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    • 1. 发明授权
    • Phase-protecting reagent flow orderings for use in sequencing-by-synthesis
    • 用于逐段合成的相保护试剂流动顺序
    • US09428807B2
    • 2016-08-30
    • US13440849
    • 2012-04-05
    • Earl HubbellJonathan Schultz
    • Earl HubbellJonathan Schultz
    • C12Q1/68
    • C12Q1/6869C12Q1/6874C12Q2533/101C12Q2565/301C12Q2565/607
    • A method for nucleic acid sequencing includes disposing template polynucleotide strands in defined spaces on a sensor array, at least some of the template polynucleotide strands having a sequencing primer and a polymerase operably bound therewith; exposing the template polynucleotide strands to a series of flows of nucleotide species flowed according to a predetermined ordering; and determining, for each of the series of flows of nucleotide species, how many nucleotide incorporations occurred for that particular flow to determine a predicted sequence of nucleotides corresponding to the template polynucleotide strands, wherein the predetermined ordering (a) is not a series of consecutive repetitions of a 4-flow permutation of four different nucleotide species, (b) is not specifically tailored to a particular combination of a particular template polynucleotide strand to be sequenced and a particular sequencing primer to be used, and (c) comprises a phase-protecting flow ordering.
    • 用于核酸测序的方法包括在传感器阵列上的限定空间中设置模板多核苷酸链,至少一些模板多核苷酸链具有测序引物和与之可操作地结合的聚合酶; 将模板多核苷酸链暴露于根据预定排序流动的一系列核苷酸类型的流; 并且对于核苷酸种类的每一系列流程,确定针对该特定流出现多少个核苷酸掺入以确定对应于模板多核苷酸链的预测的核苷酸序列,其中预定顺序(a)不是一系列连续的 重复四种不同核苷酸物种的4流置换,(b)不是特定的针对待测序的特定模板多核苷酸链和特定的待测序列的特定组合而定制的,(c) 保护流量顺序。
    • 10. 发明授权
    • Integrated sensor arrays for biological and chemical analysis
    • 用于生物和化学分析的集成传感器阵列
    • US08936763B2
    • 2015-01-20
    • US13125133
    • 2009-10-22
    • Jonathan RothbergJames BustilloMark MilgrewJonathan SchultzDavid MarranTodd RearickKim Johnson
    • Jonathan RothbergJames BustilloMark MilgrewJonathan SchultzDavid MarranTodd RearickKim Johnson
    • G01N27/403G01N27/414C12Q1/68H01L21/82
    • G01N27/4145C12Q1/6869C12Q1/6874G01N27/4148H01L21/82C12Q2565/607
    • 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.
    • 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。