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    PROGRAMMABLE MOLECULAR BARCODES
    2.
    发明申请
    PROGRAMMABLE MOLECULAR BARCODES 审中-公开

    公开(公告)号：WO2005030996A3

    公开(公告)日：2005-04-07

    申请号：PCT/US2004/031289

    申请日：2004-09-23

    Applicant: INTEL CORPORATION

    Inventor： SU, Xing ,  KOO, Tae-Woong ,  BERLIN, Andrew ,  SUN, Lei ,  SUNDARARAJAN, Narayanan ,  YAMAKAWA, Mineo

    IPC: C12Q1/68

    Abstract: 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.

    MODEL-BASED FUSION OF SCANNING PROBE MICROSCOPIC IMAGES FOR DETECTION AND IDENTIFICATION OF MOLECULAR STRUCTURES
    3.
    发明申请
    MODEL-BASED FUSION OF SCANNING PROBE MICROSCOPIC IMAGES FOR DETECTION AND IDENTIFICATION OF MOLECULAR STRUCTURES 审中-公开
    用于探测和识别分子结构的扫描探针微观图像的基于模型的融合

    公开(公告)号：WO2004036591A1

    公开(公告)日：2004-04-29

    申请号：PCT/US2003/033083

    申请日：2003-10-16

    Applicant: INTEL CORPORATION

    Inventor： HAUSSECKER, Horst ,  BERLIN, Andrew ,  CHAN, Selena ,  HANNAH, Eric ,  SUNDARARAJAN, Narayan ,  YAMAKAWA, Mineo

    IPC: G12B21/00

    CPC classification number: G01Q30/04

    Abstract: In certain embodiments of the invention, a plurality of images of one or more subjects may be captured using different imaging techniques, such as different modalities of scanning probe microscopy. Parameters may be estimated from the plurality of images, using one or more models of known molecular structures to provide a model-based analysis. The estimated parameters may be fused, with further input from physical models of known molecular structures. The fused parameters may be used to characterize the subjects. Such characterization may include the detection and/or identification of specific molecular structures, such as proteins, peptides and/or nucleic acids of known sequence and/or structure. In some embodiments of the invention the structural characterizations may be used to identify previously unknown properties of a subject molecule.

    Abstract translation: 在本发明的某些实施例中，可以使用不同的成像技术（例如扫描探针显微镜的不同方式）捕获一个或多个受试者的多个图像。 可以使用已知分子结构的一个或多个模型从多个图像估计参数以提供基于模型的分析。 估计的参数可以与已知分子结构的物理模型的进一步输入融合。 融合参数可用于表征受试者。 这种表征可以包括具体分子结构的检测和/或鉴定，例如已知序列和/或结构的蛋白质，肽和/或核酸。 在本发明的一些实施方案中，结构表征可用于鉴定受试者分子的先前未知的性质。

    DETECTING MOLECULAR BINDING BY MONITORING FEEDBACK CONTROLLED CANTILEVER DEFLECTIONS
    4.
    发明申请
    DETECTING MOLECULAR BINDING BY MONITORING FEEDBACK CONTROLLED CANTILEVER DEFLECTIONS 审中-公开

    公开(公告)号：WO2004029625A3

    公开(公告)日：2004-04-08

    申请号：PCT/US2003/030192

    申请日：2003-09-24

    Applicant: INTEL CORPORATION

    Inventor： SU, Xing ,  CHAN, Selena ,  KOO, Tae-Woong ,  YAMAKAWA, Mineo ,  BERLIN, Andrew

    IPC: G01N33/543

    Abstract: The present methods and apparatus concern the detection and/or identification of target analytes using probe molecules. In various embodiments of the invention, the probes or analytes are attached to one or more cantilevers. Binding of a probe to an analyte results in deflection of the cantilever, detected by a detection unit. A counterbalancing force may be applied to restore the cantilever to its original position. The counterbalancing force may be magnetic, electrical or radiative. The detection unit and the mechanism generating the counterbalancing force may be operably coupled to an information processing and control unit, such as a computer. The computer may regulate a feedback loop that maintains the cantilever in a fixed position by balancing the deflecting force and the counterbalancing force. The concentration of analytes in a sample may be determined from the magnitude of the counterbalancing force required to maintain the cantilever in a fixed position.

    SENSOR ARRAY INTEGRATED CIRCUITS
    5.
    发明申请
    SENSOR ARRAY INTEGRATED CIRCUITS 审中-公开
    传感器阵列集成电路

    公开(公告)号：WO2005095963A2

    公开(公告)日：2005-10-13

    申请号：PCT/US2005/010401

    申请日：2005-03-25

    Applicant: INTEL CORPORATION ,  DUBIN, Valery ,  DAVID, Ken ,  BERLIN, Andrew

    Inventor： DUBIN, Valery ,  DAVID, Ken ,  BERLIN, Andrew

    IPC: G01N33/53

    CPC classification number: B82Y30/00 ,  G01J3/02

    Abstract: An apparatus includes a condensed array addressed device; and a spectroscope optically coupled to the condensed array addressed device. A method includes determining bonding and/or lack-of-bonding of a target molecule to a condensed array addressed device by characterizing a subsequent rate of electrolysis on the condensed array addressed device. A method includes fabricating a condensed array addressed device using damascene patterning.

    Abstract translation: 一种装置包括一个聚光阵列寻址装置; 以及光学耦合到聚光阵列寻址装置的分光镜。 一种方法包括通过表征冷凝阵列寻址装置上随后的电解速率来确定目标分子与冷凝阵列寻址装置的结合和/或缺少键合。 一种方法包括使用镶嵌图案来制造聚光阵列寻址装置。

    A METHODS AND DEVICE FOR USING RAMAN-ACTIVE PROBE CONSTRUCTS TO ASSAY BIOLOGICAL SAMPLES
    7.
    发明申请
    A METHODS AND DEVICE FOR USING RAMAN-ACTIVE PROBE CONSTRUCTS TO ASSAY BIOLOGICAL SAMPLES 审中-公开
    一种使用拉曼活动探针构造来测定生物样品的方法和装置

    公开(公告)号：WO2005066373A1

    公开(公告)日：2005-07-21

    申请号：PCT/US2004/044091

    申请日：2004-12-28

    Applicant: INTEL CORPORATION ,  BERLIN, Andrew ,  SU, Xing ,  CHAN, Selena ,  KOO, Tae-Woong ,  SUN, Lei

    Inventor： BERLIN, Andrew ,  SU, Xing ,  CHAN, Selena ,  KOO, Tae-Woong ,  SUN, Lei

    IPC: C12Q1/68

    CPC classification number: G01N21/658 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y20/00 ,  C12Q1/6816 ,  C12Q1/6834 ,  G01N33/543 ,  G01N33/68 ,  G01N33/6818 ,  G01N2021/653 ,  G01N2021/655 ,  G01N2021/656 ,  C12Q2565/125 ,  C12Q2565/632

    Abstract: Various methods of using Raman-active or SERS-active probe constructs to detect analytes in biological samples, such as the protein-containing analytes in a body fluid are provided. The probe moieties in the Raman-active constructs are selected to bind to and identify specific known analytes in the biological sample or the probe moieties are designed to chemically interact with functional groups commonly found in certain amino acids so that the invention methods provide information about the amino acid composition of protein-containing analytes or fragments in the samples. In some cases, the Raman­active or SERS-active probe constructs, when used in the invention methods, can identify particular protein-containing analytes or types of such analytes so that a protein profile of a patient sample can be made. When compared to a data base of Raman or SERS spectra of normal samples, a disease state of a patient can be identified using the methods disclosed.

    Abstract translation: 提供了使用拉曼活性或SERS-活性探针构建体检测生物样品中的分析物的各种方法，例如体液中含蛋白质的分析物。 选择拉曼活性构建体中的探针部分以结合并识别生物样品中的特定已知分析物，或者将探针部分设计为与通常在某些氨基酸中发现的官能团进行化学相互作用，使得本发明方法提供关于 样品中含蛋白质的分析物或片段的氨基酸组成。 在一些情况下，当在本发明方法中使用时，拉曼活性或SERS-活性探针构建体可以鉴定特定的含蛋白质的分析物或这种分析物的类型，使得可以制备患者样品的蛋白质谱。 当与正常样品的拉曼或SERS光谱的数据库相比时，可以使用所公开的方法鉴定患者的疾病状态。

    METAL COATED NANOCRYSTALLINE SILICON AS AN ACTIVE SURFACE ENHANCED RAMAN SPECTROSCOPY (SERS) SUBSTRATE
    8.
    发明申请
    METAL COATED NANOCRYSTALLINE SILICON AS AN ACTIVE SURFACE ENHANCED RAMAN SPECTROSCOPY (SERS) SUBSTRATE 审中-公开
    金属涂层纳米晶硅作为活性表面增强拉曼光谱（SERS）基板

    公开(公告)号：WO2004074790A1

    公开(公告)日：2004-09-02

    申请号：PCT/US2003/031784

    申请日：2003-10-07

    Applicant: INTEL CORPORATION

    Inventor： CHAN, Selena ,  BERLIN, Andrew ,  KWON, Sunghoon ,  SUNDARARAJAN, Narayan ,  YAMAKAWA, Mineo

    IPC: G01J3/44

    CPC classification number: G01N21/658 ,  B01D67/0062 ,  B01D67/0086 ,  B01D67/0088 ,  B01D71/02 ,  B82Y15/00 ,  B82Y30/00 ,  C12Q1/6825 ,  G01J3/44 ,  G01N21/65 ,  G01N2021/6439 ,  G01N2021/655 ,  G01N2021/656 ,  C12Q2565/632 ,  C12Q2563/155

    Abstract: The disclosed methods and apparatus concern Raman spectroscopy using metal coated nanocrystalline porous silicon substrates. Porous silicon substrates may be formed by anodic etching in dilute hydrofluoric acid. A thin coating of a Raman active metal, such as gold or silver, may be coated onto the porous silicon by cathodic electromigration or any known technique. In certain alternatives, the metal coated porous silicon substrate comprises a plasma-oxidized, dip and decomposed porous silicon substrate. The metalcoated substrate provides an extensive, metal rich environment for SERS, SERBS, hyperRaman and/or CARS Raman spectroscopy. In certain alternatives, metal nanoparticles may be added to the metal-coated substrate to further enhance the Raman signals. Raman spectroscopy may be used to detect, identify and/or quantify a wide variety of analytes, using the disclosed methods and apparatus. In some disclosed methods, Raman spectroscopy may be used to detect nucleotides, purines or pyrimidines at the single molecule level.

    Abstract translation: 所公开的方法和装置涉及使用金属涂覆的纳米晶体多孔硅衬底的拉曼光谱。 多孔硅衬底可以通过在稀氢氟酸中的阳极蚀刻形成。 拉曼活性金属如金或银的薄涂层可以通过阴极电迁移或任何已知技术涂覆在多孔硅上。 在某些替代方案中，金属涂覆的多孔硅衬底包括等离子体氧化的，浸渍和分解的多孔硅衬底。 金属涂层底物为SERS，SERBS，超拉曼和/或CARS拉曼光谱提供了广泛的金属丰富的环境。 在某些替代方案中，可以将金属纳米颗粒加入到金属涂覆的基底中以进一步增强拉曼信号。 使用所公开的方法和装置，可以使用拉曼光谱来检测，鉴定和/或定量各种分析物。 在一些公开的方法中，可以使用拉曼光谱法在单一分子水平检测核苷酸，嘌呤或嘧啶。

    METHODS TO INCREASE NUCLEOTIDE SIGNALS BY RAMAN SCATTERING
    9.
    发明申请
    METHODS TO INCREASE NUCLEOTIDE SIGNALS BY RAMAN SCATTERING 审中-公开

    公开(公告)号：WO2003078649A3

    公开(公告)日：2003-09-25

    申请号：PCT/US2003/007641

    申请日：2003-03-11

    Applicant: INTEL CORPORATION

    Inventor： SU, Xing ,  BERLIN, Andrew ,  KOO, Tae-Woong ,  CHAN, Selena ,  SUNDARARAJAN, Narayan ,  YAMAKAWA, Mineo

    IPC: C12Q1/68

    Abstract: 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.

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