公开(公告)号：US06579685B1

公开(公告)日：2003-06-17

申请号：US08303924

申请日：1994-09-09

申请人： Thomas Russell ,  James Carey Hudson ,  Wallace H. Coulter ,  Carlos M. Rodriguez ,  Constance Mary Hajek

发明人： Thomas Russell ,  James Carey Hudson ,  Wallace H. Coulter ,  Carlos M. Rodriguez ,  Constance Mary Hajek

IPC分类号： G01N3353

CPC分类号： G01N33/56972 ,  Y10S435/808 ,  Y10S435/962 ,  Y10S436/805 ,  Y10S436/824 ,  Y10S436/825

摘要： 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.

摘要翻译： 利用至少一个光感测参数，用于进行筛选感兴趣的一个或多个感兴趣的细胞群的方法被细胞群体例如WBC群体的一个或多个感兴趣的亚群遮蔽。 通过利用与其结合的具有单克隆抗体的微球来修饰感兴趣的特定细胞的特征以区分感兴趣的细胞群和模糊细胞群体，来计算感兴趣的细胞群。

公开(公告)号：US6159740A

公开(公告)日：2000-12-12

申请号：US525231

申请日：1990-05-17

申请人： James Carey Hudson ,  Thomas Russell ,  Carlos M. Rodriguez ,  Wallace H. Coulter

发明人： James Carey Hudson ,  Thomas Russell ,  Carlos M. Rodriguez ,  Wallace H. Coulter

IPC分类号： C12M1/34 ,  G01N1/28 ,  G01N15/00 ,  G01N15/10 ,  G01N15/12 ,  G01N15/14 ,  G01N33/48 ,  G01N33/50 ,  G01N33/53 ,  G01N33/543 ,  G01N33/569 ,  G01N33/577 ,  G01N35/00 ,  G01N33/80

CPC分类号： G01N1/28 ,  G01N15/10 ,  G01N15/12 ,  G01N15/14 ,  G01N33/5094 ,  G01N33/5302 ,  G01N33/54326 ,  G01N33/56972 ,  G01N35/0098 ,  G01N2015/008 ,  G01N2015/1037 ,  G01N2015/1062 ,  G01N2015/1081 ,  G01N2015/1486 ,  G01N2015/149

摘要： 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.

摘要翻译： 用于执行遮蔽或部分模糊的细胞的筛选以枚举一个或多个细胞群体亚群的方法和装置。 例如，筛选全血样品或其一部分以提供样品中一种或多种白细胞群体亚群的期望分析。 首先计算包括所隐藏的感兴趣亚群的白细胞群，以及标准群体。 标准群体可以是白细胞群体总数中的一个，第二白血球群体不掩盖感兴趣亚群的移位或非移位感知特征，由微球形成的人造群体也不 模糊感兴趣子集的移位或未移位的感测特征或者该子集的感测特征将被完全或部分移位到其中的白细胞群。 感兴趣的白血细胞群体子集的感测特征然后通过将具有特异于感兴趣的白细胞群体子集的单克隆抗体的微球结合到细胞群体来移位。 然后再次对白细胞群体和标准群体进行计数，并将其与原始计数进行比较，以获得感兴趣的白细胞群体子集的计数。

公开(公告)号：US5231005A

公开(公告)日：1993-07-27

申请号：US849481

申请日：1992-03-10

申请人： Thomas Russell ,  Kenneth H. Kortright ,  Wallace H. Coulter ,  Carlos M. Rodriguez ,  Ronald Paul ,  Constance M. Hajek ,  James C. Hudson

发明人： Thomas Russell ,  Kenneth H. Kortright ,  Wallace H. Coulter ,  Carlos M. Rodriguez ,  Ronald Paul ,  Constance M. Hajek ,  James C. Hudson

IPC分类号： G01N15/00 ,  G01N15/10 ,  G01N15/12 ,  G01N15/14 ,  G01N33/50 ,  G01N33/53 ,  G01N33/543 ,  G01N33/569 ,  G01N35/00

CPC分类号： G01N15/12 ,  G01N33/5002 ,  G01N33/5094 ,  G01N33/5302 ,  G01N33/54326 ,  G01N33/56972 ,  G01N15/14 ,  G01N2015/008 ,  G01N2015/1037 ,  G01N2015/1062 ,  G01N2015/1081 ,  G01N35/0098 ,  Y10T436/101666 ,  Y10T436/117497 ,  Y10T436/24

摘要： 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.

摘要翻译： 一种用于自动并快速地检索，计数和/或分析全血样本或其部分的至少一个选定细胞群体或形成体，例如白细胞群体及其至少一个子集的方法和装置。 制备含有白细胞的体积的生物培养基，并将至少一种至少一种选择的生物细胞特异性或优先选择的反应物引入其中并在短时间内快速混合。 可以修改细胞的不透明度和/或体积参数，然后在一个或多个步骤中对混合物进行计数和分析，以获得所需的白细胞群体和子集分析。 生物样品可以是全血样品，并且反应物可以包括结合微球的裂解液或单克隆抗体，其将与特定细胞结合，或与结合抗体的溶血和微球体的组合。 微球可以是磁性的，并且结合的细胞可被磁性去除，用于检索和分析剩余的血细胞群体。

公开(公告)号：US5260192A

公开(公告)日：1993-11-09

申请号：US929156

申请日：1992-08-12

申请人： Thomas Russell ,  Constance M. Hajek ,  Carlos M. Rodriguez ,  Wallace H. Coulter

发明人： Thomas Russell ,  Constance M. Hajek ,  Carlos M. Rodriguez ,  Wallace H. Coulter

IPC分类号： G01N1/28 ,  G01N15/00 ,  G01N15/10 ,  G01N15/12 ,  G01N15/14 ,  G01N33/50 ,  G01N33/53 ,  G01N33/543 ,  G01N33/569 ,  G01N35/00 ,  C12Q1/00 ,  C12Q1/04 ,  C12Q1/06 ,  C12Q1/24

CPC分类号： G01N15/10 ,  G01N1/28 ,  G01N15/12 ,  G01N33/5094 ,  G01N33/5302 ,  G01N33/54326 ,  G01N33/56972 ,  G01N15/14 ,  G01N2015/008 ,  G01N2015/1037 ,  G01N2015/1062 ,  G01N2015/1081 ,  G01N2015/1486 ,  G01N2015/149 ,  G01N35/0098 ,  Y10T436/101666 ,  Y10T436/117497

摘要： 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.

摘要翻译： 一种用于自动和快速地检索计数和/或分析全血样品或其部分的至少一个选定细胞群体或形成体（例如白细胞群体及其至少一个子集）的方法和装置。 制备含有白细胞的体积的生物培养基，并将至少一种至少一种选择的生物细胞特异性或优先选择的反应物引入其中并在短时间内快速混合。 通过消耗至少一个WBC子群体，通过单个感测参数获得多部分血细胞分析。 通过减去一个或多个模糊的WBC子集群，可以获得期望的WBC群体子集的百分比或WBC子群体的重叠。 生物样品可以是全血样品，并且反应物可以包括结合微球的裂解液或单克隆抗体，其将与特定细胞结合，或与结合抗体的溶血和微球体的组合。 微球可以是磁性的，并且结合的细胞可被磁性去除，用于检索和分析剩余的血细胞群体。

公开(公告)号：US4791355A

公开(公告)日：1988-12-13

申请号：US921654

申请日：1986-10-21

申请人： Wallace H. Coulter ,  Carlos M. Rodriguez

发明人： Wallace H. Coulter ,  Carlos M. Rodriguez

IPC分类号： G01N15/12 ,  G01N33/48 ,  G01N27/00

CPC分类号： G01N15/1227 ,  G01N2015/129

摘要： 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.

摘要翻译： 用于提供测量通过Coulter型换能器的颗粒（例如血细胞）的电气不透明度所需的数据的电路包括用于提供常规直流电流的电流源。 通过传感器的感测孔径的电流，以及用于提供通过孔径的高频电流的振荡器。 振荡器包括有源器件和谐振电路，并且该孔与振荡器的谐振电路并联耦合。 振荡器可以是任何类型的振荡器，例如Hartley振荡器。 当颗粒通过孔径时，孔径的电阻增加，这又增加了振荡器电路的Q，由此根据增加的Q对振荡器输出信号进行幅度调制。该幅度调制信号可以被检测为 提供基于所检测的粒子的高频电抗的值。 d.c.的变化 以常规方式检测通过孔径的颗粒的电阻。 检测到的a.c.的振幅。 和d.c. 然后可以比较信号来确定每个粒子的不透明度。 不同频率的多个振荡器可以通过耦合电路与传感器并联耦合，该耦合电路通过低阻抗路径将每个振荡器连接到换能器，并将每个振荡器与具有其他振荡器频率的信号隔离开来。

公开(公告)号：US5125737A

公开(公告)日：1992-06-30

申请号：US479199

申请日：1990-02-13

申请人： Carlos M. Rodriguez ,  Wallace H. Coulter

发明人： Carlos M. Rodriguez ,  Wallace H. Coulter

IPC分类号： G01N33/49 ,  G01N1/38 ,  G01N15/00 ,  G01N15/10 ,  G01N15/14 ,  G01N21/53

CPC分类号： G01N15/1459 ,  G01N21/53 ,  G01N1/38 ,  G01N2015/008 ,  G01N2015/1037 ,  G01N2015/1062 ,  G01N2015/129 ,  G01N2015/1413 ,  G01N2015/1477 ,  G01N2021/4711

摘要： 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..

摘要翻译： 公开了一种用于在粒子流上进行光学和电子测量的流动粒子分析单元分辨装置，其中流体动力聚焦的流流入并通过点聚焦的辐射能量束，由此光束被流散射以照射到光 响应信号操作构件相对于梁轴线在约10°至70°的角度位置处邻近电池设置。

公开(公告)号：US5238812A

公开(公告)日：1993-08-24

申请号：US517309

申请日：1990-05-01

申请人： Wallace H. Coulter ,  John D. Hollinger ,  Thomas Russell ,  Carlos Rodriguez ,  Ronald Paul

发明人： Wallace H. Coulter ,  John D. Hollinger ,  Thomas Russell ,  Carlos Rodriguez ,  Ronald Paul

IPC分类号： G01N33/50 ,  G01N33/569

CPC分类号： G01N33/5005 ,  G01N33/56966 ,  G01N33/56972 ,  Y10S436/808

摘要： 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.

摘要翻译： 一种用于加速至少一种确定性生物反应的方法和装置，包括增加由其制备的测定精度。 该反应涉及选择的活体生物细胞，它们以小的样品体积制备，并且与具有抗体特异性至少与结合于其上的特定细胞的微球快速混合。 微球可以是磁性的，并且结合的细胞可以被磁性去除以分析剩余的血细胞群体。 微球可以顺序或同时引入。

公开(公告)号：US5223398A

公开(公告)日：1993-06-29

申请号：US587646

申请日：1990-09-20

申请人： Kenneth H. Kortright ,  Wallace H. Coulter ,  Carlos Rodriguez ,  Thomas Russell ,  Ronald Paul

发明人： Kenneth H. Kortright ,  Wallace H. Coulter ,  Carlos Rodriguez ,  Thomas Russell ,  Ronald Paul

IPC分类号： G01N15/10 ,  G01N15/12 ,  G01N15/14 ,  G01N33/50 ,  G01N33/53 ,  G01N33/543 ,  G01N33/569 ,  G01N35/00

CPC分类号： G01N33/5094 ,  G01N33/5302 ,  G01N33/54326 ,  G01N33/56972 ,  G01N15/12 ,  G01N15/14 ,  G01N2015/1037 ,  G01N2015/1062 ,  G01N2015/1081 ,  G01N35/0098 ,  Y10S436/808

摘要： 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.

摘要翻译： 一种用于自动并快速地检索，计数和/或分析全血样本或其部分的至少一个所选择的白细胞群体和/或其子集的方法和装置。 制备含有白细胞的体积的生物样品，并将至少一种特异性或优先选择的至少一些选定的生物细胞引入其中并在短时间内快速混合。 可以修改细胞的不透明度和/或体积参数，然后在一个或多个步骤中对混合物进行计数和分析以获得所需的白细胞群体分析。 生物样品可以是全血样品，并且反应物可以包括结合微球的裂解液或单克隆抗体，其将与特定细胞结合，或与结合抗体的溶血和微球体的组合。 微球可以是磁性的，并且结合的细胞可被磁性去除，用于检索和分析剩余的血细胞群体。

公开(公告)号：US5468616A

公开(公告)日：1995-11-21

申请号：US58692

申请日：1993-04-29

申请人： Wallace H. Coulter ,  John D. Hollinger ,  Kenneth H. Kortright ,  Thomas Russell ,  Carlos Rodriguez ,  Ronald Paul

发明人： Wallace H. Coulter ,  John D. Hollinger ,  Kenneth H. Kortright ,  Thomas Russell ,  Carlos Rodriguez ,  Ronald Paul

IPC分类号： G01N33/50 ,  G01N33/569 ,  C12Q1/24 ,  G01N33/543

CPC分类号： G01N33/5005 ,  G01N33/56966 ,  G01N33/56972 ,  Y10S436/808

摘要： 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.

摘要翻译： 一种用于加速至少一种确定性生物反应的方法和装置，包括增加由其制备的测定精度。 该反应涉及选择的活体生物细胞，它们以小的样品体积制备，并且与具有抗体特异性至少与结合于其上的特定细胞的微球快速混合。 微球可以是磁性的，并且结合的细胞可以被磁性去除以分析剩余的血细胞群体。 微球可以顺序或同时引入。

公开(公告)号：US5348859A

公开(公告)日：1994-09-20

申请号：US703163

申请日：1991-05-20

申请人： Robert F. Brunhouse ,  Constance M. Hajek ,  Thomas Russell ,  Wallace H. Coulter

发明人： Robert F. Brunhouse ,  Constance M. Hajek ,  Thomas Russell ,  Wallace H. Coulter

IPC分类号： G01N15/14 ,  G01N1/31 ,  G01N15/00 ,  G01N15/06 ,  G01N33/49 ,  G01N33/543 ,  G01N33/569 ,  G01N33/574 ,  G01N33/53 ,  G01N33/48 ,  G06M11/02

CPC分类号： G01N1/312 ,  G01N15/147 ,  G01N33/54313 ,  G01N33/56972 ,  G01N33/574 ,  G01N15/0625 ,  G01N15/1475 ,  G01N2015/008 ,  G01N2015/1472 ,  G01N2015/1486

摘要： 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.

摘要翻译： 用于鉴定和计数表达所选特征或性质的细胞的光学筛选方法和装置。 细胞与一个或多个不同组的微球组合，每组具有与其结合的反应物，其结合可存在于一种或多种类型细胞上的特定分子。 细胞和微球体在载玻片上的已知体积中形成，并且在光学上被观察以鉴定和计数不同组的微球体与其结合的细胞的类型。 然后，细胞计数与已知体积相关，以提供绝对细胞计数。 可以将多个不同的样品部分用于不同的反应物以获得多部分WBC差异/绝对计数。 通过具有不同的光学特性，例如尺寸，形状，颜色或其组合，不同组的微球被光学分化。