Coulter Electronics, Inc.

Coulter Corporation

Coulter International Corp.

Miltenyi Biotec, Gmbh

Wallace H Coulter

Thomas R Russell

Carlos M Rodriguez

Walter R Hogg

Ronald D Paul

Kenneth H Kortright

Constance M Hajek

James Carey Hudson

John D Hollinger

Edward N Doty

Stephen K Campbell

Robert J Schmittling

Robert K Zwerner

William F Rothermel

Charles Raymond Shambaugh, Jr

Robert E Auer

Michael R Groves

Ernesto Bello

Gerhard A Liedholz

Steven N Kolber

Ermi Roos

Millard D Longman, Jr

Millard D Longman

Walter M Mena

Robert F Brunhouse

John P Matthews

James W Walker

Hogg, Walter R

A separation procedure for separating a selected desired or undesired population from a biological sample utilizing relatively heavy, dense particles and gravity sedimentation. The particles have one or more reactants bound thereto which are specific to and will bind with the selected population. The particles preferably are mixed with the sample by repeatedly causing the particles to settle through a substantial portion of the sample to bind to the selected population. The particles with the bound selected population then are allowed to preferentially settle in the sample and the supernatant including an enriched population is separated from the particles with the selected population bound thereto. The enriched populations in the biological sample supernatant can be further enriched by multiple removal steps.

Method of selection of a population or subpopulation of a sample utilizing particles and gravity sedimentation

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.

Method and apparatus for screening microscopic cells utilizing light scatter techniques

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. The sensed characteristic of the white blood cell population subset of interest then is shifted by binding microspheres having monoclonal antibodies specific to the white blood cell population subset of interest to the cell population. The white blood cell population, and the standard population then are again counted and compared to the original counts to obtain an enumeration of the white blood cell population subset of interest.

Method and apparatus for screening obscured or partially obscured cells

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.

Closed vial transfer method and system

A separation procedure for separating a selected desired or undesired population from a biological sample utilizing relatively heavy, dense particles and gravity sedimentation. The particles have one or more reactants bound thereto which are specific to and will bind with the selected population. The particles preferably are mixed with the sample by repeatedly causing the particles to settle through a substantial portion of the sample to bind to the selected population. The particles with the bound selected population then are allowed to preferentially settle in the sample and the supernatant including the non-selected population is separated from the particles with the selected population bound thereto. The particles can be heated for sterilization and endotoxin removal.

Method of positive or negative selection of a population or

A method and apparatus for accelerating at least one definitive biological reaction including increasing the accuracy of determinations made therefrom. The reaction involves selected viable biological cells which are prepared in a small sample volume and rapidly mixed with microspheres having antibody specific at least to specific ones of the cells bound thereto. The microspheres can be magnetic and the bound cells can be magnetically removed to analyze the remaining blood cell populations. The microspheres can be introduced sequentially or simultaneously.

Method and apparatus for rapid mixing of small volumes for enhancing

A method and apparatus for automatically and rapidly, retrieving, counting and/or analyzing at least one selected white blood cell population and/or subset thereof of a whole blood sample or portion thereof. A volume of a biological sample containing the white blood cells is prepared and at least one reactant specific or preferential at least to some selected biological cells is introduced thereto and rapidly mixed for a short period of time. The opacity and/or volume parameter of the cells can be modified and the mixture is then counted and analyzed in one or more steps to obtain the desired white blood cell population analysis. The biological sample can be a whole blood sample and the reactant can include or be a lyse or a monoclonal antibody bound to microspheres, which will bind to specific ones of the cells or a combination of lyse and microspheres with antibody bound thereto. The microspheres can be magnetic and the bound cells can be magnetically removed for retrieving and analyzing the remaining blood cell population.

Automated analyzer for screening cells or formed bodies for enumeration

An optical screening method and apparatus for identifying and counting cells expressing selected characteristics or properties. The cells are combined with one or more different sets of microspheres, each set having a reactant bound thereto which will bind to a specific molecule which can exist on one or more types of the cells. The cells and microspheres are formed in a known volume on a slide and optically viewed to identify and count the type of cells to which the different sets of microspheres do or do not bind. The cell count then is related to the known volume to provide an absolute cell count. A plurality of different sample portions can be utilized with different reactants to obtain a multipart WBC differential/absolute count. The different sets of microspheres are optically differentiated by having different optical characteristics, such as size, shape, color or combinations thereof.

Method and apparatus for obtaining an absolute white blood cell subset

A method and apparatus for automatically and rapidly, retrieving counting and/or analyzing at least one selected population of cells or formed bodies, such as a white blood cell population and at least one subset thereof of a whole blood sample or portion thereof. A volume of a biological medium containing the white blood cells is prepared and at least one reactant specific or preferential at least to some selected biological cells is introduced thereto and rapidly mixed for a short period of time. A multipart blood cell analysis is obtained with a single sensing parameter by depleting at least one WBC subset population. The percentage of a desired WBC population subset or the overlapping of WBC subset populations also can be obtained by subtracting one or more obscuring WBC subset populations. The biological sample can be a whole blood sample and the reactant can include or be a lyse or a monoclonal antibody bound to microspheres, which will bind to specific ones of the cells or a combination of lyse and microspheres with antibody bound thereto. The microspheres can be magnetic and the bound cells can be magnetically removed for retrieving and analyzing the remaining blood cell population.

Method and apparatus for screening cells or formed bodies with

A method and apparatus for automatically and rapidly, retrieving, counting and/or analyzing at least one selected population of cells or formed bodies, such as a white blood cell population and at least one subset thereof of a whole blood sample or portion thereof. A volume of a biological medium containing the white blood cells is prepared and at least one reactant specific or preferential at least to some selected biological cells is introduced thereto and rapidly mixed for a short period of time. The opacity and/or volume parameter of the cells can be modified and the mixture is then counted and analyzed in one or more steps to obtain the desired white blood cell population and subset analysis. The biological sample can be a whole blood sample and the reactant can include or be a lyse or a monoclonal antibody bound to microspheres, which will bind to specific ones of the cells or a combination of lyse and microspheres with antibody bound thereto. The microspheres can be magnetic and the bound cells can be magnetically removed for retrieving and analyzing the remaining blood cell population.

Method for screening cells or formed bodies for enumeration of

Disclosed is a flow through particle analyzing cell differentiating apparatus for optical and electronic measurements on a stream of particles in which a hydrodynamically focoussed stream is passed into and through a point focussed beam of radiated energy whereby the beam is scattered by the stream to impinge upon light responsive signal operating members disposed adjacent the cell at angular positions relative to the beam axis of from about 10.degree. to 70.degree..

Multi-part differential analyzing apparatus utilizing light scatter

A circuit, which is useful to provide data needed to measure the electrical opacity of a particle, for instance a blood cell, passing through a Coulter type transducer, includes a current source for providing a conventional d.c. current through the sensing aperture of the transducer, as well as an oscillator for providing a high frequency current through the aperture. The oscillator includes an active device and a resonant circuit, and the aperture is coupled in parallel with the resonant circuit of the oscillator. The oscillator can be any type of oscillator, such as a Hartley oscillator. As a particle passes through the aperture, the resistance of the aperture increases, which in turn, increases the Q of the oscillator circuit, whereby the oscillator output signal is amplitude modulated in accordance with the increased Q. This amplitude modulated signal can be detected to provide a value based on the high frequency reactance of the particle being detected. The change in d.c. resistance due to a particle passing through the aperture is detected in a conventional manner. The detected amplitudes of the a.c. and d.c. signals then can be compared to determine the opacity of each particle. Multiple oscillators of different frequencies can be coupled in parallel with the transducer through a coupling circuit, which connects each oscillator to the transducer through a low impedance path and isolates each oscillator from signals having frequencies of the other oscillators.

Particle analyzer for measuring the resistance and reactance of a

A debris detector for a particle counter, such as a blood cell counter, of the COULTER (R) type. When a particle, or transient debris, passes through the sensing orifice of the particle detector, a voltage pulse occurs; whereas, when debris lodges in or against the orifice of the particle detector, a d.c. voltage shift occurs. The voltage at the orifice is capacitively coupled to an amplifier and the output of the amplifier is integrated. The capacitor coupling the orifice voltage to the amplifier causes an undershoot voltage at the trailing edge of each particle or transient debris pulse, such that a zero average voltage is applied to and, hence, from the amplifier for each voltage pulse. The integrated voltage is applied to a voltage comparator to provide an output signal therefrom whenever the integrated voltage exceeds a reference voltage. The comparator output signal is provided to a delay circuit having a delay related to the time required for a particle to pass through the COULTER detector orifice. If the comparator signal remains after the delay time, a debris alarm signal is provided. This occurs only if a d.c. voltage shift had occurred, since there is no trailing edge, and hence no undershoot to return the integrated voltage to zero prior to the delay time.

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Miami Springs, FL, United States of America

Wallace H Coulter