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    IMAGING OF IMMUNOMAGNETICALLY ENRICHED RARE CELLS
    2.
    发明申请
    IMAGING OF IMMUNOMAGNETICALLY ENRICHED RARE CELLS 有权
    免疫组织化学显微成像

    公开(公告)号：US20090286264A1

    公开(公告)日：2009-11-19

    申请号：US12467932

    申请日：2009-05-18

    申请人： Tyco M. Scholtens ,  Frederik Schreuder ,  Jan Greve ,  Arhjan G.J. Tibbe ,  Leon W.M.M. Terstappen

    发明人： Tyco M. Scholtens ,  Frederik Schreuder ,  Jan Greve ,  Arhjan G.J. Tibbe ,  Leon W.M.M. Terstappen

    IPC分类号： G01N33/53

    CPC分类号： G01N33/54326

    摘要： A method for removing excess unbound ferrofluid and imaging immunomagnetically enriched circulating tumor cells is provided. A vessels having a preformed grooves in the viewing surface is optimally designed for cell alignment and imaging. After separating the unbound particles by centrifugation, an externally-applied force is applied to transport magnetically responsive particle-CTC complex toward the transparent collection wall. The grooved inner surface of the viewing face of the chamber provide uniform distribution of the particles for easy imaging. The invention is also useful in conducting quantitative analysis and sample preparation in conjunction with automated cell enumeration techniques as in quantitative analysis of CTC in disease.

    摘要翻译： 提供了一种去除过量未结合的铁磁流体和成像免疫磁性富集的循环肿瘤细胞的方法。 在观察表面中具有预成形凹槽的容器被最佳设计用于细胞对准和成像。 通过离心分离未结合的颗粒后，施加外部施加的力以将磁响应颗粒-CTC复合物输送到透明收集壁。 室的观察面的带槽的内表面提供颗粒的均匀分布以便于成像。 本发明还可用于与自动细胞计数技术结合进行定量分析和样品制备，如在疾病中CTC的定量分析中。

    Methods and algorithms for cell enumeration in a low-cost cytometer
    3.
    发明申请
    Methods and algorithms for cell enumeration in a low-cost cytometer 有权
    低成本细胞计数器细胞计数的方法和算法

    公开(公告)号：US20070117158A1

    公开(公告)日：2007-05-24

    申请号：US11434321

    申请日：2006-05-12

    申请人： Frank Coumans ,  Jan Greve ,  Frank Modica ,  Leon Terstappen ,  Arian Tibbe ,  John Verrant

    发明人： Frank Coumans ,  Jan Greve ,  Frank Modica ,  Leon Terstappen ,  Arian Tibbe ,  John Verrant

    IPC分类号： G06T7/20 ,  G01N33/567 ,  C12M1/34

    CPC分类号： C12M41/36 ,  G01N15/1475

    摘要： The enumeration of cells in fluids by flow cytometry is widely used across many disciplines such as assessment of leukocyte subsets in different bodily fluids or of bacterial contamination in environmental samples, food products and bodily fluids. For many applications the cost, size and complexity of the instruments prevents wider use, for example, CD4 analysis in HIV monitoring in resource-poor countries. The novel device, methods and algorithms disclosed herein largely overcome these limitations. Briefly, all cells in a biological sample are fluorescently labeled, but only the target cells are also magnetically labeled. In addition, non-magnetically labeled cells are imaged for viability in a modified slide configuration. The labeled sample, in a chamber or cuvet, is placed between two wedge-shaped magnets to selectively move the magnetically labeled cells to the observation surface of the cuvet. An LED illuminates the cells and a CCD camera captures the images of the fluorescent light emitted by the target cells. Image analysis performed with a novel algorithm provides a count of the cells on the surface that can be related to the target cell concentration of the original sample. The compact cytometer system provides a rugged, affordable and easy-to-use technique, which can be used in remote locations.

    摘要翻译： 通过流式细胞术对流体细胞的计数被广泛应用于许多学科，例如评估不同体液中的白细胞亚群或环境样品，食品和体液中的细菌污染。 对于许多应用，仪器的成本，尺寸和复杂性阻止了更广泛的使用，例如资源贫乏国家的艾滋病毒监测中的CD 4分析。 本文公开的新颖的装置，方法和算法在很大程度上克服了这些限制。 简言之，生物样品中的所有细胞都被荧光标记，但只有靶细胞也被磁性标记。 另外，非磁性标记的细胞在修改的载玻片配置中的存活力被成像。 将标记的样品置于室或铜管中，放置在两个楔形磁体之间，以选择性地将磁性标记的细胞移动到铜管的观察表面。 LED照亮细胞，CCD相机捕获由靶细胞发射的荧光的图像。 用新算法进行的图像分析提供了与原始样品的靶细胞浓度相关的表面上的细胞计数。 紧凑型细胞仪系统提供坚固，经济实惠且易于使用的技术，可用于偏远地区。

    Methods and algorithms for cell enumeration in low-cost cytometer
    4.
    发明申请
    Methods and algorithms for cell enumeration in low-cost cytometer 有权
    低成本细胞计数器细胞计数的方法和算法

    公开(公告)号：US20060024756A1

    公开(公告)日：2006-02-02

    申请号：US10903798

    申请日：2004-07-30

    申请人： Arjan Tibbe ,  Jan Greve ,  Dhanesh Gohel ,  Erik Droog ,  Leon Terstappen

    发明人： Arjan Tibbe ,  Jan Greve ,  Dhanesh Gohel ,  Erik Droog ,  Leon Terstappen

    IPC分类号： G01N33/53

    CPC分类号： G01N15/1475 ,  G01N15/1463 ,  G01N33/5094 ,  G01N33/54333 ,  G01N2015/008 ,  G01N2015/1486 ,  Y10T436/101666 ,  Y10T436/25375

    摘要： The enumeration of cells in fluids by flow cytometry is widely used across many disciplines such as assessment of leukocyte subsets in different bodily fluids or of bacterial contamination in environmental samples, food products and bodily fluids. For many applications the cost, size and complexity of the instruments prevents wider use, for example, CD4 analysis in HIV monitoring in resource-poor countries. The novel device, methods and algorithms disclosed herein largely overcome these limitations. Briefly, all cells in a biological sample are fluorescently labeled, but only the target cells are also magnetically labeled. The labeled sample, in a chamber or cuvet, is placed between two wedge-shaped magnets to selectively move the magnetically labeled cells to the observation surface of the cuvet. An LED illuminates the cells and a CCD camera captures the images of the fluorescent light emitted by the target cells. Image analysis performed with a novel algorithm provides a count of the cells on the surface that can be related to the target cell concentration of the original sample. The compact cytometer system provides a rugged, affordable and easy-to-use technique, which can be used in remote locations.

    摘要翻译： 通过流式细胞术对流体细胞的计数被广泛应用于许多学科，例如评估不同体液中的白细胞亚群或环境样品，食品和体液中的细菌污染。 对于许多应用，仪器的成本，尺寸和复杂性阻止了更广泛的使用，例如资源贫乏国家的艾滋病毒监测中的CD4分析。 本文公开的新颖的装置，方法和算法在很大程度上克服了这些限制。 简言之，生物样品中的所有细胞都被荧光标记，但只有靶细胞也被磁性标记。 将标记的样品置于室或铜管中，放置在两个楔形磁体之间，以选择性地将磁性标记的细胞移动到铜管的观察表面。 LED照亮细胞，CCD相机捕获由靶细胞发射的荧光的图像。 用新算法进行的图像分析提供了与原始样品的靶细胞浓度相关的表面上的细胞计数。 紧凑型细胞仪系统提供坚固，经济实惠且易于使用的技术，可用于偏远地区。

    Laser Illumination System in Fluorescent Microscopy
    6.
    发明申请
    Laser Illumination System in Fluorescent Microscopy 审中-公开
    激光照明系统在荧光显微镜

    公开(公告)号：US20090311734A1

    公开(公告)日：2009-12-17

    申请号：US12300344

    申请日：2007-05-03

    申请人： Jan Greve ,  Frederik Schreuder

    发明人： Jan Greve ,  Frederik Schreuder

    IPC分类号： C12Q1/02 ,  G01N33/68 ,  G01N33/48 ,  G01N21/64 ,  C12M1/34

    CPC分类号： G01N33/54326 ,  Y10T436/143333

    摘要： Devices and methods for automated collection and image analysis are disclosed that enable identification or classification of microscopic objects aligned or deposited on surfaces. Such objects, e.g. detectably labeled rare target cells, are magnetically or non-magnetically immobilized and subjected to Time Delay Integration imaging (TDI). Incorporation of TDI technology into image cytometry analysis, like CellTracks®, makes it possible to image moving objects with very high sensitivity and signal-to-noise ratios. Implementation of TDI camera technology with dual excitation and multispectral imaging of enriched rare cells provides a rapid system for detection, enumeration, differentiation and characterization of imaged rare cells on the basis of size, morphology and immunophenotype.

    摘要翻译： 公开了用于自动收集和图像分析的装置和方法，其能够识别或分类对准或沉积在表面上的微观物体。 这些物体，例如。 可检测标记的罕见靶细胞是磁性或非磁性固定的并经受时间延迟积分成像（TDI）。 将TDI技术结合到图像细胞分析中，像CellTracks（R），使得可以以非常高的灵敏度和信噪比来对移动物体进行成像。 基于大小，形态和免疫表型，实现了具有双重激发和多光谱成像的富集稀有细胞的TDI相机技术，提供了快速检测，计数，分化和表征成像稀有细胞的系统。

    Electron microscope with raman spectroscopy
    7.
    发明授权
    Electron microscope with raman spectroscopy 失效
    电子显微镜与拉曼光谱

    公开(公告)号：US5811804A

    公开(公告)日：1998-09-22

    申请号：US682601

    申请日：1996-08-12

    申请人： Clemens Antoni Van Blitterswijk ,  Hendrick Klaas Koerten ,  Jan Greve

    发明人： Clemens Antoni Van Blitterswijk ,  Hendrick Klaas Koerten ,  Jan Greve

    IPC分类号： G01N21/65 ,  H01J37/252 ,  H01J37/256 ,  H01J37/244

    CPC分类号： H01J37/228 ,  G01N21/65 ,  H01J37/226 ,  H01J37/252 ,  H01J37/256 ,  G01N2021/656 ,  H01J2237/2445

    摘要： Electron microscope provided, in the direction of the longitudinal axis, with at least one electron beam generation system, a condenser and objective lens system, a specimen chamber with a specimen mount, a projection lens system with imaging screen for the purpose of transmission electron microscopy (TEM) and/or an electron detector for the purpose of scanning electron microscopy (SEM) . The microscope is used in combination with an externally positioned Raman spectrometer and an associated light source for injecting and extracting, via a window in the microscope wall, a light beam to be directed at the specimen, and specimen-related Raman radiation, respectively. In the specimen chamber, a light beam and Raman radiation guide system is provided with an optical guide to guide the light beam to--and the Raman radiation from--the specimen. The guide system and the specimen mount are displaceable with respect to one another for mutual alignment of the specimen and the optical axis of the Raman spectrometer.

    摘要翻译： PCT No.PCT / NL95 / 00033 Sec。 371日期：1996年8月12日 102（e）日期1996年8月12日PCT提交1995年1月24日PCT公布。 公开号WO95 / 20242 日期1995年7月27日电子显微镜在纵向方向上提供至少一个电子束产生系统，冷凝器和物镜系统，具有样本座的样本室，具有成像屏幕的投影透镜系统 用于扫描电子显微镜（SEM）的透射电子显微镜（TEM）和/或电子检测器的目的。 显微镜与外部定位的拉曼光谱仪和相关联的光源结合使用，用于通过显微镜壁中的窗口分别注射和提取指向样品的光束和与样品相关的拉曼辐射。 在样本室中，光束和拉曼辐射导向系统设置有光引导件，以将光束引导到来自样本的拉曼辐射。 引导系统和样本支架可相对于彼此移位，以使样本与拉曼光谱仪的光轴相互对准。

    Methods and algorithms for cell enumeration in a low-cost cytometer
    8.
    发明授权
    Methods and algorithms for cell enumeration in a low-cost cytometer 有权
    低成本细胞计数器细胞计数的方法和算法

    公开(公告)号：US08189899B2

    公开(公告)日：2012-05-29

    申请号：US12707578

    申请日：2010-02-17

    申请人： Frank A. W. Coumans ,  Jan Greve ,  Frank P. Modica ,  Leon W. M. M. Terstappen ,  Arjan G. J. Tibbe ,  John A. Verrant

    发明人： Frank A. W. Coumans ,  Jan Greve ,  Frank P. Modica ,  Leon W. M. M. Terstappen ,  Arjan G. J. Tibbe ,  John A. Verrant

    IPC分类号： G06K9/00

    CPC分类号： G01N15/1475 ,  G01N33/5094 ,  G01N33/54333

    摘要： The enumeration of cells in fluids by flow cytometry is widely used across many disciplines such as assessment of leukocyte subsets in different bodily fluids or of bacterial contamination in environmental samples, food products and bodily fluids. For many applications the cost, size and complexity of the instruments prevents wider use, for example, CD4 analysis in HIV monitoring in resource-poor countries. The novel device, methods and algorithms disclosed herein largely overcome these limitations. Briefly, all cells in a biological sample are fluorescently labeled, but only the target cells are also magnetically labeled. In addition, non-magnetically labeled cells are imaged for viability in a modified slide configuration. The labeled sample, in a chamber or cuvet, is placed between two wedge-shaped magnets to selectively move the magnetically labeled cells to the observation surface of the cuvet. An LED illuminates the cells and a CCD camera captures the images of the fluorescent light emitted by the target cells. Image analysis performed with a novel algorithm provides a count of the cells on the surface that can be related to the target cell concentration of the original sample. The compact cytometer system provides a rugged, affordable and easy-to-use technique, which can be used in remote locations.

    摘要翻译： 通过流式细胞术对流体细胞的计数被广泛应用于许多学科，例如评估不同体液中的白细胞亚群或环境样品，食品和体液中的细菌污染。 对于许多应用，仪器的成本，尺寸和复杂性阻止了更广泛的使用，例如资源贫乏国家的艾滋病毒监测中的CD4分析。 本文公开的新颖的装置，方法和算法在很大程度上克服了这些限制。 简言之，生物样品中的所有细胞都被荧光标记，但只有靶细胞也被磁性标记。 另外，非磁性标记的细胞在修改的载玻片配置中的存活力被成像。 将标记的样品置于室或铜管中，放置在两个楔形磁体之间，以选择性地将磁性标记的细胞移动到铜管的观察表面。 LED照亮细胞，CCD相机捕获由靶细胞发射的荧光的图像。 用新算法进行的图像分析提供了与原始样品的靶细胞浓度相关的表面上的细胞计数。 紧凑型细胞仪系统提供坚固，经济实惠且易于使用的技术，可用于偏远地区。

    Methods and algorithms for cell enumeration in low-cost cytometer
    9.
    发明授权
    Methods and algorithms for cell enumeration in low-cost cytometer 有权
    低成本细胞计数器细胞计数的方法和算法

    公开(公告)号：US07943397B2

    公开(公告)日：2011-05-17

    申请号：US10903798

    申请日：2004-07-30

    申请人： Arjan Tibbe ,  Jan Greve ,  Dhanesh Gohel ,  Erik Droog ,  Leon W. M. M. Terstappen

    发明人： Arjan Tibbe ,  Jan Greve ,  Dhanesh Gohel ,  Erik Droog ,  Leon W. M. M. Terstappen

    IPC分类号： G01N33/00 ,  G01N33/553

    CPC分类号： G01N15/1475 ,  G01N15/1463 ,  G01N33/5094 ,  G01N33/54333 ,  G01N2015/008 ,  G01N2015/1486 ,  Y10T436/101666 ,  Y10T436/25375

    摘要： The enumeration of cells in fluids by flow cytometry is widely used across many disciplines such as assessment of leukocyte subsets in different bodily fluids or of bacterial contamination in environmental samples, food products and bodily fluids. For many applications the cost, size and complexity of the instruments prevents wider use, for example, CD4 analysis in HIV monitoring in resource-poor countries. The novel device, methods and algorithms disclosed herein largely overcome these limitations. Briefly, all cells in a biological sample are fluorescently labeled, but only the target cells are also magnetically labeled. The labeled sample, in a chamber or cuvet, is placed between two wedge-shaped magnets to selectively move the magnetically labeled cells to the observation surface of the cuvet. An LED illuminates the cells and a CCD camera captures the images of the fluorescent light emitted by the target cells. Image analysis performed with a novel algorithm provides a count of the cells on the surface that can be related to the target cell concentration of the original sample. The compact cytometer system provides a rugged, affordable and easy-to-use technique, which can be used in remote locations.

    摘要翻译： 通过流式细胞术对流体细胞的计数被广泛应用于许多学科，例如评估不同体液中的白细胞亚群或环境样品，食品和体液中的细菌污染。 对于许多应用，仪器的成本，尺寸和复杂性阻止了更广泛的使用，例如资源贫乏国家的艾滋病毒监测中的CD4分析。 本文公开的新颖的装置，方法和算法在很大程度上克服了这些限制。 简言之，生物样品中的所有细胞都被荧光标记，但只有靶细胞也被磁性标记。 将标记的样品置于室或铜管中，放置在两个楔形磁体之间，以选择性地将磁性标记的细胞移动到铜管的观察表面。 LED照亮细胞，CCD相机捕获由靶细胞发射的荧光的图像。 用新算法进行的图像分析提供了与原始样品的靶细胞浓度相关的表面上的细胞计数。 紧凑型细胞仪系统提供坚固，经济实惠且易于使用的技术，可用于偏远地区。

    Methods and Algorithms For Cell Enumeration in a Low-Cost Cytometer
    10.
    发明申请
    Methods and Algorithms For Cell Enumeration in a Low-Cost Cytometer 有权
    低成本细胞计数器细胞计数的方法和算法

    公开(公告)号：US20110052037A1

    公开(公告)日：2011-03-03

    申请号：US12707578

    申请日：2010-02-17

    申请人： Frank A.W. Coumans ,  Jan Greve ,  Frank P. Modica ,  Leon W.M.M. Terstappen ,  Arjan G.J. Tibbe ,  John A. Verrant

    发明人： Frank A.W. Coumans ,  Jan Greve ,  Frank P. Modica ,  Leon W.M.M. Terstappen ,  Arjan G.J. Tibbe ,  John A. Verrant

    IPC分类号： G06K9/00

    CPC分类号： G01N15/1475 ,  G01N33/5094 ,  G01N33/54333

    摘要： The enumeration of cells in fluids by flow cytometry is widely used across many disciplines such as assessment of leukocyte subsets in different bodily fluids or of bacterial contamination in environmental samples, food products and bodily fluids. For many applications the cost, size and complexity of the instruments prevents wider use, for example, CD4 analysis in HIV monitoring in resource-poor countries. The novel device, methods and algorithms disclosed herein largely overcome these limitations. Briefly, all cells in a biological sample are fluorescently labeled, but only the target cells are also magnetically labeled. In addition, non-magnetically labeled cells are imaged for viability in a modified slide configuration. The labeled sample, in a chamber or cuvet, is placed between two wedge-shaped magnets to selectively move the magnetically labeled cells to the observation surface of the cuvet. An LED illuminates the cells and a CCD camera captures the images of the fluorescent light emitted by the target cells. Image analysis performed with a novel algorithm provides a count of the cells on the surface that can be related to the target cell concentration of the original sample. The compact cytometer system provides a rugged, affordable and easy-to-use technique, which can be used in remote locations.

    摘要翻译： 通过流式细胞术对流体细胞的计数被广泛应用于许多学科，例如评估不同体液中的白细胞亚群或环境样品，食品和体液中的细菌污染。 对于许多应用，仪器的成本，尺寸和复杂性阻止了更广泛的使用，例如资源贫乏国家的艾滋病毒监测中的CD4分析。 本文公开的新颖的装置，方法和算法在很大程度上克服了这些限制。 简言之，生物样品中的所有细胞都被荧光标记，但只有靶细胞也被磁性标记。 另外，非磁性标记的细胞在修改的载玻片配置中的存活力被成像。 将标记的样品置于室或铜管中，放置在两个楔形磁体之间，以选择性地将磁性标记的细胞移动到铜管的观察表面。 LED照亮细胞，CCD相机捕获由靶细胞发射的荧光的图像。 用新算法进行的图像分析提供了与原始样品的靶细胞浓度相关的表面上的细胞计数。 紧凑型细胞仪系统提供坚固，经济实惠且易于使用的技术，可用于偏远地区。