CN105283758B - 具有一致传感器表面区域的化学传感器 - Google Patents
具有一致传感器表面区域的化学传感器 Download PDFInfo
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Abstract
在一个实施方式中,描述了化学传感器。化学传感器包括化学灵敏的场效应晶体管,其包括具有上表面的浮栅导体。材料限定延伸至所述浮栅导体的上表面的开孔。材料包括在第二电介质下方的第一电介质。导电元件接触所述浮栅导体的上表面并且沿着开孔的侧壁延伸一定的距离,所述距离由第一电介质的厚度限定。
Description
相关申请的交叉引用
本申请要求2013年8月22日提交的美国临时申请号61/868,739、和2013年3月15日提交的61/790,866的优先权,其全部内容通过引用以它们的整体并入本文。
技术领域
本公开涉及用于化学分析的传感器,和涉及制造这样的传感器的方法。
背景技术
各种类型的化学传感器已经用于化学过程的检测。一种类型是化学灵敏的场效应晶体管(chemFET)。chemFET包括由通道区域分开的源极和漏极,和偶联至通道区域的化学灵敏区域。ChemFET的运转是基于通道电导的调制,其是由于附近发生的化学反应在灵敏区域的电荷的改变造成的。通道电导的调制改变chemFET的阈值电压,其可被测量,以检测和/或测定化学反应的特征。可例如通过施加适当的偏压电压至源极和漏极,和测量流过chemFET的所得电流测量阈值电压。作为另一实施例,可通过驱动已知电流通过chemFET,和测量在源极或漏极的所得电压。
离子灵敏的场效应晶体管(ISFET)是在灵敏区域包括离子灵敏的层的一类chemFET。分析物溶液中离子的存在改变离子灵敏的层和分析物溶液之间界面处的表面电位,其是由于分析物溶液中存在的离子造成的表面电荷基团的质子化或去质子化。ISFET的灵敏区域处表面电位的改变影响可测量的设备的阈值电压,以指示溶液中离子的存在和/或浓度。
ISFET阵列可用于监测化学反应,比如DNA测序反应,其基于反应期间存在、产生或使用的离子的检测。见,例如,Rothberg等的美国专利号7,948,015,其通过引用并入本文。更一般而言,大的chemFET阵列或其他类型的化学传感器可用于检测和测量各种过程中各种分析物(例如氢离子、其他离子、化合物等)的静态和/或动态量或浓度。过程可例如是生物或化学反应、细胞或组织培养或监测天然活性、核酸测序等。
操作大尺寸化学传感器阵列出现的问题是传感器输出信号容易遭受噪声的影响。具体而言,噪声影响用于测定通过传感器检测的化学和/或生物过程的特征的下游信号处理的精确性。另外,横跨阵列的化学传感器性能变化产生传感器输出信号的非期望的差异,其使下游信号处理更加复杂。
所以期望提供包括低噪声化学传感器的设备,和制造这样的设备的方法。
发明内容
在一个实施方式中,描述了化学传感器。化学传感器包括化学灵敏的场效应晶体管,其包括具有上表面的浮栅导体。材料限定延伸至所述浮栅导体的上表面的开孔,材料包括在第二电介质下方的第一电介质。导电元件接触所述浮栅导体的上表面并且沿着所述开孔的侧壁延伸一定的距离,所述距离由第一电介质的厚度限定。
在另一实施方式中,描述了制造化学传感器的方法。方法包括形成化学灵敏的场效应晶体管,其包括具有上表面的浮栅导体。方法进一步包括形成材料,其限定延伸至浮栅导体上表面的开孔,所述材料包括在第二电介质下方的第一电介质。方法进一步包括形成导电元件,其接触所述浮栅导体的上表面并且沿着所述开孔的侧壁延伸一定的距离,所述距离由第一电介质的厚度限定。
在本说明书中描述的主题的一个多个实施方式的具体方面阐释在附图和下面说明书中。主题的其他特征、方面和优势将从说明书、附图和权利要求中变得显而易见。
附图说明
图1根据示例性实施方式图解用于核酸测序的***组件的方块图。
图2根据示例性实施方式图解一部分集成电路设备和流动池的横截面图。
图3根据第一实施方式图解两个代表性化学传感器和它们相应的反应区域的横截面图。
图4至10根据第一实施方式阐释形成化学传感器阵列和相应的反应区域的制造工艺的阶段。
图11至12根据第二实施方式阐释用于形成化学传感器的阵列和相应的反应区域的制造工艺的阶段。
图13至14根据第三实施方式阐释用于形成化学传感器的阵列和相应的反应区域的制造工艺的阶段。
图15至16根据第三实施方式阐释用于形成化学传感器的阵列和相应的反应区域的制造工艺的阶段。
发明详述
描述的化学检测设备包括低噪声化学传感器,比如化学灵敏的场效应晶体管(chemFETs),用于检测叠加的可操作相关化学反应中的化学反应。
减小单个化学传感器和叠加反应区域的平视图或顶视图面积(或占地面积)允许更高密度的设备。但是,随着化学传感器的尺寸减小,申请人已经发现传感器的传感表面区域的相应减小可明显影响性能。
例如,对于具有在反应区域底部限定的传感表面的化学传感器,减小反应区域的平视图尺寸(例如宽度或直径)使得传感表面区域类似减小。申请人已经发现随着传感表面区域下降至技术限制,由于传感表面上电荷随机波动的流体噪声,使得增加比例的传感表面电位的总体变化。这可显著降低传感器输出信号的信噪比(SNR),其影响用于测定通过传感器检测的化学和/或生物过程的特征的下游信号处理的精确性。
本文所述的化学传感器具有不限于在反应区域底部的二维面积的传感表面区域。在本文所述的实施方式中,所述化学传感器的传感表面包括沿着反应区域的底部表面的大体上水平部分,以及沿着包含反应区域的开孔的侧壁延伸的大体上竖直部分。
大体上竖直部分沿着侧壁延伸的距离由形成开孔下部的电介质材料的厚度限定。使用在阵列间产生非常小厚度变化的过程(例如薄膜沉积)可沉积电介质材料。在这样的情况下,化学传感器的传感器表面区域可被非常良好控制,产生阵列间均匀的化学传感器性能和因此简化下游信号处理。
通过在大体竖直方向上延伸传感表面,化学传感器可具有小的占地面积,同时也具有足够大的传感表面区域,以避免与小的传感表面相关的噪声问题。化学传感器的占地面积部分由叠加反应区域的宽度(例如直径)决定并且可造小,允许高密度阵列。另外,因为传感表面在侧壁上延伸控制的距离,传感表面区域可相对大。结果,可以以高密度阵列提供低噪声化学传感器,使得可精确检测反应的特征。
图1根据示例性实施方式图解用于核酸测序的***组件的方块图。组件包括在集成电路设备100上的流动池101、参考电极108、用于测序的多个试剂114、阀组116、洗液110、阀112、流体控制器118、线路120/122/126、通路104/109/111、废物容器106、阵列控制器124,和用户界面128。集成电路设备100包括微孔阵列107叠加传感器阵列,其包括如本文所描述的化学传感器。流动池101包括入口102、出口103和流动腔105,其限定试剂114在微孔阵列107上的流动路径。
参考电极108可以是任何适当类型或形状,包括具有流体通路或***通路111内腔的导线的同心圆柱体。试剂114可通过泵、气压或其他适当的方法驱动通过流体通路、阀和流动池101,和在离开流动池101的出口103之后可丢入废物容器106。流体控制器118可用适当的软件控制用于试剂114的驱动力和阀112和阀组116的操作。
微孔阵列107包括反应区域,也本文称为微孔,其操作上与传感器阵列中相应的化学传感器相关联。例如,每个反应区域可耦联适于检测该反应区域中感兴趣的分析物或反应性质的化学传感器。微孔阵列107可整合在集成电路设备100中,从而微孔阵列107和传感器阵列是单个设备或芯片的一部分。
流动池101可具有各种构造,用于控制微孔阵列107上试剂114的通路和流速。阵列控制器124为集成电路设备100提供偏压电压和定时和控制信号,用于读取传感器阵列的化学传感器。阵列控制器124也为参考电极108提供参考偏压电压,以使流经微孔阵列107的试剂114偏置。
在实验期间,阵列控制器124通过集成电路设备100上的输出端口经总线127收集和处理来自传感器阵列的化学传感器的输出信号。阵列控制器124可以是计算机或其他计算方式。阵列控制器124可包括储存数据和软件应用的储存器,用于访问数据和执行应用的处理器,和利于与图1中的***的各种组件通信的组件。
在阐释的实施方式中,阵列控制器124在集成电路设备100的外部。在一些可选的实施方式中,一些或所有的阵列控制器124进行的功能通过集成电路设备100上的控制器或其他数据处理器进行。
来自化学传感器的输出信号的值指示在微孔阵列107中的相应反应区域中进行的一个或多个反应的物理和/或化学参数。例如,在示例性实施方式中,输出信号的值可使用下述公开的技术处理:Rearick等2011年12月29日提交的美国专利申请号13/339,846,其基于2010年12月30日提交的美国临时专利申请号61/428,743,和2011年1月3日提交的61/429,328,和Hubbell 2011年12月29日提交的美国专利申请号13/339,753,其基于2010年12月29日提交的美国临时专利申请号61/428,097,其每一篇通过引用并入本文。
用户界面128可显示与流动池101和从集成电路设备100上传感器阵列中的化学传感器接收的输出信号相关的信息。用户界面128也可显示工具设置和控制,并且允许使用者进入或设置工具设置和控制。
流体控制器118可控制递送单个试剂114以预定的流速,以预定的顺序至流动池101和集成电路设备100预定的持续时间。阵列控制器124然后可收集和分析化学传感器的输出信号,其指示响应试剂114的递送发生的化学反应。
在实验期间,***也可监测和控制集成电路设备100的温度,从而发生反应并且在预定的温度下进行测量。
***可配置为使得单个流体或试剂在操作期间全部多步骤反应中接触参考电极108。可关闭阀112,以防止任何洗液110当试剂114流动时,流入通路109。尽管可停止洗液的流动,在参考电极108、通路109和微孔阵列107之间可仍具有不间断的流体和电通信。可选择参考电极108和通路109和111之间结合点之间的距离,从而几乎没有通路109中流动并且可能扩散至通路111的试剂量达到参考电极108。在示例性实施方式中,可选择洗液110连续接触参考电极108,其可尤其用于使用频繁冲洗步骤的多步骤反应。
图2图解了一部分集成电路设备100和流动池101的横截面和展开图。集成电路设备100包括操作上与传感器阵列205相关联的反应区域的微孔阵列107。在操作期间,流动池101的流动腔105限制横跨微孔阵列107中反应区域开孔端递送的试剂的试剂流208。可选择反应区域的体积、形状、纵横比(比如基底宽度与孔深度比例)和其他尺寸特征,这基于发生的反应的性质以及采用的试剂、副产物或标记技术(如果有的话)。
传感器阵列205的化学传感器响应于微孔阵列107中相关的反应区域的化学反应(和产生与其相关的输出信号),以检测感兴趣的分析物或反应性质。传感器阵列205的化学传感器可例如是化学灵敏的场效应晶体管(chemFETs),比如离子灵敏的场效应晶体管(ISFETs)。可用于实施方式的化学传感器和阵列构造的例子描述在美国专利申请公开号2010/0300559、2010/0197507、2010/0301398、2010/0300895、2010/0137143和2009/0026082,和美国专利号7,575,865,其每一篇通过引用并入本文。
图3根据第一实施方式图解两个代表性化学传感器和它们相应的反应区域的横截面图。图3中,显示两个化学传感器350、351,表示可包括成千上万化学传感器的传感器阵列的小部分。
化学传感器350耦联至相应的反应区域301,和化学传感器351耦联至相应的反应区域302。化学传感器350是传感器阵列中化学传感器的代表。在阐释的实施例中,化学传感器350是化学灵敏的场效应晶体管(chemFET),更具体的在该实施例中是离子灵敏的场效应晶体管(ISFET)。
化学传感器350包括浮栅结构318,其具有通过导电元件370耦联至反应区域301的传感器板320。图3中可见,传感器板320是浮栅结构318中的最上浮栅导体。在阐释的实施例中,浮栅结构318包括电介质材料层319中导电材料的多个图案化层。
化学传感器350也包括半导体衬底354中的源极区域321和漏极区域322。源极区域321和漏极区域322包括掺杂的半导体材料具有的导电类型与衬底354的导电类型不同。例如,源极区域321和漏极区域322可包括掺杂的P型半导体材料,和衬底可包括掺杂的n型半导体材料。
通道区域323将源极区域321和漏极区域322分开。浮栅结构318叠加在通道区域323上,并且通过栅极电介质352与衬底354分开。栅极电介质352可以是例如二氧化硅。可选地,其他电介质可用于栅极电介质352。
如图3中所显示,反应区域301在具有侧壁303的开孔中,所述侧部303延伸通过电介质材料310、308至传感器板320的上表面。每个电介质材料310、308可包括一个或多个材料层,比如二氧化硅或氮化硅。
开孔包括下部314,其在电介质材料308中并且接近传感器板320。开孔也包括上部315,其在电介质材料310中并且从下部314延伸至电介质材料310的上表面。在阐释的实施方式中,开孔上部315的宽度大于开孔下部314的宽度。
开孔可例如具有圆形横截面。可选地,开孔可非圆形的,例如,横截面可以是正方形、矩形、六边形,或不规则形状的。开孔的尺寸,和它们的间距,可在实施方式之间不同。在一些实施方式中,开孔可具有定义为4倍平面视图横截面面积(A)除以π的平方根(例如,sqrt(4*A/π)),不大于5微米,比如不大于3.5微米,不大于2.0微米,不大于1.6微米,不大于1.0微米,不大于0.8微米,不大于0.6微米,不大于0.4微米,不大于0.2微米或甚至不大于0.1微米的特征直径。
开孔的下部314包括在电介质材料308的侧壁303上的导电元件370。在阐释的实施方式中,导电元件370的内表面371限定反应区域301的下段。即,在导电元件370的内表面371和化学传感器350的反应区域301之间没有介入沉积材料层。由于该结构,导电元件370的内表面371是杯子形状的并且用作化学传感器350的传感表面。
导电元件370是开孔的下部314中的共形材料层,使得导电元件370延伸横跨传感器板320的上表面。在阐释的实施方式中,导电元件370突出离开开孔下部314并且在电介质材料308的上表面上。
如图3中所显示,导电元件370不延伸进入开孔的上部315。而是,导电元件370通过开孔的上部315远离电介质材料310的上表面311。结果,电介质材料310的内表面限定反应区域301的上段。导电元件370可例如沿着侧壁303的至少5%,侧壁303的至少10%,至少25%,至少50%),至少75%,或甚至至少85%延伸。
杯子状导电元件370的内表面371使得化学传感器350至具有小的平面视图面积,同时也具有足够大的表面积,以避免与小的传感表面相关的噪声问题。化学传感器350的平面视图面积部分由反应区域301的宽度(或直径)决定并且可造小,允许高密度阵列。另外,因为传感表面沿着侧壁303延伸,传感表面区域取决于该延伸的距离和反应区域301的周长,并且可相对大。结果,可以以高密度阵列提供低噪声化学传感器350、351,使得可精确检测反应的特征。
在设备的制造和/或操作期间,可生长导电元件370的薄氧化物材料,其用作化学传感器350的传感材料(例如离子灵敏的传感材料)。是否形成氧化物取决于导电材料、进行的制造方法和操作设备的条件。例如,在一个实施方式中,导电元件370可以是氮化钛,并且氧化钛或氮氧化钛可在制造期间和/或暴露于溶液期间使用期间,在导电元件370的内表面371上生长。
在阐释的实施例中,导电元件370显示为单层材料。更一般而言,导电元件370可包括一层或多层各种导电材料,比如金属或陶瓷,这取决于实施方式。导电材料可以是例如金属材料或其合金,或可以是陶瓷材料,或其组合。示例性金属材料包括下述一种:铝、铜、镍、钛、银、金、铂、铪、镧、钽、钨、铱、锆、钯或其组合。示例性陶瓷材料包括下述一种:氮化钛、氮化钛铝、氮氧化钛、氮化钽或其组合。
在一些可选的实施方式中,另外的共形传感材料(未显示)沉积在导电元件370上和开孔中。传感材料可包括一个或多个各种不同的材料,以利于对具体的离子灵敏。例如,氮化硅或氮氧化硅,以及金属氧化物比如二氧化硅,氧化铝或氧化钽,一般提供对氢离子的灵敏性,而包括包含缬氨霉素的聚氯乙烯的传感材料提供对钾离子的灵敏性。也可使用对其他离子比如钠、银、铁、溴、碘、钙和硝酸根灵敏的材料,这取决于实施方式。
操作时,反应物、洗液和其他试剂可通过扩散机构340移动进入和离开反应区域301。化学传感器350响应导电元件370附近的电荷324的量(和产生与其相关的输出信号)。分析物溶液中电荷324的存在改变反应区域301中导电元件370和分析物溶液之间界面处的表面电位。电荷324的改变使得改变浮栅结构318上的电压,其接着改变晶体管的阈值电压。可通过测量源极区域321和漏极区域322之间通道区域323中的电流测量阈值电压的该改变。结果,化学传感器350可用于在与源极区域321或漏极区域322连接的阵列线上直接提供基于电流的输出信号,或用另外的电路间接提供基于电压的输出信号。
因为电荷324更高度集中在反应区域301的底部附近,导电元件370沿着开孔的侧壁303延伸的距离在响应电荷324检测的期望信号的振幅,和流体噪声之间折中,所述流体噪声是由于导电元件370和分析物溶液之间电荷的随机波动。增加导电元件370沿着侧壁303延伸的距离增加化学传感器350的流体界面面积,其用于减少流体噪声。但是,由于电荷324扩散离开反应区域310,电荷324的浓度随着距离反应区域301的底部的距离而下降。结果,导电元件370的上侧壁段检测来自具有低电荷浓度的部分信号,其可降低传感器350检测的期望的信号的总体振幅。相反,减小导电元件370沿着侧壁303延伸的距离减小传感表面区域和因此增加流体噪声,但是也增加传感器350检测的期望的信号的总体振幅。
对于非常小的传感表面区域,申请人已经发现流体噪声作为传感表面区域的函数而改变,与期望的信号的振幅不同。因为传感器输出信号的SNR是这两个量的比例,存在导电元件370沿着侧壁303延伸、其中SNR最大的最佳距离。
最佳距离可在实施方式之间不同,这取决于导电元件370和电介质材料310的材料特征,反应区域的体积、形状、纵横比(比如基底宽度与孔深度比例),和其他尺寸特征,发生的反应的性质,以及采用的试剂、副产物,或标记技术(如果有的话)。最佳距离可例如根据经验决定。
如在下面参考图4至9更详细描述,导电元件370沿着侧壁303延伸的距离由形成开孔下部314的电介质材料308的厚度309限定。可使用在阵列间产生厚度309非常小变化的方法(例如薄膜沉积)沉积电介质材料308。在这样的情况下,化学传感器的传感器表面区域可被非常良好控制,产生阵列间均匀的化学传感器性能和简化下游信号处理。
在一个实施方式中,在反应区域301中进行的反应可以是分析反应,以鉴定或测定感兴趣的分析物的特征或特性。这样的反应可直接或间接产生影响导电元件370附近电荷量的副产物。如果这样的副产物以少量产生或快速降解或与其他成分反应,可在反应区域301中同时分析多拷贝的相同分析物以便增加产生的输出信号。在一个实施方式中,多拷贝的分析物可连接至固相载体312,在沉积至反应区域301之前或之后。固相载体312可以是微粒、纳米颗粒、珠子、固体或多孔凝胶等等。为了简化和容易阐释,固相载体312在本文也称为粒子。对于核酸分析物,可通过滚环扩增(RCA),指数RCA,重组酶聚合酶扩增(RPA),聚合酶链式反应扩增(PCR),乳液PCR扩增等技术制备多个连接的拷贝,以产生扩增子,而不需要固体载体。
在各种示例性实施方式中,本文所述的方法、***和计算机可读的介质可有利地用于处理和/或分析从基于电子或电荷的核酸测序获得的数据和信号。在基于电子或电荷的测序(比如,基于pH的测序)中,可通过检测作为聚合酶-催化核苷酸延伸反应的天然副产物产生的离子(例如,氢离子)测定核苷酸并入事件。这可用于对样品或模板核酸测序,所述样品或模板核酸可以是感兴趣的核酸序列的片段,例如,并且其可直接或间接作为克隆群体附接至固体载体,比如粒子、微粒、珠子等。样品或模板核酸可以可操作地结合引物和聚合酶并且可进行重复轮或″流″的脱氧核苷三磷酸(″dNTP″)添加(其在本文可称为″核苷酸流″,由其可产生核苷酸并入)和冲洗。引物可使样品或模板退火从而引物的3′端可当添加与模板中的下一碱基互补的dNTP时通过聚合酶延伸。然后,基于核苷酸流的已知序列和指示每个核苷酸流期间,离子浓度的测量的化学传感器的输出信号,可测定类型的同一性,与耦联化学传感器的反应区域中存在的样品核酸相关的核苷酸(一种或多种)的序列和数量。
图4至10根据第一实施方式阐释形成化学传感器阵列和相应的反应区域的制造工艺的阶段。
图4图解在第一阶段形成的结构400。结构400包括用于化学传感器350、351的浮栅结构(例如浮栅结构318)。
可通过将栅极电介质材料的层沉积在半导体衬底354上,和将多晶硅(或其他导电材料)的层沉积在栅极电介质材料的层上形成结构400。多晶硅的层和栅极电介质材料的层可然后使用蚀刻掩模蚀刻,以形成栅极电介质元件(例如栅极电介质352)和浮栅结构的最下导电材料元件。在形成离子植入掩模之后,可然后进行离子植入以形成化学传感器的源极和漏极区域(例如源极区域321和漏极区域322)。
电介质材料319的第一层可然后沉积在最下导电材料元件的上方。可然后在电介质材料319的第一层中蚀刻的通孔中形成导电插头,以接触浮栅结构的最下导电材料元件。导电材料的层可然后沉积在电介质材料319的第一层上并且图案化,以形成与导电插头电连接的第二导电材料元件。可然后多次重复该过程,以形成图4中显示的完整的浮栅结构318。可选地,可进行其他和/或另外的技术,以形成该结构。
形成图4中的结构400也可包括形成另外的元件比如阵列线(例如行线、列线等),用于访问化学传感器,衬底354中另外的掺杂区域,和用于操作化学传感器的其他电路(例如选择开关、接入电路、偏置电路等),这取决于其中实施本文所述的化学传感器的设备和阵列构造。在一些实施方式中,结构的元件可例如使用下面描述的技术制造:美国专利申请公开号2010/0300559、2010/0197507、2010/0301398、2010/0300895、2010/0137143和2009/0026082和美国专利号7,575,865,其通过上面的引用并入。
接下来,具有厚度309的电介质材料308沉积在图4中阐释的结构400上,产生图5中阐释的结构。电介质材料308包括电介质的一个或多个电介质层。电介质材料308可使用产生横跨阵列的厚度309非常小变化的方法沉积。例如,电介质材料308可包括二氧化硅并且使用高密度等离子体(HDP)沉积来沉积。
接下来,蚀刻图5中结构的电介质材料308,以形成腔600、602,其延伸至化学传感器350、351的浮栅结构的上表面,产生图6中阐释的结构。
可例如通过使用光刻工艺形成腔600、602,以使电介质材料308上的光刻胶层图案化,以限定腔600、602的位置,并且然后使用图案化的光刻胶作为蚀刻掩模非均匀地蚀刻电介质材料308。电介质材料308的非均匀蚀刻可例如是干燥蚀刻工艺,比如基于氟的活性离子蚀刻(RIE)工艺。
接下来,导电材料700的共形层沉积在图6阐释的结构上,产生图7中阐释的结构。导电材料700包括一层或多层导电材料。例如,导电材料700可以是氮化钛层,或钛层。可选地,可使用其他和/或另外的导电材料,比如上面参考导电元件370描述的那些。另外,可沉积大于一个导电材料的层。
可使用各种技术沉积导电材料700,比如喷射、活性喷射、原子层沉积(ALD)、低压化学气相沉积(LPCVD)、等离子体增强的化学气相沉积(PECVD)、金属有机化学气相沉积(MOCVD)等。
接下来,蚀刻导电材料700,以形成导电元件370、800,产生图8中阐释的结构。在阐释的实施方式中,导电元件370、800突出离开腔600、602,并且在电介质材料308的上表面上。
可例如通过腔600、602中的第一形成掩模元件形成导电元件370、800。掩模元件可具有的宽度大于腔600、602的宽度,使得掩模元件在电介质材料308的一部分上表面上延伸。掩模元件可例如通过使用光刻工艺使光刻胶的层图案化形成。可选地,其他材料和方法可用于形成掩模元件。
可然后使用掩模元件作为蚀刻掩模蚀刻导电材料700。蚀刻从电介质材料308的上表面去除暴露的导电材料700并且留下残余的材料形成导电元件370、800。可然后使用例如光刻胶剥离过程去除掩模元件。
接下来,在图8中阐释的结构上形成电介质材料310,产生图9中阐释的结构。电介质材料310可包括一层或多层沉积电介质材料,比如二氧化硅或氮化硅。
接下来,蚀刻电介质材料310,以形成限定反应区域301、302延伸至导电元件370、800的开孔,产生图10中阐释的结构。
图11至12根据第二实施方式阐释用于形成化学传感器的阵列和相应的反应区域的制造工艺的阶段。
图11图解在图10结构的电介质材料310上形成硬掩模材料层1100的第一阶段。硬掩模材料层1100可包括与电介质材料310的不同的材料。例如,硬掩模材料层1100和电介质材料310可包括相对于彼此可选择性蚀刻的材料。例如,硬掩模材料层1100可包括氮化硅,和电介质材料310可包括二氧化硅。
接下来,可蚀刻硬掩模材料层1100,以在电介质材料310上形成硬掩模材料元件1102、1104、1106。可然后使用所述硬掩模材料元件1102、1104、1106作为蚀刻掩模蚀刻电介质材料310,以形成限定反应区域301、302延伸至导电元件370、800的开孔,产生图12中阐释的结构。
图13至14根据第三实施方式阐释用于形成化学传感器的阵列和相应的反应区域的制造工艺的阶段。
图13图解进行平面化工艺以从图10结构的电介质308的顶表面去除导电材料700的第一阶段。与图8的蚀刻工艺相反,图13的平面化工艺形成导电元件1300、1310,其延伸至电介质308的上表面。即,平面化工艺从电介质308的顶表面完全去除导电材料700,并且在腔600、602中留下残留的导电材料,以形成导电元件1300、1310。平面化工艺可例如是化学机械抛光(CMP)。
接下来,在图13中阐释的结构上形成电介质材料310。然后蚀刻电介质材料310形成限定反应区域301、302延伸至导电元件1300,1310的开孔,产生图14中阐释的结构。
图15至16根据第四实施方式阐释用于形成化学传感器的阵列和相应的反应区域的制造工艺的阶段。
图15图解用牺牲材料1500填充图7中阐释的结构的腔600、602的第一阶段。腔600、602的填充可通过将牺牲材料1500沉积在图7中阐释的结构上进行,并且进行平面化工艺,以暴露在腔600、602之间延伸的导电材料700。
然后蚀刻附近腔600、602之间的至少一部分导电材料700,以形成导电元件370、800。可使用上面参考图8描述的技术蚀刻导电材料700。蚀刻不去除腔600、602中的牺牲材料1500。结果,牺牲材料用作导电元件370、800的保护掩模。
然后沉积和蚀刻电介质材料310,以形成延伸至牺牲材料1500的开孔的上部,产生图16中阐释的结构。电介质材料310和牺牲材料每个可包括相对于彼此可选择性蚀刻材料。在这样的情况下,牺牲材料1500用作电介质材料310蚀刻期间的蚀刻停止。
可然后进行第二蚀刻工艺,以选择性去除牺牲材料1500并且暴露导电元件370、800,产生图10中阐释的结构。第二蚀刻工艺可例如是湿蚀刻工艺,其去除牺牲材料而不明显蚀刻电介质材料或导电元件370、800。
尽管通过参考上面详述的优选实施方式和实施例公开了本发明,但是应当理解这些实施例期望为示意性的而不是限制性的。考虑本领域技术人员容易想到修饰和组合,该修饰和组合在本发明的精神和所述权利要求的范围内。
Claims (8)
1.化学传感器,其包括:
化学灵敏的场效应晶体管,其包括具有上表面的浮栅导体;
材料,其限定延伸至所述浮栅导体的上表面的开孔;和
导电元件,其接触所述浮栅导体的上表面并且沿着所述开孔的侧壁延伸一定的距离,所述距离由第一电介质的厚度限定;
所述材料包括在第二电介质下方的第一电介质,其中所述开孔包括在所述第一电介质中的下部和在所述第二电介质中的上部,所述开孔的所述下部的宽度小于所述上部的宽度,使得所述导电元件在所述第一电介质的上表面之上延伸。
2.权利要求1所述的化学传感器,其中所述导电元件包括限定所述化学传感器的反应区域的下部的内表面,和第二电介质包括限定所述开孔的上部的内表面。
3.权利要求1所述的化学传感器,其中所述导电元件延伸横跨所述浮栅导体的上表面,以限定所述化学传感器的反应区域的底部表面。
4.权利要求1所述的化学传感器,其中所述导电元件包括导电材料,和所述导电元件的内表面包括所述导电材料的氧化物。
5.权利要求1所述的化学传感器,其中所述化学传感器的传感表面包括所述导电元件的内表面。
6.权利要求1所述的化学传感器,其中所述化学灵敏的场效应晶体管响应于在所述导电元件附近发生的化学反应而产生传感器信号。
7.制造化学传感器的方法,所述方法包括:
形成化学灵敏的场效应晶体管,其包括具有上表面的浮栅导体;
形成第一电介质材料,其限定延伸至所述浮栅导体的上表面的开孔;和
形成导电元件,其接触所述浮栅导体的上表面并且沿着所述开孔的侧壁延伸一定的距离并且在所述第一电介质的上表面上延伸,所述距离由第一电介质的厚度限定;
在所述第一电介质之上并且在所述导电元件上形成第二电介质;以及
蚀刻第二电介质,以暴露所述导电元件,其中所述开孔包括在所述第一电介质中的下部和在所述第二电介质中的上部,所述开孔的所述下部的宽度小于所述上部的宽度。
8.权利要求7所述的方法,其中所述导电元件延伸横跨所述浮栅导体的上表面,以限定所述化学传感器的反应区域的底部表面。
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Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20140367748A1 (en) * | 2013-06-14 | 2014-12-18 | International Business Machines Corporation | EXTENDED GATE SENSOR FOR pH SENSING |
US10875023B2 (en) * | 2015-01-07 | 2020-12-29 | Personal Genomics, Inc. | Oriented loading systems and method for orienting a particle loaded in a well |
CN113945621A (zh) * | 2015-08-25 | 2022-01-18 | 生命技术公司 | 深微阱设计及其制造方法 |
US20170081712A1 (en) | 2015-09-22 | 2017-03-23 | Life Technologies Corporation | Systems and methods for analysis of nucleic acids |
US10386328B2 (en) * | 2016-09-09 | 2019-08-20 | Life Technologies Corporation | Chemical sensor with air via |
WO2019145755A1 (en) * | 2018-01-26 | 2019-08-01 | Università Degli Studi Di Bari Aldo Moro | A field effect transistor sensor and a corresponding array device |
JP2022500634A (ja) | 2018-09-13 | 2022-01-04 | ライフ テクノロジーズ コーポレーション | Chemfetセンサーアレイベースのシステムを用いた細胞分析 |
US10890554B1 (en) * | 2019-06-20 | 2021-01-12 | Globalfoundries Singapore Pte. Ltd. | Sensors with a non-planar sensing structure |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4430811C1 (de) * | 1994-08-30 | 1995-09-07 | Fraunhofer Ges Forschung | Verfahren zum Herstellen eines integrierten ionensensitiven Feldeffekttransistors in CMOS-Silizium-Planartechnologie |
WO2006056226A1 (de) * | 2004-11-26 | 2006-06-01 | Micronas Gmbh | Elektrisches bauelement |
WO2012152308A1 (en) * | 2011-05-06 | 2012-11-15 | X-Fab Semiconductor Foundries Ag | Ion sensitive field effect transistor |
Family Cites Families (346)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5530312B2 (zh) | 1975-01-16 | 1980-08-09 | ||
GB2096824A (en) | 1981-04-09 | 1982-10-20 | Sibbald Alastair | Chemically sensitive field effect transistor |
DE3269784D1 (en) | 1981-05-15 | 1986-04-17 | Licentia Gmbh | Method for measuring ionic concentrations |
JPS5870155U (ja) | 1981-11-06 | 1983-05-12 | ヤマハ株式会社 | 電子機器用収納家具 |
US4411741A (en) | 1982-01-12 | 1983-10-25 | University Of Utah | Apparatus and method for measuring the concentration of components in fluids |
NL8302964A (nl) | 1983-08-24 | 1985-03-18 | Cordis Europ | Inrichting voor het bepalen van de aktiviteit van een ion (pion) in een vloeistof. |
NL8303792A (nl) | 1983-11-03 | 1985-06-03 | Cordis Europ | Inrichting voorzien van een op een isfet gebaseerd meetcircuit; voor toepassing in het meetcircuit geschikte isfet en werkwijze ter vervaardiging van een in het meetcircuit toe te passen isfet. |
JPS60128345A (ja) | 1983-12-15 | 1985-07-09 | Olympus Optical Co Ltd | イオン濃度測定装置 |
US4660063A (en) | 1985-03-18 | 1987-04-21 | General Electric Company | Immersion type ISFET |
DE3513168A1 (de) | 1985-04-12 | 1986-10-16 | Thomas 8000 München Dandekar | Biosensor bestehend aus einem halbleiter auf silizium oder kohlenstoffbasis (elektronischer teil) und nukleinbasen (od. anderen biol. monomeren) |
US4743954A (en) | 1985-06-07 | 1988-05-10 | University Of Utah | Integrated circuit for a chemical-selective sensor with voltage output |
US4863849A (en) | 1985-07-18 | 1989-09-05 | New York Medical College | Automatable process for sequencing nucleotide |
EP0213825A3 (en) | 1985-08-22 | 1989-04-26 | Molecular Devices Corporation | Multiple chemically modulated capacitance |
GB8522785D0 (en) | 1985-09-14 | 1985-10-16 | Emi Plc Thorn | Chemical-sensitive semiconductor device |
US4822566A (en) | 1985-11-19 | 1989-04-18 | The Johns Hopkins University | Optimized capacitive sensor for chemical analysis and measurement |
US4864229A (en) | 1986-05-03 | 1989-09-05 | Integrated Ionics, Inc. | Method and apparatus for testing chemical and ionic sensors |
US4722830A (en) | 1986-05-05 | 1988-02-02 | General Electric Company | Automated multiple stream analysis system |
US5113870A (en) | 1987-05-01 | 1992-05-19 | Rossenfeld Joel P | Method and apparatus for the analysis, display and classification of event related potentials by interpretation of P3 responses |
JP2825206B2 (ja) | 1988-02-08 | 1998-11-18 | アイースタット コーポレーション | 金属酸化物電極 |
US4971903A (en) | 1988-03-25 | 1990-11-20 | Edward Hyman | Pyrophosphate-based method and apparatus for sequencing nucleic acids |
US4874499A (en) | 1988-05-23 | 1989-10-17 | Massachusetts Institute Of Technology | Electrochemical microsensors and method of making such sensors |
US5200051A (en) | 1988-11-14 | 1993-04-06 | I-Stat Corporation | Wholly microfabricated biosensors and process for the manufacture and use thereof |
US4990974A (en) | 1989-03-02 | 1991-02-05 | Thunderbird Technologies, Inc. | Fermi threshold field effect transistor |
EP0394598B1 (en) | 1989-04-28 | 1996-03-06 | International Business Machines Corporation | An improved gate array cell having FETS of different and optimized sizes |
US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
US6919211B1 (en) | 1989-06-07 | 2005-07-19 | Affymetrix, Inc. | Polypeptide arrays |
JP3001104B2 (ja) | 1989-10-04 | 2000-01-24 | オリンパス光学工業株式会社 | センサー構造体及びその製造法 |
US5110441A (en) | 1989-12-14 | 1992-05-05 | Monsanto Company | Solid state ph sensor |
US5317407A (en) | 1991-03-11 | 1994-05-31 | General Electric Company | Fixed-pattern noise correction circuitry for solid-state imager |
KR940010562B1 (ko) | 1991-09-06 | 1994-10-24 | 손병기 | Ta_2O_5수소이온 감지막을 갖는 감이온 전계효과 트랜지스터의 제조방법 |
WO1993008464A1 (en) | 1991-10-21 | 1993-04-29 | Holm Kennedy James W | Method and device for biochemical sensing |
US5846708A (en) | 1991-11-19 | 1998-12-08 | Massachusetts Institiute Of Technology | Optical and electrical methods and apparatus for molecule detection |
US5637469A (en) | 1992-05-01 | 1997-06-10 | Trustees Of The University Of Pennsylvania | Methods and apparatus for the detection of an analyte utilizing mesoscale flow systems |
US5284566A (en) | 1993-01-04 | 1994-02-08 | Bacharach, Inc. | Electrochemical gas sensor with wraparound reference electrode |
US5436149A (en) | 1993-02-19 | 1995-07-25 | Barnes; Wayne M. | Thermostable DNA polymerase with enhanced thermostability and enhanced length and efficiency of primer extension |
WO1994026029A1 (en) | 1993-04-26 | 1994-11-10 | Unifet Incorporated | Method and apparatus for multiplexing devices having long thermal time constants |
JP3413664B2 (ja) | 1993-08-12 | 2003-06-03 | ソニー株式会社 | 電荷転送装置 |
US5965452A (en) | 1996-07-09 | 1999-10-12 | Nanogen, Inc. | Multiplexed active biologic array |
US5414284A (en) | 1994-01-19 | 1995-05-09 | Baxter; Ronald D. | ESD Protection of ISFET sensors |
JP3351088B2 (ja) | 1994-03-28 | 2002-11-25 | 松下電工株式会社 | 電源装置 |
US5439839A (en) | 1994-07-13 | 1995-08-08 | Winbond Electronics Corporation | Self-aligned source/drain MOS process |
US6654505B2 (en) | 1994-10-13 | 2003-11-25 | Lynx Therapeutics, Inc. | System and apparatus for sequential processing of analytes |
US5631704A (en) | 1994-10-14 | 1997-05-20 | Lucent Technologies, Inc. | Active pixel sensor and imaging system having differential mode |
US5490971A (en) | 1994-10-25 | 1996-02-13 | Sippican, Inc. | Chemical detector |
US5585069A (en) | 1994-11-10 | 1996-12-17 | David Sarnoff Research Center, Inc. | Partitioned microelectronic and fluidic device array for clinical diagnostics and chemical synthesis |
DE19512117A1 (de) | 1995-04-04 | 1996-10-10 | Itt Ind Gmbh Deutsche | Meßeinrichtung |
US5856174A (en) | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
US5702964A (en) | 1995-10-17 | 1997-12-30 | Lg Semicon, Co., Ltd. | Method for forming a semiconductor device having a floating gate |
GB9620209D0 (en) | 1996-09-27 | 1996-11-13 | Cemu Bioteknik Ab | Method of sequencing DNA |
US5958703A (en) | 1996-12-03 | 1999-09-28 | Glaxo Group Limited | Use of modified tethers in screening compound libraries |
WO1998026277A2 (en) | 1996-12-12 | 1998-06-18 | Prolume, Ltd. | Apparatus and method for detecting and identifying infectious agents |
US20030215857A1 (en) | 1996-12-20 | 2003-11-20 | Roche Diagnostics Gmbh | Method for the direct, exponential amplification and sequencing of DNA molecules and its application |
DE19653439A1 (de) | 1996-12-20 | 1998-07-02 | Svante Dr Paeaebo | Verfahren zur direkten, exponentiellen Amplifikation und Sequenzierung von DNA Molekülen und dessen Anwendung |
US6605428B2 (en) | 1996-12-20 | 2003-08-12 | Roche Diagnostics Gmbh | Method for the direct, exponential amplification and sequencing of DNA molecules and its application |
US5912560A (en) | 1997-02-25 | 1999-06-15 | Waferscale Integration Inc. | Charge pump circuit for voltage boosting in integrated semiconductor circuits |
US5793230A (en) | 1997-02-26 | 1998-08-11 | Sandia Corporation | Sensor readout detector circuit |
US6197557B1 (en) | 1997-03-05 | 2001-03-06 | The Regents Of The University Of Michigan | Compositions and methods for analysis of nucleic acids |
US6327410B1 (en) | 1997-03-14 | 2001-12-04 | The Trustees Of Tufts College | Target analyte sensors utilizing Microspheres |
US7622294B2 (en) | 1997-03-14 | 2009-11-24 | Trustees Of Tufts College | Methods for detecting target analytes and enzymatic reactions |
US6391622B1 (en) | 1997-04-04 | 2002-05-21 | Caliper Technologies Corp. | Closed-loop biochemical analyzers |
EP1003908B1 (en) | 1997-04-16 | 2006-12-06 | Applera Corporation | Nucleic acid archiving |
US6872527B2 (en) | 1997-04-16 | 2005-03-29 | Xtrana, Inc. | Nucleic acid archiving |
US5911873A (en) | 1997-05-02 | 1999-06-15 | Rosemount Analytical Inc. | Apparatus and method for operating an ISFET at multiple drain currents and gate-source voltages allowing for diagnostics and control of isopotential points |
US7220550B2 (en) | 1997-05-14 | 2007-05-22 | Keensense, Inc. | Molecular wire injection sensors |
CA2291180A1 (en) | 1997-05-23 | 1998-11-26 | Lynx Therapeutics, Inc. | System and apparatus for sequential processing of analytes |
US6969488B2 (en) | 1998-05-22 | 2005-11-29 | Solexa, Inc. | System and apparatus for sequential processing of analytes |
US6002299A (en) | 1997-06-10 | 1999-12-14 | Cirrus Logic, Inc. | High-order multipath operational amplifier with dynamic offset reduction, controlled saturation current limiting, and current feedback for enhanced conditional stability |
FR2764702B1 (fr) | 1997-06-11 | 1999-09-03 | Lyon Ecole Centrale | Procede d'identification et/ou de dosage de substances biologiques, presentes dans un liquide conducteur, dispositif et capteur d'affinite utiles pour la mise en oeuvre de ce procede |
US5923421A (en) | 1997-07-24 | 1999-07-13 | Lockheed Martin Energy Research Corporation | Chemical detection using calorimetric spectroscopy |
US6465178B2 (en) | 1997-09-30 | 2002-10-15 | Surmodics, Inc. | Target molecule attachment to surfaces |
US6511803B1 (en) | 1997-10-10 | 2003-01-28 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
US6485944B1 (en) | 1997-10-10 | 2002-11-26 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
AU737174B2 (en) | 1997-10-10 | 2001-08-09 | President & Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
KR100251528B1 (ko) | 1997-10-22 | 2000-04-15 | 김덕중 | 복수개의 센스 소오스 패드를 구비한 센스 전계효과 트랜지스터 |
US6369737B1 (en) | 1997-10-30 | 2002-04-09 | The Board Of Trustees Of The Leland Stanford Junior University | Method and apparatus for converting a low dynamic range analog signal to a large dynamic range floating-point digital representation |
US7090975B2 (en) | 1998-03-13 | 2006-08-15 | Promega Corporation | Pyrophosphorolysis and incorporation of nucleotide method for nucleic acid detection |
CA2325886C (en) | 1998-04-09 | 2009-07-21 | California Institute Of Technology | Electronic techniques for analyte detection |
CA2330673C (en) | 1998-05-01 | 2009-05-26 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and dna molecules |
US6780591B2 (en) | 1998-05-01 | 2004-08-24 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and DNA molecules |
US7875440B2 (en) | 1998-05-01 | 2011-01-25 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and DNA molecules |
ATE423314T1 (de) | 1998-06-24 | 2009-03-15 | Illumina Inc | Dekodierung von matrixartig-angeordneten sensoren durch mikropartikel |
US6195585B1 (en) | 1998-06-26 | 2001-02-27 | Advanced Bionics Corporation | Remote monitoring of implantable cochlear stimulator |
JP4137239B2 (ja) | 1998-08-03 | 2008-08-20 | 株式会社堀場製作所 | Isfetアレイ |
US6191444B1 (en) | 1998-09-03 | 2001-02-20 | Micron Technology, Inc. | Mini flash process and circuit |
EP1055121A1 (en) | 1998-12-11 | 2000-11-29 | Symyx Technologies, Inc. | Sensor array-based system and method for rapid materials characterization |
US6232075B1 (en) | 1998-12-14 | 2001-05-15 | Li-Cor, Inc. | Heterogeneous assay for pyrophosphate detection |
DE19857953C2 (de) | 1998-12-16 | 2001-02-15 | Conducta Endress & Hauser | Vorrichtung zum Messen der Konzentration von Ionen in einer Meßflüssigkeit |
US6429027B1 (en) | 1998-12-28 | 2002-08-06 | Illumina, Inc. | Composite arrays utilizing microspheres |
US6361671B1 (en) | 1999-01-11 | 2002-03-26 | The Regents Of The University Of California | Microfabricated capillary electrophoresis chip and method for simultaneously detecting multiple redox labels |
GB9901475D0 (en) | 1999-01-22 | 1999-03-17 | Pyrosequencing Ab | A method of DNA sequencing |
US20020150909A1 (en) | 1999-02-09 | 2002-10-17 | Stuelpnagel John R. | Automated information processing in randomly ordered arrays |
WO2000051191A1 (en) | 1999-02-22 | 2000-08-31 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | A hybrid electrical device with biological components |
ATE556149T1 (de) | 1999-02-23 | 2012-05-15 | Caliper Life Sciences Inc | Manipulation von mikropartikeln in mikrofluidischen systemen |
US20050191698A1 (en) | 1999-04-20 | 2005-09-01 | Illumina, Inc. | Nucleic acid sequencing using microsphere arrays |
US20030108867A1 (en) | 1999-04-20 | 2003-06-12 | Chee Mark S | Nucleic acid sequencing using microsphere arrays |
US6355431B1 (en) | 1999-04-20 | 2002-03-12 | Illumina, Inc. | Detection of nucleic acid amplification reactions using bead arrays |
US7097973B1 (en) | 1999-06-14 | 2006-08-29 | Alpha Mos | Method for monitoring molecular species within a medium |
US6818395B1 (en) | 1999-06-28 | 2004-11-16 | California Institute Of Technology | Methods and apparatus for analyzing polynucleotide sequences |
AU1429701A (en) | 1999-07-16 | 2001-02-05 | Board Of Regents, The University Of Texas System | General signaling protocols for chemical receptors in immobilized matrices |
US6459398B1 (en) | 1999-07-20 | 2002-10-01 | D.S.P.C. Technologies Ltd. | Pulse modulated digital to analog converter (DAC) |
US6977145B2 (en) | 1999-07-28 | 2005-12-20 | Serono Genetics Institute S.A. | Method for carrying out a biochemical protocol in continuous flow in a microreactor |
US6423536B1 (en) | 1999-08-02 | 2002-07-23 | Molecular Dynamics, Inc. | Low volume chemical and biochemical reaction system |
US7244559B2 (en) | 1999-09-16 | 2007-07-17 | 454 Life Sciences Corporation | Method of sequencing a nucleic acid |
US6274320B1 (en) | 1999-09-16 | 2001-08-14 | Curagen Corporation | Method of sequencing a nucleic acid |
US7211390B2 (en) | 1999-09-16 | 2007-05-01 | 454 Life Sciences Corporation | Method of sequencing a nucleic acid |
US7124221B1 (en) | 1999-10-19 | 2006-10-17 | Rambus Inc. | Low latency multi-level communication interface |
GB9926956D0 (en) | 1999-11-13 | 2000-01-12 | Koninkl Philips Electronics Nv | Amplifier |
US6518024B2 (en) | 1999-12-13 | 2003-02-11 | Motorola, Inc. | Electrochemical detection of single base extension |
JP2001175340A (ja) | 1999-12-14 | 2001-06-29 | Matsushita Electric Ind Co Ltd | 電位発生回路 |
EP1197001B1 (en) | 2000-02-14 | 2004-11-24 | Koninklijke Philips Electronics N.V. | Current-to-voltage converter with controllable gain, and signal processing circuit comprising such converter |
WO2001061044A1 (en) | 2000-02-15 | 2001-08-23 | Lynx Therapeutics, Inc. | Data analysis and display system for ligation-based dna sequencing |
EP1257668B1 (en) | 2000-02-16 | 2008-10-29 | Illumina, Inc. | Parallel genotyping of multiple patient samples |
US6649416B1 (en) | 2000-02-18 | 2003-11-18 | Trustees Of Tufts College | Intelligent electro-optical sensor array and method for analyte detection |
FR2805826B1 (fr) | 2000-03-01 | 2002-09-20 | Nucleica | Nouvelles puces a adn |
JP3442338B2 (ja) | 2000-03-17 | 2003-09-02 | 株式会社日立製作所 | Dna分析装置、dna塩基配列決定装置、dna塩基配列決定方法、および反応モジュール |
JP3701241B2 (ja) | 2000-03-30 | 2005-09-28 | インフィネオン テクノロジーズ アクチエンゲゼルシャフト | センサ配列のトランジスタの状態を検出するセンサ配列および方法 |
US7001792B2 (en) | 2000-04-24 | 2006-02-21 | Eagle Research & Development, Llc | Ultra-fast nucleic acid sequencing device and a method for making and using the same |
WO2001081896A1 (en) | 2000-04-24 | 2001-11-01 | Eagle Research & Development, Llc | An ultra-fast nucleic acid sequencing device and a method for making and using the same |
US20020042388A1 (en) | 2001-05-01 | 2002-04-11 | Cooper Mark J. | Lyophilizable and enhanced compacted nucleic acids |
US20020168678A1 (en) | 2000-06-07 | 2002-11-14 | Li-Cor, Inc. | Flowcell system for nucleic acid sequencing |
US6482639B2 (en) | 2000-06-23 | 2002-11-19 | The United States Of America As Represented By The Secretary Of The Navy | Microelectronic device and method for label-free detection and quantification of biological and chemical molecules |
US6611037B1 (en) | 2000-08-28 | 2003-08-26 | Micron Technology, Inc. | Multi-trench region for accumulation of photo-generated charge in a CMOS imager |
US6939451B2 (en) | 2000-09-19 | 2005-09-06 | Aclara Biosciences, Inc. | Microfluidic chip having integrated electrodes |
EP1330306A2 (en) | 2000-10-10 | 2003-07-30 | BioTrove, Inc. | Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof |
US6537881B1 (en) | 2000-10-16 | 2003-03-25 | Advanced Micro Devices, Inc. | Process for fabricating a non-volatile memory device |
US6558626B1 (en) | 2000-10-17 | 2003-05-06 | Nomadics, Inc. | Vapor sensing instrument for ultra trace chemical detection |
AU2002241803A1 (en) | 2000-10-20 | 2002-06-18 | The Board Of Trustees Of The Leland Stanford Junior University | Transient electrical signal based methods and devices for characterizing molecular interaction and/or motion in a sample |
US6770472B2 (en) | 2000-11-17 | 2004-08-03 | The Board Of Trustees Of The Leland Stanford Junior University | Direct DNA sequencing with a transcription protein and a nanometer scale electrometer |
KR100991573B1 (ko) | 2000-12-11 | 2010-11-04 | 프레지던트 앤드 펠로우즈 오브 하버드 칼리지 | 나노센서 |
GB2370410A (en) | 2000-12-22 | 2002-06-26 | Seiko Epson Corp | Thin film transistor sensor |
WO2002079514A1 (en) | 2001-01-10 | 2002-10-10 | The Trustees Of Boston College | Dna-bridged carbon nanotube arrays |
JP4809983B2 (ja) | 2001-02-14 | 2011-11-09 | 明彦 谷岡 | 生体高分子とリガンドとの相互作用を検出する装置及びその方法 |
EP1236804A1 (en) | 2001-03-02 | 2002-09-04 | Boehringer Mannheim Gmbh | A method for determination of a nucleic acid using a control |
DE10111458B4 (de) | 2001-03-09 | 2008-09-11 | Siemens Ag | Analyseeinrichtung |
US8114591B2 (en) | 2001-03-09 | 2012-02-14 | Dna Electronics Ltd. | Sensing apparatus and method |
GB0105831D0 (en) | 2001-03-09 | 2001-04-25 | Toumaz Technology Ltd | Method for dna sequencing utilising enzyme linked field effect transistors |
CA2440754A1 (en) | 2001-03-12 | 2002-09-19 | Stephen Quake | Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension |
JP2002272463A (ja) | 2001-03-22 | 2002-09-24 | Olympus Optical Co Ltd | 一塩基多型の型を判定する方法 |
US20050058990A1 (en) | 2001-03-24 | 2005-03-17 | Antonio Guia | Biochip devices for ion transport measurement, methods of manufacture, and methods of use |
US6418968B1 (en) | 2001-04-20 | 2002-07-16 | Nanostream, Inc. | Porous microfluidic valves |
KR100455283B1 (ko) | 2001-04-23 | 2004-11-08 | 삼성전자주식회사 | 물질 유로의 측벽에 형성된 mosfet으로 이루어진물질 검출용 칩, 이를 포함하는 물질 검출 장치, 이의제조 방법 및 물질 검출 장치를 이용한 물질 검출 방법 |
CN1325658C (zh) | 2001-04-23 | 2007-07-11 | 三星电子株式会社 | 包含mosfet分子检测芯片和采用该芯片的分子检测装置以及使用该装置的分子检测方法 |
KR100442838B1 (ko) | 2001-12-11 | 2004-08-02 | 삼성전자주식회사 | 프로브의 고정화 검출방법 및 상기 프로브와 표적시료의결합정도 검출방법 |
US6571189B2 (en) | 2001-05-14 | 2003-05-27 | Hewlett-Packard Company | System and method for scanner calibration |
US20040023253A1 (en) | 2001-06-11 | 2004-02-05 | Sandeep Kunwar | Device structure for closely spaced electrodes |
US20030096268A1 (en) | 2001-07-06 | 2003-05-22 | Michael Weiner | Method for isolation of independent, parallel chemical micro-reactions using a porous filter |
DE10133363A1 (de) | 2001-07-10 | 2003-01-30 | Infineon Technologies Ag | Messzelle und Messfeld mit solchen Messzellen sowie Verwendung einer Messzelle und Verwendung eines Messfeldes |
US7485443B2 (en) | 2001-07-17 | 2009-02-03 | Northwestern University | Solid-phase reactions |
JP2003032908A (ja) | 2001-07-19 | 2003-01-31 | Nisshinbo Ind Inc | キャパシタ組電池、その制御方法、その制御装置及び自動車用蓄電システム |
DK1412487T3 (da) | 2001-07-30 | 2010-08-30 | Meso Scale Technologies Llc | Assayelektroder der har immobiliserede lipid/proteinlag og fremgangsmåder til at fremstille og anvende disse |
US6490220B1 (en) | 2001-08-13 | 2002-12-03 | Micron Technology, Inc. | Method for reliably shutting off oscillator pulses to a charge-pump |
US6929944B2 (en) | 2001-08-31 | 2005-08-16 | Beckman Coulter, Inc. | Analysis using a distributed sample |
US20030054396A1 (en) | 2001-09-07 | 2003-03-20 | Weiner Michael P. | Enzymatic light amplification |
DE10151020A1 (de) | 2001-10-16 | 2003-04-30 | Infineon Technologies Ag | Schaltkreis-Anordnung, Sensor-Array und Biosensor-Array |
DE10151021A1 (de) | 2001-10-16 | 2003-04-30 | Infineon Technologies Ag | Sensor-Anordnung |
US6795117B2 (en) | 2001-11-06 | 2004-09-21 | Candela Microsystems, Inc. | CMOS image sensor with noise cancellation |
US20030124599A1 (en) | 2001-11-14 | 2003-07-03 | Shiping Chen | Biochemical analysis system with combinatorial chemistry applications |
WO2003042683A1 (en) | 2001-11-16 | 2003-05-22 | Bio-X Inc. | Fet type sensor, ion density detecting method comprising this sensor, and base sequence detecting method |
US20050170347A1 (en) | 2001-12-19 | 2005-08-04 | Yuji Miyahara | Potentiometric dna microarray, process for producing the same and method of analyzing nucleic acid |
US20050106587A1 (en) | 2001-12-21 | 2005-05-19 | Micronas Gmbh | Method for determining of nucleic acid analytes |
US6518146B1 (en) | 2002-01-09 | 2003-02-11 | Motorola, Inc. | Semiconductor device structure and method for forming |
US7772383B2 (en) | 2002-01-25 | 2010-08-10 | The Trustees Of Princeton University | Chemical PCR: Compositions for enhancing polynucleotide amplification reactions |
KR100403637B1 (ko) | 2002-01-26 | 2003-10-30 | 삼성전자주식회사 | 출력 일그러짐을 최소화하는 파워 앰프 클리핑 회로 |
US6614301B2 (en) | 2002-01-31 | 2003-09-02 | Intel Corporation | Differential amplifier offset adjustment |
US7276749B2 (en) | 2002-02-05 | 2007-10-02 | E-Phocus, Inc. | Image sensor with microcrystalline germanium photodiode layer |
US6926865B2 (en) | 2002-02-11 | 2005-08-09 | Matsushita Electric Industrial Co., Ltd. | Method and apparatus for detecting DNA hybridization |
JP2003258128A (ja) | 2002-02-27 | 2003-09-12 | Nec Electronics Corp | 不揮発性半導体記憶装置およびその製造方法ならびにその動作方法 |
US6953958B2 (en) | 2002-03-19 | 2005-10-11 | Cornell Research Foundation, Inc. | Electronic gain cell based charge sensor |
US6828685B2 (en) | 2002-06-14 | 2004-12-07 | Hewlett-Packard Development Company, L.P. | Memory device having a semiconducting polymer film |
US6894930B2 (en) | 2002-06-19 | 2005-05-17 | Sandisk Corporation | Deep wordline trench to shield cross coupling between adjacent cells for scaled NAND |
US20040136866A1 (en) | 2002-06-27 | 2004-07-15 | Nanosys, Inc. | Planar nanowire based sensor elements, devices, systems and methods for using and making same |
US7092757B2 (en) | 2002-07-12 | 2006-08-15 | Cardiac Pacemakers, Inc. | Minute ventilation sensor with dynamically adjusted excitation current |
US6885827B2 (en) | 2002-07-30 | 2005-04-26 | Amplification Technologies, Inc. | High sensitivity, high resolution detection of signals |
EP1525470A2 (de) | 2002-07-31 | 2005-04-27 | Infineon Technologies AG | Sensor-anordnung |
US7842377B2 (en) | 2003-08-08 | 2010-11-30 | Boston Scientific Scimed, Inc. | Porous polymeric particle comprising polyvinyl alcohol and having interior to surface porosity-gradient |
CN100392097C (zh) | 2002-08-12 | 2008-06-04 | 株式会社日立高新技术 | 使用dna微阵列的核酸检测方法以及核酸检测装置 |
US7267751B2 (en) | 2002-08-20 | 2007-09-11 | Nanogen, Inc. | Programmable multiplexed active biologic array |
GB0219541D0 (en) | 2002-08-22 | 2002-10-02 | Secr Defence | Method and apparatus for stand-off chemical detection |
US8449824B2 (en) | 2002-09-09 | 2013-05-28 | Yizhong Sun | Sensor instrument system including method for detecting analytes in fluids |
US7595883B1 (en) | 2002-09-16 | 2009-09-29 | The Board Of Trustees Of The Leland Stanford Junior University | Biological analysis arrangement and approach therefor |
SE0202867D0 (sv) | 2002-09-27 | 2002-09-27 | Pyrosequencing Ab | New sequencing method |
CN1500887A (zh) | 2002-10-01 | 2004-06-02 | 松下电器产业株式会社 | 引物伸长反应检测方法、碱基种类判别方法及其装置 |
WO2004034025A2 (en) | 2002-10-10 | 2004-04-22 | Nanosys, Inc. | Nano-chem-fet based biosensors |
DE10247889A1 (de) | 2002-10-14 | 2004-04-22 | Infineon Technologies Ag | Sensor-Anordnung und Verfahren zum Betreiben einer Sensor-Anordnung |
US20040079636A1 (en) | 2002-10-25 | 2004-04-29 | Chin Hsia | Biomedical ion sensitive semiconductor sensor and sensor array |
AU2003285092A1 (en) | 2002-10-29 | 2004-05-25 | Cornell Research Foundation, Inc. | Chemical-sensitive floating gate field effect transistor |
US6700814B1 (en) | 2002-10-30 | 2004-03-02 | Motorola, Inc. | Sense amplifier bias circuit for a memory having at least two distinct resistance states |
US7052821B2 (en) | 2002-11-01 | 2006-05-30 | Georgia Tech Research Corporation | Sacrificial compositions, methods of use thereof, and methods of decomposition thereof |
DE10251757B4 (de) | 2002-11-05 | 2006-03-09 | Micronas Holding Gmbh | Vorrichtung zur Bestimmung der Konzentration von in einer zu untersuchenden Probe enthaltenen Liganden |
US7022288B1 (en) | 2002-11-13 | 2006-04-04 | The United States Of America As Represented By The Secretary Of The Navy | Chemical detection sensor system |
DE10255755B4 (de) | 2002-11-28 | 2006-07-13 | Schneider, Christian, Dr. | Integrierte elektronische Schaltung mit Feldeffekt-Sensoren zum Nachweis von Biomolekülen |
US20040197803A1 (en) | 2002-12-06 | 2004-10-07 | Hidenobu Yaku | Method, primer and kit for determining base type |
US7575865B2 (en) | 2003-01-29 | 2009-08-18 | 454 Life Sciences Corporation | Methods of amplifying and sequencing nucleic acids |
ES2338654T5 (es) | 2003-01-29 | 2017-12-11 | 454 Life Sciences Corporation | Amplificación de ácidos nucleicos en emulsión de perlas |
US20050006234A1 (en) | 2003-02-13 | 2005-01-13 | Arjang Hassibi | Semiconductor electrochemical bio-sensor array |
US7317484B2 (en) | 2003-02-26 | 2008-01-08 | Digital Imaging Systems Gmbh | CMOS APS readout scheme that combines reset drain current and the source follower output |
US20070262363A1 (en) | 2003-02-28 | 2007-11-15 | Board Of Regents, University Of Texas System | Low temperature fabrication of discrete silicon-containing substrates and devices |
TWI235236B (en) | 2003-05-09 | 2005-07-01 | Univ Chung Yuan Christian | Ion-sensitive circuit |
US7291496B2 (en) | 2003-05-22 | 2007-11-06 | University Of Hawaii | Ultrasensitive biochemical sensor |
WO2005015156A2 (en) | 2003-08-04 | 2005-02-17 | Idaho Research Foundation, Inc. | Molecular detector |
JP2005077210A (ja) | 2003-08-29 | 2005-03-24 | National Institute For Materials Science | 生体分子検出素子及びそれを用いた核酸解析方法 |
GB0322010D0 (en) * | 2003-09-19 | 2003-10-22 | Univ Cambridge Tech | Detection of molecular interactions using field effect transistors |
US7008550B2 (en) | 2003-09-25 | 2006-03-07 | Hitachi Global Storage Technologies Netherlands B.V. | Method for forming a read transducer by ion milling and chemical mechanical polishing to eliminate nonuniformity near the MR sensor |
GB0323224D0 (en) | 2003-10-03 | 2003-11-05 | Rolls Royce Plc | A module for a fuel cell stack |
US20070087401A1 (en) | 2003-10-17 | 2007-04-19 | Andy Neilson | Analysis of metabolic activity in cells using extracellular flux rate measurements |
WO2005043160A2 (en) | 2003-10-31 | 2005-05-12 | University Of Hawaii | Ultrasensitive biochemical sensing platform |
US7067886B2 (en) | 2003-11-04 | 2006-06-27 | International Business Machines Corporation | Method of assessing potential for charging damage in SOI designs and structures for eliminating potential for damage |
US7981362B2 (en) | 2003-11-04 | 2011-07-19 | Meso Scale Technologies, Llc | Modular assay plates, reader systems and methods for test measurements |
DE10352917A1 (de) | 2003-11-11 | 2005-06-16 | Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG | Sensoranordnung mit mehreren potentiometrischen Sensoren |
US7169560B2 (en) | 2003-11-12 | 2007-01-30 | Helicos Biosciences Corporation | Short cycle methods for sequencing polynucleotides |
WO2005054431A2 (en) | 2003-12-01 | 2005-06-16 | 454 Corporation | Method for isolation of independent, parallel chemical micro-reactions using a porous filter |
US7279588B2 (en) | 2003-12-02 | 2007-10-09 | Seoul National University Foundation | Dinuclear metal complex and pyrophosphate assay using the same |
EP1697749B1 (en) | 2003-12-22 | 2013-04-17 | Imec | The use of microelectronic structures for patterned deposition of molecules onto surfaces |
US7462512B2 (en) | 2004-01-12 | 2008-12-09 | Polytechnic University | Floating gate field effect transistors for chemical and/or biological sensing |
JP4065855B2 (ja) | 2004-01-21 | 2008-03-26 | 株式会社日立製作所 | 生体および化学試料検査装置 |
US7927797B2 (en) | 2004-01-28 | 2011-04-19 | 454 Life Sciences Corporation | Nucleic acid amplification with continuous flow emulsion |
JP3903183B2 (ja) | 2004-02-03 | 2007-04-11 | 独立行政法人物質・材料研究機構 | 遺伝子検出電界効果デバイスおよびこれを用いた遺伝子多型解析方法 |
WO2005082098A2 (en) | 2004-02-27 | 2005-09-09 | President And Fellows Of Harvard College | Polony fluorescent in situ sequencing beads |
EP2436778A3 (en) | 2004-03-03 | 2012-07-11 | The Trustees of Columbia University in the City of New York | Photocleavable fluorescent nucleotides for DNA sequencing on chip constructed by site-specific coupling chemistry |
US20060057604A1 (en) | 2004-03-15 | 2006-03-16 | Thinkfar Nanotechnology Corporation | Method for electrically detecting oligo-nucleotides with nano-particles |
JP4127679B2 (ja) | 2004-03-18 | 2008-07-30 | 株式会社東芝 | 核酸検出カセット及び核酸検出装置 |
DE102004014537A1 (de) | 2004-03-23 | 2005-10-13 | Fujitsu Ltd., Kawasaki | Chipintegrierter Detektor zum Analysieren von Flüssigkeiten |
WO2005090961A1 (ja) | 2004-03-24 | 2005-09-29 | Japan Science And Technology Agency | 生体分子に関する形態及び情報をis−fetを利用して検出する測定法およびシステム |
US20050221473A1 (en) | 2004-03-30 | 2005-10-06 | Intel Corporation | Sensor array integrated circuits |
US8138496B2 (en) | 2004-04-01 | 2012-03-20 | Nanyang Technological University | Addressable transistor chip for conducting assays |
US7117605B2 (en) | 2004-04-13 | 2006-10-10 | Gyrodata, Incorporated | System and method for using microgyros to measure the orientation of a survey tool within a borehole |
US7544979B2 (en) | 2004-04-16 | 2009-06-09 | Technion Research & Development Foundation Ltd. | Ion concentration transistor and dual-mode sensors |
US7462452B2 (en) | 2004-04-30 | 2008-12-09 | Pacific Biosciences Of California, Inc. | Field-switch sequencing |
TWI261801B (en) | 2004-05-24 | 2006-09-11 | Rohm Co Ltd | Organic EL drive circuit and organic EL display device using the same organic EL drive circuit |
US7264934B2 (en) | 2004-06-10 | 2007-09-04 | Ge Healthcare Bio-Sciences Corp. | Rapid parallel nucleic acid analysis |
US7361946B2 (en) * | 2004-06-28 | 2008-04-22 | Nitronex Corporation | Semiconductor device-based sensors |
US20060024711A1 (en) | 2004-07-02 | 2006-02-02 | Helicos Biosciences Corporation | Methods for nucleic acid amplification and sequence determination |
GB2416210B (en) | 2004-07-13 | 2008-02-20 | Christofer Toumazou | Ion sensitive field effect transistors |
JP3874772B2 (ja) | 2004-07-21 | 2007-01-31 | 株式会社日立製作所 | 生体関連物質測定装置及び測定方法 |
JP4455215B2 (ja) | 2004-08-06 | 2010-04-21 | キヤノン株式会社 | 撮像装置 |
US7276453B2 (en) | 2004-08-10 | 2007-10-02 | E.I. Du Pont De Nemours And Company | Methods for forming an undercut region and electronic devices incorporating the same |
US7190026B2 (en) | 2004-08-23 | 2007-03-13 | Enpirion, Inc. | Integrated circuit employable with a power converter |
US7888013B2 (en) | 2004-08-27 | 2011-02-15 | National Institute For Materials Science | Method of analyzing DNA sequence using field-effect device, and base sequence analyzer |
US20070212681A1 (en) | 2004-08-30 | 2007-09-13 | Benjamin Shapiro | Cell canaries for biochemical pathogen detection |
US7609303B1 (en) | 2004-10-12 | 2009-10-27 | Melexis Tessenderlo Nv | Low noise active pixel image sensor using a modified reset value |
JP2006138846A (ja) | 2004-10-14 | 2006-06-01 | Toshiba Corp | 核酸検出センサ、核酸検出チップ及び核酸検出装置 |
US7534097B2 (en) | 2004-10-15 | 2009-05-19 | Nanyang Technological University | Method and apparatus for controlling multi-fluid flow in a micro channel |
US7381936B2 (en) | 2004-10-29 | 2008-06-03 | Ess Technology, Inc. | Self-calibrating anti-blooming circuit for CMOS image sensor having a spillover protection performance in response to a spillover condition |
US7785785B2 (en) | 2004-11-12 | 2010-08-31 | The Board Of Trustees Of The Leland Stanford Junior University | Charge perturbation detection system for DNA and other molecules |
CA2588095A1 (en) | 2004-11-18 | 2006-08-17 | Morgan Research Corporation | Miniature fourier transform spectrophotometer |
KR100623177B1 (ko) | 2005-01-25 | 2006-09-13 | 삼성전자주식회사 | 높은 유전율을 갖는 유전체 구조물, 이의 제조 방법, 이를포함하는 불휘발성 반도체 메모리 장치 및 그 제조 방법 |
CA2593855A1 (en) | 2005-01-31 | 2006-08-10 | Pacific Biosciences Of California, Inc. | Use of reversible extension terminator in nucleic acid sequencing |
US20060199493A1 (en) | 2005-02-04 | 2006-09-07 | Hartmann Richard Jr | Vent assembly |
US9040237B2 (en) | 2005-03-04 | 2015-05-26 | Intel Corporation | Sensor arrays and nucleic acid sequencing applications |
US7826980B2 (en) | 2005-03-11 | 2010-11-02 | National University Corporation Toyohashi University Of Technology | Cumulative chemical/physical phenomenon detecting apparatus |
EP1866055A4 (en) | 2005-04-05 | 2010-08-18 | Protein Discovery Inc | IMPROVED METHOD AND DEVICE FOR CONCENTRATING AND FRACTIONATING ANALYTES FOR CHEMICAL ANALYZES WITH MATRIX BASED LASER DESORPTION / IONIZATION MASS SPECTROMETRY (MALDI-MS) |
US20060228721A1 (en) | 2005-04-12 | 2006-10-12 | Leamon John H | Methods for determining sequence variants using ultra-deep sequencing |
TWI287041B (en) | 2005-04-27 | 2007-09-21 | Jung-Tang Huang | An ultra-rapid DNA sequencing method with nano-transistors array based devices |
US20060269927A1 (en) | 2005-05-25 | 2006-11-30 | Lieber Charles M | Nanoscale sensors |
CN1881457A (zh) | 2005-06-14 | 2006-12-20 | 松下电器产业株式会社 | 致动器控制方法和使用该方法的盘装置 |
JP5331476B2 (ja) | 2005-06-15 | 2013-10-30 | カリダ・ジェノミックス・インコーポレイテッド | 遺伝子解析および化学解析用の単分子アレイ |
WO2007002204A2 (en) | 2005-06-21 | 2007-01-04 | The Trustees Of Columbia University In The City Of New York | Pyrosequencing methods and related compostions |
TW200701588A (en) | 2005-06-29 | 2007-01-01 | Leadtrend Tech Corp | Dual loop voltage regulation circuit of power supply chip |
US7890891B2 (en) | 2005-07-11 | 2011-02-15 | Peregrine Semiconductor Corporation | Method and apparatus improving gate oxide reliability by controlling accumulated charge |
JP2007035726A (ja) | 2005-07-22 | 2007-02-08 | Rohm Co Ltd | 半導体装置、モジュールおよび電子機器 |
JP2009505045A (ja) | 2005-08-08 | 2009-02-05 | ミクロガン ゲーエムベーハー | 半導体センサ |
US7365597B2 (en) | 2005-08-19 | 2008-04-29 | Micron Technology, Inc. | Switched capacitor amplifier with higher gain and improved closed-loop gain accuracy |
SG130066A1 (en) | 2005-08-26 | 2007-03-20 | Micron Technology Inc | Microelectronic device packages, stacked microelectronic device packages, and methods for manufacturing microelectronic devices |
JP4353958B2 (ja) | 2005-09-15 | 2009-10-28 | 株式会社日立製作所 | Dna計測装置、及びdna計測方法 |
US7466258B1 (en) | 2005-10-07 | 2008-12-16 | Cornell Research Foundation, Inc. | Asynchronous analog-to-digital converter and method |
US7794584B2 (en) | 2005-10-12 | 2010-09-14 | The Research Foundation Of State University Of New York | pH-change sensor and method |
US7335526B2 (en) | 2005-10-31 | 2008-02-26 | Hewlett-Packard Development Company, L.P. | Sensing system |
TWI295729B (en) | 2005-11-01 | 2008-04-11 | Univ Nat Yunlin Sci & Tech | Preparation of a ph sensor, the prepared ph sensor, systems comprising the same, and measurement using the systems |
US7538827B2 (en) | 2005-11-17 | 2009-05-26 | Chunghwa Picture Tubes, Ltd. | Pixel structure |
US7576037B2 (en) | 2005-11-18 | 2009-08-18 | Mei Technologies, Inc. | Process and apparatus for combinatorial synthesis |
US7566913B2 (en) | 2005-12-02 | 2009-07-28 | Nitronex Corporation | Gallium nitride material devices including conductive regions and methods associated with the same |
GB2436619B (en) | 2005-12-19 | 2010-10-06 | Toumaz Technology Ltd | Sensor circuits |
KR100718144B1 (ko) | 2006-01-09 | 2007-05-14 | 삼성전자주식회사 | 이온 물질 검출용 fet 기반 센서, 그를 포함하는 이온물질 검출 장치 및 그를 이용한 이온 물질 검출 방법 |
WO2007109228A1 (en) | 2006-03-17 | 2007-09-27 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Apparatus for microarray binding sensors having biological probe materials using carbon nanotube transistors |
US20070233477A1 (en) | 2006-03-30 | 2007-10-04 | Infima Ltd. | Lossless Data Compression Using Adaptive Context Modeling |
US7923240B2 (en) | 2006-03-31 | 2011-04-12 | Intel Corporation | Photo-activated field effect transistor for bioanalyte detection |
WO2007123908A2 (en) | 2006-04-18 | 2007-11-01 | Advanced Liquid Logic, Inc. | Droplet-based multiwell operations |
KR100723426B1 (ko) | 2006-04-26 | 2007-05-30 | 삼성전자주식회사 | 이온 물질 검출용 전계 효과 트랜지스터 및 그를 이용한이온 물질 검출 방법 |
US20080014589A1 (en) | 2006-05-11 | 2008-01-17 | Link Darren R | Microfluidic devices and methods of use thereof |
JP4211805B2 (ja) | 2006-06-01 | 2009-01-21 | エプソンイメージングデバイス株式会社 | 電気光学装置および電子機器 |
JP4883812B2 (ja) | 2006-07-13 | 2012-02-22 | 国立大学法人名古屋大学 | 物質検出装置 |
KR100799577B1 (ko) | 2006-08-31 | 2008-01-30 | 한국전자통신연구원 | 가스 및 생화학물질 감지용 센서 제조 방법과 그 센서를포함하는 집적회로 및 그 제조 방법 |
US7960776B2 (en) | 2006-09-27 | 2011-06-14 | Cornell Research Foundation, Inc. | Transistor with floating gate and electret |
US8231831B2 (en) | 2006-10-06 | 2012-07-31 | Sharp Laboratories Of America, Inc. | Micro-pixelated fluid-assay structure |
US20090111705A1 (en) | 2006-11-09 | 2009-04-30 | Complete Genomics, Inc. | Selection of dna adaptor orientation by hybrid capture |
DE102006052863B4 (de) | 2006-11-09 | 2018-03-01 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Schutzstruktur für Halbleitersensoren und deren Verwendung |
EP2092320A1 (en) * | 2006-12-08 | 2009-08-26 | Koninklijke Philips Electronics N.V. | Method of manufacturing a semiconductor sensor device and semiconductor sensor device obtained with such method |
US8349167B2 (en) | 2006-12-14 | 2013-01-08 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
EP4134667A1 (en) | 2006-12-14 | 2023-02-15 | Life Technologies Corporation | Apparatus for measuring analytes using fet arrays |
US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US7972828B2 (en) | 2006-12-19 | 2011-07-05 | Sigma-Aldrich Co. | Stabilized compositions of thermostable DNA polymerase and anionic or zwitterionic detergent |
US7932034B2 (en) | 2006-12-20 | 2011-04-26 | The Board Of Trustees Of The Leland Stanford Junior University | Heat and pH measurement for sequencing of DNA |
WO2008089282A2 (en) | 2007-01-16 | 2008-07-24 | Silver James H | Sensors for detecting subtances indicative of stroke, ischemia, infection or inflammation |
JP4325684B2 (ja) | 2007-02-20 | 2009-09-02 | 株式会社デンソー | センサ制御装置、及び印加電圧特性の調整方法 |
US8031809B2 (en) | 2007-02-28 | 2011-10-04 | Seiko Epson Corporation | Template pulse generating circuit, communication device, and communication method |
JP5368321B2 (ja) | 2007-03-02 | 2013-12-18 | ディ・エヌ・エイ・エレクトロニクス・リミテッド | 固相pH検出を用いたqPCR |
EP1975246A1 (de) | 2007-03-29 | 2008-10-01 | Micronas Holding GmbH | Markierungsfreie Sequenzierung auf einer Festphase mittels Feldeffekttransistoren |
AU2008276308A1 (en) | 2007-07-13 | 2009-01-22 | The Board Of Trustees Of The Leland Stanford Junior University | Method and apparatus using electric field for improved biological assays |
US20090062132A1 (en) | 2007-08-29 | 2009-03-05 | Borner Scott R | Alternative nucleic acid sequencing methods |
WO2009041917A1 (en) | 2007-09-28 | 2009-04-02 | Agency For Science, Technology And Research | Method of electrically detecting a nucleic acid molecule |
KR100940415B1 (ko) | 2007-12-03 | 2010-02-02 | 주식회사 동부하이텍 | 배면 드레인 구조 웨이퍼의 온저항 측정방법 |
US8124936B1 (en) | 2007-12-13 | 2012-02-28 | The United States Of America As Represented By The Secretary Of The Army | Stand-off chemical detector |
CN101896624A (zh) | 2007-12-13 | 2010-11-24 | Nxp股份有限公司 | 对生物微粒进行测序的生物传感器装置和方法 |
WO2009081890A1 (ja) | 2007-12-20 | 2009-07-02 | National University Corporation Toyohashi University Of Technology | 複合検出装置 |
US20090194416A1 (en) | 2008-01-31 | 2009-08-06 | Chung Yuan Christian University | Potentiometric biosensor for detection of creatinine and forming method thereof |
DE102008012899A1 (de) | 2008-03-06 | 2009-09-10 | Robert Bosch Gmbh | Verfahren zum Betreiben eines Gassensors |
US8067731B2 (en) | 2008-03-08 | 2011-11-29 | Scott Technologies, Inc. | Chemical detection method and system |
US7885490B2 (en) | 2008-03-10 | 2011-02-08 | Octrolix Bv | Optical chemical detector and method |
US7667501B2 (en) | 2008-03-19 | 2010-02-23 | Texas Instruments Incorporated | Correlated double sampling technique |
JP5259219B2 (ja) | 2008-03-19 | 2013-08-07 | 株式会社三社電機製作所 | 電源装置 |
US7821806B2 (en) | 2008-06-18 | 2010-10-26 | Nscore Inc. | Nonvolatile semiconductor memory circuit utilizing a MIS transistor as a memory cell |
US8470164B2 (en) | 2008-06-25 | 2013-06-25 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
GB2461127B (en) | 2008-06-25 | 2010-07-14 | Ion Torrent Systems Inc | Methods and apparatus for measuring analytes using large scale FET arrays |
CN102203597A (zh) | 2008-06-26 | 2011-09-28 | 生命技术公司 | 使用fet阵列检测分子相互作用的方法和装置 |
KR101026468B1 (ko) | 2008-09-10 | 2011-04-01 | 한국전자통신연구원 | 생분자 검출 장치 및 검출 방법 |
US8546128B2 (en) | 2008-10-22 | 2013-10-01 | Life Technologies Corporation | Fluidics system for sequential delivery of reagents |
JP2012506557A (ja) * | 2008-10-22 | 2012-03-15 | ライフ テクノロジーズ コーポレーション | 生物学的および化学的分析のための集積センサアレイ |
US20100301398A1 (en) | 2009-05-29 | 2010-12-02 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US20100137143A1 (en) | 2008-10-22 | 2010-06-03 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US7898277B2 (en) | 2008-12-24 | 2011-03-01 | Agere Systems Inc. | Hot-electronic injection testing of transistors on a wafer |
US8101479B2 (en) | 2009-03-27 | 2012-01-24 | National Semiconductor Corporation | Fabrication of asymmetric field-effect transistors using L-shaped spacers |
US9309557B2 (en) | 2010-12-17 | 2016-04-12 | Life Technologies Corporation | Nucleic acid amplification |
US9334531B2 (en) | 2010-12-17 | 2016-05-10 | Life Technologies Corporation | Nucleic acid amplification |
US8776573B2 (en) | 2009-05-29 | 2014-07-15 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US20120261274A1 (en) | 2009-05-29 | 2012-10-18 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8673627B2 (en) | 2009-05-29 | 2014-03-18 | Life Technologies Corporation | Apparatus and methods for performing electrochemical reactions |
US20110037121A1 (en) | 2009-08-16 | 2011-02-17 | Tung-Hsing Lee | Input/output electrostatic discharge device with reduced junction breakdown voltage |
JP2011041205A (ja) | 2009-08-18 | 2011-02-24 | Panasonic Corp | 電圧発生回路、デジタルアナログ変換器、ランプ波発生回路、アナログデジタル変換器、イメージセンサシステム及び電圧発生方法 |
SG188863A1 (en) | 2009-09-11 | 2013-04-30 | Agency Science Tech & Res | Method of determining a sensitivity of a biosensor arrangement, and biosensor sensitivity determining system |
US9018684B2 (en) | 2009-11-23 | 2015-04-28 | California Institute Of Technology | Chemical sensing and/or measuring devices and methods |
US8545248B2 (en) | 2010-01-07 | 2013-10-01 | Life Technologies Corporation | System to control fluid flow based on a leak detected by a sensor |
US9088208B2 (en) | 2010-01-27 | 2015-07-21 | Intersil Americas LLC | System and method for high precision current sensing |
WO2011106634A2 (en) | 2010-02-26 | 2011-09-01 | Life Technologies Corporation | Modified proteins and methods of making and using same |
US8878257B2 (en) | 2010-06-04 | 2014-11-04 | Freescale Semiconductor, Inc. | Methods and apparatus for an ISFET |
CN109449171A (zh) | 2010-06-30 | 2019-03-08 | 生命科技公司 | 用于检测和测量化学反应和化合物的晶体管电路 |
EP2588851B1 (en) | 2010-06-30 | 2016-12-21 | Life Technologies Corporation | Ion-sensing charge-accumulation circuit and method |
JP5952813B2 (ja) | 2010-06-30 | 2016-07-13 | ライフ テクノロジーズ コーポレーション | Isfetアレイをテストする方法及び装置 |
JP5397333B2 (ja) * | 2010-07-01 | 2014-01-22 | セイコーエプソン株式会社 | 半導体装置、並びに、センサ素子及び半導体装置の製造方法 |
WO2012006222A1 (en) | 2010-07-03 | 2012-01-12 | Life Technologies Corporation | Chemically sensitive sensor with lightly doped drains |
CN106198656B (zh) * | 2010-08-18 | 2018-12-11 | 生命科技股份有限公司 | 用于电化学检测装置的微孔的化学涂层 |
EP2617061B1 (en) | 2010-09-15 | 2021-06-30 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
EP2619564B1 (en) | 2010-09-24 | 2016-03-16 | Life Technologies Corporation | Matched pair transistor circuits |
US10241075B2 (en) | 2010-12-30 | 2019-03-26 | Life Technologies Corporation | Methods, systems, and computer readable media for nucleic acid sequencing |
US8821798B2 (en) | 2012-01-19 | 2014-09-02 | Life Technologies Corporation | Titanium nitride as sensing layer for microwell structure |
US8747748B2 (en) | 2012-01-19 | 2014-06-10 | Life Technologies Corporation | Chemical sensor with conductive cup-shaped sensor surface |
US8786331B2 (en) | 2012-05-29 | 2014-07-22 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
-
2014
- 2014-03-05 WO PCT/US2014/020887 patent/WO2014149778A1/en active Application Filing
- 2014-03-05 CN CN201480015992.3A patent/CN105283758B/zh active Active
- 2014-03-05 US US14/198,382 patent/US9128044B2/en active Active
- 2014-03-05 EP EP14712487.9A patent/EP2972279B1/en active Active
- 2014-03-05 JP JP2016500682A patent/JP6581074B2/ja active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4430811C1 (de) * | 1994-08-30 | 1995-09-07 | Fraunhofer Ges Forschung | Verfahren zum Herstellen eines integrierten ionensensitiven Feldeffekttransistors in CMOS-Silizium-Planartechnologie |
WO2006056226A1 (de) * | 2004-11-26 | 2006-06-01 | Micronas Gmbh | Elektrisches bauelement |
WO2012152308A1 (en) * | 2011-05-06 | 2012-11-15 | X-Fab Semiconductor Foundries Ag | Ion sensitive field effect transistor |
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