公开(公告)号：WO2010016937A2

公开(公告)日：2010-02-11

申请号：PCT/US2009/004546

申请日：2009-08-07

Applicant: ION TORRENT SYSTEMS INCORPORATED ,  ROTHBERG, Jonathan, M. ,  LEAMON, John, H. ,  DAVIDSON, John, F. ,  VAN OIJEN, Antoine, M. ,  HINZ, Wolfgang ,  DAVEY, Melville ,  HANN, Bradley ,  SCHULTZ, Jonathan

Inventor： ROTHBERG, Jonathan, M. ,  LEAMON, John, H. ,  DAVIDSON, John, F. ,  VAN OIJEN, Antoine, M. ,  HINZ, Wolfgang ,  DAVEY, Melville ,  HANN, Bradley ,  SCHULTZ, Jonathan

IPC: C12Q1/68

CPC classification number: C12Q1/6874 ,  C12Q2523/303 ,  C12Q2565/131 ,  C12Q2525/204 ,  C12Q2521/101 ,  C12Q2535/122

Abstract: 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.

Abstract translation: 本发明提供了用于对受到力作用的核酸进行测序并因此在张力下考虑的装置和其使用方法。 该方法可以使用但不依赖于掺入外在可检测标记的核苷酸。

公开(公告)号：WO2008076406A2

公开(公告)日：2008-06-26

申请号：PCT/US2007/025721

申请日：2007-12-14

Applicant: ION TORRENT SYSTEMS INCORPORATED ,  ROTHBERG, Jonathan, M. ,  HINZ, Wolfgang ,  JOHNSON, Kim, L. ,  BUSTILLO, James

Inventor： ROTHBERG, Jonathan, M. ,  HINZ, Wolfgang ,  JOHNSON, Kim, L. ,  BUSTILLO, James

IPC: G01N27/414 ,  G01N33/543

CPC classification number: 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

公开(公告)号：WO2010008480A2

公开(公告)日：2010-01-21

申请号：PCT/US2009/003766

申请日：2009-06-25

Applicant: ION TORRENT SYSTEMS INCORPORATED ,  ROTHBERG, Jonathan, M. ,  HINZ, Wolfgang ,  JOHNSON, Kim, L. ,  BUSTILLO, James, M. ,  LEAMON, John, H. ,  SCHULTZ, Jonathan

Inventor： ROTHBERG, Jonathan, M. ,  HINZ, Wolfgang ,  JOHNSON, Kim, L. ,  BUSTILLO, James, M. ,  LEAMON, John, H. ,  SCHULTZ, Jonathan

IPC: C12Q1/68 ,  G01N27/414

CPC classification number: C12Q1/6874 ,  B01L3/502761 ,  B01L2300/046 ,  B01L2300/0663 ,  B01L2300/0851 ,  B01L2400/086 ,  C12Q1/6869 ,  G01N27/4145 ,  G01N27/4148 ,  C12Q2565/607 ,  C12Q2565/301 ,  C12Q2565/629

Abstract: 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.

Abstract translation: 与用于分析物测量的非常大规模的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。 在一个示例中，chemFET阵列基于监测无机焦磷酸盐（PPi），氢离子和核苷酸三磷酸盐的浓度变化来促进DNA测序技术。

公开(公告)号：WO2010138186A1

公开(公告)日：2010-12-02

申请号：PCT/US2010/001547

申请日：2010-05-27

Applicant: ION TORRENT SYSTEMS INCORPORATED ,  SCHULTZ, Jonathan ,  MARRAN, David

Inventor： SCHULTZ, Jonathan ,  MARRAN, David

IPC: A01G25/16

CPC classification number: B01L3/502715 ,  B01J2219/00389 ,  B01J2219/00394 ,  B01L3/502 ,  B01L3/50273 ,  B01L3/502738 ,  B01L3/502746 ,  B01L3/502769 ,  B01L3/502776 ,  B01L3/52 ,  B01L2200/16 ,  B01L2300/0636 ,  B01L2300/0645 ,  B01L2300/0861 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2300/0874 ,  B01L2300/0877 ,  B01L2400/0487 ,  C12Q1/6869 ,  G01N27/447 ,  G01N35/1002 ,  G01N35/1097 ,  Y10T137/0318 ,  Y10T137/0424 ,  Y10T137/85938 ,  C12Q2565/629 ,  C12Q2527/119

Abstract: . The invention provides a passive fluidics circuit for directing different fluids to a common volume, such as a reaction chamber or flow cell, without intermixing or cross contamination. The direction and rate of flow through junctions, nodes and passages of the fluidics circuit are controlled by the states of upstream valves (e.g. opened or closed), differential fluid pressures at circuit inlets or upstream reservoirs, flow path resistances, and the like. Free diffusion or leakage of fluids from unselected inlets into the common outlet or other inlets at junctions or nodes is prevented by the flow of the selected inlet fluid, a portion of which sweeps by the inlets of unselected fluids and exits the fluidics circuit by waste ports, thereby creating a barrier against undesired intermixing with the outlet flow through leakage or diffusion. The invention is particularly advantageous in apparatus for performing sensitive multistep reactions, such as pH- based DNA sequencing reactions.

Abstract translation: 。 本发明提供了一种用于将不同流体引导到公共体积（例如反应室或流动池）的无源流体回路，而不会混合或交叉污染。 通过流体回路的连接点，节点和通道的流动方向和流速由上游阀（例如打开或关闭）的状态，电路入口或上游储存器处的差分流体压力，流动阻力等来控制。 通过所选择的入口流体的流动防止流体从未选择的入口到共同的出口或其他入口处的自由扩散或泄漏，其一部分由未选择的流体的入口扫过并且通过废气口离开流体回路 ，从而产生阻止与出口流通过泄漏或扩散的不期望的混合的屏障。 本发明在用于进行敏感多步反应（例如基于pH的DNA测序反应）的装置中特别有利。

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

IPC: H01M8/04 ,  H01M8/10

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。

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.

IPC: C07H21/00 ,  G01N33/48

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。

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。