公开(公告)号：US20070155022A1

公开(公告)日：2007-07-05

申请号：US11325833

申请日：2005-12-30

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

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

IPC分类号： G01N33/543 ,  C12M1/34

CPC分类号： G01N33/54373 ,  G01N21/658

摘要： 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.

摘要翻译： 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：US20060134714A1

公开(公告)日：2006-06-22

申请号：US11202862

申请日：2005-08-11

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

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

IPC分类号： C12Q1/48 ,  C12Q1/34

CPC分类号： G01N33/6851 ,  G01N21/658 ,  G01N33/54373 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6848 ,  Y02A90/26

摘要： 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.

摘要翻译： 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：US20050221333A1

公开(公告)日：2005-10-06

申请号：US10815264

申请日：2004-03-31

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

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

IPC分类号： C12Q1/68

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

摘要： 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.

摘要翻译： 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。

公开(公告)号：US07776547B2

公开(公告)日：2010-08-17

申请号：US11027470

申请日：2004-12-30

申请人： Mark Roth ,  Andrew Berlin ,  Selena Chan ,  Tae-Woong Koo ,  Xing Su ,  Lei Sun

发明人： Mark Roth ,  Andrew Berlin ,  Selena Chan ,  Tae-Woong Koo ,  Xing Su ,  Lei Sun

IPC分类号： G01N33/53

CPC分类号： G01N33/54366 ,  G01N33/54373 ,  G01N33/58 ,  Y10T436/10

摘要： Methods and apparatus are provided for assaying cell samples, which may be living cells, using probes labeled with composite organic-inorganic nanoparticles (COINs) and microspheres with COINs embedded within a polymer matrix to which the probe moiety is attached. COINs intrinsically produce SERS signals upon laser irradiation, making COIN-labeled probes particularly suitable in a variety of methods for assaying cells, including biological molecules that may be contained on or within cells, most of which are not inherently Raman-active. The invention provides variations of the sandwich immunoassay employing both specific and degenerate binding, methods for reverse phase assay of tissue samples and cell microstructures, in solution displacement and competition assays, and the like. Systems and chips useful for practicing the invention assays are also provided.

摘要翻译： 提供了用于使用用复合有机 - 无机纳米颗粒（COIN）标记的探针和嵌入探针部分所连接的聚合物基质内的COIN的微球来测定可能为活细胞的细胞样品的方法和装置。 COIN在激光照射下固有地产生SERS信号，使得COIN标记的探针特别适用于多种测定细胞的方法，包括可能包含在细胞内或细胞内的生物分子，其中大部分不是固有的拉曼活性的。 本发明提供使用特异性和简并结合的夹心免疫测定的变体，组织样品和细胞微结构的反相测定方法，溶液置换和竞争测定等。 还提供了用于实施本发明测定的系统和芯片。

公开(公告)号：US20060009914A1

公开(公告)日：2006-01-12

申请号：US10919699

申请日：2004-08-16

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

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

IPC分类号： G06F19/00 ,  G01N33/48

CPC分类号： G01N33/6842 ,  G01N33/6803 ,  G01N33/6818 ,  Y02A90/26

摘要： Embodiments of the present invention provide devices and methods for detecting, identifying, distinguishing, and quantifying modifications to nucleic acids, proteins, and peptides using SERS and Raman spectroscopy. Applications of embodiments of the present invention include proteome wide modification profiling and analyses with applications in disease diagnosis, prognosis and drug efficacy studies, enzymatic activity profiling and assays.

摘要翻译： 本发明的实施方案提供用于使用SERS和拉曼光谱检测，鉴定，区分和定量对核酸，蛋白质和肽的修饰的装置和方法。 本发明实施方案的应用包括在疾病诊断，预后和药物功效研究，酶活性分析和测定中的应用的蛋白质组广泛修饰分析和分析。

公开(公告)号：US20060046313A1

公开(公告)日：2006-03-02

申请号：US11027470

申请日：2004-12-30

申请人： Mark Roth ,  Tae-Woong Koo ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Lei Sun

发明人： Mark Roth ,  Tae-Woong Koo ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Lei Sun

IPC分类号： G01N33/543

CPC分类号： G01N33/54366 ,  G01N33/54373 ,  G01N33/58 ,  Y10T436/10

摘要： Methods and apparatus are provided for assaying cell samples, which may be living cells, using probes labeled with composite organic-inorganic nanoparticles (COINs) and microspheres with COINs embedded within a polymer matrix to which the probe moiety is attached. COINs intrinsically produce SERS signals upon laser irradiation, making COIN-labeled probes particularly suitable in a variety of methods for assaying cells, including biological molecules that may be contained on or within cells, most of which are not inherently Raman-active. The invention provides variations of the sandwich immunoassay employing both specific and degenerate binding, methods for reverse phase assay of tissue samples and cell microstructures, in solution displacement and competition assays, and the like. Systems and chips useful for practicing the invention assays are also provided.

摘要翻译： 提供了用于使用用复合有机 - 无机纳米颗粒（COIN）标记的探针和嵌入探针部分所连接的聚合物基质内的COIN的微球来测定可能为活细胞的细胞样品的方法和装置。 COIN在激光照射下固有地产生SERS信号，使得COIN标记的探针特别适用于多种测定细胞的方法，包括可能包含在细胞内或细胞内的生物分子，其中大部分不是固有的拉曼活性的。 本发明提供使用特异性和简并结合的夹心免疫测定的变体，组织样品和细胞微结构的反相测定方法，溶液置换和竞争测定等。 还提供了用于实施本发明测定的系统和芯片。

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。

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。

公开(公告)号：US20050202468A1

公开(公告)日：2005-09-15

申请号：US11020776

申请日：2004-12-23

申请人： Tae-Woong Koo ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Narayanan Sundararajan ,  Lei Sun

发明人： Tae-Woong Koo ,  Andrew Berlin ,  Selena Chan ,  Xing Su ,  Narayanan Sundararajan ,  Lei Sun

IPC分类号： C12Q1/68 ,  G01N21/65

CPC分类号： G01N21/658 ,  C12Q1/6869 ,  C12Q2565/632 ,  C12Q2533/101

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) or surface enhanced coherent anti-Stokes Raman spectroscopy (SECARS). 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. Methods for enhancing the SERS signal of a nucleotide or nucleoside by cleaving the base from a sugar moiety are provided. Furthermore, methods for detecting single base repeats are provided.

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）或表面增强相干抗斯托克斯拉曼光谱（SECARS）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。 提供了通过从糖部分切割碱来增强核苷酸或核苷的SERS信号的方法。 此外，提供了用于检测单碱基重复的方法。

公开(公告)号：US20050148100A1

公开(公告)日：2005-07-07

申请号：US10750301

申请日：2003-12-30

申请人： Xing Su ,  Andrew Berlin ,  Tae-Woong Koo ,  Selena Chan ,  Lei Sun

发明人： Xing Su ,  Andrew Berlin ,  Tae-Woong Koo ,  Selena Chan ,  Lei Sun

IPC分类号： C12Q1/68 ,  G01J3/44 ,  G01N21/55 ,  G01N21/65 ,  G01N33/543 ,  G01N33/553 ,  G01N33/68 ,  G01N33/53

CPC分类号： 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

摘要： 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 Raman-active 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.

摘要翻译： 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，当用于本发明方法时，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类型的这种分析物，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。