【作者】 曹军；

【导师】 郑平；

【作者基本信息】 上海交通大学 ， 动力工程及工程热物理， 2009， 博士

【摘要】 基于微机电系统(Micro-Electro-Mechanical-System, MEMS)或微全分析系统(Miniaturized Total Analysis System,μ-TAS)的微流控芯片(Microfluidic Chip)将传统分析实验室的功能,包括采样、稀释、反应、分离和检测等,集成到方寸大小的芯片上,具有自动、快速以及低样品消耗等优点,已经在聚合酶链式反应、基因突变检测、蛋白质和氨基酸的分析以及单细胞的分析检测等生化分析过程中表现出了巨大的优势,并将发展成为当今世界最前沿的科技领域之一。尽管研究微流控芯片的最终目的是以产品的形式对其进行实际的应用,但由于微流控芯片加工的高成本,使用合理的模型对其中的传输现象(包括流体流动、粒子分离以及传热现象等)进行理论上的分析,对于提高实验效率、降低实验成本和优化芯片结构具有重要的作用。目前,以电场力为驱动源,以电水动力学(Electrohydrodynamics)基本原理为理论依据的微流控芯片占据着主要地位。微流控芯片中的电场驱动可以分为直流电场驱动方式和交流电场驱动方式,两种驱动方式下的传输现象都主要包括流体的电渗流动,粒子的电泳分离,以及由于电场的应用而在溶液中产生的焦耳热效应。本文以微流控芯片中的电水动力学理论为基础,主要采用理论建模和数值仿真的研究方法,并结合实验验证,分别从直流电驱动和交流电驱动微流控芯片中所涉及的电渗、电泳和焦耳热效应这三个基本传输过程中提炼出重要的基础问题进行研究,并提出了一系列新颖的流体控制方案(例如电热流增强效果的微混合器,电热流动泵等),最后通过微加工方法分别制备了具有平面电极和三维小立柱阵列电极的介电电泳芯片,以聚苯乙烯粒子为操作工质完成了正向和负向介电电泳实验,对其介电电泳频谱的分析进行了验证。论文的主要内容包括:1.直流电驱动微流控芯片中传输现象的关键问题:(1)关于直流电渗流:提出了一种通过在微通道壁面上增加可极化金属薄膜产生诱导zeta电势来控制局部电渗流场的新方法,并与通过表面涂层改变壁面zeta电势的方式进行了比较,发现诱导zeta电势并非定值,且能通过外加电压进行调节。(2)关于直流电泳:建立了预测双T型通道结构微流控芯片中样品电堆积富集过程的数学模型,通过数值模拟得到了样品粒子富集及之后“解聚”的全过程,分析了样品粒子的带电属性、缓冲溶液浓度比以及样品塞初始长度等因素对富集过程的影响,发现较高的缓冲溶液浓度比和较大的样品塞初始长度都能提高样品富集的效果。(3)关于直流电场中的焦耳热效应:分析了PDMS微流控芯片中的温度场分布,考察了缓冲溶液浓度、芯片材料及厚度等因素对温度的影响,并根据焦耳热效应对毛细管区带电泳中样品区带传输速度和电泳分离效率影响的结果,指出了PDMS微流控芯片中焦耳热效应对相应现象的影响趋势,最后指出了减小焦耳热效应的方法,发现减小芯片厚度等措施能有效降低焦耳热效应。2.交流电驱动微流控芯片中传输现象的关键问题:(1)关于交流电渗流:关于流体的流动现象:建立了交流电渗泵的数学模型,对其中的电势分布以及交流电渗流的速度分布进行了数值模拟,并分析了电解质溶液浓度和交变电场频率对交流电渗流速度的影响,发现最佳频率与溶液的电荷弛豫时间相关;建立了交流电渗泵的RC等效电路模型,对交流电渗泵的阻抗谱进行了理论分析,并分析了电极周期宽度、通道高度以及电解质溶液浓度对其阻抗特性的影响,发现增大电极周期宽度、通道高度以及电解质溶液浓度都可以降低交流电渗泵的阻抗值。(2)关于介电电泳:建立了聚苯乙烯粒子以及细胞的的介电电泳模型并对其进行了频谱分析,以聚苯乙烯粒子为例,在综合考虑了重力、浮力、介电电泳力以及由于电热流动引起的Stokes粘拽力的情况下分析了粒子的悬浮高度,发现Stokes粘拽力在较高的场强作用下对粒子的悬浮高度具有决定性的影响。(3)关于交流电场中的焦耳热效应(电热流动现象):利用电热流动在电极附近漩涡状的流型特点提出了一种新型的微混合器,并分析了电极布置方式、交变电场的大小和频率等因素对其性能的影响,发现该混合器具有较高的混合效率;提出了基于非对称“叉指型”电极结构的电热流动泵的概念,利用数值模拟对其进行了验证和性能的优化,分析了电极宽度比、电解质溶液浓度、芯片材料以及频率等因素对其电热流速的影响,发现相比于交流电渗泵,电热流动泵能在更为广泛的频率范围内工作。关于电热流微混合器和电热流动泵的原理和技术均已申请了中国发明专利。3.微流控芯片中介电电泳分离技术的实验研究:(1)制备了在通道底部沉积有不同平面电极结构的介电电泳芯片,利用聚苯乙烯粒子完成了相应的正、负向介电电泳实验,对其频谱理论分析结果进行了验证。(2)提出并制作了在平面“叉指型”电极上电铸三维小立柱阵列的介电电泳芯片,并完成了介电电泳实验,发现三维小立柱阵列的增加能提高正向介电电泳中电极对粒子的吸附能力。本文以理论仿真为主,并结合实验验证的方式,对电驱动微流控芯片中传输现象的若干关键问题进行了研究。这一课题涉及到多种学科的交叉应用,所提模型又是典型的多尺度多物理场耦合问题,具有较高的学术研究价值。本文建立的模型和得到的结论对于进一步深入理解电驱动微流控芯片中的传输现象具有一定的帮助,完成的工作在一定程度上对现有的关于电驱动微流控芯片研究中在理论建模方面的不足做了补充,对于微流控芯片的设计和优化具有良好的指导意义,而本文所提出的一些新型的微流体控制方法,也为今后的研究提供了一定的启发和借鉴。更多还原

【Abstract】 The microfluidic chip, one of the Micro-Electro-Mechanical Systems (MEMS) or Miniaturized Total Analysis System (μ-TAS), can integrate many functions of a conventional lab (including sample-getting, diluting, reaction, sample separation, as well as detection etc.) into a chip with an area of only several square centimeters. It has the advantages of automated, fast, and low reagent consumption. This kind of chip has a great potential in the processes of Polymer-enzyme Chain Reaction (PCR), nucleic acid analysis, gene mutation detection, analysis of DNA and amino acid, as well as the analysis and detection of single cell.Although the final goal for microfluidic chips are to be used as practical products, however, because of the high manufacture cost, the studies on transport phenomena (such as fluid flow, particles’separation, and heat transfer) in these microfluidic chips play very important roles in enhancing experimental efficiency, decreasing the experimental cost, as well as optimizing the chip structure. At present, microfluidic chips, which are driven by electrical field and based on the theory of electrohydrodynamics, are mainly used. There are two types of electrical field-driven methods in microfluidic chips: DC electrical field-driven technique and AC electrical field-driven technique. Both of these techniques involve the fluid driven mechanism of electroosmosis, and the particles’driven mechanism of electrophoresis. Also, because of the imposed electrical field, the Joule heating effect occurs in the flow field that led to non-isothermal temperature distribution. Based on the principles of electrohydrodynamics and transport principles, and by using numerical simulation and experimental methods, some studies of key issues on transport phenonema in electrical field-driven microfluidic chips have been carried out and several novel designs for the fluid control in microfuidic chips, such as electrothermal flow enhanced micromixer and electrothermal flow pump, have been developed in this thesis. Finally, the microfluidic chips for the dielectrophoresis experiment are also made through the micro-machine technique, and the dielectrophoresis experiments are performed by using these chips, which also validated the simulation results for the dielectrophoresis spectrum analysis.The main topics studied in this thesis are as follows:Some key problems based on the DC electrokinetics are studied. These include: (i) DC Electroosmosis Flow: Develop a new method to control the DC electroomosis field. The effect of induced zeta potential, which is caused by adding polarizable mental membrane on the microchannel wall, on the electroosmosis field is analyzed, and the effects.are compared with the effect caused by changing the zeta potential through changing the wall’s surface characteristics. It is found the induced zeta potential is not constant and the induced charge electroosmosis flow has a more significant effect on disturbing the DC electroosmotic flow flied. (ii)DC Electrophoresis: A numerical model, which can be used to predict the sample stacking process in a microfluidic chip with a double T microchannel, is developed. The impacts factors, such as the charge, concentration ratio of the buffer, as well as the initial length of the sample plug, on the stacking processes are analyzed. It is found that a better stacking effect can be obtained from a higher buffer concentration ratio and longer initial sample plug length. (iii)Joule Heating Effect Caused by the DC Electrical Field: The temperature distribution in PDMS microfluidic chip is computed, and its impact such as the buffer concentration, chip material and thickness, on the temperature distribution are also analyzed. Joule heating effects on the sample band transport velocity and electrophoresis separation efficiency in PDMS microfluidic chips are inferred from the results in capillary. The methods to decrease the Joule heating effect in PDMS microfluidic chips are also discussed. It is found that lower buffer concentration, smaller chip thickness, and chip materials with larger thermal conductivity can decrease the Joule heating effect.The key problems based on the AC electrokinetics studied in this thesis are: (i) AC Electroosmosis Flow: A model for AC electroosmosis (ACEO) pump is developed to compute the potential and AC electroosmotic velocity. The impacts of frequency and electrolyte concentration on the ACEO pump velocity are studied. It is found that the frequency at which the optimal ACEO velocity appears depends on the charge relaxation time of the electrolyte. A RC circuit is developed by analyzing the capacitance characteristic of electrical double layer and resistance characteristic of electrolyte solution, and the impedance spectra of the ACEO pump is analyzed with different electrodes widths, channel heights and electrolyte concentrations. It is found that the smaller impedance value occurs at the condition of larger electrode widths, larger channel heights and larger electrolyte concentration. (ii)Dielectrophoresis: The dielectrophoresis model for the polystyrene (PS) particles and cells are developed, and the dielectrophoresis spectrums for these particles are analyzed. The levitation heights for the PS particles in nDEP process in microfluidic chip with interdigitated electrodes is computed by considering the dielectrophoretic forec, net gravity force, as well as the Stokes drag force caused by the electrothermal flow. It is found that the Stokes drag force is the dominant factor for the particles’levitation height for small particles, especially at high electrical field. (iii) Joule Heating Effect Caused by the AC Electrical Field (Electrothermal Flow):A novel micromixer based on the vortex caused by the electrothermal flow near the microelectrodes is proposed, the impact of electrode arrangement style, magnitude and frequency of the AC potential on the mixing efficiency are also studied. It is found that this kind of micromixer has a good mixing efficiency. A new kind of electrothermal flow micropump, based on the electrothermal flow in microchannel with asymmetrical interdigitated microelectrodes is proposed, and the impacts of the electrodes width ratio, electrolyte concentration and chip materials on the velocity of this pump are studied. It is found that the electrothermal flow pump can work in a wider frequency than the ACEO pump. Chinese patents for the electrothermal flow enhanced micromixer and the electrothermal pump have been applied.The experimental and numerical simulation work on the dielectrophoresis in microfluidic chip include: (i) Microfluidic chips with different electrode structures are fabricated for the DEP experiments by using micromachine technique. Both positive and negative dielectrophoresis experiments for PS particles are performed, and the dielectrophoresis spectrum analysis results are also validated by experimental data; and (ii) The dielectrophoresis microfluidic chip with 3D columns on the planar interdigitated microelectrodes are developed and manufactured, and a better capability on attracting particles in pDEP are obtained, which agrees with the prediction well.This study covers some key issues on transport phenomena in electrical field-driven microfluidic chips, they are interdisciplinary in nature, which also involve multi-scale and multi-physics fields. Both numerical simulation and experimental investigation have been carried out for these problems. The models and results in this thesis are useful to enhance the present understanding of transport phenomena and complement the lack of model development and theory analysis in electrical field-driven microfluidic chips, and are helpful for the design and optimization of the microfluidic chip. The noval fluid control methods proposed in this thesis are also helpful for the continuing work about microfluidic chips.更多还原