Patents Represented by Attorney, Agent or Law Firm Mitchell E. Alter
  • Patent number: 6798508
    Abstract: Apparatus for detecting light scattered by a small particle (e.g., a blood cell) irradiated by a light beam comprises one or more photodetectors and a plurality of optical fibers that serve to optically couple the scattered light and the photodetector(s). To enhance the efficiency of such optical coupling, a portion of each of the optical fibers in the vicinity of its light-collecting end is supported so that its optical axis extends towards the light-scattering source. By this arrangement, scattered light enters each fiber from a direction substantially parallel to the fiber axis. Preferably, the light-collecting ends of the optical fibers are supported on a concave surface and so that the respective optical axes of the fibers converge at a point representing the apparent position of the light-scattering source, taking into account the refractive effects of an optical flow cell through which scattering is detected.
    Type: Grant
    Filed: August 23, 2002
    Date of Patent: September 28, 2004
    Assignee: Coulter International Corp.
    Inventor: Donald L. Kramer
  • Patent number: 6778910
    Abstract: A signal processing operator successfully expands the dynamic range of a histogram of digital data, such as that representative of biological cell populations, including human blood cells subjected to flow cytometry processing, without introducing binning artifacts into the transformed data. The inventive data mapping scheme effectively preserves statistical probability distribution characteristics of the original data, that would otherwise be removed or lost in the course of expanding the dynamic range of a quantized histogram data set through the use of a conventional log transformation. Filtering is unnecessary, as the binning effect is countered early in the process, to preserve statistical properties of the cell populations under study.
    Type: Grant
    Filed: February 26, 2003
    Date of Patent: August 17, 2004
    Assignee: Coulter International Corp.
    Inventors: Patricio Vidal, John S. Riley, Malek Adjouadi
  • Patent number: 6744245
    Abstract: A method is disclosed which allows more accurate counting of particles where the sample has significant size variability between particles. The method uses flight time and wait time to obtain a corrected count of particles.
    Type: Grant
    Filed: July 27, 2001
    Date of Patent: June 1, 2004
    Assignee: Coulter International Corp.
    Inventors: Richard Lee Taylor, Min Zheng
  • Patent number: 6743634
    Abstract: Blood cells of interest are readily distinguishable from other blood cells and look-a-like particles found in a blood sample by their back-scatter signature. A preferred method for differentiating platelets in a blood sample is to irradiate the cells and particles, one at a time, with a beam of radiation, and to detect back-scattered (reflected) radiation using a plurality of optical fibers to transmit the back-scattered radiation to a high-gain photodetector, e.g. a photomultiplier tube. Preferably, the back-scatter signal so obtained is combined with a second signal representing, for example, either the level of forward-scatter within a prescribed, relatively narrow angular range, or the level of side-scattered radiation, or the level of attenuation of the cell-irradiating beam caused by the presence of the irradiated cell or particle in the beam, or the electrical impedance of the irradiated cell or particle, to differentiate the cells of interest.
    Type: Grant
    Filed: August 23, 2002
    Date of Patent: June 1, 2004
    Assignee: Coulter International Corp.
    Inventor: Donald L. Kramer
  • Patent number: 6706526
    Abstract: A low formaldehyde containing aqueous blood diluent contains an effective amount of ethylenediamine tetraacetic acid, ethylenediamine tetraacetic acid derivative, or combinations thereof; an effective amount of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one; and an effective amount of 5-bromo-5-nitro-1,3-dioxane. Advantageously, less than about 1 parts per million of formaldehyde is produced in this multipurpose diluent. A method of analyzing a blood sample containing blood cells is conducted by forming a diluted blood sample by mixing a blood sample containing blood cells with this diluent and analyzing the diluted blood sample to determine a physical parameter of the blood cells.
    Type: Grant
    Filed: January 24, 2002
    Date of Patent: March 16, 2004
    Assignee: Coulter International Corp.
    Inventors: Russell F. Lang, Iris L. Payan, Barbara G. Murza, Luisa C. Oramas
  • Patent number: 6692702
    Abstract: A method for utilizing a filtration device for removing interferants from a sample containing cells in an automated apparatus is disclosed. The filtration device includes a microporous hollow fiber membrane having a plurality of pores sized to retain cells while allowing smaller diameter interferants to pass through the membrane. The apparatus also includes a means for of moving the sample from a sample container to and from the filtration device. The disclosed method utilizes a vacuum source to aspirate the sample into a lumen of the hollow fiber membrane so that the sample is retained in the lumen space until expelled into an analysis container or transported to an analyzer.
    Type: Grant
    Filed: July 7, 2000
    Date of Patent: February 17, 2004
    Assignee: Coulter International Corp.
    Inventors: Alexander Burshteyn, John W. Joubran, Nazle Kuylen, Frank J. Lucas
  • Patent number: 6692968
    Abstract: A method for utilizing a filtration device for removing interferants from a test sample containing a mixture of a composition of interest and interferants in an automated apparatus is disclosed. The filtration device includes a microporous hollow fiber membrane having a plurality of pores sized to retain the composition of interest while allowing smaller diameter interferants to pass through the membrane.
    Type: Grant
    Filed: September 20, 2001
    Date of Patent: February 17, 2004
    Assignee: Coulter International Corp.
    Inventors: Alexander Burshteyn, John W. Joubran, Nazle Kuylen, Frank J. Lucas, Carlos L. Aparicio, Michael L. Bell, Ravinder Gupta, Maria Elena Insausti, Jack D. McNeal, Paul W. Price, Sandra Socarras
  • Patent number: 6673618
    Abstract: A method for differentiating and enumerating nucleated red blood cells in a blood sample is described. The method includes the steps of lysing red blood cells of a blood sample with a lytic reagent, measuring nucleated blood cells by DC impedance measurement in a non-focused flow aperture, differentiating nucleated red blood cells from other cell types, and reporting nucleated red blood cells in the blood sample. The method further includes subtracting nucleated red blood cells and other interference materials from the count of remaining blood cells, and reporting a corrected white blood cell count of the blood sample. Additionally, the method further includes measuring spectrophotometric absorbance of the sample mixture at a predetermined wavelength of a hemoglobin chromogen formed upon lysing the blood sample, and reporting hemoglobin concentration of the blood sample.
    Type: Grant
    Filed: August 23, 2002
    Date of Patent: January 6, 2004
    Assignee: Coulter International Corp.
    Inventors: Yi Li, Jing Li, Ted W. Britton
  • Patent number: 6581012
    Abstract: An integrated clinical laboratory software system for testing a specimen. At least one specimen processing module is advantageously provided, each for performing particular predetermined tests on the specimen. Integrated work flow automation programming communicates with any of the plurality of specimen processing modules. The specimen processing modules can include instrument hardware and embedded process control software. The work flow automation programming includes request processing programming for processing a user request for any of the tests which are available to be performed by the specimen processing modules, and also includes functional control programming which provides functional control of any of the plurality of specimen processing modules for performing any of the tests, and which further includes result data management programming provides processing of test result data of any of the tests.
    Type: Grant
    Filed: July 30, 1999
    Date of Patent: June 17, 2003
    Assignee: Coulter International Corp.
    Inventors: Michael Aryev, Andrea L. Krensky, Fredric W. Huls, Gerardo Garcia, Bin Qin, David J. Roach
  • Patent number: 6579685
    Abstract: A method for performing screening of one or more cell groups of interest obscured by a cell population such as one or more subsets of interest of a WBC population utilizing at least one light sensing parameter. The cell group of interest is enumerated by utilizing microspheres having monoclonal antibodies bound thereto to modify the sensed characteristics of specified cells to differentiate the cell group of interest from the obscuring cell population.
    Type: Grant
    Filed: September 9, 1994
    Date of Patent: June 17, 2003
    Assignee: Coulter International Corp.
    Inventors: Thomas Russell, James Carey Hudson, Wallace H. Coulter, Carlos M. Rodriguez, Constance Mary Hajek
  • Patent number: 6573102
    Abstract: A lytic reagent composition for measuring nucleated blood cells in a blood sample is described. The lytic reagent composition contains a quaternary ammonium surfactant, an ethoxylated phenol, and an ethoxylated alcohol. When mixed with a blood sample, the lytic reagent composition lyses red blood cells and enables a differentiation of nucleated red blood cells from other cell types by DC impedance measurement. The lytic reagent composition can further contain an organic ligand for determining total hemoglobin concentration of a blood sample photometrically. Further disclosed is a lytic reagent system including the lytic reagent composition and a diluent. In addition, a single reagent composition containing salts is also disclosed, which can be used without a separate diluent. The lytic reagent compositions can be used for concurrent measurement of nucleated red blood cells, WBC, and hemoglobin of a blood sample.
    Type: Grant
    Filed: July 27, 2001
    Date of Patent: June 3, 2003
    Assignee: Coulter International Corp.
    Inventors: Yi Li, Jing Li
  • Patent number: 6572255
    Abstract: A physically compact (saline) solution preparation apparatus includes a solution mixing tank coupled to sources of concentrate and diluent. A concentrate transport path is configured to both homogenize and deliver concentrate to the mixing tank, while the diluent transport path is controllably purged of potential contaminates prior to supplying the diluent to the mixing tank. A mixed solution transport path recirculates and thereby homogenizes the contents of the mixing container, and actively pumps out solution that has been mixed to a prescribed conductivity-based concentration, to one or more solution on demand storage reservoirs for respective instruments. The operation of the apparatus is based upon measured conductivity of the contents of the solution mixing tank, so that there is no need to conduct precursor volumetric measurements of either diluent or concentrate.
    Type: Grant
    Filed: April 24, 2001
    Date of Patent: June 3, 2003
    Assignee: Coulter International Corp.
    Inventor: Frederick K. Husher
  • Patent number: 6569682
    Abstract: An improved blood suspension media for hematological compositions, having particular utility with a red blood cell component for devices using electronic and optical means for blood determinations, and processes for using the suspension media. The suspension media finds particular utility in providing the hematology control product with a stable and consistent MCV and RDW for an extended product shelf life.
    Type: Grant
    Filed: July 27, 2001
    Date of Patent: May 27, 2003
    Assignee: Coulter International Corp.
    Inventors: Michael Elliott, Dana B. Jacobs, Nery Ortiz, Wayne Goldson, Penny Whitley, Theodore J. Gerula
  • Patent number: 6551831
    Abstract: The dyes of the present invention are useful for many purposes that include markers or tags for detecting the presence of a molecule or compound to which they are bound. The dyes may be either red-excitable or blue-excitable. The dyes of the invention are particularly well suited for staining of nucleic acids. For example, these dyes are particularly suitable for staining of RNA in reticulocytes. In another exemplary application, these dyes are suitable for staining DNA in nucleated red blood cells. Typically, when used in staining of nucleic acids, the dyes are formulated into reagent solutions. In addition, the invention provides compositions and methods for facilitating rapid transport of dye molecules through a cell membrane. Such rapid staining requires that a sample be contacted with a dye composition of the invention in the presence of at least one surfactant and optionally, a sulfonic acid or a salt thereof.
    Type: Grant
    Filed: May 4, 2001
    Date of Patent: April 22, 2003
    Assignee: Coulter International Corp.
    Inventors: Ravinder Gupta, Song Y. Lee, Gene G.-Y. Shen, Stephen Szydlo, Chiranjit Deka
  • Patent number: 6535836
    Abstract: A method for analyzing an abnormal particle population in an experimental sample containing particles involves a particle property distribution index based on an average particle property (e.g., size) distribution curve for multiple normal samples in a particle analysis instrument. The process involves producing an experimental particle property distribution curve by analyzing an experimental sample containing particles in the instrument. The distribution curve of the experimental sample is analyzed to identify particle populations at the lower or upper region of the experimental distribution curve that differ from particle populations in the regions of an average particle property distribution curve. Thereafter, the number of particles within the lower or upper region of the experimental distribution curve that differs from the average curve is determined and employed for diagnosis of a relevant characteristic of the particle population.
    Type: Grant
    Filed: September 29, 2000
    Date of Patent: March 18, 2003
    Assignee: Coulter International Corp.
    Inventor: Eric Malcolm Grace
  • Patent number: 6514772
    Abstract: A semiconductor nanoparticle for use in analysis of biological samples is described. This semiconductor nanoparticle is composed of an aminodextran which is bound to at least one nanoparticle of the formula (X Y)n wherein X is selected from the group comprising Cd2+, Hg2+, and Zn2+ and combinations thereof, and Y is selected from the group comprising S2−, Se2− and Te2− and combinations thereof; and n=approximately 50 to 1000. Also provided are methods of making these semiconductor nanoparticles and methods of making conjugates composed of these semiconductor nanoparticles linked to ligands. Also described are uses for the conjugates in a variety of biological assays.
    Type: Grant
    Filed: May 8, 2001
    Date of Patent: February 4, 2003
    Assignee: Coulter International Corp.
    Inventors: Olavi Siiman, Egon Matijevic, Ivan Sondi
  • Patent number: 6472215
    Abstract: A method of analyzing nucleated red blood cells (NRBCs) in a blood sample and further enumerating NRBCs is disclosed. The method includes lysing a first aliquot and a second aliquot of a blood sample separately with a first lysing reagent system and a second lysing reagent system; measuring the first sample mixture in a flow cell by DC, RF, and light scatter measurements; measuring cell distributions and counting remaining blood cells in the second sample mixture by DC impedance measurements in a non-focused flow aperture; analyzing blood cell distribution patterns obtained from measuring the first sample mixture and from measuring the second sample mixture respectively; and further performing a combined analysis to differentiate NRBCs from other cell types and determine numbers of NRBCs in the blood sample.
    Type: Grant
    Filed: July 27, 2001
    Date of Patent: October 29, 2002
    Assignee: Coulter International Corp.
    Inventors: Ziling Huo, Jaesang Park, Wei Yao, Shuliang Zhang, Min Zheng
  • Patent number: 6454141
    Abstract: An apparatus and a method for dispersing and feeding dry powders without using pressurized air are disclosed. The apparatus comprises a sample holder, a suction probe, a vacuum means and a positional means. The suction probe is positioned above dry powders in the sample holder, a space between the suction probe and the sample holder is substantially small that allows non-pressurized ambient air to form an high velocity downward air flow when a vacuum is applied to the suction probe. A change of air flow direction at an orifice of the suction probe generates a high shear force above the dry powders, which disperses the dry powders into an airstream. The apparatus feeds the dry powder airstream to a particle analyzer with a controlled rate. The apparatus and method are particularly useful in sizing particles using laser diffraction or image analysis techniques.
    Type: Grant
    Filed: July 25, 2001
    Date of Patent: September 24, 2002
    Assignee: Coulter International Corp.
    Inventors: Thomas Breen, Brian Schmitz
  • Patent number: 6452372
    Abstract: A junction field effect transistor (JFET) RF oscillator-detector circuit generates an RF signal for an apparatus for conducting electrical measurements of particles contained in a carrier fluid passing through an aperture in a cytometer flow cell. The JFET oscillator includes a plurality of parallel-coupled JFETs having respectively different VDS vs. IDS characteristics, that are biased to operate at square law detection regions of their respective VDS vs. IDS characteristics. One JFET operates in Class C mode, while the other operates in Class AB mode. An RF resonant circuit is electrically coupled to the JFETs and to the measurement cell, and is operative to establish the frequency of an RF field applied to the measurement cell. An RF load change detection circuit is coupled to the RF resonator circuit and is operative to detect an RF load change associated with a modification of the RF field as a result of a particle within the measurement cell aperture.
    Type: Grant
    Filed: September 14, 2001
    Date of Patent: September 17, 2002
    Assignee: Coulter International Corp.
    Inventors: Frederick K. Husher, Gerard Schneider, Lazaro Ramirez
  • Patent number: 6410330
    Abstract: A method for differentiating and enumerating nucleated red blood cells in a blood sample is described. The method includes the steps of lysing red blood cells of a blood sample with a lytic reagent, measuring nucleated blood cells by DC impedance measurement in a non-focused flow aperture, differentiating nucleated red blood cells from other cell types, and reporting nucleated red blood cells in the blood sample. The method further includes subtracting nucleated red blood cells and other interference materials from the count of remaining blood cells, and reporting a corrected white blood cell count of the blood sample. Additionally, the method further includes measuring spectrophotometric absorbance of the sample mixture at a predetermined wavelength of a hemoglobin chromogen formed upon lysing the blood sample, and reporting hemoglobin concentration of the blood sample.
    Type: Grant
    Filed: July 27, 2001
    Date of Patent: June 25, 2002
    Assignee: Coulter International Corp.
    Inventors: Yi Li, Jing Li, Ted W. Britton