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1. 发明公开

KR1020060094521A 라만 산란에 의해 뉴클레오티드 신호를 증가시키는 방법 无效
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：KR1020060094521A
公开(公告)日：2006-08-29
申请号：KR1020067006988
申请日：2003-09-15
申请人： 인텔 코포레이션
发明人： 수싱 , 베를린앤드류에이. , 챤셀레나 , 커치스티븐제이. , 구태-웅 , 뉴바우어개비 , 라오발루리 , 선다라라쟌나라얀 , 야마카와미네오
IPC分类号： C12Q1/68 , C12Q1/00 , B82Y5/00
CPC分类号： C12Q1/6869 , B82Y5/00 , C12Q2521/319 , C12Q2563/155 , C12Q2565/632
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. 发明授权

KR100596265B1 분자 복제 도중 전구체의 흡수의 라만 모니터링에 의한핵산의 시퀀싱 失效
标题翻译：在分子复制过程中拉曼监测前列腺素的核酸序列
公开(公告)号：KR100596265B1
公开(公告)日：2006-06-30
申请号：KR1020047004230
申请日：2002-09-05
申请人： 인텔 코포레이션
发明人： 라오발러리 , 노이바우어가비 , 커치스티븐 , 야마카와미네오 , 버린앤드류
IPC分类号： C12Q1/68 , B82B3/00 , B82Y5/00
CPC分类号： G01N21/6428 , B01L3/5027 , C12Q1/6869 , G01J3/4406 , G01N21/65 , G01N21/658 , G01N2021/6441 , G01N2021/651 , G01N2021/653 , G01N2021/655 , G01N2021/656 , C12Q2565/632 , C12Q2565/101 , C12Q2533/101 , C12Q2565/629 , C12Q2565/60
摘要： The methods, compositions and apparatus disclosed herein are of use for nucleic acid sequence determination. The methods involve isolation of one or more nucleic acid template molecules and polymerization of a nascent complementary strand of nucleic acid, using a DNA or RNA polymerase or similar synthetic reagent. As the nascent strand is extended one nucleotide at a time, the disappearance of nucleotide precursors from solution is monitored by Raman spectroscopy or FRET. The nucleic acid sequence of the nascent strand, and the complementary sequence of the template strand, may be determined by tracking the order of incorporation of nucleotide precursors during the polymerization reaction. Certain embodiments concern apparatus comprising a reaction chamber and detection unit, of use in practicing the claimed methods. The methods, compositions and apparatus are of use in sequencing very long nucleic acid templates in a single sequencing reaction.

3. 发明公开

KR1020060135719A 스캐닝 프로브 현미경 및 나노코드를 이용하여 핵산을검출하는 방법 및 조성물 无效
标题翻译：使用扫描探针显微镜和纳米级检测核酸的方法和组合物
公开(公告)号：KR1020060135719A
公开(公告)日：2006-12-29
申请号：KR1020067014916
申请日：2004-12-28
申请人： 인텔 코포레이션
发明人： 버린앤드류 , 야마카와미네오
IPC分类号： C12Q1/68 , B82Y5/00
CPC分类号： C12Q1/6874 , B82Y5/00 , B82Y10/00 , C12Q1/6876 , C12Q2525/179 , C12Q2563/155 , C12Q2565/601
摘要： A method for determining a nucleotide sequence of a nucleic acid is provided that includes contacting the nucleic acid with a series of labeled oligonucleotides for binding to the nucleic acid, wherein each labeled oligonucleotide includes a known nucleotide sequence and a molecular nanocode. The nanocode of an isolated labeled oligonucleotides that binds to the nucleic acid is then detected using SPM. Nanocodes of the present invention in certain aspects include detectable features beyond the arrangement of tags that encode information about the barcoded object, which assist in detecting the tags that encode information about the barcoded object. The detectable features include structures of a nanocode or associated with a nanocode, referred to herein as detectable feature tags, for error checking/error-correction, encryption, and data reduction/compression.
摘要翻译：提供了用于确定核酸的核苷酸序列的方法，其包括使核酸与一系列用于结合核酸的标记的寡核苷酸接触，其中每个标记的寡核苷酸包括已知的核苷酸序列和分子纳代码。然后使用SPM检测与核酸结合的分离的标记寡核苷酸的纳代码。在某些方面，本发明的纳代码包括超过编码关于条形码对象的信息的标签布置的可检测特征，其有助于检测编码关于条形码对象的信息的标签。可检测特征包括用于错误校验/纠错，加密和数据缩减/压缩的纳代码或与纳代码相关联的结构，这里称为可检测特征标签。

4. 发明公开

KR1020050004177A 핵산 서열결정에 있어서의 캔틸레버의 적용법 无效
标题翻译：悬臂梁在核酸序列测定中的应用
公开(公告)号：KR1020050004177A
公开(公告)日：2005-01-12
申请号：KR1020047018770
申请日：2003-04-18
申请人： 인텔 코포레이션
发明人： 선다라라잔나라얀 , 베를린앤드류 , 야마카와미네오 , 수징 , 챈셀레나 , 구태-웅
IPC分类号： C12Q1/68 , C12M1/34 , B82B3/00 , B82Y5/00
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 100 concern nucleic acid 214 sequencing by incorporation of nucleotides 218 into nucleic acid strands 220. The incorporation of nucleotides 218 is detected by changes in the mass and/or surface stress of the structure 116, 212. In some embodiments of the invention, the structure 116, 212 comprises one or more nanoscale or microscale cantilevers. In certain embodiments of the invention, each different type of nucleotide 218 is distinguishably labeled with a bulky group and each incorporated nucleotide 218 is identified by the changes in mass and/or surface stress of the structure 116, 212 upon incorporation of the nucleotide 218. In alternative embodiments of the invention only one type of nucleotide 218 is exposed at a time to the nucleic acids 214, 220. Changes in the properties of the structure 116, 212 may be detected by a variety of methods, such as piezoelectric detection, shifts in resonant frequency of the structure 116, 212, and/or position sensitive photodetection.

5. 发明授权

KR100669589B1 분자 해체의 라만 모니터링에 의한 핵산 서열결정 장치 및방법 失效
标题翻译：通过拉曼分子分解监测的核酸序列测序
公开(公告)号：KR100669589B1
公开(公告)日：2007-01-15
申请号：KR1020047004232
申请日：2002-08-30
申请人： 인텔 코포레이션
发明人： 라오발루리 , 누바우어가비 , 커크스티븐 , 야마카와미네오 , 베를린앤드류
IPC分类号： C12Q1/68
CPC分类号： B01L3/5027 , B01L3/502761 , B01L2200/0668 , B01L2400/0454 , C12Q1/6818 , C12Q1/6825 , C12Q1/6869 , C12Q2565/632 , C12Q2521/319
摘要： The disclosed methods, apparatus and compositions are of use for nucleic acid sequencing. More particularly, the methods and apparatus concern sequencing single molecules of single stranded DNA or RNA by exposing the molecule to exonuclease activity, removing free nucleotides one at a time from one end of the nucleic acid, and identifying the released nucleotides by Raman spectroscopy or FRET.

6. 发明公开

KR1020070006728A 라만 분광분석을 사용하여 생물학적 시료의 단백질프로파일을 얻는 방법 无效
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：KR1020070006728A
公开(公告)日：2007-01-11
申请号：KR1020067015338
申请日：2004-12-29
申请人： 인텔 코포레이션
发明人： 벌린앤드류 , 수싱 , 챈셀레나 , 구태웅 , 선레이 , 선다라라잔나라얀 , 야마카와미네오
IPC分类号： G01N33/68 , G01N33/58 , G01N21/63 , G06F19/20
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. ® KIPO & WIPO 2007
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。 ®KIPO＆WIPO 2007

7. 发明公开

KR1020060094531A 프로그램가능한 분자 바코드 无效
标题翻译：可编程分子杆
公开(公告)号：KR1020060094531A
公开(公告)日：2006-08-29
申请号：KR1020067007935
申请日：2004-09-23
申请人： 인텔 코포레이션
发明人： 수싱 , 구태웅 , 버린앤드류 , 선라이 , 순다라라얀나라야난 , 야마카와미네오
IPC分类号： C12Q1/68 , B82Y5/00
CPC分类号： B82Y10/00 , B82Y5/00 , C12Q1/6816 , G06K19/06028 , C12Q2525/161 , C12Q2537/143 , C12Q2563/155 , 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。

8. 发明公开

KR1020040094803A 라만 산란법에 의해 뉴클레오타이드 신호를 증가시키는 방법 无效
标题翻译：如何用拉曼散射法增加核苷酸信号
公开(公告)号：KR1020040094803A
公开(公告)日：2004-11-10
申请号：KR1020047014486
申请日：2003-03-11
申请人： 인텔 코포레이션
发明人： 수씽 , 베를린앤드류 , 쿠태-웅 , 찬셀레나 , 선다라라잔나라얀 , 야마카와미네오
IPC分类号： C12Q1/68 , G01N21/29 , B82B3/00 , B82Y5/00
CPC分类号： C12Q1/6869 , C12Q1/6816 , C12Q1/6825 , C12Q1/6872 , B82B3/00 , B82Y5/00 , C12Q2521/319 , C12Q2563/155 , C12Q2565/632 , G01N21/29
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.

9. 发明公开

KR1020040035875A 분자 해체의 라만 모니터링에 의한 핵산 서열결정 장치 및방법 失效
标题翻译： 분자해체의라만모니터링에의한핵산서열결정장치및방분
公开(公告)号：KR1020040035875A
公开(公告)日：2004-04-29
申请号：KR1020047004232
申请日：2002-08-30
申请人： 인텔 코포레이션
发明人： 라오발루리 , 누바우어가비 , 커크스티븐 , 야마카와미네오 , 베를린앤드류
IPC分类号： C12Q1/68
CPC分类号： B01L3/5027 , B01L3/502761 , B01L2200/0668 , B01L2400/0454 , C12Q1/6818 , C12Q1/6825 , C12Q1/6869 , C12Q2521/319 , C12Q2565/632
摘要： The disclosed methods, apparatus and compositions are of use for nucleic acid sequencing. More particularly, the methods and apparatus concern sequencing single molecules of single stranded DNA or RNA by exposing the molecule to exonuclease activity, removing free nucleotides one at a time from one end of the nucleic acid, and identifying the released nucleotides by Raman spectroscopy or FRET.
摘要翻译：所公开的方法，装置和组合物可用于核酸测序。更具体地说，所述方法和装置涉及通过将分子暴露于外切核酸酶活性，从核酸的一端一次一个地除去游离的核苷酸，并通过拉曼光谱或FRET鉴定释放的核苷酸来对单链DNA或RNA的单分子测序。

10. 发明公开

KR1020040035874A 분자 복제 도중 전구체의 흡수의 라만 모니터링에 의한핵산의 시퀀싱 失效
标题翻译： 분자복제도중도중전체체의흡수의라만모니터링에의한핵산의시퀀싱
公开(公告)号：KR1020040035874A
公开(公告)日：2004-04-29
申请号：KR1020047004230
申请日：2002-09-05
申请人： 인텔 코포레이션
发明人： 라오발러리 , 노이바우어가비 , 커치스티븐 , 야마카와미네오 , 버린앤드류
IPC分类号： C12Q1/68 , B82B3/00 , B82Y5/00
CPC分类号： G01N21/6428 , B01L3/5027 , C12Q1/6869 , G01J3/4406 , G01N21/65 , G01N21/658 , G01N2021/6441 , G01N2021/651 , G01N2021/653 , G01N2021/655 , G01N2021/656 , B82B3/00 , B82Y5/00 , C12Q2533/101 , C12Q2565/101 , C12Q2565/60 , C12Q2565/629 , C12Q2565/632
摘要： The methods, compositions and apparatus disclosed herein are of use for nucleic acid sequence determination. The methods involve isolation of one or more nucleic acid template molecules and polymerization of a nascent complementary strand of nucleic acid, using a DNA or RNA polymerase or similar synthetic reagent. As the nascent strand is extended one nucleotide at a time, the disappearance of nucleotide precursors from solution is monitored by Raman spectroscopy or FRET. The nucleic acid sequence of the nascent strand, and the complementary sequence of the template strand, may be determined by tracking the order of incorporation of nucleotide precursors during the polymerization reaction. Certain embodiments concern apparatus comprising a reaction chamber and detection unit, of use in practicing the claimed methods. The methods, compositions and apparatus are of use in sequencing very long nucleic acid templates in a single sequencing reaction.
摘要翻译：本文公开的方法，组合物和装置可用于核酸序列测定。该方法包括使用DNA或RNA聚合酶或类似的合成试剂分离一个或多个核酸模板分子和聚合新生的核酸互补链。随着新生链一次延伸一个核苷酸，通过拉曼光谱或FRET监测溶液中核苷酸前体的消失。新生链的核酸序列和模板链的互补序列可以通过追踪聚合反应过程中核苷酸前体的掺入顺序来确定。某些实施例涉及用于实践所要求保护的方法的包括反应室和检测单元的装置。该方法，组合物和装置用于在单个测序反应中对非常长的核酸模板进行测序。

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