公开(公告)号：US20120148142A1

公开(公告)日：2012-06-14

申请号：US13396333

申请日：2012-02-14

申请人： William Ortyn ,  David Basiji ,  Luchuan Liang ,  Vidya Venkatachalam ,  Philip Morrissey

发明人： William Ortyn ,  David Basiji ,  Luchuan Liang ,  Vidya Venkatachalam ,  Philip Morrissey

IPC分类号： G06K9/62

CPC分类号： G01N15/147 ,  G01N15/1475 ,  G01N21/6428 ,  G01N21/6458 ,  G01N33/5005 ,  G01N33/505 ,  G01N2021/6441

摘要： Photometric and morphometric features derived from multi-mode imagery of cells in flow are used as a cell analyzer to determine if a marker corresponding to a cancer cell or precancerous cell is present in the population of cells imaged. An imaging system simultaneously acquires a plurality of images for each cell passing through the field of view of the imaging system. Acquiring a plurality of different images (i.e., bright field, dark field, and fluorescent images) facilitates the determination of different morphological and morphometric parameters. Simultaneously acquiring the plurality of images enables relatively large populations of cells to be rapidly imaged, so that relatively small numbers of cancer cells in a large population of cells can be detected. Initially, known cancer cells are imaged to enable a marker to be identified. Then, a sample that may include cancer cells is imaged to determine if the marker is present.

摘要翻译： 作为细胞分析仪，使用从流动细胞的多模式图像得到的光度和形态测定特征，以确定对应于癌细胞或癌前细胞的标志物是否存在于成像细胞群体中。 成像系统同时获取通过成像系统的视野的每个单元的多个图像。 获取多个不同的图像（即，亮场，暗场和荧光图像）有助于确定不同的形态和形态测量参数。 同时获取多个图像使得能够快速成像相对较大数量的细胞，从而可以检测大量细胞中相对少数量的癌细胞。 首先，将已知的癌细胞成像以使得能够鉴定标记。 然后，可以包含癌细胞的样品被成像以确定标记物是否存在。

公开(公告)号：US20060192955A1

公开(公告)日：2006-08-31

申请号：US11379972

申请日：2006-04-24

申请人： Ralph Jorgenson ,  David Basiji ,  William Ortyn

发明人： Ralph Jorgenson ,  David Basiji ,  William Ortyn

IPC分类号： G01J3/44 ,  G01N21/55

CPC分类号： G01N21/658 ,  B82Y15/00 ,  B82Y20/00 ,  G01J3/2803 ,  G01J3/2823 ,  G01N15/1434 ,  G01N15/147 ,  G01N21/554 ,  G01N21/6428 ,  G01N21/648 ,  G01N21/85 ,  G01N33/54346 ,  G01N2015/0294 ,  G01N2015/1006 ,  G01N2015/1472 ,  G01N2015/1486 ,  G01N2021/052 ,  G01N2021/058 ,  G01N2021/258 ,  G02B7/28 ,  G02B27/1013

摘要： A flow imaging system is used to implement surface plasmon resonance (SPR) detection to study bio-molecular interactions. The flow imaging system is used to capture SPR absorption spectra of large numbers of objects, where each object includes both a metal film capable of exhibiting SPR, and detecting molecules. Analyte molecules are added to a solution of such objects, and the result is introduced into the flow imaging system which collects full SPR spectral data from individual objects. The objects can be nanoparticles or larger particles that support metal island films. The SPR spectral data can be used to determine specificity, kinetics, affinity, and concentration with respect to the interactions between the detecting molecules and the analyte molecules.

摘要翻译： 流动成像系统用于实现表面等离子体共振（SPR）检测，以研究生物分子相互作用。 流动成像系统用于捕获大量物体的SPR吸收光谱，其中每个物体都包含能够显示SPR的金属膜和检测分子。 将分析物分子加入到这些物体的溶液中，并将结果引入到从各个物体收集完整的SPR光谱数据的流动成像系统中。 物体可以是支撑金属岛膜的纳米颗粒或更大的颗粒。 SPR光谱数据可用于确定相对于检测分子和分析物分子之间的相互作用的特异性，动力学，亲和力和浓度。

公开(公告)号：US20050127271A1

公开(公告)日：2005-06-16

申请号：US11045675

申请日：2005-01-28

申请人： William Ortyn ,  Michael Seo ,  David Basiji ,  Keith Frost ,  David Perry

发明人： William Ortyn ,  Michael Seo ,  David Basiji ,  Keith Frost ,  David Perry

IPC分类号： G01N15/10 ,  G01N15/14 ,  G02B27/00 ,  G06T7/20 ,  G01N21/00 ,  G01N15/06 ,  G02B7/04

CPC分类号： G06T7/20 ,  G01N15/1459 ,  G01N15/1463 ,  G01N2015/1018 ,  G01N2015/1443 ,  G01N2015/1447 ,  G01N2015/1452 ,  G01N2015/1497 ,  G02B27/0012 ,  G06K9/00134

摘要： A pair of optical gratings are used to modulate light from an object, and the modulated light from either grating is used to determine the velocity of the object. Each optical grating is offset from a reference focal point by the same distance, one grating being offset in a positive direction, the other in a negative direction. Signals produced in response to the modulated light can be processed to determine a direction in which a primary collection lens should be moved in order to improve a focus of the imaging system on the object. The lens is moved incrementally in the direction so determined, and the process is repeated until an optimal focus is achieved. In a preferred embodiment, the signals are weighted, so that the optical grating disposed closest to the optimal focus position contributes the most to velocity detection.

摘要翻译： 一对光栅用于调制来自物体的光，并且来自任一光栅的调制光用于确定物体的速度。 每个光栅从参考焦点偏移相同的距离，一个光栅在正方向偏移，另一个光栅在负方向上偏移。 可以处理响应于调制光产生的信号以确定主收集透镜应该移动的方向，以便改善成像系统对物体的焦点。 透镜在如此确定的方向上逐渐移动，并重复该过程，直到达到最佳聚焦。 在优选实施例中，对信号进行加权，使得最靠近最佳聚焦位置布置的光栅最有助于速度检测。

公开(公告)号：US08451524B2

公开(公告)日：2013-05-28

申请号：US12886182

申请日：2010-09-20

申请人： William Ortyn ,  David Perry ,  Tom Montague

发明人： William Ortyn ,  David Perry ,  Tom Montague

IPC分类号： G02B26/08 ,  G01N21/00

CPC分类号： G02B26/105 ,  G01N15/1434 ,  G01N15/1459 ,  G02B19/0014 ,  G02B19/0052 ,  G02B26/0858 ,  G02B27/0927 ,  G02B27/0944 ,  G02B27/0977 ,  G02F1/11 ,  G02F2203/18

摘要： A laser beam is periodically deflected before being directed into a sample volume. The beam is deflected at a frequency such that the beam makes one or more passes through the sample volume while data are collected from the sample volume. The amplitude of motion of the beam, the dwell time of the beam at any given point, and the Gaussian intensity profile of the beam cooperate to produce an effective flat topped illumination profile for the light that is incident on specimens in the sample volume. The total photon exposure at any given point in the sample volume is a function of both the beam intensity and the dwell time at that location. Therefore, a longer dwell time and lower intensity at the edge of the profile are in balance with a shorter dwell time and higher intensity at the center of the profile.

摘要翻译： 在被引导到样品体积之前，激光束被周期性地偏转。 光束以频率偏转，使得光束在从样本体积收集数据的同时使一次或多次通过样本体积。 光束的运动幅度，光束在任何给定点的停留时间以及光束的高斯强度分布协同作用，为入射到样品体积中的样本的光产生有效的平顶照明曲线。 样品体积中任何给定点处的总光子曝光是光束强度和该位置处的停留时间的函数。 因此，轮廓边缘处的较长停留时间和较低的强度与轮廓中心处的较短停留时间和较高的强度平衡。

公开(公告)号：US08406498B2

公开(公告)日：2013-03-26

申请号：US12631795

申请日：2009-12-04

申请人： William Ortyn ,  David Basiji ,  Philip Morrissey ,  Thaddeus George ,  Brian Hall ,  Cathleen Zimmerman ,  David Perry

发明人： William Ortyn ,  David Basiji ,  Philip Morrissey ,  Thaddeus George ,  Brian Hall ,  Cathleen Zimmerman ,  David Perry

IPC分类号： G06K9/00

CPC分类号： A61B1/00188 ,  G01N15/147 ,  G01N15/1475 ,  G01N2015/1488 ,  G06K9/0014

摘要： Multimodal or multispectral images of cells comprising a population of cells are simultaneously collected. Photometric and/or morphometric image features identifiable in the images are used to identify differences between first and second populations of cells. The differences can include changes in a relative percentage of different cell types in each population, or a change in a first type of cell present in the first population of cells and the same type of cell in the second population of cells. The changes may be indicative of a disease state, indicative of a relative effectiveness of a therapy, or indicative of a health of the person from whom the cells populations were obtained.

摘要翻译： 同时收集包含细胞群的细胞的多峰或多光谱图像。 图像中可识别的光度和/或形态测量图像特征用于识别第一和第二细胞群体之间的差异。 差异可以包括每个群体中不同细胞类型的相对百分比的变化，或第一细胞群体中存在的第一类细胞和第二细胞群体中相同类型的细胞的变化。 这些改变可以指示疾病状态，指示治疗的相对有效性或指示获得细胞群体的人的健康。

公开(公告)号：US20060246481A1

公开(公告)日：2006-11-02

申请号：US11364858

申请日：2006-02-27

申请人： Rosalynde Finch ,  David Basiji ,  William Ortyn

发明人： Rosalynde Finch ,  David Basiji ,  William Ortyn

IPC分类号： C12Q1/68 ,  C12N1/08

CPC分类号： G01N33/6863 ,  C12Q1/6841 ,  G01N33/56966 ,  C12Q2565/626 ,  C12Q2527/125

摘要： The present invention provides methods of detecting and/or quantifying specific cellular target molecules in intact cells. The present invention further provides methods of processing an intact cell to facilitate in situ hybridization for use in flow cytometry.

公开(公告)号：US20060066837A1

公开(公告)日：2006-03-30

申请号：US11230373

申请日：2005-09-20

申请人： William Ortyn ,  David Basiji

发明人： William Ortyn ,  David Basiji

IPC分类号： G01N21/00

CPC分类号： G02B27/148 ,  C12Q1/6816 ,  G01J3/2803 ,  G01J3/2823 ,  G01N15/1434 ,  G01N15/147 ,  G01N15/1475 ,  G01N21/6428 ,  G01N21/6456 ,  G01N21/85 ,  G01N2015/0294 ,  G01N2015/1006 ,  G01N2015/1443 ,  G01N2015/1472 ,  G01N2015/1479 ,  G01N2015/1486 ,  G01N2015/1488 ,  G01N2021/052 ,  G01N2021/058 ,  G02B7/28 ,  G02B21/00 ,  G02B27/0012 ,  G02B27/1013 ,  G02B27/144 ,  G02B27/145 ,  C12Q2563/179 ,  C12Q2563/107

摘要： Light from an object such as a cell moving through an imaging system is collected and dispersed so that it is imaged onto a plurality of separate detectors. The light is spectrally dispersed by a plurality of spaced-apart dichroic reflectors, each detector receiving light from a different one or the dichroic reflectors. Each dichroic filter reflects light of a different predefined color, passing light or other colors. The output signal from each detector is indicative of a different characteristic of the object. In one configuration, each detector is provided with a separate imaging lens. In another configuration, the detectors are spaced at varying distances from the corresponding dichroic reflectors, so that separate imaging lenses are not required.

摘要翻译： 来自诸如移动通过成像系统的细胞的物体的光被收集和分散，使得其被成像到多个单独的检测器上。 光被多个间隔开的二向色反射器光谱分散，每个检测器接收来自不同的或二向色反射器的光。 每个二向色滤光镜反射不同预定颜色的光，通过光或其他颜色。 来自每个检测器的输出信号表示对象的不同特性。 在一种配置中，每个检测器设置有单独的成像透镜。 在另一种配置中，检测器与对应的二向色反射器间隔开不同的距离，使得不需要单独的成像透镜。

公开(公告)号：US20110085221A1

公开(公告)日：2011-04-14

申请号：US12886182

申请日：2010-09-20

申请人： William Ortyn ,  David Perry ,  Tom Montague

发明人： William Ortyn ,  David Perry ,  Tom Montague

IPC分类号： G02B26/10 ,  G02F1/33

CPC分类号： G02B26/105 ,  G01N15/1434 ,  G01N15/1459 ,  G02B19/0014 ,  G02B19/0052 ,  G02B26/0858 ,  G02B27/0927 ,  G02B27/0944 ,  G02B27/0977 ,  G02F1/11 ,  G02F2203/18

摘要： A laser beam is periodically deflected before being directed into a sample volume. The beam is deflected at a frequency such that the beam makes one or more passes through the sample volume while data are collected from the sample volume. The amplitude of motion of the beam, the dwell time of the beam at any given point, and the Gaussian intensity profile of the beam cooperate to produce an effective flat topped illumination profile for the light that is incident on specimens in the sample volume. The total photon exposure at any given point in the sample volume is a function of both the beam intensity and the dwell time at that location. Therefore, a longer dwell time and lower intensity at the edge of the profile are in balance with a shorter dwell time and higher intensity at the center of the profile.

摘要翻译： 在被引导到样品体积之前，激光束被周期性地偏转。 光束以频率偏转，使得光束在从样本体积收集数据的同时使一次或多次通过样本体积。 光束的运动幅度，光束在任何给定点处的停留时间以及光束的高斯强度分布协同作用，以产生入射到样品体积中的样品的光的有效平顶照明轮廓。 样品体积中任何给定点处的总光子曝光是光束强度和该位置处的停留时间的函数。 因此，轮廓边缘处的较长停留时间和较低的强度与轮廓中心处的较短停留时间和较高的强度平衡。

公开(公告)号：US20100232675A1

公开(公告)日：2010-09-16

申请号：US12631795

申请日：2009-12-04

申请人： William Ortyn ,  David Basiji ,  Philip Morrissey ,  Thaddeus George ,  Brian Hall ,  Cathleen Zimmerman ,  David Perry

发明人： William Ortyn ,  David Basiji ,  Philip Morrissey ,  Thaddeus George ,  Brian Hall ,  Cathleen Zimmerman ,  David Perry

IPC分类号： G06K9/00 ,  G01N33/48

CPC分类号： A61B1/00188 ,  G01N15/147 ,  G01N15/1475 ,  G01N2015/1488 ,  G06K9/0014

摘要： Multimodal or multispectral images of cells comprising a population of cells are simultaneously collected. Photometric and/or morphometric image features identifiable in the images are used to identify differences between first and second populations of cells. The differences can include changes in a relative percentage of different cell types in each population, or a change in a first type of cell present in the first population of cells and the same type of cell in the second population of cells. The changes may be indicative of a disease state, indicative of a relative effectiveness of a therapy, or indicative of a health of the person from whom the cells populations were obtained.

摘要翻译： 同时收集包含细胞群的细胞的多峰或多光谱图像。 图像中可识别的光度和/或形态测量图像特征用于识别第一和第二细胞群体之间的差异。 差异可以包括每个群体中不同细胞类型的相对百分比的变化，或第一细胞群体中存在的第一类细胞和第二细胞群体中相同类型的细胞的变化。 这些改变可以指示疾病状态，指示治疗的相对有效性或指示获得细胞群体的人的健康。

公开(公告)号：US20060068371A1

公开(公告)日：2006-03-30

申请号：US11123610

申请日：2005-05-04

申请人： William Ortyn ,  David Basiji ,  David Lynch

发明人： William Ortyn ,  David Basiji ,  David Lynch

IPC分类号： C12Q1/00 ,  G01N21/25

CPC分类号： G01N33/505 ,  G01J3/2889 ,  G01J3/36 ,  G01J3/4406 ,  G01N15/1429 ,  G01N15/147 ,  G01N15/1475 ,  G01N21/53 ,  G01N21/6428 ,  G01N21/6456 ,  G01N21/6458 ,  G01N33/5005 ,  G01N2015/1006 ,  G01N2015/1497 ,  G01N2021/6421 ,  G01N2021/6441 ,  G06K9/00127

摘要： Aspects of the present invention encompass the collection of multispectral images from a population of objects, and the analysis of the collected images to measure at least characteristic of the population, using photometric and/or morphometric features identifiable in the collection of images. In an exemplary application, the objects are biological cells. In a particularly preferred, but not limiting implementation, the plurality of images for each individual object are collected simultaneously. In an empirical study the characteristic being measured involves the synapse between conjugated cells. The conjugated cells may represent a subpopulation of the overall population of objects that were imaged. In a particularly preferred, yet not limiting embodiment, the present invention enables the quantization of the redistribution of cellular molecules due to the conjugation of different biological cells. Significantly, such quantization is not feasible with standard microscopy and flow cytometry.

摘要翻译： 本发明的方面包括从对象群体收集多光谱图像，以及使用在图像集合中可识别的光度和/或形态测量特征，对所收集的图像的分析至少测量群体的特征。 在示例性应用中，对象是生物细胞。 在特别优选但不是限制的实现中，用于每个单独对象的多个图像被同时收集。 在经验研究中，被测量的特征涉及共轭细胞之间的突触。 共轭细胞可以代表成像对象的总体群体的亚群。 在特别优选的但不是限制性的实施方案中，本发明使得由于不同生物细胞的共轭而能够量化细胞分子的再分布。 值得注意的是，这种量化在标准显微镜和流式细胞术中是不可行的。