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1. 发明申请

US20080003142A1 Microfluidic devices 审中-公开
标题翻译：微流体装置
公开(公告)号：US20080003142A1
公开(公告)日：2008-01-03
申请号：US11803104
申请日：2007-05-11
申请人： Darren Link , Michael Weiner , David Marran , Jonathan Rothberg
发明人： Darren Link , Michael Weiner , David Marran , Jonathan Rothberg
IPC分类号： G01N21/64 , B01L3/00 , B29C33/38
CPC分类号： B01F3/0807 , B01F13/0062 , B01J19/0093 , B01L3/502715 , B01L3/502746 , B01L3/502784 , B01L3/565 , B01L7/525 , B01L9/527 , B01L2200/027 , B01L2200/0636 , B01L2200/0647 , B01L2200/0673 , B01L2200/10 , B01L2300/0636 , B01L2300/0816 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/165 , B01L2400/0415 , B01L2400/0424 , B01L2400/0487 , B01L2400/086 , B03C5/005 , B03C5/026 , C12N15/1068 , C12N15/1086 , C12Q1/00 , C12Q1/6806 , C12Q1/6837 , C12Q1/6844 , C12Q1/6855 , C12Q1/6869 , C12Q1/6874 , C12Q2565/628 , C12Q2565/629 , G01N15/147 , G01N21/05 , G01N21/64 , G01N27/3275 , G01N35/08 , G01N2021/0346 , G01N2035/00237 , G01N2035/00326 , G01N2201/024 , Y10T137/87571 , Y10T137/87619 , Y10T137/87652 , C12Q2525/191 , C12Q2563/159 , C12Q2535/101 , C12Q2563/149 , C12Q2531/113
摘要： The present invention provides novel microfluidic substrates and methods that are useful for performing biological, chemical and diagnostic assays. The substrates can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged such that a continuous channel is provided for flow of immiscible fluids.
摘要翻译：本发明提供了可用于进行生物学，化学和诊断测定的新型微流体底物和方法。基板可以包括多个可电寻址的通道支承流体模块，其一体地布置成使得提供用于不混溶流体流动的连续通道。

2. 发明申请

US20080014589A1 Microfluidic devices and methods of use thereof 审中-公开
标题翻译：微流体装置及其使用方法
公开(公告)号：US20080014589A1
公开(公告)日：2008-01-17
申请号：US11803101
申请日：2007-05-11
申请人： Darren Link , Michael Weiner , David Marran , Jonathan Rothberg
发明人： Darren Link , Michael Weiner , David Marran , Jonathan Rothberg
IPC分类号： C12Q1/68 , B01D57/00 , B81B1/00 , C12N9/00 , G01N1/28 , G01N27/26 , G01N33/00 , G01N11/00 , C40B50/08 , C12P19/34 , C12Q1/00
CPC分类号： B01F3/0807 , B01F13/0062 , B01J19/0093 , B01L3/502715 , B01L3/502746 , B01L3/502784 , B01L3/565 , B01L7/525 , B01L9/527 , B01L2200/027 , B01L2200/0636 , B01L2200/0647 , B01L2200/0673 , B01L2200/10 , B01L2300/0636 , B01L2300/0816 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/165 , B01L2400/0415 , B01L2400/0424 , B01L2400/0487 , B01L2400/086 , B03C5/005 , B03C5/026 , C12N15/1068 , C12N15/1086 , C12Q1/00 , C12Q1/6806 , C12Q1/6837 , C12Q1/6844 , C12Q1/6855 , C12Q1/6869 , C12Q1/6874 , C12Q2565/628 , C12Q2565/629 , G01N15/147 , G01N21/05 , G01N21/64 , G01N27/3275 , G01N35/08 , G01N2021/0346 , G01N2035/00237 , G01N2035/00326 , G01N2201/024 , Y10T137/87571 , Y10T137/87619 , Y10T137/87652 , C12Q2525/191 , C12Q2563/159 , C12Q2535/101 , C12Q2563/149 , C12Q2531/113
摘要： The present invention provides novel microfluidic substrates and methods that are useful for performing biological, chemical and diagnostic assays. The substrates can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged such that a continuous channel is provided for flow of immiscible fluids.
摘要翻译：本发明提供了可用于进行生物学，化学和诊断测定的新型微流体底物和方法。基板可以包括多个可电寻址的通道支承流体模块，其一体地布置成使得提供用于不混溶流体流动的连续通道。

3. 发明授权

US08936763B2 Integrated sensor arrays for biological and chemical analysis 有权
标题翻译：用于生物和化学分析的集成传感器阵列
公开(公告)号：US08936763B2
公开(公告)日：2015-01-20
申请号：US13125133
申请日：2009-10-22
申请人： Jonathan Rothberg , James Bustillo , Mark Milgrew , Jonathan Schultz , David Marran , Todd Rearick , Kim Johnson
发明人： Jonathan Rothberg , James Bustillo , Mark Milgrew , Jonathan Schultz , David Marran , Todd Rearick , Kim Johnson
IPC分类号： G01N27/403 , G01N27/414 , C12Q1/68 , H01L21/82
CPC分类号： G01N27/4145 , C12Q1/6869 , C12Q1/6874 , G01N27/4148 , H01L21/82 , C12Q2565/607
摘要： The invention is directed to apparatus and chips comprising a large scale chemical field effect transistor arrays that include an array of sample-retaining regions capable of retaining a chemical or biological sample from a sample fluid for analysis. In one aspect such transistor arrays have a pitch of 10 μm or less and each sample-retaining region is positioned on at least one chemical field effect transistor which is configured to generate at least one output signal related to a characteristic of a chemical or biological sample in such sample-retaining region. In one embodiment, the characteristic of said chemical or biological sample is a concentration of a charged species and wherein each of said chemical field effect transistors is an ion-sensitive field effect transistor having a floating gate with a dielectric layer on a surface thereof, the dielectric layer contacting said sample fluid and being capable of accumulating charge in proportion to a concentration of the charged species in said sample fluid. In one embodiment such charged species is a hydrogen ion such that the sensors measure changes in pH of the sample fluid in or adjacent to the sample-retaining region thereof. Apparatus and chips of the invention may be adapted for large scale pH-based DNA sequencing and other bioscience and biomedical applications.
摘要翻译：本发明涉及包括大规模化学场效应晶体管阵列的装置和芯片，其包括能够保留来自样品流体的化学或生物样品用于分析的样品保持区阵列。在一个方面，这种晶体管阵列具有10μm或更小的间距，并且每个采样保持区域位于至少一个化学场效应晶体管上，该晶体管被配置为产生与化学或生物样品的特性相关的至少一个输出信号在这样的样品保留区域中。在一个实施方案中，所述化学或生物样品的特征是带电物质的浓度，并且其中每个所述化学场效应晶体管是离子敏感场效应晶体管，其具有在其表面上具有介电层的浮置栅极，电介质层与所述样品流体接触并且能够与所述样品流体中的带电物质的浓度成比例地积累电荷。在一个实施方案中，这种带电物质是氢离子，使得传感器测量样品流体在其样品保持区域中或其附近的pH值的变化。本发明的装置和芯片可适用于大规模的基于pH的DNA测序和其他生物科学和生物医学应用。

4. 发明授权

US08673627B2 Apparatus and methods for performing electrochemical reactions 有权
标题翻译：用于进行电化学反应的装置和方法
公开(公告)号：US08673627B2
公开(公告)日：2014-03-18
申请号：US12785716
申请日：2010-05-24
申请人： John Nobile , Thomas Roth , Todd Rearick , Jonathan Schultz , Jonathan Rothberg , David Marran
发明人： John Nobile , Thomas Roth , Todd Rearick , Jonathan Schultz , Jonathan Rothberg , David Marran
IPC分类号： C12M1/34 , C12M3/00 , C12M1/00 , C12Q1/68 , G01N27/403
CPC分类号： G01N27/301 , B01J2219/00315 , B01J2219/00317 , B01J2219/005 , B01J2219/00653 , B01J2219/00722 , B01L3/502761 , B01L2200/0668 , B01L2300/0636 , B01L2300/0645 , B01L2300/0877 , G01N27/4145
摘要： The invention is directed to apparatus and methods for delivering multiple reagents to, and monitoring, a plurality of analytical reactions carried out on a large-scale array of electronic sensors underminimal noise conditions. In one aspect, the invention provides method of improving signal-to-noise ratios of output signals from the electronic sensors sensing analytes or reaction byproducts by subtracting an average of output signals measured from neighboring sensors where analyte or reaction byproducts are absent. In other aspects, the invention provides an array of electronic sensors integrated with a microwell array for confining analytes and/or particles for analytical reactions and a method for identifying microwells containing analytes and/or particles by passing a sensor-active reagent over the array and correlating sensor response times to the presence or absence of analytes or particles. Such detection of analyte- or particle-containing microwells may be used as a step in additional noise reduction methods.
摘要翻译：本发明涉及用于在最小噪声条件下向多个电子传感器阵列上进行的多个分析反应的多个试剂的输送和监测的装置和方法。一方面，本发明提供了通过减去从相邻传感器测得的输出信号的平均值来提高来自电子传感器感测分析物或反应副产物的输出信号的信噪比的方法，其中分析物或反应副产物不存在。在其它方面，本发明提供了与微孔阵列集成的电子传感器阵列，用于限制用于分析反应的分析物和/或颗粒，以及通过使传感器活性试剂通过阵列而识别含有分析物和/或颗粒的微孔的方法，以及将传感器响应时间与分析物或颗粒的存在或不存在相关联。含有分析物或含微粒微孔的这种检测可以用作额外的降噪方法中的步骤。

5. 发明申请

US20100300895A1 APPARATUS AND METHODS FOR PERFORMING ELECTROCHEMICAL REACTIONS 有权
标题翻译：用于执行电化学反应的装置和方法
公开(公告)号：US20100300895A1
公开(公告)日：2010-12-02
申请号：US12785716
申请日：2010-05-24
申请人： John Nobile , Thomas Roth , Todd Rearick , Jonathan Schultz , Jonathan Rothberg , David Marran
发明人： John Nobile , Thomas Roth , Todd Rearick , Jonathan Schultz , Jonathan Rothberg , David Marran
IPC分类号： G01N27/26
CPC分类号： G01N27/301 , B01J2219/00315 , B01J2219/00317 , B01J2219/005 , B01J2219/00653 , B01J2219/00722 , B01L3/502761 , B01L2200/0668 , B01L2300/0636 , B01L2300/0645 , B01L2300/0877 , G01N27/4145
摘要： The invention is directed to apparatus and methods for delivering multiple reagents to, and monitoring, a plurality of analytical reactions carried out on a large-scale array of electronic sensors underminimal noise conditions. In one aspect, the invention provides method of improving signal-to-noise ratios of output signals from the electronic sensors sensing analytes or reaction byproducts by subtracting an average of output signals measured from neighboring sensors where analyte or reaction byproducts are absent. In other aspects, the invention provides an array of electronic sensors integrated with a microwell array for confining analytes and/or particles for analytical reactions and a method for identifying microwells containing analytes and/or particles by passing a sensor-active reagent over the array and correlating sensor response times to the presence or absence of analytes or particles. Such detection of analyte- or particle-containing microwells may be used as a step in additional noise reduction methods.
摘要翻译：本发明涉及用于在最小噪声条件下向多个电子传感器阵列上进行的多个分析反应的多个试剂的输送和监测的装置和方法。一方面，本发明提供了通过减去从相邻传感器测得的输出信号的平均值来提高来自电子传感器感测分析物或反应副产物的输出信号的信噪比的方法，其中分析物或反应副产物不存在。在其它方面，本发明提供了与微孔阵列集成的电子传感器阵列，用于限制用于分析反应的分析物和/或颗粒，以及通过使传感器活性试剂通过阵列而识别含有分析物和/或颗粒的微孔的方法，以及将传感器响应时间与分析物或颗粒的存在或不存在相关联。含有分析物或含微粒微孔的这种检测可以用作额外的降噪方法中的步骤。

6. 发明申请

US20060134633A1 Double ended sequencing 失效
标题翻译：双端测序
公开(公告)号：US20060134633A1
公开(公告)日：2006-06-22
申请号：US10768729
申请日：2004-01-28
申请人： Yi-Ju Chen , John Leamon , Kenton Lohman , Michael Ronan , Jonathan Rothberg , Maithreyan Srinivasan , Michael Weiner
发明人： Yi-Ju Chen , John Leamon , Kenton Lohman , Michael Ronan , Jonathan Rothberg , Maithreyan Srinivasan , Michael Weiner
IPC分类号： C12Q1/68
CPC分类号： C12Q1/686 , B01L3/5027 , B01L3/502707 , B01L3/502715 , B01L3/5085 , B01L7/52 , B01L2300/0636 , B01L2300/0819 , B01L2300/0877 , C07H21/00 , C12N15/1075 , C12N15/1093 , C12Q1/6806 , C12Q1/6834 , C12Q1/6844 , C12Q1/6865 , C12Q1/6867 , C12Q1/6869 , C12Q1/6874 , G01N21/253 , G01N21/6428 , G01N21/6452 , G01N21/6458 , G01N2021/6484 , G01R33/1269 , Y02P20/582 , Y10T436/143333 , C12Q2565/119 , C12Q2531/113 , C12Q2565/537 , C12Q2547/107 , C12Q2547/101 , C12Q2537/143 , C12Q2527/125 , C12Q2525/186 , C12Q2565/301 , C12Q2563/149 , C12Q2531/125 , C12Q2537/149 , C12Q2535/119
摘要： This invention relates to methods of sequencing DNA. More specifically, this invention relates to methods of sequencing both the sense and antisense strands of DNA through the use of blocked and unblocked sequencing primers. In brief, these methods include the steps of annealing an unblocked primer to a first strand of nucleic acid; annealing a second blocked primer to a second strand of nucleic acid; elongating the nucleic acid along the first strand with a polymerase; terminating the first sequencing primer; deblocking the second primer; and elongating the nucleic acid along the second strand.
摘要翻译：本发明涉及DNA测序方法。更具体地，本发明涉及通过使用封闭和未封闭的测序引物对DNA的有义链和反义链进行测序的方法。简而言之，这些方法包括将未封闭引物退火至第一条核酸的步骤; 将第二封闭引物退火至核酸的第二链; 用聚合酶沿着第一链延长核酸; 终止第一个测序引物; 解封第二底漆; 并沿着第二链延长核酸。

7. 发明申请

US20050130173A1 Methods of amplifying and sequencing nucleic acids 有权
标题翻译：扩增和测序核酸的方法
公开(公告)号：US20050130173A1
公开(公告)日：2005-06-16
申请号：US10767779
申请日：2004-09-22
申请人： John Leamon , Kenton Lohman , Jonathan Rothberg , Michael Weiner
发明人： John Leamon , Kenton Lohman , Jonathan Rothberg , Michael Weiner
IPC分类号： B01L3/00 , C07H21/00 , C12N15/10 , C12P19/34 , C12Q1/68 , G01N21/25 , G01N21/64
CPC分类号： C12Q1/686 , B01L3/5027 , B01L3/502707 , B01L3/502715 , B01L3/5085 , B01L7/52 , B01L2300/0636 , B01L2300/0819 , B01L2300/0877 , C07H21/00 , C12N15/1075 , C12N15/1093 , C12Q1/6806 , C12Q1/6834 , C12Q1/6844 , C12Q1/6865 , C12Q1/6867 , C12Q1/6869 , C12Q1/6874 , G01N21/253 , G01N21/6428 , G01N21/6452 , G01N21/6458 , G01N2021/6484 , G01R33/1269 , Y02P20/582 , Y10T436/143333 , C12Q2565/119 , C12Q2531/113 , C12Q2565/537 , C12Q2547/107 , C12Q2547/101 , C12Q2537/143 , C12Q2527/125 , C12Q2525/186 , C12Q2565/301 , C12Q2563/149 , C12Q2531/125 , C12Q2537/149 , C12Q2535/119
摘要： An apparatus and method for performing rapid DNA sequencing, such as genomic sequencing, is provided herein. The method includes the steps of preparing a sample DNA for genomic sequencing, amplifying the prepared DNA in a representative manner, and performing multiple sequencing reaction on the amplified DNA with only one primer hybridization step.
摘要翻译：本文提供了用于进行快速DNA测序的装置和方法，例如基因组测序。该方法包括以下步骤：制备用于基因组测序的样品DNA，以代表性方式扩增所制备的DNA，并仅在一个引物杂交步骤对经扩增的DNA进行多次测序反应。

8. 发明申请

US20060040297A1 Methods of amplifying and sequencing nucleic acids 有权
公开(公告)号：US20060040297A1
公开(公告)日：2006-02-23
申请号：US11195254
申请日：2005-08-01
申请人： John Leamon , Kenton Lohman , Jonathan Rothberg , Michael Weiner
发明人： John Leamon , Kenton Lohman , Jonathan Rothberg , Michael Weiner
IPC分类号： C12Q1/68
CPC分类号： B01L3/502761 , B01L3/5027 , B01L3/5085 , B01L2300/0636 , B01L2300/0819 , B01L2300/0877 , C07H21/00 , C12N15/1075 , G01N21/253 , G01N21/6428 , G01N21/6452 , G01N21/6458 , G06F19/22
摘要： An apparatus and method for performing rapid DNA sequencing, such as genomic sequencing, is provided herein. The method includes the steps of preparing a sample DNA for genomic sequencing, amplifying the prepared DNA in a representative manner, and performing multiple sequencing reaction on the amplified DNA with only one primer hybridization step.

9. 发明申请

US20060160178A1 Methods of generating antibody diversity in vitro 审中-公开
标题翻译：体外产生抗体多样性的方法
公开(公告)号：US20060160178A1
公开(公告)日：2006-07-20
申请号：US10991309
申请日：2004-11-17
申请人： Jonathan Rothberg , Michael Weiner
发明人： Jonathan Rothberg , Michael Weiner
IPC分类号： C12P21/06 , C07K16/18 , C12N1/21 , C07H21/04 , C12N5/06 , C12N1/18 , C12N15/74
CPC分类号： C07K16/2803 , C07K16/241 , C07K2317/34 , C07K2317/622
摘要： The present invention provides a high throughput method for generating fully human monoclonal antibodies.
摘要翻译：本发明提供了用于产生完全人单克隆抗体的高通量方法。

10. 发明申请

US20050079510A1 Bead emulsion nucleic acid amplification 有权
标题翻译：珠粒乳液核酸扩增
公开(公告)号：US20050079510A1
公开(公告)日：2005-04-14
申请号：US10767899
申请日：2004-01-28
申请人： Jan Berka , Yi-Ju Chen , John Leamon , Steve Lefkowitz , Kenton Lohman , Vinod Makhijani , Jonathan Rothberg , Gary Sarkis , Maithreyan Srinivasan , Michael Weiner
发明人： Jan Berka , Yi-Ju Chen , John Leamon , Steve Lefkowitz , Kenton Lohman , Vinod Makhijani , Jonathan Rothberg , Gary Sarkis , Maithreyan Srinivasan , Michael Weiner
IPC分类号： B01L3/00 , C07H21/00 , C12N15/10 , C12P19/34 , C12Q1/68 , G01N21/25 , G01N21/64
CPC分类号： C12Q1/686 , B01L3/5027 , B01L3/502707 , B01L3/502715 , B01L3/5085 , B01L7/52 , B01L2300/0636 , B01L2300/0819 , B01L2300/0877 , C07H21/00 , C12N15/1075 , C12N15/1093 , C12Q1/6806 , C12Q1/6834 , C12Q1/6844 , C12Q1/6865 , C12Q1/6867 , C12Q1/6869 , C12Q1/6874 , G01N21/253 , G01N21/6428 , G01N21/6452 , G01N21/6458 , G01N2021/6484 , G01R33/1269 , Y02P20/582 , Y10T436/143333 , C12Q2565/119 , C12Q2531/113 , C12Q2565/537 , C12Q2547/107 , C12Q2547/101 , C12Q2537/143 , C12Q2527/125 , C12Q2525/186 , C12Q2565/301 , C12Q2563/149 , C12Q2531/125 , C12Q2537/149 , C12Q2535/119
摘要： Disclosed are methods for nucleic acid amplification wherein nucleic acid templates, beads, and amplification reaction solution are emulsified and the nucleic acid templates are amplified to provide clonal copies of the nucleic acid templates attached to the beads. Also disclosed are kits and apparatuses for performing the methods of the invention.
摘要翻译：公开了用于核酸扩增的方法，其中将核酸模板，珠粒和扩增反应溶液乳化，并扩增核酸模板以提供附着于珠粒上的核酸模板的克隆拷贝。还公开了用于执行本发明的方法的套件和装置。

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