聚合物微流控芯片模内键合温度控制与键合工艺研究
|
摘要
近年来,微流控芯片凭借快速、高效、低耗等特点,在化学与生物分析领域内,获得了越来越多的关注。聚合物材料具有成本低、易于大批量生产的优点,弥补了石英、玻璃等早期芯片材料的不足,同时聚合物以其良好的电化学性质和生物兼容性成为微流控芯片最理想的制备材料。当前聚合物微流控芯片的成型与键合相互分离,芯片制作周期长,效率低。本文旨在实现聚合物芯片低成本、批量化制造,引入芯片模内键合技术,围绕模内键合加热系统与模内键合工艺参数对芯片键合质量的影响进行研究。
本文根据聚合物分子扩散理论和吸附理论,描述芯片键合过程,从芯片表面张力和键合能的角度探明了热键合发生的原因,并对现有芯片键合工艺进行分析,在理论上证明聚合物芯片模内键合的可行性。并对微流控芯片表面微观质量、微通道变形、键合强度以及影响上述键合质量的因素进行研究,确定芯片键合质量评价方法；
采用有限元的方法对微流控芯片热键合过程中主要键合参数对微通道变形的影响进行数值模拟分析,结果表明：键合后微通道高度方向上的变形较大,在宽度方向上变形不明显,可忽略不计。微通道高度改变量随键合温度和键合压力的升高而增大,键合温度对高度改变量存在较大影响,当键合温度高于材料玻璃化转变温度时,微通道变形较为严重,综合考虑键合效率与微通道变形。
分析模内键合加热需求,选取远红外陶瓷加热器对芯片键合表面进行加热,设计开发模内键合加热及采用PID算法的温度控制系统,完成PID参数整定,使加热器稳定工作在设定温度值附近。进行键合面加热实验,得出各加热参数与键合面温度之间的关系。
设计模内键合正交实验,利用微流控芯片成型与键合模具进行芯片模内键合实验,采用极差法分析影响微通道高度的主要因素,结合芯片整体形貌、微通道变形量和键合强度等辅助评价指标,获得最佳的模内键合工艺参数组合。
In recent years, microfluidic chip has received increasing attention in the field of chemical and biological analysis by characteristics of rapidity, high effectiveness and low consumption. Polymers are less expensive and easier to manufacture in large quantities, which make up the shortcomings of quartz and glass. In addition, polymers have good electrochemical properties and biological compatibility, making them the best choice for microfluidic chip fabrication. The conditional fabricating method of microfluidic chip is ineffective, and manufacturing cycle of that is long, for molding technology and bonding technology are seperated. In this paper, bond-in-mold technology was introduced for the purpose of manufacturing chip in large quantities with low cost.
Firstly, diffusion theory and adsorption theory were used for describing the process of bonding, then searching root causes of bonding were found from the view of surface tension and bonding energy, so feasibility of bond-in-mold technology was verified.
Microchannel distortion in thermal bonding was studied by finite element software, and the results showed that distortion in the direction of height is quite large, on the contrary distortion in the direction of height is indistinctive. The distortion in the direction of height was growing with increasing bonding temperature and pressure, and bonding temperature had larger influence on it. When bonding temperature was higher than glass-transition temperature of material, distortion of microchannel was comparatively serious.
Far-infrared ceramic heaters were chosen to heat surface of the chip, after analyzing requirements of bond-in-mold technology. The heating system for bond-in-mold and temperature control system with PID algorithm were designed and developed. The temperature heater was controlled for working under SV by setting parameters of PID. Experiments of heating bonding surface were carried out, then relationships between surface temperature and heating parameters were obtained.
Bond-in-mold experiment was carried out after designing orthogonal experiment with injection and bonding mold of microfluidic chip. The effects of main factors on height of microchannel were analyzed by Range Method. Then optimal combination of bonding parameters were obtained taking chip feature and bonding strength into account.
本文根据聚合物分子扩散理论和吸附理论,描述芯片键合过程,从芯片表面张力和键合能的角度探明了热键合发生的原因,并对现有芯片键合工艺进行分析,在理论上证明聚合物芯片模内键合的可行性。并对微流控芯片表面微观质量、微通道变形、键合强度以及影响上述键合质量的因素进行研究,确定芯片键合质量评价方法；
采用有限元的方法对微流控芯片热键合过程中主要键合参数对微通道变形的影响进行数值模拟分析,结果表明：键合后微通道高度方向上的变形较大,在宽度方向上变形不明显,可忽略不计。微通道高度改变量随键合温度和键合压力的升高而增大,键合温度对高度改变量存在较大影响,当键合温度高于材料玻璃化转变温度时,微通道变形较为严重,综合考虑键合效率与微通道变形。
分析模内键合加热需求,选取远红外陶瓷加热器对芯片键合表面进行加热,设计开发模内键合加热及采用PID算法的温度控制系统,完成PID参数整定,使加热器稳定工作在设定温度值附近。进行键合面加热实验,得出各加热参数与键合面温度之间的关系。
设计模内键合正交实验,利用微流控芯片成型与键合模具进行芯片模内键合实验,采用极差法分析影响微通道高度的主要因素,结合芯片整体形貌、微通道变形量和键合强度等辅助评价指标,获得最佳的模内键合工艺参数组合。
In recent years, microfluidic chip has received increasing attention in the field of chemical and biological analysis by characteristics of rapidity, high effectiveness and low consumption. Polymers are less expensive and easier to manufacture in large quantities, which make up the shortcomings of quartz and glass. In addition, polymers have good electrochemical properties and biological compatibility, making them the best choice for microfluidic chip fabrication. The conditional fabricating method of microfluidic chip is ineffective, and manufacturing cycle of that is long, for molding technology and bonding technology are seperated. In this paper, bond-in-mold technology was introduced for the purpose of manufacturing chip in large quantities with low cost.
Firstly, diffusion theory and adsorption theory were used for describing the process of bonding, then searching root causes of bonding were found from the view of surface tension and bonding energy, so feasibility of bond-in-mold technology was verified.
Microchannel distortion in thermal bonding was studied by finite element software, and the results showed that distortion in the direction of height is quite large, on the contrary distortion in the direction of height is indistinctive. The distortion in the direction of height was growing with increasing bonding temperature and pressure, and bonding temperature had larger influence on it. When bonding temperature was higher than glass-transition temperature of material, distortion of microchannel was comparatively serious.
Far-infrared ceramic heaters were chosen to heat surface of the chip, after analyzing requirements of bond-in-mold technology. The heating system for bond-in-mold and temperature control system with PID algorithm were designed and developed. The temperature heater was controlled for working under SV by setting parameters of PID. Experiments of heating bonding surface were carried out, then relationships between surface temperature and heating parameters were obtained.
Bond-in-mold experiment was carried out after designing orthogonal experiment with injection and bonding mold of microfluidic chip. The effects of main factors on height of microchannel were analyzed by Range Method. Then optimal combination of bonding parameters were obtained taking chip feature and bonding strength into account.
引文
[1]刘静.微米／纳米尺度传热学[M].北京：科学出版社,2001：15-20.
[2]文伟力.微流控芯片的制作、检测及仿真研究[D].长春：吉林大学,2007.
[3]楚纯朋.微流控芯片注射成型工艺参数优化[D].长沙：中南大学,2009.
[4]林炳承,秦建华.微流控芯片实验室[M].北京：科学出版社,2005：1-10.
[5]Lai S Y. Design and fabrication of polymer-based microfludic platforms for biomedical applications[D]. Ohio:Ohio State University,2003.
[6]方肇伦,方群.微流控芯片发展与展望[J].现代科学仪器,2001,14(4)：3-6.
[7]Song S., Lee K.Y. Polymers for Microfluidic Chips[J]. Macromolecular Research, 2006,14(2):121-128.
[8]Lee G.B., Chen S.H., Huang G.R.,et al. Microfabricated plastic chips by hot embossing methods and their applications for DNA separation and detection[J]. Sensors and Actuators B,2001,75(1):142-148.
[9]Dittrich P. S., Tachikawa K., Manz A. Micro total analysis systems. Latest advancements and trends[J]. Anal. Chem.,2006,78(12):3887-3908.
[10]Yao X., Wu H. X., Wang J., et al. Carbon nanotube/PMMA composite electrode fabricated by in situ polymerization for microchip capillary electrophoresis[J]. Chem. Eur. J.,2007,13(3):846-853.
[11]Chen G., Lin Y. H., Wang J. Monitoring environmental pollutants by microchip capillary electrophoresis with electrochemical detection[J]. Talanta,2006,68(3): 497-503.
[12]Fan Z H, Harrison D J. Micromachining of capillary electrophoresis injectors and separators on glass chips and evaluation of flow at capillary intersections[J]. Analysis Chemistry,1994,66(1):177-184.
[13]王立顶,刘军山,于建群.集成毛细管电泳芯片研究进展[J].大连理工大学学报,2003,43(4)：385-392.
[14]慕轩,胡坪,罗国安,等.微流控芯片技术在临床检测中的应用进展[J].分析测试学报,2007,26(4)：587-591.
[15]王金光,李明,刘剑锋,等.微流控芯片在医学检测中的应用[J].现代科学仪器,2007,17(6)：60-63.
[16]方肇伦.微流控分析芯片发展与展望[J].大学化学,2001,16(2)：1-6.
[17]方肇伦.微流控分析芯片的制作及应用[M].北京：化学工业出版社,2005： 152-173.
[18]刘军山.PMMA集成毛细管电泳芯片制作工艺研究[D].大连：大连理工大学.大连,2005.
[19]Thorsen T, Maerkl S J, Quake S R. Microfluidic large-scale integration[J]. Science,2002,298(4):580-584.
[20]Dolnik V, Liu S, Jovanovich S. Capillary electrophoresis on microchip[J]. Electrophoresis,2000,21(1):41-54.
[21]Shi Y, Simpson P C, Scherer J R, et al. Radial capillary array electrophoresis microplate and scanner for high-performance nucleic acid analysis[J]. Anal. Chem., 1999,71(23):5354-5361.
[22]Emrich C A, Tian H, Medintz L L, et al. Microfabricated 384-lane capillary array electrophoresis bioanalyzer for ultrahigh-throughput genetic analysis[J]. Anal. Chem., 2002,74(19):5076-5083.
[23]Skeggs L T. An automatic method for calorimetric analysis[J]. Am J Clin Pathol, 1957,28(3):311-322.
[24]Manz A, Graber N, Widmer H M. Miniaturized total chemical analysis systems:a novel concept for chemical sensing[J]. Sensors and Actuators B,1990,1(6):244-248.
[25]Manz A, Fettinger J C, Verpoorte E, et al. Micromachining of monocrystalline silicon and glass for chemical-analysis system-a look into next century technology or just a fashionable craze[J]. Trac-Trends in a Analytical Chemistry,1991,10(5): 144-149.
[26]Harrison D J, Manz A, Fan Z H, et al. Capillary electrophoresis and sample injection systems integrated on a planar glass chip[J]. Analytical Chemistry,1992, 64(17):1926-1932.
[27]Ramsey J M. Microfabricated chemical measurement systems[J]. Nature Medicine,1995,1(10):1093-1095.
[28]Woolley A T, Mathies R A. Ultra-high speed DNA sequencing using capillary electrohoresis chips[J]. Analytical Chemistry,1995,67 (20):3676-3680.
[29]Duffy D C, McDonald J C, Schueller O J A, et al. Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)[J]. Anal.Chem.,1998,70(23): 4974-4984.
[30]Wu H, Huang B, Zare R N. Construction of microfluidic chips using polydimethylsiloxane for adhesive bonding[J]. Lab Chip,2005,5(12):1393-1398.
[31]Chen P J, Shih C Y, Tai Y C. Design, fabrication and characterization of monolithic embedded parylene microchannels in silicon substrate[J]. Lab Chip,2006, 6(6):803-810.
[32]Lee K B, Lin L. Surface micromachined glass and polysilicon microchannels using MUMPs for BioMEMS applications[J]. Sensors and Actuators A,2004,111(1): 44-50.
[33]Shen X J, Pan L W, Lin L. Microplastic embossing process:experimental and theoretical characterizations [J]. Sensors and Actuators A,2002,97 (1):428-433.
[34]Flachsbart B R, Wong K, Iannacone J M, et al. Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing[J]. Lab Chip,2006,6(5):667-674.
[35]Paul D, Pallandre A, Miserere S, et al. Lamination-based rapid prototyping of microfluidic devices using flexible thermoplastic substrates[J]. Electrophoresis,2007, 28(7):1115-1122.
[36]Tuomikoski S, Virkkala N, Rovio S, et al. Design and fabrication of integrated solid-phase extraction-zone electrophoresis microchip[J]. Journal of Chromatography A,2006,1111(2):258-266.
[37]Chiem N, Shultz L L, Andersson P, et al. Room temperature bonding of micromachined glass devices for capillary electrophoresis[J]. Sensors and Actuators B, 2000,63(3):147-152.
[38]Szekely L, Freitag R. Fabrication of a versatile microanalytical system without need for clean room conditions [J]. Analytica Chimica Acta,2004,512(1):39-47.
[39]Metz S, Holzer R, Renaud P. Polyimide-based microfluidic devices[J]. Lab Chip, 2001,1(1):29-34.
[40]Jacobson S C, Culbertson C T, Daler J E, et al. Microchip structures for submillisecond electrophoresis[J]. Anal.Chem.,1998,70(16):3476-3480.
[41]Culbertson C T, Jacobson S C, Ramsey J M. Microchip devices for high-efficiency separations[J]. Anal.Chem.,2000,72(23):5814-5819.
[42]Song L G, Fang D F, Kobos R K. Separation of double-stranded DNA fragments in plastic capillary electrophoresis chips by using E99P69E99 as separation medium[J]. Electrophoresis,1999,20(14):2847-2855.
[43]Xu J D, Locascio L, Gatitan M. Room-temperature imprinting method for plastic microchannel fabrication[J]. Anal.Chem.,2000,72(8):1930-1933.
[44]Barker S L, Ross D, Tarlov M J, et al. Control of flow direction in microfluidic devices with polyelectrolyte multilayers [J]. Anal.Chem.,2000,72(24):5925-5929.
[45]Ford S M, Kar B, McWhorter S. Microcapillary electrophoresis devices fabricated using polymeric substrates and X-ray lithography[J]. J. Microcol. Sep., 1998,10(5):413-422.
[46]Liu Y, Ganser D, Schneider A. Microfabricated polycarbonate CE devices for DNA analysis[J]. Anal.Chem.,2001,73(17):4196-4201.
[47]Effenhauser C S, Bruin G J, Paulus A, Ehrat M. Integrated capillary electrophoresis on flexible silicone microdevices:analysis of DNA restriction fragments and detection of single DNA molecules on microchips[J]. Anal.Chem., 1997,69(17):3451-3457.
[48]Ren X, Bachman M, Sims C, et al. Electroosmotic properties of microfluidic channels composed of poly(dimenthylsiloxane)[J]. Journal of Chromatography B, 2001,762(2):117-125.
[49]Roberts M A, Rossier J S, Bercier P, et al. UV laser machined polymer substrates for the development of microdiagnostic systems[J]. Anal.Chem.,1997,69(11): 2035-2042.
[50]Pugmire D L, Waddell E A, Haasch R, et al. Surface characterization of laser-ablated polymers used for microfluidics[J]. Anal.Chem.,2002,74(4):871-878.
[51]Martynova L, Locascio L E, Gaitan M, et al. Fabrication of plastic microfluid channels by imprinting methods[J]. Anal.Chem.,1997,69(23):4783-4789.
[52]Holger B, Ulf H. Hot embossing as a method for the fabrication of polymer high aspect ratio structures[J]. Sensors and Actuators A,2000,83(1):130-135.
[53]Juang Y J, Lee L J, Koelling K W. Hot embossing in microfabrication,part I: experimental [J]. Polymer Engineering And Science,2002,42(3):539-550.
[54]杜晓光,关艳霞,王福仁,等.聚甲基丙烯酸甲酯微流控分析芯片的简易热压制作法[J].高等学校化学学报,2003,24(11)：1962-1966.
[55]王晓东,罗怡,刘冲,等.塑料(PMMA)微流控芯片微通道热压成形工艺参数的确定[J].中国机械工程,2005,16(22)：2061-2063.
[56]王晓东,刘冲,王立鼎.面向聚合物微结构制作的热压成形设备的研制[J].中国机械工程,2005,16(14)：1229-1232.
[57]Liu J S, Wang L D, Liu C, et al. Hot embossing methods for plastic microchannel fabrication[J]. Chinese Journal of Mechanical Engineering,2006,19(2):223-225.
[58]罗怡,王晓东,刘冲,等.一种新型微流控芯片金属热压模具的制作工艺研究[J].中国机械工程,2005,16(17)：1505-1507.
[59]王晓东,刘冲,马骊群,等.塑料微流控芯片的制作及其自动化[J].高技术通讯,2004(7)：45-48.
[60]McCormick R M, Nelson R J, Alonso-Amigo M G, et al. Microchannel electrophoresis separations of DNA in injection-molded plastic substrates[J]. Anal.Chem.,1997,69(14):2626-2630.
[61]Loke Y.W., Tor S.B., Chun J.H., et al. Micro Injection-Molding of Cyclic Olefin Copolymer Using Metallic Glass Insert[J]. Manuf Syst Technol,2007,372(1):35-38.
[62]王岩.基于微流控芯片的微注射成型技术[D].大连：大连理工大学,2007.
[63]Mair D A, Geiger E, Pisano A P, et al. Injection molded microfluidic chips featuring integrated interconnects [J]. Lab Chip,2006,6(10):1346-1354.
[64]Lee L J, Madou M J, Koelling K W, et al. Design and Fabrication of CD-Like Microfluidic Platforms for Diagnostics:Polymer-Based Microfabrication[J]. Biomed Microdevices,2001,3(4):339-351.
[65]杨芯苹.应用于微流体组件之微射出成型研究[D].台南：国立成功大学,2003.
[66]楼夏,金星,金玉丰,等.基于粘附剂键合的圆片级MEMS塑料封装技术[J].功能材料与器件学报,2008,14(2)：293-297.
[67]张宗波,罗怡,王晓东,等.塑料超声波焊接及其用于聚合物MEMS器件键合的研究进展[J].焊接,2008,17(8)：9-15.
[68]Steven A S, Alyssa C H, Bikas V, et al. Surface modification of polymer-based microfluidic devices[J]. Analytica chemical acta,2002,470(11):87-99.
[69]Irena N, Se H L, Aigars P, et al. Characterization and performance of injection molded poly(methylmethacrylate) microchips for capillary electrophoresis[J]. Journal of Chromatography B,2007,1154(1):444-453.
[70]Huang F, Cen Y, Lee G. CE chips fabricated by injection molding and polyethylene/thermoplastic elastomer film packaging methods[J]. Electrophoresis, 2007,28(7):1130-1137.
[71]Chen Y, Duan H, Zhang L, et al. Fabrication of PMMA CE microchips by infrared-assisted polymerization[J]. Electrophoresis,2008,29(24):4922-4927.
[72]Shao P G, Kan J A, Wang L P, et al. Rapid prototyping of micro/nano poly (methyl methacrylate) fluidic systems using proton beam writing[J]. Beam Interactions with Materials & Atoms,2007,260(1):362-365.
[73]张瑜.PMMA基PCR生物芯片的准分子激光微加工、键合、封装技术研究[D].北京：北京工业大学,2004.
[74]Zhifeng C, Yunhua G, Jinming L, et al. Vacuum-assisted thermal bonding of plastic capillary electrophoresis microchip imprinted with stainless steel template[J]. Journal of Chromatography A,2004,1038(1):239-245.
[75]Thomas I W, Alfredo M M, Blake A S, et al. Low-distortion, high-strength bonding of thermoplastic microfluidic devices employing case-II diffusion-mediated permeant activation[J]. Lab Chip,2007,7(12):1825-1831.
[76]Yi S, Yien C K, Nam N. Low-pressure, high-temperature thermal bonding of polymeric microfluidic devices and their applications for eletrophoretic separation[J]. Micromechanics and Microengineering,2006,16(8):1681-1688.
[77]温敏.塑料微流控芯片微通道热压成型及键合研究[D].大连：大连理工大学,2005.
[78]朱学林,刘刚,田扬超.一种PMMA表面改性的热压键合方法研究[J].微细加工技术,2005,12(4)：52-55.
[79]蓝才红.聚合物微流控芯片模内键合微通道变形研究[D].长沙：中南大学,2009.
[80]王福亮.热超声倒装键合界面运动与界面性能的生成规律研究[D].长沙：中南大学,2007.
[81]谢海波.集成微泵式微流控芯片关键技术的研究[D].杭州：浙江大学,2004.
[82]李建华.聚合物微流控芯片制作关键技术研究[D].上海：上海交通大学,2006.
[83]Kelly R T, Woolley A T, Nam N. Thermal bonding of polymeric capillary electrophoresis microdevices in water[J]. Anal.Chem.,2003,75(8):1941-1945.
[2]文伟力.微流控芯片的制作、检测及仿真研究[D].长春：吉林大学,2007.
[3]楚纯朋.微流控芯片注射成型工艺参数优化[D].长沙：中南大学,2009.
[4]林炳承,秦建华.微流控芯片实验室[M].北京：科学出版社,2005：1-10.
[5]Lai S Y. Design and fabrication of polymer-based microfludic platforms for biomedical applications[D]. Ohio:Ohio State University,2003.
[6]方肇伦,方群.微流控芯片发展与展望[J].现代科学仪器,2001,14(4)：3-6.
[7]Song S., Lee K.Y. Polymers for Microfluidic Chips[J]. Macromolecular Research, 2006,14(2):121-128.
[8]Lee G.B., Chen S.H., Huang G.R.,et al. Microfabricated plastic chips by hot embossing methods and their applications for DNA separation and detection[J]. Sensors and Actuators B,2001,75(1):142-148.
[9]Dittrich P. S., Tachikawa K., Manz A. Micro total analysis systems. Latest advancements and trends[J]. Anal. Chem.,2006,78(12):3887-3908.
[10]Yao X., Wu H. X., Wang J., et al. Carbon nanotube/PMMA composite electrode fabricated by in situ polymerization for microchip capillary electrophoresis[J]. Chem. Eur. J.,2007,13(3):846-853.
[11]Chen G., Lin Y. H., Wang J. Monitoring environmental pollutants by microchip capillary electrophoresis with electrochemical detection[J]. Talanta,2006,68(3): 497-503.
[12]Fan Z H, Harrison D J. Micromachining of capillary electrophoresis injectors and separators on glass chips and evaluation of flow at capillary intersections[J]. Analysis Chemistry,1994,66(1):177-184.
[13]王立顶,刘军山,于建群.集成毛细管电泳芯片研究进展[J].大连理工大学学报,2003,43(4)：385-392.
[14]慕轩,胡坪,罗国安,等.微流控芯片技术在临床检测中的应用进展[J].分析测试学报,2007,26(4)：587-591.
[15]王金光,李明,刘剑锋,等.微流控芯片在医学检测中的应用[J].现代科学仪器,2007,17(6)：60-63.
[16]方肇伦.微流控分析芯片发展与展望[J].大学化学,2001,16(2)：1-6.
[17]方肇伦.微流控分析芯片的制作及应用[M].北京：化学工业出版社,2005： 152-173.
[18]刘军山.PMMA集成毛细管电泳芯片制作工艺研究[D].大连：大连理工大学.大连,2005.
[19]Thorsen T, Maerkl S J, Quake S R. Microfluidic large-scale integration[J]. Science,2002,298(4):580-584.
[20]Dolnik V, Liu S, Jovanovich S. Capillary electrophoresis on microchip[J]. Electrophoresis,2000,21(1):41-54.
[21]Shi Y, Simpson P C, Scherer J R, et al. Radial capillary array electrophoresis microplate and scanner for high-performance nucleic acid analysis[J]. Anal. Chem., 1999,71(23):5354-5361.
[22]Emrich C A, Tian H, Medintz L L, et al. Microfabricated 384-lane capillary array electrophoresis bioanalyzer for ultrahigh-throughput genetic analysis[J]. Anal. Chem., 2002,74(19):5076-5083.
[23]Skeggs L T. An automatic method for calorimetric analysis[J]. Am J Clin Pathol, 1957,28(3):311-322.
[24]Manz A, Graber N, Widmer H M. Miniaturized total chemical analysis systems:a novel concept for chemical sensing[J]. Sensors and Actuators B,1990,1(6):244-248.
[25]Manz A, Fettinger J C, Verpoorte E, et al. Micromachining of monocrystalline silicon and glass for chemical-analysis system-a look into next century technology or just a fashionable craze[J]. Trac-Trends in a Analytical Chemistry,1991,10(5): 144-149.
[26]Harrison D J, Manz A, Fan Z H, et al. Capillary electrophoresis and sample injection systems integrated on a planar glass chip[J]. Analytical Chemistry,1992, 64(17):1926-1932.
[27]Ramsey J M. Microfabricated chemical measurement systems[J]. Nature Medicine,1995,1(10):1093-1095.
[28]Woolley A T, Mathies R A. Ultra-high speed DNA sequencing using capillary electrohoresis chips[J]. Analytical Chemistry,1995,67 (20):3676-3680.
[29]Duffy D C, McDonald J C, Schueller O J A, et al. Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)[J]. Anal.Chem.,1998,70(23): 4974-4984.
[30]Wu H, Huang B, Zare R N. Construction of microfluidic chips using polydimethylsiloxane for adhesive bonding[J]. Lab Chip,2005,5(12):1393-1398.
[31]Chen P J, Shih C Y, Tai Y C. Design, fabrication and characterization of monolithic embedded parylene microchannels in silicon substrate[J]. Lab Chip,2006, 6(6):803-810.
[32]Lee K B, Lin L. Surface micromachined glass and polysilicon microchannels using MUMPs for BioMEMS applications[J]. Sensors and Actuators A,2004,111(1): 44-50.
[33]Shen X J, Pan L W, Lin L. Microplastic embossing process:experimental and theoretical characterizations [J]. Sensors and Actuators A,2002,97 (1):428-433.
[34]Flachsbart B R, Wong K, Iannacone J M, et al. Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing[J]. Lab Chip,2006,6(5):667-674.
[35]Paul D, Pallandre A, Miserere S, et al. Lamination-based rapid prototyping of microfluidic devices using flexible thermoplastic substrates[J]. Electrophoresis,2007, 28(7):1115-1122.
[36]Tuomikoski S, Virkkala N, Rovio S, et al. Design and fabrication of integrated solid-phase extraction-zone electrophoresis microchip[J]. Journal of Chromatography A,2006,1111(2):258-266.
[37]Chiem N, Shultz L L, Andersson P, et al. Room temperature bonding of micromachined glass devices for capillary electrophoresis[J]. Sensors and Actuators B, 2000,63(3):147-152.
[38]Szekely L, Freitag R. Fabrication of a versatile microanalytical system without need for clean room conditions [J]. Analytica Chimica Acta,2004,512(1):39-47.
[39]Metz S, Holzer R, Renaud P. Polyimide-based microfluidic devices[J]. Lab Chip, 2001,1(1):29-34.
[40]Jacobson S C, Culbertson C T, Daler J E, et al. Microchip structures for submillisecond electrophoresis[J]. Anal.Chem.,1998,70(16):3476-3480.
[41]Culbertson C T, Jacobson S C, Ramsey J M. Microchip devices for high-efficiency separations[J]. Anal.Chem.,2000,72(23):5814-5819.
[42]Song L G, Fang D F, Kobos R K. Separation of double-stranded DNA fragments in plastic capillary electrophoresis chips by using E99P69E99 as separation medium[J]. Electrophoresis,1999,20(14):2847-2855.
[43]Xu J D, Locascio L, Gatitan M. Room-temperature imprinting method for plastic microchannel fabrication[J]. Anal.Chem.,2000,72(8):1930-1933.
[44]Barker S L, Ross D, Tarlov M J, et al. Control of flow direction in microfluidic devices with polyelectrolyte multilayers [J]. Anal.Chem.,2000,72(24):5925-5929.
[45]Ford S M, Kar B, McWhorter S. Microcapillary electrophoresis devices fabricated using polymeric substrates and X-ray lithography[J]. J. Microcol. Sep., 1998,10(5):413-422.
[46]Liu Y, Ganser D, Schneider A. Microfabricated polycarbonate CE devices for DNA analysis[J]. Anal.Chem.,2001,73(17):4196-4201.
[47]Effenhauser C S, Bruin G J, Paulus A, Ehrat M. Integrated capillary electrophoresis on flexible silicone microdevices:analysis of DNA restriction fragments and detection of single DNA molecules on microchips[J]. Anal.Chem., 1997,69(17):3451-3457.
[48]Ren X, Bachman M, Sims C, et al. Electroosmotic properties of microfluidic channels composed of poly(dimenthylsiloxane)[J]. Journal of Chromatography B, 2001,762(2):117-125.
[49]Roberts M A, Rossier J S, Bercier P, et al. UV laser machined polymer substrates for the development of microdiagnostic systems[J]. Anal.Chem.,1997,69(11): 2035-2042.
[50]Pugmire D L, Waddell E A, Haasch R, et al. Surface characterization of laser-ablated polymers used for microfluidics[J]. Anal.Chem.,2002,74(4):871-878.
[51]Martynova L, Locascio L E, Gaitan M, et al. Fabrication of plastic microfluid channels by imprinting methods[J]. Anal.Chem.,1997,69(23):4783-4789.
[52]Holger B, Ulf H. Hot embossing as a method for the fabrication of polymer high aspect ratio structures[J]. Sensors and Actuators A,2000,83(1):130-135.
[53]Juang Y J, Lee L J, Koelling K W. Hot embossing in microfabrication,part I: experimental [J]. Polymer Engineering And Science,2002,42(3):539-550.
[54]杜晓光,关艳霞,王福仁,等.聚甲基丙烯酸甲酯微流控分析芯片的简易热压制作法[J].高等学校化学学报,2003,24(11)：1962-1966.
[55]王晓东,罗怡,刘冲,等.塑料(PMMA)微流控芯片微通道热压成形工艺参数的确定[J].中国机械工程,2005,16(22)：2061-2063.
[56]王晓东,刘冲,王立鼎.面向聚合物微结构制作的热压成形设备的研制[J].中国机械工程,2005,16(14)：1229-1232.
[57]Liu J S, Wang L D, Liu C, et al. Hot embossing methods for plastic microchannel fabrication[J]. Chinese Journal of Mechanical Engineering,2006,19(2):223-225.
[58]罗怡,王晓东,刘冲,等.一种新型微流控芯片金属热压模具的制作工艺研究[J].中国机械工程,2005,16(17)：1505-1507.
[59]王晓东,刘冲,马骊群,等.塑料微流控芯片的制作及其自动化[J].高技术通讯,2004(7)：45-48.
[60]McCormick R M, Nelson R J, Alonso-Amigo M G, et al. Microchannel electrophoresis separations of DNA in injection-molded plastic substrates[J]. Anal.Chem.,1997,69(14):2626-2630.
[61]Loke Y.W., Tor S.B., Chun J.H., et al. Micro Injection-Molding of Cyclic Olefin Copolymer Using Metallic Glass Insert[J]. Manuf Syst Technol,2007,372(1):35-38.
[62]王岩.基于微流控芯片的微注射成型技术[D].大连：大连理工大学,2007.
[63]Mair D A, Geiger E, Pisano A P, et al. Injection molded microfluidic chips featuring integrated interconnects [J]. Lab Chip,2006,6(10):1346-1354.
[64]Lee L J, Madou M J, Koelling K W, et al. Design and Fabrication of CD-Like Microfluidic Platforms for Diagnostics:Polymer-Based Microfabrication[J]. Biomed Microdevices,2001,3(4):339-351.
[65]杨芯苹.应用于微流体组件之微射出成型研究[D].台南：国立成功大学,2003.
[66]楼夏,金星,金玉丰,等.基于粘附剂键合的圆片级MEMS塑料封装技术[J].功能材料与器件学报,2008,14(2)：293-297.
[67]张宗波,罗怡,王晓东,等.塑料超声波焊接及其用于聚合物MEMS器件键合的研究进展[J].焊接,2008,17(8)：9-15.
[68]Steven A S, Alyssa C H, Bikas V, et al. Surface modification of polymer-based microfluidic devices[J]. Analytica chemical acta,2002,470(11):87-99.
[69]Irena N, Se H L, Aigars P, et al. Characterization and performance of injection molded poly(methylmethacrylate) microchips for capillary electrophoresis[J]. Journal of Chromatography B,2007,1154(1):444-453.
[70]Huang F, Cen Y, Lee G. CE chips fabricated by injection molding and polyethylene/thermoplastic elastomer film packaging methods[J]. Electrophoresis, 2007,28(7):1130-1137.
[71]Chen Y, Duan H, Zhang L, et al. Fabrication of PMMA CE microchips by infrared-assisted polymerization[J]. Electrophoresis,2008,29(24):4922-4927.
[72]Shao P G, Kan J A, Wang L P, et al. Rapid prototyping of micro/nano poly (methyl methacrylate) fluidic systems using proton beam writing[J]. Beam Interactions with Materials & Atoms,2007,260(1):362-365.
[73]张瑜.PMMA基PCR生物芯片的准分子激光微加工、键合、封装技术研究[D].北京：北京工业大学,2004.
[74]Zhifeng C, Yunhua G, Jinming L, et al. Vacuum-assisted thermal bonding of plastic capillary electrophoresis microchip imprinted with stainless steel template[J]. Journal of Chromatography A,2004,1038(1):239-245.
[75]Thomas I W, Alfredo M M, Blake A S, et al. Low-distortion, high-strength bonding of thermoplastic microfluidic devices employing case-II diffusion-mediated permeant activation[J]. Lab Chip,2007,7(12):1825-1831.
[76]Yi S, Yien C K, Nam N. Low-pressure, high-temperature thermal bonding of polymeric microfluidic devices and their applications for eletrophoretic separation[J]. Micromechanics and Microengineering,2006,16(8):1681-1688.
[77]温敏.塑料微流控芯片微通道热压成型及键合研究[D].大连：大连理工大学,2005.
[78]朱学林,刘刚,田扬超.一种PMMA表面改性的热压键合方法研究[J].微细加工技术,2005,12(4)：52-55.
[79]蓝才红.聚合物微流控芯片模内键合微通道变形研究[D].长沙：中南大学,2009.
[80]王福亮.热超声倒装键合界面运动与界面性能的生成规律研究[D].长沙：中南大学,2007.
[81]谢海波.集成微泵式微流控芯片关键技术的研究[D].杭州：浙江大学,2004.
[82]李建华.聚合物微流控芯片制作关键技术研究[D].上海：上海交通大学,2006.
[83]Kelly R T, Woolley A T, Nam N. Thermal bonding of polymeric capillary electrophoresis microdevices in water[J]. Anal.Chem.,2003,75(8):1941-1945.