CN1148579C - 一种生物电极阵列、其中的电极位点及其电学特性的控制方法 - Google Patents

一种生物电极阵列、其中的电极位点及其电学特性的控制方法 Download PDF

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CN1148579C
CN1148579C CNB971961972A CN97196197A CN1148579C CN 1148579 C CN1148579 C CN 1148579C CN B971961972 A CNB971961972 A CN B971961972A CN 97196197 A CN97196197 A CN 97196197A CN 1148579 C CN1148579 C CN 1148579C
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格雷格里・T・A・科瓦奇
格雷格里·T·A·科瓦奇
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Abstract

一种改进的生物电极阵列(12)及其使用方法。阵列(12)中的每个电极(30)与各个抽样保持电路(26)耦合。电极(30)及抽样保持电路(26)为一体，并在单个的半导体芯片内形成阵列(12)，这样每个抽样保持电路(26)可被加载上由单个的时分数模转换器(DAC)(22)所提供的预定的电压。所有的抽样保持电路(26)可被可扫描一些或全部电极位点置(30)的多路复用器进行存取。每个抽样保持电路(26)可包含电容器(32)及一个或多个晶体管开关(34，36)，当闭合时，在电容器与形成在矩阵(12)内的电源线(37)间建立电传递。

Description

一种生物电极阵列、其中的电极位点及其电学特性的控制方法
技术领域
本发明涉及用于进行及/或监控生物反应的电子系统，更具体的是涉及在显微尺寸下执行和控制多步和多级反应的自-寻址，自-组合微电子系统的设计，生产和应用。
发明背景
到目前为止，注意力已经集中在用于进行及/或监控生物反应的以阵列为基础的电子系统的设计，制造和使用。
例如，已经认识到各种类型的电子生物传感器可被用于监控(或测量)某些生物反应的进程，并可以用与集成电路领域类似的技术生产这些传感器阵列。
如图1所示，典型的现有技术的生物传感器1包括其上黏结有固定配位基3的生物定向固定表面2；能够感应在固定配位基3与特定分析物间所发生的化学反应的变送器；及用于过滤，放大和将变送器4所产生的信号转换成对于监控所选的生物反应的进程和发生有用的测量数据的放大和控制部分5。在“蛋白质固定，基础和应用，R.F.Taylor，ed(1991)”和“固定亲和配位基技术，Hermanson et al(1992)(第五章)”中对上述类型的生物传感器进行了详细描述。
在美国专利申请No.07/872,582，题目为“用于分子检测的光电方法和装置”(国际公开出版日1993，11，14，公开号为No.WO93/22678，此后指Hollis等的申请)。Hollis等的申请主要是关于生物传感器装置，其包含一阵列检测位点，这些检测位点可用多个导电线进行电子寻址。有各种的生物传感器用在检测位点，所应注意的是，检测位点可通过光刻技术形成在半导体晶片内。另外，检测位点可借助晶体管开关使用行及列的寻址技术在寻址动态随机存取存储器或有源矩阵液晶显示器中与相关的检测线路耦合。
除了上述的生物传感器外，还发展了其他的在溶液或其他场合可向所选地点(或检测位点)传送电感应(或信号)的装置。如图2所示，这些装置包含电源6(如电流源、电压源或电源)，与电流源耦合的电极7，形成在电极一个表面上的渗透层8，及形成在渗透层8上的生物附着层9。渗透层8为负离子提供在电极7与溶液(未示出)间的自由传输，附着层9用于特定结合体的耦合。
上述的典型系统在PCT申请No.PCT/US94/12270中进行了描述，其在1995年五月公开，题目为“用于分子生物分析和诊断的自寻址及自组合微电子系统和装置”，及PCT申请No.PCT/US95/08570，其在1996年一月公开，题目为“用于分子生物应用的自-寻址及自组合微电子系统和装置”(此后指“Heller等申请”)，二者在这里都作为参考。Heller等的申请描述了可用为刻蚀技术或微加工技术制造的电子设备，最好在表面上包含可寻址的微位置的矩阵。此外，所形成的各个微位置电控制并导引特定结合体与其自身的传输和附着。因此，所描述的装置具有在微型尺寸下有效控制多步及多级反应的能力。所应用的反应包含，例如核酸杂化，抗体/抗原反应，医疗诊断及多级结合生物聚合合成反应等。
其他的用于与各种溶液及/或生物体面接的电子系统在以下的文献中进行了描述：欧洲专利申请No.89-3133379.3(1990年四月7日公开，题目“电光系统”)，美国专利No.5,378,343(1995年1月3日公开，题目“基于水银紫外微电极阵列的包括铟的电极组合阵列”)，美国专利No.5,314,495(1995年4月24日公开，题目“微电子接口”)，及美国专利No.5,178,161(1993年1月12日公开，题目“微电子接口”)。
对于本领域的技术人员而言，在上述专利中所描述的用于进行及/或监控生物反应的传统的电子装置(包括以上专利和专利申请中所描述的)通常都很笨重且昂贵，有时还难于控制。因此，对本领域的技术人员而言，因为传统的生物系统经常使用芯片外(off-chip)电路产生和控制提供给检测位点阵列的电流/电压信号，不使用特定的设备很难精确的控制在特定检测位点产生的电流/电压信号。对于那些使用芯片上电路产生和控制提供给检测位点的电流/电压信号的传统系统，在某些情况下，所遇到的主要问题在于在较大的阵列内需向所选的电极位点提供单独和不同的刺激。其中一个原因在于当在传统的生物传感器阵列中需要单一位的信号特性时，该需求是通过向阵列内的每个电极位点提供单独的信号线路实现的。其结果，传统的生物传感器通常很烦琐且比所需的贵。
针对上述传统生物系统的限制，建议改进生物系统，使用最少的芯片外电路，利用大的电极位点阵列，同时在给定的电极位点对所传输的电流/电压提供非常精确的控制。
发明概要
本发明的目的在于提供用于进行及/或监控生物反应的电子系统的设计，制造及使用。
根据本发明的一方面，生物电极阵列包含电极位点的矩阵，其中每个电极位点包含通过放大电路(或驱动电路)与各个抽样保持电路耦合的电极。在最佳的实施例中，电极，放大器及抽样保持电路是集成在单个的半导体芯片内并形成阵列，从而每个抽样保持电路可被加载上由单个时分数模转换器(DAC)所提供的预定电压。此外，所有的抽样保持电路都可通过多路复用器进行存取，该多路复用器可以扫描部分或全部电极位点。在此实施例中，每个抽样保持电路包含电容器及晶体管开关电路，其中的晶体管开关电路当接通时，该电容器与在矩阵内的一电源线路之间提供电传递。然而，在另一实施例中，抽样保持电路包含一些其他类型的存储器，其可用表示将要加到相关电极上的电刺激特性的信号(或数值)进行寻址和加载。此种存储器可包含用做模拟存储器的电可擦可编程只读存储器(EEPROM)(例如由加利福尼亚的San Jose的信息存储器件公司所生产的非易失模拟信号存储芯片)，或其他类的能够存储控制信息并产生对应模拟输出数值的电路。
根据本发明的另一方面，生物电极阵列包含其上形成有存储器的单个半导体芯片(例如随机存取存储器(RAM))，与存储器耦合的数摸转换器(DAC)，计数器，与计数器和存储器耦合的行解码器，与计数器和存储器耦合的列解码器，及与行解码器和列解码器耦合的有源生物电极位点的矩阵。在使用中，通过计算机将代表将要提供给阵列内的个电极位点的电压的二进制值存入存储器中。然后，对阵列内的每个地址(或所选的地址数)从存储器中读出一个二进制数值，并提供给DAC，其依次将二进制数值转换为将要存储到所选地址处的存储电容器上的电压。如果在此时一旦阵列(或所选的地址数)的所有地址已经被扫描，依据是否需要在各个电极位点提供的电压/电流的时间变化用最初存储在存储器中的同一数值或新的数值重复该处理过程。本领域的技术人员可以知道，此扫描过程需经常重复进行，从而抽样保持电路上的所存储电压随时间的衰减(由于不可避免的漏电流)不会导致电极上的不可接受的电压/电流误差。如果使用非易失抽样保持电路(即如果使用EEPROM或类似的技术)，这种衰减不会很明显，保证用于任意的慢更新速率。
在另一实施例中，存储器，计数器及DAC可以设置在一个或多个单独的芯片上。
针对上述情况，可以看出根据本发明的生物阵列对传递到阵列内的各电极的电位/电流提供精确的控制，同时使用最少的芯片外电路，并将整个系统成本降到最低。此外，通过用抽样保持电路(或其他的局部存储电路)控制提供给特定检测位点的电刺激的电平，根据本发明的阵列与现有技术的系统相比可获得更高水平的信号特性和电极使用效果。
根据本发明的另一方面，本发明提供了在板上所含的可控加热元件的热隔离膜上整个有源阵列表面的制造方式。通过循环加热元件的温度，在例如通过聚合酶链反应的情况下可进行DNA的放大。
最后，根据本发明的另一方面，本发明提供用于生物电极阵列矩阵中的荧光或吸收检测电路的结合，以提高所发射的光子进入检测电路中的耦合。更具体的，根据本发明的一个实施例，生物有源电极是形成在一适宜的光检测器之上，例如在CMOS电路内的MOS光二极管结构之上。在此实施例中，电极至少用部分透明的物质形成，或所形成的电极允许光通过其本身而到达下面的光探测器。
针对上述情况，本发明的目的是提供一种改进的生物电极阵列，用于在微观的情况下进行和控制多步及多级的反应。
本发明的另一目的是提供一种改进的精巧的生物电极阵列，其即使对于较大数目的电极，也能小型化和最少的使用芯片外电路。
本发明的另一目的是提供一种改进的生物电极位点，其包括一抽样保持电路，其可用传统的CMOS半导体制造技术进行制造。
本发明的另一目的是提供一种改进的生物电极阵列，其包括用于加快反应进程(如DNA放大)的加热元件。
本发明的另一目的是提供一种改进的生物电极阵列，其包括多个形成在所选电极位点下面的光探测器。
附图说明
图1是现有技术的有源生物系统的示意图；
图2为现有技术的有源生物系统的示意图；
图3为根据本发明的一种形式的生物阵列的示意图；
图4(a)为根据本发明的一形式的生物电极位点的示意图；
图4(b)为更详细的描述图4(a)中所示的生物电极位点的开关电路和放大器电路中的一个的电路图；
图4(c)为用于解释图4(b)中所示的电极位点的部分生产方法的示意图；
图5为生物电极位点的示意图，其包括用于监控处于电极位点的电极的电学特性的示意图；
图6(a)为热隔离膜及生物电极阵列组合的制造示意图，其中在硅基片的背部侧面蚀刻生物电极阵列；
图6(b)示出低热导电性的室与图6(a)所示的热隔离膜和生物电极阵列组合的接合示意图；
图7为根据本发明的包括光学探测器的生物电极位点的示意图；
图8(a)为根据本发明的一种形式的开槽的部分透明电极的示意图；
图8(b)为根据本发明的部分透明电极的另一实施例的示意图。
最佳实施例的描述
现在参考附图，如图3所示，根据本发明的生物阵列包含有源生物电极位点12的矩阵，行解码器14，列解码器16，计数器18，作为搜寻表的随机存储存储器(RAM)20，及数摸转换器22。在最佳实施例中，每个上述所列的元件都设置在单个的芯片上，可用传统的CMOS半导体生产技术制造整个阵列10。此外，在最佳的形式中，可用计算机(未示出)将数据通过数据输入接口21输入RAM 20。
现在参考图4(a)，构成生物电极12矩阵的每个生物电极位点24包含抽样保持电路26，放大器28及电极30。在最佳的形式中，抽样保持电路26包含电容器32及两个晶体管开关34和36。开关34和36串联连接，并当关闭时，在电压源线路37(与DAC22连接的)与电容器32间提供电传递。开关34和36分别与矩阵12内的所指定的行选择线38和列选择线40连接。
如图4(c)及图4(b)所示，每个行选择线38和列选择线40都可包含正控制线(+控制线)41及负控制线(-控制线)43，每个开关34和36都可包含CMOS传输门，即具有与负控线耦合的栅极区47的PMOS FET45及具有与正向控线41耦合的栅极区51的NMOS FET 49。另外，放大器电路(或驱动元件)28可包含PMOS电流源53。
在另一实施例中，通过具有补偿输出(例如+控制线及-控制线)两个输入逻辑门(例如“与门”或“与非门”)控制上述的单个开关，并用于选择的将电容器32与电压源线路37相连。在此实施例中，逻辑门分别对行和列选择器上的信号的一致性作出响应。此外，需注意的是，在某些情况下，不需要两个晶体管传输门，可用单个的MOS晶体管作为开关。在此情况下，逻辑门只需向开关提供单一的输出。
在本领域中，对行解码器，列解码器，模数转换器及随机存取存储器的设计，生产及作用是公知的，因此，在这里对这些器件不做详细描述。下面仅对生物电极阵列10的作用进行描述。
在应用中，代表施加到矩阵12内的各电极位点24上的电压的二进制值用外部计算机存储到RAM 20内(或其他适宜的存储器件内)。然后，从RAM20读出矩阵12内的每个地址(或所选的地址数)的二进制值，并提供给DAC 22，DAC 22依次将二进制值转换为将要存储到位于所选位点地址的存储器32上的电压。输出放大器28连接在电容器32与电极30之间并将放大的刺激信号提供给电极30。输出放大器28包含电压放大器及/或缓冲器，并放大电容器32上的电压，将放大的电压提供给电极30。另外，输出放大器28还包含电流输出放大器(例如跨导放大器)并将电流信号提供给电极30。如果在此时一旦阵列(或所选的地址数)的所有地址已经被扫描，依据在各个电极位点是否需要电压/电流的时间变化用最初存储在RAM20中的同一数值或新的数值重复工作。本领域的技术人员可以知道，此扫描过程需经常重复进行，从而电容器32上的所存储电压随时间的衰减(由于不可避免的漏电流)不会导致电极30上的不可接受的电压/电流误差。
作为本发明的另一种变型，计数器18，RAM 20及DAC 22可设置在芯片上或芯片外，该芯片包含电泳电极阵列，作为一个设计原则，如果需要的话，可用其他类型的电路(例如简单计数器或移位寄存器)控制位于各个电极位点24的抽样保持电路26的顺序加载。
现在参考图5，在某些应用中，需要监控矩阵12内的一个或多个电极30的状态。在此情况下，假设如果用已知的电流驱动电极，可测得所产生的电压，或如果用已知的电压驱动电极，则可测得流过的电流。为保证监控所给出电极30的状态，电压读出放大器42可与电极30相连并与次级多路复用总线或输出端(未示出)相连。电压读出放大器42提供整个阵列相对于电接地(未示出)的电极30上的电压或阵列上相对于所选参考电极(未示出)的电极30上的电压的指示值。在某些情况下，参考电极的电压也可是阵列的接地电压。需注意的是，在阵列中对于电极位点24的读出放大器42的输出在公共读数信号线路上也可被多路复用，提供给公共读数信号线的信号用传统的电路(如抽样保持电路级模数转换电路(未示出))进行多路分用。公共的读数信号线和公共的信号线(即电压源线37)可分开，或可为同一根线，在此情况下，其必须是时分的，在所选的时段内用于向电极位点24的电容器32提供充电信号，并在其他的时段内，作为在电极位点24产生的读数信号的载体。
在电极30是被电压放大器28驱动而流过电极30的电流被读出时，读出电阻器(未示出)被连在电压放大器28的输出与电极30之间，而差分放大器电路的两个输入(未示出)被跨接读出电阻器。在此实施例中，在差分放大器的输出所产生的信号将与流过电极30的电流成比例。
正如上面所描述的，图4(a)及图5中所示实施例中使用了两个串联的开关34和36控制电容器32的加载(一个开关分别由行和列线进行控制)，对本领域的技术人员可知，可以用很多方式实现开关的功能。例如，等同的方式是如图4(a)及5所示，用CMOS传输门或与门和开关的结合代替开关34和36。
参考图4(c)，在最佳实施例中，可用CMOS或其他有源电路工艺制造生物阵列10。因此，对本领域的技术人员而言，可通过再加工具备部分或全部上述功能的CMOS电路，从而形成上述的完全有源生物电极电路。例如，如图7所示，生物电极30可设置在下部CMOS电路的上部，然后用用所覆盖的钝化层44进行保护。此外，可在钝化层44内形成开孔，以露出生物电极30的有源区以及任何所需的外围互连部位(例如连接焊盘)(未示出)。在此实施例中，可用电化学所适宜的材料生产电极30，例如金，铟或铂，并可用传统的薄膜沉积技术进行沉积和制作图形。钝化层44可包含等离子体沉积的氮化硅及/或炭化硅，可利用传统的微加工技术(如等离子体蚀刻)加工钝化层内的孔。最后，如果生物分子被附着在或靠近电极30的表面，可用中介连接物或中间层(如图7所示)。
现在参考图6(a)及图6(b)，在另一最佳实施例中，生物电极阵列10的整个表面可形成在包含一个或多个板上可控加热元件(未示出)的热隔离膜46上。热隔离膜可用本领域已知的微加工技术形成。例如，包含生物阵列电路和电极的整个CMOS晶片的背侧可用适宜的蚀刻掩膜覆盖(如氮化硅)。用标准的技术对氮化硅加工图形，以在该处将要形成隔离膜的地方形成开孔。通过将晶片浸入蚀刻溶液中形成隔离膜(例如，正如在Klassen et al.，“微加工热隔离电路”固态传感器及制动器工艺的前言所描述的载有溶解硅的四甲基铵氢氧化物，Hilton Head，SouthCarolina，June 3-6，1996，pp.127-131).这样通过使隔离膜温度循环从而进行DNA的放大。此外，通过使用成列的电阻或分布在隔离膜的整个面上的适当偏置的MOSFETS(金属氧化物半导体场效应晶体管)。因此，如果覆盖阵列10的溶液48(图7(b)所示)被提供DNA及适宜的化学物质以进行聚合酶链反应(PCR)以放大DNA，对隔离膜的温度进行循环以保证所需的放大。如果需要热反馈，隔离膜的温度可以很容易的确定。例如，可使用加热器电阻的温度系数或安装在隔离膜内的二极管的正向电压对溶液温度进行指示。最后，一旦包含在溶液48中的DNA被放大，可将适宜的化学物质引入室50中以完成一个或多个所需的分析步骤。此类的化学物质如限制酶，荧光标志物等。
由Northrup，et al对微加工的以隔离膜微基础的DNA放大系统进行了描述(参照Northrup et al.，“用微加工反应室的DNA放大”1993年六月7-10在日本召开的第七界固态传感器及致动器的国际会议的前言pp.924-926)，因此，这里不在详细描述基于隔离膜的DNA放大系统的具体结构和操作。然而，需注意的是，Northrup et al.系统仅提供热循环，并无分析及生物电极控制能力。因此，对本领域的技术人员可知，根据本发明的生物阵列更先进，因为此阵列对DNA的放大及随后的分析使用单一的一个设备。
参考图7，在某些情况下，需要将荧光或传输检测电路直接安装在生物阵列10内，以提高被发射和传输到检测电路中的光子的耦合。在荧光检测的情况下，整个阵列必须用对于激发荧光标志生物分子(例如DNA或DNA带间的连接基)中的荧光所公知的波长的光照射整个阵列。用位于每一位点的光检测装置检测光。在传输检测的情况下，必须用被所存在的生物分子衰减的波长的光(例如被生物分子所吸收的波长的光)照射整个阵列。在一给定电极位点生物分子的存在可用位于该处的光探测器所测得得光的衰减进行检测。这样可大大的提高使用远离生物阵列10的所使用的摄像照相机的信噪比(SNR).在某些情况下，在适宜的光探测器50(如MOS-发光二极管或电荷耦合器件(CCD)结构)上可结合一个生物有源电极(具有或无多路复用电路)。在此实施例中，可以使用透明电极(如铟锡氧化物)，或使用狭缝或增强的电极结构，如图8(a)及8(b)所示。通过在电极52的表面提供孔54(如图8(a)所示)及槽56(如图8(b)所示)，可保证光从电极52通过到光探测器50。对本领的技术人员可知，通过消除掉外部摄象机并保留进行生物控制的杂化能力(或其他分子互相作用)，可大大降低整个分析系统的成本。
本发明还可具有其他的替换及等同的形式，这里仅对具体的实施例进行了描述。需明确的是，本发明并不限于这些具体的形式及方法，但相反的，本发明包括所有在本发明的实质范围内的所有变更和等同内容。

Claims (33)

1.一种生物电极阵列，其特征在于包含：
多个可寻址生物电极位点，其中每个电极位点包含一个电极；一输出与所述电极耦合的输出放大器电路；与所述输出放大器电路的输入耦合的一电容器；至少一个与所述电容器耦合的开关。
2.根据权利要求1所述的生物电极阵列，其特征在于每个生物电极位点还包含一电压放大器，其输入端与所述电极耦合用于检测所述电极的电压。
3.根据权利要求1所述的生物电极阵列，其特征在于每个生物电极位点还包含一电流检测电路，其输入端与所述电极耦合用于检测流过所述电极的电流。
4.根据权利要求1所述的生物电极阵列，其特征在于：
所述多个生物电极位点设置在多个行和列上；
每行的生物电极位点与特定的行选择线耦合；
每列的生物电极位点与特定的列选择线耦合；及
每个生物电极位点包含与各行和列选择线上的所选信号的一致性产生响应的开关电路，所述开关电路在接到所述各行和列两种选择线上的选择信号时在所述电容器与模拟程序信号间建立连接。
5.根据权利要求4所述的生物电极阵列，其特征在于每个生物电极位点还包含设置在所述电极下面的光探测器，每个电极至少部分是透明的。
6.一种用在生物电极阵列中的电极位点，其特征在于所述位点包含：
一个电极；
一抽样保持电路；及
一与所述电极和所述抽样保持电路耦合的输出放大器。
7.根据权利要求6所述的电极位点，其特征在于所述抽样保持电路包含与开关电路耦合的电容器，所述开关电路响应个行列选择线上所选信号的一致性并在接到所述各行和列两种选择线上的选择信号时在所述电容器与模拟程序信号间建立连接。
8.根据权利要求6所述的电极位点，其特征在于所述抽样保持电路包含与开关电路耦合的电容器，所述开关电路由两输入逻辑门的输出进行控制，当闭合时，在所述电容器与所述生物电极阵列的电压源线之间建立电传递。
9.根据权利要求6所述的电极位点，其特征在于所述抽样保持电路包含与一对CMOS传输门耦合的电容器，所述CMOS传输门串联连接，并当闭和时，在电容器与形成在所述生物电极阵列内的电压源线间建立电传递。
10.用在生物电极阵列中的电极位点，其特征在于所述位点包含：
一电极及与通过放大器电路与所述电极耦合的模拟信号存储器件。
11.根据权利要求10所述的电极位点，其特征在于所述模拟信号存储器件包含与开关电路耦合的电容器。
12.根据权利要求11所述的电极位点，其特征在于所述开关电路由两输入逻辑门的输出进行控制，在从所述逻辑门接收到所选的输出信号后，在所述电容器与所述生物电极阵列的电压源线之间建立电传递。
13.根据权利要求10所述的电极位点，其特征在于所述模拟信号存储装置包含与一对CMOS传输门耦合的电容器，所述CMOS传输门串联连接，并当闭和时，在电容器与形成在所述生物电极阵列内的电压源线间建立电传递。
14.一种生物电极阵列，其特征在于包含：
一存储器；
与所述存储器耦合的数模转换器；
一计数器；
与所述计数器及存储器耦合的一行解码器；
与所述计数器及所述存储器耦合的一列解码器；
与所述数模转换器，所述行解码器及所述列解码器耦合的有源生物电极的矩阵，所述具有多个生物电极位点的有源生物电极的矩阵设置在多个行和列上；每个所述生物电极位点具有一个电极及一个通过放大器电路与所述电极耦合的抽样保持电路；所述抽样保持电路与所选的一行选择线，所选的一列选择线及所述矩阵的一电源线相连。
15.根据权利要求14所述的生物电极，其特征在于所述存储器，所述数模转换器，所述计数器，所述行解码器，所述列解码器及所述矩阵都形成在单一的半导体芯片上。
16.根据权利要求14所述的生物电极，其特征在于还包含与每个所述生物电极位点的每个所述电极耦合的读出放大器。
17.根据权利要求14所述的生物电极，其特征在于光探测器被设置在所述生物电极位点的至少一个电极的下面，且位于所述至少一个所述电极位点下面的电极是至少部分透明的。
18.根据权利要求17所述的生物电极，其特征在于所述至少一个电极包含铟锡氧化物。
19.根据权利要求17所述的生物电极，其特征在于所述至少一个电极包含用于通过光的孔径电极结构。
20.根据权利要求17所述的生物电极，其特征在于所述至少一个电极包含用于通过光的槽电极结构。
21.根据权利要求14所述的生物电极，其特征在于还包含至少一个加热元件。
22.根据权利要求14所述的生物电极，其特征在于还包括多个可被选择控制的加热元件。
23.一种用在生物电极阵列中的位点，其特征在于所述位点包含：
一个电极；
与所述电极耦合用于向所述电极提供电刺激的一放大器电路；
与所述放大器电路耦合用于接收和存储表示提供到所述电极的所述电刺激的强度的一局部存储器。
24.根据权利要求23所述的位点，其特征在于所述放大器电路包含一放大器及所述局部存储器包含一电容器。
25.根据权利要求24所述的位点，其特征在于所述电容器通过一对开关与所述生物电极阵列的信号电源线耦合，一个开关与所述生物阵列的行选择线耦合，而另一个开关与所述生物电极阵列的列选择线耦合
26.一种控制生物电极阵列中的电极的电学特性的方法，其特征在于所述方法包含如下步骤：
从存储器抽取代表被存储到所述生物电极阵列中的至少一个抽样保持电路上的电压的数值，所述抽样保持电路通过输出放大器与所述电极耦合；
向数模转换器提供所述数值，所述数模转换器产生与所述数值成比例的电压，并将所述电压提供给与所述至少一个抽样保持电路进行电传递的导体；及
在所述至少一个抽样保持电路上存储所述电压。
27.根据权利要求26所述的方法，其特征在于所述抽取、提供及存储的步骤周期性的重复，以保证存储到所述抽样保持电路上的电压仍保持在预选的电压范围内。
28.一种控制生物电极阵列中的电极的电学特性的方法，其特征在于所述方法包含如下步骤：
在所述生物电极阵列内寻址电极位点；
将表示要提供到所述电极位点的电极上的电刺激的电信号提供给位于所述被寻址电极位点的抽样保持电路；及
保证位于所述电极位点的所述抽样保持电路使所述电刺激通过驱动元件提供到所述电极。
29.根据权利要求28所述的方法，其特征在于所述生物电极阵列包含行选择线和列选择线，所述电极位点与所述所选的行选择线和所选的列选择线耦合，所述寻址步骤通过在所述所选的行和列选择线上提供电信号完成。
30.一种控制生物电极阵列中的电极的电学特性的方法，其特征在于所述方法包含如下步骤：
在所述生物电极阵列内对电极位点寻址；
将表示要提供到所述电极位点的电极上的电刺激的电信号提供给位于所述被寻址电极位点的局部存储电路；及
允许位于所述局部存储电路与位于所述电极位点的驱动元件通讯以控制要提供到所述电极上的电刺激。
31.一种生物电极阵列，包含：
形成在单一集成电路芯片上的多个可寻址生物电极位点；
其中每个电极位点包含一个电极；与所述电极耦合的输出放大器电路；与所述输出放大器电路耦合的模拟存储器件；及与所述模拟存储电路耦合的开关电路；
其中每个电极位点的电极的表面上形成渗透层，用于在电极与溶液间提供负离子的传输；
其中每个电极位点的渗透层的上面形成生物接合层，用于使其可与来自溶液中的一个或多个黏结物进行接合。
32.根据权利要求31所述的生物电极阵列，其特征在于
所述多个生物电极位点设置在多个行和列上；
每行的生物电极位点与特定的行选择线耦合；
每列的生物电极位点与特定的列选择线耦合；
每个生物电极位点的开关电路响应各行和列选择线上的选择信号的一致性，并在接收到所述各行和列选择线上的选择信号时在与其耦合的模拟存储器件与模拟程序信号间建立连接。
33.一种在集成电路芯片上形成的生物电极阵列组件，所述生物电极阵列组件包括：
一电极阵列；
至少一个与所述电极阵列中的至少一个电极相联系的金属氧化物半导体(MOS)晶体管，所述MOS晶体管可操作地将至少一个电极连接到电压源线上；
耦合到电压源线上的电压源；
与所述电极阵列中的每个电极相联系的本地寻址存储器，所述存储器控制施加到所联系的电极上的电刺激的水平；和
设置在至少一个电极上面的中间层。
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