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1. 发明授权

US07105301B2 Detecting molecular binding by monitoring feedback controlled cantilever deflections 失效
标题翻译：通过监测反馈控制的悬臂偏转来检测分子结合
公开(公告)号：US07105301B2
公开(公告)日：2006-09-12
申请号：US10667776
申请日：2003-09-22
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 , C12Q1/70 , G01N33/566 , G01N33/563
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。

2. 发明授权

US07270952B2 Detecting molecular binding by monitoring feedback controlled cantilever deflections 有权
公开(公告)号：US07270952B2
公开(公告)日：2007-09-18
申请号：US10254201
申请日：2002-09-24
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.

3. 发明授权

US06972173B2 Methods to increase nucleotide signals by raman scattering 有权
标题翻译：通过拉曼散射增加核苷酸信号的方法
公开(公告)号：US06972173B2
公开(公告)日：2005-12-06
申请号：US10099287
申请日：2002-03-14
申请人： Xing Su , Selena Chan , Andrew A. Berlin , Tae-Woong Koo , Narayan Sundararajan , Mineo Yamakawa
发明人： Xing Su , Selena Chan , Andrew A. Berlin , Tae-Woong Koo , Narayan Sundararajan , Mineo Yamakawa
IPC分类号： G01N21/65 , B01L3/00 , C12M1/00 , C12Q1/68 , G01N33/543 , C07H21/02 , C12P19/34
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 (SERRS) 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共价交联到银或金纳米颗粒140上，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。

4. 发明授权

US07291466B2 Detecting molecular binding by monitoring feedback controlled cantilever deflections 有权
标题翻译：通过监测反馈控制的悬臂偏转来检测分子结合
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。

5. 发明申请

US20060199193A1 Sensor arrays and nucleic acid sequencing applications 有权
公开(公告)号：US20060199193A1
公开(公告)日：2006-09-07
申请号：US11226696
申请日：2005-09-13
申请人： Tae-Woong Koo , Selena Chan , Xing Su , Zhang Jingwu , Mineo Yamakawa , Val Dubin
发明人： Tae-Woong Koo , Selena Chan , Xing Su , Zhang Jingwu , Mineo Yamakawa , Val Dubin
IPC分类号： C12Q1/68 , C12M1/34
CPC分类号： C12Q1/6874 , B01J2219/00317 , B01J2219/00511 , B01J2219/00605 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00641 , B01J2219/00722 , B01L3/5085 , B82Y30/00 , C12Q1/6869 , G01N27/414 , G01N27/4145 , G01N27/4148
摘要： Embodiments of the present invention provide devices methods for sequencing DNA using arrays of reaction cavities containing sensors to monitor changes in solutions contained in the reaction cavities. Additional embodiments provide devices and methods for sequencing DNA using arrays of reaction cavities that allow for optical monitoring of solutions in the reaction cavities. Test and fill reaction schemes are disclosed that allow DNA to be sequenced. By sequencing DNA using parallel reactions contained in large arrays, DNA can be rapidly sequenced.

6. 发明授权

US09040237B2 Sensor arrays and nucleic acid sequencing applications 有权
标题翻译：传感器阵列和核酸测序应用
公开(公告)号：US09040237B2
公开(公告)日：2015-05-26
申请号：US11226696
申请日：2005-09-13
申请人： Tae-Woong Koo , Selena Chan , Xing Su , Zhang Jingwu , Mineo Yamakawa , Val M. Dubin
发明人： Tae-Woong Koo , Selena Chan , Xing Su , Zhang Jingwu , Mineo Yamakawa , Val M. Dubin
IPC分类号： C12Q1/68 , C12M1/00 , C12M3/00 , C12M1/34 , B82Y30/00 , B01L3/00 , G01N27/414
CPC分类号： C12Q1/6874 , B01J2219/00317 , B01J2219/00511 , B01J2219/00605 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00641 , B01J2219/00722 , B01L3/5085 , B82Y30/00 , C12Q1/6869 , G01N27/414 , G01N27/4145 , G01N27/4148
摘要： Embodiments of the present invention provide devices methods for sequencing DNA using arrays of reaction cavities containing sensors to monitor changes in solutions contained in the reaction cavities. Additional embodiments provide devices and methods for sequencing DNA using arrays of reaction cavities that allow for optical monitoring of solutions in the reaction cavities. Test and fill reaction schemes are disclosed that allow DNA to be sequenced. By sequencing DNA using parallel reactions contained in large arrays, DNA can be rapidly sequenced.
摘要翻译：本发明的实施方案提供了使用包含传感器的反应腔阵列来测序DNA的装置方法，以监测包含在反应腔中的溶液的变化。另外的实施方案提供了使用允许对反应腔中的溶液进行光学监测的反应腔阵列对DNA进行测序的装置和方法。公开了允许DNA测序的测试和填充反应方案。通过使用大阵列中包含的平行反应测序DNA，可以快速测序DNA。

7. 发明申请

US20070155022A1 Degenerate binding detection and protein identification using Raman spectroscopy nanoparticle labels 审中-公开
标题翻译：使用拉曼光谱纳米颗粒标签的简并结合检测和蛋白质鉴定
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。

8. 发明申请

US20070059733A1 Method for sequencing nucleic acids by observing the uptake of nucleotides modified with bulky groups 审中-公开
标题翻译：通过观察用大体积改性的核苷酸摄取来测序核酸的方法
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。

9. 发明申请

US20060134714A1 Detection and identification of peptide and protein modifications 审中-公开
标题翻译：肽和蛋白质修饰的检测和鉴定
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。

10. 发明申请

US20060029969A1 Methods to increase nucleotide signals by Raman scattering 审中-公开
标题翻译：通过拉曼散射增加核苷酸信号的方法
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。

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