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。

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。

公开(公告)号：US20130302932A1

公开(公告)日：2013-11-14

申请号：US13603631

申请日：2012-09-05

Applicant: James Bustillo ,  Jonathan SCHULTZ ,  Todd Rearick ,  Mark Milgrew

Inventor： James Bustillo ,  Jonathan SCHULTZ ,  Todd Rearick ,  Mark Milgrew

IPC: G01N27/414

CPC classification number: G01N27/4145 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N27/27 ,  G01N27/414 ,  Y10T29/49002

Abstract: Methods and apparatus relating to 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: 与用于监测化学和/或生物反应的FET阵列相关的方法和装置，例如核酸序列合成反应。 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）。

公开(公告)号：US20120035062A1

公开(公告)日：2012-02-09

申请号：US13157865

申请日：2011-06-10

Applicant: Jonathan SCHULTZ ,  John DAVIDSON

Inventor： Jonathan SCHULTZ ,  John DAVIDSON

IPC: C40B30/00 ,  C12P19/34 ,  C40B60/12 ,  C12Q1/68 ,  C12M1/40

CPC classification number: C12Q1/6869 ,  B01L3/5027 ,  C12Q1/6874 ,  C12Q2537/155 ,  C12Q2563/149 ,  C12Q2565/301 ,  C12Q2565/629

Abstract: A method for sequencing a polynucleotide strand by using sequencing-by-synthesis techniques. To address the problem of incomplete extension (IE) and/or carry forward (CF) errors that can occur in sequencing-by-synthesis reactions, an alternative flow ordering of dNTPs is used. In contrast to conventional flow orderings, the dNTPs are flowed in an ordering that is not a continuous repeat of an ordering of the four different dNTPs. This alternate flow ordering may reduce the loss of phasic synchrony in the population of template polynucleotide strands that result from IE and/or CF errors.

Abstract translation: 通过使用按顺序合成技术测序多核苷酸链的方法。 为了解决在逐个合成反应中可能发生的不完全扩展（IE）和/或结转（CF）错误的问题，使用了dNTP的替代流顺序。 与常规流顺序相反，dNTP以不是四种不同dNTP的顺序的连续重复的顺序流动。 这种交替流顺序可以减少由IE和/或CF错误导致的模板多核苷酸链群体中的相位同步损失。