Fluorescent Dyes (e.g., Rhodamine, Etc.) Patents (Class 436/800)
  • Patent number: 5776709
    Abstract: A method of flow cytometric analysis of leukocyte subpopulations using a fluorescence trigger and gating on light scatter vs. fluorescence. The methods are useful where light scatter parameters are unsatisfactory for identification of leukocyte subpopulations, for example when analyzing lysed blood samples without removal of lysing reagent or unbound label prior to analysis.
    Type: Grant
    Filed: August 4, 1994
    Date of Patent: July 7, 1998
    Assignee: Becton Dickinson and Company
    Inventors: Anne Louise Jackson, Robert Alan Hoffman, Andrew D. Blidy, Kenneth Earl Murchison, Pierre Bierre, Dan E. Thiel
  • Patent number: 5773299
    Abstract: A method and reagent for the simultaneous or independent enumeration of reticulocytes in a whole blood sample, without the need to separately incubate the sample and reagent. The reagent contains a reticulocyte staining amount of an unsymmetrical cyanine dye, from about 40 mM to about 60 mM of a buffer selected from the group consisting of imidazole, Tris and Bis-Tris and a dye stabilizing amount of a non-ionic surfactant selected from the group consisting of N, N-bis?3-D-Glucon-amidopropyl! cholamide and a polyoxypropylene-polyoxyethylene block copolymer. The reagent has a pH from about 6.8 to about 7.2 and an osmolarity adjusted to about 280 to about 310 mosm/l with a mono-, or di-, valent alkali salt selected from the group consisting of NaCl, KCl, LiCl, CaCl.sub.2, MgCl.sub.2 and ZnCl.sub.2. The method utilizes the reagent in a no incubation process that also allows for the simultaneous determination of CBC as well as reticulocyte counts and maturity indices.
    Type: Grant
    Filed: December 20, 1996
    Date of Patent: June 30, 1998
    Assignee: Abbott Laboratories
    Inventors: Young Ran Kim, Johanna Kantor
  • Patent number: 5763189
    Abstract: Particles comprising an energy donor as a first component and a fluorescent dye as a second component positioned in said particles at an energy exchanging distance from one another, wherein the two components have a Stokes shift of greater than or equal to 50 nm, said particle having bound on its surface, a protein, polypeptide, nucleic acid, nucleotide or protein containing ligand analogue are disclosed and claimed. In addition, novel fluorescent dyes are described which exhibit intramolecular energy transfer for use to label various molecules, proteins, polypeptides, nucleotides and nucleic acids or to incorporate into particles.
    Type: Grant
    Filed: September 23, 1994
    Date of Patent: June 9, 1998
    Assignee: Biosite Diagnostics Incorporated
    Inventors: Kenneth F. Buechler, J. Barry Noar, Lema Tadesse
  • Patent number: 5759767
    Abstract: A method of measuring an analyte present in animal (e.g., human) tissue or fluids such as blood or plasma. The analyte is multi-photon excitable (e.g., two-photon excitable) at a first wavelength at which the animal tissue is substantially non-absorbing. The analyte fluoresces at a second wavelength upon being excited at the first wavelength. The animal tissue is irradiated with radiation at the first wavelength so as to excite the analyte through absorption by the analyte of two or more photons of the radiation at the first wavelength. Excitation of the analyte results in a fluorescent emission from the analyte of radiation at the second wavelength. The emission at the second wavelength is detected, and the concentration of analyte determined based on the detected emission.
    Type: Grant
    Filed: October 11, 1996
    Date of Patent: June 2, 1998
    Assignee: Joseph R. Lakowicz
    Inventors: Joseph R. Lakowicz, Thomas G. Burke, Ignacy Gryczynski, Henryk Malak
  • Patent number: 5756362
    Abstract: A test device for detecting or quantifying an analyte in a test sample includes an absorbent material having separate contact and measurement portions. The contact portion is positioned at or proximate to a first end of the absorbent material. The measurement portion has a receptor for a conjugate of an analyte analog and marker-encapsulating liposomes. In a method for using the test device, a binding material specific for the analyte is combined with the liposome-analyte analog conjugate and the test sample to form a test mixture. The mixture is incubated for a time sufficient to permit competition between any analyte present and the conjugate for the binding material. Following incubation, the mixture is allowed to traverse the absorbent material from the contact portion through the measurement portion of the absorbent material.
    Type: Grant
    Filed: February 1, 1995
    Date of Patent: May 26, 1998
    Assignee: Cornell Research Foundation, Inc.
    Inventors: Richard Allen Durst, Matthew A. Roberts
  • Patent number: 5750409
    Abstract: Pentacyclic derivatives having the general formulae (Ia), (Ib) and (Ic) ##STR1## denote: hydrogen, alkyl with 1 to 20 carbon atoms polyoxyhydrocarbyl, phenyl, phenylalkyl with 1 to 3 carbon atoms in the alkyl chain, wherein the alkyl residues or/and phenyl residues can be substituted by one or several hydroxy, halogen, sulfo, carboxy or alkoxycarbonyl groups in which alkoxy can have 1 to 4 carbon atoms;R.sup.7 denotes an alkyl group with 1 to 7 carbon atoms, substituted by at least one halogen, or denotes a carboxyalkyl group or a phenyl group which is substituted by a carboxy or alkoxycarbonyl group located at the o-position relative to the carbon atom bound to the pentacyclic ring system and by at least one halogen, wherein alkoxy can have 1 to 4 carbon atoms, or a carboxymethylene-oxy-alkyloxy group; the residues R.sup.14 and R.sup.
    Type: Grant
    Filed: May 30, 1995
    Date of Patent: May 12, 1998
    Assignee: Boehringer Mannheim GmbH
    Inventors: Rupert Herrmann, Hans-Peter Josel, Karl-Heinz Drexhage, Jutta Arden-Jacob
  • Patent number: 5739000
    Abstract: This invention provides a method of multi-parameter data analysis by means of a hierarchical attractor algorithmic engine. The method employs analyzing the data by construction of a population hierarchy, wherein the populations are not mutually exclusive, thereby providing an important analytical tool. The use of the hierarchical attractor algorithmic engine presents the user with far greater flexibility in such analysis, as overlapping populations can be separately examined.
    Type: Grant
    Filed: April 13, 1994
    Date of Patent: April 14, 1998
    Assignee: Becton Dickinson and Company
    Inventors: Pierre Bierre, Daniel E. Thiel
  • Patent number: 5733721
    Abstract: A system for evaluating one or more biochemical markers for evaluating individual cancer risk, cancer diagnosis and for monitoring therapeutic effectiveness and cancer recurrence, particularly of bladder cancer. The system uses automated quantitative fluorescence image analysis of a cell sample collected from a body organ. Cells are treated with a fixative solution which inhibits crystal formation. Cell images are selected and stored as grey level images for further analysis. Cell images may be corrected for autofluorescence using a novel autofluorescence correction method. A neural net computer may be used to distinguish true-positive images from false-positive images to improve accuracy of cancer risk assessment. Cells having images positive for a marker amy be compared to threshold quantities related to predetermined cancer risk.
    Type: Grant
    Filed: December 20, 1992
    Date of Patent: March 31, 1998
    Assignee: The Board of Regents of the University of Oklahoma
    Inventors: George P. Hemstreet, III, Robert E. Hurst, Rebecca B. Bonner, Jian Yu Rao
  • Patent number: 5734058
    Abstract: New intercalating cyanine dyes are provided in which the benzothiazole portion of the cyanine dye has been modified to produce dyes with improved properties for labelling nucleic acids. The fluorescent cyanine dyes have a positively charged substituent attached to the positively charged nitrogen on the benzothiazole portion of the cyanine dye.
    Type: Grant
    Filed: November 9, 1995
    Date of Patent: March 31, 1998
    Assignee: Biometric Imaging, Inc.
    Inventor: Linda G. Lee
  • Patent number: 5719027
    Abstract: A labeled complex formed by combining a labeling agent with a biological substance, where the labeling agent is a trinucleus dye represented by the general formula (I)' or (II)':ring(Xa)-La-ring(Xb)-Lb-ring(Xc) (I)'?ring(Xa)-La-ring(Xb)-Lb-ring(Xc)!.sup..sym. Y.sup..crclbar.(II)'where the ring(Xa), ring(Xb), and ring(Xc), which mean rings having Xa, Xb, or Xc respectively, are independently a heterocyclic ring having one to three heteroatoms of oxygen, sulfur, nitrogen, or selenium, the heterocyclic ring being unsubstituted or substituted by any of a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted aralkyl group; La and Lb are independently a methine chain composed of one to six substituted or unsubstituted methine linkage, and one of La and Lb may be omitted to link directly the heterocyclic rings; and Y.sup..crclbar. represents an anion.
    Type: Grant
    Filed: February 22, 1996
    Date of Patent: February 17, 1998
    Assignee: Canon Kabushiki Kaisha
    Inventors: Takeshi Miyazaki, Tadashi Okamoto, Kazumi Tanaka, Toshikazu Onishi, Tetsuro Fukui, Nobuko Yamamoto
  • Patent number: 5716855
    Abstract: A fluorescent latex with particles containing at least one encapsulated hydrophobic fluorochrome A (acceptor) and at least one encapsulated hydrophobic fluorochrome D (donor), wherein A is different from D and exposure to light radiation enables the emission from fluorochrome D to excite fluorochrome A, and a method for producing said latex and its use as a marker, particularly a biological marker, are also disclosed.
    Type: Grant
    Filed: March 1, 1996
    Date of Patent: February 10, 1998
    Assignee: Societe Prolabo
    Inventors: Dan Lerner, Frederic Ricchiero, Joel Richard, Dominique Teychenne, Sophie Vaslin
  • Patent number: 5714390
    Abstract: The invention is a device and a method for collecting samples mixing the samples with test reagents, and acting as a container in which the mixture can be incubated and the test reaction viewed by microscope or imaging device. This device enables an entire test to be performed in one simple step without complicated handling procedures. The device consists of a cartridge with a well with micro-lances imbedded in the bottom of the well and an overlying micro-baggy containing a mixture of reagents. There are two reagents present in the micro-baggy: the first consisting of antibodies coupled to paramagnetic microspheres and the second consisting of antibodies coupled with a fluorochrome. A test subject presses down onto the micro-baggy and at the same time punctures his/her finger or thumb on the micro-lances. Once the finger has been lanced, breaking the micro-baggy, the reagents mix with the test subject's blood. The well is then covered by a clear mylar strip.
    Type: Grant
    Filed: October 15, 1996
    Date of Patent: February 3, 1998
    Assignee: Bio-Tech Imaging, Inc.
    Inventors: Robert A. Hallowitz, Chester F. King
  • Patent number: 5714386
    Abstract: Novel tandem dyes comprising a conjugate of a Cy7 dye and allophycocyanin are provided. Also provided are probes comprising the subject dyes conjugated to a member of a specific binding pair. Probes comprising the subject tandem dyes find use as labels in variety of fluorescence detection assays.
    Type: Grant
    Filed: January 11, 1996
    Date of Patent: February 3, 1998
    Assignee: Board of Trustees of the Leland Stanford Junior University
    Inventor: Mario Roederer
  • Patent number: 5714089
    Abstract: A chemical moiety is disclosed which comprises a chemical, biochemical, or biological substance attached to one or more electrochemiluminescent organometallic compounds. In a preferred embodiment of the invention the substance is attached to one or more ruthenium-containing or osmium-containing luminescent organometallic compounds. Methods are disclosed for detecting low concentrations of the chemical moiety using chemiluminescent, electrochemiluminescent, and photoluminescent means. Compounds are disclosed which are useful for labeling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labeled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labeled substances are of particular use in homogeneous binding assays.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: February 3, 1998
    Assignee: IGEN International, Inc.
    Inventors: Allen J. Bard, George M. Whitesides
  • Patent number: 5707844
    Abstract: The present invention is directed to immunoassay reagents including specific antibodies to quinoline carboxylic acids, such as brequinar; novel quinoline carboxylic acid haptens useful as standards in immunoassays or for conjugating to large molecular weight carriers as immunogens or conjugating to detectable fluorescent moieties as tracer compounds. The present invention also relates to immunoassays for detecting quinoline carboxylic acids in clinical samples, and finally to kits containing said reagents.
    Type: Grant
    Filed: January 13, 1995
    Date of Patent: January 13, 1998
    Assignee: The DuPont Merck Pharmaceutical Company
    Inventors: Douglas Guy Batt, William Galbraith, Paul Moore Simon
  • Patent number: 5695930
    Abstract: A rapid and accurate test kit is discussed for the detection of antibodies to HIV in saliva. The identification of antibodies to HIV in the saliva of seropositive individuals is shown using a test kit that requires no special machinery or skill and can be conducted by a single person in the privacy of their own home.
    Type: Grant
    Filed: August 5, 1996
    Date of Patent: December 9, 1997
    Inventors: David E. Weinstein, Trevor J. Kilpatrick
  • Patent number: 5693484
    Abstract: A reagent for analyzing cells in urine and a method for analyzing cells in urine with the use of the reagent are provided. The present invention discloses a reagent for analyzing cells in urine which comprises solution(s) containing a fluorescent dye, an osmolarity compensating agent and a buffer, as well as a method for analyzing cells in urine which comprises diluting a urine sample and staining cells therein with the reagent, irradiating the cells with light in the violet or blue wavelength region by using a flow cytometer and measuring the forward or side scattered light and fluorescence from the cells.
    Type: Grant
    Filed: October 26, 1994
    Date of Patent: December 2, 1997
    Assignee: TOA Medical Electronics Co., Ltd.
    Inventors: Hiroyuki Nakamoto, Chiyose Fujiwara
  • Patent number: 5691204
    Abstract: A method and reagent for the simultaneous or independent enumeration of reticulocytes in a whole blood sample, without the need to separately incubate the sample and reagent. The reagent contains a reticulocyte staining amount of an unsymmetrical cyanine dye, from about 40 mM to about 60 mM of a buffer selected from the group consisting of imidazole, Tris and Bis-Tris and a dye stabilizing amount of a non-ionic surfactant selected from the group consisting of N, N-bis?3-D-Glucon-amidopropyl! cholamide and a polyoxypropylene-polyoxyethylene block copolymer. The reagent has a pH from about 6.8 to about 7.2 and an osmolarity adjusted to about 280 to about 310 mOsm/l with a mono-, or di-, valent alkali salt selected from the group consisting of NaCl, KCl, LiCl, CaCl.sub.2, MgCl.sub.2 and ZnCl.sub.2. The method utilizes the reagent in a no incubation process that also allows for the simultaneous determination of CBC as well as reticulocyte counts and maturity indices.
    Type: Grant
    Filed: April 21, 1995
    Date of Patent: November 25, 1997
    Assignee: Abbott Laboratories
    Inventors: Young Ran Kim, Johanna Kantor
  • Patent number: 5691205
    Abstract: Provided is a fluorometric analytical method for detecting chloride ion in a sample by quenching of fluorescence of a fluorescent dye, the fluorescent dye being one of 3,6-bis(dimethylamino)acridine and a derivative thereof of the formulae ##STR1## wherein R is alkyl having 1 to 30 carbon atoms, and X.sup.- is a halogen ion.
    Type: Grant
    Filed: June 21, 1995
    Date of Patent: November 25, 1997
    Assignee: Canon Kabushiki Kaisha
    Inventors: Yuji Kawabata, Yoshiyuki Toge
  • Patent number: 5691145
    Abstract: Oligonucleotides which form G-quartet structures have been found to be useful in fluorescence assays to detect a selected nucleic acid sequence. When one end of the oligonucleotide is labeled with a donor fluorophore and the other end is labeled with an acceptor dye, the folding of the molecule in the G-quartet structure brings the donor-acceptor pair into close proximity, allowing an interaction between the two labels which results in quenching of donor fluorescence or a change in other fluorescence properties which are the result of the interaction of two dyes in close proximity. The G-quartet structure unfolds upon hybridization to its complementary sequence, increasing the distance between the two dye labels. This results in decreased donor quenching or a change in another proximity-related fluorescence parameter. The associated increase in donor fluorescence intensity or the change in another fluorescence parameter may be monitored as an indication of the presence of a selected nucleic acid sequence.
    Type: Grant
    Filed: August 27, 1996
    Date of Patent: November 25, 1997
    Assignee: Becton, Dickinson and Company
    Inventors: J. Bruce Pitner, Glenn P. Vonk, James G. Nadeau
  • Patent number: 5683907
    Abstract: The present invention relates to the field of immunossays for metal ions. The invention presents: metal ion-ligand coordination complexes ("MLC"), novel ligands, antibodies specific for MLC, immunoassays utilizing the foregoing, and methods for selecting said antibodies.
    Type: Grant
    Filed: May 5, 1995
    Date of Patent: November 4, 1997
    Assignee: Abbott Laboratories
    Inventor: David K. Johnson
  • Patent number: 5679516
    Abstract: A process for detecting a target nucleic acid, which includes the steps of hybridizing a target single-stranded nucleic acid in a sample solution to a labeled single-stranded nucleic acid probe to form a reaction mixture containing a hybrid, subjecting the reaction mixture to capillary electrophoresis to separate the hybrid from the free labeled nucleic acid probe, and detecting the hybrid utilizing the label moiety of the nucleic acid probe constituting the hybrid.
    Type: Grant
    Filed: October 4, 1994
    Date of Patent: October 21, 1997
    Assignee: Canon Kabushiki Kaisha
    Inventors: Tadashi Okamoto, Takeshi Miyazaki
  • Patent number: 5677199
    Abstract: Marker components are provided which are compatible with aqueous solutions, exhibit favorable fluorescence properties and exhibit decreased non-specific binding to macromolecules in solution. These marker components are useful in applications such as fluorescence immunoassays and in vivo imaging.
    Type: Grant
    Filed: November 29, 1994
    Date of Patent: October 14, 1997
    Assignee: Diatron Corporation
    Inventor: Peter Olof Gustaf Arrhenuis
  • Patent number: 5677197
    Abstract: An assay system for detecting the binding of a mobile reactant to an immobilized reactant on an assay plate. The assay plate includes a substrate having an assay spot deposited thereon. The assay spot includes the immobilized reactant. In the present invention, a carrier dye is included in the assay spot, the amount of the carrier dye indicating the amount of the immobilized reactant that is present in the assay spot. In the preferred embodiment of the present invention, the assay spot is generated by depositing liquid on the assay plate at a location corresponding to the assay spot. The carrier dye is dissolved in the liquid and remains after the liquid evaporates. The amount of carrier dye in each spot may be measured spectroscopically and provides a means for identifying defective assay plates.
    Type: Grant
    Filed: November 14, 1994
    Date of Patent: October 14, 1997
    Assignee: Hewlett-Packard Company
    Inventors: Gary B. Gordon, Scott A. Conradson, Kay Lichtenwalter
  • Patent number: 5669819
    Abstract: Acridinium sulfonylamides and isomers, such as phenanthridinium sulfonylamides, may be employed in applications including chemiluminmescent immunoassays. Methods for synthesis of these compounds include contacting an amine with a sulfonylhalide to form a sulfonamide and acylating with an activated carboxylic acid of an acridine or isomer thereof. The N-sulfonyl-9-acridinium carboxamide and isomers may be conjugated to antigens, haptens, antibodies, and nucleic acids for use in chemiluminescent assays.
    Type: Grant
    Filed: May 16, 1995
    Date of Patent: September 23, 1997
    Assignee: Abbott Laboratories
    Inventors: Phillip Gregory Mattingly, Larry Gene Bennett
  • Patent number: 5665606
    Abstract: The present invention provides a new analytical method that an antigen, an antibody or a nucleic acid can be assayed at a high sensitivity in the immunoassay.The present invention provides a method for assaying a substance which comprises the steps of (a) reacting an antigen, an antibody or a nucleic acid which is the substance to be measured with an antibody, an antigen or a nucleic acid to which a polyacridinium compound is bound and which can be bound to the substance to be measured, (b) carrying out a luminescence treatment, and (c) measuring the luminescent intensity of the reaction solution.
    Type: Grant
    Filed: April 10, 1995
    Date of Patent: September 9, 1997
    Assignee: Kyowa Medex Co., Ltd.
    Inventor: Akira Miike
  • 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: 5658751
    Abstract: The invention describes the preparation and use of fluorescent stains for nucleic acids derived from unsymmetrical cyanine dyes comprising a substituted benzazolium ring system linked by a methine bridge to a pyridinium or quinolinium ring system having at least one substituent on the pyridinium or quinolinium ring that contains a heteroatom. The presence of the heteroatom-containing substituent results in higher sensitivity to oligonucleotides and larger nucleic acid polymers in a wide range of cells and gels, and for use in analysis of cell structure, membrane integrity or function.
    Type: Grant
    Filed: October 27, 1994
    Date of Patent: August 19, 1997
    Assignee: Molecular Probes, Inc.
    Inventors: Stephen T. Yue, Victoria L. Singer, Bruce L. Roth, Thomas J. Mozer, Paul J. Millard, Laurie J. Jones, Xiaokui Jin, Richard P. Haugland
  • Patent number: 5656449
    Abstract: The invention describes the preparation and use of fluorescent stains for nucleic acids derived from neutral unsymmetrical cyanine dyes comprising a substituted benzazolium ring system linked to a methine bridge to a pyridine or quinoline ring system. The fluorescence characteristics of the dyes when complexed with nucleic acids give the dyes utility for the detection of oligonucleotides and nucleic acids in cells, gels and solutions. The dyes have particular utility in the staining of reticulocytes.
    Type: Grant
    Filed: March 6, 1995
    Date of Patent: August 12, 1997
    Assignee: Molecular Probes, Inc.
    Inventor: Stephen T. Yue
  • Patent number: 5654160
    Abstract: The present invention relates to the field of immunoassays for metal ions. The invention presents: metal ion-ligand coordination complexes ("MLC"), novel ligands, antibodies specific for MLC, immunoassays utiliizing the foregoing, and methods for selecting said antibodies.
    Type: Grant
    Filed: May 5, 1995
    Date of Patent: August 5, 1997
    Assignee: Abbott Laboratories
    Inventor: David K. Johnson
  • Patent number: 5650334
    Abstract: A fluorescent labelling composition comprises a linear polysaccharide backbone molecule having a plurality of target-binding molecules, such as antibodies or nucleic acids, attached at spaced-apart intervals thereon. Each of the target-binding molecules, in turn, includes a multiplicity of fluorescent dye molecules bound thereto. In this way, fluorescent signal introduced to a single target-site on a solid phase surface may be increased without loss of binding activity.
    Type: Grant
    Filed: August 31, 1995
    Date of Patent: July 22, 1997
    Assignee: First Medical, Inc.
    Inventors: Robert F. Zuk, Sae Hyun Choo
  • Patent number: 5650331
    Abstract: An apparatus and method for determining acid concentrations in solutions having acid concentrations of from about 0.1 Molar to about 16 Molar is disclosed. The apparatus includes a chamber for interrogation of the sample solution, a fiber optic light source for passing light transversely through the chamber, a fiber optic collector for receiving the collimated light after transmission through the chamber, a coating of an acid resistant polymeric composition upon at least one fiber end or lens, the polymeric composition in contact with the sample solution within the chamber and having a detectable response to acid concentrations within the range of from about 0.1 Molar to about 16 Molar, a measurer for the response of the polymeric composition in contact with the sample solution, and, a comparer of the measured response to predetermined standards whereby the acid molarity of the sample solution within the chamber can be determined.
    Type: Grant
    Filed: October 3, 1991
    Date of Patent: July 22, 1997
    Assignee: The United States of America as represented by the United States Department of Energy
    Inventors: Betty S. Jorgensen, Howard L. Nekimken, W. Patrick Carey, Patrick E. O'Rourke
  • Patent number: 5650135
    Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.
    Type: Grant
    Filed: July 1, 1994
    Date of Patent: July 22, 1997
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Christopher H. Contag, Pamela R. Contag, David A. Benaron
  • Patent number: 5648221
    Abstract: Various methods for precisely inspecting presence or absence of an antigen-antibody reaction or a type of the antigen-antibody reaction are provided. A method comprises a first step of mixing an object to be inspected with a photosensitive material, a second step of mixing a mixture obtained in the first step with an antibody, and a third step of detecting a photon echo from a specimen obtained in the second step to examine presence or absence, or a type of an antigen-antibody reaction. A further method comprises a first step of mixing an object to be inspected with an antibody, a second step of mixing a secondary antibody for the antibody with a photosensitive material, a third step of mixing a mixture obtained in the first step with a mixture obtained in the second step, and a fourth step of detecting a photon echo from a specimen obtained in the third step to examine presence or absence, or a type of an antigen-antibody reaction.
    Type: Grant
    Filed: June 14, 1994
    Date of Patent: July 15, 1997
    Assignee: Nikon Corporation
    Inventor: Takayuki Suga
  • Patent number: 5646000
    Abstract: The invention is directed to a series of novel compounds, and their pharmaceutically acceptable salts, of the formula ##STR1## wherein R is C.sub.0-6 alkyl substituted with R.sup.5 or a mono or polycyclic aromatic or heteroaromatic system comprised of 5 or 6-membered aromatic or heteroaromatic rings that are either unsubstituted or substituted with one or more of R.sup.1 and R.sup.2 ; R.sup.1 and R.sup.2 are independently C.sub.1-6 alkyl, carboxyl, hydroxyl, azido, nitro, amino, C.sub.1-6 alkylamino, C.sub.1-6 dialkylamino, arylamino, aryl C.sub.1-6 alkylamino, hydroxysulfonyl or arylazo; aryl is a phenyl or naphthyl ring which is unsubstituted or substituted with one or more of R.sup.3 and R.sup.4 ; R.sup.3 and R.sup.4 are independently C.sub.1-6 alkyl, azido, nitro, amino, C.sub.1-6 dialkylamino or hydroxysulfonyl; R.sup.5 is ##STR2## provided that when R is an unsubstituted monocyclic ring, the monocyclic ring is not phenyl or pyridyl.
    Type: Grant
    Filed: September 29, 1994
    Date of Patent: July 8, 1997
    Assignee: Merck & Co., Inc.
    Inventors: Bohumil Bednar, Melissa Egbertson, Robert J. Gould, George D. Hartman, Jules A. Shafer
  • Patent number: 5633132
    Abstract: The present invention relates to a method of determining the presence of an antigen, particularly the HLA-B.sub.27 antigen, at the surface of cells, particularly lymphocytes, by combining the sensitivity of a cytotoxicity test, particularly a lymphotoxicity test, combined to a fluororescence detection, particularly, by using propidium iodide. The claimed method does not involve any purification of lymphocytes from a blood sample. The erythrocytes contained in the test blood sample are lysed after the immune reaction and complement action is completed. Moreover, the formation of the immune complexes, the complement fixation and reaction and the staining of the cells may take place at the same time in the test tube. This method is therefore very simple and very fast to execute. The facility of reading the positive cells is also an advantage to the claimed method over and above the methods using dyes like eosin or trypan blue, because of the direct visualization of colored cells as positive cells.
    Type: Grant
    Filed: April 28, 1994
    Date of Patent: May 27, 1997
    Assignee: Immunova Ltee
    Inventors: Raynald Roy, Jacques Hebert
  • Patent number: 5631169
    Abstract: A fluorometric luminescence immunoassay method includes forming a sample by exposing a first immune reaction reactant to a second immune reaction reactant capable of reacting with the first reactant, one of the first and second immune reaction reactants being labelled with a photoluminescent energy transfer donor and the other being labelled with a photoluminescent energy transfer acceptor complementary to the photoluminescent donor. At least the photoluminescent donor has the property of photoluminescence, and the photoluminescent donor and acceptor are chosen so that when the first immune reaction reactant reacts with the second immune reaction reactant, the donor and the acceptor are capable of interacting to produce a detectable luminescence lifetime change. The sample is excited with radiation, and the resulting emission is detected. The apparent luminescent lifetime is then calculated to determine the presence of a reaction product of the first and second immune reaction reactants.
    Type: Grant
    Filed: January 19, 1994
    Date of Patent: May 20, 1997
    Assignees: Joseph R. Lakowicz, Richard Thompson
    Inventors: Joseph R. Lakowicz, Badri P. Maliwal, Richard Thompson, Alvydas Ozinskas
  • Patent number: 5627037
    Abstract: This invention comprises a one step method for the detection and enumeration of absolute counts of one or more cell populations in a blood sample. The method employs a reagent comprising a mixture of one or more cell markers, a fluorescent microparticle and a fixative. The reagent may be combined with unlysed whole blood and analyzed by means of flow cytometry.
    Type: Grant
    Filed: August 9, 1994
    Date of Patent: May 6, 1997
    Assignee: Becton Dickinson and Company
    Inventors: Anthony J. Ward, Thomas J. Mercolino, Diether J. Recktenwald
  • Patent number: 5627040
    Abstract: This invention relates to a method for autoclustering N-dimensional datastreams. The invention has particular utility in analyzing multi-parameter data from a flow cytometer, and more particularly has utility in analyzing data from whole blood cells tagged with fluorescently labelled CD3, CD4 and CD8 monoclonal antibodies to which a known number of fluorescent microbeads has been added.
    Type: Grant
    Filed: April 26, 1993
    Date of Patent: May 6, 1997
    Assignee: Becton Dickinson and Company
    Inventors: Pierre Bierre, Ronald A. Mickaels
  • Patent number: 5627074
    Abstract: The invention relates to a method of reducing interference in a fluorescent assay of an analyte, which comprises adding fluoride ions to the measuring medium, and to its use in a fluorescent method of detecting and/or determining an analyte in a medium which may contain it.
    Type: Grant
    Filed: September 16, 1994
    Date of Patent: May 6, 1997
    Assignee: CIS Bio International
    Inventors: Gerard Mathis, Christophe DuMont, Etienne J. Jolu
  • Patent number: 5624808
    Abstract: A novel approach to study changes in protein tyrosine phosphorylation during apoptosis, and thereby identify cells committed to apoptosis is presented, methods used to study apoptosis and tyrosine phosphorylation at the single cell level are combined to study directly whether apoptosis in hematopoietic cells is associated with changes in cellular phosphotyrosine levels. The changes in cellular phosphotyrosine content strongly correlated with the appearance of features of cell death such as cell shrinkage, DNA fragmentation and loss of membrane integrity.
    Type: Grant
    Filed: March 28, 1995
    Date of Patent: April 29, 1997
    Assignee: Becton Dickinson and Company
    Inventors: Peter Thompson, Fridjtof Lund-Johannsen
  • Patent number: 5622821
    Abstract: The invention provides lanthanide chelates capable of intense luminescence. The celates comprise a lanthanide chelator covalently joined to a coumarin-like or quinolone-like sensitizer. Exemplary sensitzers include 2- or 4-quinolones, 2- or 4-coumarins, or derivatives thereof e.g. carbostyril 124 (7-amino-4-methyl-2-quinolone), coumarin 120 (7-amino-4-methyl-2-coumarin), coumarin 124 (7-amino-4-(trifluoromethyl)-2-coumarin), aminomethyltrimethylpsoralen, etc.The chelates form high affinity complexes with lanthanides, such as terbium or europium, through chelator groups, such as DTPA. The chelates may be coupled to a wide variety of compounds to create specific labels, probes, diagnostic and/or therapeutic reagents, etc. The chelates find particular use in resonance energy transfer between chelate-lanthanide complexes and another luminescent agent, often a fluorescent non-metal based resonance energy acceptor.
    Type: Grant
    Filed: June 29, 1994
    Date of Patent: April 22, 1997
    Assignee: The Regents of the University of California
    Inventors: Paul R. Selvin, John Hearst
  • Patent number: 5620842
    Abstract: A rapid, simple method for preparing beads for calibrating flow cytometers which contain a known number of fluorophores per bead is presented. Briefly, the invention utilizes beads coated with a stable complex of a fluorophore and an enzyme. the enzymatic activity of a known number of beads gives an accurate measure of fluorophore density on those beads.
    Type: Grant
    Filed: March 29, 1995
    Date of Patent: April 15, 1997
    Assignee: Becton Dickinson and Company
    Inventors: Kenneth A. Davis, James E. Bishop
  • Patent number: 5618533
    Abstract: Diagnostic means and methods for Lyme disease comprising B. burgdorferi flagellin polypeptides and antibodies. Compositions and methods comprising neuroborreliosis-associated antigens useful for the detection, treatment and prevention of neuroborreliosis, arthritis, carditis and other manifestations of Lyme disease.
    Type: Grant
    Filed: December 10, 1993
    Date of Patent: April 8, 1997
    Assignee: Yale University
    Inventors: Richard A. Flavell, Erol Fikrig, Robert Berland
  • Patent number: 5616298
    Abstract: 5(6)-methyl substituted fluorescein derivatives and a process for producing 5(6)-methyl substituted derivatives. Also provided are methods for these utilizing these derivatives as indicator reagents in assays for analytes, indicator reagents which comprise specific binding members attached to these derivatives and test kits which contain these derivatives.
    Type: Grant
    Filed: May 22, 1995
    Date of Patent: April 1, 1997
    Assignee: Abbott Laboratories
    Inventor: Phillip G. Mattingly
  • Patent number: 5610017
    Abstract: This invention relates to a new electrochemiluminescent (ECL) label for oligonucleotides using phosphoramidite chemistry.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: March 11, 1997
    Assignee: Igen, Inc.
    Inventors: Satyanarayana R. Gudibande, John H. Kenten
  • Patent number: 5607864
    Abstract: Fluorescent latices, well suited for a wide variety of analytical techniques, comprise polymer particles having at least one hydrophobic fluorochrome encapsulated therein, notably at least one condensed polyaromatic compound or derivative thereof, or a tetraphenylporphine and/or organometallic complex thereof, and have a detection threshold for fluorescence which is less than or equal to 10.sup.-12 mol of particles per liter of latex.
    Type: Grant
    Filed: October 7, 1994
    Date of Patent: March 4, 1997
    Assignee: Societe Prolabo
    Inventors: Frederic Ricchiero, Joel Richard, Sophie Vaslin
  • Patent number: 5605809
    Abstract: The present invention provides for novel reagents whose fluorescence increases in the presence of particular proteases. The reagents comprise a characteristically folded peptide backbone each end of which is conjugated to a fluorophore. When the folded peptide is cleaved, as by digestion with a protease, the fluorophores provide a high intensity fluorescent signal at a visible wavelength. Because of their high fluorescence signal in the visible wavelengths, these protease indicators are particularly well suited for detection of protease activity in biological samples, in particular in frozen tissue sections. Thus this invention also provides for methods of detecting protease activity in situ in frozen sections.
    Type: Grant
    Filed: October 28, 1994
    Date of Patent: February 25, 1997
    Assignee: Oncoimmunin, Inc.
    Inventors: Akira Komoriya, Beverly S. Packard
  • Patent number: 5605805
    Abstract: A method for automatic lineage assignment of acute leukemias. Eight four-parameter list mode data files are acquired with a flow cytometer in the following sequence: 1. unstained; 2. isotype controls; 3. CD10 FITC, CD19 PE; 4. CD20 FITC, CD5 PE; 5. CD3 FITC, CD22 PE; 6. CD7 FITC, CD33 PE; 7. HLADR FITC, CD13 PE and 8. CD34 FITC, CD38 PE. First, data files 3-8 are clustered employing an algorithm based on nearest neighbors. The clusters are then associated across the data files to form cell populations, using the assumption of light scatter invariance across tubes for each population. The mean positions of each cell population are compared to a decision tree which identifies normal cell populations. To identify leukemic cell populations, the algorithm eliminates normal cell populations from the data space and the remaining populations are classified as B-lineage ALL, T-lineage ALL, AML, AUL, B-CLL or unknown.
    Type: Grant
    Filed: October 19, 1994
    Date of Patent: February 25, 1997
    Assignee: Becton, Dickinson and Company
    Inventors: Ben J. H. Verwer, Leon W. M. M. Terstappen
  • Patent number: 5601983
    Abstract: In a method for measuring a specified component in a specimen by reacting the specimen with a first reagent formed by binding a substance active to the specified component, with carrier particles and a second reagent formed by labelling a substance active to the specified component with a first label, and measuring the substances in the complexes obtained in the reaction, there is disclosed a method featured by labelling the carrier particles with a second label different from the first label, and detecting the second label and then the first label utilizing the detection of the second label as a trigger.This method enables a highly precise measurement without the influence of noise components in the detection of specified trace components in the specimen, utilizing an antigen-antibody reaction or a nucleic acid hybridization.
    Type: Grant
    Filed: February 28, 1995
    Date of Patent: February 11, 1997
    Assignee: Canon Kabushiki Kaisha
    Inventors: Hidehito Takayama, Matsuomi Nishimura, Kazumi Tanaka, Toshikazu Ohnishi, Takeshi Miyazaki