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：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：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：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：US20050186576A1

公开(公告)日：2005-08-25

申请号：US10782014

申请日：2004-02-19

申请人： Selena Chan ,  Xing Su ,  Andrew Berlin ,  Tae-Woong Koo

发明人： Selena Chan ,  Xing Su ,  Andrew Berlin ,  Tae-Woong Koo

IPC分类号： B01L3/00 ,  C12Q1/68 ,  G01N33/48 ,  G01N33/50

CPC分类号： B82Y5/00 ,  B01L3/5027 ,  C12Q1/6874 ,  C12Q2565/629 ,  C12Q2527/113 ,  C12Q2521/319 ,  C12Q2565/631 ,  C12Q2565/601

摘要： Methods and apparatuses for sequencing single polymer molecules, such as a nucleic acid strand, are discussed. A discussed method comprises dividing a polymer sample into a number of polymer subsamples equal to the number of different monomer types and partially labeling only one of the monomer types in each polymer subsample. The method may further comprise placing a subsample into a reaction chamber, sequentially separating each monomer from the polymer subsample, and detecting the labels of each separated labeled monomer as a function of time. The time between each labeled monomer may be used to construct a monomer-time map for each polymer sub-sample using overlapping data analysis and frequency analysis. Time maps may then be assembled/aligned into a polymer sequence from the monomer-time maps of each of the polymer subsamples using non-overlapping data analysis.

摘要翻译： 讨论了用于测序单一聚合物分子（例如核酸链）的方法和装置。 所讨论的方法包括将聚合物样品分成等于不同单体类型的数量的多个聚合物子样品，并且在每个聚合物子样品中仅部分地标记单体类型之一。 该方法还可以包括将子样品放入反应室中，顺序地从聚合物子样品中分离每个单体，并检测每个分离的标记单体的标记作为时间的函数。 每个标记的单体之间的时间可以用于使用重叠的数据分析和频率分析来构建每个聚合物子样品的单体时间图。 然后可以使用不重叠的数据分析，从每个聚合物子样品的单体时间图，将时间图组装/排列成聚合物序列。

公开(公告)号：US20060046313A1

公开(公告)日：2006-03-02

申请号：US11027470

申请日：2004-12-30

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

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

IPC分类号： G01N33/543

CPC分类号： G01N33/54366 ,  G01N33/54373 ,  G01N33/58 ,  Y10T436/10

摘要： Methods and apparatus are provided for assaying cell samples, which may be living cells, using probes labeled with composite organic-inorganic nanoparticles (COINs) and microspheres with COINs embedded within a polymer matrix to which the probe moiety is attached. COINs intrinsically produce SERS signals upon laser irradiation, making COIN-labeled probes particularly suitable in a variety of methods for assaying cells, including biological molecules that may be contained on or within cells, most of which are not inherently Raman-active. The invention provides variations of the sandwich immunoassay employing both specific and degenerate binding, methods for reverse phase assay of tissue samples and cell microstructures, in solution displacement and competition assays, and the like. Systems and chips useful for practicing the invention assays are also provided.

摘要翻译： 提供了用于使用用复合有机 - 无机纳米颗粒（COIN）标记的探针和嵌入探针部分所连接的聚合物基质内的COIN的微球来测定可能为活细胞的细胞样品的方法和装置。 COIN在激光照射下固有地产生SERS信号，使得COIN标记的探针特别适用于多种测定细胞的方法，包括可能包含在细胞内或细胞内的生物分子，其中大部分不是固有的拉曼活性的。 本发明提供使用特异性和简并结合的夹心免疫测定的变体，组织样品和细胞微结构的反相测定方法，溶液置换和竞争测定等。 还提供了用于实施本发明测定的系统和芯片。

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：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：US07776547B2

公开(公告)日：2010-08-17

申请号：US11027470

申请日：2004-12-30

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

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

IPC分类号： G01N33/53

CPC分类号： G01N33/54366 ,  G01N33/54373 ,  G01N33/58 ,  Y10T436/10

摘要： Methods and apparatus are provided for assaying cell samples, which may be living cells, using probes labeled with composite organic-inorganic nanoparticles (COINs) and microspheres with COINs embedded within a polymer matrix to which the probe moiety is attached. COINs intrinsically produce SERS signals upon laser irradiation, making COIN-labeled probes particularly suitable in a variety of methods for assaying cells, including biological molecules that may be contained on or within cells, most of which are not inherently Raman-active. The invention provides variations of the sandwich immunoassay employing both specific and degenerate binding, methods for reverse phase assay of tissue samples and cell microstructures, in solution displacement and competition assays, and the like. Systems and chips useful for practicing the invention assays are also provided.

摘要翻译： 提供了用于使用用复合有机 - 无机纳米颗粒（COIN）标记的探针和嵌入探针部分所连接的聚合物基质内的COIN的微球来测定可能为活细胞的细胞样品的方法和装置。 COIN在激光照射下固有地产生SERS信号，使得COIN标记的探针特别适用于多种测定细胞的方法，包括可能包含在细胞内或细胞内的生物分子，其中大部分不是固有的拉曼活性的。 本发明提供使用特异性和简并结合的夹心免疫测定的变体，组织样品和细胞微结构的反相测定方法，溶液置换和竞争测定等。 还提供了用于实施本发明测定的系统和芯片。

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。