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1. 发明申请

US20080032297A1 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：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。

2. 发明申请

US20060166243A1 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：US20060166243A1
公开(公告)日：2006-07-27
申请号：US11329693
申请日：2006-01-10
申请人： Xing Su , Andrew Berlin , Selena Chan , Steven Kirch , Tac-Woong Koo , Gabi Neubauer , Valluri Rao , Narayanan Sundararajan , Mineo Yamakawa
发明人： Xing Su , Andrew Berlin , Selena Chan , Steven Kirch , Tac-Woong Koo , Gabi Neubauer , Valluri Rao , Narayanan Sundararajan , Mineo Yamakawa
IPC分类号： C12Q1/68 , C12P19/34
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。

3. 发明申请

US20050026163A1 Method for sequencing nucleic acids by observing the uptake of nucleotides modified with bulky groups 审中-公开
标题翻译：通过观察用大体积改性的核苷酸摄取来测序核酸的方法
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。

4. 发明申请

US20070059733A1 Method for sequencing nucleic acids by observing the uptake of nucleotides modified with bulky groups 审中-公开
标题翻译：通过观察用大体积改性的核苷酸摄取来测序核酸的方法
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。

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

US20070054288A1 Programmable molecular barcodes 审中-公开
标题翻译：可编程分子条形码
公开(公告)号：US20070054288A1
公开(公告)日：2007-03-08
申请号：US11430612
申请日：2006-05-08
申请人： Xing Su , Tae-Woong Koo , Andrew Berlin , Lei Sun , Narayanan Sundararajan , Mineo Yamakawa
发明人： Xing Su , Tae-Woong Koo , Andrew Berlin , Lei Sun , Narayanan Sundararajan , Mineo Yamakawa
IPC分类号： C12Q1/68 , C12M1/34 , G06K7/10
CPC分类号： B82Y10/00 , B82Y5/00 , C12Q1/6816 , G06K19/06028 , C12Q2525/161 , C12Q2537/143 , C12Q2565/1025
摘要： The present disclosure concerns methods for producing and/or using molecular barcodes. In certain embodiments of the invention, the barcodes comprise polymer backbones that may contain one or more branch structures. Tags may be attached to the backbone and/or branch structures. The barcode may also comprise a probe that can bind to a target, such as proteins, nucleic acids and other biomolecules or aggregates. Different barcodes may be distinguished by the type and location of the tags. In other embodiments, barcodes may be produced by hybridization of one or more tagged oligonucleotides to a template, comprising a container section and a probe section. The tagged oligonucleotides may be designed as modular code sections, to form different barcodes specific for different targets. In alternative embodiments, barcodes may be prepared by polymerization of monomeric units. Bound barcodes may be detected by various imaging modalities, such as, surface plasmon resonance, fluorescent or Raman spectroscopy.
摘要翻译：本公开涉及用于生产和/或使用分子条形码的方法。在本发明的某些实施方案中，条形码包含可包含一个或多个分支结构的聚合物主链。标签可以附加到骨干和/或分支结构。条形码还可以包含可以与靶标结合的探针，例如蛋白质，核酸和其他生物分子或聚集体。可以通过标签的类型和位置区分不同的条形码。在其它实施方案中，条形码可以通过将一个或多个标记的寡核苷酸与包含容器部分和探针部分的模板杂交来产生。标记的寡核苷酸可以被设计为模块代码部分，以形成针对不同靶标的不同条形码。在替代实施例中，条形码可以通过单体单元的聚合来制备。可以通过各种成像方式，例如表面等离子体共振，荧光或拉曼光谱来检测结合条形码。

8. 发明申请

US20050064435A1 Programmable molecular barcodes 审中-公开
标题翻译：可编程分子条形码
公开(公告)号：US20050064435A1
公开(公告)日：2005-03-24
申请号：US10670701
申请日：2003-09-24
申请人： Xing Su , Tae-Woong Koo , Andrew Berlin , Lei Sun , Narayanan Sundararajan , Mineo Yamakawa
发明人： Xing Su , Tae-Woong Koo , Andrew Berlin , Lei Sun , Narayanan Sundararajan , Mineo Yamakawa
IPC分类号： C12Q1/68 , G06K19/06 , G01N33/53 , G06K7/10
CPC分类号： B82Y10/00 , B82Y5/00 , C12Q1/6816 , G06K19/06028 , C12Q2525/161 , C12Q2537/143 , C12Q2565/1025
摘要： The present disclosure concerns methods for producing and/or using molecular barcodes. In certain embodiments of the invention, the barcodes comprise polymer backbones that may contain one or more branch structures. Tags may be attached to the backbone and/or branch structures. The barcode may also comprise a probe that can bind to a target, such as proteins, nucleic acids and other biomolecules or aggregates. Different barcodes may be distinguished by the type and location of the tags. In other embodiments, barcodes may be produced by hybridization of one or more tagged oligonucleotides to a template, comprising a container section and a probe section. The tagged oligonucleotides may be designed as modular code sections, to form different barcodes specific for different targets. In alternative embodiments, barcodes may be prepared by polymerization of monomeric units. Bound barcodes may be detected by various imaging modalities, such as, surface plasmon resonance, fluorescent or Raman spectroscopy.
摘要翻译：本公开涉及用于生产和/或使用分子条形码的方法。在本发明的某些实施方案中，条形码包含可包含一个或多个分支结构的聚合物主链。标签可以附加到骨干和/或分支结构。条形码还可以包含可以与靶标结合的探针，例如蛋白质，核酸和其他生物分子或聚集体。可以通过标签的类型和位置区分不同的条形码。在其它实施方案中，条形码可以通过将一个或多个标记的寡核苷酸与包含容器部分和探针部分的模板杂交来产生。标记的寡核苷酸可以被设计为模块代码部分，以形成针对不同靶标的不同条形码。在替代实施例中，条形码可以通过单体单元的聚合来制备。绑定的条形码可以通过各种成像模式来检测，例如表面等离子体共振，荧光或拉曼光谱。

9. 发明申请

US20070105132A1 Nucleic acid sequencing by Raman monitoring of uptake of nucleotides during molecular replication 审中-公开
标题翻译：通过拉曼监测分子复制过程中核苷酸摄取的核酸测序
公开(公告)号：US20070105132A1
公开(公告)日：2007-05-10
申请号：US11447507
申请日：2006-06-05
申请人： Andrew Berlin , Steven Kirch , Gabi Neubauer , Valluri Rao , Mineo Yamakawa
发明人： Andrew Berlin , Steven Kirch , Gabi Neubauer , Valluri Rao , Mineo Yamakawa
IPC分类号： C12Q1/68
CPC分类号： G01N21/05 , B01L3/5027 , B01L3/502761 , B01L2200/0647 , B01L2300/0896 , B01L2400/0454 , B01L2400/0463 , B82Y5/00 , B82Y15/00 , B82Y30/00 , C12Q1/6869 , G01N21/658 , G01N2021/0346 , G01N2021/651 , G01N2021/653 , G01N2021/655 , G01N2021/656 , C12Q2565/628
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). 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.
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）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。

10. 发明申请

US20060199216A1 Programmable molecular barcodes 审中-公开
标题翻译：可编程分子条形码
公开(公告)号：US20060199216A1
公开(公告)日：2006-09-07
申请号：US11430590
申请日：2006-05-08
申请人： Xing Su , Tae-Woong Koo , Andrew Berlin , Lei Sun , Narayanan Sundararajan , Mineo Yamakawa
发明人： Xing Su , Tae-Woong Koo , Andrew Berlin , Lei Sun , Narayanan Sundararajan , Mineo Yamakawa
IPC分类号： C12Q1/68 , G01N33/551
CPC分类号： B82Y10/00 , B82Y5/00 , C12Q1/6816 , G06K19/06028 , C12Q2525/161 , C12Q2537/143 , C12Q2565/1025
摘要： The present disclosure concerns methods for producing and/or using molecular barcodes. In certain embodiments of the invention, the barcodes comprise polymer backbones that may contain one or more branch structures. Tags may be attached to the backbone and/or branch structures. The barcode may also comprise a probe that can bind to a target, such as proteins, nucleic acids and other biomolecules or aggregates. Different barcodes may be distinguished by the type and location of the tags. In other embodiments, barcodes may be produced by hybridization of one or more tagged oligonucleotides to a template, comprising a container section and a probe section. The tagged oligonucleotides may be designed as modular code sections, to form different barcodes specific for different targets. In alternative embodiments, barcodes may be prepared by polymerization of monomeric units. Bound barcodes may be detected by various imaging modalities, such as, surface plasmon resonance, fluorescent or Raman spectroscopy.
摘要翻译：本公开涉及用于生产和/或使用分子条形码的方法。在本发明的某些实施方案中，条形码包含可包含一个或多个分支结构的聚合物主链。标签可以附加到骨干和/或分支结构。条形码还可以包含可以与靶标结合的探针，例如蛋白质，核酸和其他生物分子或聚集体。可以通过标签的类型和位置区分不同的条形码。在其它实施方案中，条形码可以通过将一个或多个标记的寡核苷酸与包含容器部分和探针部分的模板杂交来产生。标记的寡核苷酸可以被设计为模块代码部分，以形成针对不同靶标的不同条形码。在替代实施例中，条形码可以通过单体单元的聚合来制备。绑定的条形码可以通过各种成像模式来检测，例如表面等离子体共振，荧光或拉曼光谱。

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