Multifield Plates Or Multicontainer Arrays Patents (Class 436/809)
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Patent number: 5541070Abstract: Methods to identify and characterize a candidate drug by detecting and recording its reactivity with each member of an antibody panel are described. A characteristic profile thus obtained can be compared with the profile obtained in an analogous manner for a ligand known to bind a target so as to identify compounds which also bind the target. A similarity in the analogously obtained characteristic profile of the candidate compound and the known ligand indicated that the candidate will bind a target as well.Type: GrantFiled: September 8, 1993Date of Patent: July 30, 1996Inventor: Lawrence M. Kauvar
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Patent number: 5532128Abstract: A method and apparatus for identifying molecular structures within a sample substance using an array having a plurality of test sites upon which the sample substance is applied. Each test site includes a probe formed therein to bond with an associated target molecular structure. An electrical signal is applied to the test site and the electrical properties of the test sites are detected to determine which probes have bonded to an associated target molecular structure.Type: GrantFiled: December 12, 1994Date of Patent: July 2, 1996Assignee: Houston Advanced Research CenterInventors: Mitchell D. Eggers, Michael E. Hogan, Kenneth L. Beattie, John Shumaker, Daniel J. Ehrlich, Mark Hollis
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Patent number: 5529899Abstract: The present invention is directed to a method of detecting dioxin-like compounds in a test sample. The test sample is contacted with a heteromer formed from a plurality of proteins, one of which is an inactive Ah receptor. If dioxin-like compounds are present in the test sample, they will bind to the Ah receptor causing it to dissociate from the heteromer as a complex containing active Ah receptor bound to a dioxin-like compound ligand. The presence of the complex is then detected. The process of the present invention can be practiced utilizing solid phase capture, competitive, and sandwich immunoassay test kit formats.Type: GrantFiled: July 27, 1993Date of Patent: June 25, 1996Assignee: Cornell Research Foundation, Inc.Inventors: Geoffrey D. Wheelock, John G. Babish
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Patent number: 5527681Abstract: A synthetic strategy for the creation of large scale chemical diversity is claimed. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis of an array of polymers that are based on a target polymer. The array includes systematically substituted versions of the target polymer.Type: GrantFiled: November 5, 1992Date of Patent: June 18, 1996Assignee: Affymax Technologies N.V.Inventor: Christopher P. Holmes
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Patent number: 5512432Abstract: A suspension of inert particles is prepared in an aqueous solution, to which an antibody or an antigen and a carrier-bound antigen or antibody, respectively, are added in any desired order. After centrifuging, the positive, weakly positive, or negative reaction can easily be recognized on the basis of a simple pattern.Type: GrantFiled: August 1, 1994Date of Patent: April 30, 1996Assignee: Stiftung Fur Diagnostische ForschungInventors: Yves Lapierre, Dieter Josef, Jean Adam, Susanne Greber-Widmer
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Patent number: 5503803Abstract: A miniaturized biological assembly provides a miniature capillary environment in which a liquid medium containing microscopic-size particulate material can be placed for study under a microscope. The assembly includes components which do not wet relative to the liquid medium. A sample chamber and second chamber are disposed adjacent one another to allow a selective exchange of material, such as nutrients, between the two chambers. The assembly provides an environment that can contain the liquid medium and material for a period of time sufficient to enable observation while preventing deterioration of the medium and material.Type: GrantFiled: August 9, 1994Date of Patent: April 2, 1996Assignee: Conception Technologies, Inc.Inventor: James F. Brown
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Patent number: 5501984Abstract: The unit has three rotors, namely a reagent rotor (1), a sample rotor (2) and a reaction rotor (3). Each rotor has seats for vessels, which are arranged in circles about the respective rotor axis. At least two of the rotors (1, 2) are arranged concentrically to one another. The rotors can be brought into a plurality of rotating positions in which at least one of the openings (5b, 7b, 8b) is located in a predetermined liquid handling position (LH position).A liquid handling unit (LH unit) comprises a liquid transfer needle (18) which is movable by a transfer needle moving apparatus in such a way that the movement path (23) crosses at least one LH position of each circle of openings (5b, 7b, 8b) on each rotor (1, 2, 3).It thus become possible with a simply designed layout to carry out a wide range of heterogeneous immunological analyses in a flexible manner.Type: GrantFiled: June 17, 1993Date of Patent: March 26, 1996Assignee: Boehringer Mannheim GmbHInventors: Meinrad Hofstetter, Klaus Leckebusch, Armin Panzer
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Patent number: 5494830Abstract: Apparatus for performing determinations of immune reactants (e.g., antigens, antibodies) in bodily fluids includes multiple test units having respective elongated rods with transversely-expanded tips at their distal ends. The tips are each coated with respective immune reactants (e.g., allergens) which react in a known manner with respective allergen-specific or allergen-binding antibodies in human serum. The test units are color-coded to identify the allergen coatings and are supported at their proximal ends and positionally identified on a strip. By correlating the color code to a chart, the specific immune reactant (e.g., allergen) coating can be easily identified. The supporting strip for the test unit has through-holes which frictionally engage the proximal ends of the test unit rods with a spacing that permits all of the supported test units to be simultaneously inserted into an assembly of reaction containers arranged in a linear array.Type: GrantFiled: August 25, 1994Date of Patent: February 27, 1996Inventor: Thomas T. Hubscher
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Patent number: 5491067Abstract: A vessel for conducting blood cell agglutination assays is disclosed. A barrier retains reactants in an upper chamber during incubation, then, in response to a force, permits reagents to enter a lower chamber containing a matrix for separating agglutination.Type: GrantFiled: July 16, 1993Date of Patent: February 13, 1996Assignee: Ortho Diagnostic Systems Inc.Inventors: Thomas M. Setcavage, Kathleen J. Reis, Donald M. Davies, Edward J. Mazur
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Patent number: 5486335Abstract: Disclosed are devices and methods for detecting the presence of a preselected analyte in a fluid sample. The invention provides a device comprising a solid substrate, typically on the order of a few millimeters thick and approximately a 0.2 to 2.0 centimeters square, microfabricated to define a sample inlet port and a mesoscale flow system. A sample is passed through the mesoscale flow system, and the restriction or blockage of flow through the flow system is detected as a positive indication of the presence of the analyte. The mesoscale flow system includes in one embodiment a primary sample flow channel extending from the inlet port, and a fractal region, in fluid communication with the flow channel, comprising bifurcations leading to plural secondary flow channels. The device may be adapted for operation in conjunction with a pump, for example, to induce flow of a sample through the flow system.Type: GrantFiled: April 24, 1995Date of Patent: January 23, 1996Assignee: Trustees of the University of PennsylvaniaInventors: Peter Wilding, Larry J. Kricka
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Patent number: 5482839Abstract: An automatic immunoassay apparatus utilizes cartridges each having at least two wells, a first well of said wells containing solid phase material carrying antigen or antibody, a second well of said wells containing antibody or antigen labelled with labelling compound. The wells may be sealed with a suitable sealing film before use and the sealing film is broken when the cartridge is to be used. The cartridges are transported to a predetermined position on a steppingly movable reaction line and conveyed thereby at a predetermined interval. While the reaction line steps, a sample, labelled antigen or antibody contained in the second well and substrate, if necessary, are added to the first well and stirred at predetermined timings and reaction between the sample and a reactive solution is measured under control of a control device having memory means storing operator selectable programs for various measuring methods.Type: GrantFiled: May 4, 1993Date of Patent: January 9, 1996Inventors: Yoshihiro Ashihara, Isao Nishizono, Hidetaka Minakawa, Masahisa Okada, Yasusuke Sakurabayashi, Fumio Watanabe, Shin-ichi Wakana
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Patent number: 5478747Abstract: Test reagents incorporate immunological materials capable of recognizing specific antigens or antibodies in test sample. The materials are selected to respond differently to a control product such that they are used as a switch to control the operation of an analytical instrument.Type: GrantFiled: February 22, 1993Date of Patent: December 26, 1995Assignee: E. I. Du Pont de Nemours and CompanyInventor: Thomas P. Hartz, Jr.
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Patent number: 5460783Abstract: An apparatus for automatically removing well-strips from well-strip holders. The apparatus includes a frame and a base plate for receiving a plurality of well-strip holders, each holder having a plurality of well-receiving areas and corresponding apertures with the individual wells of the well-strips positioned in the areas so as to overlie the apertures. A pneumatically-operated movable drive member is attached to the frame so as to be movable in a substantially vertical direction toward and away from the base plate and well-strip holders. The movable member has a plurality of well-strip engaging portions secured to the underside thereof, each portion including a plurality of pegs that pass into the open end of the apertures formed in the well-strip holders to contact the well-strips and remove same from the holders.Type: GrantFiled: June 14, 1994Date of Patent: October 24, 1995Assignee: Synbiotics CorporationInventors: Nelson S. Hautea, Kenneth L. Aeschbacher, William B. Freese
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Patent number: 5460940Abstract: Methods and cards for detecting an antigen or antibody in a fluid sample are disclosed. The fluid sample is added to a microreaction vessel containing a slurry suspension of inert particles and a binding partner to the antigen or antibody to be determined. The fluid sample is added to the micro reaction vessel, with one of the antigen and antibody binding partners being carrier bound. The vessel contents are centrifuged, to cause the binding partners to contact each other to form an optically detectable binding complex. The location of the optically detectable complex is observed to determine the presence of the antibody.Type: GrantFiled: January 4, 1995Date of Patent: October 24, 1995Assignee: Stiftung fur diagnostische ForschungInventors: Lapierre Yves, Dieter Josef, Jean Adam, Susanne Greber-Widmer
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Patent number: 5445934Abstract: A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.Type: GrantFiled: September 30, 1992Date of Patent: August 29, 1995Assignee: Affymax Technologies N.V.Inventors: Stephen P. A. Fodor, Michael C. Pirrung, J. Leighton Read, Lubert Stryer
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Patent number: 5441645Abstract: An analyzer system for automatic column chromatography includes chromatographic columns which are mounted in a rack. A drop removal mechanism system shakes the rack to transfer the last drop of eluate from the tip of a chromatographic column to a receptacle below the tip before the column is repositioned over another receptacle and another fluid or operation is introduced into the column. This prevents one eluate from contaminating another. The chromatographic column may have an upper end which is sealed by a foil member. During use, the foil member is ruptured by lowering a pressure cylinder with a seal-punching head against it. The pressure cylinder, which is part of the pressure tip unit, is then withdrawn so that fluid can be introduced into the column via the ruptured foil member. The pressure tip unit is then lowered into sealing engagement with the column so that pressure can be applied via a bore in the pressure cylinder.Type: GrantFiled: September 16, 1994Date of Patent: August 15, 1995Assignee: Helena Laboratories CorporationInventors: James R. M. Sanford, Patrick M. Frank, Joseph H. Golias, William C. Jennings
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Patent number: 5441894Abstract: An improved device is used for performing solid-phase chemiluminescent immunoassays. The device comprises a container having a fibrous matrix and a porous absorbent material. An improvement in the device is the use of light absorbing material as the absorbent material or as a light barrier between the fibrous matrix and the absorbent material. A second improvement comprises a fibrous matrix of binderless fiber matrix, such as glass fiber. The invention improves the direct measurement of the chemiluminescent signal from a solid surface by reducing background signal. The device is disposable and is suitable for manual use or for use with an apparatus having programmed instructions. The device is designed to be employed in a variety of solid-phase diagnostic assays such as sandwich or competitive binding assays. The device is also designed for use with microparticle capture or ion capture methods of separating the immunochemical reaction products.Type: GrantFiled: April 30, 1993Date of Patent: August 15, 1995Assignee: Abbott LaboratoriesInventors: Carole L. Coleman, Kevin R. Genger, Hugh W. Graham, Charles F. Hanna, Omar S. Khalil, David C. Wender
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Patent number: 5441895Abstract: A stack of a plurality of substantially identical cup-like vessels pre-incorporated with reagent on the inside, each of the vessels occupying at least about 50% of the depth of the next adjacent vessel to maximize stacking density. Because the pre-incorporated reagent overlaps the occupied depth portion of the vessel and therefore runs a risk of being dislodged, the wall of the vessel is constructed to provide a gap between the inside surface bearing the reagent, and the outside surface of the occupying, nested vessel, that is at least 0.025 mm.Type: GrantFiled: December 7, 1993Date of Patent: August 15, 1995Inventors: Raymond F. Jakubowicz, Johannes J. Porte
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Patent number: 5434049Abstract: A method for simultaneously detecting a plurality of target polynucleotides in a sample on a single reaction chip and a method for separating a plurality of target polynucleotides are provided. On the reaction chip are arranged a plurality of independent cells for capturing different target polynucleotides. Different probes are immobilized onto the individual cells, and labeled probes detect the cells where the target polynucleotides are captured, thereby analyzing the species of the captured target polynucleotides. Also, the individual cells function as electrodes to elute the captured target polynucleotides therethrough, thereby separating a plurality of the target polynucleotides.Type: GrantFiled: February 24, 1993Date of Patent: July 18, 1995Assignee: Hitachi, Ltd.Inventors: Kazunori Okano, Hideki Kambara
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Patent number: 5427946Abstract: Devices and methods are provided for the clinical analysis of a sperm sample. The devices include a solid substrate, typically on the order of a few millimeters thick and approximately 0.2 to 2.0 centimeters square, microfabricated to define a sample inlet port and a mesoscale flow channel extending from the inlet port. In one embodiment, a sperm sample is applied to the inlet port, and the competitive migration of the sperm sample through the mesoscale flow channel is detected to serve as an indicator of sperm motility. In another embodiment, the substrate of the device is microfabricated with a sperm inlet port, an egg nesting chamber, and an elongate mesoscale flow channel communicating between the egg nesting chamber and the inlet port. In this embodiment, a sperm sample is applied to the inlet port, and the sperm in the sample are permitted to competitively migrate from the inlet port through the channel to the egg nesting chamber, where in vitro fertilization occurs.Type: GrantFiled: January 21, 1994Date of Patent: June 27, 1995Assignee: Trustees of the University of PennsylvaniaInventors: Larry J. Kricka, Peter Wilding
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Patent number: 5427959Abstract: On a slab-like board formed of a transparent material is closely attached a wedge-shaped transparent cover member provided with a recess in a central inner portion, thereby to form a clearance. The height of the clearance between the recess and the board is configured to decrease continuously or in steps. When an immunological active substance such as a monoclonal antibody is caused to sensitize carrier particles F, and a reagent having the carrier particles F dispersed into a liquid medium mainly composed of the water is mixed with a specimen, the reaction will occur in which the flocculate is formed from plural carrier particles. When this reaction liquid is poured into the clearance through the opening, the reaction liquid penetrates in the direction having a narrower vertical spacing due to surface tension. A single carrier particle unflocculated can move deep within the recess because it is small in diameter, but the flocculate G is trapped on its way and can not move because of its size.Type: GrantFiled: October 1, 1991Date of Patent: June 27, 1995Assignee: Canon Kabushiki KaishaInventors: Matsuomi Nishimura, Kazumi Tanaka, Takeshi Miyazaki, Hidehito Takayama, Toshikazu Ohnishi
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Patent number: 5424219Abstract: Methods of performing an assay for biomolecules and solid supports for use in such assays are disclosed. An activated polymeric material is used as a solid support for binding biomolecules. In a preferred form, the support is made of a generally hydrophobic, nonporous polymer which has been activated by treatment with solvents or by mechanical means to enhance the binding characteristics of the support. The support can be made of a copolymer, such as a copolymer of polystyrene and polybutadiene. Detection of bound biomolecules is preferably performed by means of staining reactions and gray level scanning. Emulsifying agents, such as detergents, can be applied to the surface of the support to substantially inhibit additional materials from being bound to the support.Type: GrantFiled: October 25, 1991Date of Patent: June 13, 1995Assignee: Cytech Biomedical, Inc.Inventor: Gustav F. Jirikowski
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Patent number: 5424186Abstract: A method for synthesizing oligonucleotides on a solid substrate. The method provides for the irradiation of a first predefined region of the substrate without irradiation of a first predefined region of the substrate. The irradiation of a second predefined region of the substrate. The irradiation step removes a protecting group therefrom. The substrate is contacted with a first nucleotide to couple the nucleotide to the substrate in the first predefined region. By repeating these steps, an array of diverse oligonucleotides is formed on the substrate.Type: GrantFiled: December 6, 1991Date of Patent: June 13, 1995Assignee: Affymax Technologies N.V.Inventors: Stephen P. A. Fodor, Lubert Stryer, Michael C. Pirrung, J. Leighton Read
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Patent number: 5418171Abstract: The present invention relates to an apparatus for determining the presence or absence of a target analyte in a liquid sample, comprising:(i) a container capable of accommodating the liquid sample and having a transparent portion; and(ii) an insertion member which is capable of being inserted into the container comprising;a porous member which has a main surface and a reverse surface and which has on the main surface a substance capable of specifically binding to the target analyte; andan absorbent bonded to the reverse surface of the porous member;the porous member being supported in the insertion member whereby, when the insertion member is inserted into the container, the main surface can be observed from the outside of the container through the transparent portion of the vessel and the liquid sample is absorbed into the absorbent through the porous member.According to the analyzer of the present invention, the presence or absence of a target analyte in a sample can be easily determined.Type: GrantFiled: November 30, 1992Date of Patent: May 23, 1995Assignee: Meiji Seika Kabushiki KaishaInventors: Fumio Kimura, Naohisa Koizumi, Koichi Matsuo, Minoru Aoyagi, Kiyomi Harakawa
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Patent number: 5407640Abstract: A sample container holder is provided for gripping a sample container which contains a sample. The sample container holder comprises a body having a bore for receiving a sample container. A flexible element is disposed within the bore. A fluid passage is operatively connected with the flexible element for supplying a fluid to the flexible element such that, when the sample container is received in the bore in the body of the sample container holder, the flexible element engages the sample container with a conforming, cushioning compression of sufficient magnitude to resist removal of the container from the bore.Type: GrantFiled: December 6, 1993Date of Patent: April 18, 1995Assignee: Abbott LaboratoriesInventor: Kenneth E. Iles
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Patent number: 5384261Abstract: A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are flowed through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.Type: GrantFiled: November 22, 1991Date of Patent: January 24, 1995Assignee: Affymax Technologies N.V.Inventors: James L. Winkler, Stephen P. A. Fodor, Christopher J. Buchko, Debra A. Ross, Lois Aldwin
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Patent number: 5382512Abstract: The invention describes an assay device and assembly for detecting an analyte in a liquid sample. Each assay device in the assembly includes structure defining a well, a ligand-coated particle, and a flexible particle retaining structure for holding the particle in a captured position within the well.Type: GrantFiled: August 23, 1993Date of Patent: January 17, 1995Assignee: Chiron CorporationInventors: Rick T. Smethers, Brian D. Warner
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Patent number: 5380650Abstract: In an assay in which a ligand is labelled by conjugation to a dihydrophthalazinedione (DPD), e.g. luminol or isoluminol, and the conjugated DPD is reacted with an oxidant, e.g. hydrogen peroxide, and an active heme group catalyst, e.g. microperoxidase, the light intensity is enhanced by certain sterically hindered amines defined as saturated bicyclic compounds having a nitrogen atom at one or both bridgehead positions or a piperidine ring compound having four C.sub.1-4 alkyl groups at the 2- and 6- positions. 1,4-Diazabicyclo[2.2.2]-octane, known as "DABCO" is preferred.Type: GrantFiled: March 23, 1989Date of Patent: January 10, 1995Assignee: British Technology Group Ltd.Inventors: Geoffrey J. R. Barnard, Dean Goodwin, Robert S. Davidson
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Patent number: 5378433Abstract: A sample rack with at least one receptacle for the accommodation of respective sample tubes. At least one receptacle has a removable adapter sleeve located within it for receiving a corresponding sample tube. Additionally, locking means are included for fixedly engaging the adapter sleeve within the corresponding receptacle.Type: GrantFiled: November 15, 1993Date of Patent: January 3, 1995Assignee: Akzo N.V.Inventors: G. Scott Duckett, Michael L. Bishop
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Patent number: 5378638Abstract: An analysis element for the determination of an analyte in a liquid sample, especially for medicinal uses. A carrier layer (2) contains, in a reagent domain (4), a reagent applied in a defined pattern by an ink-jet process. The pattern comprises several sets (A, B, C) of compartments (11-20), the compartments (e.g. 11, 13, 15, 17, 19) of the same set (e.g. A) having the same chemical composition, the compartments (11, 13, 15, 17, 19 or 12, 16, 20) of different sets (A or B) containing different reagents and the compartments of different sets being arranged in alteration so that the compartments containing different reagents are close together but nevertheless spatially separated.Type: GrantFiled: May 20, 1993Date of Patent: January 3, 1995Assignee: Boehringer Mannheim GmbHInventors: Rolf Deeg, Eberhard Maurer, Sigmar Klose, Bernhard Kopfer, Reiner Babiel
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Patent number: 5372786Abstract: A method of holding a container with a container holder comprises the following steps. The container is received within a bore on the container holder, and a fluid is conveyed through a fluid passage operatively connected with a flexible element within the bore such that the flexible element engages the container to retain the container within the bore.Type: GrantFiled: December 8, 1993Date of Patent: December 13, 1994Assignee: Abbott LaboratoriesInventor: Kenneth E. Iles
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Patent number: 5364591Abstract: There are described a device and method for doing confined reactions such as PCR amplification and detection, wherein solids (e.g., beads) used to obtain separation between bound and "free" label reagents, are transferred from region to region, specifically through a wash liquid so as to wash off the "free" label reagent from the solids. Separate chambers have dividers that are overcome by piercing or by liquification, to create passageways for the transfer of the solids. The passageways remain contained within the device.Type: GrantFiled: June 1, 1992Date of Patent: November 15, 1994Assignee: Eastman Kodak CompanyInventors: Nancy F. Green, Thomas J. Cummins, Fred T. Oakes
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Patent number: 5358641Abstract: An analyzer system for automatic column chromatography includes chromatographic columns which are mounted in a rack. A drop removal mechanism system shakes the rack to transfer the last drop of eluate from the tip of a chromatographic column to a receptacle below the tip before the column is repositioned over another receptacle and another fluid or operation is introduced into the column. This prevents one eluate from contaminating another. The chromatographic column may have an upper end which is sealed by a foil member. During use, the foil member is ruptured by lowering a pressure cylinder with a seal-punching head against it. The pressure cylinder, which is part of the pressure tip unit, is then withdrawn so that fluid can be introduced into the column via the ruptured foil member. The pressure tip unit is then lowered into sealing engagement with the column so that pressure can be applied via a bore in the pressure cylinder.Type: GrantFiled: May 10, 1993Date of Patent: October 25, 1994Assignee: Helena Laboratories CorporationInventors: James R. M. Sanford, Patrick M. Frank, Joseph H. Golias, William C. Jennings
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Patent number: 5356785Abstract: In one aspect, a kit for the semi-quantitative measurement, in a liquid sample, by competitive immunoassay, of a first member of a specific binding pair, the kit including a solid support bearinga reference area which provides a detectable signal in the immunoassay, anda first and a second test area exposed to contact the sample, each test area containing a different amount of second or first member of the specific binding pair,whereby the intensity of the detectable signal from the reference area can be compared with the intensity of any detectable signals from the first and second test areas in the presence of an unknown quantity of the first member in the sample.Type: GrantFiled: May 2, 1991Date of Patent: October 18, 1994Assignee: Idexx Laboratories, Inc.Inventors: Philip McMahon, Larry Chaney, Quentin Tonelli
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Patent number: 5354660Abstract: The present invention is directed to a method and a kit for diagnosing active human neurocysticercosis utilizing an immunoblot assay which comprises:detecting the presence of antibodies in the serum or cerebrospinal fluid of a human to be diagnosed, wherein the antibodies are reacted with Taenia solium larval antigens which have been isolated by lentil lectin affinity. The larval antigens are designated GP50, GP42, GP24, GP21, GP18, GP14, and GP13, wherein GP indicates that said antigen is a glycoprotein and the number indicates the molecular weight in K daltons, as determined by SDS-PAGE.Type: GrantFiled: April 2, 1992Date of Patent: October 11, 1994Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Victor C. W. Tsang, Joy A. Brand, Anne E. Boyer, Marianna Wilson, Peter M. Schantz, Shirley E. Maddison
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Patent number: 5338689Abstract: A method of detecting target antibodies or antigens by reaction with specific binding partners thereto is disclosed. One of the target or the binding partner is bound to a carrier, and the other is unbound. The complex between the target and the binding partner, with one being carrier-bound, forms an optically detectable binding complex. A microreaction vessel having an upper portion, a transition portion and a lower portion is utilized, wherein the upper portion has a greater diameter or width than the lower portion, and the transition portion is situated between the upper portion and the lower portion, and is funnel shaped. The microreaction vessel contains a slurry or suspension of inert particles, and unbound target or binding partner thereto. A solution of the carrier bound target or binding partner thereto is added to the vessel, which is then centrifuged to produce an optical determination of the target.Type: GrantFiled: October 30, 1992Date of Patent: August 16, 1994Assignee: Stiftung fur diagnostische ForschungInventors: Lapierre Yves, Dieter Josef, Jean Adam, Susanne Greber-Widmer
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Patent number: 5324633Abstract: A method and device for measuring the binding affinity of a receptor to a ligand. According to one aspect of the invention, arrays of polymers are synthesized or immobilized on a substrate (212). The array of polymers is exposed to a fluorescently-labelled receptor in solutions of varying concentration. The fluorescence intensity of the labelled receptor is measured by way of, e.g., a photon counter using a confocal microscope (316). Binding affinity is determined through analysis of the relationship between fluorescence intensity and the solution concentration of the receptor. On-rates are measured as a kinetic increase in surface fluorescence intensity, and the on-rate constant rate extracted from fits to the data.Type: GrantFiled: November 22, 1991Date of Patent: June 28, 1994Assignee: Affymax Technologies N.V.Inventors: Stephen P. A. Fodor, Laura T. Mazzola
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Patent number: 5308757Abstract: In determining the effectiveness of parameters on cells, after treatment of the cells with one or more selected parameters, the results of the treatment can be quickly determined by measuring the number n.sub.0 of cells having a predetermined cell form, subsequently mechanically stressing the cells for a sufficient period of time t to change the cell form substantially, thereafter again measuring the number n of cells having the predetermined cell form, and determining the cell viability .tau.defined by .tau.=t/1n(n.sub.0 /n).Type: GrantFiled: August 8, 1991Date of Patent: May 3, 1994Assignees: Hitachi, Ltd., Hitachi Koki Co., Ltd.Inventors: Yoshio Kawamura, Yoshu Yoshiba, Shinji Tanaka, Kazuo Sato, Jiro Kikuchi, Kahoru Takahashi
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Patent number: 5307144Abstract: The present invention intends to generally maintain the microplate having added test samples in wells therein at even temperature for measuring biochemical or biological reaction accompanying changes in absorbance such as enzyme reaction. Monochromatic lights with various wave lengths from a light source 3 are transmitted through the test samples added to a plurality of wells in a microplate 1 to measure absorbance of the test sample. For this end, a metal plate 2 with good heat conductivity is substantially contacted with the bottom of each well in the microplate 1 and a perforated board 7 is disposed with an air space over the microplate 1 at the starting position thereof. Warmed air heated by a heater 17 is blown onto the microplate 1 through the perforated board 7 and is circulated along the metal plate 2 within a chamber 9.Type: GrantFiled: December 1, 1992Date of Patent: April 26, 1994Assignee: Seikagaku Kogyo Kabushiki KaishaInventors: Tamura Hiroshi, Tanaka Shigenori
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Patent number: 5306510Abstract: An improved automated pipetting system for programmingly pipetting predetermined quantities of liquid between preselected groups of test tubes, vials or wells arranged on a horizontal table. A substantially rigid overhead frame mounted over the table on which the test tube arrays or the like are arranged. A pair of parallel X-axis guide shafts mounted in the rigid frame. A pair of helical screws rotatably mounted in the frame parallel to the pair of X-axis guide shafts. Each helical screw is driven by a stepper motor coaxially connected thereto. A pair of X-axis roller sections are movably mounted on the pair of X-axis guide shafts and support a Z-axis probe mechanism via a pair of Y-axis guide shafts and a parallel Y-axis helical screw. A stepper motor is drivingly and coaxially connected to the Y-axis screw for moving the Z-axis probe mechanism along the Y-axis guide shafts. The Z-axis probe mechanism is movably mounted on the pair of Y-axis guide shafts.Type: GrantFiled: February 1, 1991Date of Patent: April 26, 1994Assignee: Cyberlab, Inc.Inventor: Walter Meltzer
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Patent number: 5306469Abstract: A holder is pneumatically actuated to grasp and hold a plurality of sample containers during an analytical process which requires movement of the containers. The holder comprises a body having holes therein for receiving the caps and upper portions of the containers. Within each hole is a rigid cylindrical element and within each rigid element is a flexible tubular element. The outer diameter of the flexible element is smaller than the inner diameter of the rigid element so that a pneumatically sealed chamber is formed between the two elements when the ends of the flexible element are folded back over the ends and outer surface of the rigid element. The holder body and the rigid element are provided with holes forming a fluid passage through which positive and negative pressures may be applied to the chamber. When a negative pressure is applied to the chamber to draw the flexible element outward toward the rigid element, the cap and upper portion may move freely into the flexible element.Type: GrantFiled: July 2, 1993Date of Patent: April 26, 1994Assignee: Abbott LaboratoriesInventor: Kenneth E. Iles
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Patent number: 5304487Abstract: Devices are provided for analyzing a fluid cell containing sample. The devices comprise a solid substrate, microfabricated to define at least one sample inlet port and a mesoscale flow system. The mesoscale flow system includes a sample flow channel, extending from the inlet port, and a cell handling region for treating cells disposed in fluid communication with the flow channel. The devices may further include a structure inducing flow of cells in the sample through the flow system. In one embodiment, the cell-handling region may comprise a cell lysis structure to enable the lysis of cells in the sample, prior to, e.g., the detection of an intracellular component in the cell sample. In another embodiment, the cell handling region may comprise a cell capture region, comprising binding sites which reversibly bind to a specific population of cells in the cell sample, to permit the isolation of the specific cell population from the sample.Type: GrantFiled: May 1, 1992Date of Patent: April 19, 1994Assignee: Trustees of the University of PennsylvaniaInventors: Peter Wilding, Larry J. Kricka, Jay N. Zemel
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Patent number: 5300425Abstract: Screening methods to obtain suitable antibodies for use in immunoassays for analytes not ordinarily susceptible to detection by these methods involves in vitro screening of panels of cells secreting a representative selection of antibodies. An application of this method also permits the preparation of specific mimotopes which mimic the immunological activity of the desired analyte, which mimotopes can then be used as competitors in the immunoassay or can be used to immunize subject mammals in order to improve the specificity and affinity of the antibodies. Methods to identify a particular analyte by its pattern of binding strength to a panel of related antibodies and to match an arbitrary analyte with an immunoreactive member of a panel of candidate antibodies are also disclosed. These screening methods can also be employed for rational drug design.Type: GrantFiled: December 6, 1989Date of Patent: April 5, 1994Assignee: Terrapin Technologies, Inc.Inventor: Lawrence M. Kauvar
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Patent number: 5296375Abstract: Devices and methods are provided for the clinical analysis of a sperm sample. The devices comprise a solid substrate, typically on the order of a few millimeters thick and approximately 0.2 to 2.0 centimeters square, microfabricated to define a sample inlet port and a mesoscale flow channel extending from the inlet port. In one embodiment, a sperm sample is applied to the inlet port, and the competitive migration of the sperm sample through the mesoscale flow channel is detected to serve as an indicator of sperm motility. In another embodiment, the substrate of the device is microfabricated with a sperm inlet port, an egg nesting chamber, and an elongate mesoscale flow channel communicating between the egg nesting chamber and the inlet port. In this embodiment, a sperm sample is applied to the inlet port, and the sperm in the sample are permitted to competitively migrate from the inlet port through the channel to the egg nesting chamber, where in vitro fertilization occurs.Type: GrantFiled: May 1, 1992Date of Patent: March 22, 1994Assignee: Trustees of the University of PennsylvaniaInventors: Larry J. Kricka, Peter Wilding
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Patent number: 5273718Abstract: An apparatus for carrying out biochemical reactions in microtiter plates includes a device (42, 43) for receiving and holding microtiter plate (44) to be processed, the microtiter plate being provided with a plurality of wells and each well having a bottom outlet, and a movably mounted device (47) for the application of gas pressure to the wells of the microtiter plate (44), the pressure device including a sealing collar (48) and being movable between a position where it leaves the upper part of the microtiter plate accessible, and a position where it sealingly contacts the microtiter plate through the sealing collar (48) so that a gas pressure may be applied to the inlets of the microtiter plate wells for pressing out liquid present therein through the bottom outlet of each well.Type: GrantFiled: March 19, 1992Date of Patent: December 28, 1993Assignee: Pharmacia LKB Biotechnology ABInventors: Sven-Erik Skold, Kent Andersson
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Patent number: 5266499Abstract: An apparatus and method for detecting antibodies specific to non-protein antigens. The apparatus is an immunological plate containing a plurality of plastic projections coated with a non-protein material. Assays utilizing the plate are capable of stabilizing the non-protein antigens with detection levels for antibodies specific to the antigens on a nanogram level. A screening assay with the apparatus allows for early detection of exposure to non-protein materials. Specifically metallic elements are detected.Type: GrantFiled: February 25, 1992Date of Patent: November 30, 1993Assignee: The United States of America as represented by the United States Department of EnergyInventors: Charles W. Barrick, Sara M. Clarke, Carl W. Nordin
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Patent number: 5262128Abstract: An injection device injects small amounts of injectate into each of a plurality of cells. A first plate, which may be made from a silicon chip, includes a large number of evenly spaced cell wells, in a regular array. Each well includes a through hole in the chip. A top plate, also formed from a silicon chip, includes a plurality of injection needles, arranged in a regular array corresponding to the position of the cell wells. A suspension of cells is washed over the first plate and individual cells are retained by the individual wells. A vacuum may be applied to the cell wells through a manifold beneath the first plate, thus to retain the cells in place. Excess cells and suspension are removed by washing the plate. The second plate, including the injection needles, is positioned on the first plate so that the needles pierce the plurality of cells retained in the wells, thus simultaneously introducing the injectate into a large number of individual cells.Type: GrantFiled: October 23, 1989Date of Patent: November 16, 1993Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Stephen B. Leighton, Michael J. Brownstein
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Patent number: 5256543Abstract: Physiological samples are typed for HLA-B27 by contacting the sample with an antibody which binds to HLA-B7 and is not cross-reactive between HLA-B7 and B27, separating the sample from any complexes which are formed, and then testing the sample for the presence of HLA-B27 with an antibody which is cross-reactive for HLA-B7 and B27 in a STAT test. Particularly, an enzyme conjugate is used which binds to a membrane allowing for the detection of any HLA-B27 bound to the membrane.Type: GrantFiled: May 10, 1991Date of Patent: October 26, 1993Assignee: Sangstat Medical CorporationInventors: Philippe Pouletty, Peter Chun
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Patent number: 5256376Abstract: A method and apparatus are provided for use with a centrifuge to analyze reactants. The apparatus includes at least one cuvette having at least one chamber. The chamber has a radially outward wall which provides a base upon which reactants can be pelleted when the device is rotated about a centrifugal axis. Each cuvette includes one or more openings for introducing fluids to the cuvette and includes a channel positioned adjacent to the radially outward wall for removing fluids from the chamber. Pressure is applied to the chamber to force fluids therefrom, through the channel. A hold down device is also provided through which fluid and/or pressure may be passed with respect to the cuvette. The invention also provides a method for determining the existence and degree of agglutination of reactants in a first fluid suspension and contained in a single reaction vessel using a photodetector.Type: GrantFiled: September 12, 1991Date of Patent: October 26, 1993Assignee: Medical Laboratory Automation, Inc.Inventors: Gerald W. Callan, William D. Corry, Richard E. Scordato, John G. Gorman
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Patent number: 5240861Abstract: A device for concentrating liquid specimens and the process of using the device. The device has a receptacle containing a membrane. The sample to be concentrated is placed in the receptacle on the upper surface of the membrane. A piston is then screwed down toward the upper surface of the membrane increasing the pressure above the membrane. The process for using the device involves supporting the device at a small angle from the vertical so that once the specimen has been concentrated to a given volume, the tilted membrane is exposed allowing air to reach the membrane and equalizing the pressure thereby rapidly decreasing any further concentration.Type: GrantFiled: July 29, 1988Date of Patent: August 31, 1993Assignee: Spectrum Medical Industries, Inc.Inventor: Daniel Y. Bieri