Enzyme Or Microbial Cell Is Immobilized On Or In An Inorganic Carrier Patents (Class 435/176)
  • Patent number: 5770416
    Abstract: Permeable substantially spherical hollow particles of 1-5000 .mu.m in size are formed having an outer shell of a mechanically rigid porous material. Pores of the shell are through-going pores that connect the inside of the particles to surroundings and allow chemical species to traverse the outer shell. To prepare the particles, impermeable hollow particles are treated with an acid or base under reflux conditions to form pores. The outer shell is formed of anhydrous forms of silicon dioxide, metal silicates, metal borosilicates, metal oxides or boric oxide. Metals and metal alloys are not used in forming the outer shell. Particles containing a polymer are formed by immersing the permeable hollow particles in a solution of components that polymerize to form the polymer, allowing the solution to partially fill the particles via the pores and polymerizing the components.
    Type: Grant
    Filed: June 3, 1993
    Date of Patent: June 23, 1998
    Assignee: UpFront Chromatography A/S
    Inventors: Allan Otto Fog Lihme, Thorkild Christian B.o slashed.g-Hansen, Claus Schafer Nielsen
  • Patent number: 5750103
    Abstract: A method for grafting a cell in the brain of a mammalian subject is accomplished by attaching the cell to a support matrix so that the cell attaches to the matrix surface, and implanting the support matrix with the attached cell into the brain. A syringe containing viable cells that are attached to a matrix surface may be used to transplant the cells into the brain or spinal cord of a mammalian subject. Preferred support matrices are glass or plastic microbeads, either solid or porous, having a diameter from about 90 to about 125 .mu.m. The method employs cells of different types, preferably cells of neural or paraneural origin, such as adrenal chromaffin cells. Also useful are cell lines grown in vitro. Cells not of neural or paraneural origin, such as fibroblasts, may also be used following genetic alteration to express a desired neural product such as a neurotransmitter or a neuronal growth factor.
    Type: Grant
    Filed: June 2, 1995
    Date of Patent: May 12, 1998
    Assignee: The New York University Medical Center
    Inventor: Bruce D. Cherksey
  • Patent number: 5747311
    Abstract: The present invention relates to a method for chemically modifying a reactant using microbes. The method includes providing a particulate material which includes a plastic carrier and microbes attached to the carrier. The particulate material is dispersed in a dispersing fluid and has a specific gravity less than that of the dispersing fluid. When the microbe is anaerobic the particulate material has an operating interfacial surface area of from about 2,000 to about 240,000 square meters per cubic meter of reactor volume. When the microbe is aerobic the particulate material has an operating interfacial surface area of from about 1,000 to about 30,000 square meters per cubic meter of reactor volume. The method further includes establishing a flow of the reactant through the particulate material effective to contact the reactant with the microbes for a time sufficient to chemically modify the reactant. Use of the methods in wastewater treatment, aquaculture fish production, and ethanol production are disclosed.
    Type: Grant
    Filed: August 22, 1995
    Date of Patent: May 5, 1998
    Assignee: Microgen Corporation
    Inventor: William J. Jewell
  • Patent number: 5747276
    Abstract: The present invention relates to screening methods for the identification of compounds and compositions useful as novel antibiotics and antibacterial agents. In particular, the present invention relates to methods utilizing two-component regulatory switches, for example, those comprising a prokaryotic enzyme such as histidine protein kinase that is activated to autophosphorylate by a signal transduction mechanism. The invention also relates to methods of identifying inhibitors of enzyme activity, particularly in bacterial cells. In particular, a high-throughput assay system useful in the large-scale screening of protein kinase inhibitors is disclosed.
    Type: Grant
    Filed: September 15, 1995
    Date of Patent: May 5, 1998
    Assignee: The Scripps Research Institute
    Inventors: James A. Hoch, Shaoming Huang
  • Patent number: 5741686
    Abstract: A method is provided for preparing a labeled protein, immobilized protein or protein-bioactive agent composition by attaching a label, support or bioactive agent to a protein by exopeptidase catalysis at a site that is remote from the active site of the protein. More specifically, an amine or alcohol group of an amino acid, amine or alcohol nucleophile is reacted by exopeptidase catalysis with a C-terminus carboxylic acid group of a protein such as an antibody, enzyme or hormone to couple the nucleophile to the protein to form an adduct, and the adduct is bound to an auxiliary substance such as a support, label or bioactive agent or its combination with a linker arm by reacting a reactive substituent of the nucleophile with a reactive group of the auxiliary substance. Alternatively, the nucleophile is bound to the auxiliary substance or its combination with a linker arm to form an intermediate, and the intermediate is coupled by exopeptidase catalysis to the protein.
    Type: Grant
    Filed: October 3, 1994
    Date of Patent: April 21, 1998
    Assignee: Board of Regents of the University of Nebraska
    Inventors: Fred W. Wagner, Thomas R. Coolidge, Dwane E. Wylie, Sheldon M. Schuster, William Lewis, Jay Stout
  • Patent number: 5739020
    Abstract: Living animal tissue cells and microbial cells such as yeast cells are encapsulated in an inorganic gel prepared from an organosilicon. Encapsulation of tissue cells is performed by mixing an organosilicon precursor with a highly acidic aqueous solution to hydrolyze the organosilicon precursor and provide a gel forming solution, cooling the gel forming solution, forming a mixture of living tissue cells and Hank's balanced salt solution, adding a base solution to the gel forming solution, immediately thereafter adding the mixture containing tissue cells to the gel forming solution, and pouring the resultant mixture into a container where an inorganic gel forms encapsulating the tissue cells. The organosilicon precursor may be tetraethoxysilane, tetrabutoxysilane, tetramethoxysilane or tetrapropoxysilane.
    Type: Grant
    Filed: January 10, 1995
    Date of Patent: April 14, 1998
    Inventor: Edward J. A. Pope
  • Patent number: 5736624
    Abstract: The present invention provides crosslinking, conjugating and reducing agents which are functional with at least one phosphorothioate monoester group (--SPO.sub.3.sup.-2). Crosslinking and conjugation methods as well as solid phase reagents and conjugates which are useful in immunoassays are also provided. Crosslinking and conjugating agents of the invention generally comprise a compound corresponding to the formula (I), shown below, wherein n is at least 1 and Q is a straight or branched monomer, polymer or oligomer having an average molecular weight between about 200 and about 1,000,000. Additionally, when n is 1, Q comprises at least 1 additional reactive functionality.Q--(S--PO.sub.3.sup.-2)n (I)The reducing agents that are provided conform to a compound of the formula (Y), shown below, wherein (A) and (Z) can be independently selected from C.sub.1 -C.sub.5 alkyl and CONH(CH.sub.2).sub.p wherein p is an integer between 1 and 5.
    Type: Grant
    Filed: December 2, 1994
    Date of Patent: April 7, 1998
    Assignee: Abbott Laboratories
    Inventors: Christopher Bieniarz, Douglas F. Young, Michael J. Cornwell, Mazhar Husain
  • Patent number: 5733763
    Abstract: An enzyme-containing granulate is prepared containing a core and a shell wherein the core and/or shell contain an enzyme and the shell contains artificial or cellulose fibers in an amount of 1.5-40%. The core may also contain the fibers in an amount of 1.5-40%. In a preferred embodiment, the core contains a primary enzyme, the fibers, a coating of a sustained release agent, and the shell contains a secondary enzyme and the fibers. The sustained release coating causes the primary enzyme to be released more slowly than the secondary enzyme in a washing solution. In another embodiment, the core contains a primary detergent additive, a coating of a protective agent, and the shell contains a secondary detergent additive and the fibers. The protective coating separates the primary and secondary detergent additives so they do not harm each other during storage. Preferably, the core and shell also contain a binder, a filler and a granulating agent.
    Type: Grant
    Filed: May 1, 1996
    Date of Patent: March 31, 1998
    Assignee: Novo Nordisk A/S
    Inventors: Erik Kj.ae butted.r Markussen, Per Falholt
  • Patent number: 5734020
    Abstract: Magnetic porous inorganic siliceous materials having a particle size of about 1 to about 200 microns useful as solid supports in various chromatography, immunoassays, synthesis and other separation and purification procedures is disclosed.
    Type: Grant
    Filed: June 2, 1995
    Date of Patent: March 31, 1998
    Assignee: CPG, Inc.
    Inventor: Yuan N. Wong
  • Patent number: 5723304
    Abstract: The invention relates to a method of detection, a sensor and a test-kit which find application in immunological detection (e.g., immunoassay). The invention provides, inter alia, a method of detection, suitable for use in immunological detection of an entity, which method includes the use of a secondary species (as defined in the specification), the use of a first detectable species, and the use of a second detectable species. The method may include, for example, the use of a primary species, a secondary species, a first detectable species and a second detectable species. The primary species may be, for example, an antibody or a ligand. The secondary species may be, for example, an auxiliary species such as an auxiliary binder or an auxiliary ligand, or a species which has a part which is an auxiliary function. The entity to be detected may be an analyte species as such or may be an entity which carries or includes analytes species.
    Type: Grant
    Filed: February 27, 1995
    Date of Patent: March 3, 1998
    Assignee: GEC-Marconi Limited
    Inventor: Ramadan Arbi Abuknesha
  • Patent number: 5723325
    Abstract: Compositions containing two species of indolyl-3-alkane alpha-hydroxylase (INDH) are isolated from Pseudomonas XA. An INDH1 composition contains protein subunits having molecular weights of 75,000, 34,500 and 32,500 daltons. An INDH2 composition contains protein subunits having molecular weights of 60,000, 44,000 and 42,000 daltons. Molecular weights are determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The compositions have a Specific INDH Activity of at least 10 international Units of INDH activity per milligram of protein, and contain less than 1 nanogram of endotoxin per International Unit of Specific INDH Activity. The INDH compositions may be immobilized on an insoluble matrix such as silica beads to provide at least 2.5 international Units of INDH activity per gram of Immobilized INDH composition. The INDH compositions are isolated by lysing Pseudomonas XA cells at a temperature of no more than 15.degree. C.
    Type: Grant
    Filed: May 16, 1996
    Date of Patent: March 3, 1998
    Assignee: Automedix Sciences, Inc.
    Inventors: Robert L. Murtfeldt, Allan J. Bream, Kathryn K. McCarthy
  • Patent number: 5719051
    Abstract: The invention resides in a matrix, i.e. in a carrier material, with human or animal cells adherently bound thereto, the cells being infected with virus. It has shown that surface-dependent cells suitable for virus propagation remain adherently bound to a matrix even in the virus-infected state, continuously produce virus antigen over relatively long periods of time and deliver them into the culture medium. For producing TBE virus antigen by growing tick-borne encephalitis (TBE) virus in cell cultures, a surface-dependent permanent cell line, preferably the Vero cell line ATCC CCL 81, is inoculated with TBE virus, and the cells are kept bound to carriers in a non-lyric serum-free system while maintaining the cell growth, so as to maintain antigen formation, whereupon the antigen-containing medium is separated form the carrier-bound cells and, in a known manner, is processed to a galencially acceptable preparation by concentration, inactivation and purification.
    Type: Grant
    Filed: December 13, 1994
    Date of Patent: February 17, 1998
    Assignee: Immuno Aktiengesellschaft
    Inventors: Wolfgang Mundt, Noel Barrett, Friedrich Dorner, Johann Eibl
  • Patent number: 5717075
    Abstract: A solid support having surface-attached carboxylic acid groups is reacted with an isoxazolium salt to form an activated support having enol ester and sulfonate groups. After washing to remove residual isoxazolium salt and base, the activated support is dried. A polypeptide is covalently or non-covalently bound to the support. The resultant immobilized polypeptide can be conveniently sequenced by N- and C-terminal sequencing methods. The support can be a polyvinylidene difluoride membrane or a glass fiber membrane having surface attached carboxylic acid groups, and the enol and sulfonate groups are provided by reacting the support with 2-ethyl-5'-phenylisoxazolium sulfonate. The dry support can be stored for at least about 3 months to achieve a peptide immobilization yield that is substantially the same as the yield obtained in the absence of drying.
    Type: Grant
    Filed: March 28, 1996
    Date of Patent: February 10, 1998
    Assignee: The Perkin-Elmer Corporation
    Inventors: Victoria Lee Boyd, Pau-Miau Yuan
  • Patent number: 5707859
    Abstract: Two-dimensional microcarriers for culture of anchorage dependent cells are formed having two opposed and parallel anchorage surfaces and a thickness so thin that cells attach only to the surfaces and not between the surfaces. Preferably, each of the surfaces is less than about 500 microns in each of its two dimensions, the thickness is not more than about 35 microns, the microcarriers have a shape resulting from the orthogonal or oblique intersection of two parallel planes separated by a distance of not more than 35 microns with a solid cylinder and the microcarriers are made from a hydrophobic polymeric material such as polystyrene, polycarbonate or polyterephthalate. The microcarriers can be microdisks having a density of between 0.90 and 1.10 g/cm.sup.3. The anchorage surfaces may be treated to enable cell attachment by applying a thin metallic deposit such as a titanium deposit or by electrical corona discharge. The microcarriers may be transparent to light waves and capable of withstanding sterilization.
    Type: Grant
    Filed: December 1, 1993
    Date of Patent: January 13, 1998
    Assignee: Nunc, A/S
    Inventors: Alain O. A. Miller, Guy De Hollain, Dominique Masquelier
  • Patent number: 5702910
    Abstract: The present invention relates to a sandwich immunoassay for rapidly and readily measuring N-peptide using two kinds of monoclonal antibodies recognizing different portions of the N-peptide. The method for measuring N-peptide or a precursor thereof includes the steps of: incubating a mixture containing a sample and a first monoclonal antibody recognizing a portion of N-peptide; adding a labelled second monoclonal antibody recognizing a portion of N-peptide to the mixture, followed by further incubation; and detecting the resulting antigen-antibody complex in the mixture. Alternatively, the method includes the steps of: incubating a mixture containing a sample, a first monoclonal antibody recognizing a portion of N-peptide, and a labelled second monoclonal antibody recognizing another portion of N-peptide; and detecting the resulting antigen-antibody complex.
    Type: Grant
    Filed: December 8, 1995
    Date of Patent: December 30, 1997
    Assignee: Shionogi & Co., Ltd.
    Inventors: Yoshito Numata, Hidehisa Asada, Keiji Dohi, Takahiro Fukunaga, Yasushi Taniguchi
  • Patent number: 5695968
    Abstract: The present invention is directed to a gene which is related to a D-N-carbamoyl-.alpha.-amino acid amidohydrolase which is an enzyme capable of converting D-N-carbamoyl-.alpha.-amino acids into D-.alpha.-amino acids; a recombinant plasmid in which a DNA fragment containing the gene is incorporated into a vector; a microorganism belonging to the genus Escherichia, Pseudomonas, Flavobacterium, Bacillus, Serratia, Corynebacterium, or Brevibacterium, which is transformed by incorporating the recombinant plasmid thereinto; a process for the production of D-N-carbamoyl-.alpha.-amino acid amidohydrolases, comprising the steps of cultivating the transformed microorganism and collecting the desired product therefrom; a D-N-carbamoyl-.alpha.-amino acid amidohydrolase obtained by the method; and a process for the production of D-.alpha.-amino acids with the aid of an action of the enzyme.The D-N-carbamoyl-.alpha.-amino acid amidohydrolase can be fixed on a support for immobilization and used as an immobilized enzyme.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: December 9, 1997
    Assignee: Kanegafuchi Kagaku Kogyo Kabushiki Kaisha
    Inventors: Hirokazu Nanba, Yukio Yamada, Masayuki Takano, Yasuhiro Ikenaka, Satomi Takahashi, Kazuyoshi Yajima
  • Patent number: 5693513
    Abstract: Living tissue cells such as animal or plant tissue cell are encapsulated in an inorganic gel by mixing an organosilicon precursor with an aqueous acidic solution to form a gel forming solution and hydrolyze the organosilicon precursor, cooling the gel forming solution, forming a mixture of living tissue cells and Hank's balanced salt solution, adding a base solution to the gel forming solution to form a mixture, immediately thereafter adding the mixture containing living tissue cells to the mixture containing the gel forming solution, and pouring the resultant mixture into a container where an inorganic gel forms encapsulating the cells. The organosilicon precursor may be tetraethoxysilane, tetrabutoxysilane, tetramethoxysilane or tetrapropoxysilane.
    Type: Grant
    Filed: November 8, 1995
    Date of Patent: December 2, 1997
    Inventor: Edward J. A. Pope
  • Patent number: 5688642
    Abstract: Patterns of pre-formed hybridizable nucleic acid oligomers are formed upon a substrate. The substrate is coated with molecules, such as aminosilanes, whose reactivity with nucleic acid molecules can be transformed by irradiation. The coated substrate exposed to patterned irradiation then contacted with pre-formed nucleic acid oligomers. The binding of the preformed nucleic acid oligomers to the coating molecules may be covalent or non-covalent (for example, ionic bonding or hydrogen bonding). If desired, a heterobifunctional crosslinker may be employed, before or after irradiation, with the coating to promote covalent binding of the nucleic acid oligomers to the coating molecules. Also, the irradiation step may be performed with the assistance of a positive-tone or negative-tone photoresist.
    Type: Grant
    Filed: December 1, 1994
    Date of Patent: November 18, 1997
    Assignee: The United States of America as represented by the Secretary of the Navy
    Inventors: Linda A. Chrisey, Walter J. Dressick, Jeffrey M. Calvert
  • Patent number: 5674725
    Abstract: The combination of a phosphatase enzyme with a biocompatible carrier material produces materials which are useful in the repair of the skeleton and the promotion of new bone growth. The combination preferably involves covalent coupling between the enzyme and the carrier. The preferred carrier materials include fibrillar collagen and may be obtained by the demineralization of calcified tissues. The materials may include phosphoproteins or dentinal phosphophoryns which may be residual or may be added during the preparation of the materials. The incorporation of other organophosphates and inorganic phosphates may improve the rate of mineralization especially in older animals.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: October 7, 1997
    Assignee: British Technology Group Limited
    Inventors: Wouter Beertsen, Theo van den Bos
  • Patent number: 5674696
    Abstract: There is disclosed an apparatus for the determination of a trace amount of an analyte substance or organism. A substrate solution is brought into contact with a small diameter tube which has captured, at least on its inner surface, a trace amount of an analyte substance or organism. The trace amount has the ability to change the pH of the substrate solution.
    Type: Grant
    Filed: October 24, 1994
    Date of Patent: October 7, 1997
    Assignee: Biosensor Laboratories Co., Ltd.
    Inventors: Michihiro Nakamura, Satomi Matsui, Keiko Oka, Hitoshi Tsuruta
  • Patent number: 5662824
    Abstract: Magnetically attractable particles comprise a core of magnetic material encapsulated in a metal oxide coating. They may be made by emulsifying an aqueous solution or dispersion of the magnetic material or precursor, and an aqueous solution or sol of a coating inorganic oxide or precursor, in an inert water-immiscible liquid. The aqueous droplets are gelled, e.g. by ammonia or an amine, recovered, and heated at 250.degree.-2000.degree. C. The resulting particles are generally smooth spheres below 100 microns in diameter and often of sub-micron size.
    Type: Grant
    Filed: November 29, 1994
    Date of Patent: September 2, 1997
    Assignee: Alfa Biotech SpA
    Inventors: Jean Victor Sang, Paul Groves, Robert Edward Burrell, Gerard Flynn
  • Patent number: 5663057
    Abstract: Process for rapid, ultrasensitive and automatic counting of fluorescent biological cells such as microorganims, carried by a solid support such as a filter.The process includes: scanning a solid support on which a specimen potentially containing microorganisms has been deposited, with an incident beam from a laser, forming a laser spot on the solid support, the laser spot being substantially greater than the microorganisms to be detected, the laser spot size being between 4 and 14 .mu.m and simultaneously: detecting the resultant fluorescent light at least at one wavelength; establishing a set of correlated-features by a line-to-line correlation of individual features; comparing said correlated-features on each pair of adjacent lines in time synchrony, at least at two different wavelengths .lambda..sub.1 and .lambda..sub.
    Type: Grant
    Filed: June 21, 1995
    Date of Patent: September 2, 1997
    Assignee: Chemunex
    Inventors: Jean-Louis Drocourt, Patrick Desfetes, Jaspal Sanghera
  • Patent number: 5658769
    Abstract: Esters in which the alcohol part is sterically hindered around the ester bond, i.e. derived from tertiary alcohols are enzymatically prepared under low water conditions using Candida antarctica lipase A or a lipase species having a substrate activity similar to that of Candida antarctica lipase A with respect to tertiary alcohol esters.
    Type: Grant
    Filed: April 8, 1996
    Date of Patent: August 19, 1997
    Assignee: Unichem Chemie BV
    Inventors: John Anthony Bosley, John Casey, Alasdair Robin Macrae, Gary MyCock
  • Patent number: 5650311
    Abstract: A metod is proposed of obtaining a chemical interaction between at least one reagent trapped in sol-gel glass by doping it with the reagent(s), and diffusible solutes or components in an adjacent liquid or gas phase. The reagents, the solutes or the components can be any organic or inorganic compounds or materials of biological origins including enzymes. The doped sol-gel glass in various forms may be useful as analytical test, chromatographic medium, sensor, catalyst or biocatalyst, electrode or enzyme electrode, or other detection device.
    Type: Grant
    Filed: June 28, 1994
    Date of Patent: July 22, 1997
    Assignee: Yissum, Research Development Company of the Hebrew University of Jerusalem, Israel
    Inventors: David Avnir, Michael Ottolenghi, Sergei Braun, Rivka Zusman
  • Patent number: 5639657
    Abstract: A process for the formation of an artificial seaweed bed comprises depositing a structure as an artificial fish reef in the sea. According to the present invention, the structure is made of a glassy material having a specific composition, or a surface of the structure is covered with the specific glassy material. The glassy material contains silicon in an amount of 30 to 70 wt. % in terms of SiO.sub.2. The glassy material further contains sodium and/or potassium in an amount of 10 to 50 wt. % in terms of Na.sub.2 O and/or K.sub.2 O. The glassy material furthermore contains iron in an amount of 5 to 50 wt. % in terms of Fe.sub.2 O.sub.3. All or a part of the iron is present in a ferrous state. The glassy material contains the ferrous iron in an amount of not less than 1 wt. %.
    Type: Grant
    Filed: March 24, 1994
    Date of Patent: June 17, 1997
    Assignees: Nippon Tetrapod Co., Ltd., Toyo Glass Co., Ltd.
    Inventors: Masamichi Saiki, Sadao Ueda, Shuji Kitao
  • Patent number: 5624831
    Abstract: Acetylcholinesterase and/or a receptor of acetylcholinesterase is immobilized on a solid support and stabilized by covering with a protective film of gelatin and/or albumin containing trehalose. The film is applied by covering the immobilized acetylcholinesterase and/or receptor of acetylcholinesterase with a layer of a gel-forming solution of gelatin or albumin in an evaporable solvent containing dissolved trehalose, and evaporating the solvent to leave the film. The film provides stability against dry heat, organic solvents, proteases and changes in pH. Other additives such as polyhydric alcohols, organic solvents, polymers and/or ionic and non-ionic components may be present to increase stabilization. A diagnostic kit or chromatography column may be formed containing the stabilized immobilized acetylcholinesterase and/or receptor of acetylcholinesterase.
    Type: Grant
    Filed: March 16, 1995
    Date of Patent: April 29, 1997
    Inventors: Nguyen Vu Khue, Phillippe Poindron, Roland Maes
  • Patent number: 5618531
    Abstract: A method for increasing the viability of viable cells which are administered to the brain or spinal cord of a mammalian subject. This method is accomplished by attaching the cell to a support matrix so that the cell attaches to the matrix surface, and implanting the support matrix with the attached cell into the brain or spinal cord. Preferred support matrices are glass or plastic microbeads, either solid or porous, having a diameter from about 90 to about 125 .mu.m. The method employs cells of different types, preferably cells of neural or paraneural origin, such as adrenal chromaffin cells. Also useful are cell lines grown in vitro. Cells not of neural or paraneural origin, such as fibroblasts, may also be used following genetic alteration to express a desired neural product such as a neurotransmitter or a neuronal growth factor. The method is used to treat neurological diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, epilepsy, and traumatic brain injury.
    Type: Grant
    Filed: July 13, 1993
    Date of Patent: April 8, 1997
    Assignee: New York University
    Inventor: Bruce D. Cherksey
  • Patent number: 5618736
    Abstract: A process using hydrothermally synthesized porous kaolinite as a carrier for use in a bioreactor. A carrier-biocatalyst composite body for use in a bioreactor, includes the synthesized kaolinite as a carrier and a biocatalyst fixed onto the synthesized kaoline. A bioreactor system includes a bioreactor vessel, and such a carrier-biocatalyst composite body placed in the bioreactor vessel.
    Type: Grant
    Filed: June 20, 1994
    Date of Patent: April 8, 1997
    Assignee: NGK Insulators, Ltd.
    Inventor: Kisato Tone
  • Patent number: 5614401
    Abstract: An enzyme immobilizing carrier is formed from a porous powder. The powder uses kaolin mineral as a starting material, which starting material is subjected to acid treatment by a strong acid. The acid treated kaolin mineral is then subjected to a hydrothermal treatment. The acid and hydrothermal treated kaolin mineral is then subjected to a baking treatment.
    Type: Grant
    Filed: June 21, 1994
    Date of Patent: March 25, 1997
    Assignee: Toyo Denka Kogyo Co., Ltd.
    Inventors: Joji Takahashi, Eiji Kanazawa, Yoshitaka Yamashita, Tomio Kashiwai, Hideo Takenaka
  • Patent number: 5605662
    Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridization, antibody/antigen reaction, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micromachining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific microlocations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.
    Type: Grant
    Filed: November 1, 1993
    Date of Patent: February 25, 1997
    Assignee: Nanogen, Inc.
    Inventors: Michael J. Heller, Eugene Tu
  • Patent number: 5593779
    Abstract: A fiber for clothing, the fiber having a layer of crosslinked enzyme protein on a surface of a single fiber or a monofilament thereof; and a method for producing the fiber for clothing having the steps of immersing a fiber into a solution containing an enzyme protein to adsorb the enzyme protein onto a surface of a single fiber or a monofilament thereof, and crosslinking the enzyme protein adsorbed on the surface of the single fiber or the monofilament with a crosslinking agent.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: January 14, 1997
    Assignee: Kao Corporation
    Inventors: Kazuo Mori, Kazunori Nishizawa, Yoshifumi Niki
  • Patent number: 5587128
    Abstract: Disclosed are devices for amplifying a preselected polynucleotide in a sample by conducting a polynucleotide amplification reaction. The devices are provided with a substrate microfabricated to include a polynucleotide amplification reaction chamber, having at least one cross-sectional dimension of about 0.1 to 1000 .mu.m. The device also includes at least one port in fluid communication with the reaction chamber, for introducing a sample to the chamber, for venting the chamber when necessary, and, optionally, for removing products or waste material from the device. The reaction chamber may be provided with reagents required for amplification of a preselected polynucleotide. The device also may include means for thermally regulating the contents of the reaction chamber, to amplify a preselected polynucleotide. Preferably, the reaction chamber is fabricated with a high surface to volume ratio, to facilitate thermal regulation.
    Type: Grant
    Filed: November 14, 1994
    Date of Patent: December 24, 1996
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Peter Wilding, Larry J. Kricka
  • Patent number: 5580770
    Abstract: A biologically active support for removing pollutants from a fluid stream such as waste water is prepared. The support is formed of a polymeric foam substrate coated with a composition containing a particulate adsorbent which adsorbs, then releases pollutants, and a polymeric binder that binds the adsorbent to the surface of the substrate. The binder contains a suspension aid, and one or more pollutant-degrading microorganisms are adhered to the surface of the coated support. The binder preferably has a T.sub.g of lower than or equal to about 250.degree. C. and may be a latex. Examples of suspension aids are surfactants and polyanionic polypeptides such as ammonium caseinate. The adsorbent is preferably a carbon material such as coal, charcoal, carbon black and activated carbon. Other adsorbents are silica gel, active clays, zeolites, hydrophobic and ion exchange resins, and molecular sieves.
    Type: Grant
    Filed: December 27, 1993
    Date of Patent: December 3, 1996
    Assignee: AlliedSignal Inc.
    Inventor: Louis J. DeFilippi
  • Patent number: 5569634
    Abstract: Porous bodies are produced which are suitable for use as supports for catalysts, including living cells, such as bacteria and which are upset resistant to acids and bases. The bodies have a significantly large average pore diameter of about 0.5 to 100 microns, (i.e. 5,000 to 1,000,000 .ANG.) and a total pore volume of about 0.1 to 1.5 cc/g with the large pores contributing a pore volume of from about 0.1 to 1.0 cc/g. The bodies are made by preparing a mixture of ultimate particles containing a zeolite and one or more optional ingredients such as inorganic binders, extrusion or forming aids, burnout agents, or a forming liquid, such as water. In a preferred embodiment, the ultimate particles are formed by spray drying.
    Type: Grant
    Filed: December 12, 1994
    Date of Patent: October 29, 1996
    Assignee: W. R. Grace & Co.-Conn.
    Inventors: James G. Miller, Michael J. Wax, Richard F. Wormsbecher, Leo B. Aller, Donald R. Durham, Alan B. Chmurny
  • Patent number: 5565344
    Abstract: The present invention is directed to a gene which is related to a D-N-carbamoyl-.alpha.-amino acid amidohydrolase which is an enzyme capable of converting D-N-carbamoyl-.alpha.-amino acids into D-.alpha.-amino acids; a recombinant plasmid in which a DNA fragment containing the gene is incorporated into a vector; a microorganism belonging to the genus Escherichia, Pseudomonas, Flavobacterium, Bacillus, Serratia, Corynebacterium, or Brevibacterium, which is transformed by incorporating the recombinant plasmid thereinto; a process for the production of D-N-carbamoyl-.alpha.-amino acid amidohydrolases, comprising the steps of cultivating the transformed microorganism and collecting the desired product therefrom; a D-N-carbamoyl-.alpha.-amino acid amidohydrolase obtained by the method; and a process for the production of D-.alpha.-amino acids with the aid of an action of the enzyme.The D-N-carbamoyl-.alpha.-amino acid amidohydrolase can be fixed on a support for immobilization and used as an immobilized enzyme.
    Type: Grant
    Filed: August 7, 1992
    Date of Patent: October 15, 1996
    Assignee: Kanegafuchi Kagaku Kogyo Kabushiki Kaisha
    Inventors: Hirokazu Nanba, Yukio Yamada, Masayuki Takano, Yasuhiro Ikenaka, Satomi Takahashi, Kazuyoshi Yajima
  • Patent number: 5552276
    Abstract: A simplified measuring apparatus for use in the qualitative or quantitative measurement of substances to be assayed in test samples, such as proteins, antibodies and the like, in a small amount of test samples by a simple and easy operation without requiring a B/F separation step comprises: (a) a liquid permeable porous reaction membrane whose surface having at least one reaction area to which an affinity substance capable of directly or indirectly capturing a substance to be assayed or a soluble agent is immobilized; (b) a porous body arranged on the upper part of the porous reaction membrane, to which a soluble agent capable of being solubilized by the addition of a test sample is adhered in a releasable manner; (c) an absorption member arranged on the lower part of the porous reaction membrane, which contacts with a periphery, excluding the reaction area, of the porous reaction membrane via a liquid non-permeable sheet; (d) a liquid non-permeable transparent cover arranged on the lower part of the absorpti
    Type: Grant
    Filed: March 9, 1994
    Date of Patent: September 3, 1996
    Assignee: Mochida Pharmaceutical Co., Ltd.
    Inventors: Ei Mochida, Yasuhiko Miyauchi, Takashi Matsuura, Tomoaki Katamine
  • Patent number: 5545317
    Abstract: Packing materials for liquid chromatographic or catalytic columns are prepared by contacting a porous protein-adsorptive particulate or membranous support, such as a porous silica particulate support, with an aqueous solution into which a protein has been dissolved to form a saturated coating of protein on the external surfaces of the porous protein-adsorptive support, removing excess protein that remains in solution by washing, and, then crosslinking the protein in the coating. The result is a packing material which resists further adsorption by many different proteins but which continues to provide the adsorptive or catalytic properties of the groups on the internal surfaces of the porous protein-adsorptive support for separations, analysis, or alteration of small molecules. The packing material of the present invention is particularly useful in HPLC or solid phase extraction columns for direct injection drug analysis in plasma, serum, and urine.
    Type: Grant
    Filed: April 17, 1995
    Date of Patent: August 13, 1996
    Assignee: Dow Corning Corporation
    Inventor: Dwight E. Williams
  • Patent number: 5540995
    Abstract: A granular polymer composite comprising polymeric granules having coated on a surface thereof a calcium phosphate compound, at least a part of the particles of the calcium phosphate compound penetrates into the polymeric granules. The composite has a high bonding strength between the polymeric granules as a matrix and a coating of the calcium phosphate compound and also can fully exhibit the functions of a calcium phosphate compound. Using the granular polymer composite, a diagnostic agent which comprises of an antigen or antibody is adsorbed and immobilized on the composite and is therefore useful in diagnostic tests utilizing an antigen-antibody reaction for a number of infectious diseases.
    Type: Grant
    Filed: October 5, 1994
    Date of Patent: July 30, 1996
    Assignee: Asahi Kogaku Kogyo Kabushiki Kaisha
    Inventors: Tadahiko Kitano, Mikio Nakayama, Tetsuro Ogawa, Tsuneo Hiraide
  • Patent number: 5541096
    Abstract: A photocatalyst comprising inorganic porous particles having photosemiconductor particles deposited on at least a part of the surfaces and at least a part of the walls of the pores of the particles, and a photocatalyst comprising inorganic porous particles having photosemiconductor particles and microorganisms possessing water purification activity deposited on at least a part of the surfaces and at least a part of the walls of the pores of the particles are disclosed. The photocatalysts have a stable photocatalytic function for an extended period of time and easy separability from the treated water system so that it is useful for various photocatalytic reactions. Particularly they can be effectively used in water purification, and allow annihilation of harmful organisms such as algae, fungi and bacteria, decomposition of deleterious materials, as well as deodorization and decoloration to be conveniently and easily accomplished.
    Type: Grant
    Filed: July 11, 1994
    Date of Patent: July 30, 1996
    Assignee: Ishihara Sangyo Kaisha, Ltd.
    Inventors: Eiji Nomura, Tokuo Suita
  • Patent number: 5541097
    Abstract: A method for preparing an immobilized enzyme conjugate, whereby the enzyme is treated with a polyfunctional amine reactive material for forming a treated enzyme-containing adduct before being immobilized on a solid support which has been contacted with a solution of a polyamine compound. The method is especially preferred for use with glucoamylase, fungal .alpha.-amylase and .beta.-amylase. Immobilized enzyme conjugates formed by use of this method include treated enzyme-containing adducts. The immobilized enzyme conjugates disclosed herein are more stable and the enzymes immobilized therein are more tightly-held than those otherwise obtained and provided.
    Type: Grant
    Filed: February 9, 1995
    Date of Patent: July 30, 1996
    Assignee: Solvay Enzymes, Inc.
    Inventors: Oreste J. Lantero, Jack W. Brewer, Sharon M. Sarber
  • Patent number: 5521101
    Abstract: A method of determining an analyte in the gaseous or vapour phase and in which a bioreceptor or biomimic is retained at an electrode. The bioreceptor or biomimic is preferably retained at a support at the electrode which comprises a solid or gel matrix of an electrolyte, especially organic salt electrolytes. Electrochemical detection of analytes in this way has several advantages over existing methods which rely on solution monitoring. For example gas sensors can be prepared for monitoring an analyte by the occurrence of a reaction with a bioreceptor or biomimic, in addition to monitoring the presence of toxins due to inhibition of the bioreceptor or biomimic reaction. Furthermore, the invention enables gas or vapour analyte monitoring with increased sensitivity and speed and greater stability of the sensors can be achieved. The invention also relates to novel media for carrying out bioelectrochemical reactions.
    Type: Grant
    Filed: August 26, 1993
    Date of Patent: May 28, 1996
    Assignee: Cranfield University
    Inventors: Selwayan Saini, Anthony P. F. Turner
  • Patent number: 5518910
    Abstract: A bioremediation support for the support of microorganisms used in the biotreatment of an aqueous waste stream or contaminated vapor is made of a low-density siliceous glassy material. This material has a cellular or frothy texture, large pores of greater than 1,000 Anstrom units in diameter dispersed throughout the material, a high macropore volume in pores of greater than 1,000 .ANG. of more than 0.3 cc/cc and a BET surface area of greater than 10 m.sup.2 /g. A preferred material is pumice.
    Type: Grant
    Filed: December 5, 1994
    Date of Patent: May 21, 1996
    Assignee: W. R. Grace & Co.-Conn.
    Inventors: Frederick J. Parker, Awdhoot V. Kerkar, Rasto Brezny
  • Patent number: 5516648
    Abstract: Reference microorganisms are sealed into an interior cavity of a microporous membrane (14, 20). In one embodiment, the reference microbes are inoculated on a element (12) which is sealed in a microporous envelope (14) (FIG. 1). In another embodiment, the reference microbes (22) are loaded into an interior bore or cavity of a microporous plastic tube or envelope (20) (FIG. 3). The microporous membrane and the reference microbes, such as spores, are immersed concurrently with items to be microbially decontaminated separately into an anti-microbial fluid. The microporous membrane is constructed of a material which is sufficiently resistant to temperature, water, strong oxidants, and other anti-microbial agents or processes used for microbial decontamination or sterilization that it retains its integrity during the immersion in any common steam, gas, or liquid microbial decontamination or sterilization fluid or system.
    Type: Grant
    Filed: August 18, 1994
    Date of Patent: May 14, 1996
    Assignee: Steris Corporation
    Inventors: Paul S. Malchesky, Donna M. Richardson
  • Patent number: 5512169
    Abstract: Packing materials for liquid chromatographic or catalytic columns are prepared by contacting a porous protein-adsorptive particulate or membranous support, such as a porous silica particulate support, with an aqueous solution into which a protein has been dissolved to form a saturated coating of protein on the external surfaces of the porous protein-adsorptive support, removing excess protein that remains in solution by washing, and, then crosslinking the protein in the coating. The result is a packing material which resists further adsorption by many different proteins but which continues to provide the adsorptive or catalytic properties of the groups on the internal surfaces of the porous protein-adsorptive support for separations, analysis, or alteration of small molecules. The packing material of the present invention is particularly useful in HPLC or solid phase extraction columns for direct injection drug analysis in plasma, serum, and urine.
    Type: Grant
    Filed: December 30, 1992
    Date of Patent: April 30, 1996
    Assignee: Dow Corning Corporation
    Inventor: Dwight E. Williams
  • Patent number: 5496701
    Abstract: A method for determining one member of an enzyme-substrate pair (the analyte), comprises bringing the members of the pair into contact so as to form, directly or indirectly, a soluble reaction product at or adjacent the surface of an optical waveguide biosensor. The biosensor is preferably a resonant optical biosensor based on the principle of frustrated total reflection.
    Type: Grant
    Filed: December 3, 1993
    Date of Patent: March 5, 1996
    Assignee: Fisons plc
    Inventor: Denise V. Pollard-Knight
  • Patent number: 5494815
    Abstract: Biochemical substances, such as enzymes, are immobilized using an olefinic-unsaturated, epoxyfunctional polysiloxane. The polysiloxane is applied to a carrier material. The polysiloxane on the carrier is cross-linked by using high-energy radiation or a peroxide to form a polymer matrix. The polymer matrix is treated with an aqueous solution of a biochemical substance that reacts with epoxy groups and becomes immobilized. The polymer matrix is stabilized by the reaction of non-reacted epoxy groups with a compound containing an amino group, a carboxyl group or an amino group and a carboxyl group. The crosslinked polysiloxane can be hydrophilized after cross-linking and prior to immobilization of the biochemical substance by the reaction of a portion of the epoxy groups with a hydrophilic compound.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: February 27, 1996
    Inventors: Wolfgang von Gentzkow, Hans-Dieter Feucht, Helmut Formanek, Gerhard Wanner
  • Patent number: 5491082
    Abstract: A plasminogen activator such as urokinase or tissue plasminogen activator is covalently bonded to a porous body composed of calcium phosphate to form a plasminogen activator-porous body complex. The tricalcium phosphate can be .alpha.-tricalcium phosphate, .beta.-tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, octacalcium phosphate and mixtures thereof. In a preferred embodiment, .beta.-tricalcium phosphate which has excellent biocompatibility with the body or a mixture of .beta.-tricalcium phosphate and hydroxyapatite is used. Preferably, synthetic calcium phosphate is used is to avoid impurities contained by natural calcium phosphate. Covalent bonding is by crosslinking with glutaraldehyde, bismaleimides, dihalogenic aryls or diisocyanates, or by using cyanogen bromide, diazotization or periodic acid. The complex can be filled into a column to form a bioreactor.
    Type: Grant
    Filed: May 20, 1994
    Date of Patent: February 13, 1996
    Assignees: Director-General of Agency of Industrial Science and Technology, Olympus Optical Co., Ltd.
    Inventors: Takahiro Suzuki, Sukezo Kawamura, Motohiro Toriyama, Yoshiyuki Yokokawa, Yukari Kawamoto, Yasuharu Hakamatsuka, Hiroyuki Irie
  • Patent number: 5476776
    Abstract: A reusable, miniature, implantable electrochemical sensor, a method of making the same, and a powder therefor are provided. Enzyme material is immobilized on bulk particulate matter, and a reaction chamber of the sensor is then filled therewith. The sensor is implanted in an environment where it comes into contact with a specific component of a fluid with which the enzyme material chemically reacts to produce electrical signals for measuring the reaction. The method preferred for preparing the powder which is used in the electrochemical sensor involves first covalently bonding a quantity of an enzyme to fine particles in powder form to immobilize the enzyme is cross-linked to a non-enzyme protein with a cross-linking agent. Finally, the particles are added containing the immobilized enzyme cross-linked to a protein from the first step to the enzyme cross-linked to a protein from the second step to obtain the powder.
    Type: Grant
    Filed: July 15, 1994
    Date of Patent: December 19, 1995
    Assignee: University of New Mexico
    Inventor: Ebtisam S. Wilkins
  • Patent number: 5472861
    Abstract: A method for preparing an immobilized enzyme conjugate, whereby the enzyme is treated with a polyfunctional amine reactive material for forming a treated enzyme-containing adduct before being immobilized on a solid support which has been contacted with a solution of a polyamine compound. The method is especially preferred for use with glucoamylase, fungal .alpha.-amylase and .beta.-amylase. Immobilized enzyme conjugates formed by use of this method include treated enzyme-containing adducts. The immobilized enzyme conjugates disclosed herein are more stable and the enzymes immobilized therein are more tightly-held than those otherwise obtained and provided.
    Type: Grant
    Filed: January 9, 1995
    Date of Patent: December 5, 1995
    Assignee: Solvay Enzymes, Inc.
    Inventors: Oreste J. Lantero, Jack W. Brewer, Sharon M. Sarber
  • Patent number: 5472859
    Abstract: The present invention discloses a method of synthesizing a novel form of cellulose I as well as methods of synthesizing a novel form of cellulose I in vitro. One method comprises contacting an activated saccharide substrate with an endoglucanase in an appropriate organic solvent/buffer ratio. The invention also encompasses a partially purified endoglucanase and a method of synthesizing cellooligosaccharides. A second method comprises contacting a nucleotide sugar with a purified glycosyl transferase in an appropriate buffer medium to insure polymerization and crystallization of parallel glucan chains from the enzyme/micelle complex to form cellulose I.
    Type: Grant
    Filed: August 2, 1993
    Date of Patent: December 5, 1995
    Inventors: R. Malcolm Brown, Jr., Shiro Kobayashi, Krystyna Kudlicka, Shigenori Kuga, Jong Lee, Likun Li, Kazuo Okuda, Shin-Ichiro Shoda