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    • 1. 发明授权
    • Differentially encoded biological analyzer planar array apparatus and methods
    • 差分编码生物分析仪平面阵列设备及方法
    • US08298831B2
    • 2012-10-30
    • US12466943
    • 2009-05-15
    • David D. NolteManoj VarmaFred E. RegnierLeilei PengMing Zhao
    • David D. NolteManoj VarmaFred E. RegnierLeilei PengMing Zhao
    • G01N21/76
    • G01N33/54373G01N21/45G01N21/553G01N21/645
    • A method of probing a plurality of analyzer molecules distributed about a detection platform is disclosed. The method includes contacting a test sample to the plurality of analyzer molecules, scanning the plurality of analyzer molecules at a rate relating to a carrier frequency signal, and detecting the presence or absence of a biological molecule based at least in part upon the presence or absence of a signal substantially at a sideband of the carrier frequency signal. A molecule detection platform including a substrate and a plurality of targets positioned about the substrate is also disclosed. Specific analyzer molecules adapted to bind a specific analyte are immobilized about a first set of the targets. Nonspecific analyzer molecules are immobilized about a second set of the targets. The targets positioned about the substrate along at least a segment of a scanning pathway alternate between at least one of the first set and at least one of the second set. A method including providing a substrate for supporting biological analyzer molecules the substrate including at least one scanning pathway is also disclosed. The scanning pathway includes a plurality of scanning targets. Specific biological analyzer molecules adapted to detect a specific target analyte are distributed about a first set of the targets which alternate in groups of at least one with a second set of the targets the second set of the targets not including the specific biological analyzer molecules.
    • 公开了一种探测分布在检测平台周围的多个分析器分子的方法。 该方法包括使测试样本与多个分析器分子接触,以与载波频率信号相关的速率扫描多个分析器分子,并且至少部分地基于存在或不存在检测生物分子的存在或不存在 基本上在载波频率信号的边带处的信号。 还公开了一种分子检测平台,其包括基板和围绕基板定位的多个靶。 适于结合特定分析物的特异性分析仪分子被固定在第一组靶上。 非特异性分析仪分子被固定在第二组靶上。 沿着扫描通道的至少一段定位在基底周围的靶在第一组和第二组中的至少一个之间交替。 还公开了一种包括提供用于支持生物分析器分子的基板的方法,所述基板包括至少一个扫描路径。 扫描路径包括多个扫描目标。 适于检测特定目标分析物的特异性生物分析仪分子围绕第一组靶标分布,其中至少一组与第二组靶标交替,第二组靶标不包括特定生物分析仪分子。
    • 2. 发明申请
    • DIFFERENTIALLY ENCODED BIOLOGICAL ANALYZER PLANAR ARRAY APPARATUS AND METHODS
    • 不同编码的生物分析仪平面阵列装置和方法
    • US20090263913A1
    • 2009-10-22
    • US12466943
    • 2009-05-15
    • David D. NolteManoj VarmaFred E. RegnierLeilei PengMing Zhao
    • David D. NolteManoj VarmaFred E. RegnierLeilei PengMing Zhao
    • G01N21/01
    • G01N33/54373G01N21/45G01N21/553G01N21/645
    • A method of probing a plurality of analyzer molecules distributed about a detection platform is disclosed. The method includes contacting a test sample to the plurality of analyzer molecules, scanning the plurality of analyzer molecules at a rate relating to a carrier frequency signal, and detecting the presence or absence of a biological molecule based at least in part upon the presence or absence of a signal substantially at a sideband of the carrier frequency signal. A molecule detection platform including a substrate and a plurality of targets positioned about the substrate is also disclosed. Specific analyzer molecules adapted to bind a specific analyte are immobilized about a first set of the targets. Nonspecific analyzer molecules are immobilized about a second set of the targets. The targets positioned about the substrate along at least a segment of a scanning pathway alternate between at least one of the first set and at least one of the second set. A method including providing a substrate for supporting biological analyzer molecules the substrate including at least one scanning pathway is also disclosed. The scanning pathway includes a plurality of scanning targets. Specific biological analyzer molecules adapted to detect a specific target analyte are distributed about a first set of the targets which alternate in groups of at least one with a second set of the targets the second set of the targets not including the specific biological analyzer molecules.
    • 公开了一种探测分布在检测平台周围的多个分析器分子的方法。 该方法包括使测试样本与多个分析器分子接触,以与载波频率信号相关的速率扫描多个分析器分子,并且至少部分地基于存在或不存在检测生物分子的存在或不存在 基本上在载波频率信号的边带处的信号。 还公开了一种分子检测平台,其包括基板和围绕基板定位的多个靶。 适于结合特定分析物的特异性分析仪分子被固定在第一组靶上。 非特异性分析仪分子被固定在第二组靶上。 沿着扫描通道的至少一段定位在基底周围的靶在第一组和第二组中的至少一个之间交替。 还公开了一种包括提供用于支持生物分析器分子的基板的方法,所述基板包括至少一个扫描路径。 扫描路径包括多个扫描目标。 适于检测特定目标分析物的特异性生物分析仪分子围绕第一组靶标分布,其中至少一组与第二组靶标交替,第二组靶标不包括特定生物分析仪分子。
    • 3. 发明授权
    • Method and apparatus for phase contrast quadrature interferometric detection of an immunoassay
    • 用于免疫测定的相位差正交干涉检测的方法和装置
    • US07663092B2
    • 2010-02-16
    • US11345462
    • 2006-02-01
    • David D. NolteLeilei PengFred E. RegnierMing Zhao
    • David D. NolteLeilei PengFred E. RegnierMing Zhao
    • H01J40/14
    • G01N21/45G01B11/2441G01N21/4788G01N21/75G01N2021/757G01N2021/7779Y10T436/111666
    • A phase contrast quadrature interferometric method and apparatus for determining the presence or absence of a target analyte in a sample. The method includes probing a substrate exposed to the sample with a laser beam. The substrate includes a reflecting surface with a first region having recognition molecules specific to the target analyte and a second region without recognition molecules. The method also includes probing the first and second region, and measuring time dependent intensity on a photodetector at one or both of a pair of quadrature angles of a reflected diffraction signal. The apparatus includes a laser source, a platform for receiving the planar array, an objective lens offset from the platform by approximately a focal length, and a split photodetector means for measuring a first quadrature and a second quadrature in a signal resulting from reflection of the laser beam.
    • 用于确定样品中目标分析物的存在或不存在的相差正交干涉测量方法和装置。 该方法包括用激光束探测暴露于样品的衬底。 衬底包括具有第一区域的反射表面,该第一区域具有对靶分析物特异性的识别分子和不具有识别分子的第二区域。 该方法还包括探测第一和第二区域,并且在反射的衍射信号的一对正交角中的一个或两个上测量光电检测器上的时间依赖强度。 该装置包括激光源,用于接收平面阵列的平台,从平台偏移大约焦距的物镜,以及分离光电检测器装置,用于测量由反射产生的信号中的第一正交和第二正交 激光束。
    • 4. 发明申请
    • Differentially encoded biological analyzer planar array apparatus and methods
    • 差分编码生物分析仪平面阵列设备及方法
    • US20070023643A1
    • 2007-02-01
    • US11345566
    • 2006-02-01
    • David NolteManoj VarmaFred RegnierLeilei PengMing Zhao
    • David NolteManoj VarmaFred RegnierLeilei PengMing Zhao
    • H01J49/00
    • G01N33/54373G01N21/45G01N21/553G01N21/645
    • A method of probing a plurality of analyzer molecules distributed about a detection platform is disclosed. The method includes contacting a test sample to the plurality of analyzer molecules, scanning the plurality of analyzer molecules at a rate relating to a carrier frequency signal, and detecting the presence or absence of a biological molecule based at least in part upon the presence or absence of a signal substantially at a sideband of the carrier frequency signal. A molecule detection platform including a substrate and a plurality of targets positioned about the substrate is also disclosed. Specific analyzer molecules adapted to bind a specific analyte are immobilized about a first set of the targets. Nonspecific analyzer molecules are immobilized about a second set of the targets. The targets positioned about the substrate along at least a segment of a scanning pathway alternate between at least one of the first set and at least one of the second set. A method including providing a substrate for supporting biological analyzer molecules the substrate including at least one scanning pathway is also disclosed. The scanning pathway includes a plurality of scanning targets. Specific biological analyzer molecules adapted to detect a specific target analyte are distributed about a first set of the targets which alternate in groups of at least one with a second set of the targets the second set of the targets not including the specific biological analyzer molecules.
    • 公开了一种探测分布在检测平台周围的多个分析器分子的方法。 该方法包括使测试样本与多个分析器分子接触,以与载波频率信号相关的速率扫描多个分析器分子,并且至少部分地基于存在或不存在检测生物分子的存在或不存在 基本上在载波频率信号的边带处的信号。 还公开了一种分子检测平台,其包括基板和围绕基板定位的多个靶。 适于结合特定分析物的特异性分析仪分子被固定在第一组靶上。 非特异性分析仪分子被固定在第二组靶上。 沿着扫描通道的至少一段定位在基底周围的靶在第一组和第二组中的至少一个之间交替。 还公开了一种包括提供用于支持生物分析器分子的基板的方法,所述基板包括至少一个扫描路径。 扫描路径包括多个扫描目标。 适于检测特定目标分析物的特异性生物分析仪分子围绕第一组靶标分布,其中至少一组与第二组靶标交替,第二组靶标不包括特定生物分析仪分子。
    • 5. 发明申请
    • SYSTEM WITH EXTENDED RANGE OF MOLECULAR SENSING THROUGH INTEGRATED MULTI-MODAL DATA ACQUISITION
    • 通过一体化多模式数据采集扩展分子量感测系统
    • US20080186477A1
    • 2008-08-07
    • US12018108
    • 2008-01-22
    • Xuefeng WangDavid D. NolteManoj VarmaBrian WeichelTimothy NorwoodFouad SayeghMing Zhao
    • Xuefeng WangDavid D. NolteManoj VarmaBrian WeichelTimothy NorwoodFouad SayeghMing Zhao
    • G01N21/00
    • G01N21/6452G01N21/253
    • A multi-modal data acquisition system for detecting target material on a biological reaction surface, the system comprising a radiation source for generating an incoming beam that impinges on the biological reaction surface at an oblique incidence angle and produces a reflected beam, an interferometric detector for detecting an interferometric signal from the illuminated surface, the reflected beam being directed to the interferometric detector, a fluorescence detector for detecting a fluorescence signal from the illuminated surface; the fluorescence detector being positioned to substantially minimize the incidence of the reflected beam; and a processing system for receiving the interferometric and fluorescence signals and determining the presence or absence of target material on the biological reaction surface. A reaction surface conditioned for the simultaneous collection of fluorescence, interferometric and other signals. A multi-modal data acquisition system for collecting and processing additional modes, including multiple interferometric, fluorescence and scattering channels.
    • 一种多模式数据采集系统,用于检测生物反应表面上的目标材料,所述系统包括用于产生入射光束的辐射源,该入射光束以倾斜入射角度撞击在生物反应表面上并产生反射光束,干涉检测器 检测来自所述照射表面的干涉信号,所述反射光束被引导到所述干涉检测器;荧光检测器,用于检测来自被照射表面的荧光信号; 荧光检测器被定位成基本上最小化反射光束的入射; 以及用于接收干涉测量和荧光信号并确定生物反应表面上目标材料的存在或不存在的处理系统。 用于同时收集荧光,干涉仪和其他信号的反应表面。 一种多模式数据采集系统,用于收集和处理其他模式,包括多个干涉仪,荧光和散射通道。
    • 6. 发明授权
    • System with extended range of molecular sensing through integrated multi-modal data acquisition
    • 通过综合多模态数据采集扩展分子感测范围的系统
    • US07659968B2
    • 2010-02-09
    • US12018108
    • 2008-01-22
    • Xuefeng WangDavid D. NolteManoj VarmaBrian WeichelTimothy NorwoodFouad SayeghMing Zhao
    • Xuefeng WangDavid D. NolteManoj VarmaBrian WeichelTimothy NorwoodFouad SayeghMing Zhao
    • G01N21/00G01N21/64
    • G01N21/6452G01N21/253
    • A multi-modal data acquisition system for detecting target material on a biological reaction surface, the system comprising a radiation source for generating an incoming beam that impinges on the biological reaction surface at an oblique incidence angle and produces a reflected beam, an interferometric detector for detecting an interferometric signal from the illuminated surface, the reflected beam being directed to the interferometric detector, a fluorescence detector for detecting a fluorescence signal from the illuminated surface; the fluorescence detector being positioned to substantially minimize the incidence of the reflected beam; and a processing system for receiving the interferometric and fluorescence signals and determining the presence or absence of target material on the biological reaction surface. A reaction surface conditioned for the simultaneous collection of fluorescence, interferometric and other signals. A multi-modal data acquisition system for collecting and processing additional modes, including multiple interferometric, fluorescence and scattering channels.
    • 一种多模式数据采集系统,用于检测生物反应表面上的目标材料,所述系统包括用于产生入射光束的辐射源,该入射光束以倾斜入射角度撞击在生物反应表面上并产生反射光束,干涉检测器 检测来自所述照射表面的干涉信号,所述反射光束被引导到所述干涉检测器;荧光检测器,用于检测来自被照射表面的荧光信号; 荧光检测器被定位成基本上最小化反射光束的入射; 以及用于接收干涉测量和荧光信号并确定生物反应表面上目标材料的存在或不存在的处理系统。 用于同时收集荧光,干涉仪和其他信号的反应表面。 一种多模式数据采集系统,用于收集和处理其他模式,包括多个干涉仪,荧光和散射通道。
    • 7. 发明授权
    • System with extended range of molecular sensing through integrated multi-modal data acquisition
    • 通过综合多模态数据采集扩展分子感测范围的系统
    • US08072585B2
    • 2011-12-06
    • US12650692
    • 2009-12-31
    • Xuefeng WangDavid D. NolteManoj VarmaBrian WeichelTimothy NorwoodFouad SayeghMing Zhao
    • Xuefeng WangDavid D. NolteManoj VarmaBrian WeichelTimothy NorwoodFouad SayeghMing Zhao
    • G01N21/00G01N21/64
    • G01N21/6452G01N21/253
    • A multi-modal data acquisition system for detecting target material on a biological reaction surface, the system comprising a radiation source for generating an incoming beam that impinges on the biological reaction surface at an oblique incidence angle and produces a reflected beam, an interferometric detector for detecting an interferometric signal from the illuminated surface, the reflected beam being directed to the interferometric detector, a fluorescence detector for detecting a fluorescence signal from the illuminated surface; the fluorescence detector being positioned to substantially minimize the incidence of the reflected beam; and a processing system for receiving the interferometric and fluorescence signals and determining the presence or absence of target material on the biological reaction surface. A reaction surface conditioned for the simultaneous collection of fluorescence, interferometric and other signals. A multi-modal data acquisition system for collecting and processing additional modes, including multiple interferometric, fluorescence and scattering channels.
    • 一种多模式数据采集系统,用于检测生物反应表面上的目标材料,所述系统包括用于产生入射光束的辐射源,该入射光束以倾斜入射角度撞击在生物反应表面上并产生反射光束,干涉检测器 检测来自所述照射表面的干涉信号,所述反射光束被引导到所述干涉检测器;荧光检测器,用于检测来自被照射表面的荧光信号; 荧光检测器被定位成基本上最小化反射光束的入射; 以及用于接收干涉测量和荧光信号并确定生物反应表面上目标材料的存在或不存在的处理系统。 用于同时收集荧光,干涉仪和其他信号的反应表面。 一种多模式数据采集系统,用于收集和处理其他模式,包括多个干涉仪,荧光和散射通道。
    • 8. 发明申请
    • SYSTEM WITH EXTENDED RANGE OF MOLECULAR SENSING THROUGH INTEGRATED MULTI-MODAL DATA ACQUISITION
    • 通过一体化多模式数据采集扩展分子量感测系统
    • US20100145627A1
    • 2010-06-10
    • US12650692
    • 2009-12-31
    • Xuefeng WangDavid D. NolteManoj VarmaBrian WeichelTimothy NorwoodFouad SayeghMing Zhao
    • Xuefeng WangDavid D. NolteManoj VarmaBrian WeichelTimothy NorwoodFouad SayeghMing Zhao
    • G01N33/48G01N21/00G06F19/00
    • G01N21/6452G01N21/253
    • A multi-modal data acquisition system for detecting target material on a biological reaction surface, the system comprising a radiation source for generating an incoming beam that impinges on the biological reaction surface at an oblique incidence angle and produces a reflected beam, an interferometric detector for detecting an interferometric signal from the illuminated surface, the reflected beam being directed to the interferometric detector, a fluorescence detector for detecting a fluorescence signal from the illuminated surface; the fluorescence detector being positioned to substantially minimize the incidence of the reflected beam; and a processing system for receiving the interferometric and fluorescence signals and determining the presence or absence of target material on the biological reaction surface. A reaction surface conditioned for the simultaneous collection of fluorescence, interferometric and other signals. A multi-modal data acquisition system for collecting and processing additional modes, including multiple interferometric, fluorescence and scattering channels.
    • 一种多模式数据采集系统,用于检测生物反应表面上的目标材料,所述系统包括用于产生入射光束的辐射源,该入射光束以倾斜入射角度撞击在生物反应表面上并产生反射光束,干涉检测器 检测来自所述照射表面的干涉信号,所述反射光束被引导到所述干涉检测器;荧光检测器,用于检测来自被照射表面的荧光信号; 荧光检测器被定位成基本上最小化反射光束的入射; 以及用于接收干涉测量和荧光信号并确定生物反应表面上目标材料的存在或不存在的处理系统。 用于同时收集荧光,干涉仪和其他信号的反应表面。 一种多模式数据采集系统,用于收集和处理其他模式,包括多个干涉仪,荧光和散射通道。
    • 9. 发明申请
    • Method and apparatus for phase contrast quadrature interferometric detection of an immunoassay
    • 用于免疫测定的相位差正交干涉检测的方法和装置
    • US20070003436A1
    • 2007-01-04
    • US11345462
    • 2006-02-01
    • David NolteLeilei PengFred RegnierMing Zhao
    • David NolteLeilei PengFred RegnierMing Zhao
    • G01N21/00
    • G01N21/45G01B11/2441G01N21/4788G01N21/75G01N2021/757G01N2021/7779Y10T436/111666
    • A phase contrast quadrature interferometric method for determining the presence or absence of a target analyte in a sample. The method comprises using a laser beam having a wavelength λ and a waist wo to probe at least a portion of a substrate having a reflecting surface that has been exposed to the sample. The reflecting surface includes at least a first region having a layer of recognition molecules specific to the target analyte and a second region that does not include a layer of recognition molecules specific to the target analyte. The method further comprises measuring a time dependent intensity on a photodetector of a substantially only first quadrature at one of a pair of quadrature angles ⊖q of a reflected diffraction signal of the probe beam while probing the first region and the second region. An apparatus for phase-contrast quadrature interferometric detection of the presence or absence of a target molecule on a planar array, comprises a laser source for generating a probe beam. The apparatus includes a platform for receiving the planar array and a first optical train for directing the probe beam at the platform in a substantially surface normal manner. The apparatus also includes an objective lens having a first side and a second side and having a focal length, the objective lens being offset on the first side of the lens from the platform by a first distance approximately equal to the focal length. The apparatus further includes split photodetector means for measuring a first quadrature and a second quadrature in a signal resulting from reflection of the probe laser beam.
    • 用于确定样品中目标分析物的存在或不存在的相差正交干涉法。 该方法包括使用具有波长λ和腰围的激光束来探测具有暴露于样品的反射表面的基底的至少一部分。 反射表面至少包括具有对靶分析物特异性的识别分子层的第一区域和不包括对靶分析物特异性的识别分子层的第二区域。 该方法还包括:在探测第一区域时,在探测光束的反射衍射信号的一对正交角度θ1中的一个处测量基本上仅第一正交的光电检测器上的时间依赖强度,以及 第二个地区。 用于在平面阵列上存在或不存在靶分子的相位对比正交干涉测量的装置包括用于产生探针光束的激光源。 该装置包括用于接收平面阵列的平台和用于以基本上正常的方式将探测光束引导到平台处的第一光学列。 该装置还包括具有第一侧和第二侧并具有焦距的物镜,该物镜在透镜的第一侧与平台偏移大约等于焦距的第一距离。 该装置还包括用于测量由探头激光束的反射产生的信号中的第一正交和第二正交的分离光电检测器装置。
    • 10. 发明申请
    • IN-LINE QUADRATURE AND ANTI-REFLECTION ENHANCED PHASE QUADRATURE INTERFEROMETRIC DETECTION
    • 在线渐近和抗反射增强相位差分干涉检测
    • US20070212257A1
    • 2007-09-13
    • US11675359
    • 2007-02-15
    • David NolteManoj VarmaMing Zhao
    • David NolteManoj VarmaMing Zhao
    • G01N21/00
    • G01N21/45G01N21/253G01N21/47G01N21/75G01N21/77G01N33/54373G01N2021/4707G01N2021/7773G01N2021/7779
    • Method and apparatus for use with a probe beam and detector for detecting the presence of a target analyte in a sample. The apparatus includes a substrate; and a biolayer located on the substrate designed to react to target analyte when the sample is deposited on the biolayer. The substrate can be selected to substantially minimize reflectance by the substrate while substantially maintaining scattering by the target analyte. The substrate can be designed so waves reflected by the substrate are substantially in quadrature with waves scattered by target analyte; or so waves reflected by the substrate and scattered by target analyte interfere in the far field and directly create intensity modulation detectable by the detector. The biolayer can include a plurality of spots, and the spots can be grouped into unit cells having specific antibodies and non-specific antibodies for reacting with target analyte.
    • 用于探测束和检测器的用于检测样品中目标分析物的存在的方法和装置。 该装置包括基板; 以及位于衬底上的生物层,设计成当样品沉积在生物层上时与靶分析物反应。 可以选择衬底以基本上最小化衬底的反射率,同时基本上保持靶分析物的散射。 可以设计衬底,使得由衬底反射的波基本上与被靶分析物散射的波正交; 由基板反射并被目标分析物散射的波浪会在远场干扰,并直接产生由检测器可检测的强度调制。 生物层可以包括多个斑点,并且斑点可以分组成具有特异性抗体的单位细胞和用于与靶分析物反应的非特异性抗体。