用户名: 密码: 验证码:
低电压电泳芯片分析系统的关键技术研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
微流控电泳芯片是微全分析系统的重要组成部分,它以高效、快速、样品消耗少等优点,在DNA测序、氨基酸分离、药物筛选等方面得到了广泛的应用,已经成为当前生物科学和化学分析领域的重要研究平台。但是,传统微流控电泳芯片需要几百伏甚至数千伏的电压完成样品的进样和分离,不仅存在安全隐患,而且通常高压电源体积较大,不利于系统的微型化和集成化。针对上述问题,有学者提出低电压电泳芯片的设想,但目前它还处于初级研究阶段,需要完成以下关键技术才能使芯片系统得到更好的应用。包括解决阵列电极直接与样品溶液接触产生气泡影响样品迁移问题,芯片结构的优化设计,芯片制作的最佳工艺,芯片简易低成本的亲水改性方法,小型化控制系统与检测系统的研制等。为此,本文针对低电压电泳芯片系统的关键技术开展研究。
     低电压电泳芯片和传统电泳芯片的工作原理相似,都以电泳技术为基础,区别在于具体的控制方式有所不同。依据传统电泳芯片驱动原理,分析了低电压电泳芯片的驱动原理,设计了十字形和螺旋形通道的两种低电压电泳芯片,并使用ANSOFT有限元软件对芯片进样和分离过程的电势、电场分布进行了仿真,验证了低电压驱动方式的可行性。分析了低电压电泳芯片通道深度、电极宽度、电极间距、绝缘材料及薄膜厚度等参数对通道内电场分布的影响,得出了芯片结构的优化参数。
     根据设计参数制作出低电压电泳芯片,使用磁控溅射法制作了铂金属阵列电极基片,利用湿法腐蚀工艺制作了玻璃盖片。分别选取硅和SU-8两种材料利用模具复制法制作了PDMS盖片,SU-8以其加工周期短、图形复制准确、微结构边缘陡直等优点,成为制作PDMS模具的最佳选择。
     为了解决严重制约低电压电泳芯片实际应用的气泡问题,采用在阵列电极表面制作绝缘薄膜的方案,开展了二氧化硅和PDMS两种绝缘薄膜的制备研究。使用电子束蒸发方法制作了二氧化硅绝缘膜,实验结果表明,在基片温度300℃条件下生长的4μm二氧化硅薄膜,可以承受500KV/cm场强,耐压200V,能够满足低电压电泳芯片应用的需要。采用旋涂法制作了PDMS绝缘薄膜,测试结果表明,厚度为4μm的PDMS可以承受560KV/cm的场强,耐压220V。从电绝缘特性可以看出,两种绝缘膜都适用于低电压电泳芯片的制作,但是PDMS绝缘膜与二氧化硅薄膜相比,具有工艺简单、成本低廉等特点,因此芯片最终选用PDMS绝缘膜进行制作。
     直接固化的PDMS盖片和绝缘薄膜因材料的固有特性,表面能比较低,呈疏水性,不利于生物样品在通道内的移动,需要对PDMS表面进行亲水改性。实验采用臭氧紫外法对PDMS表面进行改性,并与无臭氧紫外方法的处理效果进行了对比,使用多种表征方法分析了改性机理。在相同的处理时间内,经臭氧紫外处理的PDMS表面水接触角更小,亲水性明显增强。红外光谱测试表明,臭氧紫外改性后的PDMS表面各种官能团变化较大,其中-CH3疏水基团随着处理时间的增加大幅减少,Si-OH和-OH两种亲水基团大量增加,并出现了二氧化硅的典型红外光谱峰。使用X射线衍射、扫描电镜与能谱测试的结果证明,PDMS表面改性后生成了类玻璃态二氧化硅物质,亲水基团的增多和二氧化硅物质的生成是PDMS表面亲水性显著增强的主要原因。实验结果表明,臭氧紫外处理方法是一种操作简单、低成本的PDMS亲水改性手段。
     设计并制作了低电压电泳芯片的电极控制系统。系统以STM32芯片为主控制器,结合驱动芯片、阵列光耦、放大滤波电路、D/A及A/D电路,实现对芯片阵列电极电压幅值、进样时间、电极切换的精确控制。研究并设计了以FPGA芯片为核心,包括激光器、CCD传感器、预处理电路的荧光检测系统,通过上位机数据处理程序,系统可以实现低电压电泳芯片样品检测和电泳谱图实时显示的功能。
     利用低电压电泳芯片、电极控制系统和荧光检测系统,组建了低电压电泳芯片分析系统。使用该系统进行了两种绝缘薄膜消除气泡效果的测试,选用罗丹明6G和罗丹明B溶液为样品,在十字形和螺旋形通道的低电压电泳芯片上分别进行了电泳分离实验。测试结果表明,二氧化硅和PDMS绝缘薄膜在样品电泳过程中完全抑制了通道内气泡的产生,两种低电压电泳芯片都可以在90V电压作用下实现样品的电泳分离。螺旋形通道低电压电泳芯片比十字形通道具有更好的分离效果,低浓度样品分离度大于1,两种样品能够完全分开。本文研制的低电压电泳芯片分析系统,在100V以内就可以实现样品电泳分离的功能,与传统电泳芯片近千伏的驱动电压相比,不仅工作电压下降了一个数量级,而且系统体积明显减小,为电泳芯片系统的进一步微型化与集成化奠定了良好基础。
The microfluidic electrophoresis chip is an important part of micro total analysis systems (μTAS). They have some advantages including reduced reagent usage, decreased operation times and added capabilities, which was widely used in genome sequencing project, epidemic disease testing and drug screening. It has become a better research platform for the life science and chemical analysis field. But the injection and separation of samples in the conventional microfluidic electrophoresis chips system is to apply high voltage from several hundreds to thousand volts, there are some safety risks for operators and the large power equipment is difficult to integrate, which limit the microminiaturization and integration of chip system. Therefore, a proposal of developing the low voltage electrophoresis chip system has been given by some researches. However, this system is still in the stage of research, and there are several key techniques, which need to be solved before this kind chip is used for commercial purpose. They include the bubble issue, optimization of the chip structure, low cost of surface modification for the chip, manufacture of miniaturized control and detection system. To solve these problems, the research of key technologies for low voltage electrophoresis chip analysis system has been developed in this work.
     The principle based on the electrophoresis technique of sample driving for the low voltage electrophoresis chip is similar to the way of conventional electrophoresis chip, but the control mode is different. According to the theory of the conventional electrophoresis chip, the concept of the low voltage electrophoresis chip was proposed. The cross channel and helix channel low voltage electrophoresis chip were designed, and the finite element analysis software ANSOFT was using to simulate the potential and electric filed of the chips. The simulation result indicated the feasibility of the low voltage driving method. In addition, the parameters of the chip structure such as depth of the micro channel, the thickness of the insulation film, size and position of electrodes were optimized.
     The fabrication procedures for the low voltage electrophoresis chip were discussed in details. The arrayed Pt electrodes were deposited on a piece of glass by magnetron sputtering. The glass cover was using wet etching method. The PDMS cover was fabricated by mold replication technology, which using silicon and SU-8mold. By comparison, SU-8mold has the advantages of short cycle time manufacturing, high precision, vertical edge, which became the best choice.
     In order to eliminate bubbles in the channel of low voltage electrophoresis chip, the PDMS film and the silicon dioxide film as the insulation film were proposed deposited on the Pt electrodes. Simultaneously, the electrical and structural characteristics of the two kind films were investigated. SiO2film was deposited by electron-beam evaporation. Experiment results showed that the surface of SiO2film became smooth and uniform for the growth temperature at300℃, the breakdown electric field strength was500KV/cm and the breakdown voltage was200V for the thickness of the film at4μm. The breakdown strength and breakdown voltage of the PDMS film with the same thickness was560KV/cm and220V. The electric insulation property of the two films is close, but PDMS film has low cost and simple manufacturing process.
     PDMS is a hydrophobic material, which makes a difficult transferring sample solution in the channel of electrophoresis chips, so the PDMS is needed to improve the surface hydrophily for decreasing non-specific adsorption of hydrophobic. In this work, UV/ozone method was utilized to hydrophilize the surface of PDMS and compared to UV method. Contact angle measurements show that the hydrophilic of the PDMS sample by UV/ozone was significantly enhanced compared with UV method within the same time. The results of FTIR spectroscopy indicate that many chemical functional groups of PDMS surface have been changed by UV/ozone modification,-CH3hydrophobic group gradually decreased with the time,-OH and Si-OH hydrophilic groups increased obviously, and the characteristic peaks of SiO2gradually appear. XRD and SEM/EDS results show that the glass-like SiCO2layer formed on the PDMS surface. The hydrophilic groups and SiO2layer are the main reason for the enhancement of the PDMS hydrophilic. The experiment results demonstrate that the UV/ozone treatment was a simple operation and low cost hydrophilic modification method.
     The control system for the arrayed electrodes of the low voltage electrophoresis chip was present. This system consists of STM32chip, driver chip, optocouplers, the amplifier-filter circuit, D/A and A/D circuit which controlled the switch time, driving mode and voltage output of the arrayed electrodes. The fluorescence detection system was designed for the low voltage electrophoresis chip that included a main control FPGA chip, CCD sensor, laser light source and pre-processing circuits. With the application software of the host PC, the detection system could test the sample and realize the real-time display of the sample fluorescence spectra.
     The low voltage electrophoresis chip, control system, detection system constituted the whole sample analysis system. The Rhodamine B and Rhodamine6G as the sample were used in the electrophoresis separation experiments on the two kind low voltage electrophoresis chips. Test results show that the electrophoresis separation of the sample was achieved by applying voltage90V on the two chips. In addition, the helix channel chip has better separation than the cross channel chip, and the degree of separation for the low concentration sample was more than one. The sample can be successfully separated below the100V using the low voltage electrophoresis chip system in this work. Compare with the conventional electrophoresis chips system, the applied voltage declined an order of magnitude and the size became smaller. This work will lay the foundation for the further miniaturization, integration of the electrophoresis chip system.
引文
[1]MANZ A, GRABER N, WIDMER H M. Miniaturized total chemical analysis systems:a novel concept for chemical sensing[J]. Sensors And Actuators B:Chemical.1990,1(1-6):244-248.
    [2]方肇伦.微流控分析芯片[M].北京:科学出版社,2003.
    [3]林炳承,秦建华.图解微流控芯片实验室[M].北京:科学出版社,2008.
    [4]陈文元,张卫平.集成微流控聚合物PCR芯片[M].上海:上海交通大学出版社,2009.
    [5]HAEBERLE S, ZENGERLE R.Microfluidic platforms for lab-on-a-chip applications [J]. Lab On A Chip.2007,7(9):1094-1110.
    [6]STEINERT C P, MUELLER-DIECKMANN J, WEISS M, et al. Miniaturized and highly parallel protein crystallization on a microfluidic disc[M]. IEEE,2007.
    [7]WIXFORTH A, STROBL C, GAUER C, et al. Acoustic manipulation of small droplets [J]. Analytical And Bioanalytical Chemistry.2004,379(7-8):982-991.
    [8]LIU P, MATHIES R A. Integrated microfluidic systems for high-performance genetic analysis. [J]. Trends In Biotechnology.2009,27(10):572.
    [9]沃兴德.蛋白质电泳与分析[M].北京:军事医学科学出版社,2009.
    [10]陈义.毛细管电泳技术及应用[M].北京:化学工业出版社,2006.
    [11]罗国安,王义明,陈令新,等.毛细管电色谱及其在生命科学中的应用[M].北京:科学出版社,2005.
    [12]JORGENSON J W, LUKACS K D A. Zone electrophoresis in open-tubular glass capillaries [J]. Analytical Chemistry.1981,53(8):1298-1302.
    [13]HIERTEN S J. High-performance electrophoresis elimination of electroendosmsis and solute adsorption. [J].J. Chromatogr.1985,347:191-198.
    [14]OLIVARES J A, NGUYEN N T, YONKER C R, et al. On-line mass spectrometric detection for capillary zone electrophoresis[J]. Analytical Chemistry.1987,59(8):1230-1232.
    [15]ROSE JR D J, JORGENSON J W. Characterization and automation of sample introduction methods for capillary zone electrophoresis [J]. Analytical Chemistry.1988,60 (7):642-648.
    [16]HARRISON D J, MANZ A, FAN Z, et al. Capillary electrophoresis and sample injection systems integrated on a planar glass chip[J]. Analytical Chemistry.1992,64 (17):1926-1932.
    [17]SHANG F, GUIHEN E, GLENNON J D. Recent advances in miniaturisation- The role of microchip electrophoresis in clinical analysis [J].Electrophoresis.2012,33 (1):105-116.
    [18]SEBASTIAN J M. Next generation microfluidic platforms for high-throughput protein biochemistry[J]. Current Opinion in Biotechnology.2011,22 (1):59-65.
    [19]FENG X, DU W, LUO Q, et al. Microfluidic chip:Next-generation platform for systems biology[J].Analytica Chimica Acta.2009,650(1):83-97.
    [20]MARKD, HAEBERL ES, ROTH G, et al. Microf luidic lab-on-a-chip platforms:requirements, characteristics and applications [J]. Chemical Society Reviews.2010,39 (3):1153-1182.
    [21]SHANG F, GUIHEN E, GLENNON J D. Recent advances in miniaturisation-The role of microchip electrophoresis in clinical analysisCJ]. Electrophoresis.2012,33 (1):105-116.
    [22]KOVARIK M L, ORNOFF D M, MELVIN A T, et al. Micro Total Analysis Systems:Fundamental Advances and Applications in the Laboratory, Clinic, and Field[J]. ANALYTICAL CHEMISTRY.2013,85(2SIC):451-472.
    [23]BREADMORE M C, SHALLAN A I, RABANES H R, et al.Recent advances in enhancing the sensitivity of electrophoresis and electrochromatography in capillaries and microchips (2010-2012)[J]. Electrophoresis.2013,34(1SI):29-54.
    [24]CHAO T, HANSMEIER N. Microf luidic devices for high-throughput proteome analyses [J]. PROTEOMICS.2013,13(3-4SI):467-479.
    [25]HARRISON D J, MANZ A, FAN Z, et al. Capillary electrophoresis and sample injection systems integrated on a planar glass chip [J]. Analytical Chemistry.1992,64 (17):1926-1932.
    [26]JACOBSON S C, HERGENRODER R, KOUTNY L B, et al. Effects of injection schemes and column geometry on the performance of microchip electrophoresis devices[J]. Analytical Chemistry.1994,66(7):1107-1113.
    [27]WOOLLEY ATM R. Ultra-high-speed DNA sequencing using capillary electrophoresis chips[J]. Analytical Chemistry.1995,67(20):3676-3680.
    [28]WOOLLEY A T, HADLEY D, LANDRE P, et al. Functional Integration of PCR Amplification and Capillary Electrophoresis in a Microfabricated DNA Analysis Device[J]. Analytical Chemistry.1996,68(23):4081-4086.
    [29]WOOLLEY A T S G.High-speed DNA genotyping using microfabricated capillary array electrophoresis chips. [J]. Analytical chemistry.1997,69(11):2181-2186.
    [30]SIMPSON P C R D. High-throughput genetic analysis using microfabricated 96-sample capillary array electrophoresis microplates[J]. Proceedings of the National Academy of Sciences of the United States of America.1998,95(5):2256-2261.
    [31]EMRICH C A T H. Microfabricated 384-lane capillary array electrophoresis bioanalyzer for ultrahigh-throughput genetic analysis[J]. Analytical Chemistry.2002,74(19): 5076-5083.
    [32]SKELLEY A M, SCHERER J R, AUBREY A D, et al. Development and evaluation of a micro-device for amino acid biomarker detection and analysis on Mars[J]. Proceedings of the National Academy of Sciences of the United States of America.2005,102(4): 1041-1046.
    [33]BLAZEJ R G, KUMARESAN P, MATHIES R A. Microfabricated bioprocessor for integrated nanoliter-scale Sanger DNA sequencing[J]. Proceedings of the National Academy of Sciences.2006,103(19):7240-7245.
    [34]LIU P, YEUNG S H, CRENSHAW K A, et al. Real-time forensic DNA analysis at a crime scene using a portable microchip analyzer[J]. Forensic Science International: Genetics.2008,2(4):301-309.
    [35]MORA M F, STOCKTON A M, WILLIS P A. Microchip capillary electrophoresis instru-mentation for in situ analysis in the search for extraterrestrial life [J]. Electrophoresis.2012,33(17):2624-2638.
    [36]JENSEN E C, STOCKTON A M, CHIESL T N, et al. Digitally programmable microfluidic automaton for multiscale combinatorial mixing and sample processing[J]. Lab on a Chip.2013,13(2):288-296.
    [37]NUCHTAVORN N, SMEJKAL P, BREADMORE M C, et al. Exploring chipcapillary electro-phoresis laser induced fluorescence field deployable platform flexibility: Separations of fluorescent dyes by chip based non aqueous capillary electrophoresis. [J]. Journal of chromatography. A.2013,1286:216-221.
    [38]AGILENT. http://www. genomics. agilent. com[M].2012.
    [39]文伟力.聚合物微流控芯片的制作、检测及仿真研究[D].吉林大学,2007.
    [40]李永刚.PDMS微流控芯片关键工艺技术研究[D].中国科学院长春光学精密机械与物理研究所,2006.
    [41]BODAS D, KHAN-MALEK C. Hydrophilization and hydrophobic recovery of PDMS by oxygen plasma and chemical treatment-An SEM investigation[J].Sensors And Actuators B-Chemical.2007,123(1):368-373.
    [42]MARTIN I T, DRESSEN B, BOGGS M, et al. Plasma modification of PDMS microfluidic devices for control of electroosmotic flow[J]. Plasma Processes And Polymers.2007, 4(4):414-424.
    [43]PATRITO N, MCLACHLAN J M, FARIA S N, et al. A novel metal-protected plasma treatment for the robust bonding of polydimethylsiloxane[J]. Lab On A Chip.2007,7 (12): 1813-1818.
    [44]TAN S H, NGUYEN N, CHUA Y C, et al. Oxygen plasma treatment for reducing hydrophobicity of a sealed polydimethylsiloxane microchannel[J]. Biomicrofluidics.2010,40322043
    [45]MORA M F, GIACOMELLI C E, GARCIA C D. Electrophoretic effects of the adsorption of anionic surfactants to poly (dimethylsiloxane)-coated capillaries[J]. Analytical chemistry.2007,79(17):6675-6681.
    [46]HAN B, XU Y, ZHANG L, et al. Surface modification of poly (dimethylsiloxane) microchips using a double-chained cationic surfactant for efficiently resolving fluorescent dye adsorption[J]. Talanta.2009,79(3):959-962.
    [47]ZHANG H, ANNICH G M, MISKULIN J, et al. Nitric oxide releasing silicone rubbers with improved blood compatibility:preparation, characterization, and in vivo evaluation [J]. Biomaterials.2002,23(6):1485-1494.
    [48]CHEN H, BROOK M A, SHEARDOWN H. Silicone elastomers for reduced protein adsorption [J]. Biomaterials.2004,25(12):2273-2282.
    [49]MIKHAIL A S, RANGER J J, LIU L, et al.Rapid and Efficient Assembly of Functional Silicone Surfaces Protected by PEG:Cell Adhesion to Peptide-Modified PDMS [J]. Journal Of Biomaterials Science-Polymer Edition.2010,21(6-7):821-842.
    [50]孟斐,陈恒武,方群,等.聚二甲基硅氧烷微流控芯片的紫外光照射表面处理研究[J].高等学校化学学报.2002,23(7):1264-1268.
    [51]CHEN L, REN J, BI R, et al. Ultraviolet sealing and poly (dimethylaeryl1amide) modification for poly(dimethylsiloxane)/glass microchips [J]. Electrophoresis. 2004,25 (6):914-921.
    [52]SCHNYDER B, LIPPERT T, KOTZ R, et al.UV-irradiation induced modification of PDMS films investigated by XPS and spectroscopic ellipsometry[J]. Surface science.2003, 532:1067-1071.
    [53]EBARA M, HOFFMAN J M, STAYTON P S, et al. Surface modification of microfluidic channels by UV-mediated graft polymerization of non-foul ing and'smart'polymers[J]. Radiation Physics and Chemistry.2007,76(8):1409-1413.
    [54]文伟力.聚合物微流控芯片的制作、检测及仿真研究[D].吉林大学,2007.
    [55]李钢.基于微流控芯片激光诱导荧光检测系统的研究与应用[D].华东师范大学,2010.
    [56]李伟.共聚焦式激光诱导荧光检测装置的研究[D].大连理工大学,2006.
    [57]陈继锋.微通道电泳芯片及其检测系统的研究[D].中国科学院研究生院(上海微系统与信息技术研究所),2002.
    [58]LIN Y, WU W.Arrayed-electrode design for moving electric field driven capillary electrophoresis chips[J]. Sensors and Actuators B:Chemical.2001,73 (1):54-62.
    [59]YU-CHENG L. Design of low voltage-driven capillary electrophoresis chips using moving electrical fields [J]. Sensors and Actuators B:Chemical.2001,80(1):33-40.
    [60]吴英,温志渝,蒋子平,等.电泳芯片的低电压分离模型及讨论[J].光电工程.2002,S1:28-31.
    [61]李霞,温志渝,李星海,等.电泳芯片的低电压分离模型及控制系统[J].微纳电子技术.2003,Z1:344-346.
    [62]陈超,赵湛.线阵电极电泳芯片与单片机控制系统[J].传感器技术.2004,01):77-80.
    [63]陈里铭,闫卫平,刘军民.低电压驱动毛细管电泳芯片电势分布的数值计算[J].仪器仪表学报.2005,S1:183-184.
    [64]李鹤楠,闫卫平,刘军民.低电压驱动阵列电极式毛细管电泳芯片的研究[J].仪器仪表学报.2006,S3:2488-2489.
    [65]XU Y, SHEN J W, LU J L, et al. Fabrication and testing investigation of low-voltage integrated electrophoresis chip based on silicon-on-insulator-MEMS[J]. Journal of Micro/Nanolithography, MEMS, and MOEMS.2007,6(3):33009.
    [66]徐溢.集成生化低电压芯片电泳系统的基础理论及关键技术研究[D].重庆大学,2006.
    [67]廖红华,于军,王俊,等.基于SOPC的低电压电泳芯片系统平台设计[J].微计算机信息.2008,(17):129-131.
    [68]廖红华,廖宇,易金桥,等.基于ITO玻璃-PDMS复合式低电压电泳芯片的快速制备[J].湖北民族学院学报(自然科学版).2009,(03):320-323.
    [69]MOINI M, CAO P, BARD A J. Hydroquinone as a buffer additive for suppression of bubbles formed by electrochemical oxidation of the CE buffer at the outlet electrode in capillary electrophoresis electrospray ionization-mass spectrometry[J]. Analytical chemistry.1999,71(8):1658-1661.
    [70]SMITH A D, MOINI M. Control of electrochemical reactions at the capillary electro-phoresis outlet/electrospray emitter electrode under CE/ESI-MS through the application of redox buffers[J]. Analytical chemistry.2001,73(2):240-246.
    [71]GUZMAN K A D, KARNIK R N, NEWMAN J S, et al. Spatially controlled microf luidics using low-voltage electrokinetics[J].Microelectromechanical Systems, Journal of.2006, 15(1):237-245.
    [72]王溢仲,赵湛.基于电泳分离的生物芯片的设计与改进[J].仪表技术与传感器.2006,(03):6-8.
    [73]邹汉法,刘震,叶明亮,等.毛细管电色谱及其应用[M].北京:科学出版社,2001.
    [74]HUX R A, PUON S, CANTWELL F F. Differential potentiometric titrations of mixed charge type acids in a two-phase system[J]. Analytical Chemistry.1980,52(14):2388-2392.
    [75]DELGADO A V, GONZALEZ-CABALLERO F, HUNTER R J, et al. Measurement and interpretation of electrokinetic phenomena[J]. Journal of colloid and interface science.2007, 309 (2):194-224.
    [76]LIM J, WHITCOMB J, BOYD J, et al. Transient finite element analysis of electric double layer using Nernst Planck Poisson equations with a modified Stern layer [J]. Journal of colloid and interface science.2007,305(1):159-174.
    [77]TANDON V, BHAGAVATULA S K, NELSON W C, et al. Zeta potential and electroosmotic mobility in microfluidic devices fabricated from hydrophobic polymers:1. The origins of charge[J]. Electrophoresis.2008,29(5):1092-1101.
    [78]ARULANANDAM S, LI D Q. Determining zeta potential and surface conductance by monito-ring the current in electro-osmotic flow[J]. Journal Of Colloid And Interface Science.2000,225(2):421-428.
    [79]HUNTER R J. Zeta potential in colloid science:principles and applications [M]. Academic press London,1981.
    [80]USUI S. Electrical double-layer interaction between oppositely charged dissimilar oxide surfaces with charge regulation and Stern-Grahame layers[J]. Journal of colloid and interface science.2008.320(1):353-359.
    [81]计光华,计洪苗.微流动及其元器件[M].北京:高等教育出版社,2009.
    [82]RICE C L, WHITEHEA. R.Electrokinetic flow in a narrow cylindrical capillary[J]. Journal Of Physical Chemistry.1965,69(11):4017.
    [83]Van De GOOR A, WANDERS B J, EVERAERTS F M.Modified methods for off-and on-line determination of electroosmosis in capillary electrophoretic separations[J]. Journal of Chromatography A.1989,470(1):95-104.
    [84]刘国强,赵凌志,蒋继娅Ansoft工程电磁场有限元分析[M].北京:电子工业出版社,2005.
    [85]赵博,张洪亮Ansoft12在工程电磁场中的应用[M].北京:中国水利水电出版社,2010.
    [86]谢路冰.基于ARM的毛细管电泳高压电源设计[D].大连理工大学,2010.
    [87]HOFMANN 0 C D C. Adaptation of capillary isoelectric focusing to microchannels on a glass chip[J]. Analytical Chemistry.1999,71 (3):678-686.
    [88]HOFMANN 0, CHE D P, CRUICKSHANK K A, et al. Adaptation of capillary isoelectric focusing to microchannels on a glass chip [J]. Analytical Chemistry.1999,71 (3):678-686.
    [89]ROTTING 0, ROPKE W, BECKER H, et al. Polymer microfabrication technologies[J]. MICROSYSTEM TECHNOLOGIES.2002,8(1):32-36.
    [90]SCHIFT H, HEYDERMAN L J, GOBRECHT J. Efficient replication of nanostructured surfaces [J].Chimia.2002,56(10):543-546.
    [91]BARKER S, TARLOV M J, CANAVAN H, et al. Plastic microfluidic devices modified with polyelectrolyte multilayers[J]. Analytical Chemistry.2000,72(20):4899-4903.
    [92]SOPER S A, FORD S M, QI S, et al.Peer Reviewed:Polymeric Microelectromechanical Systems. [J]. Analytical chemistry.2000,72(19):642-651.
    [93]MCDONALD J C, DUFFY D C, ANDERSON J R, et al. Fabrication of microfluidic systems in poly(dimethylsiloxane)[J]. Electrophoresis.2000,21 (1):27-40.
    [94]陈超.线性阵列电极电控生物芯片及其控制系统的研制[D].中国科学院研究生院(电子学研究所),2003.
    [95]伍择希,张卫平,陈俊杰,等.集成电极的PDMS-玻璃微流控芯片的制备[J].微纳电子技术.2012,01:56-61.
    [96]李鹤楠.基于光纤耦合的低电压驱动毛细管电泳芯片研究[D].大连理工大学,2006.
    [97]WANG L F, JI Q, GLASS T E, et al. Synthesis and characterization of organosiloxane modified segmented polyether polyurethanes[J].Polymer.2000,41(13):5083-5093.
    [98]LOTTERS J C, OLTHUIS W, VELTINK P H, et al.The mechanical properties of the rubber elastic polymer polydimethylsiloxane for sensor applications[J].Journal of Micromechanics and Microengineering.1997,7(3):145.
    [99]MATA A, FLEISCHMAN A J, ROY S. Characterization of polydimethylsiloxane (PDMS) properties for biomedical micro/nanosystems[J]. Biomedical microdevices.2005, 7(4):281-293.
    [100]http://www.dowcorning.com.cn/.
    [101]XIA Y, WHITESIDES G M. Soft lithography[J]. Annual review of materials science.1998, 28(1):153-184.
    [102]JO B H, Van LERBERGHE L M, MOTSEGOOD K M, et al. Three-dimensional micro-channel fabrication in polydimethylsiloxane (PDMS) elastomer[J].Microelectromechanical Systems, Journal of.2000,9(1):76-81.
    [103]LANG W. Silicon microstructuring technology[J]. Materials Science & Engineering R-Reports.1996,17(1):1-55.
    [104]郭立.基于锯齿型微沟道的双腔并联无阀微泵研究[D].大连理工大学,2011.
    [105]SHAW J M, GELORME J D, LABIANCA N C, et al. Negative photoresists for optical lithography[J].IBM Journal of Research and Development.1997,41(1.2):81-94.
    [106]ABGRALL P, CONEDERA V, CAMON H, et al. SU-8 as a structural material for labs-on-chips and microelectromechanical systems[J]. Electrophoresis.2007,28(24):4539-4551.
    [107]NORDSTROM M, KELLER S, LILLEMOSE M, et al. SU-8 cantilevers for bio/chemical sensing; Fabrication, characterisation and development of novel read-out methods [J]. SENSORS.2008,8(3):1595-1612.
    [108]BECHE B. Integrated photonics devices on SU8 organic materials[J]. International Journal Of The Physical Sciences.2010,5(6):612-618.
    [109]LORENZ H, DESPONT M, FAHRNI N, et al. SU-8:a low-cost negative resist for MEMS[J]. Journal Of Micromechanics And Microengineering.1997,7(3):121-124.
    [110]吕春华.基于SU-8负光胶的微流控芯片加工技术的研究[D].浙江大学,2007.
    [111]SHAMALA K S, MURTHY L, RAO K N. Studies on optical and dielectric properties of A1203 thin films prepared by electron beam evaporation and spray pyrolysis method [J]. Materials Science And Engineering B-Solid State Materials For Advanced Technology.2004,106 (3):269-274.
    [112]SAYILKAN H, SENER S, SENER E, et al. The sol-gel synthesis and application of some anticorrosive coating materials [J]. Materials Science.2003,39(5):733-739.
    [113]ALAYO M I, PEREYRA I, CARRENO M. Thick SiOxNy and SiO2 films obtained by PECVD technique at low temperatures [J].Thin Solid Films.1998,332(1-2):40-45.
    [114]PEROZ C, CHAUVEAU V, BARTHEL E, et al. Nanoimprint Lithography on Silica Sol-Gels: A Simple Route to Sequential Pat tern ing[J]. Advanced Materials.2009,21 (5):555-558.
    [115]SAHU D R, LIN S Y, HUANG J L. Improved properties of Al-doped ZnO film by electron beam evaporation technique[J].Microelectronics journal.2007,38(2):245-250.
    [116]ZYWITZKI 0, HOETZSCH G. Correlation between structure and properties of reactively deposited Al_2O_ 3coatings by pulsed magnetron sputtering[J]. Surface and Coatings Technology.1997,94:303-308.
    [117]翁卫祥,贾贞,于光龙,等.电子束蒸发Al_2O_3/SiO_2复合薄膜电学性能的研究[J].福州大学学报(自然科学版).2011,01:67-71.
    [118]HOURDAKIS E, NASSIOPOULOU A G. High performance MIM capacitor using anodic alumina dielectric[J]. Microelectronic Engineering.2012,90:12-14.
    [119]THISSEN P, SCHINDLER B, DIESING D, et al. Optical response of metal-insulator-metal heterostructures and their application for the detection of chemicurrents [JJ.New Journal of Physics.2010,12(11):113014.
    [120]PRIME D, PAUL S, JOSEPHS-FRANKS P. Electrical properties of nanometre thin film polystyrene for organic electronic applications[J]. Dielectrics and Electrical Insulation, IEEE Transactions on.2008,15(4):905-909.
    [121]BONDOUX C, PRENE P, BELLEVILLE P, et al. MgO insulating films prepared by sol-gel route for SiC substrate [J].Journal of the European Ceramic Society.2005,25 (12):2795-2798.
    [122]ANJANEYULU P, SANGEETH C S, MENON R. Negative differential resistance in doped poly (3-methylthiophene)devices[J]. JournalofPhysicsD:Applied Physics.2010,43:425103.
    [123]MEACHAM K W, GIULY R J, GUO L, et al.A lithographically-patterned, elastic multi-electrode array for surface stimulation of the spinal cord[J].Biomedical microdevices.2008,10(2):259-269.
    [124]MAKAMBA H, KIM J H, LIM K, et al. Surface modification of poly(dimethylsiloxane) microchannels[J]. Electrophoresis.2003,24(21):3607-3619.
    [125]XIAO D Q, Van LE T, WIRTH M J. Surf ace modification of the channels of poly (dimethylsiloxane) microfluidic chips with polyacrylamide for fast electrophoretic separations of proteins[J]. Analytical Chemistry.2004,76(7):2055-2061.
    [126]HAN B, XU Y, ZHANG L, et al. Surface modification of poly(dimethylsiloxane) microchips using a double-chained cationic surfactant for efficiently resolving fluorescent dye adsorption[J]. Talanta.2009,79(3):959-962.
    [127]HE T, LIANG Q, ZHANG K, et al.A modified microfluidic chip for fabrication of paclitaxel loaded polyl-lacticacid microspheres[J]. Microf luidics And Nanof luidics. 2011,10(6):1289-1298.
    [128]BELDER D, LUDWIG M. Surface modification in microchip electrophoresis [J]. Electro-phoresis.2003,24(21):3595-3606.
    [129]BODAS D, KHAN-MALEK C. Hydrophilization and hydrophobic recovery of PDMS by oxygen plasma and chemical treatment—An SEM investigation[J]. Sensors and Actuators B: Chemical.2007,123(1):368-373.
    [130]薛向尧,张平,黎海文,等PDMS氧等离子体长效活性表而处理及与Si的键合[J].功能材料与器件学报.2008,(05):877-882.
    [131]SCHNYDER B, LIPPERT T, KOTZ R, et al. UV-irradiation induced modification of PDMS films investigated by XPS and spectroscopic ellipsometryt[J]. Surface Science.2003, 532:1067-1071.
    [132]YAMAMOTO T.Study on 172-nm vacuum ultraviolet light surface modifications of polydimethylsiloxane for micro/nanofluidic applications[J].Surface and Interface Analysis.2011,43(9):1271-1276.
    [133]张华.现代有机波谱分析[M].北京:化学工业出版社,2005.
    [134]BERDICHEVSKY Y, KHANDURINA J, GUTTMAN A, et al. UV/ozone modification of poly (dimethylsiloxane) microfluidic channels[J]. Sensors and Actuators B:Chemical. 2004,97 (2-3):402-408.
    [135]WADDELL E A, SHREEVES S, CARRELL H, et al. Surface modification of Sylgard 184 polydimethylsiloxane by 254nm excimer radiation and characterization by contact angle goniometry, infrared spectroscopy, atomic force and scanning electron microscopy [J]. Applied Surface Science.2008,254(17):5314-5318.
    [136]URKMEZ G, SAR B, UNAL H I. Synthesis and characterization of novel poly (dimethylsiloxane)/polyindole composites[J]. Journal of Applied Polymer Science. 2011,121 (3):1600-1609.
    [137]郑伟涛.薄膜材料与薄膜技术(第二版)[M].北京:化学工业出版社,2008.
    [138]MAJI D, LAHIRI S K, DAS S. Study of hydrophilicity and stability of chemically modified PDMS surface using piranha and KOH solution[J]. Surface and Interface Analysis.2011,44(1):62-69.
    [139]姚树寅,吴仲岿,杨军,等.PDMS真空紫外光表面亲水改性研究[J].湖北大学学报(自然科学版).2010,32(2):188-191.
    [140]KUNG K H S, HAYES K F.Fourier transform infrared spectroscopic study of the adsorption of cetyltrimethylammonium bromide and cetylpyridinium chloride on silica [J]. Langmuir.1993,9(1):263-267.
    [141]MIRLEY C L, KOBERSTEIN J T. A Room Temperature Method for the Preparation of Ultrathin SiOx Films from Langmuir-Blodgett Layers[J]. Langmuir.1995,11(4):1049-1052.
    [142]廖燕平,黄金英,郜峰利,等.激光晶化多晶硅的制备与XRD谱[J].吉林大学学报(理学版).2004,01:99-102.
    [143]KIM C, GURAU M C, CREMER P S, et al. Chain conformation of poly (dimethyl siloxane) at the air/water interface by sum frequency generation[J]. Langmuir.2008,24 (18):10155-10160.
    [144]JADAV G L, ASWAL V K, BHATT H, et al. Influence of film thickness on the structure and properties of PDMS membrane[J]. Journal of Membrane Science.2012, 415-416(0):624-634.
    [145]HILLBORG H, GEDDE U W. Hydrophobicity changes in silicone rubbers[J]. Dielectrics and Electrical Insulation, IEEE Transactions on.1999,6(5):703-717.
    [146]CHEN L, REN J, BI R, et al. Ultraviolet sealing and poly(dimethylacrylamide) modi -fication for poly (dimethylsiloxane)glass microchips[J]. Electrophoresis.2004, 25(6):914-921.
    [147]MA K, RIVERA J, HIRASAKI G J, et al. Wettability control and patterning of PDMS using UV-ozone and water immersion [J]. Journal of Colloid and Interface Science.2011, 363(1):371-378.
    [148]李宁.基于MDK的STM32处理器开发应用[M].北京:北京航空航天大学出版社,2009.
    [149]王永虹,徐炜,郝立平ARM Cortex-M3微控制器原理与实践[M].北京:北京航空航天大学出版社,2009.
    [150]内山明治,村野靖.运算放大器电路[M].北京:科学出版社,2009.
    [151]康华光.电子技术基础:模拟部分(第四版)[M].北京:高等教育出版社,2003.
    [152]Instruments T. Tlc5618a-Programmable Dual 12-Bit Digital-To-Analog Converters[M]. 1999.
    [153]SEMICONDUCTORS P.8-bit serial-in, serial or parallel-out shift register with output latches-3-state[M].1998.
    [154]徐爱钧IAR EWARM V5嵌入式系统应用编程与开发[M].北京:北京航空航天大学出版社,2009.
    [155]LIN S W, CHANG C H, LIN C H. High-throughput Fluorescence Detections in Microfluidic Systems[J].Genomic Medicine, Biomarkers, and Health Sciences.2011,3(1):27-38.
    [156]KORNAROS G. A soft multi-core architecture for edge detection and data analysis of microarray images[J].Journal of Systems Architecture.2010,56(1):48-62.
    [157]东芝公司TCD1208AP数据手册[M].1997.
    [158]许成才.光纤嵌入式毛细管电泳芯片的信号检测及其小波消噪[D].大连理工大学,2006.
    [159]熊少祥,李建军,程介克.高效毛细管电泳-电荷耦合器件检测器联用技术研究Ⅱ.混合荧光染料分离[J].分析化学.1996,(01):54-56.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700