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公开(公告)号：WO2010138188A1
公开(公告)日：2010-12-02
申请号：PCT/US2010/001553
申请日：2010-05-27
Applicant: ION TORRENT SYSTEMS INCORPORATED , NOBILE, John , ROTH, George, Thomas , REARICK, Todd , SCHULTZ, Jonathan , ROTHBERG, Jonathan, M. , MARRAN, David
Inventor： NOBILE, John , ROTH, George, Thomas , REARICK, Todd , SCHULTZ, Jonathan , ROTHBERG, Jonathan, M. , MARRAN, David
CPC classification number: G01N27/301 , B01J2219/00315 , B01J2219/00317 , B01J2219/005 , B01J2219/00653 , B01J2219/00722 , B01L3/502761 , B01L2200/0668 , B01L2300/0636 , B01L2300/0645 , B01L2300/0877 , G01N27/4145
Abstract: 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 under minimal 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.
Abstract translation: 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。
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42.发明申请SCAFFOLDED NUCLEIC ACID POLYMER PARTICLES AND METHODS OF MAKING AND USING 审中-公开SCAFFEDED核酸聚合物颗粒及其制备和使用方法
公开(公告)号：WO2010138187A1
公开(公告)日：2010-12-02
申请号：PCT/US2010/001549
申请日：2010-05-27
Applicant: ION TORRENT SYSTEMS INCORPORATED , HINZ, Wolfgang , LEAMON, John H. , LIGHT, David , ROTHBERG, Jonathan M.
Inventor： HINZ, Wolfgang , LEAMON, John H. , LIGHT, David , ROTHBERG, Jonathan M.
CPC classification number: C12N15/1093 , C12Q1/6806 , C12Q1/6834 , C12Q1/6853 , C12Q2535/122 , C12Q2563/155 , C12Q2563/159 , C12Q2565/607 , C12Q2565/537 , C12Q2565/629
Abstract: The invention provides particle compositions having applications in nucleic acid analysis. Nucleic acid polymer particles of the invention allow polynucleotides to be attached throughout their volumes for higher loading capacities than those achievable solely with surface attachment. In one aspect, nucleic acid polymer particles of the invention comprise polyacrylamide particles with uniform size distributions having low coefficients of variations, which result in reduced particle-to-particle variation in analytical assays. Such particle compositions are used in various amplification reactions to make amplicon libraries from nucleic acid fragment libraries.
Abstract translation: 本发明提供了在核酸分析中具有应用的颗粒组合物。 本发明的核酸聚合物颗粒允许多核苷酸在其整个体积中被连接，以便比仅通过表面附着可实现的更高的负载能力。 在一个方面，本发明的核酸聚合物颗粒包含具有低变异系数的具有均匀尺寸分布的聚丙烯酰胺颗粒，这导致分析测定中颗粒 - 颗粒变化的降低。 这种颗粒组合物用于各种扩增反应以制备来自核酸片段文库的扩增子文库。
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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
Applicant: 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
Inventor： 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
CPC classification number: G01N27/4145 , C12Q1/6869 , C12Q1/6874 , G01N27/27 , G01N27/414 , Y10T29/49002
Abstract: 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.
Abstract translation: 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）。
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公开(公告)号：WO2010047804A8
公开(公告)日：2010-04-29
申请号：PCT/US2009/005745
申请日：2009-10-22
Applicant: LIFE TECHNOLOGIES CORPORATION , ROTHBERG, Jonathan, M. , SCHULTZ, Jonathan, C. , JOHNSON, Kim, L. , REARICK, Todd, M. , MILGREW, Mark, James , MARRAN, David , BUSTILLO, James, M.
Inventor： ROTHBERG, Jonathan, M. , SCHULTZ, Jonathan, C. , JOHNSON, Kim, L. , REARICK, Todd, M. , MILGREW, Mark, James , MARRAN, David , BUSTILLO, James, M.
IPC: G01N27/416 , C12M1/34
Abstract: 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.
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45.发明申请METHODS AND APPARATUS FOR DETECTING MOLECULAR INTERACTIONS USING FET ARRAYS 审中-公开使用FET阵列检测分子相互作用的方法和装置
公开(公告)号：WO2009158006A2
公开(公告)日：2009-12-30
申请号：PCT/US2009/003797
申请日：2009-06-26
Applicant: ION TORRENT SYSTEMS INCORPORATED , ROTHBERG, Jonathan, M.
Inventor： ROTHBERG, Jonathan, M.
IPC: G01N27/414 , C12Q1/68 , H01L29/786 , H01L29/06 , G01N27/416
CPC classification number: G01N27/4145 , G01N27/4148
Abstract: 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.
Abstract translation: 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。
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Patent Agency Ranking
公开(公告)号：WO2007133710A3
公开(公告)日：2007-11-22
申请号：PCT/US2007/011462
申请日：2007-05-11
Applicant: RAINDANCE TECHNOLOGIES, INC. , LINK, Darren, R. , WEINER, Michael , MARREN, David , ROTHBERG, Jonathan, M.
Inventor： LINK, Darren, R. , WEINER, Michael , MARREN, David , ROTHBERG, Jonathan, M.
Abstract: 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.
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公开(公告)号：WO2007133710A2
公开(公告)日：2007-11-22
申请号：PCT/US2007011462
申请日：2007-05-11
Applicant: RAINDANCE TECHNOLOGIES INC , LINK DARREN R , WEINER MICHAEL , MARREN DAVID , ROTHBERG JONATHAN M
Inventor： LINK DARREN R , WEINER MICHAEL , MARREN DAVID , ROTHBERG JONATHAN M
CPC classification number: 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
Abstract: 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.
Abstract translation: 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。
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公开(公告)号：WO2004070007A3
公开(公告)日：2005-12-22
申请号：PCT/US2004002571
申请日：2004-01-28
Applicant: 454 CORP , COSTA GINA L , WEINER MICHAEL P , LEAMON JOHN , ROTHBERG JONATHAN
Inventor： COSTA GINA L , WEINER MICHAEL P , LEAMON JOHN , ROTHBERG JONATHAN
CPC classification number: 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
Abstract: This invention relates to methods of generating single stranded DNA libraries for use in amplification and sequencing reactions. In various aspects, the disclosed methods include: fragmenting DNA; polishing the fragments' ends; lighting the fragments to universal adapters; performing strand displacement and extension of the nicked fragments; purifying the double-stranded libation products; capturing the double-stranded libation products onto a solid support; and isolating single stranded DNA library fragments, and binding these fragments to another solid support.
Abstract translation: 本发明涉及产生用于扩增和测序反应的单链DNA文库的方法。 在各方面，所公开的方法包括：片段化DNA; 抛光片段的末端; 将碎片照亮通用适配器; 进行缝合位移和切口碎片的延伸; 纯化双链奠基产品; 将双链奠基产品捕获到固体支持物上; 并分离单链DNA文库片段，并将这些片段结合到另一种固体支持物上。
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公开(公告)号：WO2004070005B1
公开(公告)日：2005-01-20
申请号：PCT/US2004002485
申请日：2004-01-28
Applicant: 454 CORP , CHEN YI-JU , LEAMON JOHN H , LOHMAN KENTON , RONAN MICHAEL T , SRINIVASAN MAITHREYAN , ROTHBERG JONATHAN , WEINER MICHAEL
Inventor： CHEN YI-JU , LEAMON JOHN H , LOHMAN KENTON , RONAN MICHAEL T , SRINIVASAN MAITHREYAN , ROTHBERG JONATHAN , WEINER MICHAEL
CPC classification number: 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
Abstract: 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.
Abstract translation: 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。
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50.发明申请
公开(公告)号：WO2003004690A3
公开(公告)日：2003-01-16
申请号：PCT/US2002/021579
申请日：2002-07-08
Applicant: 454® CORPORATION , WEINER, Michael , ATTIYA, Said , CRENSHAW, Hugh , ROTHBERG, Jonathan, M. , MATSON, Steve
Inventor： WEINER, Michael , ATTIYA, Said , CRENSHAW, Hugh , ROTHBERG, Jonathan, M. , MATSON, Steve
IPC: G01N21/03
Abstract: The present invention relates to the field of fluid dynamics. More specifically, this invention relates to methods and apparatus for conducting densely packed, independent chemical reactions in parallel in a substantially two-dimensional array. Accordingly, this invention also focuses on the use of this array for applications such as DNA sequencing, most preferably pyrosequencing, and DNA amplification.
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