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    FLUIDICS SYSTEM FOR SEQUENTIAL DELIVERY OF REAGENTS
    3.
    发明申请
    FLUIDICS SYSTEM FOR SEQUENTIAL DELIVERY OF REAGENTS 有权
    用于顺序递送试剂的流体系统

    公开(公告)号：US20100300559A1

    公开(公告)日：2010-12-02

    申请号：US12785667

    申请日：2010-05-24

    Applicant: Jonathan Schultz ,  David Marran

    Inventor： Jonathan Schultz ,  David Marran

    IPC: F16L41/00

    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物端口离开流体回路 ，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。 本发明在用于进行灵敏多步反应（例如基于pH的DNA测序反应）的装置中特别有利。

    Integrated sensor arrays for biological and chemical analysis
    4.
    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。

    Apparatus and methods for performing electrochemical reactions
    6.
    发明授权
    Apparatus and methods for performing electrochemical reactions 有权
    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

    Applicant: John Nobile ,  Thomas Roth ,  Todd Rearick ,  Jonathan Schultz ,  Jonathan Rothberg ,  David Marran

    Inventor： John Nobile ,  Thomas Roth ,  Todd Rearick ,  Jonathan Schultz ,  Jonathan Rothberg ,  David Marran

    IPC: C12M1/34 ,  C12M3/00 ,  C12M1/00 ,  C12Q1/68 ,  G01N27/403

    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 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.

    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。

    INTEGRATED SENSOR ARRAYS FOR BIOLOGICAL AND CHEMICAL ANALYSIS
    7.
    发明申请
    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：US20110263463A1

    公开(公告)日：2011-10-27

    申请号：US13125133

    申请日：2009-10-22

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

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

    IPC: C40B60/12 ,  B82Y15/00

    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。

    APPARATUS AND METHODS FOR PERFORMING ELECTROCHEMICAL REACTIONS
    8.
    发明申请
    APPARATUS AND METHODS FOR PERFORMING ELECTROCHEMICAL REACTIONS 有权
    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

    Applicant: John Nobile ,  Thomas Roth ,  Todd Rearick ,  Jonathan Schultz ,  Jonathan Rothberg ,  David Marran

    Inventor： John Nobile ,  Thomas Roth ,  Todd Rearick ,  Jonathan Schultz ,  Jonathan Rothberg ,  David Marran

    IPC: G01N27/26

    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 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.

    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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