公开(公告)号：US20110200239A1

公开(公告)日：2011-08-18

申请号：US13016392

申请日：2011-01-28

申请人： Joshua D. Levine ,  Robert A. Levine ,  Stephen C. Wardlaw ,  Craig Stout ,  David A. Clipper

发明人： Joshua D. Levine ,  Robert A. Levine ,  Stephen C. Wardlaw ,  Craig Stout ,  David A. Clipper

IPC分类号： G06K9/00

CPC分类号： G01N33/491 ,  B01L3/50215 ,  B01L9/065 ,  B01L2300/027 ,  B01L2300/0609 ,  B01L2300/0654 ,  B01L2300/0838 ,  G01N15/042 ,  G01N15/05 ,  G01N2015/045 ,  G01N2800/22 ,  G06T7/0012 ,  G06T2207/30024

摘要： An apparatus for and method of analyzing hematologic samples deposited within a capillary tube is provided. The method includes the steps of: a) imaging a region of sample centrifuged within a capillary tube using a first analysis device, which region is defined by substantially all of the radial width and axial length of the sample residing within the internal cavity of the tube where the float resides after centrifugation, and producing signals representative of the image; b) communicating the signals representative of the image to a second analysis device independent of, and remotely located from, the first analysis device; c) processing the signals representative of the image using the second analysis device and producing analysis data based on the signals; and d) displaying the image of the region of the sample using the second analysis device.

摘要翻译： 提供了一种用于分析沉积在毛细管内的血液样品的方法和方法。 该方法包括以下步骤：a）使用第一分析装置对在毛细管内离心的样品的区域进行成像，该区域由位于管内腔内的样品的基本上所有的径向宽度和轴向长度限定 离心后浮子位于其中，并产生代表图像的信号; b）将表示所述图像的信号传送到与所述第一分析装置无关并且远离所述第一分析装置的第二分析装置; c）使用第二分析装置处理表示图像的信号，并基于该信号产生分析数据; 以及d）使用所述第二分析装置显示所述样品的区域的图像。

公开(公告)号：US07995194B2

公开(公告)日：2011-08-09

申请号：US12417246

申请日：2009-04-02

申请人： Stephen C. Wardlaw ,  Robert A. Levine

发明人： Stephen C. Wardlaw ,  Robert A. Levine

IPC分类号： G01N33/48 ,  G01N21/03

CPC分类号： G01N33/48 ,  G01N21/6428 ,  G01N33/5304 ,  G01N33/54373 ,  G01N33/54386

摘要： Detection and characterization of immunologically detected substances are performed electronically on human and animal biological fluids such as whole blood, serum, plasma, urine, milk, pleural and peritoneal fluids, and semen, which fluids are contained in a thin chamber forming a quiescent fluid sample, which chamber has at least two parallel planar walls, at least one of which is transparent.

摘要翻译： 免疫检测物质的检测和表征以人和动物生物流体如全血，血清，血浆，尿，牛奶，胸膜和腹膜液以及精液电子方式进行，这些流体包含在形成静态流体样品的薄室中 该室具有至少两个平行的平面壁，其中至少一个是透明的。

公开(公告)号：US07929121B2

公开(公告)日：2011-04-19

申请号：US12408500

申请日：2009-03-20

申请人： Stephen C. Wardlaw ,  Robert A. Levine ,  Niten V. Lalpuria

发明人： Stephen C. Wardlaw ,  Robert A. Levine ,  Niten V. Lalpuria

IPC分类号： G01N33/48

CPC分类号： G01N33/49 ,  G01N15/147 ,  G01N15/1475 ,  G01N2015/0076 ,  G01N2015/008 ,  G01N2015/0084 ,  G01N2015/0092 ,  G01N2015/1486

摘要： A method for enumerating platelets within a blood sample is provided. The method includes the steps of: 1) depositing the sample into an analysis chamber adapted to quiescently hold the sample for analysis, the chamber defined by a first panel and a second panel, both of which panels are transparent; 2) admixing a colorant with the sample, which colorant is operative to cause the platelets to fluoresce upon exposure to one or more predetermined first wavelengths of light; 3) illuminating at least a portion of the sample containing the platelets at the first wavelengths; 4) imaging the sample, including producing image signals indicative of fluorescent emissions from the platelets, which fluorescent emissions have an intensity; 5) identifying the platelets by their fluorescent emissions, using the image signals; 6) determining an average fluorescent emission intensity value for the individual platelets identified within the sample; 7) identifying clumps of platelets within the sample using one or more of their fluorescent emissions, area, shape, and granularity; and 8) enumerating platelets within each platelet clump using the average fluorescent emission intensity value determined for the individual platelets within the sample.

摘要翻译： 提供了一种用于列举血液样品中的血小板的方法。 该方法包括以下步骤：1）将样品沉积到适于静态保持样品进行分析的分析室中，所述室由第一面板和第二面板限定，两个面板都是透明的; 2）将着色剂与所述样品混合，所述着色剂在暴露于一个或多个预定的第一波长的光时会使血小板发荧光; 3）以第一波长照射含有血小板的样品的至少一部分; 4）对样品进行成像，包括产生指示来自血小板的荧光发射的图像信号，该荧光发射具有强度; 5）使用图像信号通过荧光发射识别血小板; 6）确定样品内识别的各个血小板的平均荧光发射强度值; 7）使用其荧光发射，面积，形状和粒度中的一种或多种来鉴定样品中的血小板团块; 和8）使用为样品中的各个血小板确定的平均荧光发射强度值来列举每个血小板聚集体内的血小板。

公开(公告)号：US20100317106A1

公开(公告)日：2010-12-16

申请号：US12817012

申请日：2010-06-16

申请人： Robert A. Levine ,  Stephen C. Wardlaw

发明人： Robert A. Levine ,  Stephen C. Wardlaw

IPC分类号： C12N5/078

CPC分类号： G01N33/491 ,  Y10T436/25 ,  Y10T436/25375

摘要： Embodiments of the present invention are directed to harvesting a target material from a suspension using a tube and float system. A suspension suspected of containing a target material is combined with a solution having one or more labels that distinguish the target material from other materials in the suspension. The tube, float, and suspension are centrifuged to separate various materials in the suspension according to associated specific gravities. The float expands the axial length of the target material layer and displaces the target material to a narrow space between the float and the inner wall of the tube. The space is illuminated with light that causes the labels to emit light identifying the location of the target material within the tube. One or more openings can then be formed in the tube at or near the point where the target material is located and the target material harvested.

摘要翻译： 本发明的实施方案涉及使用管和浮子系统从悬浮液中收获目标材料。 怀疑含有目标材料的悬浮液与具有一种或多种将目标材料与悬浮液中的其它材料区分开的标签的溶液合并。 将管，浮子和悬浮液离心以根据相关的比重分离悬浮液中的各种材料。 浮子膨胀目标材料层的轴向长度，并将目标材料移位到浮子和管内壁之间的狭窄空间。 该空间用光照亮，导致标签发光，以识别目标材料在管内的位置。 然后可以在管中或其附近位于目标材料所在的点附近形成一个或多个开孔，并且收集目标材料。

公开(公告)号：US20090252399A1

公开(公告)日：2009-10-08

申请号：US12417333

申请日：2009-04-02

申请人： Stephen C. Wardlaw ,  Robert A. Levine

发明人： Stephen C. Wardlaw ,  Robert A. Levine

IPC分类号： G06K9/00

CPC分类号： G01N33/48 ,  G01N21/6428 ,  G01N33/5304 ,  G01N33/54373 ,  G01N33/54386

摘要： A method and apparatus for measuring antibody titers in a thin film sample in an automated system which does not require multiple dilutions. The system provides a simple method for creating an in-situ dilution within a sample analysis chamber without the use of any precision fluid-handling components, and further, to use the same principles to provide a wide range of sample dilutions within the chamber so as to obviate the need for additional dilution steps when dealing with samples possibly containing wide ranges of analyte concentrations.

摘要翻译： 一种在不需要多次稀释的自动化系统中测量薄膜样品中抗体滴度的方法和装置。 该系统提供了一种用于在样品分析室内创建原位稀释而不使用任何精密流体处理组件的简单方法，此外，使用相同的原理在腔室内提供范围广泛的样品稀释度，以便 以避免在处理可能含有大范围分析物浓度的样品时需要额外的稀释步骤。

公开(公告)号：US20090238437A1

公开(公告)日：2009-09-24

申请号：US12408256

申请日：2009-03-20

申请人： Robert A. Levine ,  Stephen C. Wardlaw ,  Darryn W. Unfricht ,  Niten V. Lalpuria

发明人： Robert A. Levine ,  Stephen C. Wardlaw ,  Darryn W. Unfricht ,  Niten V. Lalpuria

IPC分类号： G06K9/00

CPC分类号： G01N33/80 ,  A61B5/145 ,  G01N15/1463 ,  G01N15/1475 ,  G01N33/48 ,  G01N33/49 ,  G01N33/721 ,  G01N33/86

摘要： A method for determining the hematocrit of a blood sample is provided that includes the steps of: 1) depositing the sample into an analysis chamber adapted to quiescently hold the sample for analysis, the chamber defined by the interior surfaces of first and second panels and a height extending there between, wherein both panels are transparent, and the height is such that at least some of the red blood cells within the sample contact both interior surfaces of the panels and one or more lacunae within the quiescent sample extend between the interior surfaces; 2) imaging at least a portion of the quiescent sample, which sample portion contains the red blood cells and one or more lacunae to determine an optical density of the imaged portion of the sample on a per image unit basis; 3) selecting and averaging the optical density values of the image units aligned with the red blood cells contacting the interior surfaces, and assigning an upper boundary value of 100% to the average optical density value of those image units; 4) selecting the optical density values of the image units aligned with the one or more lacunae, and assigning a lower boundary value of 0% to the optical density values of those image units; and 5) determining the hematocrit of the sample by assigning relative values to the optical density value of each image of the imaged sample portion as a function of the upper and lower boundary values, and averaging the relative values.

摘要翻译： 提供了一种用于确定血液样本的血细胞比容的方法，其包括以下步骤：1）将样品沉积到适于静态保持样品进行分析的分析室中，由第一和第二面板的内表面限定的腔室和 高度在其间延伸，其中两个面板是透明的，并且高度使得样品中的至少一些红细胞接触面板的两个内表面，并且静止样品内的一个或多个空隙在内表面之间延伸; 2）对静止样品的至少一部分进行成像，该样品部分包含红细胞和一个或多个空隙，以基于每个图像单位确定样品的成像部分的光密度; 3）选择和平均与内表面接触的红细胞对准的图像单元的光密度值，并将上限边界值分配给这些图像单元的平均光密度值; 4）选择与一个或多个空白对齐的图像单元的光密度值，并为这些图像单元的光密度值分配0％的下边界值; 以及5）通过将所述成像样本部分的每个图像的光密度值分配相对值作为上边界值和下边界值的函数来确定样本的血细胞比容，并平均相对值。

公开(公告)号：US07129056B2

公开(公告)日：2006-10-31

申请号：US11155856

申请日：2005-06-20

申请人： David L. Rimm ,  Paul Fiedler ,  Robert A. Levine ,  Stephen C. Wardlaw

发明人： David L. Rimm ,  Paul Fiedler ,  Robert A. Levine ,  Stephen C. Wardlaw

IPC分类号： G01N33/53

CPC分类号： G01N33/56972 ,  C07K16/109 ,  G01N15/042 ,  G01N33/57484 ,  G01N33/6878 ,  G01N2015/045 ,  Y10S436/81

摘要： A method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence of target cells which have expressed surface epitopes that indicate intracellular infection by various viruses or other infectious agents, and also cells which have expressed surface epitopes that indicate the presence of non-infectious medical conditions. The analysis involves the examination of cells in the blood sample for the presence or absence of particular surface epitopes while the blood sample is disposed in a centrifuged blood sampling container. The epitopic analysis for the presence or absence of infected cells, or cells which indicate the presence of non-infectious medical conditions relies on the detection of known target expressed epitopes. The target epitopes on the target cell types are epitopes which are also known to be absent on normal circulating cells in the blood. Fluorophores or other labels with distinct wavelength emissions are coupled with specific binding agents such as lectins, antibodies, aptamers, or the like, which are directed against the target expressed epitopes. The epitopic analyses may be performed in or near the expanded buffy coat layer in the centrifuged blood sample. The epitopic analysis may be performed under magnification either visually and/or photometrically. The blood sampling container is sized to hold between about 1 and about 20 ml, preferably about 10 ml of blood, and contains an insert that occupies about 90–98% of the volume of the container bore in the area of the container where the target cells will, if present, be detected. The insert forces the target cells in question to reside in an annular space in the container which is adjacent to the circumference of the container bore. The entire analysis can be performed in a relatively short period of time which is typically a matter of minutes to single digit hours.

公开(公告)号：US06911315B2

公开(公告)日：2005-06-28

申请号：US10042016

申请日：2002-01-10

申请人： David L. Rimm ,  Paul Fiedler ,  Robert A. Levine ,  Stephen C. Wardlaw

发明人： David L. Rimm ,  Paul Fiedler ,  Robert A. Levine ,  Stephen C. Wardlaw

IPC分类号： C07K16/10 ,  C12Q1/70 ,  G01N15/04 ,  G01N33/569 ,  G01N33/574 ,  G01N33/68 ,  G01N33/53

CPC分类号： G01N33/56972 ,  C07K16/109 ,  G01N15/042 ,  G01N33/57484 ,  G01N33/6878 ,  G01N2015/045 ,  Y10S436/81

摘要： A method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence of target cells which have expressed surface epitopes that indicate intracellular infection by various viruses or other infectious agents, and also cells which have expressed surface epitopes that indicate the presence of non-infectious medical conditions. The analysis involves the examination of cells in the blood sample for the presence or absence of particular surface epitopes while the blood sample is disposed in a centrifuged blood sampling container. The epitopic analysis for the presence or absence of infected cells, or cells which indicate the presence of non-infectious medical conditions relies on the detection of known target expressed epitopes. The target epitopes on the target cell types are epitopes which are also known to be absent on normal circulating cells in the blood. Fluorophores or other labels with distinct wavelength emissions are coupled with specific binding agents such as lectins, antibodies, aptamers, or the like, which are directed against the target expressed epitopes. The epitopic analyses may be performed in or near the expanded buffy coat layer in the centrifuged blood sample. The epitopic analysis may be performed under magnification either visually and/or photometrically. The blood sampling container is sized to hold between about 1 and about 20 ml, preferably about 10 ml of blood, and contains an insert that occupies about 90-98% of the volume of the container bore in the area of the container where the target cells will, if present, be detected. The insert forces the target cells in question to reside in an annular space in the container which is adjacent to the circumference of the container bore. The entire analysis can be performed in a relatively short period of time which is typically a matter of minutes to single digit hours.

公开(公告)号：US06670197B2

公开(公告)日：2003-12-30

申请号：US09800344

申请日：2001-03-05

申请人： David L. Rimm ,  Stephen C. Wardlaw ,  Robert A. Levine ,  Paul Fiedler

发明人： David L. Rimm ,  Stephen C. Wardlaw ,  Robert A. Levine ,  Paul Fiedler

IPC分类号： G01N33543

CPC分类号： G01N15/042 ,  G01N33/56972 ,  G01N33/57484 ,  G01N2015/045

摘要： This method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of fragments of target analyte cancer cells which are circulating in blood. The analysis is performed in a sample of centrifuged anticoagulated whole blood. The analysis of the presence or absence of fragments of cancer cells relies on the detection of external or internal binding sites which are known to be present only in or on tumorous cancer cells. Fluorophors with distinct wavelength emissions are coupled with antibodies, or other binding moieties such as complementary nucleotide sequences, which antibodies are directed against the epithelial cell fragment membrane binding sites, such as internal or external surface epitopes on the cell fragments, or internal binding sites on cell organelles; and which nucleotide sequences are complementary to portions of cell fragment RNA and/or DNA. The labled binding agents are humoric or soluble in the blood sample. The labeled fluorometric binding site-specific materials may be coupled to small plastic beads which have a density or specific gravity that is preferably greater than the specific gravity or density of the red blood cells. The target cell fragments are less dense than the red cells, and typically have the same density or specific gravity as the platelets or white blood cells in the blood sample. Any of the labeled beads which couple with target cell analyte fragments will have a density or specific gravity that is less than the red cells in the blood sample. Thus cell fragment/labeled bead couples will gravitate into an area in the centrifuged blood sample which area is somewhere above the centrifuged red cell layer. The detection of the labeled target analyte/particle couples can be performed in situ in the centrifuged blood sample either visually or photometrically.

摘要翻译： 用于分析血液的方法使得能够在放大下分离，检测，枚举和确认在血液中循环的靶分析物癌细胞的片段的存在或不存在。 在离心的抗凝全血样品中进行分析。 对癌细胞片段的存在或不存在的分析依赖于已知仅存在于肿瘤细胞中或肿瘤细胞中的外部或内部结合位点的检测。 具有不同波长发射的荧光体与抗体或其它结合部分例如互补核苷酸序列偶联，所述抗体针对上皮细胞片段膜结合位点，例如细胞片段上的内部或外部表面表位或内部结合位点 细胞器 哪些核苷酸序列与细胞片段RNA和/或DNA的部分互补。 标记的粘合剂是幽默的或可溶于血液样品。 标记的荧光结合位点特异性材料可以耦合到具有优选大于红细胞的比重或密度的密度或比重的小塑料珠粒。 靶细胞碎片比红细胞密度低，通常具有与血液样品中的血小板或白细胞相同的密度或比重。 与靶细胞分析物片段偶联的任何标记珠粒将具有小于血液样品中红细胞的密度或比重。 因此，细胞碎片/标记的珠子对将被引入离心的血液样品中的该区域位于离心红细胞层上方的区域中。 标记的目标分析物/颗粒对的检测可以在离心的血液样品中在视觉上或光度下原位进行。

公开(公告)号：US06444436B1

公开(公告)日：2002-09-03

申请号：US09507635

申请日：2000-02-22

申请人： David L. Rimm ,  Paul Fiedler ,  Robert A. Levine ,  Stephen C. Wardlaw

发明人： David L. Rimm ,  Paul Fiedler ,  Robert A. Levine ,  Stephen C. Wardlaw

IPC分类号： G01N33574

CPC分类号： G01N33/57488 ,  Y10S436/81

摘要： A method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of target cancer cells and/or hematologic progenitor cells, or other rare events which are known to circulate in blood. The analysis is performed in a sample of centrifuged anticoagulated whole blood. The analysis involves both morphometric and epitopic examination of the blood sample while the blood sample is disposed in a centrifuged blood sampling container. The epitopic analysis of the presence or absence of cancer cells relies on the detection of epitopes which are known to be present on cancer cells and not on normal circulating blood cells; and the epitopic analysis of the presence or absence of hematologic progenitor cells relies on the detection of epitopes which are known to be present on hematologic progenitor cells and not on normal circulating blood cells. The targeted epitopes on the target cell types are epitopes which are also known to be absent on normal circulating blood cells; and the target cancer cell epitopes are epitopes which are known to be absent on target hematologic progenitor cells. Fluorophors with distinct emissions are coupled with antibodies which are directed against the targeted epitopes. The morphometric analysis is performed by staining the cells in the blood sample with an intracellular stain, such as acridine orange, which highlights the intracellular cell structure. Both the morphometric and epitopic analyses are preferably performed in the expanded buffy coat layer in the centrifuged blood sample. The morphometric analysis and/or the epitopic analysis may be performed under magnification both visually and/or photometrically.

摘要翻译： 用于分析血液的方法使得能够在放大下分离，检测，枚举和确认靶癌细胞和/或血液祖细胞的存在或不存在，或已知在血液中循环的其它罕见事件。 在离心的抗凝全血样品中进行分析。 该分析涉及血液样品的形态测定和表征检查，同时将血液样品置于离心取样容器中。 癌细胞存在或不存在的表位分析依赖于已知存在于癌细胞而不是正常循环血细胞上的表位的检测; 并且血液祖细胞存在或不存在的表征分析依赖于已知存在于血液祖细胞而不是正常循环血细胞上的表位的检测。 目标细胞类型上的靶向表位是已知在正常循环血细胞上不存在的表位; 并且目标癌细胞表位是已知在靶血液祖细胞上不存在的表位。 具有明显排放的荧光素与针对靶向表位的抗体相结合。 通过用细胞内染色剂如吖啶橙染色血液样品中的细胞进行形态测定分析，其突出显示细胞内细胞结构。 形态测定和表征分析优选在离心血液样品中的膨胀的血沉棕黄层中进行。 形态测定分析和/或表征分析可以在视觉上和/或光度下放大进行。