligand-antibody complex, then incubating the immobilized ligand-antibody complex with a solution of a soluble complex of a second antibody (to the ligand) and a labeled binding protein, such as protein A. The labeled binding protein is specifically bound to the Fc portion of the second antibody. The unbound second antibody and labeled binding protein are washed from the immobilized complex, and the presence of bound labeled binding protein is determined as a measure of the concentration of the ligand in the aqueous fluid.Type: GrantFiled: May 14, 1982Date of Patent: September 4, 1984Assignee: Mallinckrodt Inc.Inventors: James W. Woods, John N. St. Denis, Dana A. Chapman
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Patent number: 4456690Abstract: The present invention relates to a method which eliminates centrifugation and decantation steps, to be performed in an automatic manner for carrying out specific binding assay tests, wherein liquid and solid phases are present.According to the invention, use is made of a specially designed device, consisting of a mixing reservoir into which is fitted snugly a mixer separator having a channel in the vertical axis of the mixer-separator. A rack holding a number of said mixing reservoirs containing the incubated reagents and analytes, capped with the mixer separators, is placed into a press-device designed to perform at a controlled rate a downward movement. The mixer separators are pushed downwards into the mixing reservoirs at a chosen rate for a preselected distance to complete the mass transport and separation operations. The separation devices are removed and either one of the separated phases can be measured in the desired analytical instrument for a quantitative or qualitative determination.Type: GrantFiled: June 29, 1982Date of Patent: June 26, 1984Assignee: Technion Research and Development Foundation, Ltd.Inventors: Michael Cais, Moshe Shimoni
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Patent number: 4454231Abstract: The present invention relates to a new technique and device for mass transfer of one or more components from one liquid phase to another liquid phase, involving a physical separation of said two phases.According to the new technique, the mass transfer and physical separation are carried out in the same device. The device consists of a mixing-reservoir into which is fitted snugly a mixer-separator, having a channel in the vertical axis of the mixer-separator. The two substantially immiscible liquid solutions are introduced into the mixing reservoir, the phases are thoroughly mixed, by moving the mixer-separator in and out the mixing reservoir. After the spontaneous separation into an upper and lower phase, the upper phase is removed by pushing in the mixer-separator said upper phase being accumulated in a collecting container.Type: GrantFiled: December 4, 1980Date of Patent: June 12, 1984Assignee: Technion Research and Development Foundation, Ltd.Inventors: Michael Cais, Moshe Shimoni
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Patent number: 4446238Abstract: The use of colloidal gold as a bright field light microscopic marker for the immunocytochemical localization of antigens in histological sections, namely the two step or the bridge immuno gold staining method.Type: GrantFiled: January 25, 1982Date of Patent: May 1, 1984Assignee: Janssen Pharmaceutica N.V.Inventors: Jan R. De Mey, Marc K. J. J. Moeremans