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：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：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：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：US07787126B2

公开(公告)日：2010-08-31

申请号：US12079352

申请日：2008-03-26

申请人： David D. Nolte ,  Xuefeng Wang

发明人： David D. Nolte ,  Xuefeng Wang

IPC分类号： G01B9/02

CPC分类号： G01N21/45 ,  G01N2021/7776 ,  G01N2021/7779

摘要： A detection system for detecting target material is provided. The system comprises a photonic structure having a reflectance-band and associated side bands; an illumination source for illuminating at a wavelength in at least one of an edge of the reflectance-band and the side bands of the photonic structure and for generating a return beam; a detector system having an intensity-sensitive channel configured to detect an in-line signal from the return beam and a phase-sensitive channel configured to detect a differential phase contrast signal from the return beam; and a processing system for receiving and adding in quadrature the in-line signal and the differential phase contrast signal to generate a joint signal, and for determining one of the presence or the absence of the target material on the photonic structure using the joint signal.

摘要翻译： 提供了一种用于检测目标材料的检测系统。 该系统包括具有反射带和相关联的边带的光子结构; 用于在所述反射带的边缘和所述光子结构的所述边带中的至少一个中的波长处照射并用于产生返回光束的照明源; 具有强度敏感通道的检测器系统，其被配置为检测来自所述返回光束的直线信号;以及相敏通道，被配置为检测来自所述返回光束的差分相位差信号; 以及处理系统，用于接收并相加所述在线信号和所述差分相位对比信号以产生联合信号，并且使用所述联合信号来确定所述光子结构上的所述目标材料的存在或不存在。

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：US5900935A

公开(公告)日：1999-05-04

申请号：US995655

申请日：1997-12-22

申请人： Marvin B. Klein ,  G. David Bacher ,  David D. Nolte ,  Indrajit Lahiri

发明人： Marvin B. Klein ,  G. David Bacher ,  David D. Nolte ,  Indrajit Lahiri

IPC分类号： G01H9/00 ,  G01B9/021

CPC分类号： G01H9/00

摘要： Faults, dimensions and other characteristics of a material or structure are sensed by a coherent beam's reflection from the material during ultrasonic or very fast vibration. The reflected beam acquires a phase substantially different from its original phase and from the phase of a reference beam split from the common source beam. The reflected beam and the reference beam are superimposed by diffraction in a multiple quantum well adaptive holographic beamsplitter, and the superimposed beams are detected by a photodetector capable of detecting small interference changes from ultrasonic surface displacements or perturbations. An apparatus and method defining an improved homodyne interferometer for performing the method is described.

摘要翻译： 材料或结构的故障，尺寸和其他特性在超声波或非常快速的振动期间通过相干光束从材料的反射来感测。 反射光束获得与其原始相位大致不同的相位，并且从与公共源光束分离的参考光束的相位获得相位。 反射光束和参考光束通过衍射叠加在多量​​子阱自适应全息分光器中，并且叠加的光束由能够从超声表面位移或扰动中检测小的干涉变化的光电检测器检测。 描述了一种定义用于执行该方法的改进的零差干涉仪的装置和方法。

公开(公告)号：US20130088568A1

公开(公告)日：2013-04-11

申请号：US13704438

申请日：2011-06-17

申请人： David D. Nolte

发明人： David D. Nolte

IPC分类号： G01N21/27

CPC分类号： G06F19/10 ,  A61B5/0075 ,  A61B5/4845 ,  G01N21/27 ,  G03H1/0443 ,  G03H1/0866 ,  G03H1/32 ,  G03H2001/0445 ,  G03H2001/0447 ,  G03H2001/045 ,  G03H2001/0467 ,  G03H2222/24

摘要： Motility contrast imaging (MCI) is a depth-resolved holographic technique to extract cellular and subcellular motion inside tissue. The holographic basis of the measurement technique makes it highly susceptible to mechanical motion. The motility contrast application, in particular, preferably includes increased mechanical stability because the signal is based on time-varying changes caused by cellular motion, which should not be confused with mechanical motion of the system. Apparatus for motility contrast imaging that provides increased mechanical stability is disclosed. It is based on common-path configurations, in which the signal and reference beams share optical elements in their paths to the detector. The two beams share mechanical motions in common, and hence these motions do not contribute to the signal.

摘要翻译： 运动对比成像（MCI）是一种深度分辨全息技术，用于提取组织内的细胞和亚细胞运动。 测量技术的全息基础使其非常易受机械运动的影响。 运动对比应用尤其优选包括增加的机械稳定性，因为信号是基于由细胞运动引起的随时间变化的变化，其不应该与系统的机械运动相混淆。 公开了提供增加的机械稳定性的运动对比成像装置。 它基于共通路径配置，其中信号和参考光束在其到达检测器的路径中共享光学元件。 两束共享共享机械运动，因此这些运动对信号无贡献。