公开(公告)号：US06297061B1

公开(公告)日：2001-10-02

申请号：US09501732

申请日：2000-02-10

申请人： Caicai Wu ,  Bernhard Weigl ,  Margaret A. Kenny ,  Paul Yager

发明人： Caicai Wu ,  Bernhard Weigl ,  Margaret A. Kenny ,  Paul Yager

IPC分类号： G01N33543

CPC分类号： G01N33/5005 ,  G01N33/54313 ,  Y10T436/117497 ,  Y10T436/118339 ,  Y10T436/25375 ,  Y10T436/255 ,  Y10T436/2575

摘要： This invention provides a method and apparatus for detecting the presence of analyte particles in a sample fluid also comprising larger particles, particularly blood. It exploits diffusion to provide simultaneous filtering of the larger particles and reaction of the analyte particles. A sample stream and a reagent stream join on the upstream end of a laminar flow reaction channel and flow in adjacent laminar streams. The reagents can be in solution or immobilized on a bead. The analyte particles diffuse from the sample stream into the reagent stream, leaving behind the larger particles in the residual sample stream. In the reagent stream the analyte particles react with reagent particles and form product particles, thereby creating a product stream. At the downstream end of the reaction channel, the residual sample stream and the product stream are divided. The product particles are then detected, preferably optically, in the product stream. Prior to detection, the product stream can undergo further filtering or separation, or can join a second reagent stream to form secondary product particles. This apparatus and method can be used to implement competitive immunoassays or sandwich immunoassays using enzymatically or fluorescently labeled immunoreagents. The apparatus and method can also be used to synthesize products, in which case two reagent streams join in the laminar flow reaction channel.

公开(公告)号：US06221677B1

公开(公告)日：2001-04-24

申请号：US09335930

申请日：1999-06-18

申请人： Caicai Wu ,  Bernhard Weigl ,  Margaret A. Kenny ,  Paul Yager

发明人： Caicai Wu ,  Bernhard Weigl ,  Margaret A. Kenny ,  Paul Yager

IPC分类号： G01N33543

CPC分类号： G01N33/5005 ,  G01N33/54313 ,  Y10T436/117497 ,  Y10T436/118339 ,  Y10T436/25375 ,  Y10T436/255 ,  Y10T436/2575

摘要： This invention provides a method and apparatus for detecting the presence of analyte particles in a sample fluid also comprising larger particles, particularly blood. It exploits diffusion to provide simultaneous filtering of the larger particles and reaction of the analyte particles. A sample stream and a reagent stream join on the upstream end of a laminar flow reaction channel and flow in adjacent laminar streams. The reagents can be in solution or immobilized on a bead. The analyte particles diffuse from the sample stream into the reagent stream, leaving behind the larger particles in the residual sample stream. In the reagent stream the analyte particles react with reagent particles and form product particles, thereby creating a product stream. At the downstream end of the reaction channel, the residual sample stream and the product stream are divided. The product particles are then detected, preferably optically, in the product stream. Prior to detection, the product stream can undergo further filtering or separation, or can join a second reagent stream to form secondary product particles. This apparatus and method can be used to implement competitive immunoassays or sandwich immunoassays using enzymatically or fluorescently labeled immunoreagents. The apparatus and method can also be used to synthesize products, in which case two reagent streams join in the laminar flow reaction channel.

摘要翻译： 本发明提供了一种用于检测样品流体中分析物颗粒的存在的方法和装置，其还包括较大的颗粒，特别是血液。 它利用扩散来提供较大颗粒的同时过滤和分析物颗粒的反应。 样品流和试剂流在层流反应通道的上游端连接并在相邻层流中流动。 试剂可以溶于或固定在珠粒上。 分析物颗粒从样品流扩散到试剂流中，留下残余样品流中较大的颗粒。 在试剂流中，分析物颗粒与试剂颗粒反应并形成产物颗粒，从而产生产物流。 在反应通道的下游端，残留的样品流和产物流被分开。 然后在产品流中优选地以光学方式检测产物颗粒。 在检测之前，产物流可以经历进一步的过滤或分离，或可以连接第二试剂流以形成次级产物颗粒。 该装置和方法可用于实施使用酶或荧光标记免疫试剂的竞争性免疫测定或夹心免疫测定。 该装置和方法也可用于合成产物，在这种情况下，两个试剂流连接在层流反应通道中。

公开(公告)号：US6136272A

公开(公告)日：2000-10-24

申请号：US938584

申请日：1997-09-26

申请人： Bernhard Weigl ,  Diane M. Zebert ,  Margaret A. Kenny

发明人： Bernhard Weigl ,  Diane M. Zebert ,  Margaret A. Kenny

IPC分类号： B01F5/04 ,  B01F5/06 ,  B01F13/00 ,  B81B1/00 ,  G01N21/64

CPC分类号： B01F13/0059 ,  B01F13/0093 ,  B01F5/0471 ,  B01F5/0604 ,  B01F2005/0031 ,  Y10S366/01 ,  Y10S366/03 ,  Y10T436/255

摘要： A device and method for introducing a second laminar fluid layer to, or removing a second laminar fluid layer from, a first laminar fluid layer are provided. Each laminar fluid layer can contain two or more side by side laminar streams. The device includes a main flow channel, and at least one tributary channel in fluid connection with a bridge channel which is in fluid connection with main flow channel. The device can be formed in a single piece of material, which can be optically transparent. Optionally, the channels can be formed in a first plate, the first and optionally the second surfaces of which are sealed to a second and optionally a third plate. The second and third plates can be optically transparent to allow for optical detection and analysis. A first laminar fluid layer is introduced into the main flow channel. If a second laminar fluid layer is to be added to the first laminar fluid layer, then the former is introduced into the tributary channel, from whence it flows into the bridge channel and then into the main flow channel, where it flows below the first laminar fluid layer and diffusionally mixes with it. Preferably, the width of the main flow channel is relatively small, so that particles in an added second laminar fluid layer diffusionally mix into the first laminar fluid layer rapidly. If a second laminar fluid layer is to be removed from a first laminar fluid layer, then the latter is split into two portions: one portion continues flowing down the main flow channel and one portion flows into the bridge channel from whence it flows into the tributary channel.

摘要翻译： 提供了用于将第二层流体层引导到第一层流体层或从第一层流体层移除第二层流体层的装置和方法。 每个层流层可以包含两个或更多个并排层流。 该装置包括主流道，以及至少一个与与主流道流体连接的桥梁通道流体连接的支流通道。 该装置可以形成为单一材料，其可以是光学透明的。 可选地，通道可以形成在第一板中，第一和第二表面的第二表面被密封到第二和第三板。 第二和第三板可以是光学透明的，以允许光学检测和分析。 第一层流体层被引入到主流动通道中。 如果要将第二层流体层添加到第一层流体层中，则将前者引入支流通道中，从其流入桥通道然后进入主流动通道，在主流道中流动到第一层流 流体层并与其扩散混合。 优选地，主流动通道的宽度相对较小，使得添加的第二层流体层中的颗粒迅速地混合到第一层流体层中。 如果要从第一层流体层去除第二层流体层，则将其分成两部分：一部分继续沿着主流动通道向下流动，一部分流入桥梁通道，从而从其流入支流 渠道。

公开(公告)号：US20060073599A1

公开(公告)日：2006-04-06

申请号：US11054711

申请日：2005-02-08

申请人： Bernhard Weigl ,  Paul Yager

发明人： Bernhard Weigl ,  Paul Yager

IPC分类号： G01N33/00

CPC分类号： B01D11/0492 ,  A61M1/14 ,  B01D11/0496 ,  B01L3/5027 ,  B01L3/502761 ,  B01L3/502776 ,  B01L2200/0636 ,  B01L2300/0816 ,  B01L2300/0867 ,  B01L2400/0406 ,  B01L2400/0487 ,  G01N15/1484 ,  Y10T436/25375

摘要： A channel-cell system is provided for detecting the presence and/or measuring the presence of analyte particles in a sample stream comprising: a) a laminar flow channel; b) two inlet means in fluid connection with said laminar flow channel for respectively conducting into said laminar flow channel (1) an indicator stream which may comprise an indicator substance which indicates the presence of said analyte particles by a detectable change in property when contacted with said analyte particles, and (2) said sample stream; c) wherein said laminar flow channel has a depth sufficiently small to allow laminar flow of said streams and a length sufficient to allow particles of said analyte to diffuse into said indicator stream to the substantial exclusion of said larger particles in said sample stream to form a detection area; and d) outlet means for conducting said streams out of said laminar flow channel to form a single mixed stream.

摘要翻译： 提供了一种通道细胞系统，用于检测样品流中存在和/或测量分析物颗粒的存在，其包括：a）层流通道; b）与所述层流通道流体连接的两个入口装置，用于分别导入所述层流通道（1）中的指示剂流，所述指示物流可包含指示物质，所述指示物质当与 所述分析物颗粒，和（2）所述样品流; c）其中所述层流通道具有足够小的深度以允许所述料流的层流，并且足够长度以允许所述分析物的颗粒扩散到所述指示物流中，以使所述样品流中的所述较大颗粒基本排除，形成 检测区; 以及d）用于将所述物流从所述层流通道引导以形成单一混合流的出口装置。

公开(公告)号：US6159739A

公开(公告)日：2000-12-12

申请号：US823747

申请日：1997-03-26

申请人： Bernhard Weigl ,  Paul Yager ,  James P. Brody

发明人： Bernhard Weigl ,  Paul Yager ,  James P. Brody

IPC分类号： G01N15/14 ,  G01N37/00 ,  G01N35/08

CPC分类号： G01N15/1404 ,  Y10S366/03 ,  Y10T436/117497 ,  Y10T436/118339

摘要： The present invention provides a sheath flow module made from a first plate of material having formed therein a laminar fluid flow channel; at least two inlets, each inlet joining the laminar flow channel at a junction, the first inlet junction being wider than the second inlet junction, and an outlet from the flow channel. A second plate, e.g. a transparent cover plate, seals the module and allows for optical measurements. A first inlet allows for introduction of a first fluid into the flow channel. The first fluid is the sheath fluid. A second inlet allows for introduction of a second fluid into the sheath fluid while it is flowing through the flow channel. The second fluid is the center fluid. Because the second inlet junction is narrower than the first inlet junction, the center fluid becomes surrounded on both sides by the sheath fluid. After all fluids have been introduced and sheath flow has been achieved, the depth of the flow channel can be decreased, leading to vertical hydrodynamic focusing. Optionally, the width of the flow channel can be decreased, leading to horizontal hydrodynamic focusing. The decrease in depth and width can be gradual or abrupt. The device of the present invention can function in two modes, the sheath flow mode and the particle injector mode, depending on the relative densities of the sheath fluid, the center fluid, and any particles in either fluid.

摘要翻译： 本发明提供了一种由第一板材料制成的鞘流模块，其中形成有层流流体通道; 至少两个入口，每个入口在接合处连接层流通道，第一入口接合部比第二入口接合部宽，以及来自流动通道的出口。 第二板，例如 透明的盖板，密封模块并允许进行光学测量。 第一入口允许将第一流体引入流动通道。 第一种液体是鞘液。 第二入口允许在鞘流体流过流动通道时将第二流体引入鞘液中。 第二种液体是中心流体。 因为第二入口接合点比第一入口接合点窄，所以中心流体在两侧被护套液体包围。 在所有流体已经被引入并且鞘流已经实现之后，可以减小流动通道的深度，导致垂直的流体动力学聚焦。 可选地，可以减小流动通道的宽度，导致水平的流体动力学聚焦。 深度和宽度的减小可以是渐进的或突然的。 本发明的装置可以根据鞘液，中心流体和任一液体中的任何颗粒的相对密度，以鞘流模式和颗粒注射模式两种模式起作用。

公开(公告)号：US08289520B2

公开(公告)日：2012-10-16

申请号：US12558874

申请日：2009-09-14

申请人： Johannes Kraus ,  Alois Herkommer ,  Bernhard Weigl ,  Michel Le Maire ,  Holger Muenz

发明人： Johannes Kraus ,  Alois Herkommer ,  Bernhard Weigl ,  Michel Le Maire ,  Holger Muenz

IPC分类号： G01J3/45

CPC分类号： G01J3/26 ,  G01J3/36

摘要： A spectrometer arrangement for measuring a spectrum of a light beam emitted by a narrowband light source, such as a bandwidth-narrowed laser, includes at least one etalon, a beam splitter for splitting the light beam into a first partial beam and a second partial beam, one or more optical directing elements for directing the first partial beam n times and the second partial beam (n+k) times through the at least one etalon, wherein n and k are integers ≧1. The spectrometer arrangement further has at least one light-sensitive detector and an evaluation device for evaluating the spectra—recorded by the at least one detector—of the first partial beam that has passed through the at least one etalon n times and of the second partial beam that has passed through the at least one etalon (n+k) times in order to determine the light spectrum corrected for the apparatus function of the at least one etalon.

摘要翻译： 用于测量由窄带光源（例如带宽变窄的激光器）发射的光束的光谱的光谱仪装置包括至少一个标准具，用于将光束分成第一部分光束的分束器和第二部分光束 一个或多个用于通过至少一个标准具指导第一部分光束n次和第二部分光束（n + k）的光学引导元件，其中n和k是整数≥1。 光谱仪布置还具有至少一个光敏检测器和评估装置，用于评估已经通过至少一个标准具的第一部分光束的至少一个检测器记录的光谱n次和第二部分光束 已经通过至少一个标准具（n + k）次的光束，以便确定校正了至少一个标准具的装置功能的光谱。

公开(公告)号：US20100182710A1

公开(公告)日：2010-07-22

申请号：US12626437

申请日：2009-11-25

申请人： Udo DINGER ,  Ulrich Bingel ,  Jeffrey Erxmeyer ,  Eral Erzin ,  Bernhard Weigl ,  Stephane Bruynooghe

发明人： Udo DINGER ,  Ulrich Bingel ,  Jeffrey Erxmeyer ,  Eral Erzin ,  Bernhard Weigl ,  Stephane Bruynooghe

IPC分类号： G02B7/192 ,  C25D1/06 ,  B23P17/00 ,  G02B5/08

CPC分类号： C25D1/06 ,  B82Y10/00 ,  C23C14/0005 ,  C23C28/023 ,  C23C28/322 ,  C23C28/345 ,  C23C28/42 ,  C25D7/08 ,  G02B5/0816 ,  G02B5/0891 ,  G03F7/70166 ,  G03F7/70958 ,  G21K1/062 ,  G21K2201/061 ,  G21K2201/064 ,  G21K2201/067 ,  Y10T29/49812

摘要： A method for producing an optical element or part of an optical element having a base body, including:—providing a mold body (21, 1000, 2000) which has a surface corresponding to the geometry of the optical element;—depositing a layer system (7) including at least one separation layer system (15, 1010, 2010) on the surface of the mold body (21, 1000, 2000);—electroforming a base body (4, 1030, 2030) on the layer system (7); and—detaching at least the base body from the mold body (21, 1000, 2000) at the separation layer system (15, 1010, 2010).

摘要翻译： 一种用于制造具有基体的光学元件或光学元件的一部分的方法，包括： - 提供具有对应于所述光学元件的几何形状的表面的模具体（21,1000,2000）; - 沉积层系统 （7），包括在所述模体（21,1000,2000）的表面上的至少一个分离层系统（15,1010,2010）; - 在所述层系统（7）上电铸基体（4,1030,2030） ）; 并且在分离层系统（15,1010,2010）将至少基体从模体（21,1000,2000）分离。

公开(公告)号：US07629572B2

公开(公告)日：2009-12-08

申请号：US11418872

申请日：2006-05-05

申请人： Vitaliy Shklover ,  Holger Kierey ,  Holger Muenz ,  Michel Le Maire ,  Bernhard Weigl

发明人： Vitaliy Shklover ,  Holger Kierey ,  Holger Muenz ,  Michel Le Maire ,  Bernhard Weigl

IPC分类号： G01J1/32 ,  G02B13/08

CPC分类号： G02B27/0988 ,  G02B1/115 ,  G02B5/22 ,  G02B13/08 ,  G02B27/0966 ,  G03F7/70591 ,  G03F7/70958 ,  G03F7/70975

摘要： The disclosure relates to a light beam intensity non-uniformity correction device that includes an optical element having a light entrance face with an antireflective property. According to the invention the antireflective property is locally amended in order to enhance light beam intensity uniformity. The disclosure further relates to a method for amending intensity distribution of a light beam in an optical system having one or more optical elements, where the method includes: a) assembling the optical system with the one or more optical elements arranged in predetermined positions, b) measuring intensity distribution, c) calculating locally required increase or decrease in absorption and/or reflection of one of the optical elements to amend measured intensity distribution into a predetermined intensity distribution, d) removing the optical element from the optical system, e) locally amending absorption and/or reflection of the one of the optical elements according to the calculation, f) installing the optical element in the predetermined position in the optical system.

摘要翻译： 本发明涉及一种光束强度不均匀性校正装置，其包括具有防反射性的光入射面的光学元件。 根据本发明，为了增强光束强度的均匀性，局部地修改了防反射特性。 本发明还涉及一种用于修正具有一个或多个光学元件的光学系统中的光束的强度分布的方法，其中所述方法包括：a）将光学系统与布置在预定位置的一个或多个光学元件组合，b ）测量强度分布，c）计算局部所需的光学元件之一的吸收和/或反射的增加或减少以将测量的强度分布修改为预定的强度分布，d）从光学系统中去除光学元件，e）局部地 根据计算修正光学元件之一的吸收和/或反射，f）将光学元件安装在光学系统中的预定位置。

公开(公告)号：US20090036665A1

公开(公告)日：2009-02-05

申请号：US12172086

申请日：2008-07-11

申请人： Gonzalo Domingo ,  Bernhard Weigl ,  Paul Labarre ,  Jay Gerlach

发明人： Gonzalo Domingo ,  Bernhard Weigl ,  Paul Labarre ,  Jay Gerlach

IPC分类号： C07H21/00 ,  B01L11/00

CPC分类号： C12Q1/6806 ,  B01L3/502 ,  B01L7/00 ,  B01L2200/10 ,  B01L2300/0681 ,  B01L2300/1855 ,  B01L2300/1877 ,  B01L2400/0478 ,  B01L2400/0622 ,  B01L2400/0644

摘要： A low-cost, non-instrumented, easy-to-use disposable platform for extraction, stabilization, and preservation of viral RNA in specimens at the point of collection is described. The system may use chemical heating. The platform performs the following steps: specimen lysis, RNA extraction, and RNA stabilization in a modular approach. This modular approach confers versatility to the product for application to multiple targets such as avian flu, and HIV, specimens such as blood, nasal swabs, and downstream applications such as PCR or transcription-mediated amplification. The technology described is a point-of-care specimen-processing platform generically applicable to both emerging point-of-care and central-facility molecular diagnostic tests, as well as to surveillance applications.

摘要翻译： 描述了一种低成本，非仪器化，易于使用的一次性平台，用于在收集点提取，稳定和保存样品中的病毒RNA。 该系统可以使用化学加热。 该平台执行以下步骤：模块化方法中的样品裂解，RNA提取和RNA稳定。 这种模块化方法赋予产品多种多样性，适用于多种靶点，如禽流感和HIV，标本如血液，鼻拭子和下游应用如PCR或转录介导的扩增。 所描述的技术是通常适用于新兴护理点和中心设施分子诊断测试以及监视应用的点护理样本处理平台。

公开(公告)号：US20080272275A1

公开(公告)日：2008-11-06

申请号：US11418872

申请日：2006-05-05

申请人： Vitaliy Shklover ,  Holger Kierey ,  Holger Muenz ,  Michel Le Maire ,  Bernhard Weigl

发明人： Vitaliy Shklover ,  Holger Kierey ,  Holger Muenz ,  Michel Le Maire ,  Bernhard Weigl

IPC分类号： G01J1/32

CPC分类号： G02B27/0988 ,  G02B1/115 ,  G02B5/22 ,  G02B13/08 ,  G02B27/0966 ,  G03F7/70591 ,  G03F7/70958 ,  G03F7/70975

摘要： The disclosure relates to a light beam intensity non-uniformity correction device that includes an optical element having a light entrance face with an antireflective property. According to the invention the antireflective property is locally amended in order to enhance light beam intensity uniformity. The disclosure further relates to a method for amending intensity distribution of a light beam in an optical system having one or more optical elements, where the method includes: a) assembling the optical system with the one or more optical elements arranged in predetermined positions, b) measuring intensity distribution, c) calculating locally required increase or decrease in absorption and/or reflection of one of the optical elements to amend measured intensity distribution into a predetermined intensity distribution, d) removing the optical element from the optical system, e) locally amending absorption and/or reflection of the one of the optical elements according to the calculation, f) installing the optical element in the predetermined position in the optical system.

摘要翻译： 本发明涉及一种光束强度不均匀性校正装置，其包括具有防反射性的光入射面的光学元件。 根据本发明，为了增强光束强度的均匀性，局部地修改了防反射特性。 本发明还涉及一种用于修正具有一个或多个光学元件的光学系统中的光束的强度分布的方法，其中所述方法包括：a）将光学系统与布置在预定位置的一个或多个光学元件组合，b ）测量强度分布，c）计算局部所需的光学元件之一的吸收和/或反射的增加或减少以将测量的强度分布修改为预定的强度分布，d）从光学系统中去除光学元件，e）局部地 根据计算修正光学元件之一的吸收和/或反射，f）将光学元件安装在光学系统中的预定位置。