公开(公告)号：US20070059733A1

公开(公告)日：2007-03-15

申请号：US11445884

申请日：2006-06-02

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

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

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

CPC分类号： C12Q1/6825 ,  B82Y5/00 ,  B82Y15/00 ,  B82Y30/00 ,  C12Q1/6869 ,  C12Q2563/155 ,  C12Q2565/607

摘要： 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.

摘要翻译： 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：US07291466B2

公开(公告)日：2007-11-06

申请号：US11111308

申请日：2005-04-20

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

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

IPC分类号： C12Q1/68

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悬臂的偏转，由检测单元检测。 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：US20060029969A1

公开(公告)日：2006-02-09

申请号：US11235796

申请日：2005-09-26

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

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

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6869 ,  C12Q1/6816 ,  C12Q1/6825 ,  C12Q1/6872 ,  C12Q2565/632 ,  C12Q2563/155 ,  C12Q2521/319

摘要： 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 (SERFS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus 10, 100, 210 for nucleic acid sequencing.

摘要翻译： 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，核苷酸在掺入核酸13之前共价连接到拉曼标记上。 标记核酸13的核酸外切酶15处理导致通过拉曼光谱法检测的标记核苷酸16,130的释放。 在本发明的替代实施方案中，通过核酸外切酶15处理从核酸13释放的核苷酸16,130与银或金纳米颗粒140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（SERFS ）和/或相干的反斯托克斯拉曼光谱（CARS）。 本发明的其它实施方案涉及用于核酸测序的装置10,100,210。

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：US20050026163A1

公开(公告)日：2005-02-03

申请号：US10705389

申请日：2003-11-10

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

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

IPC分类号： G01N33/483 ,  C12M1/00 ,  C12M1/34 ,  C12N15/09 ,  C12Q1/68 ,  G01N27/06 ,  G01N33/53 ,  C12P19/34

CPC分类号： C12Q1/6825 ,  B82Y5/00 ,  B82Y15/00 ,  B82Y30/00 ,  C12Q1/6869 ,  C12Q2563/155 ,  C12Q2565/607

摘要： 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.

摘要翻译： 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：US20060234248A1

公开(公告)日：2006-10-19

申请号：US11081772

申请日：2005-03-15

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

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

IPC分类号： C12Q1/68 ,  G01N33/53

CPC分类号： G01N21/658 ,  B82Y30/00 ,  G01N2021/653 ,  G01N2021/655 ,  G01N2021/656

摘要： 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.

摘要翻译： 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：US20090169466A1

公开(公告)日：2009-07-02

申请号：US11344712

申请日：2006-01-31

申请人： Mineo Yamakawa ,  Yuegang Zhang ,  Xing Su ,  Lei Sun ,  Andrew A. Berlin ,  Narayanan Sundararajan

发明人： Mineo Yamakawa ,  Yuegang Zhang ,  Xing Su ,  Lei Sun ,  Andrew A. Berlin ,  Narayanan Sundararajan

IPC分类号： D01F9/12 ,  C07H21/04

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.

公开(公告)号：US20080076119A9

公开(公告)日：2008-03-27

申请号：US11081772

申请日：2005-03-15

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

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

IPC分类号： C12Q1/68 ,  G01N33/53

CPC分类号： G01N21/658 ,  B82Y30/00 ,  G01N2021/653 ,  G01N2021/655 ,  G01N2021/656

摘要： 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.

摘要翻译： 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：US20090170725A1

公开(公告)日：2009-07-02

申请号：US11344713

申请日：2006-01-31

申请人： Mineo Yamakawa ,  Yuegang Zhang ,  Xing Su ,  Lei Sun ,  Andrew A. Berlin ,  Narayanan Sundararajan

发明人： Mineo Yamakawa ,  Yuegang Zhang ,  Xing Su ,  Lei Sun ,  Andrew A. Berlin ,  Narayanan Sundararajan

IPC分类号： C40B40/08 ,  B82B1/00

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。

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。