公开(公告)号：US06806543B2

公开(公告)日：2004-10-19

申请号：US10243089

申请日：2002-09-12

申请人： Mineo Yamakawa ,  John Heck ,  Selena Chan ,  Narayan Sundararajan

发明人： Mineo Yamakawa ,  John Heck ,  Selena Chan ,  Narayan Sundararajan

IPC分类号： H01L2714

CPC分类号： B01L3/502715 ,  B01J2219/00639 ,  B01L3/50255 ,  B01L3/502753 ,  B01L2300/0636 ,  B01L2300/0681 ,  B01L2300/0887 ,  B81B2201/0214 ,  Y10T137/2224

摘要： Microfluidic apparatus including integrated porous substrate/sensors that may be used for detecting targeted biological and chemical molecules and compounds. In one aspect, upper and lower microfluidic channels are defined in respective halves of a substrate, which are sandwiched around a porous membrane upon assembly. In another aspect, the upper and lower channels are formed such that a portion of the lower channel passes beneath a portion of the upper channel to form a cross-channel area, wherein the membrane is disposed between the two channels. In various embodiments, one or more porous membranes are disposed proximate to corresponding cross-channel areas defined by one or more upper and lower channels. The porous membrane may also have sensing characteristics, such that it produces a change in an optical and/or electronic characteristic. Accordingly, the apparatus may further include instrumentation or detection equipment to measure the changes, such as optic-based detectors and electronic instrumentation.

摘要翻译： 微流体设备包括可用于检测目标生物和化学分子和化合物的综合多孔底物/传感器。 在一个方面，上和下微流体通道限定在基底的相应的两半中，其在组装时夹在多孔膜周围。 在另一方面，上通道和下通道形成为使得下通道的一部分在上通道的一部分下方通过以形成交叉通道区域，其中膜设置在两个通道之间。 在各种实施例中，一个或多个多孔膜设置在由一个或多个上部和下部通道限定的相应交叉通道区域附近。 多孔膜也可以具有感测特性，使得其产生光学和/或电子特性的变化。 因此，该装置还可以包括用于测量变化的仪器或检测设备，例如基于光学的检测器和电子仪器。

公开(公告)号：US08153079B2

公开(公告)日：2012-04-10

申请号：US10856372

申请日：2004-05-27

申请人： Mineo Yamakawa ,  John Heck ,  Selena Chan ,  Narayan Sundararajan

发明人： Mineo Yamakawa ,  John Heck ,  Selena Chan ,  Narayan Sundararajan

IPC分类号： B01L3/00

CPC分类号： B01L3/502715 ,  B01J2219/00639 ,  B01L3/50255 ,  B01L3/502753 ,  B01L2300/0636 ,  B01L2300/0681 ,  B01L2300/0887 ,  B81B2201/0214 ,  Y10T137/2224

摘要： Microfluidic apparatus including integrated porous substrate/sensors that may be used for detecting targeted biological and chemical molecules and compounds. In one aspect, upper and lower microfluidic channels are defined in respective halves of a substrate, which are sandwiched around a porous membrane upon assembly. In other aspect, the upper and lower channels are formed such that a portion of the lower channel passes beneath a portion of the upper channel to form a cross-channel area, wherein the membrane is disposed between the two channels. In various embodiments, one or more porous membranes are disposed proximate to corresponding cross-channel areas defined by one or more upper and lower channels. The porous membrane may also have sensing characteristics, such that it produces a change in an optical and/or electronic characteristic. Accordingly, the apparatus may further include instrumentation or detection equipment to measure the changes, such as optic-based detectors and electronic instrumentation.

摘要翻译： 微流体设备包括可用于检测目标生物和化学分子和化合物的综合多孔底物/传感器。 在一个方面，上和下微流体通道限定在基底的相应的两半中，其在组装时夹在多孔膜周围。 在另一方面，上通道和下通道形成为使得下通道的一部分穿过上通道的一部分以形成交叉通道区域，其中隔膜设置在两个通道之间。 在各种实施例中，一个或多个多孔膜设置在由一个或多个上部和下部通道限定的相应交叉通道区域附近。 多孔膜也可以具有感测特性，使得其产生光学和/或电子特性的变化。 因此，该装置还可以包括用于测量变化的仪器或检测设备，例如基于光学的检测器和电子仪器。

公开(公告)号：US08465698B2

公开(公告)日：2013-06-18

申请号：US13272858

申请日：2011-10-13

申请人： Mineo Yamakawa ,  John Heck ,  Selena Chan ,  Narayan Sundararajan

发明人： Mineo Yamakawa ,  John Heck ,  Selena Chan ,  Narayan Sundararajan

IPC分类号： G01N21/01 ,  B01L3/00

CPC分类号： B01L3/502715 ,  B01J2219/00639 ,  B01L3/50255 ,  B01L3/502753 ,  B01L2300/0636 ,  B01L2300/0681 ,  B01L2300/0887 ,  B81B2201/0214 ,  Y10T137/2224

摘要： Microfluidic apparatus including integrated porous substrate/sensors that may be used for detecting targeted biological and chemical molecules and compounds. In one aspect, upper and lower microfluidic channels are defined in respective halves of a substrate, which are sandwiched around a porous membrane upon assembly. In other aspect, the upper and lower channels are formed such that a portion of the lower channel passes beneath a portion of the upper channel to form a cross-channel area, wherein the membrane is disposed between the two channels. In various embodiments, one or more porous membranes are disposed proximate to corresponding cross-channel areas defined by one or more upper and lower channels. The porous membrane may also have sensing characteristics, such that it produces a change in an optical and/or electronic characteristic. Accordingly, the apparatus may further include instrumentation or detection equipment to measure the changes, such as optic-based detectors and electronic instrumentation.

摘要翻译： 微流体设备包括可用于检测目标生物和化学分子和化合物的综合多孔底物/传感器。 在一个方面，上和下微流体通道限定在基底的相应的两半中，其在组装时夹在多孔膜周围。 在另一方面，上通道和下通道形成为使得下通道的一部分穿过上通道的一部分以形成交叉通道区域，其中隔膜设置在两个通道之间。 在各种实施例中，一个或多个多孔膜设置在由一个或多个上部和下部通道限定的相应交叉通道区域附近。 多孔膜也可以具有感测特性，使得其产生光学和/或电子特性的变化。 因此，该装置还可以包括用于测量变化的仪器或检测设备，例如基于光学的检测器和电子仪器。

公开(公告)号：US07279134B2

公开(公告)日：2007-10-09

申请号：US10246049

申请日：2002-09-17

申请人： Selena Chan ,  Narayan Sundararajan ,  Andrew A. Berlin ,  Mineo Yamakawa

发明人： Selena Chan ,  Narayan Sundararajan ,  Andrew A. Berlin ,  Mineo Yamakawa

IPC分类号： B01L3/02 ,  B31D3/00

CPC分类号： B01D61/18 ,  B01D61/022 ,  B01D61/142 ,  B01D61/20 ,  B01D69/02 ,  B01D71/02 ,  B01D2325/02 ,  B01D2325/04 ,  B01L3/502753 ,  B01L2200/12 ,  B01L2300/0681 ,  B01L2300/087 ,  B01L2300/0874 ,  B01L2300/0887 ,  Y10T436/25375 ,  Y10T436/255 ,  Y10T436/2575

摘要： Microfluidic devices with porous membranes for molecular sieving, metering, and separation of analyte fluids. In one aspect, a microfluidic device includes a substrate having input and output microfluidic channel sections separated by a porous membrane formed integral to the substrate. In another aspect, the porous membrane may comprise a thin membrane that is sandwiched between upper and lower substrate members. The microfluidic device may include one or a plurality of porous membranes. In one embodiment, a plurality of porous membranes having increasingly smaller pores are disposed along portions of a microfluidic channel. In another embodiment, a cascading series of upper and lower channels are employed, wherein each upper/lower channel interface is separated by a respective porous membrane. In another aspect, a porous membrane is rotatably coupled to a substrate within a microfluidic channel via a MEMS actuator to enable the porous membrane to be positioned in filtering and pass-through positions.

摘要翻译： 具有多孔膜的微流体装置用于分析筛分，计量和分析分析液体。 在一个方面，微流体装置包括具有输入和输出微流体通道部分的基底，所述输入和输出微流体通道部分由与所述基底一体形成的多孔膜隔开。 在另一方面，多孔膜可以包括夹在上部和下部衬底构件之间的薄膜。 微流体装置可以包括一个或多个多孔膜。 在一个实施例中，具有越来越小的孔的多个多孔膜沿着微流体通道的部分设置。 在另一个实施例中，采用了上下通道的级联系列，其中每个上/下通道界面由相应的多孔膜隔开。 在另一方面，多孔膜通过MEMS致动器可旋转地联接到微流体通道内的衬底，以使得多孔膜能够位于过滤位置和穿过位置。

公开(公告)号：US20060029969A1

公开(公告)日：2006-02-09

申请号：US11235796

申请日：2005-09-26

申请人： Xing Su ,  Selena Chan ,  Andrew Berlin ,  Tae-Woong Koo ,  Narayan Sundararajan ,  Mineo Yamakawa

发明人： Xing Su ,  Selena Chan ,  Andrew Berlin ,  Tae-Woong Koo ,  Narayan Sundararajan ,  Mineo Yamakawa

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6869 ,  C12Q1/6816 ,  C12Q1/6825 ,  C12Q1/6872 ,  C12Q2565/632 ,  C12Q2563/155 ,  C12Q2521/319

摘要： The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation into a nucleic acid 13. Exonuclease 15 treatment of the labeled nucleic acid 13 results in the release of labeled nucleotides 16, 130, which are detected by Raman spectroscopy. In alternative embodiments of the invention, nucleotides 16, 130 released from a nucleic acid 13 by exonuclease 15 treatment are covalently cross-linked to silver or gold nanoparticles 140 and detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERFS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus 10, 100, 210 for nucleic acid sequencing.

摘要翻译： 本文公开的方法和装置涉及通过增强拉曼光谱进行的核酸测序。 在本发明的某些实施方案中，核苷酸在掺入核酸13之前共价连接到拉曼标记上。 标记核酸13的核酸外切酶15处理导致通过拉曼光谱法检测的标记核苷酸16,130的释放。 在本发明的替代实施方案中，通过核酸外切酶15处理从核酸13释放的核苷酸16,130与银或金纳米颗粒140共价交联并通过表面增强拉曼光谱（SERS），表面增强共振拉曼光谱（SERFS ）和/或相干的反斯托克斯拉曼光谱（CARS）。 本发明的其它实施方案涉及用于核酸测序的装置10,100,210。

公开(公告)号：US20100267013A1

公开(公告)日：2010-10-21

申请号：US11753361

申请日：2007-05-24

申请人： Xing Su ,  Andrew Arthur Berlin ,  Selena Chan ,  Steven J. Kirch ,  Tae-Woong Koo ,  Gabi Neubauer ,  Valluri Rao ,  Narayan Sundararajan ,  Mineo Yamakawa

发明人： Xing Su ,  Andrew Arthur Berlin ,  Selena Chan ,  Steven J. Kirch ,  Tae-Woong Koo ,  Gabi Neubauer ,  Valluri Rao ,  Narayan Sundararajan ,  Mineo Yamakawa

IPC分类号： C12Q1/68 ,  C12M1/34

CPC分类号： C12Q1/6869 ,  C12Q2565/632 ,  C12Q2563/155 ,  C12Q2521/319

摘要： The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation into a nucleic acid. In other embodiments, unlabeled nucleic acids are used. Exonuclease treatment of the nucleic acid results in the release of labeled or unlabeled nucleotides that are detected by Raman spectroscopy. In alternative embodiments of the invention, nucleotides released from a nucleic acid by exonuclease treatment are covalently cross-linked to nanoparticles and detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus for nucleic acid sequencing.

摘要翻译： 本文公开的方法和装置涉及通过增强拉曼光谱进行的核酸测序。 在本发明的某些实施方案中，在掺入核酸之前，核苷酸与拉曼标记物共价连接。 在其它实施方案中，使用未标记的核酸。 核酸外切核酸处理导致通过拉曼光谱法检测的标记或未标记的核苷酸的释放。 在本发明的替代实施方案中，通过外切核酸酶处理从核酸释放的核苷酸与纳米颗粒共价交联，并通过表面增强拉曼光谱（SERS），表面增强共振拉曼光谱（SERRS）和/或相干反斯托克斯拉曼 光谱学（CARS）。 本发明的其它实施方案涉及用于核酸测序的装置。

公开(公告)号：US06972173B2

公开(公告)日：2005-12-06

申请号：US10099287

申请日：2002-03-14

申请人： Xing Su ,  Selena Chan ,  Andrew A. Berlin ,  Tae-Woong Koo ,  Narayan Sundararajan ,  Mineo Yamakawa

发明人： Xing Su ,  Selena Chan ,  Andrew A. Berlin ,  Tae-Woong Koo ,  Narayan Sundararajan ,  Mineo Yamakawa

IPC分类号： G01N21/65 ,  B01L3/00 ,  C12M1/00 ,  C12Q1/68 ,  G01N33/543 ,  C07H21/02 ,  C12P19/34

CPC分类号： C12Q1/6869 ,  C12Q1/6816 ,  C12Q1/6825 ,  C12Q1/6872 ,  C12Q2565/632 ,  C12Q2563/155 ,  C12Q2521/319

摘要： The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation into a nucleic acid 13. Exonuclease 15 treatment of the labeled nucleic acid 13 results in the release of labeled nucleotides 16, 130, which are detected by Raman spectroscopy. In alternative embodiments of the invention, nucleotides 16, 130 released from a nucleic acid 13 by exonuclease 15 treatment are covalently cross-linked to silver or gold nanoparticles 140 and detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus 10, 100, 210 for nucleic acid sequencing.

摘要翻译： 本文公开的方法和装置涉及通过增强拉曼光谱进行的核酸测序。 在本发明的某些实施方案中，核苷酸在掺入核酸13之前共价连接到拉曼标记上。 标记核酸13的核酸外切酶15处理导致通过拉曼光谱法检测的标记核苷酸16,130的释放。 在本发明的替代实施方案中，通过核酸外切酶15处理从核酸13释放的核苷酸16,130共价交联到银或金纳米颗粒140上，并通过表面增强拉曼光谱（SERS），表面增强共振拉曼光谱（SERRS ）和/或相干的反斯托克斯拉曼光谱（CARS）。 本发明的其它实施方案涉及用于核酸测序的装置10,100,210。

公开(公告)号：US20070155022A1

公开(公告)日：2007-07-05

申请号：US11325833

申请日：2005-12-30

申请人： Mineo Yamakawa ,  Narayan Sundararajan ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Tae-Woong Koo ,  Lei Sun ,  Kung-Bin Sung ,  Mark Roth

发明人： Mineo Yamakawa ,  Narayan Sundararajan ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Tae-Woong Koo ,  Lei Sun ,  Kung-Bin Sung ,  Mark Roth

IPC分类号： G01N33/543 ,  C12M1/34

CPC分类号： G01N33/54373 ,  G01N21/658

摘要： Embodiments of the present invention provide methods for determining the degenerate binding capabilities of antibodies. The methods provide information about degenerate binding capabilities without the use of involved procedures. Optionally, a molecule toward which an antibody exhibits degenerate binding ability may be identified through the use of a reporter, such as, a composite organic inorganic nanocluster (COIN). COINs are sensitive SERS (surface enhanced Raman spectroscopy) reporters capable of multiplex analysis of analytes.

摘要翻译： 本发明的实施方案提供了确定抗体的简并结合能力的方法。 该方法提供了关于退化绑定功能的信息，而不使用涉及的过程。 任选地，可以通过使用报告物如复合有机无机纳米簇（COIN）来鉴定抗体显示简并结合能力的分子。 COINs是敏感的SERS（表面增强拉曼光谱）报告人能够多分析分析物。

公开(公告)号：US20060134714A1

公开(公告)日：2006-06-22

申请号：US11202862

申请日：2005-08-11

申请人： Narayan Sundararajan ,  Lei Sun ,  Xing Su ,  Mineo Yamakawa ,  Zhang Jingwu ,  Selena Chan ,  Andrew Berlin ,  Tae-Woong Koo ,  Mark Roth ,  Phil Gafken

发明人： Narayan Sundararajan ,  Lei Sun ,  Xing Su ,  Mineo Yamakawa ,  Zhang Jingwu ,  Selena Chan ,  Andrew Berlin ,  Tae-Woong Koo ,  Mark Roth ,  Phil Gafken

IPC分类号： C12Q1/48 ,  C12Q1/34

CPC分类号： G01N33/6851 ,  G01N21/658 ,  G01N33/54373 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6848 ,  Y02A90/26

摘要： Embodiments of the present invention provide devices and methods for detecting, identifying, distinguishing, and quantifying modification states of proteins and peptides using Surface Enhanced Raman (SERS) and Raman spectroscopy. Applications of embodiments of the present invention include, for example, proteome wide modification profiling and analyses with applications in disease diagnosis, prognosis and drug efficacy studies, enzymatic activity profiling and assays.

摘要翻译： 本发明的实施方案提供了使用表面增强拉曼（SERS）和拉曼光谱法检测，鉴定，区分和定量蛋白质和肽的修饰状态的装置和方法。 本发明的实施方案的应用包括例如蛋白质组广泛的修饰分析和分析，应用于疾病诊断，预后和药物疗效研究，酶活性分析和测定。

公开(公告)号：US20060009914A1

公开(公告)日：2006-01-12

申请号：US10919699

申请日：2004-08-16

申请人： Narayan Sundararajan ,  Lei Sun ,  Xing Su ,  Mineo Yamakawa ,  Zhang Jingwu ,  Selena Chan ,  Andrew Berlin ,  Tae-Woong Koo ,  Mark Roth ,  Phil Gafken

发明人： Narayan Sundararajan ,  Lei Sun ,  Xing Su ,  Mineo Yamakawa ,  Zhang Jingwu ,  Selena Chan ,  Andrew Berlin ,  Tae-Woong Koo ,  Mark Roth ,  Phil Gafken

IPC分类号： G06F19/00 ,  G01N33/48

CPC分类号： G01N33/6842 ,  G01N33/6803 ,  G01N33/6818 ,  Y02A90/26

摘要： Embodiments of the present invention provide devices and methods for detecting, identifying, distinguishing, and quantifying modifications to nucleic acids, proteins, and peptides using SERS and Raman spectroscopy. Applications of embodiments of the present invention include proteome wide modification profiling and analyses with applications in disease diagnosis, prognosis and drug efficacy studies, enzymatic activity profiling and assays.

摘要翻译： 本发明的实施方案提供用于使用SERS和拉曼光谱检测，鉴定，区分和定量对核酸，蛋白质和肽的修饰的装置和方法。 本发明实施方案的应用包括在疾病诊断，预后和药物功效研究，酶活性分析和测定中的应用的蛋白质组广泛修饰分析和分析。