METHODS TO INCREASE NUCLEOTIDE SIGNALS BY RAMAN SCATTERING

    公开(公告)号:CA2478881A1

    公开(公告)日:2003-09-25

    申请号:CA2478881

    申请日:2003-03-11

    Applicant: INTEL CORP

    Abstract: The methods and apparatus disclosed herein concern nucleic acid sequencing b y enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation int o 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 (1 0, 100, 210) for nucleic acid sequencing.

    METHODS OF PRODUCING CARBON NANOTUBES USING PEPTIDE OR NUCLEIC ACID MICROPATTERNING
    12.
    发明申请
    METHODS OF PRODUCING CARBON NANOTUBES USING PEPTIDE OR NUCLEIC ACID MICROPATTERNING 审中-公开
    使用肽或核酸微生物生产碳纳米管的方法

    公开(公告)号:WO2005066367A3

    公开(公告)日:2007-03-01

    申请号:PCT/US2004043364

    申请日:2004-12-24

    Abstract: The methods, apparatus and systems disclosed herein concern ordered arrays of carbon nanotubes. In particular embodiments of the invention, the nanotube arrays are formed by a method comprising attaching catalyst nanoparticles (140, 230) to polymer (120, 210) molecules, attaching the polymer (120, 210) molecules to a substrate, removing the polymer (120, 210) molecules and producing carbon nanotubes on the catalyst nanoparticles (140, 230). The polymer (120, 210) molecules alignment techniques. The nanotube arrays can be attached to selected areas (110, 310) of the substrate. Within the selected areas (110, 310), the nanotubes are distributed non-randomly. Other embodiments disclosed herein concern apparatus that include ordered arrays of nanotubes attached to a substrate and systems that include ordered arrays of carbon nanotubes attached to a substrate, produced by the claimed methods. In certain embodiments, provided herein are methods for aligning a molecular wire, by ligating the molecular wire to a double stranded DNA molecule.

    Abstract translation: 本文公开的方法,装置和系统涉及碳纳米管的有序阵列。 在本发明的具体实施方案中,纳米管阵列通过包括将催化剂纳米颗粒(140,230)附着到聚合物(120,210)分子上的方法形成,将聚合物(120,210)分子附着到基底上,去除聚合物 120,210)分子并在催化剂纳米颗粒(140,230)上产生碳纳米管。 聚合物(120,210)分子对齐技术。 纳米管阵列可以附着到基板的选定区域(110,310)。 在所选择的区域(110,310)内,纳米管是非随机分布的。 本文公开的其它实施方案涉及包括连接到衬底的纳米管的有序阵列和包括通过所要求保护的方法产生的连接到衬底的碳纳米管的有序阵列的系统的装置。 在某些实施方案中,本文提供了通过将分子线连接到双链DNA分子来对齐分子线的方法。

    LASER EXPOSURE OF PHOTOSENSITIVE MASKS FOR DNA MICROARRAY FABRICATION
    14.
    发明申请
    LASER EXPOSURE OF PHOTOSENSITIVE MASKS FOR DNA MICROARRAY FABRICATION 审中-公开
    激光曝光用于DNA微量制备的光敏掩模

    公开(公告)号:WO2004065635A3

    公开(公告)日:2005-02-03

    申请号:PCT/US0337839

    申请日:2003-11-26

    Applicant: INTEL CORP

    Abstract: A method and apparatus for forming a polymer array on a substrate suitable for synthesizing polymer sequences. This includes forming an array, each location of the array having at least one strand end, forming photosensitive protection on the strand ends, and selectively scanning and modulating at least one energy beam to expose a pattern on the photosensitive protection. In some embodiments, the method further includes removing a protective group from selected strand ends based on the exposed pattern. The method then includes adding a predetermined one or more polymeric subunits to the deprotected strand ends. In some embodiments the photosensitive protection includes a layer of photoresist to cover the strand ends. Some embodiments use an ultra-violet laser.

    Abstract translation: 一种在适于合成聚合物序列的基材上形成聚合物阵列的方法和装置。 这包括形成阵列,阵列的每个位置具有至少一个绞合端,在绞合端上形成感光保护,并且选择性地扫描和调制至少一个能量束以暴露感光保护上的图案。 在一些实施方案中,该方法还包括基于暴露图案从选定的链末端去除保护基团。 该方法然后包括将预定的一个或多个聚合物亚单位加入去保护的末端。 在一些实施例中,感光保护包括一层光致抗蚀剂以覆盖绞合端。 一些实施例使用紫外激光。

    NUCLEIC ACID SEQUENCING BY RAMAN MONITORING OF UPTAKE OF PRECURSORS DURING MOLECULAR REPLICATION
    15.
    发明申请
    NUCLEIC ACID SEQUENCING BY RAMAN MONITORING OF UPTAKE OF PRECURSORS DURING MOLECULAR REPLICATION 审中-公开
    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:WO03027307A2

    公开(公告)日:2003-04-03

    申请号:PCT/US0228443

    申请日:2002-09-05

    Applicant: INTEL CORP

    Abstract: 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.

    Abstract translation: 本文公开的方法,组合物和装置用于核酸序列测定。 所述方法包括使用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核酸的新生互补链的聚合。 当新生链一次延伸一个核苷酸时,通过拉曼光谱法或FRET监测核苷酸前体从溶液中的消失。 新生链的核酸序列和模板链的互补序列可以通过跟踪聚合反应期间核苷酸前体的掺入顺序来确定。 某些实施例涉及包括在实施所要求保护的方法中使用的反应室和检测单元的装置。 方法,组合物和装置在用于在单次测序反应中测序非常长的核酸模板中有用。

    A METHOD AND DEVICE FOR DETECTING SMALL NUMBERS OF MOLECULES USING SURFACE-ENHANCED COHERENT ANTI-STOKES RAMAN SPECTROSCOPY
    17.
    发明申请
    A METHOD AND DEVICE FOR DETECTING SMALL NUMBERS OF MOLECULES USING SURFACE-ENHANCED COHERENT ANTI-STOKES RAMAN SPECTROSCOPY 审中-公开
    使用表面增强的相干反驻波拉曼光谱检测分子小数的方法和装置

    公开(公告)号:WO2005038419A3

    公开(公告)日:2005-09-22

    申请号:PCT/US2004034598

    申请日:2004-10-18

    Applicant: INTEL CORP

    CPC classification number: G01N21/658 G01J3/44 G01N2021/653

    Abstract: The device and method disclosed herein concern detecting, identifying, and or quantifying analytes, such as nucleic acids, with high resolution and fast response times using surface enhanced coherent anti-Stokes Raman spectroscopy. In certain embodiments of the invention, a small number molecular sample of the analyte (210) such as a nucleotide, passes through a microfluidic channel, microchannel, or nanochannel (185) and sample cell (175) that contains Raman-active surfaces, and is detected by surface enhanced, coherent anti-Stokes Raman spectroscopy (SECARS). Other embodiments of the invention concern an apparatus for analyte detection.

    Abstract translation: 本文公开的装置和方法涉及使用表面增强的相干反斯托克斯拉曼光谱以高分辨率和快速响应时间来检测,鉴定和或定量分析物例如核酸。 在本发明的某些实施方案中,分析物(210)的少量分子样品例如核苷酸穿过含有拉曼活性表面的微流体通道,微通道或纳米通道(185)和样品池(175),并且 通过表面增强的相干反斯托克斯拉曼光谱(SECARS)检测。 本发明的其他实施例涉及用于分析物检测的装置。

    METHODS FOR USING RAMAN SPECTROSCOPY TO OBTAIN A PROTEIN PROFILE OF A BIOLOGICAL SAMPLE
    18.
    发明申请
    METHODS FOR USING RAMAN SPECTROSCOPY TO OBTAIN A PROTEIN PROFILE OF A BIOLOGICAL SAMPLE 审中-公开
    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:WO2005065541A2

    公开(公告)日:2005-07-21

    申请号:PCT/US2004043769

    申请日:2004-12-29

    Abstract: 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.

    Abstract translation: 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处保持分离状态。 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。

    CONTROLLED ALIGNMENT OF NANO-BARCODES ENCODING SPECIFIC INFORMATION FOR SCANNING PROBE MICROSCOPY (SPM) READING
    19.
    发明申请
    CONTROLLED ALIGNMENT OF NANO-BARCODES ENCODING SPECIFIC INFORMATION FOR SCANNING PROBE MICROSCOPY (SPM) READING 审中-公开
    编码用于扫描探针显微镜(SPM)读取的特定信息的纳米棒的对照

    公开(公告)号:WO2004038037A3

    公开(公告)日:2004-11-11

    申请号:PCT/US0329726

    申请日:2003-09-22

    Applicant: INTEL CORP

    Abstract: The methods, apparatus and compositions disclosed herein concern the detection, identification and/or sequencing of biomolecules, such as nucleic acids or proteins. In certain embodiments of the invention, coded probes comprising a probe molecule attached to one or more nano-barcodes may be allowed to bind to one or more target molecules. After binding and separation from unbound coded probes, the bound coded probes may be aligned on a surface and analyzed by scanning probe microscopy. The nano-barcodes may be any molecule or complex that is distinguishable by SPM, such as carbon nanotubes, fullerenes, submicrometer metallic barcodes, nanoparticles or quantum dots. Where the probes are oligonucleotides, adjacent coded probes hybridized to a target nucleic acid may be ligated together before alignment and SPM analysis. Compositions comprising coded probes are also disclosed herein. Systems for biomolecule analysis may comprise an SPM instrument and at least one coded probe attached to a surface.

    Abstract translation: 本文公开的方法,装置和组合物涉及生物分子如核酸或蛋白质的检测,鉴定和/或测序。 在本发明的某些实施方案中,包含与一个或多个纳米条形码连接的探针分子的编码探针可以被允许与一个或多个靶分子结合。 在结合和分离未结合的编码探针之后,结合编码的探针可以在表面上排列并通过扫描探针显微镜进行分析。 纳米条形码可以是通过SPM可区分的任何分子或复合物,例如碳纳米管,富勒烯,亚微米金属条形码,纳米粒子或量子点。 当探针是寡核苷酸时,与靶核酸杂交的相邻编码探针可以在对准和SPM分析之前连接在一起。 包含编码探针的组合物也在本文中公开。 用于生物分子分析的系统可以包括SPM仪器和附接到表面的至少一个编码探针。

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