Patents Represented by Attorney, Agent or Law Firm Mitchell E. Alter
  • Patent number: 5834315
    Abstract: A reagent composition which does not contain cyanide ions and a method for measuring hemoglobin concentration in a blood sample. In addition, the reagent composition can be used to measure hemoglobin concentration and differentiate at least two subpopulations of leukocytes from the same reaction product of the reagent composition and a blood sample. The reagent composition comprises at least one lysing agent selected from the group consisting of a quaternary ammonium salt, a pyridinium salt, and combinations thereof, in an amount effective to adequately lyse the erythrocytes and elute the hemoglobin, an antioxidant in an amount effective to convert the released hemoglobin into to a hemochromogen. The pH can be adjusting with a pH agent to provide a pH ranging from 5 to 11.5.
    Type: Grant
    Filed: December 23, 1994
    Date of Patent: November 10, 1998
    Assignee: Coulter Corporation
    Inventors: Mirta I. Riesgo, Carole Jo Young
  • Patent number: 5817518
    Abstract: This invention relates to a lytic reagent and a method of using the lytic reagent for automatically determining leukocyte subpopulations in blood. More specifically, the new lytic reagent lyses red blood cells and affects the eosinophils which enables the differentiation of at least one subpopulation of leukocytes. The lytic reagent is an acidic, hypertonic aqueous solution containing alkali metal salt of alkyl sulfite, an eosinolytic agent, a nonionic surfactant and a physiological salt. When used in combination with a second lytic reagent system, one is able to obtain at least a five part differential of leukocytes using DC and RF measurements.
    Type: Grant
    Filed: December 18, 1995
    Date of Patent: October 6, 1998
    Assignee: Coulter International Corp.
    Inventors: Yi Li, Carole Young, Sergio C. Veulens
  • Patent number: 5798827
    Abstract: The present invention provides an apparatus and method to determine individual red blood cell shape within a flow cytometric aperture. Cell shape is determined by measuring the asymmetry of a light scatter pattern produced by laser illumination of the cell within the aperture by light scatter detectors which collect light from specific angular regions of light scatter, and analyzing the asymmetry of the light scatter patters to determine the individual red blood cell shape. Embodiments of the invention further provide for the determination of red blood cell shape by measuring the asymmetry of a light scatter pattern and measuring electrical resistance of the red blood cell.
    Type: Grant
    Filed: November 26, 1996
    Date of Patent: August 25, 1998
    Assignee: Coulter International Corp.
    Inventors: Robert S. Frank, James L. Wyatt, Weiyan Gong, Carlos M. Rodriguez, Robert C. Leif
  • Patent number: 5786224
    Abstract: A lytic reagent composition is provided which selectively stromatolyses red blood cells in a blood sample. In addition, a lytic reagent system is provided which enables the differentiation of at least three subpopulations of leukocytes. A method for using the lytic reagent system is also provided. Still further, the lytic reagent system finds use in the determination of the hemoglobin in the blood. The lytic reagent system utilizes an alkyl sulfate, polyoxyethylene based surfactant and acid with a hypertonic, alkaline, stabilizing reagent. The system and analysis method maintains the cellular morphology of the leukocytes and can be used to analyze normal and abnormal blood samples, fresh and aged blood, human and non-human animal blood samples.
    Type: Grant
    Filed: June 29, 1995
    Date of Patent: July 28, 1998
    Assignee: Coulter Corporation
    Inventors: Yi Li, Carole Young, Timothy J. Fischer
  • Patent number: 5776720
    Abstract: An assay compound or a salt thereof for assaying the activity of an enzyme inside a metabolically active whole cell is disclosed. The assay compound includes a leaving group and an indicator group. The leaving group is selected from the group comprising amino acids, peptides, saccharides, sulfates, phosphates, esters, phosphate esters, nucleotides, polynucleotides, nucleic acids, pyrimidines, purines, nucleosides, lipids and mixtures thereof. The indicator group is selected from compounds which have a first state when joined to the leaving group, and a second state when the leaving group is cleaved from the indicator group by the enzyme. Preferably, the indicator compounds are rhodamine 110, rhodol, and fluorescein and analogs of these compounds. A method of synthesizing the compound as well as methods of using these compounds to measure enzyme activity are also disclosed.
    Type: Grant
    Filed: May 18, 1995
    Date of Patent: July 7, 1998
    Assignee: Coulter Corporation
    Inventors: Gerald E. Jaffe, Frank J. Lucas, James H. Carter
  • Patent number: 5763280
    Abstract: A cyanide-free lytic reagent composition and method for measuring the total hemoglobin concentration in a blood sample, for counting the number of leukocytes and for deferential counting of three leukocyte subpopulations including lymphocytes, monocytes, and granulocytes are described. The cyanide-free lytic reagent composition includes a hemolytic surfactant chosen from quaternary ammonium salts, pyridinium salts, organic phosphate esters, and alkyl sulfonates to lyse erythrocytes and release hemoglobin, and an organic ligand chosen from triazole and its derivatives, tetrazole and its derivatives, alkaline metal salts of oxonic acid, melamine, aniline-2-sulfonic acid, quinaldic acid, 2-amino-1,3,4-thiadiazole, triazine and its derivatives, urazole, DL-pipecolinic acid. isonicotinamide, anthranilonitrile, 6-aza-2-thiothymine, adenine, 3-(2-thienyl)acrylic acid, benzoic acid and alkali metal and ammonium salts of benzoic acid, and pyrazine and its derivatives to form a stable chromogen with hemoglobin.
    Type: Grant
    Filed: January 21, 1997
    Date of Patent: June 9, 1998
    Assignee: Coulter International Corp.
    Inventors: Yi Li, Carole Young
  • Patent number: 5733719
    Abstract: An assay compound or a salt thereof for assaying the activity of an enzyme inside a metabolically active whole cell is disclosed. The assay compound includes a leaving group and an indicator group. The leaving group is selected from the group comprising amino acids, peptides, saccharides, sulfates, phosphates, esters, phosphate esters, nucleotides, polynucleotides, nucleic acids, pyrimidines, purines, nucleosides, lipids and mixtures thereof. The indicator group is selected from compounds which have a first state when joined to the leaving group, and a second state when the leaving group is cleaved from the indicator group by the enzyme. Preferably, the indicator compounds are rhodamine 110, rhodol, and fluorescein and analogs of these compounds. A method of synthesizing the compound as well as methods of using these compounds to measure enzyme activity are also disclosed.
    Type: Grant
    Filed: May 18, 1995
    Date of Patent: March 31, 1998
    Assignee: Coulter Corporation
    Inventors: Gerald E. Jaffe, Frank J. Lucas, James H. Carter
  • Patent number: 5731206
    Abstract: A lytic reagent composition and a kit of a lytic reagent system are disclosed for the rapid isolation, identification and/or analysis of at least five subpopulations of leukocytes from a whole blood sample. The composition and system have application to any environment in which the study and/or analysis of the leukocyte fraction of whole blood requires their isolation in their native or near native state. The lytic reagent composition of this invention comprises saponin and a carboxylic acid of the formula RCOOH wherein R is H or a C.sub.1-3 aliphatic hydrocarbon radial optionally substituted by one or more carbonyl and/or hydroxy groups. The kit of a lytic reagent system comprises the lytic reagent composition and a quench reagent.
    Type: Grant
    Filed: March 29, 1996
    Date of Patent: March 24, 1998
    Assignee: Coulter Electronics, Inc.
    Inventors: Stephen L. Ledis, Harold R. Crews, Timothy J. Fischer, Ted Sena
  • Patent number: 5698411
    Abstract: A method for assaying the activity of an enzyme inside a metabolically active whole cell is disclosed. The assay compound includes a leaving group and an indicator group. The leaving group is selected from the group comprising amino acids, peptides, saccharides, sulfates, phosphates, esters, phosphate esters, nucleotides, polynucleotides, nucleic acids, pyrimidines, purines, nucleosides, lipids and mixtures thereof. The indicator group is selected from compounds which have a first state when joined to the leaving group, and a second state when the leaving group is cleaved from the indicator group by the enzyme. Preferably, the indicator compounds are rhodamine 110, rhodol, and fluorescein and analogs of these compounds. A method of synthesizing the compound is also disclosed.
    Type: Grant
    Filed: May 18, 1995
    Date of Patent: December 16, 1997
    Assignee: Coulter Corporation
    Inventors: Frank J. Lucas, Gerald E. Jaffe, Steven E. Bott, James H. Carter
  • Patent number: 5686308
    Abstract: A lytic reagent composition is provided which selectively stromatolyses red blood cells in a blood sample. In addition, a lytic reagent system is provided which enable the differentiation of at least two subpopulations of leukocytes. A method for using the lytic reagent system is also provided. Still further, the lytic reagent system find use in the determination of the hemoglobin in the blood. The lytic reagent system utilizes an ethoxylated long chain compound based lysis reagent with an acid and a hypertonic, alkaline, stabilizing reagent. The system and analysis method maintains the cellular morphology of the leukocytes and can be used to analyze normal and abnormal blood samples, fresh and aged blood, human and non-human animal blood samples, as well as other fluid samples such as bone marrow.
    Type: Grant
    Filed: June 8, 1995
    Date of Patent: November 11, 1997
    Assignee: Coulter Corporation
    Inventors: Yi Li, Carole Young, Timothy J. Fischer, James H. Carter
  • Patent number: 5686309
    Abstract: This invention is related to an apparatus and method to determine the hemoglobin concentration of individual red blood cells by measuring the radio frequency resistance (RF) and direct current (DC) resistance resulting during the flow of the cells through a measurement aperture. The hemoglobin concentration of the cell is determined using the ratio of these two resistances. This determination can be made using a focused flow cell and a non-focused flow cell. In addition, the determination can be made with red blood cells which are either in their native, deformable state or with red blood cells that have been isovolumetrically sphered.
    Type: Grant
    Filed: January 19, 1996
    Date of Patent: November 11, 1997
    Assignee: Coulter International Corp.
    Inventors: Robert Stewart Frank, James Lynn Wyatt
  • Patent number: 5653686
    Abstract: A method and transfer device for transferring fluids between closed vials. The transfer device includes a cylinder having a pair of opposing open tubes or tubular portions into which a pair of vials can be inserted to transfer fluid therebetween. The tubes are separated by a wall through which extends a fluid transfer needle and a vent needle which first is inserted into a first vial to vent the first vial into a vent chamber or reservoir formed in the transfer device before the transfer needle is inserted into the first vial. The first vial, stopper first, is inserted into first tube until seated onto an exposed end of the transfer needle. A second vial, stopper first, then is inserted into the second tube until seated onto the opposite exposed end of the transfer needle. A pressure differential between the closed vials preferably can be utilized to transfer a desired fluid portion between the vials.
    Type: Grant
    Filed: January 13, 1995
    Date of Patent: August 5, 1997
    Assignee: Coulter Corporation
    Inventors: Wallace H. Coulter, Charles R. Shambaugh
  • Patent number: 5646335
    Abstract: A wickless temperature controlling apparatus and method to analyze the characteristics of an adsorbent is provided. The apparatus provides a heat transfer between a cooling liquid and a sample vessel immersed in the cooling liquid and further provides a stabilized temperature to the sample vessel. The apparatus further comprises a thermal bridge between a saturation vapor pressure thermometer, which is also immersed in the cooling liquid, and the sample vessel to provide a uniform temperature between the thermometer and the vessel. The method to analyze the adsorbent utilizes the apparatus. In addition, the method includes a novel method of dosing an adsorptive gas to an adsorbent.
    Type: Grant
    Filed: August 24, 1995
    Date of Patent: July 8, 1997
    Assignee: Coulter Corporation
    Inventors: Richard A. Wenman, Jon Fong
  • Patent number: 5616501
    Abstract: A reticulocyte analyzing method and apparatus in which a biological sample stream of ghosted red cells is passed into and through a point focused beam of light, such as laser light. A light detector structure is positioned with respect to the axis of the light beam to provide a light output pulse indicative of the passage of each cell. Electrically conductive contacts within the fluid stream can provide additional electrical pulse outputs of each cell. A staining reagent can be utilized with a ghosting reagent to further differentiate the reticulocytes. The light and the light and electronic produced output pulses or signals can be combined to define and quantify reticulocytes as distinct from other known cell types.
    Type: Grant
    Filed: November 17, 1995
    Date of Patent: April 1, 1997
    Assignee: Coulter Corporation
    Inventors: Carlos M. Rodriguez, Stephen L. Ledis
  • Patent number: 5529933
    Abstract: A hematology control product comprising leukocyte analogs and an aqueous solution of a plasma substance for use in a blood counting instrument is described. The instrument employs a lytic reagent system for the lysable red blood cells in the control product. The plasma substance is in an amount effective to enable the differentiation of each of said leukocyte analogs relative to the physical attributes of the analogs, said physical attributes of the analog are similar to human leukocytes. Preferably, the plasma substance comprises cholesterol or its derivatives.A method for using the cell suspension media comprising an aqueous solution of a plasma substance is also described. The method provides a quality control to determine whether an instrument is operating within manufacturer's specifications.
    Type: Grant
    Filed: February 8, 1995
    Date of Patent: June 25, 1996
    Assignee: Coulter Corporation
    Inventors: Carole Young, Michael N. Elliott, Nancy R. Naylor, Timothy J. Fischer
  • Patent number: 5512485
    Abstract: A hematology control product comprising leukocyte analogs is described. The analogs comprise red blood cells which simulate at least two physical properties of human leukocytes. A method for making leukocyte analogs from blood cells having desired physical properties is also described. The process comprises expanding the cell volume, changing the hemoglobin content of the cell and fixing the cell. Generally, the monocyte and lymphocyte analogs leak hemoglobin from the cell while the eosinophil analog has the hemoglobin precipitated in the cell. A further method is described to use the control product to determine whether an automatic instrument is operating within manufacturer's specification.
    Type: Grant
    Filed: November 21, 1994
    Date of Patent: April 30, 1996
    Assignee: Coulter Corporation
    Inventors: Carole Young, Michael N. Elliott, Timothy J. Fischer, Nancy R. Naylor
  • Patent number: 5492833
    Abstract: A reticulocyte analyzing method and apparatus in which a biological sample stream of ghosted red cells is passed into and through a point focused beam of light, such as laser light. A light detector structure is positioned with respect to the axis of the light beam to provide a light output pulse indicative of the passage of each cell. Electrically conductive contacts within the fluid stream can provide additional electrical pulse outputs of each cell. A staining reagent can be utilized with a ghosting reagent to further differentiate the reticulocytes. The light and the light and electronic produced output pulses or signals can be combined to define and quantify reticulocytes as distinct from other known cell types.
    Type: Grant
    Filed: September 15, 1994
    Date of Patent: February 20, 1996
    Assignee: Coulter Corporation
    Inventors: Carlos M. Rodriguez, Stephen L. Ledis
  • Patent number: 5455007
    Abstract: A universal stripper plate for operating on a plurality of different types of collection containers or tubes. The universal stripper plate includes a universal button for aligning and seating the various tube stoppers or caps for piercing. The universal button is mounted onto a stripper plate, which can be driven into the tube seating/alignment, tube piercing and aspiration and tube release positions. The universal stripper plate also can include a bar code tab to provide a bar code reference and a piercing needle alignment for the various tubes.
    Type: Grant
    Filed: May 27, 1994
    Date of Patent: October 3, 1995
    Assignee: Coulter Corporation
    Inventors: Manuel Calvo, Nicholas Parker, James N. Hoskinson, Etzer Ketant, Kyriakos Christou
  • Patent number: 5451525
    Abstract: A method is provided to ascertain the total number of cells per unit volume of a cell specimen in an apparatus which does not measure the volume of a suspension containing the specimen as it is being analyzed. The method includes mixing a suspension of a known quantity of particles having a first light scatter signal with a known volume of a cell specimen having a second light scatter signal different from the first light scatter signal to obtain a suspension having a concentration of particles per specimen volume, passing each of said particles and each cell in said cell specimen, in turn, through a light beam, each of said particles and cells producing at least one forward light scattering pattern, counting the number of cells and the number of particles in a portion of said suspension, and determining the total number of cells per unit volume of the specimen.
    Type: Grant
    Filed: February 14, 1992
    Date of Patent: September 19, 1995
    Assignee: Coulter Corporation
    Inventors: Mark L. Shenkin, Ronald M. Hamelik, James C. S. Wood
  • Patent number: 5439645
    Abstract: An apparatus which provides an automatic, signal controlled, sample mixing/resuspending, aspiration and delivery system; wherein a demountable, rotatable carousel temporarily holds a multiplicity of sample containers. Electro-mechanical means, including optical sensors, is programmed to automatically move the carousel to a pre-selected position. A self centering vortexer/mixer lifts a selected sample container from the carousel, sealingly engages the sample container within a sample container support and thereafter orbitally mixes and resuspends the sample container contents. An aspiration probe enters the sample container through the support to receive the sample, which is forced out of the sample container by means of compressed air introduced into the sample container via the sample container support. The sample is delivered to an operably associated flow cytometer via the aspiration probe, after which the probe is washed and readied for the next cycle of operation.
    Type: Grant
    Filed: January 25, 1993
    Date of Patent: August 8, 1995
    Assignee: Coulter Corporation
    Inventors: Francisco J. Saralegui, Alex W. Schlinkmann