公开(公告)号：US20070128615A1

公开(公告)日：2007-06-07

申请号：US11414681

申请日：2006-04-28

申请人： Xing Su

发明人： Xing Su

IPC分类号： C12Q1/68 ,  C12M3/00

CPC分类号： C12Q1/6818 ,  C12Q1/6874 ,  C12Q2565/632

摘要： Provided herein, is a nucleic acid sequencing method based on detection of Raman signatures of oligonucleotide probes. Raman signatures of individually captured nucleic acid probes, optionally labeled by a Raman label or a positively charged enhancer, are detected. The sequences of captured probes are used to identify the nucleotide sequences of captured probes and complementary target nucleic acids, which are then aligned and used to obtain nucleic acid sequence information. In another embodiment, a method is provided for determining a nucleotide occurrence at a target nucleotide position of a target nucleic acid, that utilizes binding of the target nucleic acid to a labeled oligonucleotide probe that binds to the target nucleic acid, wherein the labeled oligonucleotide probe includes a first label and a second label, the first label being capable of affecting an optical property of the second label.

公开(公告)号：US20070054288A1

公开(公告)日：2007-03-08

申请号：US11430612

申请日：2006-05-08

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

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

IPC分类号： C12Q1/68 ,  C12M1/34 ,  G06K7/10

CPC分类号： B82Y10/00 ,  B82Y5/00 ,  C12Q1/6816 ,  G06K19/06028 ,  C12Q2525/161 ,  C12Q2537/143 ,  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。 可以通过各种成像方式，例如表面等离子体共振，荧光或拉曼光谱来检测结合条形码。

公开(公告)号：US20070048746A1

公开(公告)日：2007-03-01

申请号：US11216112

申请日：2005-09-01

申请人： Xing Su ,  Lei Sun ,  Mineo Yamakawa ,  Jingwu Zhang ,  Qing Ma ,  Tae-Woong Koo ,  Richard Jones

发明人： Xing Su ,  Lei Sun ,  Mineo Yamakawa ,  Jingwu Zhang ,  Qing Ma ,  Tae-Woong Koo ,  Richard Jones

IPC分类号： C12Q1/68 ,  G01N33/53 ,  C12M1/34

CPC分类号： G01N33/53 ,  B82Y15/00 ,  B82Y30/00 ,  G01N33/54366 ,  G01N33/5438

摘要： Method and device to collect multiplex data simultaneously in analyte detection and analyze the data by experimentally trained software (machine-learning) is disclosed. Various ways (magnetic particles and microcoils) are disclosed to collect multiple reporter (tag) signals. Multiplex detection can increase the biomolecule analysis efficiency by using small sample size and saving assay reagents and time. Machine learning and data analysis schemes are also disclosed. Multiple affinity binding partners, each labeled by a unique reporter, are contacted with a sample and a green spectrum is taken to detect multiple reporter signals. The spectrum is deconvoluted by experimentally trained software to identify multiple analytes.

摘要翻译： 公开了通过实验训练的软件（机器学习）在分析物检测中同时收集多重数据并分析数据的方法和装置。 公开了各种方式（磁性颗粒和微型线圈）以收集多个报道（标签）信号。 多重检测可以通过使用小样本量和节省测定试剂和时间来增加生物分子分析效率。 还披露了机器学习和数据分析方案。 将多个亲和力结合配偶体（各自由唯一报道分子标记）与样品接触，并采用绿色光谱来检测多个报道信号。 通过实验训练的软件对光谱进行去卷积，以识别多个分析物。

公开(公告)号：US20060147941A1

公开(公告)日：2006-07-06

申请号：US11026857

申请日：2004-12-30

申请人： Xing Su

发明人： Xing Su

IPC分类号： C12Q1/68

CPC分类号： B82Y30/00 ,  C12Q1/6874 ,  C12Q2565/632

摘要： SERS technology is used for high throughput screening of biological analytes and samples. For polynucleotide sequencing, sets of oligonucleotide probes are labeled with composite organic-inorganic nanoparticles (COIN) that produce distinguishable SERS signals when excited by a laser. Detection of a hybridization complex containing members of two such COIN-labeled probe sets will reveal a 12 nucleotide sequence segment of the target polynucleotide. Also provided are surface-modified arrays and chips with multiple arrays to which sets of probe-conjugated COIN or other reporter substrates are immobilized. Analytes are detected by contacting a sample, such as a bodily fluid, with the array-anchored probes. Captured analytes are tagged with an additional target-specific Raman-active tag. Two or more Raman signatures emanating from the detection complexes reveal the identity of the captured analytes.

摘要翻译： SERS技术用于生物分析物和样品的高通量筛选。 对于多核苷酸测序，寡核苷酸探针组用复合有机 - 无机纳米粒子（COIN）标记，当由激光激发时产生可区分的SERS信号。 含有两个这样的COIN标记的探针组成员的杂交复合物的检测将显示靶多核苷酸的12个核苷酸序列片段。 还提供了具有多个阵列的表面改性阵列和芯片，固定有探针缀合的COIN或其它报告基质的组。 通过使样品（例如体液）与阵列锚定的探针接触来检测分析物。 捕获的分析物用额外的目标特异性拉曼活性标签进行标记。 从检测复合物中发出的两个或多个拉曼标记揭示了捕获的分析物的身份。

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：US20050260628A1

公开(公告)日：2005-11-24

申请号：US11075121

申请日：2005-03-07

申请人： Hajime Matsuzaki ,  Xing Su ,  Guilia Kennedy

发明人： Hajime Matsuzaki ,  Xing Su ,  Guilia Kennedy

IPC分类号： C12Q1/68 ,  C12P19/34

CPC分类号： C12Q1/6855 ,  C12Q2527/143 ,  C12Q2527/113

摘要： The presently claimed invention provides for novel methods and kits for reducing the complexity of a nucleic acid sample by providing non-gel based methods for size fractionation. In a preferred embodiment, size fractionation can be accomplished by varying conditions or reagents of a PCR reaction to amplify fragments of specific size ranges. The invention further provides for analysis of the above sample by hybridization to an array, which may be specifically designed to interrogate the desired fragments for particular characteristics, such as, for example, the presence or absence of a polymorphism.

摘要翻译： 目前要求保护的发明提供了用于通过提供用于尺寸分级分离的非基于凝胶的方法来降低核酸样品的复杂性的新颖方法和试剂盒。 在优选的实施方案中，大小分级可以通过改变PCR反应的条件或试剂来扩增特定大小范围的片段来实现。 本发明进一步提供了通过与阵列的杂交分析上述样品，所述阵列可被特别设计成询问特定特征的期望片段，例如多态性的存在或不存在。

公开(公告)号：US20050244820A1

公开(公告)日：2005-11-03

申请号：US11111308

申请日：2005-04-20

申请人： Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Mineo Yamakawa ,  Andrew Berlin

发明人： Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Mineo Yamakawa ,  Andrew Berlin

IPC分类号： C12Q1/68 ,  G01N33/543 ,  C12Q1/70 ,  C12Q1/04

CPC分类号： C12Q1/6825 ,  B82Y5/00 ,  G01N33/54373 ,  G01N2800/52 ,  Y10S977/924 ,  C12Q2565/501

摘要： 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.

摘要翻译： 本方法和装置涉及使用探针分子检测和/或鉴定目标分析物。 在本发明的各种实施方案中，探针或分析物附着到一个或多个悬臂。 将探针与分析物结合导致由检测单元检测到的悬臂的偏转。 可以应用平衡力将悬臂恢复到其原始位置。 平衡力可以是磁性的，电的或辐射的。 生成平衡力的检测单元和机构可以可操作地耦合到诸如计算机的信息处理和控制单元。 计算机可以通过平衡偏转力和平衡力来调节将悬臂维持在固定位置的反馈回路。 样品中分析物的浓度可以从将悬臂维持在固定位置所需的平衡力的大小来确定。

公开(公告)号：US20050221506A1

公开(公告)日：2005-10-06

申请号：US10814695

申请日：2004-03-30

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

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

IPC分类号： G01N21/65 ,  G01N33/553

CPC分类号： G01N21/658

摘要： 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：US20050208554A1

公开(公告)日：2005-09-22

申请号：US11077577

申请日：2005-03-11

申请人： Selena Chan ,  Xing Su ,  Mineo Yamakawa

发明人： Selena Chan ,  Xing Su ,  Mineo Yamakawa

IPC分类号： C12M1/34 ,  C12Q1/68 ,  G01N33/48 ,  G01N33/50 ,  G01N33/543 ,  G01N33/573 ,  G01Q60/00 ,  G01Q70/12 ,  G01Q70/18 ,  G01Q80/00 ,  G06F19/00

CPC分类号： C12Q1/6816 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y30/00 ,  Y10S977/702 ,  Y10S977/704 ,  Y10S977/705 ,  Y10S977/728 ,  Y10S977/729 ,  Y10S977/734 ,  Y10S977/742 ,  Y10S977/773 ,  Y10S977/774 ,  Y10S977/924 ,  C12Q2565/601 ,  C12Q2563/185

摘要： 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 nanobarcodes 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 nanobarcodes 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.

摘要翻译： 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，包含连接至一个或多个纳米糖基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对准并通过扫描探针显微镜进行分析。 纳米线可以是通过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，纳米颗粒或量子点。 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。

公开(公告)号：US20050151126A1

公开(公告)日：2005-07-14

申请号：US10750141

申请日：2003-12-31

申请人： Mineo Yamakawa ,  Yeugang Zhang ,  Xing Su ,  Lei Sun ,  Andrew Berlin ,  Narayanan Sundararajan

发明人： Mineo Yamakawa ,  Yeugang Zhang ,  Xing Su ,  Lei Sun ,  Andrew Berlin ,  Narayanan Sundararajan

IPC分类号： C01B31/02 ,  D01F9/127 ,  H01L51/00 ,  H01L51/30 ,  D01F9/12 ,  H01L29/06

CPC分类号： B82Y40/00 ,  B82Y10/00 ,  B82Y30/00 ,  C01B32/162 ,  C01B2202/08 ,  C01B2202/36 ,  D01F9/127 ,  H01L51/0048 ,  H01L51/0052

摘要： 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 can be attached to the substrate in ordered patterns, using self-assembly or molecular 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.

摘要翻译： 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连接到聚合物120,210分子，将聚合物120,210分子连接到基底上的方法形成，除去聚合物120,210分子并产生碳 催化剂纳米颗粒140,230上的纳米管。聚合物120,210分子可以使用自组装或分子对准技术以有序图案附着到基底上。 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。