公开(公告)号：US08298831B2

公开(公告)日：2012-10-30

申请号：US12466943

申请日：2009-05-15

申请人： David D. Nolte ,  Manoj Varma ,  Fred E. Regnier ,  Leilei Peng ,  Ming Zhao

发明人： David D. Nolte ,  Manoj Varma ,  Fred E. Regnier ,  Leilei Peng ,  Ming Zhao

IPC分类号： G01N21/76

CPC分类号： G01N33/54373 ,  G01N21/45 ,  G01N21/553 ,  G01N21/645

摘要： 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.

摘要翻译： 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。

公开(公告)号：US07910356B2

公开(公告)日：2011-03-22

申请号：US11345477

申请日：2006-02-01

申请人： David D. Nolte ,  Manoj Varma ,  Fred E. Regnier ,  Leilei Peng

发明人： David D. Nolte ,  Manoj Varma ,  Fred E. Regnier ,  Leilei Peng

IPC分类号： C12M1/34

CPC分类号： G01N33/543 ,  C12Q1/6837

摘要： A planar array having plurality of biological recognition molecules including at least two types of biological recognition molecules distributed about a substrate is disclosed. A first type of biological recognition molecules is distributed according to a first frequency and a second type of biological recognition molecules is distributed according to a second frequency. Another planar array having a plurality of biological recognition molecules including at least two kinds of biological recognition molecules is disclosed. The recognition molecules are distributed about a substrate with first kind of biological recognition molecules distributed at a first height or depth relative to a surface of the substrate and a second kind of biological recognition molecules distributed at a second height or depth relative to the surface. An apparatus including a surface normal interferometry platform including a scanning pathway and a plurality of analyzer molecules adapted to detect the presence or absence of a plurality of target analytes is also disclosed. The plurality of analyzer molecules are distributed about the scanning pathway according to a multiplexing scheme. A method including multiplexing a plurality of kinds of capture molecules about a detection pathway is further disclosed. The method also includes contacting a biological sample to the array, detecting the presence or absence of binding of the plurality of kinds of capture molecules and a plurality of target analytes using interferometry.

摘要翻译： 公开了一种具有多个生物识别分子的平面阵列，其包括分布在基底周围的至少两种类型的生物识别分子。 第一类生物识别分子根据第一频率分布，第二类生物识别分子根据第二频率分布。 公开了具有包括至少两种生物识别分子的多个生物识别分子的另一平面阵列。 识别分子围绕基底分布，第一种生物识别分子分布在相对于基底的表面的第一高度或深度处，以及分布在相对于该表面的第二高度或深度处的第二种生物识别分子。 还公开了一种包括包括扫描路径的表面正常干涉测量平台和适于检测多个目标分析物的存在或不存在的多个分析器分子的装置。 多个分析器分子根据复用方案围绕扫描路径分布。 进一步公开了一种包括关于检测通路复用多种捕获分子的方法。 该方法还包括使生物样品与阵列接触，使用干涉测定法检测多种捕获分子和多种目标分析物的结合的存在或不存在。

公开(公告)号：US20090263913A1

公开(公告)日：2009-10-22

申请号：US12466943

申请日：2009-05-15

申请人： David D. Nolte ,  Manoj Varma ,  Fred E. Regnier ,  Leilei Peng ,  Ming Zhao

发明人： David D. Nolte ,  Manoj Varma ,  Fred E. Regnier ,  Leilei Peng ,  Ming Zhao

IPC分类号： G01N21/01

CPC分类号： G01N33/54373 ,  G01N21/45 ,  G01N21/553 ,  G01N21/645

摘要： 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.

摘要翻译： 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。

公开(公告)号：US06685885B2

公开(公告)日：2004-02-03

申请号：US10022670

申请日：2001-12-17

申请人： David D. Nolte ,  Fred E. Regnier ,  Manoj Varma

发明人： David D. Nolte ,  Fred E. Regnier ,  Manoj Varma

IPC分类号： G01N2145

CPC分类号： G01N21/45 ,  Y10T436/111666

摘要： A device for identifying analytes in a biological sample, including a substrate having a surface lying substantially in a first plane, a plurality of targets, each having a wall lying substantially in a second plane offset from the first plane, and a receptor coating applied to one of the surface and the target walls for binding analytes present in the biological sample when the biological sample is applied to the substrate. A laser beam is sequentially directed onto each of the plurality of target, the laser being positioned relative to the substrate such that when the beam is directed onto a target, a first half of the beam is reflected back to the laser from the wall of the target and a second half of the beam is reflected back to the laser from the surface of the substrate adjacent the target. The laser combines the first and second reflected halves to produce a diffraction signal that has a first value when an analyte is not bound to the receptor coating associated with a target and a second value when an analyte is bound to the receptor coating associated with the target, thereby indicating the presence of the analyte.

摘要翻译： 一种用于识别生物样品中的分析物的装置，包括具有基本上位于第一平面中的表面的基底，多个靶，每个具有基本上位于与第一平面偏移的第二平面中的壁，以及受体涂层， 当将生物样品施加到基底上时，用于结合存在于生物样品中的分析物的表面和靶壁之一。 激光束被顺序地引导到多个靶中的每一个上，激光器相对于基板定位，使得当光束被引导到目标上时，光束的前半部分从反射镜的壁反射回到激光器 目标和光束的后半部分从邻近靶的衬底的表面反射回激光器。 激光器组合第一和第二反射半部以产生衍射信号，当分析物不与靶标相关的受体涂层结合时具有第一值，当分析物结合到与靶标相关的受体涂层时，第二值 ，从而表明分析物的存在。

公开(公告)号：US20090002716A1

公开(公告)日：2009-01-01

申请号：US12181043

申请日：2008-07-28

申请人： David Nolte ,  Manoj Varma ,  Fred E. Regnier

发明人： David Nolte ,  Manoj Varma ,  Fred E. Regnier

IPC分类号： G01B9/02

CPC分类号： G01B11/2441 ,  G01N21/4788

摘要： An apparatus for assessing topology of a surface of a target. The apparatus includes an optical source for generating a probe laser beam. The apparatus also includes means for scanning the probe laser beam across at least a portion of the surface of the target. The apparatus further includes a beamsplitter for redirecting a return signal toward means for detecting the return signal in a substantially quadrature condition, the return signal resulting from reflection of the probe laser beam off the surface of the target. A quadrature interferometric method for determining the presence or absence of a target analyte in a sample. The method comprises generating a laser probe 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 also comprises scanning the first region and the second region while the substrate is maintained in a substantially fixed position. The method further comprises measuring a time dependent intensity of a reflected diffraction signal of the probe beam while scanning the probe beam across the first region and the second region.

摘要翻译： 用于评估目标表面的拓扑的装置。 该装置包括用于产生探针激光束的光源。 该装置还包括用于在探针的表面的至少一部分上扫描探针激光束的装置。 该装置还包括分束器，用于将返回信号重定向到用于检测基本正交条件下的返回信号的装置，该返回信号是由探针激光束从目标表面反射而产生的。 用于确定样品中目标分析物的存在或不存在的正交干涉法。 该方法包括产生具有波长λ和腰围的激光探针束，以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。 该方法还包括扫描第一区域和第二区域，同时基板保持在基本上固定的位置。 该方法还包括在跨越第一区域和第二区域扫描探针束时，测量探测光束的反射衍射信号的时间依赖强度。

公开(公告)号：US07405831B2

公开(公告)日：2008-07-29

申请号：US11345564

申请日：2006-02-01

申请人： David Nolte ,  Manoj Varma ,  Fred E. Regnier

发明人： David Nolte ,  Manoj Varma ,  Fred E. Regnier

IPC分类号： G01B11/02

CPC分类号： G01N21/45 ,  G01B11/2441 ,  G01N21/4788 ,  G01N21/75 ,  G01N2021/757 ,  G01N2021/7779 ,  Y10T436/111666

摘要： An apparatus for assessing topology of a surface of a target including an optical source for generating a probe laser beam. The apparatus also includes a means for scanning the probe laser beam across at least a portion of the surface of the target and a beamsplitter for redirecting a return signal toward the means for detecting the return signal in a substantially quadrature condition. A quadrature interferometric method for determining the presence or absence of a target analyte in a sample comprising a laser probe beam having a wavelength λ and a waist wo to probe at least a portion of a substrate having a reflecting surface that 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.

摘要翻译： 一种用于评估包括用于产生探针激光束的光源的目标表面的拓扑的装置。 该装置还包括用于扫描探针激光束穿过目标表面的至少一部分的装置，以及用于将返回信号转向用于检测基本正交条件下的返回信号的装置的分束器。 一种用于确定样品中目标分析物的存在或不存在的正交干涉法，其包括具有波长λ和腰围的激光探针束以探测具有反射的基底的至少一部分 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。

公开(公告)号：US20070023643A1

公开(公告)日：2007-02-01

申请号：US11345566

申请日：2006-02-01

申请人： David Nolte ,  Manoj Varma ,  Fred Regnier ,  Leilei Peng ,  Ming Zhao

发明人： David Nolte ,  Manoj Varma ,  Fred Regnier ,  Leilei Peng ,  Ming Zhao

IPC分类号： H01J49/00

CPC分类号： G01N33/54373 ,  G01N21/45 ,  G01N21/553 ,  G01N21/645

摘要： 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.

摘要翻译： 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。

公开(公告)号：US20070003925A1

公开(公告)日：2007-01-04

申请号：US11345477

申请日：2006-02-01

申请人： David Nolte ,  Manoj Varma ,  Fred Regnier ,  Leilei Peng

发明人： David Nolte ,  Manoj Varma ,  Fred Regnier ,  Leilei Peng

IPC分类号： C12Q1/70 ,  C12Q1/68 ,  G01N33/554 ,  C12M1/34 ,  G01N33/543 ,  G01N33/569

CPC分类号： G01N33/543 ,  C12Q1/6837

摘要： A planar array having plurality of biological recognition molecules including at least two types of biological recognition molecules distributed about a substrate is disclosed. A first type of biological recognition molecules is distributed according to a first frequency and a second type of biological recognition molecules is distributed according to a second frequency. Another planar array having a plurality of biological recognition molecules including at least two kinds of biological recognition molecules is disclosed. The recognition molecules are distributed about a substrate with first kind of biological recognition molecules distributed at a first height or depth relative to a surface of the substrate and a second kind of biological recognition molecules distributed at a second height or depth relative to the surface. An apparatus including a surface normal interferometry platform including a scanning pathway and a plurality of analyzer molecules adapted to detect the presence or absence of a plurality of target analytes is also disclosed. The plurality of analyzer molecules are distributed about the scanning pathway according to a multiplexing scheme. A method including multiplexing a plurality of kinds of capture molecules about a detection pathway is further disclosed. The method also includes contacting a biological sample to the array, detecting the presence or absence of binding of the plurality of kinds of capture molecules and a plurality of target analytes using interferometry.

摘要翻译： 公开了一种具有多个生物识别分子的平面阵列，其包括分布在基底周围的至少两种类型的生物识别分子。 第一类生物识别分子根据第一频率分布，第二类生物识别分子根据第二频率分布。 公开了具有包括至少两种生物识别分子的多个生物识别分子的另一平面阵列。 识别分子围绕基底分布，第一种生物识别分子分布在相对于基底的表面的第一高度或深度处，以及分布在相对于该表面的第二高度或深度处的第二种生物识别分子。 还公开了一种包括包括扫描路径的表面正常干涉测量平台和适于检测多个目标分析物的存在或不存在的多个分析器分子的装置。 多个分析器分子根据复用方案围绕扫描路径分布。 进一步公开了一种包括关于检测通路复用多种捕获分子的方法。 该方法还包括使生物样品与阵列接触，使用干涉测定法检测多种捕获分子和多种目标分析物的结合的存在或不存在。

公开(公告)号：US20080186477A1

公开(公告)日：2008-08-07

申请号：US12018108

申请日：2008-01-22

申请人： Xuefeng Wang ,  David D. Nolte ,  Manoj Varma ,  Brian Weichel ,  Timothy Norwood ,  Fouad Sayegh ,  Ming Zhao

发明人： Xuefeng Wang ,  David D. Nolte ,  Manoj Varma ,  Brian Weichel ,  Timothy Norwood ,  Fouad Sayegh ,  Ming Zhao

IPC分类号： G01N21/00

CPC分类号： G01N21/6452 ,  G01N21/253

摘要： 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.

摘要翻译： 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。

公开(公告)号：US07659968B2

公开(公告)日：2010-02-09

申请号：US12018108

申请日：2008-01-22

申请人： Xuefeng Wang ,  David D. Nolte ,  Manoj Varma ,  Brian Weichel ,  Timothy Norwood ,  Fouad Sayegh ,  Ming Zhao

发明人： Xuefeng Wang ,  David D. Nolte ,  Manoj Varma ,  Brian Weichel ,  Timothy Norwood ,  Fouad Sayegh ,  Ming Zhao

IPC分类号： G01N21/00 ,  G01N21/64

CPC分类号： G01N21/6452 ,  G01N21/253

摘要： 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.

摘要翻译： 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。