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    Integrated sensor arrays for biological and chemical analysis
    1.
    发明授权
    Integrated sensor arrays for biological and chemical analysis 有权
    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

    Applicant: Jonathan Rothberg ,  James Bustillo ,  Mark Milgrew ,  Jonathan Schultz ,  David Marran ,  Todd Rearick ,  Kim Johnson

    Inventor： Jonathan Rothberg ,  James Bustillo ,  Mark Milgrew ,  Jonathan Schultz ,  David Marran ,  Todd Rearick ,  Kim Johnson

    IPC: G01N27/403 ,  G01N27/414 ,  C12Q1/68 ,  H01L21/82

    CPC classification number: G01N27/4145 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N27/4148 ,  H01L21/82 ,  C12Q2565/607

    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.

    Abstract translation: 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。

    Chemically-sensitive sample and hold sensors
    3.
    发明授权
    Chemically-sensitive sample and hold sensors 有权
    化学敏感的采样和保持传感器

    公开(公告)号：US08502278B2

    公开(公告)日：2013-08-06

    申请号：US13556001

    申请日：2012-07-23

    Applicant: Jonathan Rothberg ,  Wolfgang Hinz ,  Kim Johnson ,  James Bustillo

    Inventor： Jonathan Rothberg ,  Wolfgang Hinz ,  Kim Johnson ,  James Bustillo

    IPC: G01N27/403

    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

    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 hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

    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。 在一个实例中，chemFET阵列基于监测氢离子浓度（pH），其他分析物浓度变化和/或与DNA合成相关的化学过程相关联的结合事件的变化来促进DNA测序技术。

    Methods and Apparatus for Detecting Molecular Interactions Using FET Arrays
    4.
    发明申请
    Methods and Apparatus for Detecting Molecular Interactions Using FET Arrays 有权
    使用FET阵列检测分子相互作用的方法和装置

    公开(公告)号：US20120065093A1

    公开(公告)日：2012-03-15

    申请号：US13229456

    申请日：2011-09-09

    Applicant: Jonathan Rothberg ,  Wolfgang Hinz

    Inventor： Jonathan Rothberg ,  Wolfgang Hinz

    IPC: C40B30/04 ,  C40B40/06

    CPC classification number: C12Q1/6825 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N27/26 ,  G01N27/4145 ,  G01N27/4148 ,  G01N33/54373 ,  G01N33/6818 ,  H01L29/78 ,  H01L29/788 ,  H01L2924/01006

    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。

    Methods of Primer Extension Using Porous Particle Supports
    5.
    发明申请
    Methods of Primer Extension Using Porous Particle Supports 审中-公开
    使用多孔粒子载体的引物延伸方法

    公开(公告)号：US20110201506A1

    公开(公告)日：2011-08-18

    申请号：US13029611

    申请日：2011-02-17

    Applicant: Wolfgang HINZ ,  John Leamon ,  David Light ,  Jonathan Rothberg

    Inventor： Wolfgang HINZ ,  John Leamon ,  David Light ,  Jonathan Rothberg

    IPC: C40B10/00 ,  C40B50/00

    CPC classification number: C12N15/1093 ,  B01J19/0046 ,  B01J2219/00466 ,  B01J2219/005 ,  B01J2219/00596 ,  B01J2219/00722 ,  C12Q1/6874 ,  C40B40/08 ,  C40B50/06 ,  Y10T428/2982

    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，这导致分析测定中粒子与粒子变化的减少。 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。

    Chemically sensitive sensors with sample and hold capacitors
    10.
    发明授权
    Chemically sensitive sensors with sample and hold capacitors 有权
    具有采样和保持电容器的化学敏感传感器

    公开(公告)号：US08492800B2

    公开(公告)日：2013-07-23

    申请号：US13554585

    申请日：2012-07-20

    Applicant: Jonathan Rothberg ,  Wolfgang Hinz ,  Kim Johnson ,  James Bustillo

    Inventor： Jonathan Rothberg ,  Wolfgang Hinz ,  Kim Johnson ,  James Bustillo

    IPC: G01N27/403

    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

    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 hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

    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。 在一个实例中，chemFET阵列基于监测氢离子浓度（pH），其他分析物浓度变化和/或与DNA合成相关的化学过程相关联的结合事件的变化来促进DNA测序技术。

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