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1. 发明申请

WO2010016937A3 METHODS FOR SEQUENCING INDIVIDUAL NUCLEIC ACIDS UNDER TENSION 审中-公开
标题翻译：用于在张力下测定个体核酸的方法
公开(公告)号：WO2010016937A3
公开(公告)日：2010-07-08
申请号：PCT/US2009004546
申请日：2009-08-07
申请人： ION TORRENT SYSTEMS INC , ROTHBERG JONATHAN M , LEAMON JOHN H , DAVIDSON JOHN F , VAN OIJEN ANTOINE M , HINZ WOLFGANG , DAVEY MELVILLE , HANN BRADLEY , SCHULTZ JONATHAN
发明人： ROTHBERG JONATHAN M , LEAMON JOHN H , DAVIDSON JOHN F , VAN OIJEN ANTOINE M , HINZ WOLFGANG , DAVEY MELVILLE , HANN BRADLEY , SCHULTZ JONATHAN
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12Q2523/303 , C12Q2565/131 , C12Q2525/204 , C12Q2521/101 , C12Q2535/122
摘要： The invention provides apparatuses and methods of use thereof for sequencing nucleic acids subjected to a force, and thus considered under tension. The methods may employ but are not dependent upon incorporation of extrinsically detectably labeled nucleotides.
摘要翻译：本发明提供了用于测序经受力的核酸的装置及其使用方法，并因此在张力下考虑。所述方法可以采用但不依赖于外源可检测标记的核苷酸的引入。

2. 发明申请

WO2010138182A2 METHODS AND APPARATUS FOR MEASURING ANALYTES 审中-公开
标题翻译：测量分析仪的方法和装置
公开(公告)号：WO2010138182A2
公开(公告)日：2010-12-02
申请号：PCT/US2010001543
申请日：2010-05-27
申请人： ION TORRENT SYSTEMS INC , ROTHBERG JONATHAN M , HINZ WOLFGANG , DAVIDSON JOHN F , VAN OIJEN ANTOINE M , LEAMON JOHN H , HUBER MARTIN , BUSTILLO JAMES M , MILGREW MARK JAMES , SCHULTZ JONATHAN , MARRAN DAVID , REARICK TODD , JOHNSON KIM L
发明人： ROTHBERG JONATHAN M , HINZ WOLFGANG , DAVIDSON JOHN F , VAN OIJEN ANTOINE M , LEAMON JOHN H , HUBER MARTIN , BUSTILLO JAMES M , MILGREW MARK JAMES , SCHULTZ JONATHAN , MARRAN DAVID , REARICK TODD , JOHNSON KIM L
IPC分类号： C40B20/00 , C12P19/34 , C12Q1/68 , C40B40/06 , C40B60/10
CPC分类号： G01N27/4145 , C12Q1/6869 , C12Q1/6874 , G01N27/27 , G01N27/414 , Y10T29/49002
摘要： Methods and apparatus relating to FET arrays including large FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by- synthesis reactions. Some methods provided herein relate to improving signal (and also signal-to-noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.
摘要翻译：涉及FET阵列的方法和装置，包括用于监测化学和/或生物反应的大型FET阵列，例如通过合成反应的核酸测序。本文提供的一些方法涉及在核酸测序反应期间从释放的氢离子改进信号（以及信噪比）。

3. 发明申请

WO2010008480A3 METHODS AND APPARATUS FOR MEASURING ANALYTES USING LARGE SCALE FET ARRAYS 审中-公开
标题翻译：用大尺寸FET阵列测量分析物的方法和设备
公开(公告)号：WO2010008480A3
公开(公告)日：2010-06-03
申请号：PCT/US2009003766
申请日：2009-06-25
申请人： ION TORRENT SYSTEMS INC , ROTHBERG JONATHAN M , HINZ WOLFGANG , JOHNSON KIM L , BUSTILLO JAMES M , LEAMON JOHN H , SCHULTZ JONATHAN
发明人： ROTHBERG JONATHAN M , HINZ WOLFGANG , JOHNSON KIM L , BUSTILLO JAMES M , LEAMON JOHN H , SCHULTZ JONATHAN
IPC分类号： C12Q1/68 , G01N27/414
CPC分类号： C12Q1/6874 , B01L3/502761 , B01L2300/046 , B01L2300/0663 , B01L2300/0851 , B01L2400/086 , C12Q1/6869 , G01N27/4145 , G01N27/4148 , C12Q2565/607 , C12Q2565/301 , C12Q2565/629
摘要： Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in the concentration of inorganic pyrophosphate (PPi), hydrogen ions, and nucleotide triphosphates.
摘要翻译：涉及用于分析物测量的超大规模FET阵列的方法和装置。可以使用基于改善的FET像素和阵列设计的常规CMOS处理技术来制造ChemFET（例如，ISFET）阵列，这些技术增加了测量灵敏度和准确度，并且同时促进了显着小的像素尺寸和密集阵列。改进的阵列控制技术可以从大型密集阵列中快速获取数据。这种阵列可用于检测各种化学和/或生物过程中各种分析物类型的存在和/或浓度变化。在一个实例中，chemFET阵列基于监测无机焦磷酸（PPi），氢离子和三磷酸核苷酸浓度的变化来促进DNA测序技术。

4. 发明申请

WO2008076406A8 METHODS AND APPARATUS FOR MEASURING ANALYTES USING LARGE SCALE FET ARRAYS 审中-公开
标题翻译：使用大规模FET阵列测量分析仪的方法和装置
公开(公告)号：WO2008076406A8
公开(公告)日：2008-09-12
申请号：PCT/US2007025721
申请日：2007-12-14
申请人： ION TORRENT SYSTEMS INC , ROTHBERG JONATHAN M , HINZ WOLFGANG , JOHNSON KIM L , BUSTILLO JAMES
发明人： ROTHBERG JONATHAN M , HINZ WOLFGANG , JOHNSON KIM L , BUSTILLO JAMES
IPC分类号： G01N27/414 , G01N33/543
CPC分类号： G01N27/4148 , C12Q1/6818 , C12Q1/6874 , G01N27/4145 , G01N33/54373 , G01N33/5438 , H01L27/088 , H01L29/42324 , H01L29/78 , H01L2924/01006 , H01L2924/01013 , H01L2924/01015 , H01L2924/01073 , H01L2924/14 , H01L2924/1433 , Y10T436/22 , C12Q2565/607 , C12Q2565/301 , C12Q2533/101
摘要： A method for sequencing a nucleic acid may include disposing a plurality of template nucleic acids into a plurality of reaction chambers, wherein the plurality of reaction chambers is in contact with a chemical-sensitive field effect transistor (chemFET) array comprising at least one chemFET for each reaction chamber, wherein the at least one chemFET has a floating gate, and wherein each of the template nucleic acids is hybridized to a sequencing primer and is bound to a polymerase. The method may further include synthesizing a new nucleic acid strand by incorporating one or more known nucleotide triphosphates sequentially at the 3' end of the sequencing primer and detecting the incorporation of the one or more known nucleotide triphosphates by a change in current at the at least one chemFET within the array.

5. 发明申请

WO2010047804A1 INTEGRATED SENSOR ARRAYS FOR BIOLOGICAL AND CHEMICAL ANALYSIS 审中-公开
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：WO2010047804A1
公开(公告)日：2010-04-29
申请号：PCT/US2009005745
申请日：2009-10-22
申请人： ION TORRENT SYSTEMS INC , ROTHBERG JONATHAN M , SCHULTZ JONATHAN C , JOHNSON KIM L , REARICK TODD M , MILGREM MARK JAMES , MARRAN DAVID , BUSTILLO JAMES M
发明人： ROTHBERG JONATHAN M , SCHULTZ JONATHAN C , JOHNSON KIM L , REARICK TODD M , MILGREM MARK JAMES , MARRAN DAVID , BUSTILLO JAMES M
IPC分类号： G01N27/416 , C12M1/34
CPC分类号： G01N27/4145
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。

6. 发明申请

WO2011106629A3 MODIFIED PROTEINS AND METHODS OF MAKING AND USING SAME 审中-公开
标题翻译：改良蛋白质及其制备方法和使用方法
公开(公告)号：WO2011106629A3
公开(公告)日：2012-01-19
申请号：PCT/US2011026219
申请日：2011-02-25
申请人： LIFE TECHNOLOGIES CORP , DAVIDSON JOHN F , HINZ WOLFGANG , ROTHBERG JONATHAN M , WHITAKER RICHARD
发明人： DAVIDSON JOHN F , HINZ WOLFGANG , ROTHBERG JONATHAN M , WHITAKER RICHARD
IPC分类号： C12Q1/68 , C12N9/12 , C12Q1/48
CPC分类号： C12N9/1252
摘要： Methods, compositions, systems, apparatuses and kits comprising modified proteins, particularly modified nucleic acid-binding proteins with altered buffering properties are provided. For example, in some embodiments, methods of forming modified proteins including one or more amino acid modifications to achieve desired pKa values are described. Furthermore, the invention provides methods for using such modified proteins in ion-producing reactions, such as ion-based nucleic acid sequencing reactions.
摘要翻译：提供了包含修饰的蛋白质，特别是具有改变的缓冲性质的经修饰的核酸结合蛋白质的方法，组合物，系统，装置和试剂盒。例如，在一些实施方案中，描述了形成包含一个或多个氨基酸修饰以获得所需pKa值的修饰蛋白质的方法。此外，本发明提供了在离子产生反应中使用这些修饰蛋白质的方法，例如基于离子的核酸测序反应。

7. 发明申请

WO2009158006A3 METHODS AND APPARATUS FOR DETECTING MOLECULAR INTERACTIONS USING FET ARRAYS 审中-公开
标题翻译：使用FET阵列检测分子相互作用的方法和装置
公开(公告)号：WO2009158006A3
公开(公告)日：2010-05-06
申请号：PCT/US2009003797
申请日：2009-06-26
申请人： ION TORRENT SYSTEMS INC , ROTHBERG JONATHAN M
发明人： ROTHBERG JONATHAN M
IPC分类号： G01N27/414 , C12Q1/68 , G01N27/416 , H01L29/06 , H01L29/786
CPC分类号： G01N27/4145 , G01N27/4148
摘要： Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.
摘要翻译：提供了与用于分析物检测和测量的大规模FET阵列相关的方法和装置。可以使用基于提高测量灵敏度和精度的改进的FET像素和阵列设计的传统CMOS处理技术来制造ChemFET（例如，ISFET）阵列，并且同时促进显着小的像素尺寸和致密阵列。改进的阵列控制技术提供了从大型和密集阵列的快速数据采集。可以使用这样的阵列来检测各种化学和/或生物过程中各种分析物类型的存在和/或浓度变化。

8. 发明申请

WO2005003375A3 METHODS OF AMPLIFYING AND SEQUENCING NUCLEIC ACIDS 审中-公开
标题翻译：放大和测序核酸的方法
公开(公告)号：WO2005003375A3
公开(公告)日：2007-08-23
申请号：PCT/US2004002570
申请日：2004-01-28
申请人： 454 CORP , LEAMON JOHN H , LOHMAN KENTON , ROTHBERG JONATHAN M , WEINER MICHAEL P
发明人： LEAMON JOHN H , LOHMAN KENTON , ROTHBERG JONATHAN M , WEINER MICHAEL P
IPC分类号： C12Q1/68 , B01L3/00 , C07H21/00 , C12N15/10 , C12P19/34 , 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。

9. 发明申请

WO2007081386A2 MICROFLUIDIC DEVICES AND METHODS OF USE 审中-公开
标题翻译：微流体装置及其使用方法
公开(公告)号：WO2007081386A2
公开(公告)日：2007-07-19
申请号：PCT/US2006021286
申请日：2006-06-01
申请人： RAINDANCE TECHNOLOGIES INC , LINK DARREN R , BOITARD LAURENT , BRANCIFORTE JEFFREY , CHARLES YVES , FEKE GILBERT , LU JOHN Q , MARRAN DAVID , TABATABAI AHMADALI , WEINER MICHAEL , HINZ WOLFGANG , ROTHBERG JONATHAN M
发明人： LINK DARREN R , BOITARD LAURENT , BRANCIFORTE JEFFREY , CHARLES YVES , FEKE GILBERT , LU JOHN Q , MARRAN DAVID , TABATABAI AHMADALI , WEINER MICHAEL , HINZ WOLFGANG , ROTHBERG JONATHAN M
IPC分类号： B01L3/00 , B01F13/00 , G01N15/14
CPC分类号： C12N15/1075 , B01F3/0807 , B01F13/0071 , B01F13/0076 , B01J19/0046 , B01J2219/00286 , B01J2219/00459 , B01J2219/00466 , B01J2219/00468 , B01J2219/00479 , B01J2219/005 , B01J2219/00576 , B01J2219/00599 , B01J2219/00702 , B01J2219/0072 , B01J2219/00743 , B01L3/5027 , B01L3/502715 , B01L3/50273 , B01L3/502746 , B01L3/502761 , B01L3/502784 , B01L3/502792 , B01L3/565 , B01L7/52 , B01L2200/027 , B01L2200/0621 , B01L2200/0647 , B01L2200/0652 , B01L2200/0673 , B01L2300/0816 , B01L2300/0864 , B01L2300/0867 , B01L2300/0896 , B01L2400/0415 , B01L2400/0424 , B01L2400/0487 , B01L2400/084 , B82Y5/00 , B82Y30/00 , C07K1/047 , C12Q1/6804 , C12Q1/6816 , C12Q1/6825 , C12Q1/6834 , C12Q1/686 , C12Q1/6869 , C12Q1/6874 , C12Q1/6876 , C12Q2525/161 , C12Q2561/119 , C12Q2563/103 , C12Q2563/107 , C12Q2563/159 , C12Q2565/537 , C12Q2565/629 , C12Q2600/16 , C40B30/04 , C40B40/04 , C40B50/08 , C40B60/08 , C40B60/12 , C40B70/00 , G01N21/6428 , G01N21/6445 , G01N21/6458 , G01N33/536 , G01N33/542 , G01N33/543 , G01N33/6845 , G01N33/6854 , G01N2500/10
摘要： The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The device can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged on a microfabricated substrate 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高通量筛选测定和组合化学的新型微流体装置和方法。该装置可以包括多个可电寻址的通道支承流体模块，其一体地布置在微加工基板上，使得提供用于不混溶流体流动的连续通道。

10. 发明申请

WO2007081385A2 MICROFLUIDIC DEVICES AND METHODS OF USE IN THE FORMATION AND CONTROL OF NANOREACTORS 审中-公开
标题翻译：微流体装置和用于形成和控制纳米反应器的方法
公开(公告)号：WO2007081385A2
公开(公告)日：2007-07-19
申请号：PCT/US2006021280
申请日：2006-06-01
申请人： RAINDANCE TECHNOLOGIES INC , LINK DARREN R , BOITARD LAURENT , BRANCIFORTE JEFFREY , CHARLES YVES , FEKE GILBERT , LU JOHN Q , MARRAN DAVID , TABATABAI AHMADALI , WEINER MICHAEL , HINZ WOLFGANG , ROTHBERG JONATHAN M
发明人： LINK DARREN R , BOITARD LAURENT , BRANCIFORTE JEFFREY , CHARLES YVES , FEKE GILBERT , LU JOHN Q , MARRAN DAVID , TABATABAI AHMADALI , WEINER MICHAEL , HINZ WOLFGANG , ROTHBERG JONATHAN M
IPC分类号： G01N33/536 , B01J19/00 , C07B61/00 , C07K1/04 , C12Q1/68 , G01N33/68
CPC分类号： C12N15/1075 , B01F3/0807 , B01F13/0071 , B01F13/0076 , B01J19/0046 , B01J2219/00286 , B01J2219/00459 , B01J2219/00466 , B01J2219/00468 , B01J2219/00479 , B01J2219/005 , B01J2219/00576 , B01J2219/00599 , B01J2219/00702 , B01J2219/0072 , B01J2219/00743 , B01L3/5027 , B01L3/502715 , B01L3/50273 , B01L3/502746 , B01L3/502761 , B01L3/502784 , B01L3/502792 , B01L3/565 , B01L7/52 , B01L2200/027 , B01L2200/0621 , B01L2200/0647 , B01L2200/0652 , B01L2200/0673 , B01L2300/0816 , B01L2300/0864 , B01L2300/0867 , B01L2300/0896 , B01L2400/0415 , B01L2400/0424 , B01L2400/0487 , B01L2400/084 , B82Y5/00 , B82Y30/00 , C07K1/047 , C12Q1/6804 , C12Q1/6816 , C12Q1/6825 , C12Q1/6834 , C12Q1/686 , C12Q1/6869 , C12Q1/6874 , C12Q1/6876 , C12Q2525/161 , C12Q2561/119 , C12Q2563/103 , C12Q2563/107 , C12Q2563/159 , C12Q2565/537 , C12Q2565/629 , C12Q2600/16 , C40B30/04 , C40B40/04 , C40B50/08 , C40B60/08 , C40B60/12 , C40B70/00 , G01N21/6428 , G01N21/6445 , G01N21/6458 , G01N33/536 , G01N33/542 , G01N33/543 , G01N33/6845 , G01N33/6854 , G01N2500/10
摘要： The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. Such methods can include labeling a library of compounds by emulsifying aqueous solutions of the compounds and aqueous solutions of unique liquid labels on a microfluidic device, which includes a plurality of electrically addressable, channel bearing fluidic modules integrally arranged on a microfabricated substrate such that a continuous channel is provided for flow of immiscible fluids, whereby each compound is labeled with a unique liquid label, pooling the labeled emulsions, coalescing the labeled emulsions with emulsions containing a specific cell or enzyme, thereby forming a nanoreactor, screening the nanoreactors for a desirable reaction between the contents of the nanoreactor, and decoding the liquid label, thereby identifying a single compound from a library of compounds.
摘要翻译：本发明提供了用于进行高通量筛选测定和组合化学的新型微流体装置和方法。这样的方法可以包括通过乳化化合物的水溶液和独特液体标签的水溶液在微流体装置上标记化合物文库，所述微流体装置包括整体地布置在微制造基底上的多个可电寻址的流道承载流体模块，通道用于不混溶流体的流动，由此每种化合物用独特的液体标签标记，汇集标记的乳液，使标记的乳液与含有特定细胞或酶的乳液聚结，由此形成纳米反应器，筛选纳米反应器以获得期望的反应在纳米反应器的内容物之间，以及解码液体标签，从而从化合物文库中鉴定单一化合物。

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