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1. 发明申请

US20060009914A1 Detection and identification of nucleic acid, peptide, and protein modifications 审中-公开
标题翻译：检测和鉴定核酸，肽和蛋白质修饰
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。

2. 发明申请

US20060134714A1 Detection and identification of peptide and protein modifications 审中-公开
标题翻译：肽和蛋白质修饰的检测和鉴定
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。

3. 发明申请

US20070155022A1 Degenerate binding detection and protein identification using Raman spectroscopy nanoparticle labels 审中-公开
标题翻译：使用拉曼光谱纳米颗粒标签的简并结合检测和蛋白质鉴定
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。

4. 发明申请

US20060029969A1 Methods to increase nucleotide signals by Raman scattering 审中-公开
标题翻译：通过拉曼散射增加核苷酸信号的方法
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。

5. 发明申请

US20050148098A1 Methods for using raman spectroscopy to obtain a protein profile of a biological sample 审中-公开
标题翻译：使用拉曼光谱法获得生物样品的蛋白质谱的方法
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。

6. 发明申请

US20050250159A1 Methods for using Raman spectroscopy to obtain a protein profile of a biological sample 审中-公开
标题翻译：使用拉曼光谱法获得生物样品的蛋白质谱的方法
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。

7. 发明申请

US20060046313A1 Cellular analysis using Raman surface scanning 有权
标题翻译：使用拉曼表面扫描的细胞分析
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。

8. 发明授权

US07776547B2 Cellular analysis using Raman surface scanning 有权
标题翻译：使用拉曼表面扫描的细胞分析
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。

9. 发明申请

US20100267013A1 METHODS TO INCREASE NUCLEOTIDE SIGNALS BY RAMAN SCATTERING 审中-公开
标题翻译：通过拉曼散射增加核苷酸信号的方法
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。

10. 发明授权

US06972173B2 Methods to increase nucleotide signals by raman scattering 有权
标题翻译：通过拉曼散射增加核苷酸信号的方法
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。

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