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    Magnetic separation apparatus and methods
    12.
    发明授权
    Magnetic separation apparatus and methods 有权
    磁分离装置及方法

    公开(公告)号：US06890426B2

    公开(公告)日：2005-05-10

    申请号：US10733829

    申请日：2003-12-10

    申请人： Leon W. M. M. Terstappen ,  Gerald Dolan

    发明人： Leon W. M. M. Terstappen ,  Gerald Dolan

    IPC分类号： B01D35/06 ,  B03C1/00 ,  G01N33/53

    CPC分类号： B03C1/002 ,  B03C2201/18 ,  B03C2201/26 ,  Y10T436/25375

    摘要： Apparatuses and methods for separating, immobilizing, and quantifying biological substances from within a fluid medium. Biological substances are observed by employing a vessel (6) having a chamber therein, the vessel comprising a transparent collection wall (5). A high internal gradient magnetic capture structure may be on the transparent collection wall (5), magnets (3) create an externally-applied force for transporting magnetically responsive material toward the transparent collection wall (5). The magnetic capture structure comprises a plurality of ferromagnetic members and has a uniform or non-uniform spacing between adjacent members. There may be electrical conductor means supported on the transparent collection wall (5) for enabling electrical manipulation of the biological substances. The chamber has one compartment or a plurality of compartments with differing heights. The chamber may include a porous wall. The invention is also useful in conducting quantitative analysis and sample preparation in conjunction with automated cell enumeration techniques.

    摘要翻译： 从流体介质中分离，固定和定量生物物质的装置和方法。 通过使用其中具有室的容器（6）观察生物物质，所述容器包括透明收集壁（5）。 高的内部梯度磁捕获结构可以在透明收集壁（5）上，磁体（3）产生用于将磁响应材料传送到透明收集壁（5）的外部施加的力。 磁捕获结构包括多个铁磁构件，并且在相邻构件之间具有均匀或不均匀的间隔。 可以存在支撑在透明收集壁（5）上的电导体装置，用于实现生物物质的电操作。 该室具有一个隔室或多个具有不同高度的隔间。 腔室可以包括多孔壁。 本发明还可用于结合自动细胞计数技术进行定量分析和样品制备。

    Method to select and transfect cell subpopulations
    13.
    发明授权
    Method to select and transfect cell subpopulations 有权
    选择和转染细胞亚群的方法

    公开(公告)号：US06228624B1

    公开(公告)日：2001-05-08

    申请号：US09230394

    申请日：1999-01-27

    申请人： Leon W. M. M. Terstappen

    发明人： Leon W. M. M. Terstappen

    IPC分类号： C12N1587

    CPC分类号： C12N15/87

    摘要： A method for transfecting and separating cells is disclosed. The method comprises preparing magnetic particles coated with genetic material and a cell-specific ligand, and using the particles to transfect target cells. The target cells may then be separated from the non-target cells by using a magnetic field.

    摘要翻译： 公开了转染和分离细胞的方法。 该方法包括制备涂覆有遗传物质的磁性颗粒和细胞特异性配体，并使用该颗粒转染靶细胞。 然后可以通过使用磁场将目标细胞与非靶细胞分离。

    Indirect fluorescent assay of blood samples
    15.
    发明授权
    Indirect fluorescent assay of blood samples 失效
    血液样品的间接荧光检测

    公开(公告)号：US5460979A

    公开(公告)日：1995-10-24

    申请号：US192629

    申请日：1994-02-07

    申请人： Robert A. Levine ,  Stephen C. Wardlaw ,  Leon W. M. M. Terstappen ,  Thomas J. Mercolino ,  Diether J. Recktenwald

    发明人： Robert A. Levine ,  Stephen C. Wardlaw ,  Leon W. M. M. Terstappen ,  Thomas J. Mercolino ,  Diether J. Recktenwald

    IPC分类号： G01N33/543 ,  B01L3/14 ,  G01N33/49 ,  G01N33/537 ,  G01N33/569 ,  G01N33/58 ,  G01N33/538 ,  G01N33/546

    CPC分类号： B01L3/5021 ,  G01N33/491 ,  G01N33/5375 ,  G01N33/56972 ,  G01N33/585 ,  Y10S435/81 ,  Y10S435/967 ,  Y10S435/971 ,  Y10S435/973 ,  Y10S436/805 ,  Y10S436/81 ,  Y10S436/824 ,  Y10S436/829 ,  Y10T436/111666

    摘要： A patient's health is diagnosed by centrifuging blood samples in a transparent tube, which tube contains one or more groups of particles such as lyposomes or plastic beads of different densities for each group. Each group of density-defined particles carries antigens or antibodies which are specific to a complement antigen or antibody which may be in the blood sample being tested, and which are indicative of the patient's health. A label-tagged antibody which is specific to all bound antibody/antigen couples is added to the blood sample so as to form labelled antibody+antigen-antibody complexes (AAAC) in the blood sample. Upon centrifugation, the complexed particles will settle out in different areas in the tube according to the respective density of the particles, and the degree of label emission of the particle layers can enable qualitative or quantitative analyses of the blood sample to be made. Unbound labelled antibodies will be washed away from the complexed layers by the washing action of the descending blood cells during the centrifugation step. Unbound labelled antibodies will thus not interfere with the analysis.

    摘要翻译： 通过在透明管中离心血液样品来诊断患者的健康，该管含有一组或多组颗粒，例如每组的不同密度的溶血细胞或塑料珠。 每组密度定义的颗粒携带对可能在被测试的血液样品中的补体抗原或抗体特异性的抗原或抗体，并且其表示患者的健康。 向血液样品中加入对所有结合的抗体/抗原对特异性的标记标签抗体，以在血液样品中形成标记抗体+抗原 - 抗体复合物（AAAC）。 离心后，根据颗粒的相应密度，络合的颗粒将沉淀在管中的不同区域中，并且颗粒层的标签发射程度可以使得要进行血液样品的定性或定量分析。 在离心步骤中，未结合的标记抗体将通过下降血细胞的洗涤作用从复合层中洗去。 因此，未结合的标记抗体不会干扰分析。

    Imaging of immunomagnetically enriched rare cells
    17.
    发明授权
    Imaging of immunomagnetically enriched rare cells 有权
    免疫磁性富集稀有细胞成像

    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。

    Methods and algorithms for cell enumeration in a low-cost cytometer
    18.
    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：US08128890B2

    公开(公告)日：2012-03-06

    申请号：US12917000

    申请日：2010-11-01

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

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

    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。

    Methods and algorithms for cell enumeration in a low-cost cytometer
    19.
    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：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。