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1. 发明授权

US07064823B2 Consumable tube for use with a flow cytometry-based hematology system 有权
公开(公告)号：US07064823B2
公开(公告)日：2006-06-20
申请号：US10159944
申请日：2002-05-31
申请人： John W. Roche , W. Peter Hansen , Michelle L. Coleman , Harold R. Crews
发明人： John W. Roche , W. Peter Hansen , Michelle L. Coleman , Harold R. Crews
IPC分类号： G01N1/10 , G01N21/00
CPC分类号： H04L25/063 , G01N1/38 , G01N15/1434 , G01N15/1459 , G01N15/147 , G01N35/1095 , G01N2015/0069 , G01N2015/0076 , G01N2015/008 , G01N2015/0084 , G01N2015/1486 , G01N2015/1493
摘要： The present invention is a flow cytometry-based hematology system useful in the analysis of biological samples, particularly whole blood or blood-derived samples. The system is capable of determining at least a complete blood count (CBC), a five-part white blood cell differential, and a reticulocyte count from a whole blood sample. The system preferably uses a laser diode that emits a thin beam to illuminate cells in a flow cell and a lensless optical detection system to measure one or more of axial light loss, low-angle forward scattered light, high-angle forward scattered light, right angle scattered light, and time-of-flight measurements produced by the cells. The lensless optical detection system contains no optical components, other than photoreactive elements, and does not include any moving parts. Finally, the system uses a unique system of consumable reagent tubes that act as reaction chambers, mixing chambers, and waste chambers for the blood sample analyses. The consumable tubes incorporate reference particles, which act as internal standards to ensure that the dilutions made during processing of the samples have been carried out correctly, and to ensure that the instrument is working properly. The present invention also relates to methods for using the system.

2. 发明授权

US06784981B1 Flow cytometry-based hematology system 有权
标题翻译：基于流式细胞术的血液系统
公开(公告)号：US06784981B1
公开(公告)日：2004-08-31
申请号：US09715593
申请日：2000-11-17
申请人： John W. Roche , W. Peter Hansen , Marcus F. Julian , Harold C. Flynn, Jr.
发明人： John W. Roche , W. Peter Hansen , Marcus F. Julian , Harold C. Flynn, Jr.
IPC分类号： G01N3348
CPC分类号： H04L25/063 , G01N1/38 , G01N15/1434 , G01N15/1459 , G01N15/147 , G01N35/1095 , G01N2015/0069 , G01N2015/0076 , G01N2015/008 , G01N2015/0084 , G01N2015/1486 , G01N2015/1493
摘要： The present invention is a flow cytometry-based hematology system useful in the analysis of biological samples, particularly whole blood or blood-derived samples. The system is capable of determining at least a complete blood count (CBC), a five-part white blood cell differential, and a reticulocyte count from a whole blood sample. The system preferably uses a laser diode that emits a thin beam to illuminate cells in a flow cell and a lensless optical detection system to measure one or more of axial light loss, low-angle forward scattered light, high-angle forward scattered light, right angle scattered light, and time-of-flight measurements produced by the cells. The lensless optical detection system contains no optical components, other than photoreactive elements, and does not include any moving parts. Finally, the system uses a unique system of consumable reagent tubes that act as reaction chambers, mixing chambers, and waste chambers for the blood sample analyses. The consumable tubes incorporate reference particles, which act as internal standards to ensure that the dilutions made during processing of the samples have been carried out correctly, and to ensure that the instrument is working properly. The present invention also relates to methods for using the system.
摘要翻译：本发明是用于分析生物样品，特别是全血或血液衍生样品的基于流式细胞术的血液学系统。该系统能够从全血样品中确定至少一个完整的血细胞计数（CBC），五部分白细胞差异和网织红细胞计数。该系统优选使用发射细束以照射流动池中的细胞的激光二极管和无透镜光学检测系统，以测量轴向光损失，低角度前向散射光，高角度前向散射光，右角散射光和由细胞产生的飞行时间测量。透镜式光学检测系统不包含除光反应元件之外的光学部件，并且不包括任何移动部件。最后，该系统使用独特的消耗性试剂管系统作为反应室，混合室和废液室进行血液样品分析。消耗品管包含参考颗粒，其作为内部标准，以确保样品处理过程中进行的稀释度已经正确进行，并确保仪器正常工作。本发明还涉及使用该系统的方法。

3. 发明授权

US06618143B2 High numerical aperture flow cytometer and method of using same 有权
公开(公告)号：US06618143B2
公开(公告)日：2003-09-09
申请号：US09969242
申请日：2001-10-02
申请人： John W. Roche , W. Peter Hansen , Harold C. Flynn, Jr.
发明人： John W. Roche , W. Peter Hansen , Harold C. Flynn, Jr.
IPC分类号： G01N2100
CPC分类号： G01N15/1434 , G01N15/1456 , G01N2015/0065 , G01N2021/4704
摘要： The high numerical aperture flow cytometer of the present invention includes a flow cell and a laser input. The laser input emits a beam of light that is oriented substantially orthogonally to the flow of blood cells through the flow cell such that laser light impinges upon the blood cells as they pass through the flow cell. A portion of the beam from the laser input that impinges upon the blood cells in the flow cell is scattered at a substantially right angle to the beam of laser input (“right angle scatter”). A second portion of the beam from the laser input that impinges upon the cells in the flow cell is scattered at a much lower angle than 90°. This scatter is termed forward scatter light” and is collected on two distinct photo detectors, that represent ‘forward scatter low’ (FSL) which has an angle of from about 1° to about 3°, and ‘forward scatter high’ (FSH) which has an angle of from about 9° to about 12° from the orientation of the original beam from laser input. A third photo detector is placed in between these two forward scatter detectors, that is axial with the impinging laser light. This detector measures axial light loss, or light extinction (EXT) which is the sum of all the light that is absorbed and scattered by the blood cells. A right angle scatter light detector is oriented to receive the previously mentioned right angle scatter light. A forward scatter light detector is oriented to capture the previously mentioned forward scatter light oriented different angles from the beam of the laser input.

4. 发明授权

US4661451A Methods for immobilizing and translocating biological cells 失效
标题翻译：固定和移位生物细胞的方法
公开(公告)号：US4661451A
公开(公告)日：1987-04-28
申请号：US577120
申请日：1984-02-06
申请人： W. Peter Hansen
发明人： W. Peter Hansen
IPC分类号： C12N11/00 , C12N11/14 , C12N11/16 , C12N13/00
CPC分类号： C12N11/00 , Y10T436/25375 , Y10T436/255
摘要： Apparatus for immobilizing biological cells based on the dielectric properties of biological cells. An inhomogeneous electric field emanating from a grid point location or other contact area is created and attracts the biological cell into contact therewith. Appropriate controls over a series of grid points permits controlled inter-grid point movement of cells thereby permitting sequential testing or sorting processes to be carried out.
摘要翻译：基于生物细胞的介电特性固定生物细胞的装置。产生从网格点位置或其他接触区域发出的不均匀电场，并吸引生物细胞与其接触。对一系列网格点进行适当的控制可以允许单元格的可控网格间移动，从而允许执行顺序测试或排序过程。

5. 发明授权

US4325483A Method for detecting and controlling flow rates of the droplet forming stream of an electrostatic particle sorting apparatus 失效
标题翻译：用于检测和控制静电颗粒分选装置的液滴形成流的流速的方法
公开(公告)号：US4325483A
公开(公告)日：1982-04-20
申请号：US68231
申请日：1979-08-20
申请人： Igino Lombardo , Donald E. Barry , W. Peter Hansen
发明人： Igino Lombardo , Donald E. Barry , W. Peter Hansen
IPC分类号： G01N15/14 , B07C5/342
CPC分类号： G01N15/1404 , G01N2015/1406 , G01N2015/149 , Y10S209/906
摘要： A novel method is disclosed for detecting and controlling the flow rate of a perturbed, droplet-forming stream in an electrostatic particle sorting apparatus. Detection apparatus is located at two points along the stream, at a first particle sensing point for sensing the presence of particles within a core portion of the stream, and at a second downstream point, preferably the stream breakpoint, for sensing light scatter and extinction characteristics which are proportional to the surface characteristics of the sheath portion of the stream. Changes in phase shift, pulse width, duty cycle, pulse area, or breakpoint location are detected by analyzing these sheath surface-related characteristics. An error signal is produced in response to such changes which drives an electromechanical fluid flow regulator to increase or decrease the fluid flow rate in a direction which tends to minimize the error signal. The flow rate is thus maintained at a reference flow rate setting.
摘要翻译：公开了一种用于检测和控制静电颗粒分选装置中扰动的液滴形成流的流速的新方法。检测装置位于沿着流的两个点处，在用于感测流的核心部分内的颗粒的存在的第一颗粒感测点处，以及在第二下游点，优选地，流断点处，用于感测光散射和消光特性其与流的护套部分的表面特性成比例。通过分析这些鞘表面相关特征来检测相移，脉冲宽度，占空比，脉冲区域或断点位置的变化。响应于这样的变化而产生误差信号，这些变化驱动机电流体流量调节器以使倾向于最小化误差信号的方向增加或减小流体流速。因此，流速保持在参考流量设置。

6. 发明授权

US07116407B2 System for axial pattern analysis of multicellular organisms 有权
公开(公告)号：US07116407B2
公开(公告)日：2006-10-03
申请号：US10076363
申请日：2002-02-15
申请人： W. Peter Hansen , Anthony A. Ferrante , Russell J. Gershman , Petra B. Krauledat , Donald F. Perrault, Jr.
发明人： W. Peter Hansen , Anthony A. Ferrante , Russell J. Gershman , Petra B. Krauledat , Donald F. Perrault, Jr.
IPC分类号： G01N21/00 , G01N33/553 , B07C5/36
CPC分类号： G01N33/5085 , G01N15/1427 , G01N15/1429 , G01N15/147 , G01N15/1475 , G01N2015/145 , G01N2015/1477 , G01N2015/149 , G01N2015/1497
摘要： A method of using elongate multicellular organisms in conjunction with a specialized flow cytometer for drug discovery and compound screening. A stable, optically detectable linear marker pattern on each organism is used to construct a longitudinal map of each organism as it passes through the analysis region of the flow cytometer. This pattern is used to limit complex data analysis to particular regions of each organism thereby simplifying and speeding analysis. The longitudinal marker pattern can be used to alter signal detection modes at known regions of the organism to enhance sensitivity and overall detection effectiveness. A repeating pattern can also be used to add a synchronous element to data analysis. The marker patterns are established using known methods of molecular biology to express various indicator molecules. Inherent features of the organism can be rendered detectable to serve as marker patterns.

7. 发明授权

US06200820B1 Light scatter-based immunoassay 失效
标题翻译：基于光散射的免疫测定
公开(公告)号：US06200820B1
公开(公告)日：2001-03-13
申请号：US08473187
申请日：1995-06-07
申请人： W. Peter Hansen , Michael Cennerazzo , Carl Theodore Edens , Manish Kochar
发明人： W. Peter Hansen , Michael Cennerazzo , Carl Theodore Edens , Manish Kochar
IPC分类号： G01N33543
CPC分类号： G01N33/54346 , G01N15/0205 , G01N15/14 , G01N33/553
摘要： Disclosed are an optical flow particle apparatus and method for conducting a particle light scatter-based immunoassay for simultaneously measuring the presence or amount of one or more analytes in a fluid sample which involves the use of a reagent set for each analyte including first binding molecule-coated monodisperse microspheres and second binding molecule-coated colloidal particles in which at least one of the first or second binding molecules specifically binds a respective one of the analytes. In the case where more than one analytes are detected, each monodisperse microperse microsphere of a particular reagent set has a light scatter signal resolvable from that of microspheres of any other reagent set. Changes determined in the distributions of the measured light scatter signals for individual microspheres of each of the particular reagent sets are indicative of the presence or amount of the respective analyte(s) in the sample.
摘要翻译：公开了一种用于同时测量流体样品中一种或多种分析物的存在或量的用于进行基于粒子光散射的免疫测定的光学流动颗粒装置和方法，其涉及使用每种分析物的试剂组，包括第一结合分子 - 涂覆的单分散微球和第二结合分子涂覆的胶体颗粒，其中第一或第二结合分子中的至少一个特异性结合相应的一种分析物。在检测到多于一种分析物的情况下，特定试剂组的每个单分散微粉末微球具有可从任何其它试剂组的微球分解的光散射信号。每个特定试剂组的单个微球的测量的光散射信号的分布中确定的变化指示样品中相应分析物的存在或量。

8. 发明授权

US4791069A Methods for attaching ligands or anti-ligands to a solid phase 失效
标题翻译：将配体或反配体连接到固相的方法
公开(公告)号：US4791069A
公开(公告)日：1988-12-13
申请号：US47826
申请日：1987-05-08
申请人： George Hovorka , W. Peter Hansen
发明人： George Hovorka , W. Peter Hansen
IPC分类号： G01N33/543 , G01N33/531
CPC分类号： G01N33/543 , Y10S436/807 , Y10S436/809
摘要： Methods for attaching one component of a ligand-anti-ligand pair onto a solid phase surface. The component may be attached to a photoactivatable cross-linker capable of coupling the component to a colloidal medium coating the surface or alternatively, the component may be coupled to a bead and held in place against the surface by an overlay of the colloidal media having voids and spaces smaller than the diameter of the particle but large enough to permit diffusion of the other of the ligand-anti-ligand pair to be detected.
摘要翻译：将配体 - 抗 - 配体对的一个组分连接到固相表面上的方法。组分可以连接到能够将组分偶联到涂覆表面的胶体介质的可光活化交联剂中，或者可选择地，组分可以与珠结合并通过具有空隙的胶体介质的覆盖物保持在表面上和小于颗粒直径的空间，但足够大以允许待检测的配体 - 抗配体对中的另一个扩散。

9. 发明授权

US06413786B1 Binding assays using optical resonance of colloidal particles 失效
标题翻译：使用胶体颗粒的光学共振的结合测定
公开(公告)号：US06413786B1
公开(公告)日：2002-07-02
申请号：US09372444
申请日：1999-08-11
申请人： W. Peter Hansen , Petra Krauledat
发明人： W. Peter Hansen , Petra Krauledat
IPC分类号： G01N33553
CPC分类号： G01N33/54346 , C12Q1/6816 , G01N33/54313 , G01N33/553 , G01N33/585 , G01N33/587 , Y10S435/975 , Y10S436/805 , Y10S436/808 , C12Q2565/632 , C12Q2563/149 , C12Q2537/101 , C12Q2545/114
摘要： A device and a method enable the rapid, quantitative evaluation of a large collection of ligands for binding affinity with a certain immobilized receptor, the improvements being that binding pan be detected without the need for a label and that binding is carried out in solution phase at a high rate. The instrument has at least two embodiments, one is based on a sensitive absorption photometer and the other on a sensitive light scatter photometer operating at a specific resonance wavelength, &lgr;R, of small, metallic, colloidal particles. The resonance is present in small particles having a complex refractive index with real part n(&lgr;) approaching 0 and imaginary part k(&lgr;) approaching 2 simultaneously at a specific wavelength &lgr;R. The particles are substantially spherical and substantially smaller than &lgr;R. The receptor is immobilized on a suspension of such particles and ligand binding is detected by a change in optical absorption or light scatter at the resonance wavelength.
摘要翻译：一种装置和方法使得能够快速，定量地评估大量的配体与一定固定化受体结合亲和力的配体，改进之处在于检测结合盘而不需要标记，并且在溶液相中进行结合高利率。仪器具有至少两个实施例，一个是基于敏感的吸收光度计，另一个基于在小的金属，胶体颗粒的特定共振波长（lambdR）下操作的敏感光散射光度计上。共振存在于具有复数折射率的小颗粒中，实际部分n（lambd）接近0，虚部k（lambd）在特定波长lambdR下同时接近2。颗粒基本上是球形的并且基本上小于lambdR。受体被固定在这样的颗粒的悬浮液上，通过在共振波长处的光吸收或光散射的变化来检测配体结合。

10. 发明授权

US5589401A Light scatter-based immunoassay without particle self aggregation 失效
标题翻译：基于光散射的免疫测定，无颗粒自聚集
公开(公告)号：US5589401A
公开(公告)日：1996-12-31
申请号：US286778
申请日：1994-08-05
申请人： W. Peter Hansen , Michael Cennerazzo
发明人： W. Peter Hansen , Michael Cennerazzo
IPC分类号： G01N15/02 , G01N15/14 , G01N33/543 , G01N33/553 , G01N33/538 , G01N33/544
CPC分类号： G01N15/14 , G01N33/54313 , G01N33/553 , G01N15/0205
摘要： A homogeneous immunoassay method for the simultaneous determination of one or more antibody, antigen or hapten analytes in a fluid sample, that comprises the quantification of the effect of said analytes on the statistical changes in a dimension of a light scatter pulse height distribution histogram of relatively large diameter monodisperse binding molecule-coated polymeric microspheres induced by the binding to said microspheres of polydisperse binding molecule-coated colloid metal particles of relatively small diameter. For simultaneous assays of multiple analytes, different diameter or refractive index microspheres are assigned to each analyte. The assay may be used in forward binding, displacement, inhibition, and competition type systems, with the direction of the change in histogram dimension depending on the system. A convenient dimension to measure is the normalized peak width of a graphical representation of the histogram. For simultaneous assays for multiple analytes, a monodisperse polymeric microsphere of unique diameter or refractive index is dedicated to each analyte, so as to generate multiple histograms, one for each analyte. Polydisperse binding molecule-coated colloid metal particles, when used in effective concentrations, will also serve as a scavenger means to reduce the interfering effects of non-specific substances in the analyte-containing fluid samples, particularly when said samples are of biological origin.
摘要翻译：用于同时测定流体样品中一种或多种抗体，抗原或半抗原分析物的均匀免疫测定方法，其包括对所述分析物对相对较轻的光散射脉冲高度分布直方图的维度的统计变化的量化的量化通过与所述微球体结合相对小直径的多分散结合分子包被的胶体金属颗粒诱导的大直径单分散结合分子包被的聚合物微球。对于多个分析物的同时测定，将不同直径或折射率微球分配给每个分析物。该测定可用于正向结合，置换，抑制和竞争类型系统，其中取决于系统的直方图尺寸的变化方向。一个方便的测量尺寸是直方图的图形表示的归一化峰宽。对于多个分析物的同时测定，独特直径或折射率的单分散聚合物微球专用于每个分析物，以便产生多个直方图，每个分析物一个。当以有效浓度使用时，多分散结合分子涂覆的胶体金属颗粒也将用作清除剂手段，以减少非特异性物质在含分析物的流体样品中的干扰作用，特别是当所述样品是生物来源时。

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