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1. 发明授权

US5504337A Method and apparatus for performing phase fluorescence lifetime measurements in flow cytometry 失效
标题翻译：用于在流式细胞仪中进行相位荧光寿命测量的方法和装置
公开(公告)号：US5504337A
公开(公告)日：1996-04-02
申请号：US50122
申请日：1993-04-12
申请人： Joseph R. Lakowicz , Klaus W. Berndt , Robert A. Hoffman , Bertram G. Pinsky
发明人： Joseph R. Lakowicz , Klaus W. Berndt , Robert A. Hoffman , Bertram G. Pinsky
IPC分类号： G01N15/14 , G01N21/64
CPC分类号： G01N15/1434 , G01N21/6408 , G01N15/1459 , G01N2015/1454
摘要： A method and apparatus for identifying individual particles or cells which have been labeled with different fluorochromes, on the basis of the lifetime of their fluorescence, or based on different decay times for a fluorochrome in different cells.
摘要翻译： PCT No.PCT / US91 / 07259 Sec。 371日期：1993年4月12日 102（e）日期1993年4月12日PCT 1991年10月10日PCT PCT。公开号WO92 / 07245 日期：1992年4月30日。一种用于识别已经用不同荧光染料标记的单个颗粒或细胞的方法和装置，基于其荧光的寿命，或者基于不同细胞中的荧光染料的不同衰减时间。

2. 发明授权

US5317162A Apparatus and method for phase resolved fluorescence lifetimes of independent and varying amplitude pulses 失效
标题翻译：独立和变化幅度脉冲的相位分辨荧光寿命的装置和方法
公开(公告)号：US5317162A
公开(公告)日：1994-05-31
申请号：US941780
申请日：1992-09-09
申请人： Bertram G. Pinsky , Robert A. Hoffman
发明人： Bertram G. Pinsky , Robert A. Hoffman
IPC分类号： G01N15/04 , G01N15/14 , G01N21/64
CPC分类号： G01N15/1459 , G01N21/6408 , G01N15/04 , G01N2015/1477 , G01N21/6428
摘要： A flow cytometer measures phase fluorescence lifetimes by the phase shift of a reference signal and an emission from a particle or cell in a flow chamber. An acoustic optic modulator modulates laser light with a sinusoidal wave of a predetermined frequency to excite particles or cells. Detectors respond to emissions of individual particles or cells in the form of an output signal pulse at the predetermined frequency. The output signal pulse is divided into equal pulses with each at the modulation frequency, the same amplitude and fidelity and amplitude. One part of the divided pulse is stripped of its envelope to pass the width thereof and out of band components are rejected. A variable amplifier passes a portion of the pulse above a present level. A delay line sets a central part of the signal at a predetermined point in time. A circuit limits the attenuated one part. A double balance mixer multiplies and the relates the limited signal with a reference signal to determine the phase shift. A method measures phase fluorescence lifetimes of cells or particles with fluorescent markers by passing individual cells or particles in a flow stream of a flow chamber in a flow cytometer.
摘要翻译：流式细胞仪通过参考信号的相移和来自流动室中的颗粒或细胞的发射来测量相位荧光寿命。声光调制器用预定频率的正弦波调制激光以激发粒子或细胞。检测器以预定频率以输出信号脉冲的形式响应单个颗粒或单元的排放。输出信号脉冲被分成相等的脉冲，每个脉冲在调制频率下，相同的幅度和保真度和幅度。划分的脉冲的一部分被剥离其信封以通过其宽度，并且带外部件被拒绝。可变放大器将脉冲的一部分传递到当前电平之上。延迟线在预定的时间点设置信号的中心部分。电路限制了衰减的一部分。双平衡混频器相乘并将有限信号与参考信号相关联以确定相移。一种方法通过使流式细胞仪中的流动室的流动流中的各个细胞或颗粒通过荧光标记来测量细胞或颗粒的相位荧光寿命。

3. 发明授权

US08415161B2 Instrument setup system for a fluorescence analyzer 有权
标题翻译：荧光分析仪仪器设置系统
公开(公告)号：US08415161B2
公开(公告)日：2013-04-09
申请号：US12616001
申请日：2009-11-10
申请人： Ming Yan , Alan M. Stall , Joseph T. Trotter , Robert A. Hoffman
发明人： Ming Yan , Alan M. Stall , Joseph T. Trotter , Robert A. Hoffman
IPC分类号： G01N31/00 , G01N21/76
CPC分类号： G01N21/6486 , G01N21/6428 , G01N2021/6421 , G01N2021/6441 , G01N2201/121 , Y10S435/967 , Y10T436/10 , Y10T436/101666 , Y10T436/13
摘要： The present invention reagents and methods for setting up an instruments having a multiplicity of detector channels for analyzing a multiplicity of fluorescent dyes. The present invention is particularly applicable in the field of flow cytometry.
摘要翻译：本发明的试剂和用于设置具有多个用于分析多种荧光染料的检测器通道的仪器的方法。本发明特别适用于流式细胞仪领域。

4. 发明授权

US06329158B1 Use of dimly fluorescing nucleic acid dyes in the identification of nucleated cells 失效
标题翻译：在识别有核细胞中使用浅色荧光核酸染料
公开(公告)号：US06329158B1
公开(公告)日：2001-12-11
申请号：US08528828
申请日：1995-09-15
申请人： Robert A. Hoffman , Thomas Frey
发明人： Robert A. Hoffman , Thomas Frey
IPC分类号： G01N33533
CPC分类号： G01N33/582 , C12Q1/6816 , G01N21/6428 , G01N33/56972 , C12Q2565/625 , C12Q2563/107
摘要： This invention presents improved methodology for identification of nucleated cells in flow cytometric analysis when immunofluorescent dyes are also used. Briefly, in the method nucleic acids are stained with a fluorescent dye which can then be used to identify the nucleated cells by measurement of fluorescence on a flow cytometer. The improvement presented by this invention is the use of a saturating (or near saturating) amount of a nucleic acid dye, or mixture of dyes, which gives low fluorescence at excitation conditions, so as not to greatly interfere with the signals of the immunofluorescent dyes.
摘要翻译：当使用免疫荧光染料时，本发明提出了用于在流式细胞术分析中鉴定有核细胞的改进方法。简而言之，在该方法中，核酸用荧光染料染色，然后可以通过在流式细胞仪上测量荧光来鉴定有核细胞。本发明提出的改进是使用饱和（或近饱和）量的核酸染料或染料混合物，其在激发条件下产生低荧光，以免大大干扰免疫荧光染料的信号。

5. 发明授权

US5076472A Cleaning cycle for flow cytometers 失效
标题翻译：流式细胞仪的清洗周期
公开(公告)号：US5076472A
公开(公告)日：1991-12-31
申请号：US627795
申请日：1990-12-14
申请人： Hans-Joachim Gross , Robert A. Hoffman
发明人： Hans-Joachim Gross , Robert A. Hoffman
IPC分类号： A61L2/18 , G01N15/14
CPC分类号： A61L2/18 , B01L99/00 , B01L2300/0867 , B01L2400/0622 , B01L2400/0633 , G01N35/1097 , Y10T137/3127
摘要： A method and apparatus for cleaning cellular contamination in flow cytometer comprising the sequential use of a strong oxidizing solution, particle-free neutral pH fluid and a weak acid.
摘要翻译：用于清洗流式细胞仪中细胞污染的方法和装置，其包括依次使用强氧化溶液，无颗粒的中性pH流体和弱酸。

6. 发明授权

US4665553A Methods and apparatus for analysis of particles and cells 失效
标题翻译：用于分析颗粒和细胞的方法和装置
公开(公告)号：US4665553A
公开(公告)日：1987-05-12
申请号：US605732
申请日：1984-05-01
申请人： Russell J. Gershman , Robert A. Hoffman , J. Garland O'Connell
发明人： Russell J. Gershman , Robert A. Hoffman , J. Garland O'Connell
IPC分类号： G01N33/49 , G01N15/14 , G01N21/59 , G01N33/48 , G06K9/00
CPC分类号： G01N15/1456 , G01N2021/4704 , G01N21/59 , G01N2201/04
摘要： Samples are prepared and applied to a cuvette, and the cuvette is translated in a given direction. Laser light is coupled to the sample through a Bragg cell, which causes the beam to scan the sample transversely to the given direction. Select optical parameters are monitored, and when they occur, the scan is stopped or slowed for a more complete analysis of the illuminated cell.
摘要翻译：制备样品并将其应用于比色皿，并将反应杯沿给定方向平移。激光通过布拉格细胞耦合到样品，这使得光束横向于给定方向扫描样品。选择光学参数进行监控，当它们发生时，扫描被停止或减慢，以便对照明单元进行更完整的分析。

7. 发明授权

US4475236A Method for counting overlapping cell populations in a distribution histogram 失效
标题翻译：计算分布直方图中重叠细胞群的方法
公开(公告)号：US4475236A
公开(公告)日：1984-10-02
申请号：US320822
申请日：1981-11-12
申请人： Robert A. Hoffman
发明人： Robert A. Hoffman
IPC分类号： G01N15/14 , G06K9/00
CPC分类号： G01N15/1427 , G01N15/1012 , G06K9/00147 , G01N15/1459 , G01N2015/1402 , G01N2015/1477 , G01N2015/1486 , G01N2015/1488
摘要： A sample having a mixture of unknown stained cells and known cells having different staining characteristics is analyzed rapidly, a cell at a time, in a flow cytometry system having a sample stream dimension in the range of expected cell dimensions. The cells are illuminated with focused illumination and fluorescence is detected and related to the number of cells. The resulting histogram of the mixture sample may be analyzed by counting the cells in a controlled population below a relatively low threshold value of fluorescence intensity to form a first fraction and relating this fraction to the fraction of cells in the sample mixture below the threshold value of fluorescence intensity to determine the number of unknown cells in the sample mixture.
摘要翻译：具有未知染色细胞和具有不同染色特征的已知细胞的混合物的样品在流式细胞术系统中快速分析细胞，流式细胞仪系统中样品流尺寸在预期细胞尺寸范围内。细胞用聚焦照明照射，荧光检测并与细胞数量相关。可以通过将受控群体中的细胞计数低于相对低的荧光强度阈值来分析混合物样品的所得直方图，以形成第一级分，并将该级分与样品混合物中的细胞级分相关联，低于阈值荧光强度来确定样品混合物中未知细胞的数量。

8. 发明申请

US20100120059A1 INSTRUMENT SETUP SYSTEM FOR A FLUORESCENCE ANALYZER 有权
标题翻译：荧光分析仪仪器设置系统
公开(公告)号：US20100120059A1
公开(公告)日：2010-05-13
申请号：US12616001
申请日：2009-11-10
申请人： Ming Yan , Alan M. Stall , Joseph T. Trotter , Robert A. Hoffman
发明人： Ming Yan , Alan M. Stall , Joseph T. Trotter , Robert A. Hoffman
IPC分类号： G01N33/53
CPC分类号： G01N21/6486 , G01N21/6428 , G01N2021/6421 , G01N2021/6441 , G01N2201/121 , Y10S435/967 , Y10T436/10 , Y10T436/101666 , Y10T436/13
摘要： The present invention reagents and methods for setting up an instruments having a multiplicity of detector channels for analyzing a multiplicity of fluorescent dyes. The present invention is particularly applicable in the field of flow cytometry.
摘要翻译：本发明的试剂和用于设置具有多个用于分析多种荧光染料的检测器通道的仪器的方法。本发明特别适用于流式细胞仪领域。

9. 发明授权

US5880474A Multi-illumination-source flow particle analyzer with inter-location emissions crosstalk cancelation 失效
标题翻译：具有位置间排放串扰消除的多照明源流量粒子分析仪
公开(公告)号：US5880474A
公开(公告)日：1999-03-09
申请号：US920382
申请日：1997-08-29
申请人： Pierce Owen Norton , Robert A. Hoffman
发明人： Pierce Owen Norton , Robert A. Hoffman
IPC分类号： G01N15/14 , G01J1/58 , G01N21/25 , G01N33/48
CPC分类号： G01N15/1459 , G01N15/1429 , G01N2015/1402 , G01N2015/1438
摘要： A multi-laser flow-cytometry system provides for inter-location emissions crosstalk cancellation, through either pulse subtraction or gating, to avoid false triggering based on shadow (pre- and post-) pulses that occur when red-excited red emissions are detected by a photodetector arranged to detect blue-excited red emissions. This overcomes a problem of undercounting of counting beads that led to misdeterminations of cell counts when blue-excited red fluorescence detections were used as a trigger. The approach also provides for more accurate quantitative data regarding fluorochrome emissions amplitudes.
摘要翻译：多激光流式细胞术系统通过脉冲减法或门控提供位置间发射串扰消除，以避免基于由红色激发红色发射被检测到的红色（红色）红色发射时产生的阴影（前后）脉冲的错误触发布置成检测蓝色激发的红色发射的光电检测器。这克服了当蓝色激发红色荧光检测用作触发剂时导致细胞计数误判的计数珠的计数不足的问题。该方法还提供了关于荧光染料发射幅度的更准确的定量数据。

10. 发明授权

US5528045A Particle analyzer with spatially split wavelength filter 失效
标题翻译：具有空间分离波长滤波器的粒子分析仪
公开(公告)号：US5528045A
公开(公告)日：1996-06-18
申请号：US417743
申请日：1995-04-06
申请人： Robert A. Hoffman , William J. Treytl
发明人： Robert A. Hoffman , William J. Treytl
IPC分类号： G01N15/14 , G01N21/64 , F21V9/00 , G01J1/58 , G01N21/25 , G21K5/10
CPC分类号： G01N21/645 , G01N15/14 , G01N2021/6421 , G01N2021/6441
摘要： A fluorescence particle analyzer includes a flow tube through which particles marked with different fluorochromes pass from a first location to a second location. Emissions from the first and second locations are respectively imaged at respective first and second filter elements so that emissions that reach a photodetector from said first location are primarily filtered by the first filter element, while emission that reach the same photodetector from the second location are primarily filtered by the second filter element. The first filter element is selected to preferentially transmit emissions from a first fluorochrome at the expense of emissions from a second fluorochrome, while the second filter element is selected to preferentially transmit emissions from the second fluorochrome at the expense of emissions from the first fluorochrome. The first location is illuminated by a laser that preferentially excites the first fluorochrome at the expense of the second fluorochrome, while the second location is illuminated by a laser that preferentially excites the second fluorochrome at the expense of the first fluorochrome. The photodetector output includes a first pulse that corresponds predominately to the quantity of the first fluorochrome in the particle; subsequently, a second pulse appears corresponding predominantly to the quantity of the second fluorochrome in the particle. The use of the two filters minimizes cross talk between the fluorochrome emissions in the photodetector output pulses.
摘要翻译：荧光粒子分析仪包括流管，标记有不同荧光染料的颗粒通过该流管从第一位置传递到第二位置。来自第一和第二位置的排放物分别在相应的第一和第二滤光元件上成像，使得从所述第一位置到达光电检测器的发射主要被第一滤光元件滤波，而从第二位置到达相同光电检测器的发射主要由第二过滤元件过滤。选择第一过滤元件优先以来自第二荧光染料的排放物的方式传输来自第一荧光染料的发射，而第二过滤元件被选择为以来自第一荧光染料的排放为代价优先传输来自第二荧光染料的发射。第一位置由以第二荧光染料为代价优先激发第一荧光染料的激光器照亮，而第二位置由以第一荧光染料为代价优先激发第二荧光染料的激光器照射。光电检测器输出包括主要对应于颗粒中第一荧光染料的量的第一脉冲; 随后，第二脉冲出现主要与颗粒中第二荧光染料的量相对应。使用两个滤光器可以最大限度地减少光电检测器输出脉冲中的荧光染料发射之间的串扰。

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