含阵列电极的硅基电泳芯片微管道性能的表征和分析

以含阵列电极的SOI硅基芯片与PDMS盖片制成的复合电泳芯片为对象,研究芯片电泳过程中芯片微管道的特殊表面电化学性质.实验采用电流监测法,利用溶液探针测试体系来表征微管道的电绝缘性,由于工艺缺陷或芯片长时间使用引起的绝缘层不同程度的损坏,导致在充液管道中产生的10-500μA的基底电流,这又导致不同程度焦耳热,进而导致电渗流无法稳定和芯片电泳过程无法正常进行.实验提出通过优化硅-PDMS电泳芯片的结构设计来避免和减小基体电流,同时采用以导热硅酯为介质的散热器对硅片试验体系进行散热,进一步减小焦耳热的影响以获得稳定的电渗流.在此基础之上,实验测得硅-PDMS微管道中的电渗迁移率为3.9×10-4 cm2/V·s,伏安曲线显示5 mmol硼砂缓冲中最大施加电压为260 V/cm;采用本文提出的复合芯片系统,分离FITC标记的精氨酸和苯丙氨酸混合样品,分离度达到3.14,柱效分别达到18 000和25 000.     

电泳微芯片进样口与微沟道形状的优化设计

基于电渗流场的理论,建立电泳芯片的不同结构模型,以计算流体力学(CFD)方法来模拟不同设计参数和电压组合下的电泳微芯片微沟道中流体流动现象.最终优化基本型毛细管微沟道交叉口形状为矩形,微沟道宽度为20 μm,进样与分离场强为200～250V/cm.为在有限芯片面积下增加有效分离距离,设计螺旋形沟道电泳芯片模式.     

基于微环形阵列电极的细胞分离富集芯片的设计与实验研究

根据介电泳操作原理,设计了微环形阵列电极结构,建立了细胞分离富集芯片模型,采用COMSOL软件分析微环形阵列电极的电场分布和介电泳力方向并确定了最大和最小电场强度的位置,利用ITO玻璃和PDMS制备了细胞分离富集芯片.通过酵母菌细胞的介电泳富集实验和酵母菌细胞与聚苯乙烯小球的分离富集实验,明确了酵母菌细胞的临界频率,实现了酵母菌细胞和聚苯乙烯小球的分离富集.结果显示,在溶液电导率为60μs/cm,交流信号电压为8Vp-p时,酵母菌细胞在1kHz~45kHz频率范围内做负介电泳运动并富集在环形内部,45kHz为酵母菌细胞的临界频率,在45kHz~10MHz频率范围内做正介电泳运动并富集在环形边缘;1.5MHz时聚苯乙烯小球做负介电泳运动并富集在环形内部,富集倍数达到11.66.     

基于介电泳的电极阵列电场仿真研究

介电泳方法被广泛地应用于微纳颗粒的分离和操纵中,实现介电泳操作的关键是设计满足所需电场分布的电极阵列.针对目前在微电极阵列设计中尚缺乏简单有效的电场解析方法的现状,提出一种基于格林公式的电极阵列电场的解析方法.首先介绍了传统介电泳和行波介电泳的概念和计算模型,分析了介电泳过程与电极上所施加的交变电压的频率和幅度的关系,然后在确立电极电势的边界条件的基础上,采用基于格林公式的电场解析方法,建立了非均匀电场的解析模型,得出不同条件下的电极阵列电场分布的仿真结果,最后利用FEMLAB有限元仿真软件对解析模型进行了对比仿真, 验证了该解析模型的可行性.基于格林公式的电场解析求解方法能够有效地提高电极阵列设计中的针对性以及缩短电极设计的时间.     

线阵电极电泳芯片与单片机控制系统

介绍了用于生化分析的一种微全分析控制系统,包括电泳芯片的设计制作、微机控制系统以及初步实验结果。新型电泳芯片基于线性阵列电极,可灵活设定分离时间、长度、电压等电泳的各项条件,满足多种分离需求。以C8051F020单片机为控制核心,扩展出大量并行I/O口,并与高压系统实现良好的控制与衔接。突出了单片机系统的高度集成、低功耗、高扩展性等特点,给出了扩展大量I/O口并灵活控制多路高压器件的实例。     

基于单片机的电泳微型化控制检测系统

电泳芯片分离控制系统微型化及其片上检测是生化分析的发展方向。本文基于一种阵列电极低压电泳芯片,以Cygnal公司的C8051F020单片机搭建了微型化电泳控制检测系统,通过继电器网络对芯片电极进行分离控制,利用比例法电阻检测原理,采用了TI公司的24位A/D芯片MSC1210进行分离结果检测。实验结果表明,该系统可以实现低压电泳分离及片上高精度电阻检测。     

绝缘体介电电泳细胞分离器件数值分析和优化

绝缘体介电电泳(iDEP)利用微流体管道中均匀绝缘柱阵列产生介电电泳(DEP)所需要的非均匀电场,实现微全分析系统(μTAS)和芯片实验室(LOC)中细胞等生物粒子的分离.对这种新型的iDEP器件进行理论分析,建立了数值计算方法.基于有限元数值计算理论,利用Ansys软件,计算了细胞的介电电泳力,验证了iDEP的富集原理,对iDEP器件的介质形状、尺寸、间距和微管道长度等参数进行了优化,提出了设计准则.选用间距10 μm,圆形,微管道长度3550 μm的5×5绝缘柱阵列,器件性能最优.     

面向微粒操纵的介电泳芯片系统研究

针对目前在纳米器件及传感器的制造中尚无对大量粒子进行有效操纵的方法,我们利用介电泳方法对大量微粒进行定位和传输操纵,介绍了利用MEMS工艺进行介电泳芯片加工的过程以及整个观测与实验系统的建立,通过有限元软件对传统介电泳和行波介电泳中电极阵列的电场分布进行求解,并在该实验系统下实现了对微通道中的悬浮高度和微粒的运动速度的测量.该实验系统的研究为液体环境下微纳颗粒的装配和分离提供了一条有效的技术路径.     

介电泳芯片的研制及不同细胞介电分离的应用

制备了包括指状交叉、城墙状和梯形的微电极阵列芯片装置.并用这些芯片探索了生物细胞的介电响应.另外观察了酵母和鸡血红细胞的迁移、旋转和融合以及几种细胞收集图片.发现了两种细胞的正、负介电泳现象,确定了这两种细胞的分离条件.讨论了两种细胞正、负介电泳的原因.利用同一芯片在相同的条件下一种细胞移向强场区(正介电泳),另一种细胞移向弱场区(负介电泳).因此可用同一芯片分离不同的细胞.有望建立一种非接触式细胞分离技术,而且在分离过程中不需要添加任何试剂.     

基于静电力的微液滴驱动芯片

为了精确操控微流体,设计并制作了一种基于静电力的微液滴驱动芯片.介绍了驱动原理和工艺流程,搭建了驱动检测实验平台.芯片采用开放式的结构,只需单层共平面控制电极,以硅作衬底,氧化硅和多晶硅作绝缘层,重掺杂多晶硅为驱动电极阵列,高质量Si3N4作介质层,碳氟聚合物为疏水层.实验表明:微液滴可在芯片上按程序设定方式在二维平面...     

A circular microchannel with integrated electrodes for DNA electrophoresis

The development of a novel microfluidic device that includes a circular microchannel and integrated electrodes for DNA electrophoresis is reported. The geometry of the separation channel and the arrangement of the embedded electrodes provide several advantages in relation to conventional linear microchannels. The paper describe the design, modeling, construction, and testing of the micro device. Numerical simulations were used to investigate the electric field into the microchannel. In addition, the electrophoretic transport of DNA samples was studied under different voltage configurations. The experiments reported show the functionality of the device, and illustrate interesting features of DNA transport.     

集成毛细管电泳芯片的设计

利用ANSYS软件对集成毛细管电泳芯片微沟道内样品流动情况进行模拟,获得了不同进样模式下微沟道的结构与流体流速之间的关系,并以此为依据对芯片整体结构参数进行设计:毛细管沟道最终尺寸为宽度16μm,深度10μm,有效分离长度为3.5cm的圆角转弯形沟道,从而确定整个芯片设计。     

Silicon–glass instrumented solid-phase extraction–zone electrophoresis microchip with thin amorphous silicon film electrodes: performance in immunoaffinity analysis

Silicon–glass microchips were designed and fabricated for on-chip solid phase extraction (SPE) and zone electrophoresis studies. The solvent channels for extraction and the separation channels for analyses were fabricated sequentially on the silicon device. Electrical contacts were integrated in a fused silica glass lid. Amorphous silicon thin film electrodes were fabricated for high voltage and conductivity detection. A chip installation rack with electrical and fluidic contacts was constructed to facilitate the experiments. Simulation was used to elucidate both the liquid flow and the electric field distribution. The operational performance of the microchips was demonstrated by using a fluorescein isothiocyanate (FITC)-labelled testosterone derivative as the model analyte and fluorescein as both the negative control and the calibration compounds. In SPE an immunosorbent, based on recombinant anti-testosterone Fab-fragments, was immobilized to activated Sepharose gel. Simultaneous monitoring of the movement of FITC-testosterone from SPE cavity through the channel to the detection point was performed with a laser-induced fluorescence detector. The observed limit of detection for FITC-testosterone was 2 μM.     

集成微流体测控芯片的研制

设计、研制了集成有微泵、微沟道、微流量传感器、温度传感器的微流体测控芯片.采用有限元软件ANSYS模拟分析了将其作为冷却芯片时微沟道的散热作用,分析确定了芯片上各元件的结构.该集成芯片为硅-玻璃结构,在硅片上,利用ICP法刻蚀无阀微泵泵体和微沟道;在7740玻璃片上,以溅射、剥离法制作微流量和温度传感器;图形精确对准后硅/玻璃以静电键合方法封接.无阀微泵采用压电元件驱动.测试结果表明:集成芯片具有冷却功能,循环水的流速最大可达25.4mm/s.     

集成惯性聚焦结构的介电泳微流控芯片的粒子连续分离

设计并制造了一种带有惯性聚焦结构的介电泳微流控芯片,以实现不同介电性质的粒子连续分离.采用MEMS工艺制作了介电泳微流控芯片:通道入口侧壁设置一对梯形结构使经过的粒子受惯性升力的作用聚焦到通道两侧;通道底部光刻一组夹角为90°的倾斜叉指电极产生非均匀电场,利用介电泳力和流体曳力的合力使通道两侧不同的粒子发生角度不同的偏转进入不同通道,从而实现分离.将酵母菌细胞和聚苯乙烯小球作为实验样本,分析了流速和交流电压对分离的影响,确定了二者分离的最优条件并进行分离.实验结果表明,将电导率为20μS/cm的样本溶液以5μL/min的流速注入到通道中,施加6 Vp-p、10 kHz的正弦信号,酵母菌细胞沿电极运动至夹角处后沿通道中心排出,聚苯乙烯小球沿通道两侧排出,成功实现分离,平均分离效率达92.8％、平均分离纯度达90.7％.     

基于uC/OS-II的微流体芯片嵌入式实时系统构建

本文构建具有DNA聚合酶链式反应(PCR)和毛细管电泳(CE)分离检测功能的微流体芯片uC/OS-II嵌入式实时控制系统。本系统采用32位嵌入式微控制器ARM实现PCR扩增所需的闭环温度控制功能,毛细管电泳分离功能所需的高压电场自动调度功能。uC/OS-II嵌入式实时操作系统加强了系统的实时性。模糊免疫PID控制算法实现对温度的精确控制,其控制性能远优于常规PID控制器。试验结果表明本系统不但完全满足设计要求,而且与同功能的仪器平台相比,实时性强,不再需要昂贵的个人电脑进行控制运算和常用的DNA检测设备进行检测,实现了PCR-CE微流体芯片系统的低成本和小型化。     

Differential C<Superscript>4</Superscript>D sensor for conductive and non-conductive fluidic channel

This paper presents a novel design of a differential C⁴D (DC⁴D) sensor based on three electrodes for both conductive and non-conductive fluidic channel. This structure consists of two single C⁴D with an applied carrier sinusoidal signal to the center electrode as the excitation electrode. The electrodes are directly bonded on the PCB with built-in differential amplifier and signal processing circuit in order to reduce the parasitic component and common noise. In the non-conductive fluidic channel, the output voltage and capacitance changes 214.39 mV and 14 fF, respectively when a 3.83 μl tin particle crosses an oil channel. In conductive fluidic channel, the output voltage and admittance change up to 300 mV and 0.07 μS for the movement of a 4.88 μl plastic particle through channel. Moreover, the voltage change of this sensor is linear relation with the volume of investigated particle. This sensor also allows measuring velocity of particle inside fluidic channel and resistivity of the conductive fluidic.     

Automating fluid delivery in a capillary microfluidic device using low-voltage electrowetting valves

A multilayer capillary polymeric microfluidic device integrated with three normally closed electrowetting valves for timed fluidic delivery was developed. The microfluidic channel consisted two flexible layers of poly (ethylene terephthalate) bonded by a pressure-sensitive adhesive spacer tape. Channels were patterned in the spacer tape using laser ablation. Each valve contained two inkjet-printed silver electrodes in series. Capillary flow within the microchannel was stopped at the second electrode which was modified with a hydrophobic monolayer (valve closed). When a potential was applied across the electrodes, the hydrophobic monolayer became hydrophilic and allowed flow to continue (valve opened). The relationship between the actuation voltage, the actuation time, and the distance between two electrodes was performed using a microfluidic chip containing a single microchannel design. The results showed that a low voltage (4.5 V) was able to open the valve within 1 s when the distance between two electrodes was 1 mm. Increased voltages were needed to open the valves when the distance between two electrodes was increased. Additionally, the actuation time required to open the valve increased when voltage was decreased. A multichannel device was fabricated to demonstrate timed fluid delivery between three solutions. Our electrowetting valve system was fabricated using low-cost materials and techniques, can be actuated by a battery, and can be integrated into portable microfluidic devices suitable for point-of-care analysis in resource-limited settings.     

Minute particle detection using a light-wave-guide incorporated optical total analysis system

An optical sensor combined total analysis system (TAS) is thought to be one of the most effective functional elements in realizing a ubiquitous human healthcare system. In accordance with this concept, we have proposed a fundamental structure of a light-wave-guide incorporated TAS and have developed a micro fluidic channel fabricated chip, where two light waveguides having approximately 10-??m cores were facing each other across a fluidic channel with a width of 12???m. By passing 5-??m-diameter polystyrene particles across the portion where a light-wave-guide and the fluidic channel intersect at a right angles, we confirmed that changes to transmitted light and scattered light were detectable even with an extremely low laser source power of 5???W, and they increased proportionally as the introduced laser power became higher. Increasing the introduced laser power clearly increased the correlation between the transmitted and scattered light change. Here we discuss in detail the two different correlation tendencies that appeared in the correlation maps.