應用於疾病檢測及新藥物篩檢及開發的過程中，細胞培養扮演著極其重要的角色，不僅是研究初期的研究材料提供者，也是研究末期的成果驗收者。傳統上，細胞培養是一個手動、反覆且耗時的過程。操作者必須經過嚴格訓練及具備相當的操作熟練度，以確保操作步驟的一致性及避免可能的污染問題。而且在培養過程中必須小心地全程控制培養環境，包括培養箱的溫度、二氧化碳含量及培養液的酸鹼值等，以確保每次培養成果的一致性。為了避免可能的人為疏失及全程提供適當的培養環境，以獲得大量且一致的培養成果，大型的研究機構及藥廠皆已採用自動化的細胞培養系統。在實驗室中，一個典型的應用於癌症藥物篩檢過程，是在細胞培養過程的末期給予細胞特定藥物，再從細胞的細胞質或代謝物中檢測是否有預期的目標蛋白質產出。像這樣一個典型藥物篩選的過程需要結合三個機制來完成，包括細胞培養、精確的給藥以及對產出物的取樣及檢測。本論文針對這些機制需求，整合微機電系統技術(micro-electro-mechanical-systems technologies)以及微流體理論(microfluidics)發展出對應的微流體晶片系統，這些晶片系統包括：微流體細胞培養晶片系統(microfluidic cell culture system)、微流體精確給藥晶片(micropipette)及微流體取樣及檢測系統 (microautosampler)。微流體細胞培養系統將整合微型幫浦(micropump)、微型止回閥門(micro check valve)、微型加熱器(microheater)、微型溫度感測器(micro temperature sensor)、微管道(microchannel)等；而微流體取樣及檢測系統將整合可變體積的多樣本取樣及檢測系統(microautosampler)與分流收集系統(microswitch)。
本論文的主要內容將針對上述的微流體晶片及系統，首先進行相關文獻的調查與回顧，並介紹開發過程中所採用的基礎理論與製程，最後針對各種設計參數設定進行性能測試及實際生物應用展出。本研究已經利用所開發的微流體細胞培養系統，於細胞培養箱外，且無二氧化碳供應的環境下，藉由內建的溫度控制系統進行溫度調控，成功地完成人類肺癌細胞(A549)的培養，此細胞培養平台將可廣泛應用於各種貼附型的細胞株(adherent cell)。此細胞培養系統若能整合前述的微流體取樣及檢測系統及微流體精確給藥晶片，就能完成一個應用於藥物分析的微全程分析系統(Micro-Total-Analysis-System)。

Cell culture systems have been widely used as in vitro cell-based models for the evaluation of drugs or diseases. Traditionally, growing a cell culture is a labor-intensive process that requires many hours of repetitive routine work. Furthermore, living cells require that a favorable environment be maintained throughout the whole cell culturing process including cell growth, harvesting, reseeding and analysis. Cell culturing also requires careful control of media conditions in order to maintain viable and consistent cell lines. Experienced personnel are essential to the success of maintaining viable cell lines. In order to improve the consistency of the cell culturing process and to reduce the chances of cell contamination in laboratories that have high volume cell culturing needs, large-scale automated cell culture systems have been used, especially by the pharmaceutical companies. A typical pharmaceutical analysis usually involves a cell culture, drug dosing, and the subsequent analysis and evaluation of the target biomarkers or the relevant biological substances that representing the cell response to the administered drug conditions. To achieve this, several large-scale systems such as cell culture system, a drug dosing system and cell harvesting sampling and detection systems are required. This study will present such systems. These systems are designed based on microfluidic theories, and fabricated using micro-electro- mechanical-systems (MEMS) technologies. The microfluidic cell culture system is comprised of microheaters, a micro temperature sensor, micropumps, microvalves, microchannels, a cell culture area and several reservoirs. Traditional manual cell culture processes can be performed on this chip. A microautosampler capable of performing discrete injection and dispensing of variable-volume samples is integrated with a microswitch to facilitate the continuous monitoring and analysis of multiple bio-samples. Besides, a micropipette capable of precise sampling and variable-volume pipetting is proven feasible for drug dosing at the sub-micro liter level.
The content of this dissertation includes a literature review, an introduction to the theories and methods used to design and fabricate these microfluidic systems and the demonstration of the performance as well as the bio-application of these systems. In this study, we have successfully cultured human lung cancer cells (A549) by using the developed microfluidic cell culture system outside of an incubator. It would be applicable to any adherent cell line. This automatic cell culture system could be eventually integrated with the developed micro auto-sampler and micropipette to form a cell-based, micro-total-analysis-system for pharmaceutical analysis.

[1] Kempner M E and Felder R A 2002 A review of cell culture automation Journal of the Association for Laboratory Automation 7 56-62
[2] Gómez R, Bashir R, Sarikaya A, Ladisch M R, Sturgis J, Robinson J P, Geng T, Bhunia A K, Apple H L and Wereley S 2001 Microfluidic biochip for impedance spectroscopy of biological species Biomedical Microdevices 3 201-209
[3] Gómez R, Bashir R and Bhunia A K 2002 Microscale electronic detection of bacterial metabolism Sensors and Actuators B 86 198-208
[4] Chang W J, Akin D, Sedlak M, Ladisch M R and Bashir R 2003 Poly(dimethylsiloxane) (PDMS) and silicon hybrid biochip for bacterial culture Biomedical Microdevices 5 281-290
[5] Balagaddé F K, You L, Hansen C L, Arnold F H and Quake S R 2005 Long-term monitoring of bacteria undergoing programmed population control in a microchemostat Science 309 137-140
[6] Walker G M, Ozers M S and Beebe D J 2002 Insect cell culture in microfluidic channels Biomedical Microdevices 4 161-166
[7] Yu H, Meyvantsson I, Shkel I A and Beebe D J 2005 Diffusion dependent cell behavior in microenvironments Lab on a Chip 5 1089-1095
[8] Raty S, Davis J A, Beebe D J, Rodriguez-Zas S L and Wheeler M B 2001 Culture in microchannels enhances in vitro embryonic development of preimplantation mouse embryos Theriogenology 55 241
[9] Beebe D, Wheeler M, Zeringue H, Walters E and Raty S 2002 Microfluidic technology for assisted reproduction Theriogenology 57 125-135
[10] Raty S, Walters E M, Davis J, Zeringue H, Beebe D J, Rodriguez-Zax S L and Wheeler M B 2004 Embryonic development in the mouse is enhanced via microchannel culture Lab on a Chip 4 186-190
[11] Powers M J, Domansky K, Kaazempur-Mofrad M R, Kalezi A, Capitano A, Upadhyaya A, Kurzawski P, Wack K E, Stolz D B, Kamm R and Griffith L G 2002 A microfabricated array bioreactor for perfused 3D liver culture Biotechnology and Bioengineering 78 257-269
[12] Borenstein J T, Terai H, King K R, Weinberg E J, Kaazempur-Mofrad M R and Vacanti J P 2002 Microfabrication technology for vascularized tissue engineering, Biomedical Microdevices 4 167-175
[13] Moriguchi H, Wakamoto Y, Sugio Y, Takahashi K, Inoue I and Yasuda K 2002 An agar-microchamber cell-cultivation system: flexible change of microchamber shapes during cultivation by photo- thermal etching Lab on a Chip 2 125-130
[14] Kojima K, Moriguchi H, Hattori A, Kaneko T and Yasuda K 2003 Two-dimensional network formation of cardiac myocytes in agar microculture chip with 1480 nm infrared laser photo-thermal etching Lab on a Chip 3 292-296
[15] Taylor A M, Blurton-Jones M, Rhee S W, Cribbs D H, Cotman C W and Jeon N L 2005 A microfluidic culture platform for CNS axonal injury, regeneration and transport Nature Methods 2 599-605
[16] Tourovskaia A, Figueroa-Masot X and Folch A 2005 Differentiation-on-a-chip: a microfluidic platform for long-term cell culture studies Lab on a Chip 5 14-19
[17] Stangegaard M, Petronis S, Jørgensen A M, Christensen C B V and Dufva M 2006 A biocompatible micro cell culture chamber (μCCC) for the culturing and on-line monitoring of eukaryote cells Lab on a Chip 6 1045-1051
[18] Kaji H, Nishizawa M and Matsue T 2003 Localized chemical stimulation to micropatterned cells using multiple laminar fluid flows Lab on a Chip 3 208-211
[19] Viravaidya K, Sin A and Shuler M L 2004 Development of a microscale cell culture analog to probe naphthalene toxicity Biotechnology Progress 20 316-323
[20] Sin A, Chin K C, Jamil M F, Kostov Y, Rao G and Shuler M L 2004 The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors Biotechnology Progress 20 338-345
[21] Hung P J, Lee P J, Sabounchi P, Lin R and Lee L P 2004 Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays Biotechnology and Bioengineering 89 1-8
[22] Hung P J, Lee P J, Sabounchi P, Aghdam N, Lin R and Lee L P 2005 A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array Lab on a Chip 5 44-48
[23] Chung B G, Flanagan L A, Rhee S W, Schwartz P H, Lee A P, Monuki E S and Jeon N L 2005 Human neural stem cell growth and differentiation in a gradient-generating microfluidic device Lab on a Chip 5 401-406
[24] Laser D J and Santiago J G. 2004 A review of micropumps Journal of Micromechanics and Microengineering 14 R35-R64
[25] Huang C W and Lee G B 2005 Microautosamplers for discrete sample injection and dispensation Electrophoresis 26 1807-1813
[26] Zeng S, Chen C H, Mikkelsen J C and Santiago J G. 2001 Fabrication and characterization of electroosmotic micropumps Sensors and Actuators B 79 107-114
[27] Chen C H and Santiago J G. 2002 A planar electroosmotic micropump Journal of Microelectromechanical Systems 11 672-683
[28] Wang P, Chen Z L and Chang H C 2006 A new electro-osmotic pump based on silica monoliths Sensors and Actuators B 113 500-509
[29] Brask A, Kutter J P and Bruus H 2005 Long-term stable electroosmotic pump with ion exchange membranes Lab on a Chip 5 730-738
[30] Tripp J A, Svec F, Frechet J M J, Zeng S L, Mikkelsen J C and Santiago J G. 2004 High-pressure electroosmotic pumps based on porous polymer monoliths Sensors and Actuators B 99 66-73
[31] Van Lintel H T G, Van de Pol F C M and Bouwstra S 1988 A piezoelectric micropump based on micromachining of silicon Sensors and Actuators A 15 153-167
[32] Koch M, Harris N, Evans A, White N and Brunnschweiler A 1998 A novel micromachined pump based on thick-film piezoelectric actuation Sensors and Actuators A 70 98-103
[33] Nguyen N T and Truong T Q 2004 A fully polymeric micropump with piezoelectric actuator Sensors and Actuators B 97 137-143
[34] Kan J W, Yang Z G, Peng T J, Cheng G M and Wu B 2005 Design and test of a high-performance piezoelectric micropump for drug delivery Sensors and Actuators A 121 156-161
[35] Jeong O C and Yang S S 2000 Fabrication and test of a thermopneumatic micropump with a corrugated p+ diaphragm Sensors and Actuators A 83 249-255
[36] Van de Pol F C M, Van Lintel H T G, Elwenspoek M and Fluitman J H J 1990 Thermopneumatic micropump based on microengineering techniques Sensors and Actuators A 21 198-202
[37] Cooney C G. and Towe B C 2004 A thermopneumatic dispensing micropump Sensors and Actuators A 116 519-524
[38] Zengerle R, Ulrich J, Kluge S, Richter M and Richter A 1995 A bidirectional silicon micropump Sensors and Actuators A 50 81-86
[39] Bourouina T, Bosseboeuf A and Grandchamp J 1997 Design and simulation of an electrostatic micropump for drug-delivery applications, J. Micromechanics and Microengineering 7 186-188
[40] Ng T Y, Jiang T Y, Li H, Lam K Y and Reddy J N 2004 A coupled field study on the non-linear dynamic characteristics of electrostatic micropump Journal of Sound Vibration 273 989-1006
[41] Khoo M and Liu C 2001 Micro magnetic silicone elastomer membrane actuator Sensors and Actuators A 89 259-266
[42] Santra S, Hollaway P and Batich C D 2002 Fabrication and testing of a magnetically actuated micropump Sensors and Actuators B 87 358-364
[43] Yamahata C, Lacharme F and Gijs M A M 2005 Glass valveless micropump using electromagnetic actuation Microelectronic Engineering 78-79 132-137
[44] Hatch A, Kamholz A E, Holman G, Yager P. and Böhringer K F 2001 A ferrofluidic magnetic micropump Journal of Microelectromechanical Systems 10 215-221
[45] Hartshorne H, Backhouse C J and Lee W E 2004 Ferrofluid-based microchip pump and valve Sensors and Actuators B 99 592-600
[46] Yamahata C, Chastellain M, Parashar V K, Petri A, Hofmann H and Gijs M A M 2005 Plastic micropump with ferrofluidic actuation Journal of Microelectromechanical Systems 14 96-102
[47] Unger M A, Chou H P, Thorsen T, Scherer A and Quake S R 2000 Monolithic microfabricated valves and pumps by multilayer soft lithography Science 288 113-116
[48] Wang C H and Lee G B 2005 Automatic bio-sampling chips integrated with micro-pumps and micro-valve for disease detection Biosensors and Bioelectronics 21 419-425
[49] Wang C H and Lee G B 2006 Pneumatically driven peristaltic micropumps utilizing serpentine-shape channels Journal of Micromechanics and Microengineering 16 341-348
[50] Bae B, Kee H, Kim S, Lee Y, Sim T, Kim Y and Park K 2003 In vitro experiment of the pressure regulating valve for a glaucoma implant Journal of Micromechanics and Microengineering 13 613-619
[51] Bae B, Kim N, Kee H, Kim S H, Lee Y, Lee S and Park K 2002 Feasibility test of an electromagnetically driven valve actuator for glaucoma treatment Journal of Microelectromechanical Systems 11 344-54
[52] Takao H, Miyamura K, Ebi H, Ashiki M, Sawada K and Ishida K 2005 A MEMS microvalve with PDMS diaphragm and two-chamber configuration of thermo-pneumatic actuator for integrated blood test system on silicon Sensors and Actuators A 119 468-475
[53] Baechi D and Buser R 2000 Suspension handling system Sensors and Actuators B 63 195-200
[54] Baechi D, Buser R and Dual J 2002 A high density microchannel network with integrated valves and photodiodes Sensors and Actuators A 95 77-83
[55] Kim J H, Na K H, Kang C J, Jeon D and Kim Y S 2004 A disposable thermopneumatic-actuated microvalve stacked with PDMS layers and ITO-coated glass Microelectronic Engineering 73-74 864-869
[56] Tamanaha C R, Whitman L J and Colton R J 2002 Hydric macro-micro fluidics system for a chip-based biosensor Journal of Micromechanics and Microengineering 12 N7-17
[57] Grover W H, Skelley A M, Liu C N, Lagally E T and Mathies R A 2003 Monolithic membrane valves and diaphragm pumps for practical large-scale integration into glass microfluidic devices Sensors and Actuators B 89 315-323
[58] Lagally E T, Scherer J R, Blazej R G, Toriello N M, Diep B A, Ramchandani M, Sensabaugh G F, Riley L W and Mathies R A 2004 Integrated portable genetic analysis microsystem for pathogen/infectious disease detection Analytical Chemistry 76 3162-3170
[59] Ohori T, Shoji S, Miura K and Yotsumoto A 1998 Partly disposable three-way microvalve for a medical micro total analysis system Sensors and Actuators A 64 57-62
[60] Go J S and Shoji S 2004 A disposable, dead volume-free and leak-free in-plane PDMS microvalve Sensors and Actuators A 114 438-444
[61] Kanai M, Abe H, Munaka T, Fujiyama Y, Uchida D, Yamayoshi A, Nakanishi H, Murakamid A and Shoji S 2004 Micro chamber for cellar analysis integrated with negligible dead volume sample injector Sensors and Actuators A 114 129-34
[62] Lee S, Jeong W and Beebe D J 2003 Microfluidic valve with cored glass microneedle for microinjection Lab on a Chip 3 164-167
[63] Baek J Y, Park J Y, Ju J I, Lee T S and Lee S H 2005 A pneumatically controllable flexible and polymeric microfluidic valve fabricated via in situ development Journal of Micromechanics and Microengineering 15 1015-1020
[64] Hosokawa K and Maeda R 2000 A pneumatically-actuated three-way microvalve fabricated with polydimethylsiloxane using the membrane transfer technique Journal of Micromechanics and Microengineering 10 415-420
[65] Unger M A, Chou H-P, Thorsen T, Scherer A and Quake S R 2000 Monolithic microfabricated valves and pumps by multilayer soft lithography Science 288 113-116
[66] Quake S R and Scherer A 2000 From micro to nano fabrication with soft materials Science 290 1536-1540
[67] Studer V, Jameson R, Pellereau E, Pepin A and Chen Y 2004 A microfluidic mammalian cell sorter based on fluorescence detection Microelectronic Engineering 73-74 852-857
[68] Wheeler A R, Throndset W R, Whelan R J, Leach A M, Zare R N, Liao Y H, Farrell K, Manger I D and Daridon A 2003 Microfluidic device for single-cell analysis Analytical Chemistry 75 3581-3586
[69] Wang Y C, Choi M H and Han J 2004 Two-dimensional protein separation with advanced sample and buffer isolation using microfluidic valves Analytical Chemistry 76 4426-4431
[70] Yamahata C, Lacharme F, Burri Y and Gijs M A M 2005 A ball valve micropump in glass fabricated by powder blasting Sensors and Actuators B 110 1-7
[71] Pan T, McDonald S J, Kai E M and Ziaie B 2005 A magnetically driven PDMS micropump with ball check-valves Journal of Micromechanics and Microengineering 15 1021-1026
[72] Yamada M and Seki M 2004 Nanoliter-sized liquid dispenser array for multiple biochemical analysis in microfluidic devices Analytical Chemistry 76 895-899
[73] Duffy D C, Gillis H L, Lin J, Sheppard N F and Kellogg G J 1999 Microfabricated centrifugal microfluidic systems: characterization and multiple enzymatic assays Analytical Chemistry 71 4669-4678
[74] Andersson H, van der Wijngaart W, Griss P, Niklaus F and Stemme G 2001 Hydrophobic valves of plasma deposited octafluorocyclobutane in DRIE channels Sensors and Actuators B 75 136-141
[75] Andersson H, van der Wijngaart W and Stemme G 2001 Micromachined filter-chamber array with passive valves for biochemical assays on beads Electrophoresis 22 249-257
[76] Sung W C, Huang S Y, Liao P C, Lee G B, Li C W and Chen S H 2003 Poly(dimethylsiloxane)-based microfluidic device with electrospray ionization-mass spectrometry interface for protein identification Electrophoresis 24 3648-3654
[77] Hulsman M, Bos M and van der Linden W E 1996 Automated injection of slurry samples in flow-injection analysis Analytic Chimica Acta 324 13-19
[78] Tůma P, Opekar F and Jelínek I 2000 Split-flow injector for capillary zone electrophoresis Journal of Chromatography A 883 223-230
[79] Foster M D, Arnold M A, Nichols J A and Bakalyar S R 2000 Performance of experimental sample injectors for high-performance liquid chromatography microcolumns Journal of Chromatography A 869 231-241
[80] Manz A, Graber N and Widmer H M 1990 Miniaturized total chemical-analysis systems-a novel concept for chemical sensing Sensors and Actuators B1 244-248
[81] Reyes D R, Iossifidis D, Auroux P A and Manz A 2002 Micro total analysis systems. 1. Introduction, theory, and technology Analytical Chemistry 74 2623-2636
[82] Auroux P A, Iossifidis D, Reyes D R and Manz A 2002 Micro total analysis systems. 2. Analytical standard operations and applications Analytical Chemistry 74 2637-2652
[83] Verpoorte E and de Rooij N F 2003 Microfluidics meets MEMS Proceedings of the IEEE 91 930-953
[84] Vilkner T, Janasek D and Manz A 2004 Micro total analysis systems. Recent developments Analytical Chemistry 76 3373-3386
[85] Towns J K and Regnier F E 1992 Impact of polycation addorption on efficiency and electroosmotically driven transport in capillary electrophoresis Analytical Chemistry 64 2473-2478
[86] Long D, Stone H A and Ajdari A 1999 Electroosmotic flows created by surface defects in capillary electrophoresis Journal of Colloid and Interface Science 212 338-349
[87] Harrison D J, Manz A and Glavina P G 1991 Electroosmotic pumping within a chemical sensor system integrated on silicon 1991 International Conference on Solid-State Sensors and Actuators (Transducers ’91) (San Francisco, CA, 24-27 Jun 1991) 792-795
[88] Manz A, Harrison D J, Fettinger J C, Verpoorte E, Ludi M and Widmer H M Integrated electroosmotic pumps and flow manifolds for total chemical analysis systems 1991 International Conference on Solid-State Sensors and Actuators (Transducers ’91) (San Francisco, CA, 24-27 Jun 1991) 939-941
[89] Seller K, Fan Z H and Harrison D J 1994 Electroosmotic pumping and valveless control of fluid flow within a manifold of capillaries on a glass chip Analytical Chemistry 66 3485-3491
[90] Jacobson S C and Ramsey J M 1997 Electrokinetic focusing in microfabricated channel structures Analytical Chemistry 69 3212-3217
[91] Patankar N A and Hu H H 1998 Numerical simulation of electroosmotic flow Analytical Chemistry 70 1870-1881
[92] Jacobson S C, Culbertson C T, Daler J E and Ramsey J M 1998 Microchip structures for submillisecond electrophoresis Analytical Chemistry 70 3476-3480
[93] Jacobson S C, Ermakov S V and Ramsey J M 1999 Minimizing the number of voltage sources and fluid reservoirs for electrokinetic valving in microfluidic devices Analytical Chemistry 71 3273-3276
[94] Ermakov S V, Jacobson S C and Ramsey J M 2000 Computer simulations of electrokinetic injection techniques in microfluidic devices Analytical Chemistry 72 3512-3517
[95] Alarie J P, Jacobson S C, Culbertson C T and Ramsey J M 2000 Effects of the electric field distribution on microchip valving performance Eletrophoresis 21 100-106
[96] Ren L, Sinton D and Li D 2003 Numerical simulation of microfluidic injection processes in crossing microchannels Journal of Micromechanics and Microengineering 13 739-747
[97] Harrison D J, Manz A, Fan Z, Ludi H and Widmer H M 1992 Capillary electrophoresis and sample injection systems integrated on a planar glass chip Analytical Chemistry 64 1926-1932
[98] Effenhauser C S, Maze A and Widmer H M 1993 Glass chips for high-speed capillary electrophoresis separations with submicrometer plate heights Analytical Chemistry 65 2637-2642
[99] Koutny L B, Schmalzing D, Taylor T A and Fuchs M 1996 Microchip electrophoretic immunoassay for serum cortisol Analytical Chemistry 68 18-22
[100] Ocvirk G, Munroe M, Tang T, Oleschuk R, Westra K and Harrison D J 2000 Electrokinetic control of fluid flow in native poly(dimethylsiloxane) capillary electrophoresis devices Electrophoresis 21 107-115
[101] Blom M T, Chmela E, Gardeniers J G E, Tijssen R, Elwenspoek M and van den Berg A 2002 Design and fabrication of a hydrodynamic chromatography chip Sensors and Actuators B 82 111-116
[102] Fu L M, Yang R J, Lee G B and Liu H H 2002 Electrokinetic injection techniques in microfluidic chips Analytical Chemistry 74 5084-5091
[103] Fu L M, Yang R J and Lee G B 2002 Variable-volume-injection methods using electrokinetic focusing on microfluidic chips Journal of Separation Science 25 996-1010
[104] Fu L M, Yang R J and Lee G. B 2003 Electrokinetic focusing injection methods on microfluidic devices Analytical Chemistry 75 1905-1910
[105] Lee G B, Huang C I, Ke B J, Huang G R and Hwei B H 2001 Micromachined pre-focused 1 x N flow switches for continuous sample injection Journal of Micromechanics and Microengineering 11 567-573
[106] Lee G B, Hwei B H and Huang G R 2001 Micromachined pre-focused M x N flow switches for continuous multi-sample injection Journal of Micromechanics and Microengineering 11 654-661
[107] Dittrich P S and Schwille P 2003 An integrated microfluidic system for reaction, high-sensitivity detection, and sorting of fluorescent cells and particles Analytical Chemistry 75 5767-5774
[108] Gass V, van der Schoot B H, Jeanneret S and de Rooij N F 1993 Micro liquid handling using a flow-regulated silicon micropump Journal of Micromechanics and Microengineering 3 214-215
[109] Lannerink T S J, Elwenspoek M and Fluitman J H J Integrated micro-liquid dosing system Proceedings of the IEEE 1993 Micro Electro Mechanical System Workshop( MEMS ’93) (Fort Lauderdale, FL, 7-10 Feb 1993) 254-259
[110] Nguyn N T, Schubert S, Richter S and Dötzel W 1998 Hybrid-assembled micro dosing system using silicon-based micropump/valve and mass flow sensor Sensors and Actuators A 69 85-91
[111] Szita N, Sutter R, Dual J and Buser R A 2001 A micropipettor with integrated sensors Sensors and Actuators A 89 112-118
[112] Kane R, Takayama S, Ostuni E, Ingber D E and Whitesides G M 1999 Patterning proteins and cells using soft lithography Biomaterials 20 2363-2376
[113] Kim E, Xia Y and Whitesides G M 1995 Polymer microstructures formed by moulding in capillaries Nature 376 581-584
[114] Smoluchowski M V 1903 Bulletin International Academy Science (Cracovie, Pologne) 184
[115] Hiemenz, P C 1986 Principles of Colloid and Surface Chemistry. (New York: Marcel Dekker)
[116] Grossman P D and Colburn J C 1992 Capillary Electrophoresis: Theory and Practice (San Diego, CA: Academic Press)
[117] Mammen M, Carbeck J D, Simanek E E and Whitesides G M 1997 Treating electrostatic shielding at the surface of silica as discrete siloxide-cation interactions Journal of the American Chemical Society 119 3469-3476
[118] Zhou M X and Foley J P 2006 Quatitative theory of electroosmotic flow in fused-silica capillaries using an extended site-dissociation site-binding model Analytical Chemistry 78 1849-1858
[119] Timoshenko S and Woinowsky-krieger S 1959 Theory of Plates and Shells (New York: McGraw-Hill)
[120] Kerr A D and Alexander H, 1968 An application of the extended Kantorovich method to the stress analysis of a clamped rectangular plate Acta Mechanica 6 180-196
[121] de Silva C W 1999 Vibration: Fundamentals and Practice (Boca Raton, FL: CRC Press)
[122] Lammerink T S J, Tas N R, Berenschot J W, Elwenspoek M C and Fluitman J H J 1995 Micromachined hydraulic astable multivibrator Proceedings of the IEEE 1995 Micro Electro Mechanical System Workshop (MEMS ’95) (Amsterdam, Netherlands, 29 Jan – 2 Feb 1995) 13-18
[123] Kovacs G T A 2000 Micromachined Transducers Sourcebook (New York: McGraw-Hill)
[124] McNeely M R, Spute M K, Tusneem A and Oliphant A R 1999 Hydrophobic microfluidics The SPIE Conference on Microfluidic Devices and Systems (Santa Clara, California, September 1999) 210-220
[125] Huang C W, Huang S B and Lee G B 2006 Pneumatic micropumps with serially connected actuation chambers Journal of Micromechanics and Microengineering 16 2265-2272
[126] Fujii T 2002 PDMS-based microfluidic devices for biomedical application Microelectronic Engineering 61-62 907-914
[127] Van Oudheusden B W 1999 The determination of the effective ambient temperature for thermal flow sensors in a non-isothermal environment Sensors and Actuators A 72 38-45
[128] Sabatè N, Santander J, Fonseca L, Grãcia I and Canè C 2004 Multi-range silicon micromachined flow sensor Sensors and Actuators A 110 282-288
[129] Hsieh T M, Luo C H, Lee G B, Liao C S and Huang F C 2006 A micromachined low-power-consumption portable PCR system Journal of Medical and Biological Engineering 26 43-49
[130] Xuan X, Sinton D and Li D 2004 Thermal end effects on electroosmotic flow in a capillary International Journal of Heat and Mass Transfer 47 3145-3157
[131] Ross D, Johnson T J and Locascio L E 2001 Imaging of electroosmotic flow in plastic microchannels Analytical Chemistry 73 2509-2515