公开(公告)号：US07351591B2

公开(公告)日：2008-04-01

申请号：US10814695

申请日：2004-03-30

Applicant: Tae-Woong Koo ,  Selena Chan ,  Xing Su ,  Jingwu Zhang ,  Lei Sun

Inventor： Tae-Woong Koo ,  Selena Chan ,  Xing Su ,  Jingwu Zhang ,  Lei Sun

IPC: G01N33/553

CPC classification number: G01N21/658

Abstract: The present invention is based on the discovery that the methods described herein for the production of metallic colloids result in colloids exhibiting increased signal enhancement and reproducibility for the SERS detection of biomolecules. Thus, using the methods of the invention, a wide variety of biomolecules can be detected with a greater sensitivity and reliability.

公开(公告)号：US20080076119A9

公开(公告)日：2008-03-27

申请号：US11081772

申请日：2005-03-15

Applicant: Lei Sun ,  Xing Su ,  Mineo Yamakawa ,  Zhang Jingwu ,  Narayan Sundararajan

Inventor： Lei Sun ,  Xing Su ,  Mineo Yamakawa ,  Zhang Jingwu ,  Narayan Sundararajan

IPC: C12Q1/68 ,  G01N33/53

CPC classification number: G01N21/658 ,  B82Y30/00 ,  G01N2021/653 ,  G01N2021/655 ,  G01N2021/656

Abstract: Metallic nanoclusters capable of providing an enhanced Raman signal from an organic Raman-active molecule incorporated therein are provided. The nanoclusters may be further functionalized, for example, with coatings and layers, such as adsorption layers, metal coatings, silica coatings, probes, and organic layers. The nanoclusters are generally referred to as COINs (composite organic inorganic nanoparticles) and are capable of acting as sensitive reporters for analyte detection. A variety of organic Raman-active compounds and mixtures of compounds can be incorporated into the nanocluster.

Abstract translation: 提供能够从其中并入的有机拉曼活性分子提供增强的拉曼信号的金属纳米团簇。 纳米团簇可以进一步官能化，例如具有涂层和层，例如吸附层，金属涂层，二氧化硅涂层，探针和有机层。 纳米团簇通常被称为COIN（复合有机无机纳米粒子），并且能够作为敏感的报告物进行分析物检测。 可以将多种有机拉曼活性化合物和化合物的混合物掺入纳米团簇中。

公开(公告)号：US20070231795A1

公开(公告)日：2007-10-04

申请号：US11233933

申请日：2005-09-22

Applicant: Xing Su

Inventor： Xing Su

IPC: C12Q1/68 ,  G06F19/00

CPC classification number: C12Q1/6869 ,  B82Y5/00 ,  Y10S977/853 ,  C12Q2565/631

Abstract: The methods and apparatus 100 disclosed herein concern DNA sequencing. In some embodiments of the invention, the methods comprise measuring the distance between labeled nucleotides 220, such as nucleotides labeled with bulky groups. The methods may further comprise placing identical template DNA 200 into four reaction chambers 110, 120, 130, 140, each containing a different labeled nucleotide precursor, synthesizing complementary strands 230, 240, 250 and detecting labeled nucleotides 220. The distances between labeled nucleotides 220 may be used to construct 450 distance maps 310, 320, 330, 340 for each type of labeled nucleotide 220. The distance maps 310, 320, 330, 340 may be aligned 520 to obtain a nucleic acid sequence 210. Overlapping data analysis and frequency analysis may be used to construct 450 the distance maps 310, 320, 330, 340 and non-overlapping data analysis may be used to align 520 the distance maps into a sequence 210.

Abstract translation: 本文公开的方法和装置100涉及DNA测序。 在本发明的一些实施方案中，所述方法包括测量标记的核苷酸220之间的距离，例如用大体积标记的核苷酸。 所述方法可以进一步包括将相同的模板DNA 200置于四个反应室110,120,130,140中，每个反应室含有不同的标记的核苷酸前体，合成互补链230,240,250和检测标记的核苷酸220。 标记的核苷酸220之间的距离可用于为每种类型的标记核苷酸220构建450个距离图310,320,330,340。 距离图310,320,330,340可以对齐520以获得核酸序列210。 可以使用重叠数据分析和频率分析来构造距离映射310,320,330,340，并且可以使用不重叠的数据分析来将距离图对准520到序列210中。

公开(公告)号：US20070155022A1

公开(公告)日：2007-07-05

申请号：US11325833

申请日：2005-12-30

Applicant: Mineo Yamakawa ,  Narayan Sundararajan ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Tae-Woong Koo ,  Lei Sun ,  Kung-Bin Sung ,  Mark Roth

Inventor： Mineo Yamakawa ,  Narayan Sundararajan ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Tae-Woong Koo ,  Lei Sun ,  Kung-Bin Sung ,  Mark Roth

IPC: G01N33/543 ,  C12M1/34

CPC classification number: G01N33/54373 ,  G01N21/658

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US07238477B2

公开(公告)日：2007-07-03

申请号：US10660902

申请日：2003-09-12

Applicant: Xing Su ,  Andrew A. Berlin ,  Selena Chan ,  Steven J. Kirch ,  Tac-Woong Koo ,  Gabi Neubauer ,  Valluri Rao ,  Narayanan Sundararajan ,  Mineo Yamakawa

Inventor： Xing Su ,  Andrew A. Berlin ,  Selena Chan ,  Steven J. Kirch ,  Tac-Woong Koo ,  Gabi Neubauer ,  Valluri Rao ,  Narayanan Sundararajan ,  Mineo Yamakawa

IPC: C12Q1/68 ,  C12P19/34 ,  C07H21/02 ,  G01N21/63

CPC classification number: C12Q1/6869 ,  C12Q2565/632 ,  C12Q2563/155 ,  C12Q2521/319

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. 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.

Abstract translation: 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。

公开(公告)号：US07192703B2

公开(公告)日：2007-03-20

申请号：US10367071

申请日：2003-02-14

Applicant: Lei Sun ,  Xing Su

Inventor： Lei Sun ,  Xing Su

IPC: C12Q1/68 ,  C12P19/34

CPC classification number: C12Q1/6804 ,  C12Q1/6816 ,  C12Q1/682 ,  G01N21/658 ,  C12Q2565/632 ,  C12Q2565/518 ,  C12Q2531/125 ,  C12Q2563/179

Abstract: The present methods, compositions and systems are concerned with biomolecule 130 detection, identification and/or quantification by rolling circle amplification (RCA) and Raman detection. In particular embodiments of the invention, the RCA is exponential RCA or linear RCA. In some embodiments of the invention, the Raman detection is SERS or SERRS. The circular DNA template 150, 210, 310 to be amplified may comprise one or more polythymidine 320 residues, resulting in amplification products 170, 230, 250, 330, 410 containing multiple polyadenylate 340, 420 residues. The polyadenylates 340, 420 may be directly detected by Raman detection. Alternatively, one or more Raman labels may be incorporated into the amplification products 170, 230, 250, 330, 410 to facilitate Raman detection. Because of the amplification produced by LRCA or ERCA and the enhanced Raman signal produced by multiple polyadenylates 340, 420 and/or Raman labels, detection of single copy biomolecules 130 is feasible using the disclosed methods, compositions and/or systems.

Abstract translation: 本方法，组合物和系统涉及通过滚环扩增（RCA）和拉曼检测的生物分子130检测，鉴定和/或定量。 在本发明的特定实施例中，RCA是指数RCA或线性RCA。 在本发明的一些实施方案中，拉曼检测是SERS或SERRS。 要扩增的环状DNA模板150,210,310可以包含一个或多个多胸苷320残基，导致扩增产物170,230,250,330,410含有多个聚腺苷酸340,420个残基。 多聚腺苷酸酯340,420可以通过拉曼检测直接检测。 或者，可以将一个或多个拉曼标记掺入扩增产物170,230,250,330,410以促进拉曼检测。 由于由LRCA或ERCA产生的扩增和由多个多腺苷酸340,420和/或拉曼标记产生的增强的拉曼信号，使用所公开的方法，组合物和/或系统检测单拷贝生物分子130是可行的。

公开(公告)号：US20070059733A1

公开(公告)日：2007-03-15

申请号：US11445884

申请日：2006-06-02

Applicant: Narayanan Sundararajan ,  Andrew Berlin ,  Mineo Yamakawa ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo

Inventor： Narayanan Sundararajan ,  Andrew Berlin ,  Mineo Yamakawa ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo

IPC: C12Q1/68 ,  G06F19/00 ,  C12M3/00

CPC classification number: C12Q1/6825 ,  B82Y5/00 ,  B82Y15/00 ,  B82Y30/00 ,  C12Q1/6869 ,  C12Q2563/155 ,  C12Q2565/607

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20060134714A1

公开(公告)日：2006-06-22

申请号：US11202862

申请日：2005-08-11

Applicant: Narayan Sundararajan ,  Lei Sun ,  Xing Su ,  Mineo Yamakawa ,  Zhang Jingwu ,  Selena Chan ,  Andrew Berlin ,  Tae-Woong Koo ,  Mark Roth ,  Phil Gafken

Inventor： Narayan Sundararajan ,  Lei Sun ,  Xing Su ,  Mineo Yamakawa ,  Zhang Jingwu ,  Selena Chan ,  Andrew Berlin ,  Tae-Woong Koo ,  Mark Roth ,  Phil Gafken

IPC: C12Q1/48 ,  C12Q1/34

CPC classification number: G01N33/6851 ,  G01N21/658 ,  G01N33/54373 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6848 ,  Y02A90/26

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20060068440A1

公开(公告)日：2006-03-30

申请号：US11270211

申请日：2005-11-08

Applicant: Selena Chan ,  Xing Su

Inventor： Selena Chan ,  Xing Su

IPC: C12Q1/68

CPC classification number: C12Q1/6869 ,  B01L3/5027 ,  G01N21/65 ,  G01N21/658 ,  G01N2021/653 ,  G01N2021/656 ,  C12Q2565/632 ,  C12Q2521/319 ,  C12Q2563/155 ,  C12Q2565/629

Abstract: The methods and apparatus disclosed herein concern nucleic acid characterization by enhanced Raman spectroscopy. In certain embodiments of the invention, exonuclease treatment of the nucleic acids results in the release of nucleotides. The nucleotides may pass from a reaction chamber through a microfluidic channel and enter a nanochannel or microchannel. The nanochannel or microchannel may be packed with nanoparticle aggregates containing hot spots for Raman detection. As the nucleotides pass through the nanoparticle hot spots, they may be detected by Raman spectroscopy. Identification of the sequence of nucleotides released from the nucleic acid is used to characterize the nucleic acid, for example by sequencing or identifying the nucleic acid. Other embodiments of the invention concern apparatus for nucleic acid sequencing.

Abstract translation: 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表征。 在本发明的某些实施方案中，核酸外切核酸酶处理导致核苷酸的释放。 核苷酸可以从反应室通过微流体通道并进入纳米通道或微通道。 纳米通道或微通道可以填充含有用于拉曼检测的热点的纳米颗粒聚集体。 当核苷酸通过纳米颗粒热点时，它们可以通过拉曼光谱法检测。 使用从核酸释放的核苷酸序列的鉴定来表征核酸，例如通过测序或鉴定核酸。 本发明的其它实施方案涉及用于核酸测序的装置。

公开(公告)号：US20050221333A1

公开(公告)日：2005-10-06

申请号：US10815264

申请日：2004-03-31

Applicant: Narayanan Sundararajan ,  Lei Sun ,  Yuegang Zhang ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Andrew Berlin

Inventor： Narayanan Sundararajan ,  Lei Sun ,  Yuegang Zhang ,  Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Andrew Berlin

IPC: C12Q1/68

CPC classification number: C12Q1/6827 ,  C12Q1/6869 ,  G01N21/658 ,  Y10T436/11 ,  Y10T436/117497 ,  Y10T436/143333 ,  C12Q2565/629 ,  C12Q2521/319 ,  C12Q2565/632 ,  C12Q2565/619

Abstract: Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

Abstract translation: 本文公开了用于在微流体通道中进行核酸测序反应和分子结合反应的方法，装置和系统。 方法，装置和系统可以包括限制核酸附着的颗粒运动的限制障碍。 此外，方法，装置和系统可以包括输送流的流体动力聚焦。 此外，方法，装置和系统可以通过在表面和输送流之间提供保护流来减少与微流体通道的表面的非特异性相互作用。