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公开(公告)号：US08128890B2
公开(公告)日：2012-03-06
申请号：US12917000
申请日：2010-11-01
IPC分类号： G01N33/52 , 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。
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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。
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公开(公告)号：US08569077B2
公开(公告)日：2013-10-29
申请号：US12467932
申请日：2009-05-18
申请人： Tyco M. Scholtens , Frederik Schreuder , Jan Greve , Arjan G. J. Tibbe , Leon W. M. M. Terstappen
发明人： Tyco M. Scholtens , Frederik Schreuder , Jan Greve , Arjan G. J. Tibbe , Leon W. M. M. Terstappen
IPC分类号： G01N33/553
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。
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公开(公告)号：US07764821B2
公开(公告)日：2010-07-27
申请号：US11434321
申请日：2006-05-12
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： 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。
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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。
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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。
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公开(公告)号：US20110044527A1
公开(公告)日：2011-02-24
申请号：US12917000
申请日：2010-11-01
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： G06K9/00
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。
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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。
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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。
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公开(公告)号：US5017497A
公开(公告)日：1991-05-21
申请号：US327416
申请日：1989-03-20
CPC分类号： G01N15/1434 , G01N2015/0065 , G01N2015/149 , G01N2021/4704 , G01N21/21 , G01N21/6445
摘要： Method and apparatus for analyzing particles based on different depolarizing structure associated with the different particle types. Cells in a flow cytometer are illuminated with a linearly polarized light, producing scattered depolarized light whose intensity range, at a selected measuring angle, and in a suitable discriminating space, is used to analyze different particle types.
摘要翻译： 基于与不同粒子类型相关的不同去极化结构分析颗粒的方法和装置。 用线性偏振光照射流式细胞仪中的细胞，产生散射的去偏振光，其强度范围以选定的测量角度和合适的辨别空间用于分析不同的粒子类型。
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