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：US20080175755A1

公开(公告)日：2008-07-24

申请号：US11331631

申请日：2006-01-13

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

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

IPC分类号： G01N21/00

CPC分类号： G01N21/45 ,  B01L3/5027 ,  G01N33/54373 ,  G01N35/00069

摘要： A device for identifying analytes in a biological sample, including a substrate configured to bind the analyte and a detection system to determine the presence or absence of the analyte in the biological sample.

摘要翻译： 一种用于识别生物样品中分析物的装置，包括配置成结合分析物的底物和检测系统，以确定生物样品中分析物的存在或不存在。

公开(公告)号：US20070223006A1

公开(公告)日：2007-09-27

申请号：US11624455

申请日：2007-01-18

申请人： Guillermo Tearney ,  Brett Bouma ,  Jason Motz ,  Leilei Peng

发明人： Guillermo Tearney ,  Brett Bouma ,  Jason Motz ,  Leilei Peng

IPC分类号： G01B11/02

CPC分类号： G01N21/6408 ,  G01J3/10 ,  G01J3/2889 ,  G01J3/433 ,  G01J3/4406 ,  G01J3/453 ,  G01N21/6445 ,  G01N2021/6417 ,  G01N2021/6419

摘要： Exemplary systems and methods for obtaining information associated with at least one portion of a sample can be provided. For example, a first radiation can be received and at least one second radiation and at least one third radiation can be provided as a function of the first radiation. Respective intensities of the second and third radiations can be modulated, whereas the second and third radiations may have different modulation frequencies, and the modulated second and third radiations can be directed toward the portion. The photoluminescence radiation can be received from the portion based on the modulated second and third radiations to generate a resultant signal. The signal can be processed to obtain the information which is/are photoluminescence lifetime characteristics and/or a polarization anisotropy of the portion. According to another exemplary embodiment, the photoluminescence radiation can be received and the photoluminescence radiation may be based on wavelengths thereof.

摘要翻译： 可以提供用于获得与样品的至少一部分相关联的信息的示例性系统和方法。 例如，可以接收第一辐射，并且可以根据第一辐射提供至少一个第二辐射和至少一个第三辐射。 可以调制第二和第三辐射的相应强度，而第二和第三辐射可以具有不同的调制频率，并且调制的第二和第三辐射可以指向该部分。 可以基于调制的第二和第三辐射从该部分接收光致发光辐射以产生结果信号。 可以处理该信号以获得该部分的光致发光寿命特性和/或偏振各向异性的信息。 根据另一示例性实施例，可以接收光致发光辐射，并且光致发光辐射可以基于其波长。

公开(公告)号：US07663092B2

公开(公告)日：2010-02-16

申请号：US11345462

申请日：2006-02-01

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

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

IPC分类号： H01J40/14

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

摘要： 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.

摘要翻译： 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。

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：US20080206804A1

公开(公告)日：2008-08-28

申请号：US12016051

申请日：2008-01-17

申请人： Guillermo J. Tearney ,  Brett E. Bouma ,  Leilei Peng ,  Tayyaba Hasan ,  Sarika Verma

发明人： Guillermo J. Tearney ,  Brett E. Bouma ,  Leilei Peng ,  Tayyaba Hasan ,  Sarika Verma

IPC分类号： C12Q1/02 ,  C12M1/34 ,  G01N21/63 ,  G01N21/76

CPC分类号： G01N21/6408 ,  G01N21/6428 ,  G01N21/6445 ,  G01N21/6456 ,  G01N21/6489 ,  G01N33/582 ,  G01N2201/1296

摘要： Exemplary embodiments of arrangements and methods providing information associated with a sample are described. For example, using such exemplary arrangements and methods, it is possible to receive an unpartitioned electro-magnetic radiation from the sample. Further, first data associated with first luminescent characteristics of at least one first molecule of the sample and second data associated with second luminescent characteristics of at least one second molecule of the sample can be obtained based on the unpartitioned electro-magnetic radiation. At least two of the photo-luminescent properties of the sample may be measured simultaneously as a function of the first and second data. Further, the information regarding the molecules of the sample may be determined as a function of the photo-luminescent properties.

摘要翻译： 描述了提供与样本相关联的信息的布置和方法的示例性实施例。 例如，使用这样的示例性布置和方法，可以从样品接收未分割的电磁辐射。 此外，可以基于未分割的电磁辐射获得与样品的至少一个第一分子的第一发光特性相关联的第一数据和与样品的至少一个第二分子的第二发光特性相关的第二数据。 可以同时测量样品的至少两种光致发光性质作为第一和第二数据的函数。 此外，关于样品分子的信息可以根据光致发光性质来确定。

公开(公告)号：US20070003436A1

公开(公告)日：2007-01-04

申请号：US11345462

申请日：2006-02-01

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

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

IPC分类号： G01N21/00

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

摘要： 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.

摘要翻译： 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。

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：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。