公开(公告)号：US20050250159A1

公开(公告)日：2005-11-10

申请号：US11083418

申请日：2005-03-17

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

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

IPC分类号： G01N21/65 ,  G01N33/58 ,  G01N33/68 ,  G01N33/53 ,  G01N33/00

CPC分类号： G01N21/658 ,  G01N33/6803 ,  G01N2021/653 ,  G01N2021/655 ,  G01N2021/656

摘要： The invention provides methods for analyzing the protein content of a biological sample, for example to obtain a protein profile of a sample provided by a particular individual. The proteins and protein fragments in the sample are separated on the basis of chemical and/or physical properties and maintained in a separated state at discrete locations on a solid substrate or within a stream of flowing liquid. Raman spectra are then detected as produced by the separated proteins or fragments at the discrete locations such that a spectrum from a discrete location provides information about the structure or identity of one or more particular proteins or fragments at the discrete location. The proteins or fragments at discrete locations can be coated with a metal, such as gold or silver, and/or the separated proteins can be contacted with a chemical enhancer to provide SERS spectra. Method and kits for practicing the invention are also provided.

摘要翻译： 本发明提供了用于分析生物样品的蛋白质含量的方法，例如获得由特定个体提供的样品的蛋白质谱。 样品中的蛋白质和蛋白质片段基于化学和/或物理性质分离，并在固体基质上或流动液体流中的离散位置保持分离状态。 然后检测拉曼光谱，由离散位置处的分离的蛋白质或片段产生，使得离散位置的光谱提供关于在离散位置处的一种或多种特定蛋白质或片段的结构或身份的信息。 离散位置处的蛋白质或片段可以用金属（例如金或银）涂覆，和/或分离的蛋白质可与化学增强剂接触以提供SERS光谱。 还提供了用于实施本发明的方法和试剂盒。

公开(公告)号：US20050202468A1

公开(公告)日：2005-09-15

申请号：US11020776

申请日：2004-12-23

申请人： Tae-Woong Koo ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Narayanan Sundararajan ,  Lei Sun

发明人： Tae-Woong Koo ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Narayanan Sundararajan ,  Lei Sun

IPC分类号： C12Q1/68 ,  G01N21/65

CPC分类号： G01N21/658 ,  C12Q1/6869 ,  C12Q2565/632 ,  C12Q2533/101

摘要： The methods and apparatus disclosed herein are useful for detecting nucleotides, nucleosides, and bases and for nucleic acid sequence determination. The methods involve detection of a nucleotide, nucleoside, or base using surface enhanced Raman spectroscopy (SERS) or surface enhanced coherent anti-Stokes Raman spectroscopy (SECARS). The detection can be part of a nucleic acid sequencing reaction to detect uptake of a deoxynucleotide triphosphate during a nucleic acid polymerization reaction, such as a nucleic acid sequencing reaction. The nucleic acid sequence of a synthesized nascent strand, and the complementary sequence of the template strand, can be determined by tracking the order of incorporation of nucleotides during the polymerization reaction. Methods for enhancing the SERS signal of a nucleotide or nucleoside by cleaving the base from a sugar moiety are provided. Furthermore, methods for detecting single base repeats are provided.

摘要翻译： 本文公开的方法和装置可用于检测核苷酸，核苷和碱基并用于核酸序列测定。 该方法涉及使用表面增强拉曼光谱（SERS）或表面增强相干抗斯托克斯拉曼光谱（SECARS）检测核苷酸，核苷或碱基。 检测可以是在核酸聚合反应（例如核酸测序反应）期间检测脱氧核苷酸三磷酸的摄取的核酸测序反应的一部分。 合成的新生链的核酸序列和模板链的互补序列可以通过跟踪在聚合反应期间核苷酸掺入的顺序来确定。 提供了通过从糖部分切割碱来增强核苷酸或核苷的SERS信号的方法。 此外，提供了用于检测单碱基重复的方法。

公开(公告)号：US20050147979A1

公开(公告)日：2005-07-07

申请号：US10749527

申请日：2003-12-30

申请人： Tae-Woong Koo ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Narayanan Sundararajan ,  Lei Sun

发明人： Tae-Woong Koo ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Narayanan Sundararajan ,  Lei Sun

IPC分类号： C12Q1/68 ,  G01N21/65 ,  C12P19/34

CPC分类号： G01N21/658 ,  C12Q1/6869 ,  C12Q2565/632 ,  C12Q2533/101

摘要： The methods and apparatus disclosed herein are useful for detecting nucleotides, nucleosides, and bases and for nucleic acid sequence determination. The methods involve detection of a nucleotide, nucleoside, or base using surface enhanced Raman spectroscopy (SERS) or surface enhanced coherent anti-Stokes Raman spectroscopy (SECARS). The detection can be part of a nucleic acid sequencing reaction to detect uptake of a deoxynucleotide triphosphate during a nucleic acid polymerization reaction, such as a nucleic acid sequencing reaction. The nucleic acid sequence of a synthesized nascent strand, and the complementary sequence of the template strand, can be determined by tracking the order of incorporation of nucleotides during the polymerization reaction. Methods for enhancing the SERS signal of a nucleotide or nucleoside by cleaving the base from a sugar moiety are provided. Furthermore, methods for detecting single base repeats are provided.

公开(公告)号：US20050221333A1

公开(公告)日：2005-10-06

申请号：US10815264

申请日：2004-03-31

申请人： Narayanan Sundararajan ,  Lei Sun ,  Yuegang Zhang ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Andrew Berlin

发明人： Narayanan Sundararajan ,  Lei Sun ,  Yuegang Zhang ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Andrew Berlin

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6827 ,  C12Q1/6869 ,  G01N21/658 ,  Y10T436/11 ,  Y10T436/117497 ,  Y10T436/143333 ,  C12Q2565/629 ,  C12Q2521/319 ,  C12Q2565/632 ,  C12Q2565/619

摘要： Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

摘要翻译： 本文公开了用于在微流体通道中进行核酸测序反应和分子结合反应的方法，装置和系统。 方法，装置和系统可以包括限制核酸附着的颗粒运动的限制障碍。 此外，方法，装置和系统可以包括输送流的流体动力聚焦。 此外，方法，装置和系统可以通过在表面和输送流之间提供保护流来减少与微流体通道的表面的非特异性相互作用。

公开(公告)号：US20050148098A1

公开(公告)日：2005-07-07

申请号：US10749528

申请日：2003-12-30

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

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

IPC分类号： G01N21/65 ,  G01N33/58 ,  G01N33/68 ,  G06F19/00 ,  G01N33/48 ,  G01N33/50 ,  G01N33/543 ,  G01N33/553

CPC分类号： G01N21/658 ,  G01N33/6803 ,  G01N2021/653 ,  G01N2021/655 ,  G01N2021/656

摘要： The invention provides methods for analyzing the protein content of a biological sample, for example to obtain a protein profile of a sample provided by a particular individual. The proteins and protein fragments in the sample are separated on the basis of chemical and/or physical properties and maintained in a separated state at discrete locations on a solid substrate or within a stream of flowing liquid. Raman spectra are then detected as produced by the separated proteins or fragments at the discrete locations such that a spectrum from a discrete location provides information about the structure or identity of one or more particular proteins or fragments at the discrete location. The proteins or fragments at discrete locations can be coated with a metal, such as gold or silver, and/or the separated proteins can be contacted with a chemical enhancer to provide SERS spectra. Method and kits for practicing the invention are also provided.

摘要翻译： 本发明提供了用于分析生物样品的蛋白质含量的方法，例如获得由特定个体提供的样品的蛋白质谱。 样品中的蛋白质和蛋白质片段基于化学和/或物理性质分离，并在固体基质上或流动液体流中的离散位置保持分离状态。 然后检测拉曼光谱，由离散位置处的分离的蛋白质或片段产生，使得离散位置的光谱提供关于在离散位置处的一种或多种特定蛋白质或片段的结构或身份的信息。 离散位置处的蛋白质或片段可以用金属（例如金或银）涂覆，和/或分离的蛋白质可与化学增强剂接触以提供SERS光谱。 还提供了用于实施本发明的方法和试剂盒。

公开(公告)号：US20050026163A1

公开(公告)日：2005-02-03

申请号：US10705389

申请日：2003-11-10

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

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

IPC分类号： G01N33/483 ,  C12M1/00 ,  C12M1/34 ,  C12N15/09 ,  C12Q1/68 ,  G01N27/06 ,  G01N33/53 ,  C12P19/34

CPC分类号： C12Q1/6825 ,  B82Y5/00 ,  B82Y15/00 ,  B82Y30/00 ,  C12Q1/6869 ,  C12Q2563/155 ,  C12Q2565/607

摘要： The present methods and apparatus concern nucleic acid sequencing by incorporation of nucleotides into nucleic acid strands. The incorporation of nucleotides is detected by changes in the mass and/or surface stress of the structure. In some embodiments of the invention, the structure comprises one or more nanoscale or microscale cantilevers. In certain embodiments of the invention, each different type of nucleotide is distinguishably labeled with a bulky group and each incorporated nucleotide is identified by the changes in mass and/or surface stress of the structure upon incorporation of the nucleotide. In alternative embodiments of the invention only one type of nucleotide is exposed at a time to the nucleic acids. Changes in the properties of the structure may be detected by a variety of methods, such as piezoelectric detection, shifts in resonant frequency of the structure, and/or position sensitive photodetection.

摘要翻译： 本发明的方法和装置涉及通过将核苷酸掺入核酸链而进行的核酸测序。 通过结构的质量和/或表面应力的变化来检测核苷酸的掺入。 在本发明的一些实施例中，该结构包括一个或多个纳米级或微尺寸悬臂。 在本发明的某些实施方案中，每种不同类型的核苷酸可以用大体积区分地标记，并且每个掺入的核苷酸通过结合核苷酸时结构的质量和/或表面应力的变化来鉴定。 在本发明的替代实施方案中，一次仅将一种类型的核苷酸暴露于核酸。 可以通过各种方法来检测结构的性质的变化，例如压电检测，结构的谐振频率偏移和/或位置敏感的光电检测。

公开(公告)号：US20080032297A1

公开(公告)日：2008-02-07

申请号：US11704231

申请日：2007-02-09

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

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

IPC分类号： C12Q1/68

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：US20070059733A1

公开(公告)日：2007-03-15

申请号：US11445884

申请日：2006-06-02

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

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

IPC分类号： C12Q1/68 ,  G06F19/00 ,  C12M3/00

CPC分类号： C12Q1/6825 ,  B82Y5/00 ,  B82Y15/00 ,  B82Y30/00 ,  C12Q1/6869 ,  C12Q2563/155 ,  C12Q2565/607

摘要： The present methods and apparatus concern nucleic acid sequencing by incorporation of nucleotides into nucleic acid strands. The incorporation of nucleotides is detected by changes in the mass and/or surface stress of the structure. In some embodiments of the invention, the structure comprises one or more nanoscale or microscale cantilevers. In certain embodiments of the invention, each different type of nucleotide is distinguishably labeled with a bulky group and each incorporated nucleotide is identified by the changes in mass and/or surface stress of the structure upon incorporation of the nucleotide. In alternative embodiments of the invention only one type of nucleotide is exposed at a time to the nucleic acids. Changes in the properties of the structure may be detected by a variety of methods, such as piezoelectric detection, shifts in resonant frequency of the structure, and/or position sensitive photodetection.

摘要翻译： 本发明的方法和装置涉及通过将核苷酸掺入核酸链而进行的核酸测序。 通过结构的质量和/或表面应力的变化来检测核苷酸的掺入。 在本发明的一些实施例中，该结构包括一个或多个纳米级或微尺寸悬臂。 在本发明的某些实施方案中，每种不同类型的核苷酸可以用大体积区分地标记，并且每个掺入的核苷酸通过结合核苷酸时结构的质量和/或表面应力的变化来鉴定。 在本发明的替代实施方案中，一次仅将一种类型的核苷酸暴露于核酸。 可以通过各种方法来检测结构的性质的变化，例如压电检测，结构的谐振频率偏移和/或位置敏感的光电检测。

公开(公告)号：US20100151454A1

公开(公告)日：2010-06-17

申请号：US12256409

申请日：2008-10-22

申请人： Narayanan Sundararajan ,  Lei Sun ,  Yuegang Zhang ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Andrew A. Berlin

发明人： Narayanan Sundararajan ,  Lei Sun ,  Yuegang Zhang ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Andrew A. Berlin

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6827 ,  C12Q1/6869 ,  G01N21/658 ,  Y10T436/11 ,  Y10T436/117497 ,  Y10T436/143333 ,  C12Q2565/629 ,  C12Q2521/319 ,  C12Q2565/632 ,  C12Q2565/619

摘要： Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

摘要翻译： 本文公开了用于在微流体通道中进行核酸测序反应和分子结合反应的方法，装置和系统。 方法，装置和系统可以包括限制核酸附着的颗粒运动的限制障碍。 此外，方法，装置和系统可以包括输送流的流体动力聚焦。 此外，方法，装置和系统可以通过在表面和输送流之间提供保护流来减少与微流体通道的表面的非特异性相互作用。

公开(公告)号：US07442339B2

公开(公告)日：2008-10-28

申请号：US10815264

申请日：2004-03-31

申请人： Narayanan Sundararajan ,  Lei Sun ,  Yuegang Zhang ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Andrew A. Berlin

发明人： Narayanan Sundararajan ,  Lei Sun ,  Yuegang Zhang ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Andrew A. Berlin

IPC分类号： G01N21/65 ,  G01J3/44 ,  G01N33/48

CPC分类号： C12Q1/6827 ,  C12Q1/6869 ,  G01N21/658 ,  Y10T436/11 ,  Y10T436/117497 ,  Y10T436/143333 ,  C12Q2565/629 ,  C12Q2521/319 ,  C12Q2565/632 ,  C12Q2565/619

摘要： Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

摘要翻译： 本文公开了用于在微流体通道中进行核酸测序反应和分子结合反应的方法，装置和系统。 方法，装置和系统可以包括限制核酸附着的颗粒运动的限制障碍。 此外，方法，装置和系统可以包括输送流的流体动力聚焦。 此外，方法，装置和系统可以通过在表面和输送流之间提供保护流来减少与微流体通道的表面的非特异性相互作用。