公开(公告)号：US06441894B1

公开(公告)日：2002-08-27

申请号：US09430418

申请日：1999-10-29

申请人： Bala S. Manian ,  David M. Heffelfinger ,  Edward M. Goldberg

发明人： Bala S. Manian ,  David M. Heffelfinger ,  Edward M. Goldberg

IPC分类号： G01J100

CPC分类号： G02B21/34 ,  G01N21/6452 ,  G02B21/241

摘要： A method and apparatus for autofocus on a target layer contained within a microplate well is provided. The instrument is capable of optically sensing a reference point on the underside of a microplate. This reference point is then used to focus light onto a target layer within the microplate well, the target layer having a location that is in defined relation to the reference point. The reference point is either a surface of the bottom of the microplate well or is an optically detectable mark on the underside of the microplate. In an alternate embodiment, a light position sensitive detector is used to enable deterministic autofocus for a plurality of wells on a microplate.

摘要翻译： 提供了一种用于在微孔板中包含的靶层上的自动聚焦的方法和装置。 该仪器能够光学感测微孔板底面上的参考点。 然后将该参考点用于将光聚焦到微孔板内的目标层上，目标层具有与参考点限定的位置。 参考点是微孔板底部的表面，或者是微孔板下面的光学可检测标记。 在替代实施例中，使用光位置敏感检测器来使得微孔板上的多个孔的确定性自动聚焦。

公开(公告)号：US6130745A

公开(公告)日：2000-10-10

申请号：US245782

申请日：1999-02-05

申请人： Bala S. Manian ,  David M. Heffelfinger ,  Edward M. Goldberg

发明人： Bala S. Manian ,  David M. Heffelfinger ,  Edward M. Goldberg

IPC分类号： G01B11/00 ,  G01J1/00 ,  G01N21/03 ,  G01N21/55 ,  G01N21/64 ,  G01N33/483 ,  G02B7/28 ,  G02B21/24 ,  G02B21/34

CPC分类号： G02B21/34 ,  G01N21/6452 ,  G02B21/241

摘要： A method and apparatus for autofocus on a target layer contained within a microplate well is provided. The instrument is capable of optically sensing a reference point on the underside of a microplate. This reference point is then used to focus light onto a target layer within the microplate well, the target layer having a location that is in defined relation to the reference point. The reference point is either a surface of the bottom of the microplate well or is an optically detectable mark on the underside of the microplate. In an alternate embodiment, a light position sensitive detector is used to enable deterministic autofocus for a plurality of wells on a microplate.

公开(公告)号：US07016087B2

公开(公告)日：2006-03-21

申请号：US09925124

申请日：2001-08-08

申请人： David M. Heffelfinger ,  Aram P. Schiffman ,  Bala S. Manian

发明人： David M. Heffelfinger ,  Aram P. Schiffman ,  Bala S. Manian

IPC分类号： H04N1/04

CPC分类号： G01N21/6452 ,  G01N21/6428 ,  G01N2021/6419 ,  G01N2021/6421

摘要： A system for optical interrogation of a sample adaptable for multiple wavelength illumination and multiple wavelength fluorescent or luminescent light collection, wherein the illumination wavelength profile and the light collection profile may overlap. In the system, coherent light from one or more lasers is focused onto a target layer on a sample to excite fluorescent or luminescent light from the target layer. Emitted light is collected from a selected depth by a reflective light collector that transmits the collected light to detection optics. The reflective light collector directs collected light at an angle to the optical axis of the illumination light, thereby separating collected emitted light from illumination light. The light collector may collect light from a focus, whereby the focused illumination light combined with the focused light collection aid in limitation of the depth of field to a selected depth. Additionally, a spatial filter positioned between the light collector and the detection optics may be used to confine the depth of field to a selected depth. This device may be incorporated into an optical scanner by scanning of illumination light in a first direction and translation of the sample in a tangent direction. Alternatively, the illumination and detection optics may remain stationary and the detectable targets moved past a scanning location (e.g. as in electrophoretic analysis).

公开(公告)号：US06750457B2

公开(公告)日：2004-06-15

申请号：US09942472

申请日：2001-08-29

申请人： David M. Heffelfinger ,  Aram P. Schiffman ,  Bala S. Manian

发明人： David M. Heffelfinger ,  Aram P. Schiffman ,  Bala S. Manian

IPC分类号： G01N2100

CPC分类号： G01N21/6452 ,  G01J3/10 ,  G01J3/14 ,  G01J3/36 ,  G01J3/4406 ,  G01N27/44721 ,  G01N2021/6463

摘要： An apparatus and method in which illumination light and collected emitted light share a pathway and subsequently are physically separated. The optical configuration is designed such that at the point of separation, the illumination light is at has a smaller cross sectional area than the collected light. Collected light is directed away from the pathway of the illumination light and to detection optics. This configuration is adaptable to illumination and light collection across a broad wavelength spectrum. This configuration is adaptable to scanning in a limited depth of field to allow high throughput optical analysis of samples.

摘要翻译： 照明光和收集的发射光共享通路并随后物理分离的装置和方法。 光学构造被设计成使得在分离点处，照明光具有比收集的光更小的横截面面积。 收集的光被引导离开照明光的路径和检测光学器件。 该配置适用于宽波长光谱下的照明和光采集。 该配置适用于在有限的景深中的扫描，以允许样品的高通量光学分析。

公开(公告)号：USD719666S1

公开(公告)日：2014-12-16

申请号：US29449047

申请日：2013-03-14

申请人： Bala S. Manian

设计人： Bala S. Manian

公开(公告)号：USD717352S1

公开(公告)日：2014-11-11

申请号：US29449078

申请日：2013-03-14

申请人： Bala S. Manian

设计人： Bala S. Manian

公开(公告)号：US20120105842A1

公开(公告)日：2012-05-03

申请号：US13034380

申请日：2011-02-24

申请人： Bala S. Manian

发明人： Bala S. Manian

IPC分类号： G01J3/44 ,  G01N30/00

CPC分类号： G01N21/274 ,  G01N21/278 ,  G01N21/64 ,  G01N21/65

摘要： The invention provides a method of calibrating measurement device using a Raman-active composition, wherein the composition is active, in one embodiment, in a wavelength region that ranges from about 300 nm to about 1200 nm, and in another embodiment, from about 550 nm to about 650 nm. The method is especially useful in the calibration of fluorescent measurement devices. The method of the invention provides several advantages, such as, in facile identification of problems with the device when it occurs, in not having to tune and adjust the device very often, and neutralizing variations between different runs and different instruments. In another aspect, the invention also provides a device that is calibrated using the method of the invention. In one embodiment, the Raman-active composition useful in the invention is a derivative of 1,4-bis(2-methyl-styryl)-benzene.

摘要翻译： 本发明提供了使用拉曼活性组合物校准测量装置的方法，其中在一个实施方案中，组合物在波长范围为约300nm至约1200nm，在另一个实施方案中为约550nm 至约650nm。 该方法在荧光测量装置的校准中特别有用。 本发明的方法提供了几个优点，例如在容易识别出现设备的问题时，不需要经常地调整和调整设备，并且中和不同的运行和不同的仪器之间的变化。 在另一方面，本发明还提供了使用本发明的方法校准的装置。 在一个实施方案中，可用于本发明的拉曼活性组合物是1,4-双（2-甲基 - 苯乙烯基） - 苯的衍生物。

公开(公告)号：US20120107950A1

公开(公告)日：2012-05-03

申请号：US13034515

申请日：2011-02-24

申请人： Bala S. Manian

发明人： Bala S. Manian

IPC分类号： G01N21/64 ,  C12M1/34

CPC分类号： G01N21/6428 ,  G01N21/6452

摘要： In one aspect, the invention provides a measurement system, wherein the measurement system comprises a sample module to receive a sample, wherein the sample module comprises at least one fluorophore; an optics module to generate an incident beam to impinge on the sample to yield a laser spot; a detector module to detect fluorescence signals arising out of the sample; a processor module to process the fluorescence signals and provide relevant output; an output module; a control module to control the sample module, the optics module, the detector module and the output module. The measurement system of the invention is capable of measuring both bulk and event fluorescences of a sample containing at least one fluorophore. In another aspect, the invention provides a method for testing a fluid based on the measurement system of the invention.

摘要翻译： 一方面，本发明提供了一种测量系统，其中测量系统包括用于接收样品的样品模块，其中样品模块包括至少一种荧光团; 光学模块，用于产生入射光束以撞击样品以产生激光光斑; 用于检测由样品产生的荧光信号的检测器模块; 处理器模块，用于处理荧光信号并提供相关输出; 输出模块; 用于控制样品模块，光学模块，检测器模块和输出模块的控制模块。 本发明的测量系统能够测量含有至少一个荧光团的样品的体积和事件荧光。 另一方面，本发明提供了一种基于本发明的测量系统测试流体的方法。

公开(公告)号：US5932428A

公开(公告)日：1999-08-03

申请号：US739131

申请日：1996-10-28

申请人： Robert S. Dubrow ,  Bala S. Manian

发明人： Robert S. Dubrow ,  Bala S. Manian

IPC分类号： G01N33/49 ,  G01N15/14 ,  G01N33/533 ,  G01N33/569 ,  G01N33/53

CPC分类号： G01N15/1468 ,  G01N33/569 ,  G01N33/56972 ,  Y10S435/962 ,  Y10S435/968 ,  Y10S436/805 ,  Y10S436/825 ,  Y10S436/826 ,  Y10T436/101666 ,  Y10T436/107497 ,  Y10T436/108331

摘要： An assay and sample mixture for the enumeration of fluorescently stained target components of a whole blood sample by an imaging instrument. The sample preparation method ensures that the amount of target components per unit of volume of the whole blood sample is preserved by elimination of certain non-quantitative preparation steps while producing an even hematocrit layer within a scan capillary. Typical target components include white blood cells that express certain surface antigens, such as CD-4 and CD-8 proteins. To inhibit aggregation of the red blood cells, a reagent is added to an aliquot of whole blood sample. The aliquot of whole blood is mixed and with a preselected amount of a fluorescent dye and ligand complex which tags the target components. The sample and fluorescent complex are allowed to incubate a sufficient amount of time to bind enough of the fluorescent complex to the target components to provide a fluorescent signal from the target components which will be distinguishable from the fluorescent signal from the unbound fluorescent complex in the sample. The resulting mixture allows the imaging instrument to detect peak intensities of fluorescence from the target components, thereby allowing the target components to be volumetrically enumerated with an improved level of accuracy and efficiency.

摘要翻译： 用于通过成像仪计数全血样品的荧光染色的靶组分的测定和样品混合物。 样品制备方法确保通过消除某些非定量制备步骤同时在扫描毛细管内产生均匀的血细胞比容层来保存全血样品每单位体积的目标成分的量。 典型的靶组分包括表达某些表面抗原的白细胞，例如CD-4和CD-8蛋白。 为了抑制红细胞的聚集，将试剂加入到全血样品的等分试样中。 将全血的等分试样混合，并与预选量的荧光染料和配体复合物标记靶组分。 允许样品和荧光复合物孵育足够的时间以将足够的荧光复合物与目标组分结合，以提供来自靶组分的荧光信号，其将与来自样品中未结合的荧光复合物的荧光信号区分开 。 所得到的混合物允许成像仪器检测来自目标组分的荧光的峰值强度，从而允许目标组分以精确度和效率提高的水平进行体积计数。

公开(公告)号：US5296341A

公开(公告)日：1994-03-22

申请号：US908575

申请日：1992-06-24

申请人： Bala S. Manian

发明人： Bala S. Manian

IPC分类号： G03C5/16 ,  H04N1/23 ,  G03C5/17

CPC分类号： G03C5/16 ,  H04N1/23 ,  Y10S430/146 ,  Y10S430/168

摘要： A method for digital imaging employing a green light laser. The method comprises obtaining a digitized picture image, modulating a green light laser beam in accord with the digitized picture image, and directing the modulated laser beam onto film that is sensitive to green-blue light. The film is then developed to create a gray-scale image useful in radiography and other imaging fields.

摘要翻译： 一种使用绿光激光的数字成像方法。 该方法包括获得数字化图像，根据数字化图像图像调制绿光激光束，并将调制的激光束引导到对绿蓝光敏感的膜上。 然后，该电影被开发以产生用于放射照相和其它成像领域的灰度图像。