本文研究實驗所設計之電容耦合晶片不需額外輸入能量，利用玻璃材料親水的特性產生毛細力作為驅動源，讓流體在微流道中達到自驅動。導入交流電和透過晶片上下蓋之電極不同幾何形狀設計，在微流道中產生不均勻電場，促使血液中紅血球在微流道裡極化，進而增加紅血球間的粒子作用力，由於紅血球間作用力增加的影響，紅血球會有聚集的現象形成血球團因而使得流速降低，搭配毛細力的推動，紅血球團與血漿產生流速上的差異，於此紅血球與血漿的分離作用。而值得一提的是，本實驗中所使用之血液樣本是未經過任何稀釋動作，即為全血。之後更在晶片微流道尾端內濺鍍上鉑感應電極，檢測分離後血漿內血糖之濃度搭建生醫重點照顧檢測平台之可能性與可行性。
由實驗結果得知，此一電容耦合晶片有良好的長時效自驅動能力，即使是高黏滯流體血液也能輕易推動。當血液注入晶片後，施加電壓使得微流道內產生不均勻之電場，可以觀察到血球因極化後之間作用力增強，產生聚集的現象。透過改變電壓(1~3 V)和改變頻率(500 kHz~10 MHz)量測發現血液平均分離時間上有明顯的改變。之後在不同血液流速下施加電壓發現，血液平均分離時間也有明顯隨之改變的變化。最後為了檢測此晶片之有效作用，透過創新分析方法得出此晶片擁有高血漿產率、高血球與血漿分離效率，約90%，與高血球與血漿分離品質，約89.4%。而這些實驗結果證明了低電壓電容耦合非接觸式微流體血液晶片可確實用於血液分離的應用，配合後續結合的血漿內血糖濃度檢測，實現了生醫重點照顧檢測的核心定義，結合『驅動』、『應用』與『檢測』於一小型實驗晶片內。

The core value of point-of-care is to create a platform that combines many critical techniques in a micro-chip included “transportation”, “application” and “detection” which is the goal of this thesis. A plasma separating biochip is designed and demonstrated using capillary-driven contactless capacitively-coupled method. The long-term capillary drive force was produced by hydrophilic surface of the chip. With low voltage (~1 V) and high frequency induced electrostatics between the red blood cells. The polarized red blood cells were aggregated and separated from plasma with high volume separation and 89.4% removal rate of red blood cells. Combined the Pt detect electrode in the very end of the channel, the glucose concentration in the separated plasma was detected with good results.

[1] W. F. Huang, Q. S. Liu, and Y. Li, "Capillary filling flows inside patterned-surface microchannels," Chemical Engineering & Technology, vol. 29, pp. 716-723, Jun 2006.
[2] J. Darabi, M. Rada, M. Ohadi, and J. Lawler, "Design, fabrication, and testing of an electrohydrodynamic ion-drag micropump," Journal of Microelectromechanical Systems, vol. 11, pp. 684-690, Dec 2002.
[3] C. C. Wong, D. R. Adkins, and D. Chu, "Development of a micropump for microelectronic cooling," Micro-Electro-Mechanical Systems (MEMS). 1996 International Mechanical Engineering Congress and Exposition, pp. 239-244, 1996 1996.
[4] Z. W. Zhang, X. J. Feng, Q. M. Luo, and B. F. Liu, "Environmentally friendly surface modification of PDMS using PEG polymer brush," Electrophoresis, vol. 30, pp. 3174-3180, Sep 2009.
[5] A. Si-Hong and K. Yong-Kweon, "Fabrication and experiment of a planar micro ion drag pump," Sensors and Actuators A (Physical), vol. A70, pp. 1-5, 1 1998.
[6] A. Furuya, F. Shimokawa, T. Matsuura, and R. Sawada, "Fabrication of fluorinated polyimide microgrids using magnetically controlled reactive ion etching (MC-RIE) and their applications to an ion drag integrated micropump," Journal of Micromechanics and Microengineering, vol. 6, pp. 310-319, Sep 1996.
[7] S. H. Yao, D. E. Hertzog, S. L. Zeng, J. C. Mikkelsen, and J. G. Santiago, "Porous glass electroosmotic pumps: design and experiments," Journal of Colloid and Interface Science, vol. 268, pp. 143-153, Dec 2003.
[8] D. J. Laser and J. G. Santiago, "A review of micropumps," Journal of Micromechanics and Microengineering, vol. 14, pp. R35-R64, Jun 2004.
[9] S. Bouaidat, O. Hansen, H. Bruus, C. Berendsen, N. K. Bau-Madsen, P. Thomsen, et al., "Surface-directed capillary system; theory, experiments and applications," Lab on a Chip, vol. 5, pp. 827-836, 2005.
[10] A. A. Kornyshev, A. R. Kucernak, M. Marinescu, C. W. Monroe, A. E. S. Sleightholme, and M. Urbakh, "Ultra-Low-Voltage Electrowetting," Journal of Physical Chemistry C, vol. 114, pp. 14885-14890, Sep 2010.
[11] Y. Y. Lin, R. D. Evans, E. Welch, B. N. Hsu, A. C. Madison, and R. B. Fair, "Low voltage electrowetting-on-dielectric platform using multi-layer insulators," Sensors and Actuators B-Chemical, vol. 150, pp. 465-470, Sep 2010.
[12] D. S. Lee, J. S. Ko, and Y. T. Kim, "Bidirectional pumping properties of a peristaltic piezoelectric micropump with simple design and chemical resistance," Thin Solid Films, vol. 468, pp. 285-290, Dec 2004.
[13] T. Y. Ng, T. Y. Jiang, H. Li, K. Y. Lam, and J. N. Reddy, "A coupled field study on the non-linear dynamic characteristics of an electrostatic micropump," Journal of Sound and Vibration, vol. 273, pp. 989-1006, Jun 2004.
[14] M. M. Teymoori and E. Abbaspour-Sani, "Design and simulation of a novel electrostatic peristaltic micromachined pump for drug delivery applications," Sensors and Actuators a-Physical, vol. 117, pp. 222-229, Jan 2005.
[15] O. Francais and I. Dufour, "Dynamic simulation of an electrostatic micropump with pull-in and hysteresis phenomena," Sensors and Actuators a-Physical, vol. 70, pp. 56-60, Oct 1998.
[16] E. Makino, T. Shibata, and K. Kato, "Dynamic thermo-mechanical properties of evaporated TiNi shape memory thin film," Sensors and Actuators a-Physical, vol. 78, pp. 163-167, Dec 1999.
[17] E. Makino, T. Mitsuya, and T. Shibata, "Fabrication of TiNi shape memory micropump," Sensors and Actuators a-Physical, vol. 88, pp. 256-262, Mar 2001.
[18] A. Machauf, Y. Nemirovsky, and U. Dinnar, "A membrane micropump electrostatically actuated across the working fluid," Journal of Micromechanics and Microengineering, vol. 15, pp. 2309-2316, Dec 2005.
[19] M. Koch, N. Harris, A. G. R. Evans, N. M. White, and A. Brunnschweiler, "A novel micromachined pump based on thick-film piezoelectric actuation," Sensors and Actuators a-Physical, vol. 70, pp. 98-103, Oct 1998.
[20] S. Bohm, W. Olthuis, and P. Bergveld, "A plastic micropump constructed with conventional techniques and materials," Sensors and Actuators a-Physical, vol. 77, pp. 223-228, Nov 1999.
[21] J. H. Tsai and L. W. Lin, "A thermal-bubble-actuated micronozzle-diffuser pump," Journal of Microelectromechanical Systems, vol. 11, pp. 665-671, Dec 2002.
[22] M. Elwenspoek, T. S. J. Lammerink, R. Miyake, and J. H. J. Fluitman, "Towards Integrated Microliquid Handling Systems," Journal of Micromechanics and Microengineering, vol. 4, pp. 227-245, Dec 1994.
[23] L. D. Qin, O. Vermesh, Q. H. Shi, and J. R. Heath, "Self-powered microfluidic chips for multiplexed protein assays from whole blood," Lab on a Chip, vol. 9, pp. 2016-2020, 2009.
[24] S. H. Ahn and Y. K. Kim, "Fabrication and experiment of a planar micro ion drag pump," Sensors and Actuators a-Physical, vol. 70, pp. 1-5, Oct 1998.
[25] S. Mukhopadhyay, S. S. Roy, A. Mathur, M. Tweedie, and J. A. McLaughlin, "Experimental study on capillary flow through polymer microchannel bends for microfluidic applications," Journal of Micromechanics and Microengineering, vol. 20, p. 055018, May 2010.
[26] H. A. Pohl and J. S. Crane, "Dielectrophoresis Of Cells," Biophysical Journal, vol. 11, pp. 711-&, 1971.
[27] E. Du and S. Manoochehri, "Electrohydrodynamic-mediated dielectrophoretic separation and transport based on asymmetric electrode pairs," Electrophoresis, vol. 29, pp. 5017-5025, Dec 2008.
[28] J. T. Huang, G. C. Wang, K. M. Tseng, and S. B. Fang, "A chip for catching, separating, and transporting bio-particles with dielectrophoresis," Journal of Industrial Microbiology & Biotechnology, vol. 35, pp. 1551-1557, Nov 2008.
[29] S. K. Srivastava, P. R. Daggolu, S. C. Burgess, and A. R. Minerick, "Dielectrophoretic characterization of erythrocytes: Positive ABO blood types," Electrophoresis, vol. 29, pp. 5033-5046, Dec 2008.
[30] H. H. Cui, J. Voldman, X. F. He, and K. M. Lim, "Separation of particles by pulsed dielectrophoresis," Lab on a Chip, vol. 9, pp. 2306-2312, 2009.
[31] P. R. C. Gascoyne, J. Noshari, T. J. Anderson, and F. F. Becker, "Isolation of rare cells from cell mixtures by dielectrophoresis," Electrophoresis, vol. 30, pp. 1388-1398, Apr 2009.
[32] Y. Nakashima, S. Hata, and T. Yasuda, "Blood plasma separation and extraction from a minute amount of blood using dielectrophoretic and capillary forces," Sensors and Actuators B-Chemical, vol. 145, pp. 561-569, Mar 2010.
[33] B. Cetin and D. Q. Li, "Dielectrophoresis in microfluidics technology," Electrophoresis, vol. 32, pp. 2410-2427, Sep 2011.
[34] S. H. Liao, I. F. Cheng, and H. C. Chang, "Precisely sized separation of multiple particles based on the dielectrophoresis gradient in the z-direction," Microfluidics and Nanofluidics, vol. 12, pp. 201-211, Jan 2012.
[35] Y. Demircan, E. Ozgur, and H. Kulah, "Dielectrophoresis: Applications and future outlook in point of care," Electrophoresis, vol. 34, pp. 1008-1027, Apr 2013.
[36] M. Kersaudy-Kerhoas and E. Sollier, "Micro-scale blood plasma separation: from acoustophoresis to egg-beaters," Lab on a Chip, vol. 13, pp. 3323-3346, 2013.
[37] M. Li, S. Li, W. Li, W. Wen, and G. Alici, "Continuous manipulation and separation of particles using combined obstacle- and curvature-induced direct current dielectrophoresis," Electrophoresis, vol. 34, pp. 952-960, Apr 2013.
[38] Y. Takahashi, S. Takeuchi, and S. Miyata, "High throughput cell sorting device using dielectrophoresis and fluid-induced shear force," 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 4466-4469, 2013 2013.
[39] S. Y. Tang, W. Zhang, P. Yi, S. Baratchi, K. Kalantar-zadeh, and K. Khoshmanesh, "Reorientation of microfluidic channel enables versatile dielectrophoretic platforms for cell manipulations," Electrophoresis, vol. 34, pp. 1407-1414, May 2013.
[40] H. Yun, K. Kim, and W. G. Lee, "Cell manipulation in microfluidics," Biofabrication, vol. 5, p. 022001, Jun 2013.
[41] N. C. Chen, C. H. Chen, M. K. Chen, L. S. Jang, and M. H. Wang, "Single-cell trapping and impedance measurement utilizing dielectrophoresis in a parallel-plate microfluidic device," Sensors and Actuators B-Chemical, vol. 190, pp. 570-577, Jan 2014.
[42] T. A. Crowley and V. Pizziconi, "Isolation of plasma from whole blood using planar microfilters for lab-on-a-chip applications," Lab on a Chip, vol. 5, pp. 922-929, 2005.
[43] M. Yamada and M. Seki, "Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics," Lab on a Chip, vol. 5, pp. 1233-1239, 2005.
[44] Y. Gu and N. Miki, "A microfilter utilizing a polyethersulfone porous membrane with nanopores," Journal of Micromechanics and Microengineering, vol. 17, pp. 2308-2315, Nov 2007.
[45] X. Chen, D. F. Cui, C. C. Liu, and H. Li, "Microfluidic chip for blood cell separation and collection based on crossflow filtration," Sensors and Actuators B-Chemical, vol. 130, pp. 216-221, Mar 2008.
[46] J. S. Shim, A. W. Browne, and C. H. Ahn, "An on-chip whole blood/plasma separator with bead-packed microchannel on COC polymer," Biomedical Microdevices, vol. 12, pp. 949-957, Oct 2010.
[47] M. M. Gong, B. D. MacDonald, T. V. Nguyen, K. V. Nguyen, and D. Sinton, "Field tested milliliter-scale blood filtration device for point-of-care applications," Biomicrofluidics, vol. 7, p. 044111, Jul 2013.
[48] S. Chang and Y. H. Cho, "A continuous size-dependent particle separator using a negative dielectrophoretic virtual pillar array," Lab on a Chip, vol. 8, pp. 1930-1936, 2008.
[49] J. Takagi, M. Yamada, M. Yasuda, and M. Seki, "Continuous particle separation in a microchannel having asymmetrically arranged multiple branches," Lab on a Chip, vol. 5, pp. 778-784, 2005.
[50] A. Oki, M. Takai, H. Ogawa, Y. Takamura, T. Fukasawa, J. Kikuchi, et al., "Healthcare chip for checking health condition from analysis of trace blood collected by painless needle," Japanese Journal of Applied Physics Part 1-Regular Papers Short Notes & Review Papers, vol. 42, pp. 3722-3727, Jun 2003.
[51] T. Kobayashi, T. Funamoto, M. Hosaka, and S. Konishi, "Centrifugal Separation Device Based on Two-Layer Laminar Flow in Microchannels for High-Throughput and Continuous Blood Cell/Plasma Separation," Japanese Journal of Applied Physics, vol. 49, pp. 077001- 5, 2010.
[52] J. Sun, C. Liu, M. Li, J. Wang, Y. Xianyu, G. Hu, et al., "Size-based hydrodynamic rare tumor cell separation in curved microfluidic channels," Biomicrofluidics, vol. 7, p. 011802, Jan 2013.
[53] K. H. Han and A. B. Frazier, "Paramagnetic capture mode magnetophoretic microseparator for high efficiency blood cell separations," Lab on a Chip, vol. 6, pp. 265-273, Feb 2006.
[54] B. Y. Qu, Z. Y. Wu, F. Fang, Z. M. Bai, D. Z. Yang, and S. K. Xu, "A glass microfluidic chip for continuous blood cell sorting by a magnetic gradient without labeling," Analytical and Bioanalytical Chemistry, vol. 392, pp. 1317-1324, Dec 2008.
[55] J. S. Shim and C. H. Ahn, "An on-chip whole blood/plasma separator using hetero-packed beads at the inlet of a microchannel," Lab on a Chip, vol. 12, pp. 863-866, 2012.
[56] A. I. Rodriguez-Villarreal, M. Arundell, M. Carmona, and J. Samitier, "High flow rate microfluidic device for blood plasma separation using a range of temperatures," Lab on a Chip, vol. 10, pp. 211-219, 2010.
[57] S. H. Liao, C. Y. Chang, and H. C. Chang, "A capillary dielectrophoretic chip for real-time blood cell separation from a drop of whole blood," Biomicrofluidics, vol. 7, p. 024110, Mar 2013.
[58] K. K. Lee and C. H. Ahn, "A new on-chip whole blood/plasma separator driven by asymmetric capillary forces," Lab on a Chip, vol. 13, pp. 3261-3267, 2013.
[59] T. J. Cheng, H. C. Chang, and T. M. Lin, "A piezoelectric quartz crystal sensor for the determination of coagulation time in plasma and whole blood," Biosensors & Bioelectronics, vol. 13, pp. 147-156, Feb 1998.
[60] H. Song, H. W. Li, M. S. Munson, T. G. Van Ha, and R. F. Ismagilov, "On-chip titration of an anticoagulant argatroban and determination of the clotting time within whole blood or plasma using a plug-based microfluidic system," Analytical Chemistry, vol. 78, pp. 4839-4849, Jul 2006.
[61] M. Zimmermann, H. Schmid, P. Hunziker, and E. Delamarche, "Capillary pumps for autonomous capillary systems," Lab on a Chip, vol. 7, pp. 119-125, 2007.
[62] M. Wolf, R. Gulich, P. Lunkenheimer, and A. Loidl, "Broadband dielectric spectroscopy on human blood," Biochimica Et Biophysica Acta-General Subjects, vol. 1810, pp. 727-740, Aug 2011.
[63] 李政庭, "毛細力微流體晶片的製作與在血液凝固檢測的應用，成功大學碩士論文," 2011.
[64] 陳育聖, "新型菱形混合器與毛細驅動晶片設計與製作，成功大學碩士論文," 2009.
[65] C. K. Chung, Y. C. Sung, G. R. Huang, E. J. Hsiao, W. H. Lin, and S. L. Lin, "Crackless linear through-wafer etching of Pyrex glass using liquid-assisted CO2 laser processing," Applied Physics a-Materials Science & Processing, vol. 94, pp. 927-932, Mar 2009.
[66] 張恩旗, "毛細力驅動流體晶片的設計和混合應用，成功大學碩士論文," 2010.
[67] R. Pethig and D. B. Kell, "The Passive Electrical-Properties Of Biological-systems - Their Significance In Physiology, Biophysics And Biotechnology," Physics in Medicine and Biology, vol. 32, pp. 933-970, Aug 1987.
[68] L. N. M. DUYSENS, "The flattering of the absorption spectrum of suspensions, as compared to that of solutions," Biochimica et Biophysica Acta, vol. 19, pp. 1–12, 1956.
[69] M. D. B. Daniel C. Harris, "Symmetry and Spectroscopy: An Introduction to Vibrational and Electronic Spectroscopy," 1978.