CN1224498A - 通过电力在包含流体的结构中对电渗透和/或电泳力的变量控制 - Google Patents
通过电力在包含流体的结构中对电渗透和/或电泳力的变量控制 Download PDFInfo
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Abstract
在运用电动力的微型流体系统(由在图中的元件178和其上的元件部分示出)中,本发明运用电流或电参数,而不是电压,来控制流体流过系统的沟道。时间多路复用电源(200和202)还通过改变在连到微型流体系统的流体容器的电极上的电压,通过改变期间把电压施加在电极上的工作循环或者两者组合,还对流体流动进行进一步控制。还可以把时间多路复用电源连到多个电极上以减小成本。
Description
与相关申请的前后对照
本申请是美国专利申请第08/678,436号(1996年7月3日申请,全部作为参考资料并在此引入)的部分续展申请。
发明背景
现在,对制造和运用显微流体(microfluidic)系统以获得化学和生化信息的兴趣越来越大。一般与半导体电子工业相关的技术(诸如,影印石版术(photolithography)、湿式化学蚀刻,等)正用于这些显微流体系统的制造中。术语“显微流体”是指具有一般以微米或亚微米标定构成的沟道和小室(例如,在从大约0.1μm到大约500μm的范围内具有至少一个界面尺寸)的系统或装置。最早在Manz等人的Trends in Anal.Chem.(1990)10(5):144-149和Manz等人的Avd.inChromatog(1993)33:1-66中描述了对用于构成显微流体系统的平面芯片的应用,其中在上述论文中描述了在硅和玻璃衬底中这些流体装置,特别是微细管装置的构成。
对显微流体系统的应用由很多种。例如,国际专利申请WO 96/04547(在1996年2月15日公开)描述了对毛细管电泳、液体彩色照片、流入分析(flow injectionanalysis)和化学反应及合成的显微流体系统的应用。相关美国专利申请第___,名称为“微标度流体装置中的高通过量筛选分析系统”(1996年6月28日由J.WallaceParce等人申请,并转让给本发明的受让人)揭示了对显微流体系统在快速分析混合物对各种化学,特别是生化系统的影响中的广泛应用。词组“生化系统”一般指包括通常在有生命的有机体中找到的那类分子的化学相互作用。这些相互作用包括在有生命系统中(包括,酶的、粘合、信令(signaling)和其它反应)的异化和同化反应和其它反应的全部范围。例如,特别感兴趣的生化系统包括接收器-配合体(receptor-ligand)相互作用、酶衬底相互作用、蜂窝网信令路径、包括用于生物利用率筛选的模型障碍系统(例如,细胞或小薄膜片)的传输反应和其它各种一般系统。
用于在这些显微流体系统或装置中传输和定向流体(例如,采样、分析、缓冲和反应物)的多种方法已被描述过。一种方法通过在微型构造的装置中的机械微型泵和阀使流体在该装置中流动。参见,公开的英国专利申请第2 248 891号(10/18/90),公开欧洲专利申请第568 902号(5/2/92)美国专利第5,271,724号(8/21/91)和5,277,556号(7/3/91)。再参见,Miyazaki等人获得的美国专利第5,171,132号(12/21/90)。另一种方法运用声能使流体采样在声音流动的影响下在装置中流动。参见,由Northrup和White公开的PCT申请第94/05414号。一种直接施加外压以使流体在装置中流动的方法。参见,由Wilding等人获得的美国专利第5,304,487号中的描述。
另一种方法运用电场以及所得的电动(electrokinetic)力使流体材料流过微型流体系统的沟道。例如,参见,由Kovacs,Harrision等人Anal.Chem.(1992)64:1926-1932和Manz等人,J.Chromatog.(1992)593:253-258申请的公开的欧洲专利申请第376 611(12/30/88),由Soane获得的美国专利第5,126,022号。电动力具有直接控制、快速反应和简单的优点。然而,用这种方法操作微型流体系统也有一些缺点。
本装置运用在电气绝缘材料的衬底中的沟道网络。沟道把与高压电极接触的多个流体容器(fluid reservoir)连接起来。为了使流体材料流过沟道网络,把特定电压同时施于各个电极。当试图控制在一个沟道中的材料流动,而不影响在另一个沟道中的流动时,确定在系统中每个电极的电压值变得很复杂。例如,在四个沟道以十字形交叉同时容器和电极在沟道尾部的相对简单的结构中,在两个容器之间的流体流动的独立增长不仅仅是两个容器电压差增长的问题。如果要保留其它两个容器内的元素流动的原方向,那么还必需调节这两个容器之间的电压。此外,当沟道、交叉点和容器的数量增加时,对流过沟道的流体控制变得越来越复杂。
此外,施加在装置中的电极上的电压可以很高,即,达到几千伏电压的程度。稳高压供电是昂贵的、庞大的,而且经常不精确,而且每个电极需要高压供电。于是,任何复杂的微型流体系统的成本都很高。
本发明解决或者实质上缓解了在用另一种电参数(而不受电压)来简化对流过系统沟道的材料的控制的微型流体系统中电动传输的这些问题。在大量应用中(诸如,在化学、生化、生物工艺和分子生物的领域和多个其它领域中),对流过微型流体系统的沟道的材料移动具有直接、快速和简单控制的高通过量微型流体系统是可行的。
发明概述
本发明提供微型流体系统,它具有多个相互连接的毛细沟道和在毛细沟道的不同节点处的多个电极,以在毛细沟道中产生电场以使在流体中的材料电动流过毛细沟道。根据本发明,通过响应于在第一和第二电极之间的电流把电压施加在第一电极和第二电极之间,以使材料在它们之间流动,来操作微型流体系统。电流可以直接测量通过微型流体系统的沟道的离子流。除了电流之外,可以使用其它电参数(诸如功率)。
此外,本发明提供时间多路复用在微型流体系统的电极上的电源电压,以更加精确和有效地进行控制。通过改变电极与电源相连的工作循环、改变在该工作循环期间加在电极时的电源或者两者结合,可以控制加在电极上的电压。用这种方法,一个电源可以对多个电极提供服务。
本发明还提供直接监测在微型流体系统的沟道内的电压。在沟道中,在微型流体系统的表面上的导电线的宽度足够窄,以防止电分解。把电线连到同样在衬底的表面上的分压电路上。分压电路降低沟道节点的读取电压,从而不需要特定的高电压伏特计。还把分压电路设计成能够从沟道中引出很小的电流,从而使不想要的电化学效应(例如,气体产生、减小/氧化反应)减至最小。
如上所述的本发明可以用于不同的用途,而这些用途本身也具有发明性,例如:
对于至少具有一个沟道的衬底的运用,其中通过响应于在电极处的电流在与沟道相关的两个电极之间施加电压,电动地传输目的材料。
如对上述发明的运用,衬底具有多个相互连接的沟道和相关的电极,通过响应于在电极上的电流把电压加在预定电极,沿着加入一个或多个沟道的预定通道传输目的材料。
对于至少具有一个沟道的衬底的运用,其中通过对根据时间在与沟道相关的电极之间加电参数的控制,电动传输目的材料。
如对上述发明的运用,电参数包括电压、电流或功率。
对于具有多个沟道和与沟道相关的多个电极的绝缘衬底的运用,在电极上施加电压使得在沟道中产生电场,而且在衬底上的至少一个导电线延伸至沟道位置,从而可以确定在沟道位置上的电参数。
如对上述发明的运用,导电线具有很小的宽度,从而在沟道位置上与导电线的交叉点上产生小于1V的电压,最好是小于0.1V的电压。
对于绝缘衬底的运用,绝缘衬底具有多个相互连接的毛细沟道、在毛细管电场不同节点处的多个电极以在毛细沟道中产生电场以使在流体中的材料电动流过毛细沟道,连到至少一个电极的电源、电源具有用于接收参考电压的第一输入端和第二输入端及输出端的混合单元;连到混合单元输出端的电压放大器,电压放大器具有第一和第二输出端,第一输出端连到至少一个电极;和连到电压放大器的第一输出端的反馈单元,反馈单元具有连到混合单元的第二输入端的输出端,从而提供负反馈以稳定电源。
如对上述发明的运用,反馈单元还连到电压放大器的第二输出端,反馈单元响应于在第一输出端处的电压生成第一反馈电压,而响应于通过第一输出端中至少一个电极发出或接收的电流量生成第二反馈电压,反馈单元具有用于响应于控制信号把第一或第二反馈电压通到混合单元的开关,从而通过电压或电流反馈有选择地稳定电源。
对于连到微型流体系统的至少一个电极的电源的运用,电源具有包括用于接收可控参考电压的第一输入端和第二输入端及输出端的混合单元;连到混合单元输出端的电压放大器,电压放大器具有第一和第二输出端,第一输出端连到至少一个电极;和反馈单元连到电压放大器的第一和第二输出端和混合单元的第二输入端,反馈单元响应于在第一输出端处的电压生成第一反馈电压,和响应于通过第一输出端至少一个电极发出或接收的电流量生成第二反馈电压,反馈单元具有用于响应于控制信号使第一或第二反馈电压通到混合单元的开关,从而通过负反馈有选择地稳定电源的电压或电流。
对于微型流体系统的运用,衬底具有多个相互连接的毛细沟道,在毛细沟道的不同节点处的多个电极以在毛细沟道中产生电场以使在流体中的材料电动流过毛细沟道,而且连到每个电极的多个电源,每个电源能够有选择地提供所选电压和所选电流量作为连接的电极的源或接收端。
附图说明
图1示出微型流体系统的代表图;
图2A示出如图1所示的微型流体系统的示范沟道;图2B表示沿着在图2A中沟道产生的电路;
图3A是对于现有技术电源的输出电压对时间的代表图;图3B是根据本发明对于时间多路复用电源的输出电压对时间的示图;
图4A是表示根据本发明,根据时间多路复用电压操作的微型流体系统;图4B是示出在图4A中电源单元的方框图;
图5A是表示根据本发明的带有电压受监测波节(voltage-monitored node)的微型流体系统的示图;
图5B为图5A中分压电路的详细图;和
图6A是图4B的电源单元的方框图;图6B是图6A的直流-直流变换器的放大方框图。
本发明的详细描述
图1是根据本发明操作的一部分示范微型流体系统100的代表图。如图所示,在平面衬底102中,构成整个系统100。一般根据它们对出现在由该装置执行的特殊操作中的情况的兼容性,选择适当的衬底材料。这种情况可以包括pH极点、温度、离子集中和施加电场。此外,还选择衬底材料以使由该系统执行的分析或合成的临界成分稳定。
如图1所示的系统包括在衬底102的表面中构成的一系列沟道110、112、114和116。如在“微型流体”的定义中所讨论的那样,这些沟道一般具有很小的截面尺寸。对于下面将要描述的特定应用中,虽然可以偏离这些尺寸,但是深度为10μm而宽度大约是60μm的沟道很有效。微型流体系统100通过用于多个目的(包括分析、测试与其它材料混合、化验和这些操作组合)的衬底102的各种沟道,传输目的材料(subject material)。术语“目的材料”简单地指诸如所关心的化学或生物复合物材料。目的复合物可以包括各种不同的复合物,包括化学复合物、化学复合物的混合物(例如,多糖、小有机或无机分子)、生物大分子(例如,缩氨酸、蛋白质、核酸)或者从生物材料中的提取物(诸如,细菌、植物、真菌或动物细胞或组织、一般发生或合成的组织)。
例如,有用的衬底材料包括,玻璃、石英、陶瓷和硅以及聚合衬底(例如,塑料)。在导电或者半导电的衬底的情况下,在衬底上应有绝缘层。这很重要,因为该系统运用电渗透力使材料在系统内移动(如下所述)。在聚合衬底的情况下,衬底材料可以是硬的、半硬的或者不硬的、不透明的、半透明的或者透明的,这依赖于它们的用途。例如,一般至少部分用透明材料来构造包括光学或者视觉检测元件的系统,以至少有助于上述检测。作为替代,例如,玻璃或石英制成的透明窗可嵌入该装置作为这些检测元件。作为替代,聚合材料可以具有线性或者分支主链,而且可以交叉链接或者非交叉链接。较佳的聚合物材料的例子包括聚二甲基硅氧烷(PDMS)、聚亚胺酯、聚氯乙烯(PVC)、聚苯乙烯聚甲基丙烯酸甲酯(PMMA)等。
可用现有技术中已知的任何一种微型制造技术在衬底102的表面中制造这些沟道和其它微型元件。例如,通过在半导体制造工业中已知的方法,可将石版印刷术用于制造玻璃、石英或硅衬底。影印石版术掩蔽、等离子或湿式蚀刻和其它半导体处理技术限定在衬底表面中或上的微型元件。作为替代,可以采用微型机械(micromachining)方法(诸如,激光钻孔、微型研磨(micromilling)等。类似地,对于聚合衬底,还可以运用制造技术。这些技术包括注模技术或冲压模方法或者聚合物微型铸造技术,其中在注模技术或冲压模方法中可以用滚冲(rolling stamp)产生大片微型衬底来产生大量衬底,而在聚合物微型铸造技术中在用微型机械构成的模具中聚合衬底。
除了衬底102之外,微型流体系统100包括附加平面元件(未图示),它覆盖形成沟道的衬底102以包围和流动(fluidly)密封各种沟道以形成导管。可以通过各种方法把平面覆盖元件附着在衬底上,上述方法包括热粘合、黏合剂或在某种衬底的情况下(例如,玻璃或半硬的和不硬的聚合衬底)在两个元件之间自然粘合。此外,平面覆盖元件还设有入口和/或容器以加入特定屏幕所需的各种流体元件。
如图1所示的系统100还包括容器104、106和108,它们分别设在和流动连接在沟道114、116和110的末端。如图所示,用沟道112把多个不同的目的材料加到该装置。如此,例如,沟道112流动连接在分别被加到沟道112且随后被加到另一个沟道110以进行电泳分析的大量分开的目的材料源。在具有预定离子体浓度的流体慢流区域(fluid slug region)120中传输目的材料。由离子体浓度变化并在图1中示为缓冲区域121的缓冲区域隔开上述区域。相关专利申请,美国申请号第08/671,986号(1996年6月28日申请)和美国申请第08/760,446号(1996年12月6日申请)(两个申请的名称都是“用于电泳偏置的电子吸移(electropipettor)和补偿装置”,J.Wallace Parce和Michael R.Knapp申请,并已转让给本发明的受让人)解释了各种慢流布局和高低离子体浓度的缓冲区域在用电动力传输目的材料中的作用。将这些申请全部作为参考资料在此引入。
为了通过沟道110、112、114和116移动材料,可以使用能够同时把所选电压电平(包括地线)加在每个容器的压控器。运用多个分压器和继电器可以实现这样的压控器,以获得可选电压电平。作为替代,可以使用多个独立电压源。通过位于每个容器104、106和108中的或在其中每个容器中构成的电极,把压控器电气连接到每个容器。例如,见Ramsey申请的国际专利申请公布号WO96/04547,全部作为参考资料在此引入。
除了复杂之外,在微型流体系统中,电压控制还存在着其它问题。图2A示出在两个容器132和134之间的示范沟道130,每个容器分别与引至衬底128外的电极133和135相接触。为了使该例子更加现实,示出沟道130与其它两个沟道136和138相连。在操作中,容器132是包含目的资料的慢流区120的来源。慢流区120移向作为接收器(sink)的容器134。沟道136和138向在沟道130中的各个慢流区120提供缓冲区121。
在沟道130中的慢流区120和缓冲区121的不同电阻产生在这个简单的例子中用符号表示的电路。加在两个电极133和135之间的电压V是: 其中,I是在两个电极133和135之间的电流(假设,没有电流流入136、138),而Ri是不同慢流区120和缓冲区121的电阻。
电压控制系统存在许多可能影响该系统操作的因素。例如,在接触在电极和流体之间的界面可能是问题的来源。例如,当电极-流体触点的有效电阻随着污染物质、泡沫、氧化而变化时,加在流体上的电压也随之变化。当在电极处设定V,在电极上形成泡沫使接触溶液的电极面积减小导致从电极到溶液的电阻增加。这减小了电极之间的电流,而它又反过来减小在沟道130中的感应电渗透和电泳力。
其它问题可能影响沟道电流。意想不到的微粒可能通过有效地改变沟道的截面积,影响沟道电阻。再者,随着沟道电阻的改变,物理电流(physical current)也同时改变。
对于其它沟道(诸如,连到示范沟道130的沟道136和138),在衬底102中沟道的几何尺寸的变化可以严重地影响电压控制系统的操作过程。例如,沟道130、136和138的交叉点离在沟道136的终点处的容器上的电极(未图示)有X那么远,而离在沟道138的终点处的容器上的电极(未图示)有Y那么远。由于在影印石版处理中侧面稍微不对准,对于在另一个衬底上的微型流体系统,距离X和Y就不再相同。必需从衬底到衬底重新校准电压控制(这是一个费时间和昂贵的处理过程),从而可以适当控制在交叉点处的流体流动。
为了避免这些问题,本发明在微型流体系统100中运用电流控制。在给定电极处的电流与沿着与设有电极的容器相连的沟道的离子流直接相关。这与在电压控制系统中确定在沿着沟道的各个交叉点处的电压的要求相反。于是,响应于通过系统100的各个电极的电流设定在微型流体系统100的电极处的电压。在衬底102上产生微型流体系统的过程中,电压控制对尺寸的变化的敏感度较小。电流控制使得在复杂的微型流体系统中进行抽运(pumping)、装阀(valving)、分散、混合和集中目的材料及缓冲流体的操作更加容易。电流控制更利于调节在沟道内的不想要的温度效应。
当然,除了直接测量在电极之间的离子流的电流之外,与电流相关的其它电气参数(诸如,功率)也可用于控制微型流体系统100。功率间接测量通过电极的电流。于是,可由通过电极的功率检测在电极(和离子流)之间的物理电流。
即使对于上述电流控制系统,仍然必需为微型流体系统的电极提供高电压。为了消除对能够产生连续和精确的高电压的昂贵电源的需要,本发明提供经时间多路复用(time-multiplex)的电源,这些时间多路复用电源还减小了系统100所需的电源数量,这是因为时间多路复用电源可以对多个电极提供服务。
图3A示出当今在电动系统中用到的示范高电源的输出。随着时间变化,在两个电极之间的电压输出是恒定的250V。相反,图3B示出根据本发明操作的电源的输出。为了保持250V的恒定电压,在1000V下,把输出电压与四分之一工作循环时间多路复用。在时间上求平均,经时间多路复用的电压源的输出是250V(如图中水平虚线所示)。注意,如果电压必需改变,即,如上所述,响应于电流控制,经时间多路复用的电源的输出电源随着施加的电压变化,或者随着工作循环的变化或者两者结合而改变。
在上述尺寸的沟道中,可以按μ秒级,开始和停止电渗透流体。因此,由于流体的突变移动,导致低于1MHz的电压调节频率。由于电渗透流体的自然活塞式流动,使得这应对流体处理没有任何反作用。由于大多数混合、酝酿(incubating)和分离事件都以0.1至100秒的时间规模发生,所以对于电压处理的更低频率是可以接受的。根据经验,调节周期应小于最短的转换事件(例如,从一个沟道转换到另一个沟道的转换流)的1%以使混合或吸移(pipetting)误差保持在1%下。对于0.1秒的转换事件,电压调节频率应为1Khz或更高。
图4A是复接电源系统的方框图,其中复接电源系统具有两个电源200和202以及控制器单元(block)204用于具有与沟道182、184、186和188相交的沟道180的示范简单微型流体系统。沟道180在分别具有电极190和191的容器179和181中终止。沟道182在具有电极193的容器中终止;沟道184在具有电极195的容器185中终止;沟道186在具有电极197的容器187中终止;和沟道188在具有电极199的容器中终止。
把电源200和202连到微型流体系统的不同电极190、191、193、195、197和199。把电源200连到三个电极190、193和195上,而把电源202连到剩余的三个电极191、197和199上。把控制器单元204连到每个电源200和202上以协调它们的操作。例如,为了控制通过沟道182、184、186和188的流体的移动,必须适当地安排把电压施加在电极190、191、193、195、197和199上的的时间。如上所述,例如,当控制器单元204控制(direct)电源200和202时,响应于电流流动,施加在电极上的电压也变化。
把每个电源200和202组成单元(如图4B所示)。控制单元212接收来自控制单元204的控制信号,并控制转换单元214的操作。连到电源单元216的转换单元214形成或破坏与电源单元216与所连接的电极的连接。换句话说,转换单元214在它所连接的电极中,时间多路复用来自电源单元216的功率。还把电源单元216连到控制单元212,它控制从电源单元216到转换单元214的输出变化。在另一种结构中,如果电源单元216提供恒定电源,并且通过转换单元214改变连接工作循环,改变到电极的平均电源,那么不需要到控制单元212的连接。
图6A是可用作如图4B所示的电源单元216的电源的方框图。作为替代,如果不使用时间多路复用,那么可以把所示的电源直接连到微型流体系统的电极上。电源可以向电极提供稳定的电压以提供或接收(sink)稳定的电流。
电压具有设有从-5至+5V的可控制参考电压的输入端240,而在输出端241处它的电压升至几百V。把输入端通过电阻227连到输入运算放大器230的负输入端。运算放大器230的正输入端接地,而通过串联的反馈电容220和电阻228,把它的输出端连到负输入端。还把输出端连到直流-直流变换器231的输入端。第二输入端接地。把增至从放大器230接收到的电压增大的变换器231的输出端连到电源输出端241。通过电阻器222把变换器231的第二输出端接地。
还通过串联的电阻221和223(它们形成分压电路),把电源输出端241接地。把在两个电阻221和223之间的节点连到电流/电压模式开关234的一个输入端。还通过电阻225把该节点连到反馈运算放大器232的负输入端。还通过电阻器224把负输入端连到变换器231的输出端,并且通过反馈电阻器226连到放大器232的输出端。还把放大器232的输出端连到开关234的第二输入端,其中通过电阻器226把开关的输出端连到输入运算放大器230的负输入端。
开关234对在控制端242上的信号作出响应。如图6A所示,开关234把它的输出端连到反馈运算放大器232的输出端,或者在两个电阻器221和223之间的分压器节点上。连接确定电源电路以电压模式操作(连到分压节点)还是以电流模式(连到反馈运算放大器232的输出端)操作。注意,电阻器221的阻值很大(大约15MΩ),从而当电源操作时,可以容易地反馈在输出端241上的电压。
图6A所示电路可以分成不同操作单元。运算放大器230、电阻器226-228和电容器220是混合单元的一部分。混合单元接受在输入端240处的电源在其周围操作的可控制参考电压Vref和反馈电源(如下所述)以生成对于直流-直流变换器231的输出电压(Vref和反馈电压组合)。变换器231(如图6B中的电压放大器所示)简单地放大来自运算放大器230的电压。把电压放大器的输出端连到输出端241和电阻器221的一端上。通过电阻器222把电压放大器的另一输出端接地。电阻器221-223可看作反馈单元的一部分,其中反馈单元还具有电阻器224-226和运算放大器232。开关234也是反馈单元的一部分,并连到混合单元的第二输入端(如前所示)。
在操作期间,混合单元具有运算放大器230,它作为加法放大器与电阻226-228相连。作为在运算放大器230的反馈环中的电容器220,运算放大器230的电压是参考电压Vref和来自开关234的反馈电压之和(或之差)对时间求积分所得的电压。当然,电阻226和227的阻值可对参考电压Vref和反馈电压有选择地加权。电容器220和放大器230还作为滤波器以从电源中滤去高频波动部分。
附加元件(未图示)可以调节(例如,校正或缓冲)来自运算放大器230的输出信号。然而,为了更好的理解本发明,可以认为由直流-直流变换器231接收到的电压VIN与运算放大器230的输出电压相同。如图6B所示,VIN被放大增益因子A倍,而且在输出端241上生成电压AVIN。
反馈单元具有由连接在输出端241和地之间的电阻221和223组成的分压器电路。在电阻器221和223之间的节点处的电压与在输出端241处的电压成正比。当开关234响应于在控制端242上的信号选择电压反馈模式时,直接把节点电压发送到混合单元和运算放大器230。负反馈稳定在端241处的输出。例如,如果在端241处的电压很高,那么反馈电压很高。反过来,这导致运算放大器230的输出电压下降,从而补偿在输出端241处的高电压。对于监测在输出端241处的电压,还把节点连到运算放大器251(构成简单的缓冲器)以把反馈电压馈送到监测电路(未图示)。
反馈电源还具有运算放大器232和电阻224-226,它们连接起来构成运算放大器232作为加法放大器。把到加法放大器232的一个输入连到在电阻器221和223之间的节点。把第二输入连到在接地的电阻器222和直流-直流变换器231的第二输出端之间的节点。加法放大器测量通过串联的电阻器221和223和变换器231(通过电阻222和224的全部电流)的电流量之差。实际上,加法放大器测量通过输出端241传递(deliver)的电流量。然后,当开关234设定在电流反馈模式下时,把作为加法放大器的运算放大器232的输出送到混合单元并使电源电路稳定在通过电源端241接到微型流体系统的连接极点的电流量附近。
还把加法放大器的输出连到运算放大器250(构成简单的缓冲器),以把输出电压送到监测电路(未图示)。根据运算放大器250和251的输出端,监测电路测量在输出端241处的电压和通过终端的电流。这还允许监测电路确定和调整由电源电路提供的功率量。
上述电源作为变量源的能力使得流体流过微型流体系统的微型沟道的方向因电而改变。如果把所有电极连到一个或多个上述电源,那么大大增强微型流体系统的操作,而且流体在系统中的沟道网络中的理想流动会变得更加灵活。
尽管作为电流控制系统操作,仍然需要确定在微型流体系统中的节点处的电压。本发明还提供用于这种电压监测的装置。如图5A所示,在微型流体系统中,在衬底178靠近所需节点173的的表面上形成电线160。节点173位于在每个末端具有容器169和171的沟道170和沟道172及174的交叉点上。沟道174的终点具有容器175,而图中未示出沟道172的终点(和容器)。
最好由用于集成电路的导电金属的沉积物或者合金(最好是贵金属,诸如,铬上的黄金或者钛上的白金)形成电线160。运用半导体影印石版术,可以把电线160的宽度限定在小于1μm。为了防止电分解,在沟道170中的电线160的宽度足够窄以至于在任何时候,在沟道170中的电线两端的电压应小于1V,最好小于0.1V。
在微型流体系统中用到的电压很高。直接测量在通过电线160的沟道节点173处的电压的伏特计必须具有很高的输入阻抗以能够测量这种高压。这种伏特计很昂贵。此外,对微型流体系统的衬底处理增加了污染的可能性。这种污染可能严重影响在微型流体系统的沟道中的电动力的适当操作所需的电压(和电场)。
为了避免这种问题和成本,把电线160连到在衬底178的表面上形成的分压电路163。由导电输出线161携带分压电路163的输出。还由导电线162把电路163连到电压参考(voltage reference)。
用于标准半导体制造技术,由电阻器165和166连接成如图5B中详细示出的分压电路163。电线160连到电路163的输入端,它是线性模式(lihear pattern)的高电阻材料(诸如,不涂料的或者轻轻涂上聚硅酸盐或矾士)的一端。线性模式的另一端连到也在衬底168上形成的参考电线162,并通向外参考电压(推定为地)。为了说明目的示出,以10比1的比率划分线160的电压把线性模式分成电阻器165和电阻器166。电阻器165具有比电阻器166多9倍的圈,即,电阻器165的电阻比电阻器166的电阻大9倍。当然,可以采用其它比率,而且一般比率是1000∶1。连接两个电阻器165和166的输出线161通向外连线,以由伏特计读取低压。然后覆盖薄板保护电线160-162、分压电路163和衬底的表面不手污染。
虽然为了说明和理解目的,已详细地描述了本发明,但是熟悉本技术领域的人员通过熟读本说明书可知可以进行形式和细节上的各种变化,而不偏离本发明的真实范围。在所有情况下,在本发明中引证的所有出版物和专利文件全部作为参考资料在此引入,就象个别表示每个出版物或专利文件。
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1.在一种微型流体系统中,其中所述微型流体系统具有多个相互连接的毛细沟道和在所述毛细沟道的不同节点处的多个电极以在所述毛细沟道中产生电场以使在流体中的材料电动流过所述毛细沟道,其特征在于,操作所述微型流体系统的方法包括:
响应于所述电极上的电流,对所述电极施加相对于系统中其它电极的电压,使材料在所述电极的沟道来回移动。
2.如权利要求1所述的方法,其特征在于,所述微型流体系统至少具有三个电极。
3.如权利要求2所述的方法,其特征在于,所述施加电压的步骤包括控制所述电压,从而所述电流实质上是恒定的。
4.在一种微型流体系统中,其中所述微型流体系统具有多个毛细沟道和在所述毛细沟道的不同节点处的多个电极以在所述毛细沟道中产生电场以使在流体中的材料电动流过所述毛细沟道,其特征在于,操作所述微型流体系统的方法包括:
及时控制施于所述系统中电极之间的电参数以使材料在它们之间流动。
5.如权利要求4所述的方法,其特征在于,控制所述施加的电参数,从而所述材料同等移动,以把所述电参数恒定施加在所述系统中的所述电极之间。
6.如权利要求5所述的方法,其特征在于,通过改变施加电参数的时间百分比,控制所述施加。
7.如权利要求4所述的方法,其特征在于,所述电参数包括电压。
8.如权利要求4所述的方法,其特征在于,所述电参数包括电流。
9.如权利要求4所述的方法,其特征在于,所述电参数包括功率。
10.一种微型流体系统,其特征在于,包括:
在绝缘衬底中的多个毛细沟道;
在所述毛细沟道的不同节点处的多个电极以在所述毛细沟道中产生电场,从而使在流体中的材料电动流过所述毛细沟道;和
在所述衬底上的至少一根导电线,它延伸至毛细沟道位置,从而可以确定在所述毛细沟道位置处的电压。
11.如权利要求10所述的微型流体系统,其特征在于,所述导电线具有很小的宽度,从而在所述毛细沟道位置上与所述导电线的交叉点上产生小于1V的电压。
12.如权利要求11所述的微型流体系统,其特征在于,所述导电线具有很小的宽度,从而在所述毛细沟道位置上与所述导电线的交叉点上产生小于0.1V的电压。
13.如权利要求10所述的微型流体系统,其特征在于,排列所述导电线,以在所述衬底上形成所述分压电路,从而从所述导电线接收到的电压是在所述毛细沟道位置上的所述电压的一小部分。
14.如权利要求10所述的微型流体系统,其特征在于,还包括覆盖所述衬底的绝缘板,所述导电线延伸至所述衬底的边缘。
15.一种微型流体系统,其特征在于,包括:
具有多个相互连接的毛细沟道的衬底;
在所述毛细沟道的不同节点处的多个电极以在所述毛细沟道中产生电场,从而使在流体中的材料电动流过所述毛细沟道;
与至少一个所述电极相连的电源,所述电源还包括:
具有用于接收可控制参考电压的第一输入端、第二输入端和输出端的混合单元;
连到所述混合单元输出端的电压放大器,所述电压放大器具有第一和第二输出端,所述第一输出端与至少一个所述电极相连;和
连到所述电压放大器的所述第一输出端的反馈单元,所述反馈单元具有连到所述混合单元的所述第二输入端的输出端,从而提供负反馈以稳定所述电源。
16.如权利要求15所述的微型流体系统,其特征在于,通过分压电路把所述反馈单元连到所述第一输出端。
17.如权利要求16所述的微型流体系统,其特征在于,所述反馈单元响应于在所述第一输出端处的电压,向所述混合单元提供反馈。
18.如权利要求16所述的微型流体系统,其特征在于,把所述反馈单元连到所述电压放大器的所述第二输出端,从而所述反馈单元响应于通过所述第一输出端来源或变换的电流量,生成输出电压,所述反馈单元响应于通过所述第一输出端发出或接收的所述电流量,向所述混合单元提供反馈。
19.如权利要求18所述的微型流体系统,其特征在于,所述反馈单元具有加法放大器,所述加法放大器具有连到所述分压电路的第一输入端和连到所述电压放大器的所述第二输出端的第二输入端,所述加法放大器响应于通过所述第一输出端发出或接收的所述电流量,生成所述输出电压。
20.如权利要求16所述的微型流体系统,其特征在于,把所述放电单元连到所述电压放大器的所述第二输出端,所述反馈单元响应于在所述第一输出端处的电压生成第一反馈电压,并响应于通过所述第一输出端发出或接收到的电流量生成第二反馈电压,所述反馈单元具有用于响应于控制信号把所述第一或第二反馈电压通到所述混合单元的开关,从而通过电压和电流反馈有选择地稳定所述电源。
21.如权利要求20所述的微型流体系统,其特征在于,还包括连到所述反馈单元的第一和第二缓冲器,所述第一缓冲器发出所述第一反馈电压,而所述第二缓冲器发出所述第二反馈电压,从而可以监测所述第一和第二反馈电压。
22.如权利要求15所述的微型流体电源,其特征在于,所述混合单元包括作为加法放大器连接的运算放大器。
23.如权利要求22所述的微型流体电源,其特征在于,所述运算放大器还作为积分器连接。
24.一种用于连到微型流体系统的至少一个电极的电源,其特征在于,包括:
具有用于接收可控制参考电压的第一输入端、第二输入端和输出端的混合单元;
连到所述混合单元输出端的电压放大器,所述电压放大器具有第一和第二输出端,所述第一输出端连到所述至少一个电极;和
连到所述电压放大器的所述第一和第二输出端以及所述混合单元的所述第二输入端的反馈单元,所述反馈单元响应于在所述第一输入端处的电压生成第一反馈电压并响应于通过所述第一输出端发出或接收的电流量生成第二反馈电压,所述反馈单元具有用于响应于控制信号使所述第一和第二反馈单元通到所述混合单元的开关,从而通过负反馈有选择地稳定电源的电压或电流。
25.如权利要求24所述的电源,其特征在于,通过分压电路把所述反馈单元连到所述电压放大器的所述第一输出端。
26.如权利要求24所述的电源,其特征在于,把所述反馈单元连到所述电压放大器的所述第二输出端,从而所述反馈单元响应于通过所述第一输出端发出或接收的电流量生成输出电压。
27.如权利要求24所述的电源,其特征在于,还包括:连到所述反馈单元的第一和第二缓冲器,所述第一缓冲器送出所述第一反馈电压,而所述第二缓冲器送出所述第二反馈电压,从而可以监测所述第一和第二反馈电压。
28.如权利要求26所述的电源,其特征在于,所述反馈单元具有加法放大器,该所述加法放大器具有连到所述分压电路的第一输入端和连到所述电压放大器的所述第二输出端的第二输入端,所述加法放大器响应于通过所述第一输出端发出或接收的所述电流量生成所述输出电压。
29.如权利要求24所述的电源,其特征在于,混合单元包括作为加法放大器连接的运算放大器。
30.如权利要求29所述的电源,其特征在于,运算放大器进一步连接作为积分器。
31.一种微型流体系统,其特征在于,包括:
具有多个互相连接的毛细沟道的衬底;
在所述毛细沟道的不同节点处的多个电极以在所述毛细沟道中产生电场,以使在流体中的材料电动流过所述毛细沟道;
连到每个所述电极的多个电源,每个所述电源能够有选择地向所述连接的电极提供作为源或接收端的所选电压或所选电流量。
32.对于至少具有一个沟道的衬底的运用,其中通过响应于在所述电极处的电流在与所述沟道相关的两个电极之间施加电压,电动地传输目的材料。
33.如权利要求32所述的运用,其特征在于,所述衬底具有多个相互连接的沟道和相关的电极,通过响应于在所述电极上的电流把电压加在预定电极,沿着加入一个或多个所述沟道的预定通道传输目的材料。
34.对于至少具有一个沟道的衬底的运用,其中通过对根据时间在与所述沟道相关的电极之间加电参数的控制,电动传输目的材料。
35.如权利要求34所述的运用,其特征在于,所述电参数包括电压。
36.如权利要求34所述的运用,其特征在于,所述电参数包括电流。
37.如权利要求34所述的运用,其特征在于,所述电参数包括功率。
38.对于具有多个沟道和与所述沟道相关的多个电极的绝缘衬底的运用,在所述电极上施加电压使得在所述沟道中产生电场,而且在所述衬底上的至少一个导电线延伸至沟道位置,从而可以确定在所述沟道位置上的电参数。
39.如权利要求38所述的运用,其特征在于,所述导电线具有很小的宽度,从而在所述沟道位置上与所述导电线的交叉点上产生小于1V的电压,最好是小于0.1V的电压。
40.对于绝缘衬底的运用,其特征在于,所述绝缘衬底具有多个相互连接的毛细沟道、在所述毛细沟道不同节点处的多个电极以在所述毛细沟道中产生电场以使在流体中的材料电动流过所述毛细沟道,连到至少一个所述电极的电源、所述电源具有用于接收参考电压的第一输入端和第二输入端及输出端的混合单元;连到所述混合单元输出端的电压放大器,所述电压放大器具有第一和第二输出端,所述第一输出端连到所述至少一个电极;和连到所述电压放大器的所述第一输出端的反馈单元,所述反馈单元具有连到所述混合单元的所述第二输入端的输出端,从而提供负反馈以稳定所述电源。
41.如权利要求40所述的运用,其特征在于,所述反馈单元还连到所述电压放大器的所述第二输出端,所述反馈单元响应于在所述第一输出端处的电压生成第一反馈电压,而响应于通过所述第一输出端发出或接收的电流量生成第二反馈电压,所述反馈电压具有用于响应于控制信号把所述第一或第二反馈电压通到所述混合单元的开关,从而通过电压或电流反馈有选择地稳定所述电源。
42.对于连到微型流体系统的至少一个电极的电源的运用,其特征在于,所述电源具有包括用于接收参考电压的第一输入端和第二输入端及输出端的混合单元;连到所述混合单元输出端的电压放大器,所述电压放大器具有第一和第二输出端,所述第一输出端连到所述至少一个电极;和所述反馈单元连到所述电压放大器的所述第一和第二输出端和所述混合单元的所述第二输入端,所述反馈单元响应于在所述第一输出端处的电压生成第一反馈电压,和响应于通过所述第一输出端发出或接收的电流量生成第二反馈电压,所述反馈电压具有用于响应于控制信号使所述第一或第二反馈电压通到所述混合单元的开关,从而通过负反馈有选择地稳定所述电源的电压或电流。
43.对于微型流体系统的运用,其特征在于,衬底具有多个相互连接的毛细沟道,在所述毛细沟道的不同节点处的多个电极以在所述毛细沟道中产生电场以使在流体中的材料电动流过所述毛细沟道,而且连到每个所述电极的多个电源,每个所述电源能够有选择地提供所选电压和所选电流量作为所述连接的电极的源或接收端。
44.一种微型流体系统,其特征在于,它包括具有其中电动传输目的材料的至少一个沟道的衬底、用于测量电流的装置和用于响应于在所述电极处的所述电流在与所述沟道相关的两个电极之间施加电压的装置。
45.如权利要求44所述的系统,其特征在于,所述衬底具有多个相互连接的沟道和相关电极,通过响应于在所述电极处的电流把电压施加在预定电极上,沿着加入一个或多个所述沟道的预定通道传输目的材料。
46.一种微型流体系统,其特征在于,它包括具有其中电动传输目的材料的至少一个沟道的衬底和用于控制根据时间在与所述沟道相关的电极之间施加电参数的装置。
47.如权利要求46所述的系统,其特征在于,所述电参数包括电压。
48.如权利要求46所述的系统,其特征在于,所述电参数包括电压。
49.如权利要求46所述的系统,其特征在于,所述电参数包括电压。
50.一种微型流体系统,其特征在于,包括具有多个沟道和与所述沟道相关的电极的衬底、用于把电压加在所述电极上以在所述沟道中生成电场的装置和在所述衬底上延伸至沟道位置以确定在所述沟道位置上的电参数的至少一个导电线。
51.如权利要求50所述的系统,其特征在于,所述导电线具有很小的宽度,从而在所述沟道位置上与所述导电线的交叉点上产生小于1V的电压,最好是小于0.1V的电压。
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- 1997-07-03 ZA ZA9705948A patent/ZA975948B/xx unknown
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JP2000513813A (ja) | 2000-10-17 |
CN1143129C (zh) | 2004-03-24 |
DE69735739D1 (de) | 2006-06-01 |
EP0909386A4 (en) | 2005-01-19 |
BR9710193A (pt) | 2000-01-11 |
EP0909386A1 (en) | 1999-04-21 |
EP1241472A3 (en) | 2003-12-17 |
EP1241472A2 (en) | 2002-09-18 |
AU718697C (en) | 2001-07-26 |
DE69735739T2 (de) | 2007-05-10 |
JP3496156B2 (ja) | 2004-02-09 |
ATE324584T1 (de) | 2006-05-15 |
AU3672497A (en) | 1998-01-21 |
CA2258699A1 (en) | 1998-01-08 |
US6413401B1 (en) | 2002-07-02 |
TW345683B (en) | 1998-11-21 |
US5800690A (en) | 1998-09-01 |
EP0816837B1 (en) | 2006-04-26 |
WO1998000707A1 (en) | 1998-01-08 |
NZ333438A (en) | 2000-08-25 |
EP0816837A1 (en) | 1998-01-07 |
US5965001A (en) | 1999-10-12 |
AU718697B2 (en) | 2000-04-20 |
ZA975948B (en) | 1998-03-19 |
CA2258699C (en) | 2003-04-01 |
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