公开(公告)号：WO2012092545A1

公开(公告)日：2012-07-05

申请号：PCT/US2011/068063

申请日：2011-12-30

Applicant: BIO-RAD LABORATORIES, INC. ,  HENG, Xin

Inventor： HENG, Xin

IPC: H01S3/00

CPC classification number: G01N33/54366 ,  B01L3/502761 ,  B01L2200/0652 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2400/0454 ,  B01L2400/0487 ,  G01N15/1463 ,  G01N15/1484 ,  G01N21/6458 ,  G01N21/648 ,  G01N2021/6441 ,  Y10T436/143333

Abstract: A system for characterizing and sorting individual molecules, for example chromatin or DNA molecules. In some configurations, the system can immobilize molecules of interest suspended in fluid in a sample stage for characterization, and selectively release the immobilized molecules to different output reservoirs, depending on the characterization result. For example, fluorescent markers may be hybridized onto molecules, which may then be attached to dielectric beads and immobilized using holographic optical tweezers or other means. The system may provide elongational flow to elongate molecules, and may detect the presence and spacing of multiple fluorescent markers hybridized to the molecules. Using advanced techniques, the system may be able to characterize features with a resolution better than the theoretical resolution of the system optics. The system may utilize a microfluidic cartridge.

Abstract translation: 用于表征和分选单个分子的系统，例如染色质或DNA分子。 在一些配置中，系统可以将悬浮在流体中的目标分子固定在样品台中以进行表征，并且根据表征结果选择性地将固定的分子释放到不同的输出储存器。 例如，荧光标记物可以杂交到分子上，然后可以将其附着到电介质珠粒上，并使用全息光学镊子或其他方式固定。 该系统可以向细长分子提供伸长流，并且可以检测与分子杂交的多个荧光标记的存在和间隔。 使用先进的技术，该系统可能能够以比系统光学元件的理论分辨率更好的分辨率来表征特征。 该系统可以利用微流控筒。

公开(公告)号：WO2010108020A1

公开(公告)日：2010-09-23

申请号：PCT/US2010/027843

申请日：2010-03-18

Applicant: BIO-RAD LABORATORIES, INC. ,  HENG, Xin ,  PATT, Paul

Inventor： HENG, Xin ,  PATT, Paul

IPC: G01N21/00

CPC classification number: G01N21/6486 ,  G01J3/02 ,  G01J3/0208 ,  G01J3/04 ,  G01J3/10 ,  G01J3/36 ,  G01J3/4406 ,  G01N15/1425 ,  G01N15/1429 ,  G01N15/147 ,  G01N15/1475 ,  G01N21/6458 ,  G01N2021/6419 ,  G01N2021/6421

Abstract: A system for performing high-speed, high-resolution imaging cytometry utilizes a line-scan sensor. A cell to be characterized is transported past a scan region. An optical system focuses an image of a portion of the scan region onto at least one linear light sensor, and repeated readings of light falling on the sensor are taken while a cell is transported though the scan region. The system may image cells directly, or may excite fluorescence in the cells and image the resulting light emitted from the cell by fluorescence. The system may provide a narrow band of illumination at the scan region. The system may include various filters and imaging optics that enable simultaneous multicolor fluorescence imaging cytometry. Multiple linear sensors may be provided, and images gathered by the individual sensors may be combined to construct an image having improved signal-to-noise characteristics.

Abstract translation: 用于执行高速，高分辨率成像细胞计数的系统利用线扫描传感器。 待特征化的细胞被运送通过扫描区域。 光学系统将扫描区域的一部分的图像聚焦到至少一个线性光传感器上，并且在单元格被传送通过扫描区域的同时拍摄落在传感器上的光的重复读数。 该系统可以直接对细胞进行成像，或者可以激发细胞中的荧光，并通过荧光对从细胞发出的所得光进行成像。 该系统可以在扫描区域提供窄带照明。 该系统可以包括能够同时进行多色荧光成像细胞计数的各种滤光器和成像光学元件。 可以提供多个线性传感器，并且可以组合由各个传感器收集的图像以构建具有改进的信噪比特性的图像。

公开(公告)号：WO2012115979A1

公开(公告)日：2012-08-30

申请号：PCT/US2012/025969

申请日：2012-02-21

Applicant: BIO-RAD LABORATORIES, INC. ,  HENG, Xin ,  PATT, Paul

Inventor： HENG, Xin ,  PATT, Paul

IPC: G01N21/00

CPC classification number: G01N15/1459 ,  G01N15/1434 ,  G01N2015/144

Abstract: Systems and methods for performing cytometry using a linear light sensor. An illumination field, a line scanned by the linear light sensor, or both are swept across a cell to be imaged. Relative motion between the cell and the swept illumination may be created using a movable optical component or components, by adhering cells to a plate and transporting the plate or by other techniques.

Abstract translation: 使用线性光传感器进行细胞计数的系统和方法。 照明场，由线性光传感器扫描的线或两者都扫过要成像的细胞。 电池和扫描照明之间的相对运动可以通过使用可移动的光学部件或组件，通过将电池附着到板上并传送该板或通过其它技术来产生。

公开(公告)号：WO2012068446A1

公开(公告)日：2012-05-24

申请号：PCT/US2011/061363

申请日：2011-11-18

Applicant: BIO-RAD LABORATORIES, INC. ,  HENG, Xin ,  BRENIMAN, Eugene

Inventor： HENG, Xin ,  BRENIMAN, Eugene

IPC: C12Q1/02 ,  G01N33/48

CPC classification number: C12Q1/02 ,  G01N2015/1486

Abstract: Cell counts that distinguish between live and dead cells while providing an accurate count of the total of live and dead cells are obtained by the use of a vital stain in conjunction with illumination of the cell population and the taking of light images at different wavelengths, one which is not absorbed by the stain and one that is absorbed by the stain. Masking and inaccuracies in the counting of dead cells is thereby avoided.

Abstract translation: 通过使用生命染色结合细胞群的照射和摄取不同波长的光图像获得活细胞和死细胞之间的细胞计数，同时提供活细胞和死细胞的总数的精确计数。 其不被污渍吸收并被污渍所吸收。 从而避免了计数死细胞的掩蔽和不准确。

公开(公告)号：WO2012024633A1

公开(公告)日：2012-02-23

申请号：PCT/US2011/048496

申请日：2011-08-19

Applicant: BIO-RAD LABORATORIES, INC. ,  HENG, Xin ,  PATT, Paul

Inventor： HENG, Xin ,  PATT, Paul

IPC: G01N21/00

CPC classification number: G01N15/1434 ,  G01N15/1436 ,  G01N15/147 ,  G01N15/1475 ,  G01N21/645 ,  G01N2021/6421

Abstract: Flow cytometry system includes a flow element through which a cell is transported in a flowing fluid. Flow element includes a bore bounded by a wall. Light source is configured to illuminate the cell. Optical system receives light emanating from the cell and directs at least some of received light to a light sensor. The optical system includes a numerical-aperture-increasing lens at a wall of the flow element. At least some of the received light passes through the numerical-aperture-increasing lens. The flow cytometry system may also include a beam splitter that directs two wavelength bands of emanating light such that light in two wavelength band preferentially reach different sensing locations via different paths. The system may also include an optical element placed in one of the paths, shifting a focal location of the affected path to compensate for chromatic aberration of the numerical-aperture-increasing lens.

Abstract translation: 流式细胞术系统包括流动元件，细胞通过该元件在流动的流体中输送。 流动元件包括由壁限定的孔。 光源被配置为照亮单元。 光学系统接收从单元发出的光，并将至少一些接收的光引导到光传感器。 光学系统在流动元件的壁处包括数字孔径增加透镜。 所接收的光中的至少一些通过数字孔径增加透镜。 流式细胞术系统还可以包括分束器，其引导发射光的两个波长带，使得两个波长带中的光优先通过不同的路径到达不同的感测位置。 该系统还可以包括放置在路径之一中的光学元件，移动受影响的路径的焦点位置以补偿数值孔径增加透镜的色差。

公开(公告)号：WO2011116003A1

公开(公告)日：2011-09-22

申请号：PCT/US2011/028538

申请日：2011-03-15

Applicant: BIO-RAD LABORATORIES, INC. ,  HENG, Xin

Inventor： HENG, Xin

IPC: G01N15/14 ,  G06T5/30 ,  G06K9/00

CPC classification number: G01N15/147 ,  G01N15/1475 ,  G01N15/1484 ,  G01N21/6428 ,  G01N2015/149

Abstract: A microassembled imaging cytometer includes a sensing location that undergoes relative motion with a cell. Light from a light source is focused by a focusing element to a plurality of focused illumination spots or lines at the sensing location, illuminating the cell as the cell traverses the sensing location. A collection lens collects light emanating from the cell and refocuses the collected light onto an array light sensor. The focusing element may include an array of microlenses having spherical or aspheric surfaces. The system may include a processing unit that constructs a digital image of the cell based at least in part on signals produced by the array light sensor indicating the intensity and distribution of light falling on the array light sensor. The system may characterize cells using light emanating from the cells by fluorescence.

Abstract translation: 微组装成像细胞计数器包括与细胞经历相对运动的感测位置。 来自光源的光通过聚焦元件聚焦到感测位置处的多个聚焦照明点或线，当小区穿过感测位置时照亮该小区。 收集透镜收集从细胞发出的光并将收集的光重新聚焦到阵列光传感器上。 聚焦元件可以包括具有球面或非球面的微透镜阵列。 系统可以包括处理单元，其至少部分地基于由阵列光传感器产生的指示落在阵列光传感器上的光的强度和分布的信号构成单元的数字图像。 该系统可以使用通过荧光从细胞发出的光来表征细胞。

公开(公告)号：WO2011032130A1

公开(公告)日：2011-03-17

申请号：PCT/US2010/048725

申请日：2010-09-14

Applicant: BIO-RAD LABORATORIES, INC. ,  HENG, Xin

Inventor： HENG, Xin

IPC: G06K9/00

CPC classification number: A61B18/203 ,  A61B2018/00452 ,  A61B2018/00642 ,  A61B2018/00779 ,  G01N21/4795 ,  G01N2201/0675 ,  G02B26/06 ,  G03H1/0443 ,  G03H1/2294 ,  G03H2001/0072

Abstract: An optical system and associated method enable near real time optical phase conjugation. In the method, a translucent medium is illuminated by a sample illumination beam. Light scattered by the medium is directed to an electronic image sensor while a reference beam is also directed to the electronic image sensor. The scattered light and the reference beam form an interference pattern at the electronic image sensor. A digital representation of the interference pattern is recorded using the electronic image sensor, and the characteristics of a conjugate of the sample beam are computed from the numerical representation. A conjugate beam having the computed characteristics is generated using a configurable optical element and directed back to the translucent medium. The generation of the conjugate beam may be accomplished using a spatial light modulator.

Abstract translation: 光学系统和相关联的方法实现近实时光学相位共轭。 在该方法中，半透明介质由样本照明光束照射。 由介质散射的光被引导到电子图像传感器，而参考光束也被引导到电子图像传感器。 散射光和参考光束在电子图像传感器处形成干涉图案。 使用电子图像传感器记录干涉图案的数字表示，并且从数字表示计算样本波束的共轭的特征。 使用可配置光学元件产生具有计算特性的共轭光束并且被引导回到半透明介质。 可以使用空间光调制器来实现共轭光的产生。

公开(公告)号：WO2011026029A1

公开(公告)日：2011-03-03

申请号：PCT/US2010/047143

申请日：2010-08-30

Applicant: BIO-RAD LABORATORIES, INC. ,  McCOLLUM, Tom ,  PATT, Paul ,  SHEN, Frank ,  CHU, Daniel Y. ,  FLORY, Don ,  GRIFFIN, Mike ,  HENG, Xin ,  HEFNER, Eli

Inventor： McCOLLUM, Tom ,  PATT, Paul ,  SHEN, Frank ,  CHU, Daniel Y. ,  FLORY, Don ,  GRIFFIN, Mike ,  HENG, Xin ,  HEFNER, Eli

IPC: G06K9/00 ,  C12M1/34

CPC classification number: C12Q1/06 ,  G01N15/1434 ,  G02B21/0008 ,  G02B21/34

Abstract: Biological cells in a liquid suspension are counted in an automated cell counter that focuses an image of the suspension on a digital imaging sensor that contains at least 4,000,000 pixels each having an area of 2 x 2 μm or less and that images a field of view of at least 3 mm 2 . The sensor enables the counter to compress the optical components into an optical path of less than 20 cm in height when arranged vertically with no changes in direction of the optical path as a whole, and the entire instrument has a footprint of less than 300 cm 2 . Activation of the light source, automated focusing of the sensor image, and digital cell counting are all initiated by the simple insertion of the sample holder into the instrument. The suspension is placed in a sample chamber in the form of a slide that is shaped to ensure proper orientation of the slide in the cell counter.

Abstract translation: 液体悬浮液中的生物细胞在自动细胞计数器中计数，其将悬浮液的图像聚焦在数字成像传感器上，该数字成像传感器包含至少4,000,000个像素，每个具有2×2μm或更小的面积，并且图像的视场 至少3 mm2。 该传感器使得计数器能够将光学部件压缩成高度小于20cm的光路，当垂直布置时，整个光路的方向没有变化，并且整个仪器的占地面积小于300cm 2。 光源的激活，传感器图像的自动聚焦和数字单元计数都是通过将样品架简单插入到仪器中来启动的。 将悬浮液置于样品室中，其形状为成形以确保细胞计数器中载玻片的正确取向。

公开(公告)号：EP2640843B1

公开(公告)日：2016-02-24

申请号：EP11841246.9

申请日：2011-11-18

Applicant: Bio-Rad Laboratories, Inc.

Inventor： HENG, Xin ,  BRENIMAN, Eugene

IPC: C12Q1/02 ,  G01N33/48

CPC classification number: C12Q1/02 ,  G01N2015/1486

公开(公告)号：EP2409133A1

公开(公告)日：2012-01-25

申请号：EP10754123.7

申请日：2010-03-18

Applicant: Bio-Rad Laboratories, Inc.

Inventor： HENG, Xin ,  PATT, Paul

IPC: G01N21/00

CPC classification number: G01N21/6486 ,  G01J3/02 ,  G01J3/0208 ,  G01J3/04 ,  G01J3/10 ,  G01J3/36 ,  G01J3/4406 ,  G01N15/1425 ,  G01N15/1429 ,  G01N15/147 ,  G01N15/1475 ,  G01N21/6458 ,  G01N2021/6419 ,  G01N2021/6421

Abstract: A system for performing high-speed, high-resolution imaging cytometry utilizes a line-scan sensor. A cell to be characterized is transported past a scan region. An optical system focuses an image of a portion of the scan region onto at least one linear light sensor, and repeated readings of light falling on the sensor are taken while a cell is transported though the scan region. The system may image cells directly, or may excite fluorescence in the cells and image the resulting light emitted from the cell by fluorescence. The system may provide a narrow band of illumination at the scan region. The system may include various filters and imaging optics that enable simultaneous multicolor fluorescence imaging cytometry. Multiple linear sensors may be provided, and images gathered by the individual sensors may be combined to construct an image having improved signal-to-noise characteristics.