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1. 发明授权

US06210891B1 Method of sequencing DNA 有权
标题翻译： DNA测序方法
公开(公告)号：US06210891B1
公开(公告)日：2001-04-03
申请号：US09269436
申请日：1999-07-06
申请人： Pål Nyren , Mathias Uhlen , Mostafa Ronaghi
发明人： Pål Nyren , Mathias Uhlen , Mostafa Ronaghi
IPC分类号： C12Q168
CPC分类号： C12Q1/6869 , C12Q2565/518 , C12Q2565/301 , C12Q2535/101
摘要： The present invention provides a method of identifying a base at a target position in a single-stranded sample DNA sequence wherein an extension primer, which hybridizes to the sample DNA immediately adjacent to the target position, is provided and the sample DNA and extension primer are subjected to a polymerization reaction in the presence of a deoxynucleotide or dideoxynucleotide, whereby the deoxynucleotide or dideoxynucleotide will only become incorporated and release pyrophosphate if it is complementary to the base in the target position. Release of pyrophosphate is detected enzymatically and pyrophosphate detection enzyme(s) are included in the polymerization step.
摘要翻译：本发明提供了在单链样品DNA序列中鉴定目标位置的碱基的方法，其中提供了与紧邻目标位置的样品DNA杂交的延伸引物，并且样品DNA和延伸引物为在脱氧核苷酸或双脱氧核苷酸的存在下进行聚合反应，由此脱氧核苷酸或双脱氧核苷酸仅在靶位置与碱基互补时才被引入并释放焦磷酸盐。检测到焦磷酸盐的释放，聚合步骤中包括焦磷酸盐检测酶。

2. 发明授权

US07459311B2 Method of sequencing DNA 有权
标题翻译： DNA测序方法
公开(公告)号：US07459311B2
公开(公告)日：2008-12-02
申请号：US10363231
申请日：2001-09-07
申请人： Pål Nyren , Mostafa Ronaghi , Annika Tallsjö
发明人： Pål Nyren , Mostafa Ronaghi , Annika Tallsjö
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6869 , C12Q2565/301
摘要： The present invention provides a method of identifying a base at a target position in a sample nucleic acid sequence, said method comprising: subjecting a primer hybridised to said sample nucleic acid immediately adjacent to the target position, to a polymerase primer extension reaction in the presence of a nucleotide, whereby the nucleotide will only become incorporated if it is complementary to the base in the target position, and determining whether or not said nucleotide is incorporated by detecting whether Ppi is released, the identity of the target base being determined from the identity of any nucleotide incorporated, wherein, where said nucleotide comprises an adenine base, an α-thio triphosphate analogue of said nucleotide is used, and the Rp isomer of said analogue and/or the degradation products of said analogue are eliminated from the polymerase reaction step.
摘要翻译：本发明提供了鉴定样品核酸序列中目标位置的碱基的方法，所述方法包括：使与所述目标位置相邻的所述样品核酸杂交的引物在存在的情况下进行聚合酶引物延伸反应的核苷酸，其核苷酸仅在与目标位置的碱基互补时才被引入，并且通过检测Ppi是否被释放来确定所述核苷酸是否被并入，靶基因的身份是根据身份确定的其中，当所述核苷酸包含腺嘌呤碱基时，使用所述核苷酸的α-硫代三磷酸类似物，并且所述类似物的Rp异构体和/或所述类似物的降解产物从聚合酶反应步骤中消除。

3. 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。

4. 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。

5. 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。

6. 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。

7. 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.

8. 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。

9. 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。

10. 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。

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