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：US20060256676A1

公开(公告)日：2006-11-16

申请号：US11331503

申请日：2006-01-13

申请人： David Nolte ,  Fred Regnier ,  Leilei Peng

发明人： David Nolte ,  Fred Regnier ,  Leilei Peng

IPC分类号： G11B5/09 ,  G11B7/24

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：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：US20060256350A1

公开(公告)日：2006-11-16

申请号：US11345564

申请日：2006-02-01

申请人： David Nolte ,  Manoj Varma ,  Fred Regnier

发明人： David Nolte ,  Manoj Varma ,  Fred Regnier

IPC分类号： G01B11/24

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. 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上正交状态的返回信号的装置，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：US06358692B1

公开(公告)日：2002-03-19

申请号：US09267993

申请日：1999-03-12

申请人： Satish Jindal ,  Fred Regnier ,  Kevin Williams ,  Noubar Afeyan ,  Sandeep Paliwal ,  David Evans ,  Aruna Pingali

发明人： Satish Jindal ,  Fred Regnier ,  Kevin Williams ,  Noubar Afeyan ,  Sandeep Paliwal ,  David Evans ,  Aruna Pingali

IPC分类号： G01N3350

CPC分类号： G01N30/461 ,  G01N30/463 ,  G01N30/7233 ,  G01N30/88 ,  G01N2030/027 ,  G01N2030/8804 ,  G01N2030/8813 ,  G01N2030/8831

摘要： The invention provides novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics. Specifically, the claimed multi-dimensional methods involve combining a solution of heterogeneous ligands with the target of interest to screen the ligands on the basis of one or more binding characteristics. Ligands having the first binding characteristic bind to the target of interest thereby to form a target/ligand complex. The complex then optionally is separated from the unbound components using any of a variety of separation techniques, e.g., size exclusion. At least one of the complex or unbound components then is introduced to a second “dimension”. The second dimension is capable of separating components based upon a second binding characteristic. One then elutes the ligand having the desired binding characteristics.

摘要翻译： 本发明提供了筛选样品以选择目的靶标的配体并获得关于配体及其结合特征的信息的新方法。 具体地，所要求保护的多维方法包括将异构配体的溶液与感兴趣的靶结合在一个或多个结合特征的基础上筛选配体。 具有第一结合特征的配体与感兴趣的靶结合，从而形成靶/配体复合物。 然后任选地使用各种分离技术（例如尺寸排阻）中的未结合组分分离复合物。 然后将至少一个复杂的或未结合的组件引入第二个“维度”。 第二维能够基于第二结合特征分离组分。 然后，然后将具有所需结合特征的配体洗脱出来。

公开(公告)号：US5372719A

公开(公告)日：1994-12-13

申请号：US860450

申请日：1992-03-30

申请人： Noubar B. Afeyan ,  Laszlo Varady ,  Fred Regnier

发明人： Noubar B. Afeyan ,  Laszlo Varady ,  Fred Regnier

IPC分类号： B01J20/285 ,  B01D15/08 ,  B01J20/22 ,  B01J20/30 ,  B01J20/32 ,  G01N30/88 ,  G01N33/543 ,  G01N33/545

CPC分类号： G01N33/54353 ,  B01J20/321 ,  B01J20/3219 ,  B01J20/3248 ,  B01J20/3251 ,  B01J20/3285 ,  G01N33/545 ,  G01N2600/00

摘要： Disclosed are chemically-produced specific binding, "molecular imaged" sorbents which reversibly bind a preselected macromolecule by spacially matched multipoint interactions between functional groups synthesized on the surface of the sorbent and functional groups on the surface of the macromolecule. Also disclosed are methods of producing such sorbents. The sorbents typically are high surface area solids comprising surface binding regions which have charged groups, metal coordinating groups, hydrophobic moities, or various combination thereof anchored thereto and spaced in the mirror image of complementary interactive groups on a surface of the macromolecule.

摘要翻译： 公开了化学产生的特异性结合，“分子成像”吸附剂，其通过在吸附剂表面上合成的官能团和大分子表面上的官能团之间的空间匹配的多点相互作用可逆地结合预选的大分子。 还公开了生产这种吸附剂的方法。 吸附剂通常是高表面积固体，其包含表面结合区域，其具有带电荷基团，金属配位基团，疏水性单元或其锚定到其上的各种组合并且在大分子表面上的互补相互作用基团的镜像中隔开。

公开(公告)号：US06794148B2

公开(公告)日：2004-09-21

申请号：US10006630

申请日：2001-12-05

申请人： Satish Jindal ,  Fred Regnier ,  Kevin Williams ,  Noubar Afeyan ,  Sandeep Paliwal ,  David Evans ,  Aruna Pingali

发明人： Satish Jindal ,  Fred Regnier ,  Kevin Williams ,  Noubar Afeyan ,  Sandeep Paliwal ,  David Evans ,  Aruna Pingali

IPC分类号： G01N3350

CPC分类号： G01N30/463 ,  G01N30/7233 ,  G01N30/88 ,  G01N2030/027 ,  G01N2030/8813 ,  G01N2030/8831

摘要： The invention provides novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics. Specifically, the claimed multi-dimensional methods involve combining a solution of heterogeneous ligands with the target of interest to screen the ligands on the basis of one or more binding characteristics. Ligands having the first binding characteristic bind to the target of interest thereby to form a target/ligand complex. The complex then optionally is separated from the unbound components using any of a variety of separation techniques, e.g., size exclusion. At least one of the complex or unbound components then is introduced to a second “dimension”. The second dimension is capable of separating components based upon a second binding characteristic. One then elutes the ligand having the desired binding characteristics.

摘要翻译： 本发明提供了筛选样品以选择目的靶标的配体并获得关于配体及其结合特征的信息的新方法。 具体地，所要求保护的多维方法包括将异构配体的溶液与感兴趣的靶结合在一个或多个结合特征的基础上筛选配体。 具有第一结合特征的配体与感兴趣的靶结合，从而形成靶/配体复合物。 然后任选地使用各种分离技术（例如尺寸排阻）中的未结合组分分离复合物。 然后将至少一个复杂的或未结合的组件引入第二个“维度”。 第二维能够基于第二结合特征分离组分。 然后，然后将具有所需结合特征的配体洗脱出来。

公开(公告)号：US06170981B2

公开(公告)日：2001-01-09

申请号：US09306547

申请日：1999-05-06

申请人： Fred Regnier ,  Bing He

发明人： Fred Regnier ,  Bing He

IPC分类号： B01F506

CPC分类号： B01F13/0059 ,  B01F5/0645 ,  B01F13/0093 ,  B01F2215/0037 ,  B01L3/5027 ,  B01L3/502746 ,  B01L2300/0867 ,  B01L2400/0421 ,  Y10S366/03

摘要： The present invention relates to an in situ micromachined mixer for microfluidic analytical systems. In a preferred embodiment, a 100 pL mixer for liquids transported by electroosmotic flow (EOF) is described. Mixing was achieved in multiple intersecting channels with a bimodal width distribution and varying lengths. Five &mgr;m width channels ran parallel to the direction of flow whereas larger 27 &mgr;m width channels ran back and forth through the network at a 45° angle. All channels were approximately 10 &mgr;m deep. It was observed that little mixing of confluent streams occurred in the 100 &mgr;m wide mixer inlet channel where mixing would be achieved almost exclusively by diffusion. In contrast, mixing was complete after passage through the channel network in the ≈200 &mgr;m length mixer. Solvent composition was altered by varying the voltage on solvent reservoirs. The high efficiency attained in this mixer was attributed to the presence of a 2 pL vortex in the center of the mixer. Video tracking of fluorescent particles with a fluorescence microscope allowed the position and volume of this vortex to be determined.

摘要翻译： 本发明涉及用于微流体分析系统的原位微加工混合器。 在优选实施例中，描述了通过电渗流（EOF）输送的液体的100pL混合器。 在具有双峰宽度分布和变化长度的多个相交通道中实现混合。 五个mam宽度的通道平行于流动方向，而较大的27 mam宽度的通道以45°的角度来回穿过网络。 所有通道深度约为10毫米。 观察到在100m宽的混合器入口通道中几乎没有混合的混合流混合，几乎完全通过扩散实现混合。 相反，在≈200毫米长度混合器中通过通道网络后，混合完成。 通过改变溶剂储存器上的电压来改变溶剂组成。 在该混合器中获得的高效率归因于在混合器中心存在2pL涡流。 使用荧光显微镜对荧光颗粒的视频跟踪可以确定该涡流的位置和体积。

公开(公告)号：US20080050827A1

公开(公告)日：2008-02-28

申请号：US11824698

申请日：2007-07-02

申请人： Hamid Mirzaei ,  Fred Regnier ,  Wen-Chu Yang

发明人： Hamid Mirzaei ,  Fred Regnier ,  Wen-Chu Yang

IPC分类号： G01N33/68 ,  G01N33/00 ,  G01N37/00

CPC分类号： G01N33/6824 ,  G01N33/6806 ,  Y10T436/10 ,  Y10T436/13

摘要： The present invention provides compositions and methods for enhanced detection and quantification of amino acids by derivatization. Also provided are compositions and methods for enhanced detection and quantification of peptides by derivatization.

摘要翻译： 本发明提供通过衍生化增强氨基酸检测和定量的组合物和方法。 还提供了通过衍生化来增强肽的检测和定量的组合物和方法。