Patents Represented by Attorney, Agent or Law Firm Mitchell E. Alter
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Patent number: 6159740Abstract: A method and apparatus for performing screening of obscured or partially obscured cells to enumerate one or more cell population subsets. For example, a whole blood sample or portion thereof is screened to provide the desired analysis of one or more white blood cell population subsets in the sample. A white blood cell population including the obscured subset of interest is first counted, along with a standard population. The standard population can be one of the total number of white blood cell populations, a second white blood cell population which does not obscure the shifted or non-shifted sensed characteristic of the subset of interest, an artificial population formed by microspheres which also do not obscure the shifted or non-shifted sensed characteristic of the subset of interest or a white blood cell population into which the sensed characteristic of the subset will be wholly or partially shifted.Type: GrantFiled: May 17, 1990Date of Patent: December 12, 2000Assignee: Coulter CorporationInventors: James Carey Hudson, Thomas Russell, Carlos M. Rodriguez, Wallace H. Coulter
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Patent number: 6110425Abstract: A blood smear slide outloader including a platen for transferring a succession of slides from a dryer to a slide storage basket. The slides are sequentially discharged from one end of the dryer onto a platen and held firmly in place by a gripper. A single stepper motor then rotates the platen to a vertical position as it lowers both into alignment above a slot in the storage basket. A linear actuator causes the gripper to release the slide and deposit it into the slot. The platen then returns to the discharge end of the dryer to receive the next slide.Type: GrantFiled: December 3, 1998Date of Patent: August 29, 2000Assignee: Coulter International Corp.Inventors: Daniel Dashui Gao, Thomas Wollitzer, Daniel B. Roberts
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Patent number: 6111398Abstract: Apparatus for sensing and characterizing particles (e.g., blood cells or ceramic powders) suspended in a liquid medium comprises a conduit through which the particle suspension is caused to pass simultaneously with an electrical current. According to the invention, the interior wall of the conduit effectively varies in resistivity along the length of the conduit to define a delimited central region of high electrical resistivity which is smoothly contiguous on its opposing boundaries to uninsulated distal elements of lesser electrical resistivity. The delimited central region of the conduit functions as a Coulter volumeter conduit. The uninsulated distal elements of the conduit are made to have a dimension along the conduit wall which is at least equal to the axial extent of the effective ambit electric fields of a traditional Coulter volumeter conduit having a cross-sectional geometry identical to that of the delimited central region of high resistivity in the improved volumeter conduit.Type: GrantFiled: July 3, 1997Date of Patent: August 29, 2000Assignee: Coulter International Corp.Inventor: Marshall Donnie Graham
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Patent number: 6079836Abstract: A droplet travel path monitoring mechanism for a flow cytometer is operative to adjust the droplet break-off point back to an initially calibrated spatial location, in the event of the departure from calibrated timing of gaps in the unsorted fluid droplet stream that have been created by the deflection of charged droplets. In addition, the flow cytometer is operative to monitor prescribed characteristics of deflected droplet streams, and to controllably adjust drop-sorting deflection parameters, so as to maintain the deflected travel path of sorted droplets coincident with the opening into a sorted droplet collection container, thereby maximizing collection of all sorted droplets.Type: GrantFiled: July 20, 1998Date of Patent: June 27, 2000Assignee: Coulter International Corp.Inventors: Robert Burr, Todd Lary, Erich Frazier, Osvaldo E. Miranda, Jr.
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Patent number: 6068150Abstract: An elastic stopper and an enclosure cap incorporating the stopper for sealing a vial while allowing piercing of the stopper. The stopper includes a disk-shaped upper portion and a cylindrical-shaped lower portion defining an interior hollow space. The lower portion is divided into a plurality of longitudinal segments by a plurality of slots. A plurality of longitudinal grooves are provided on the inside surface of the lower portion to break the surface tension between the stopper and the liquid contents of the vial that flow into the hollow space of the cap. The enclosure cap allows multiple piercing without leakage of the vial contents and prevents the vial contents from aspirating out when the stopper is pierced with a single lumen needle.Type: GrantFiled: January 27, 1999Date of Patent: May 30, 2000Assignee: Coulter International Corp.Inventors: John Allen Mitchell, Kimberlee Elizabeth Guitar, David Borenstein
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Patent number: 6060322Abstract: A reagent composition and method is provided for identification of reticulated cells from other cell types in a blood cell sample by using optical measurement. More particularly, the reagent composition contains a nucleic acid dye and sphering agent. More particularly, the method enables the identification of reticulated platelets and reticulated erythrocytes. In addition, the method provides for a concurrent determination of cell by cell hemoglobin of the reticulated erythrocytes and mature erythrocytes in the blood cell sample.Type: GrantFiled: October 20, 1998Date of Patent: May 9, 2000Assignee: Coulter International Corp.Inventors: Allan Horton, James L. Wyatt
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Patent number: 5994139Abstract: The present invention relates to a hematology control product for automated hematology instruments containing an aqueous solution of at least one blood cell analog, an absorbance agent in an amount sufficient to simulate a hemoglobin concentration, and a stabilizing agent in an amount sufficient to stabilize the size of the blood cell analog when the control product is subjected to temperature ranging from -15.degree. C. to 45.degree. C. The control product does not require controlled temperature storage for product stability. In addition, a novel method of using a hematology control product is provided wherein the control product contains a single blood cell analog and is used to simulate both red blood cells and white blood cells on an automated hematology instrument.Type: GrantFiled: April 7, 1998Date of Patent: November 30, 1999Assignee: Coulter International Corp.Inventors: Dana B. Jacobs, Ted Gerula, Wayne M. Goldson, Michael N. Elliott
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Patent number: 5976822Abstract: The ability to determine the stage or pathway of cysteine proteases in a single cell assay has long been desired as a material event in apoptosis. The present invention relates to a method and assay reagents for determining enzyme activity and relating said activity to the apoptotic pathway. In addition, the method find utility in distinguishing apoptotic activity from necrotic activity.Type: GrantFiled: August 20, 1997Date of Patent: November 2, 1999Assignee: Coulter International Corp.Inventors: Eileen Landrum, Adry Galiounghi, Nancy Garcia, Ursino Del Valle, Frank J. Lucas
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Patent number: 5968831Abstract: The invention provides a cell control product for use with a cytoenzymology assay to confirm enzymatic activity in devices employing electronic and/or optical means. The cell control product comprises a lyophilized mammalian cell which is capable of being rehydrated in water to exhibit cellular structure and cellular enzymatic activity so that said lyophilized cells can function effectively as a cytoenzymology cell control in an enzymatic analysis. The cellular structure of the cell control is capable of being authenticated by light scatter or microscopy analysis and the cellular enzymatic activity is capable of being authenticated by fluorescence analysis. The cell control exhibits a real time stability when stored at between 2 and 8.degree. C. for at least a two month period of time. Preferably the mammalian cell is an abnormal cell selected from Molt 4, CCRF-CEM and HL-60 cell lines.Type: GrantFiled: October 29, 1996Date of Patent: October 19, 1999Assignee: Coulter International Corp.Inventors: Ravindra S. Shukla, Harold R. Crews, Adry Galiounghi, Eileen Landrum, Frank J. Lucas
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Patent number: 5935801Abstract: A monoclonal antibody which specifically binds to an antigen on the membrane of mitochondria in apoptotic cells. The antigen is a 38 kD protein that is detectable in cells undergoing apoptosis and undetectable in normal cells. This selectivity of the monoclonal antibody provides a method of distinguishing between normal and apoptotic cells in a sample of human hemopoietic cell populations. A method for detecting and measuring cells undergoing apoptosis is also provided.Type: GrantFiled: March 29, 1996Date of Patent: August 10, 1999Assignee: Dana-Farber Cancer InstituteInventors: Stuart Franklin Schlossman, Chonghui Zhang
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Patent number: 5935857Abstract: An improved isotonic multipurpose blood diluent, and a method for use of this diluent is provided. The diluent is especially suitable for electronic enumeration and sizing of blood cells, determination of hemoglobin parameters and differentiation of leukocyte subpopulations in a single blood cell sample using a cyanide free lytic reagent. The diluent finds particular applicability over wide operating temperatures.Type: GrantFiled: August 1, 1997Date of Patent: August 10, 1999Assignee: Coulter International Corp.Inventors: Mirta I. Riesgo, Carole Jo Young
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Patent number: 5917584Abstract: A method is provided for differentiation of nucleated red blood cells. In addition, the method provides for a concurrent differentiation of leukocytes in a blood cell sample by suitable electronic and optical measurements. The method includes exposing a blood cell sample to a reagent system to lyse mature red blood cells and subsequently analyzing nucleated red blood cells in a flow cell by optical analysis. A concurrent differentiation of nucleated blood cells and leukocytes can be performed using electronic and optical analysis. The electronic and optical analysis includes light scatter and impedance measurements. This method eliminates the use of nuclear stain for identification of nucleated red blood cells. The method of the present invention, for the first time, reports differentiation and enumeration of nucleated red blood cells without using fluorescence.Type: GrantFiled: January 22, 1998Date of Patent: June 29, 1999Assignee: Coulter International Corp.Inventors: Yi Li, Jing Li, Carole Young
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Patent number: 5905031Abstract: The necessity to detect blast cells in a patient sample to determine a treatment regime for leukemia has long been desired. The present invention relates to a method and assay reagents for identification of blast cells in a fluid sample. The method further enables the determination of the lineage of the blast cells. The new method provides a determination of blast cells in less time than prior art methods.Type: GrantFiled: November 1, 1996Date of Patent: May 18, 1999Assignee: Coulter International Corp.Inventors: Nazle Kuylen, Harold R. Crews, Gerald E. Jaffe, Maria Barcelon, Francis J. Lucas, Nancy M. Garcia
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Patent number: 5882934Abstract: 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 leukocyte subpopulations are described. The cyanide-free lytic reagent composition cotains a quaternary ammonium salt or a pyridinium salt to lyse erythrocytes and release hemoglobin, and an organic ligand including 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, 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, and a salt to adjust conductivity of the reagent for impedance measurement.Type: GrantFiled: March 24, 1998Date of Patent: March 16, 1999Assignee: Coulter International Corp.Inventors: Yi Li, Carole Young
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Patent number: 5882933Abstract: A method is provided for differentiating leukocyte subpopulations, immunophenotyping of lymphocytes and counting white blood cells. The method preserves leukocyte morphology and surface markers without using fixatives. In addition, the method finds utility in determination of hemoglobin concentration without using cyanide. The stable hemoglobin chromogen formed is measured at approximately 540 nm.Type: GrantFiled: July 25, 1997Date of Patent: March 16, 1999Assignee: Coulter International Corp.Inventors: Yi Li, Carole Young, Robert H. Raynor
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Patent number: 5874310Abstract: A method is provided for differentiation of nucleated red blood cells. In addition, the method provides for a concurrent differentiation of leukocytes in a blood cell sample by suitable electronic and optical measurements. The method includes exposing a blood cell sample to a reagent system to lyse mature red blood cells and subsequently analyzing nucleated red blood cells in a flow cell by optical analysis. A concurrent differentiation of nucleated blood cells and leukocytes can be performed using electronic and optical analysis. The electronic and optical analysis includes light scatter and impedance measurements. This method eliminates the use of nuclear stain for identification of nucleated red blood cells. The method of the present invention, for the first time, reports differentiation and enumeration of nucleated red blood cells without using fluorescence.Type: GrantFiled: November 21, 1997Date of Patent: February 23, 1999Assignee: Coulter International Corp.Inventors: Yi Li, Jing Li, Carole Young
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Patent number: 5874311Abstract: A method is provided for differentiation of reticulocytes. In addition, the method provides for a concurrent differentiation of leukocyte subpopulations in a blood cell sample by suitable electronic and optical measurements. The method includes exposing a blood cell sample to a reagent system to lyse mature red blood cells and subsequently analyzing reticulocytes in a flow cell by optical analysis. A concurrent differentiation of reticulocytes and leukocytes can be performed using electronic and optical analysis. The electronic and optical analysis includes light scatter and impedance measurements. This method does not require the use of nuclear stain for differentiation of reticulocytes.Type: GrantFiled: November 21, 1997Date of Patent: February 23, 1999Assignee: Coulter International Corp.Inventors: Yi Li, Jing Li, Carole Young
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Patent number: 5871946Abstract: 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: GrantFiled: May 18, 1995Date of Patent: February 16, 1999Assignee: Coulter CorporationInventors: Frank J. Lucas, Gerald E. Jaffe, Steven Bott, James H. Carter
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Patent number: 5849513Abstract: 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: GrantFiled: July 31, 1997Date of Patent: December 15, 1998Assignee: Coulter CorporationInventors: Gerald E. Jaffe, Frank J. Lucas, James H. Carter
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Patent number: 5843608Abstract: 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 solubilizer, 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: GrantFiled: November 4, 1997Date of Patent: December 1, 1998Assignee: Coulter International Corp.Inventors: Yi Li, Carole Young, Timothy J. Fischer, James H. Carter, Sergio C. Veulens