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1. 发明授权

US09353412B2 Conformational probes and methods for sequencing nucleic acids 有权
标题翻译：构象探针和核酸测序方法
公开(公告)号：US09353412B2
公开(公告)日：2016-05-31
申请号：US13162325
申请日：2011-06-16
申请人： Molly He , Cheng-Yao Chen , Eric Kool , Mostafa Ronaghi , Michael Previte , Rigo Pantoja
发明人： Molly He , Cheng-Yao Chen , Eric Kool , Mostafa Ronaghi , Michael Previte , Rigo Pantoja
IPC分类号： C12P19/34 , C12Q1/68
CPC分类号： C12Q1/6874 , C12Q1/6806 , C12Q1/6818 , C12Q2565/133 , C12Q2563/125 , C12Q2525/101 , C12Q2565/1015
摘要： This disclosure provides a method of determining a sequence of nucleotides for a nucleic acid template. The method can include the steps of contacting the nucleic acid template with a conformationally labeled polymerase and at least four different nucleotide species under conditions wherein the conformationally labeled polymerase catalyzes sequential addition of the nucleotide species to form a nucleic acid complement of the nucleic acid template, wherein the sequential addition of each different nucleotide species produces a conformational signal change from the conformationally labeled polymerase and wherein the rate or time duration for the conformational signal change is distinguishable for each different nucleotide species; detecting a series of changes in the signal from the conformationally labeled polymerase under the conditions; and determining the rates or time durations for the changes in the signal, thereby determining the sequence of nucleotides for the nucleic acid template.
摘要翻译：本公开提供了确定核酸模板的核苷酸序列的方法。该方法可以包括以下步骤：使构象标记的聚合酶和至少四种不同的核苷酸物种在其中所述构象标记的聚合酶催化核苷酸物种的顺序加入以形成核酸模板的核酸补体的条件下接触，其中每个不同核苷酸类型的顺序加入从所述构象标记的聚合酶产生构象信号变化，并且其中所述构象信号变化的速率或持续时间对于每个不同的核苷酸种类是可区分的; 在条件下检测来自构象标记的聚合酶的信号的一系列变化; 并确定信号变化的速率或时间，从而确定核酸模板的核苷酸序列。

2. 发明授权

US08702948B2 Method and apparatus using electric field for improved biological assays 失效
标题翻译：使用电场改进生物测定的方法和装置
公开(公告)号：US08702948B2
公开(公告)日：2014-04-22
申请号：US13618228
申请日：2012-09-14
申请人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
发明人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
IPC分类号： G01N27/26 , B81B1/00
CPC分类号： B01L3/502761 , B01J2219/00317 , B01J2219/00459 , B01J2219/00466 , B01J2219/00596 , B01J2219/00648 , B01J2219/00653 , B01J2219/00702 , B01L2200/0668 , B01L2300/0819 , B01L2400/0415
摘要： Disclosed are a method and apparatus that use an electric field for improved biological assays. The electric field is applied across a device having wells, which receive reactants, which carry a charge. The device thus uses a controllable voltage source between the first and second electrodes, which is controllable to provide a positive charge and a negative charge to a given electrode. By controlled use of the electric field charged species in a fluid in a fluid channel are directed into or out of the well by an electric field between the electrodes. The present method involves the transport of fluids, as in a microfluidic device, and the electric field-induced movement of reactive species according to various assay procedures, such as DNA sequencing, synthesis or the like.
摘要翻译：公开了使用电场进行改进的生物测定的方法和装置。电场被施加在具有井的装置上，该装置具有承载电荷的反应物。因此，该器件在第一和第二电极之间使用可控电压源，其可控制以向给定电极提供正电荷和负电荷。通过控制使用流体通道中的流体中的电场带电物质通过电极之间的电场被引导进入或流出阱。本方法涉及如在微流体装置中的流体的运输，以及根据各种测定程序（例如DNA测序，合成等）的反应物种的电场诱导运动。

3. 发明授权

US08476022B2 Method of making an array of nucleic acid colonies 有权
标题翻译：制作核酸集落阵列的方法
公开(公告)号：US08476022B2
公开(公告)日：2013-07-02
申请号：US13545682
申请日：2012-07-10
申请人： Mostafa Ronaghi , Helmy A. Eltoukhy
发明人： Mostafa Ronaghi , Helmy A. Eltoukhy
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6874 , C12Q1/6837 , C12Q1/6869 , C12Q2535/122 , C12Q2565/543
摘要： A method of making an array of nucleic acid colonies, by (a) providing a substrate having a patterned surface of features, wherein the features are spatially separated from each other on the surface of the substrate; (b) contacting the substrate with a solution of different target nucleic acids to seed a subset of the features that contact the solution, wherein each feature in the subset is seeded with a single nucleic acid from the solution, wherein a plurality of the features that contact the solution are not seeded with a nucleic acid from the solution; (c) amplifying the nucleic acids to form a nucleic acid colony at each of the features in the subset; and (d) repeating steps (b) and (c) to increase the number of the features on the surface that have a nucleic acid colony, thereby making an array of nucleic acid colonies.
摘要翻译：通过（a）提供具有特征图案化表面的基底，制备核酸集落阵列的方法，其中所述特征在所述基底的表面上彼此空间上分离; （b）使所述底物与不同靶核酸的溶液接触以接种与所述溶液接触的特征的子集，其中所述亚组中的每个特征从所述溶液中接种单个核酸，其中所述多个特征接触溶液不会从溶液中接种核酸; （c）扩增核酸以在子集中的每个特征上形成核酸集落; 和（d）重复步骤（b）和（c）以增加具有核酸集落的表面上的特征的数目，由此形成核酸集落阵列。

4. 发明申请

US20120065091A1 DIRECT MULTIPLEX CHARACTERIZATION OF GENOMIC DNA 有权
标题翻译：基因DNA的直接多重表征
公开(公告)号：US20120065091A1
公开(公告)日：2012-03-15
申请号：US13206120
申请日：2011-08-09
申请人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
发明人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
IPC分类号： C40B30/04 , C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.
摘要翻译：本发明涉及复制核酸反应的新方法，包括扩增，检测和基因分型。本发明依赖于在相应靶核酸存在下被环化的前循环探针的使用，被切割，然后扩增。

5. 发明申请

US20090032401A1 Method and Apparatus Using Electric Field for Improved Biological Assays 有权
标题翻译：使用电场改进生物测定的方法和装置
公开(公告)号：US20090032401A1
公开(公告)日：2009-02-05
申请号：US12170941
申请日：2008-07-10
申请人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
发明人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
IPC分类号： B01D59/42
CPC分类号： B01L3/502761 , B01J2219/00317 , B01J2219/00459 , B01J2219/00466 , B01J2219/00596 , B01J2219/00648 , B01J2219/00653 , B01J2219/00702 , B01L2200/0668 , B01L2300/0819 , B01L2400/0415
摘要： Disclosed are a method and apparatus that use an electric field for improved biological assays. The electric field is applied across a device having wells, which receive reactants, which carry a charge. The device thus uses a controllable voltage source between the first and second electrodes, which is controllable to provide a positive charge and a negative charge to a given electrode. By controlled use of the electric field charged species in a fluid in a fluid channel are directed into or out of the well by an electric field between the electrodes. The present method involves the transport of fluids, as in a microfluidic device, and the electric field-induced movement of reactive species according to various assay procedures, such as DNA sequencing, synthesis or the like.
摘要翻译：公开了使用电场进行改进的生物测定的方法和装置。电场被施加在具有井的装置上，该装置具有承载电荷的反应物。因此，该器件在第一和第二电极之间使用可控电压源，其可控制以向给定电极提供正电荷和负电荷。通过控制使用流体通道中的流体中的电场带电物质通过电极之间的电场被引导进入或离开阱。本方法涉及如在微流体装置中的流体的运输，以及根据各种测定程序（例如DNA测序，合成等）的反应物种的电场诱导运动。

6. 发明申请

US20060008824A1 Methods and compositions for clonal amplification of nucleic acid 失效
公开(公告)号：US20060008824A1
公开(公告)日：2006-01-12
申请号：US11134683
申请日：2005-05-19
申请人： Mostafa Ronaghi , Foad Mashayekhi
发明人： Mostafa Ronaghi , Foad Mashayekhi
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6874 , B01J2219/00497 , B01J2219/005 , B01J2219/00547 , B01J2219/00572 , B01J2219/00722 , C12Q2565/518 , C12Q2563/185
摘要： Described herein are methods and compositions relating to amplifying nucleic acid. In certain embodiments, the invention provides methods for labeling and amplifying a nucleic acid molecule.

7. 发明授权

US08753816B2 Sequencing methods 有权
标题翻译：测序方法
公开(公告)号：US08753816B2
公开(公告)日：2014-06-17
申请号：US13881320
申请日：2011-10-26
申请人： Roberto Rigatti , Jonathan Mark Boutell , Jason Richard Betley , Niall Anthony Gormley , Mostafa Ronaghi , Dirk Evers
发明人： Roberto Rigatti , Jonathan Mark Boutell , Jason Richard Betley , Niall Anthony Gormley , Mostafa Ronaghi , Dirk Evers
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6874 , C12Q2565/514 , C12Q2537/155 , C12Q2525/186 , C12Q2525/185 , C12Q2537/113 , C12Q2525/204
摘要： The present technology relates to molecular sciences, such as genomics. More particularly, the present technology relates to nucleic acid sequencing.
摘要翻译：本技术涉及分子科学，如基因组学。更具体地，本技术涉及核酸测序。

8. 发明申请

US20130008789A1 METHOD AND APPARATUS USING ELECTRIC FIELD FOR IMPROVED BIOLOGICAL ASSAYS 失效
标题翻译：使用电场改进生物测定的方法和装置
公开(公告)号：US20130008789A1
公开(公告)日：2013-01-10
申请号：US13618228
申请日：2012-09-14
申请人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
发明人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
IPC分类号： B03C7/02 , B81B1/00
CPC分类号： B01L3/502761 , B01J2219/00317 , B01J2219/00459 , B01J2219/00466 , B01J2219/00596 , B01J2219/00648 , B01J2219/00653 , B01J2219/00702 , B01L2200/0668 , B01L2300/0819 , B01L2400/0415
摘要： Disclosed are a method and apparatus that use an electric field for improved biological assays. The electric field is applied across a device having wells, which receive reactants, which carry a charge. The device thus uses a controllable voltage source between the first and second electrodes, which is controllable to provide a positive charge and a negative charge to a given electrode. By controlled use of the electric field charged species in a fluid in a fluid channel are directed into or out of the well by an electric field between the electrodes. The present method involves the transport of fluids, as in a microfluidic device, and the electric field-induced movement of reactive species according to various assay procedures, such as DNA sequencing, synthesis or the like.
摘要翻译：公开了使用电场进行改进的生物测定的方法和装置。电场被施加在具有井的装置上，该装置具有承载电荷的反应物。因此，该器件在第一和第二电极之间使用可控电压源，其可控制以向给定电极提供正电荷和负电荷。通过控制使用流体通道中的流体中的电场带电物质通过电极之间的电场被引导进入或离开阱。本方法涉及如在微流体装置中的流体的运输，以及根据各种测定程序（例如DNA测序，合成等）的反应物种的电场诱导运动。

9. 发明申请

US20120142016A1 Array-based bioactivated nanopore devices 有权
标题翻译：基于阵列的生物活化纳米孔装置
公开(公告)号：US20120142016A1
公开(公告)日：2012-06-07
申请号：US11904345
申请日：2007-09-27
申请人： Mostafa Ronaghi , Amir Ali Haj Hossein Talasaz , Ronald W. Davis
发明人： Mostafa Ronaghi , Amir Ali Haj Hossein Talasaz , Ronald W. Davis
IPC分类号： G01N33/53 , G01N27/00 , B05D5/12 , B05D1/38 , B01L99/00 , C12M1/34 , B82Y5/00
CPC分类号： B82Y15/00
摘要： A nanopore device capable of single molecule detection is described. The nanopores are formed in thin, rigid membranes and modified by a sputtered metal that forms an overhang during application. The overhang causes the pore to be narrower in a certain region, allowing passage of only a single molecule through the pore at a time, or binding to a biomolecule on the pore to be detected by a change in ionic current flow through the nanopore. Embodiments include a silicon nitride membrane formed on a silicon substrate and having a nanopore drilled with a focused ion beam system, followed by gold sputtering onto the membrane. Devices are formed with one or more nanopores and chambers having electrodes on either side of the nanopore.
摘要翻译：描述了能够进行单分子检测的纳米孔装置。纳米孔形成在薄的刚性膜中，并且通过在施加期间形成悬垂体的溅射金属进行改性。突出端导致孔在一定区域内变窄，允许一次仅通过一个分子通过孔，或者通过纳米孔的离子电流的变化与待检测的孔上的生物分子结合。实施例包括形成在硅衬底上并具有用聚焦离子束系统钻孔的纳米孔的氮化硅膜，随后在膜上进行金溅射。器件由一个或多个在纳米孔的两侧具有电极的纳米孔和腔室形成。

10. 发明授权

US07993880B2 Precircle probe nucleic acid amplification methods 有权
标题翻译：前置探针核酸扩增方法
公开(公告)号：US07993880B2
公开(公告)日：2011-08-09
申请号：US12709319
申请日：2010-02-19
申请人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
发明人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
IPC分类号： C12P19/34 , C07H21/02 , C07H21/04 , C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.
摘要翻译：本发明涉及复制核酸反应的新方法，包括扩增，检测和基因分型。本发明依赖于在相应靶核酸存在下被环化的前循环探针的使用，被切割，然后扩增。

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