塑料微流控芯片微通道热压成形及键合工艺研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
微流控芯片是微全分析系统(Miniaturized Total Analysis System,μTAS)的主要研究方向,在生命科学、医学、化学、新药开发、食品和环境卫生监测等领域应用前景广阔。聚合物材料具有加工简单、低成本、易于实现批量生产等优点,本文研究了塑料微流控芯片微通道的热压成形和芯片的键合工艺,制作了微流控芯片,实际应用于药物分离检测。
     对微通道热压成形过程中,塑料力学性能对时间、温度的依赖性进行了研究,采用弹簧、粘壶的组合模型分析了塑料在玻璃化温度附近的粘弹性行为特征。
     在分析塑料玻璃化温度附近的流变行为基础上,研究了微通道热压过程中的材料传热数学模型、应力场分布数学模型。根据应力场分布的数学模型,应力在芯片的分布不均匀,中央最大,边缘最小。随着热压冷却阶段压力的提高,应力分布的不均匀对降温脱模后的微通道不一致性的影响将有效地降低。
     进行了塑料微流控芯片微通道热压成形工艺试验,研究了温度、压力和时间3个可控因素对微通道热压成形质量的影响。提出了试验确定微通道热压成形工艺参数的方法,并确定了选用材料的热压工艺参数,在该工艺参数下热压获得的芯片微通道复制精度高,片内不一致性小于5%。该试验方法对不同厂家材料微通道热压成形工艺参数的确定具指导意义和实际应用价值。
     研究了塑料微流控芯片基片和盖片的键合方法,对键合前PMMA芯片进行了表面预处理,采用热粘合法实现了PMMA芯片的键合。键合质量经测量,键合强度不低于0.1Mpa。键合后的芯片在20mmol/L的硼砂缓冲溶液中,微通道的伏安特性的线性段为2000~6000V,电渗流为2.8×10~(-4)cm~2V~(-1)S(-1)。芯片用于电泳分离安非他明-FITC衍生溶液,峰高RSD为4.4%(n=6),理论塔板数为11.4×10~4m~(-1)。此外,试验了溶剂粘合法进行塑料微流控芯片的键合,键合强度大于热粘合法
The Microfluidic Chips is the main research orientation of Miniaturized Total Analysis Syatem (uTAS). It's widely application in the field of life sciences, iatrology, new drugs exploitation, chemistry, foodstuff and environment inspecting etc. Polymers represent certain advantages such as process simple, normally low cost and esay to high volume production. In this dissertation, hot embossing and bonding techniques were researched for fabrication plastic Microfluidic Chips. The drug was detected on the Microfluidic Chips produced by this method.In hot embossing polymers microchannels, the material was processed near the glass transition temperature. The viso-elastic behaviors of material are studied by parallel model combined with spring and viscous dashpots. It's found that polymer's mechanical properties behave strongly in time and temperature dependent manner.After discussing flow behaviors of polymers near the glass transition temperature, the mathematical model of heat transmission through thermal medium and the mathematical model of pressure distribution within polymer were studied. This finding indicates that a non-uniform pressure distribution in the radius direction produced by embossing processl. However, a higher embossing pressure during cooling leads to a more uniform shrinkage in the elastically deformed. And thus reduces the variation of microchannel.Experiment on hot embossing microchannels was carried out. Embossing parameters temperature, embossing force and time governing hot embossing were investigated. An experiment method was put forward to establish PMMA microchannels' hot embossing process. In this process, the replication rate of microchannels is high, and microchannels within 5% variance are obtained. This method gives guidance to establish hot embossing process of materials from different source.A substrate with microchannels is bonded with a cover to form close channels. The pretreatment process of PMMA surface before bonding was discussed. The Microfuidic Chips was bonded by thermal bonding method. Its bonding intensity is higher than 0.1 Mpa. The electro-osmotic flow is 2.8x10-4cm-2V-1s-1, and voltage-ampere curves of PMMA microchannel in 20nmol/L buffer solution of borax were tested too. The performance of the PMMA chips is demonstrated in the electrophoretic separation of methamphetamine from byproducts with a precision of 4.4% RSD (n=6) and an efficiency of 11.4x104m-1'. In addition, adhesive bonding
    
    method was tried out to bond the plastic Microfluidic Chips, and the bonding intensity is higher than that of thermal bonding method.
引文
[1] Manz A, Becker H. Microsystem Technology in Chemistry and Life Sciences. Berlin: Springer-Verlag, 1999: 3-4.
    [2] Fan Z H, Harrison D J. Micromachining of capillary electrophoresis injectors and separators on glass chips and evaluation of flow at capillary intersections. Anal Chem, 1994, 66 (1): 177-184.
    [3] 王立鼎,刘军山,于建群等.集成毛细管电泳芯片研究进展.大连理工大学学报,2003,43(4):385-392.
    [4] 方肇伦.微流控分析芯片.北京:科技出版社,2003.
    [5] Skeggs L T. An automatic method for calorimetric analysis. Am J Clin Pathol, 1957, 28: 311-322.
    [6] Manz A, Harrison D J, Verpoorte E M et al. An international journal devoted to research and development of chemical transducers. Chromatogr, 1992, 593 (3): 253-258.
    [7] Harrison D J, Manz A, Fan Z H et al. Capillary Electrophoresis and Sample Injection Systems Integrated on a Planar Glass Chip. Anal Chem, 1992, 64(17): 1926-1932.
    [8] Woolley A T, Sensabaugh G F, Mathies R A. High-Speed DNA Genotyping Using Microfabricated Capillary Array Electrophoresis Chips. Anal Chem, 1997, 69 (11): 2181-2186.
    [9] 周小棉,戴忠鹏,罗勇等.一种微流控芯片.中国,实用新型专利,02274236.0.2003.
    [10] Xia Y, Zhao X M, Whitesides G M, Pattern transfer: Self-assembled monolayers as ultrathin resists. Microelectronic Eng, 1996, 32 (1-4): 255-268.
    [11] Jackman R, Wilbur J, Whitesides G M, Fabrication of Submicrometer Features on Curved Substrates by Microcontact Printing. Science, 1995, 269 (5224): 664-666.
    [12] Xia Y, Whitesides G M, Extending Microcontact Printing as a Microlithographic Technique. Lang muir, 1997, 13: 2059-2067.
    [13] Kim E, Xia Y, Whitesides G M, Polymer Microstructures Formed by Moulding in Capillaries. Nature 1995, 376: 581-584.
    [14] Zhao X M, Xia Y, Whitesides G M, Fabrication of Three-dimensional Microstructures: Microtransfer Molding. Adv Mater, 1996, 8: 837-840.
    [15] Xia Y, Kim R, Zhao X M et al. Complex Optical Surfaces Formed by Replica Molding Against Elastomeric Masters, Science, 1996, 273 (5273): 347-349.
    [16] Roberts M A., Rossier J S, Bercier P et al. UV Laser Machined Polymer Substrates for the Development of Microdiagnostic Systems. Anal Chem, 1997, 69 (11): 2035-2042.
    
    [17] Lade R J, Morley I W, May P W et al. ArF (193nm) laser ablation of poly(methyl methacrylate). Diamond and Related Materials 1999, 8(8-9): 1654-1658.
    [18] Gra(?) B, Neyer A, J(?)hnck M et al. A new PMMA microchip device for isotachophoresis with integrated conductivity detector. Sensors and Actuators, 2001, 72 (3): 249-258.
    [19] Niggemann M, Ehrfeld W, Weber L. Fabrication of miniaturized biotechnical devices. Proc. SPIE Micromachining and Microfabrication Process Technology Ⅳ, Santa Clara, 1998.
    [20] Liu Z Y, Lob N H, Tor S B et al. Binder system for micropowder injection molding. Materials Letters, 2001, 48 (1): 31-38.
    [21] Soper S A, Ford S M, Qi S, McCarley R L, Kelly K, Murphy M C, Polymeric Microelectromechanical Systems. Anal Chem, 2000, 72 (19): 643-651.
    [22] Becker H, G(?)rtner C. Polymer microfabrication methods for microfluidic analytical applications. Electrophoresis, 2000, 21 (1): 12-26.
    [23] Heckele M, Bather W, Muller K D. Hot embossing-The molding technique for plastic micro-structures. Microsystem Technologies, 1998, 4: 122-124.
    [24] Ehrfeld W, Hessel V, Lowe H et al. Materials of LIGA technology, Microsystem technologies, 1999, 5:105-112.
    [25] Heyderman L J, Schift H, David C et al. Flow behaviour of thin polymer films used for hot embossing lithography. Microelectronic Engineering, 2000(54): 229-245.
    [26] Bachman M, Chiang Y M, Chu C et al. Laminated microfluidic structures using a micromolding technique. Proceedings of SPIE-The International Society for Optical Engineering, 1999, 3877: 139-146.
    [27] Larisa M, Laurie E L, Michael G et al. Fabrication of Plastic Microfluid Channels by Imprinting Methods. Anal. Chem. 1997, 69 (23): 4683-4789.
    [28] Jaszewski R W, Schift H, Gobrecht J, Smith P. Hot embossing in polymers as a direct way to pattern resist. Microelectronic Engineering, 1998, 41/42: 575-578.
    [29] 水雯箐.高聚物微流控芯片的制作和分离性质的研究.复旦大学莙政学者论文集,2002:333-347.
    [30] Ong N S, Koh Y H, Fu Y Q. Microlens array produced using hot embossing process. Microelectronic Engineering, 2002, 60 (3-4): 365-379.
    [31] Shen X J, Pan L W, Lin L W. Microplastic embossing process: experimental and theoretical characterizations. Sensors and Actuators, 2002, 97-98: 428-433.
    [32] Juang Y J, M S. Polymer processing and rheological analysis near the glass transition temperature: [dissertation]. The Ohio State University, 2001.
    
    [33] Holger B, Ulf H. Hot embossing as a method for the fabrication of polymer high aspect ratio structures. Sensors and Actuators, 2000, 83 (1-3): 130-135.
    [34] Roos N, Luxbacher T, Glinsner T et al. Nanaoimprint Lithography with a Commercial 4Inch Bond System for Hot Embossing. SPIE'S Microlithography, Santa Clara, CA, 2001.
    [35] Quenzer H J, Schulz A V, Kinkopf T et al. Silicon-silicon anodic bonding with intermediate glass layers using spin on glass. The 11th International Conference on Solid-State Sensors and Actuators, 2001.
    [36] Xiao Z X, Wu G Y, Li Z H et al. Silicon-glass wafer bonding with silicon hydrophilic fusion bonding technology. Sensors and Actuators, 1999, 72 (1): 46-48.
    [37] Berthold A, Nicola L, Sarro P M, Vellekoop M J. Glass-to-glass anodic bonding with standard IC technology thin films as intermediate layers. Sensors and Actuators, 2000, 82 (1-3): 224-228.
    [38] Madou M J, Lee L J, Kurt W et al. Design and fabrication of polymer microfluidic platforms for biomedical applications. ANTEC, 2001: 2534-2538.
    [39] Lee G B, Chen S H, Huang G R, Sung W C, Lin Y H. Microfabricated plastic chips by hot embossing methods and their application for DNA separation and detection. Sensors and Actuators, 2001, 75(3): 147-152.
    [40] Ryan T, Kelly, Adam T et al. Thermal Bonding of Polymeric Capillary Electrophoresis Microdevices in Water. Anal Chem, 2003, 75 (8): 1941-1945.
    [41] Jackman R J, Floyd T M, Ghodssiz R et al. Microfluidic systems with on-line UV detection fabricated in photodefinable epoxy. J Micromech. Microeng, 2001, 11: 1-8.
    [42] 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.高等化学学报,2003,24(11):1962-1966.
    [43] 温敏,王晓东,刘冲等.PMMA微流控芯片微通道热压成形与键合工艺研究.光学精密工程,2004,12(3):272-276.
    [44] Truckenmuller R, Henzi P, Herrmann D et al. A new bonding process for polymer microand nanostructures based on near-surface degradation. IEE MEMS 2004, Maastricht, 2004.
    [45] Arum H, Olivia W. A multi-layer plastic packaging technology for miniaturized bio analysis systems containing integrated electrical and mechanical functionality. 2nd Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine & Biology, Madison, Wisconsin USA, 2002.
    [46] R.M.奥戈凯威斯(英).热塑性塑料的性能和设计.北京:科技出版社,1986.
    [47] 何平笙.高聚物的力学性能.合肥:中国科学技术大学出版社,1997.
    
    [48] Scheer H C, Schulz H. A contribution to the flow behavior of thin polymer films during hot embossing lithography. Microelectronic Engineering, 2001, 56 (3-4): 311-332.
    [49] 王瑁成,邵敏.有限单元法基本原理和数值方法.北京:清华大学出版社,1997.
    [50] 翁中杰,程惠尔.传热学.上海:上海交通大学出版社,1987.
    [51] Kelly S S. Relaxation behavior of the amorphous components of wood. Journal of material science, 1987, 22: 617-624.
    [52] Lin C R, Chen R H, Hung C. Preventing non-uniform shrinkage in open-die hot embossing of PMMA microstmctures. Journal of Materials Processing Technology, 2003, 140 (1-3): 173-178.
    [53] Becker H, Klotzbücher T. Polymer nanowell plates with variable well slope angles. Proc. 3nd International conference on Microreaction Technology, Frankfurt, 1999.
    [54] R(?)tting O, K(?)hler B, Reuther F et al. Production of movable microstructures by aligned hot embossing and reactive ion etching. Proceedings of SPIE 1999, 3680 (2): 1038-1045.
    [55] 张玉龙.粘接技术手册.北京:中国轻工业出版社,2001.
    [56] 李健民,秦莉,帅中意.粘接密封技术.北京:化学工业出版社,2003.

© 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