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研究生: 陳智鈞
Chih-Chun Chen
論文名稱: 開發一適用於高壓下微型過濾晶片
The development of a microfiltration chip in an high operation pressure environment
指導教授: 陳品銓
Pin-Chuan Chen
口試委員: 董奕鐘
Yi-Chung Tung
王孟菊
Meng-Jiy Wang
吳夢楚
Meng-chu Wu
學位類別: 碩士
Master
系所名稱: 工程學院 - 機械工程系
Department of Mechanical Engineering
論文出版年: 2016
畢業學年度: 104
語文別: 中文
論文頁數: 109
中文關鍵詞: 微型過濾晶片利用環形結構增強晶片結合強度螺旋型流道黏合強度。
外文關鍵詞: Increase the bonding strength by ring structure, Spiral microchannel.
相關次數: 點閱:193下載:2
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本研究之主要目的為開發一微型過濾晶片,可以適用在低壓及高壓的操作環境中,整合於晶片中之濾膜為商用濾膜,擁有成本低廉、易於取得的優點,然而此種濾膜材質為與晶片基材不同,在晶片封裝時屬於異質黏合,製程較為複雜。本研究以PMMA作為晶片材料並提出環形結構晶片設計,配合UV光固化膠黏合製程進行黏合,改善橫向洩漏的問題及提升晶片黏合強度;並以螺旋型流道幾何改善檢體於晶片內流動情況,降低檢體流動不順的現象。由於過濾晶片應用領域廣泛,高壓應用的部分,實驗將以黏度較高的矽油做為檢體進行過濾壓力量測,並對於不同流道尺寸之晶片進行黏合強度測試,並分析其影響;低壓應用則以人類全血作為檢體並分析流量、濾膜孔徑、血細胞比容對於血漿與血細胞的分離效率之影響。


Integration a filter into a microfluidic chip with the benefit from the easily selecting of the pore size due to the availability of the market was approached and reported from various studies. One of the major drawbacks of this approach is the leakage between the filter and the polymeric microfluidic chip/microchannel therefore a novel assembly approach to create a microfluidic chip with embedding the filter for sample separation without the leakage was conducted in this study The microchannel was fabricated on the PMMA substrates and the polycarbonate-based filter was sandwiched between PMMA substrates. The bonding between the PMMA substrates was based on UV glue, the UV glue was injected into a designed ring structure around the filter to prevent the leakage across the edge of the filter. Spiral microchannel geometry was designed to improve the flow situation in the flow channel, reducing ineffective filtration area. Several microfluidic chips with various pore size filters were fabricated for experiments. In order to test the functionality of the fabricated chip, various experiments including the bonding strength test, filtration pressure measurement and blood separation experiment were conducted.

目錄 摘要 I Abstract IX 誌謝 XI 目錄 XIII 圖目錄 XVII 表目錄 XXII 符號表 XXIII 第一章 導論 1 1.1研究背景 1 1.2研究動機 3 1.3研究方法 6 1.4論文架構 7 第二章 文獻回顧 9 2.1主動式分離技術 9 2.2被動式分離技術 12 2.2.1柱型過濾(Pillar filter)、掃流式過濾(Crossflow filter) 14 2.2.2堰型過濾(Weir filter) 17 2.2.3濾膜過濾(Membrane filter) 19 第三章 過濾晶片初步設計及結果 21 3.1晶片設計介紹 21 3.2環形結構設計 23 3.3流動情況相關設計 25 第四章 晶片製程介紹 27 4.1 微銑削 27 4.1.1前言 27 4.1.2 操作與使用方法 29 4.2晶片製造 32 4.2.1上蓋、下蓋晶片加工(流道尺寸與銑刀直徑相同) 34 4.2.2上蓋、下蓋晶片加工(流道尺寸與銑刀直徑不同) 37 4.2.3入口流道、出口流道晶片加工 40 4.2.4圓柱母模加工與製作 42 4.2.5聚二甲基矽氧烷圓柱製作 43 4.3晶片黏合 45 4.3.1聚二甲基矽氧烷、塑膠材料化學黏合 45 4.3.2 UV膠黏合 46 第五章 研究設備與實驗方法 49 5.1研究設備 49 5.1.1製程設備與軟體 49 5.1.2量測設備與軟體 54 5.2實驗方法 60 5.2.1過濾晶片功能評估 60 5.2.2過濾壓力量測 62 5.2.3晶片黏合強度測試 64 5.2.4血漿分離實驗 67 5.2.5晶片最大注射量量測 71 第六章 實驗結果與討論 72 6.1過濾晶片功能評估結果 72 6.2過濾壓力量測結果 73 6.2晶片黏合強度結果 75 6.2.1流道寬度及有無環形結構密封對黏合強度之影響 75 6.2.2環形結構寬度-黏合強度之影響 78 6.3血漿分離實驗 80 6.3.1濾膜孔徑與分離效率之影響 81 6.3.2血細胞比容與分離效率之影響 85 6.3.3流量與分離效率之影響 88 6.4晶片最大注射量量測 90 第七章 結論與未來展望 91 7.1結論 91 7.2未來展望 94 參考文獻 96 附錄A 黏合強度實驗數據 104 附錄B 黏合強度實驗數據 105 附錄C血液分析數據(全血) 106 附錄D血液分析數據(Hct25%) 107 附錄E血液分析數據(Hct10%) 108 附錄F血液分析數據(流量) 109

[1] S. C. Terry, J. H. Jerman, J. B. Angell, "A gas chromatographic air analyzer fabricated on a silicon wafer," IEEE Trans. Electron Devices 26, pp. 1880-1886, 1979.
[2] C. T. Wittwer, G. C. Fillmore, D. J. Garling, "Minimizing the time required for DNA amplification by efficient heat transfer to small samples," Analytical Biochemistry 186, pp. 328–331, 1990.
[3] C. T. Wittwer, D. J. Garling, "Rapid cycle DNA amplification: time and temperature optimization," BioTechniques 10, pp. 76–83, 1991.
[4] Lab-on-Chip.gene-quantification.info.Available: http://www.gene-quantification.de/lab-on-chip.html
[5] G. M. Whitesides, "The origins and the future of microfluidics," Nature 442, pp. 368-373, 2006.
[6] D. J. Beebe, G. A. Mensing, G. M. Walker, "Physics and application of microfluidics in biology," Annu. Rev. Biomed. Eng 4, pp. 261-286, 2002.
[7] J. E. Drewes, B. Christopher, O. Matthew, X. Pei, T. U. Kim, A. Gary, "Rejection of wastewater-derived micropollutants in high-pressure membrane applications leading to indirect potable reuse," Environmental Progress 24, pp. 400-409, 2005.
[8] K. Aran, A. Fok, L. A. Sasso, N. Kamdar, Y. Guan, Q. Sun, A. Ündar, J. D. Zahn, "Microfiltration platform for continuous blood plasma protein extraction from whole blood during cardiac surgery," Lab Chip 11, pp. 2858–2868, 2011.

[9] S. Thorslund, O. Klett, F. Nikolajeff, K. Markides, J. Bergquist, "A hybrid poly (dimethylsiloxane) microsystem for on-chip whole blood filtration optimized for steroid screening," Biomed Microdevices 8, pp. 73–79, 2006.
[10] H. Lee, A. M. purdon, R. M. Westervelt, "Manipulation of biological cells using a microelectromagnet matrix," Physics Letters 85, pp.1063-1065, 2004.
[11] Y. F. Anne, S. Charles, S. Axel, H. A. Frances, R. Q. Stephen, "A microfabricated fluorescence-activated cell sorter," Nature biotechnology 17, pp. 1109-1111, 1999.
[12] I. Doh, Y. H. Cho, "A continuous cell separation chip using hydrodynamic dielectrophoresis (DEP) process," Sensor and Actuators A 121, pp. 59-65, 2005.
[13] X. B. Zhang, Z. Q. Wu, K. Wang, J. Zhu, J. J. Xu, X. H. Xia, H. Y. Chen, "Gravitational Sedimentation Induced Blood Delamination for Continuous Plasma Separation on a Microfluidics Chip," Anal. Chem. 84, pp. 3780−3786, 2012.
[14] T. Tachi, N. Kaji, M. Tokeshi, Y. Baba, "Simultaneous separation, metering, and dilution of plasma from human whole blood in a microfluidic system," Anal. Chem . 81, pp. 3194–3198, 2009.
[15] M. Yamada, M.Nakashima ,M. Seki, "Pinched Flow Fractionation:  Continuous Size Separation of Particles Utilizing a Laminar Flow Profile in a Pinched Microchannel,"Anal. Chem. 76, pp. 5465-5471, 2004.
[16] S. Tripathi, A. Prabhakar, N. Kumar, S. G. Singh, A Agrawal, "Blood plasma separation in elevated dimension T-shaped microchannel," Biomedical microdevices, 15(3), pp.415-425, 2013. 
[17] H. M. Ji, V. Samper, Y. Chen, C. K.Heng, T. M. Lim, L. Yobas, " Silicon-based microfilters for whole blood cell eparation," Biomed. Microdevices 10, pp. 251–257, 2008.
[18] Y. C. Kim, S. H. Kim, D. Kim, S. J. Park, J. K. Park, "Plasma extraction in a capillary-driven microfluidic device using surfactant-added poly (dimethylsiloxane) ," Sensors Actuators 145, pp. 861–868, 2010.
[19] Z. Geng, Y. Ju, Q. Wang, W. Wang, Z. Li, "Multi-component continuous separation chip composed of micropillar arrays in a split-level spiral channel," RSC Adv. 3, pp. 14798–14806, 2013.
[20] T. G. Kang, Y. J. Yoon, H. Ji, P. Y. Lim, Y. Chen, "A continuous flow micro filtration device for plasma/blood separation using submicron vertical pillar gap structures," J. Micromech. Microeng. 24, pp.1-5, 2014.
[21] J. M. Li, C. Liu, X. D. Dai, H. H. Chen, Y. Liang, H. L. Sun, H . Tian, X. P. Ding, "PMMA microfluidic devices with three-dimensional features for blood cell filtration," J. Micromech. Microeng. 18, pp. 1-7, 2008.
[22] J. N. Kuo,Y. H. Zhan, "Microfluidic chip for rapid and automatic extraction of plasma from whole human blood,"Microsyst Techno 21, pp. 255–261, 2015.
[23] C. K. Malek and V. Saile, "Applications of LIGA technology to precision manufacturing of high-aspect-ratio micro-components and -systems: a review," Microelectronics Journal 35, pp. 131-143, 2004.
[24] S. C. Terry, J. H. Jerman, and J. B. Angell, "A gas chromatographic air analyzer fabricated on a silicon wafer," Electron Devices, IEEE Transactions on 26, pp. 1880-1886, 1979.
[25] D. J. Harrison, A. Manz, Z. Fan, H. Luedi, and H. M. Widmer, "Capillary electrophoresis and sample injection systems integrated on a planar glass chip," Analytical Chemistry 64, pp. 1926-1932, 1992.
[26] C. H. Ahn, C. Jin-Woo, G. Beaucage, J. H. Nevin, L. Jeong-Bong, A. Puntambekar, et al., "Disposable smart lab on a chip for point-of-care clinical diagnostics, " Proceedings of the IEEE 92, pp. 154-173, 2004.
[27] P. Mela, A. van den Berg, Y. Fintschenko, E. B. Cummings, B. A. Simmons, and B. J. Kirby, "The zeta potential of cyclo-olefin polymer microchannels and its effects on insulative (electrodeless) dielectrophoresis particle trapping devices,"ELECTROPHORESIS 26, pp.1792-1799, 2005.
[28] Y. Yang, C. Li, J. Kameoka, K. H. Lee, and H. G. Craighead, "A polymeric microchip with integrated tips and in situ polymerized monolith for electrospray mass spectrometry," Lab on a Chip 5, pp. 869-876, 2005.
[29] M. Bua, T. Melvin, G.J. Ensell, J.S. Wilkinson, A.G.R. Evans, "A new masking technology for deep glass etching and its microfluidic application," Sensors and Actuators A, 115, pp.476-482, 2004.
[30] A. Berthold, P. M. Sarro, M.J. Vellekoop, "Two-step glass wet-etching for micro-fluidic devices," Proceedings of the SeSens workshop, 2000.
[31] L. Ceriottia, K. Weibleb, N.F. de Rooija, E. Verpoortea, "R ectangular channels for lab-on-a-chip applications," Microelectronic Engineering, 67-68, pp.865-871, 2003.
[32] D. Mijatovic, J.C.T. Eijkel, A. van den Berg, "Technologies for nanofluidic systems: top-down vs. bottom-up—a review," Lab chip, 5, pp.492-500, 2005.
[33] T.D. Boone, Z.H. Fan, H.H. Hooper, A.J. Ricco, H. Tan, S.J. Williams, "Plastic advances microfluidic devices," Anal. Chem., 74, pp. 78A-86A, 2002.

[34] L. Martynova, L.E. Locascio, M. Gaitan, G.W. Kramer, R.G. Christensen, W.A. MacCrehan, "Fabrication of Plastic Microfluid Channels by Imprinting Methods," Anal. Chem., 69, pp.4783-4789, 1997.
[35] H.Takaoa, K. Miyamurab, H. Ebib, M. Ashikia, K. Sawadaa, M. Ishidaa, "A MEMS microvalve with PDMS diaphragm and two-chamber configuration of thermo-pneumatic actuator for integrated blood test," Sensors and Actuators A, 119, pp.468-475, 2005.
[36] J. Melin, N. Roxhed, G. Gimenez, P. Griss, W. van der Wijngaart, G. Stemme, "A liquid-triggered liquid microvalve for on-chip flow control," Sensors and Actuators B, 100, pp.463-468, 2004.
[37] R.Pal, M. Yang, B.N. Johnson, D.T. Burke, M.A. Burns, "Phase Change Microvalve for Integrated Devices," Anal. Chem., 76, pp.3740-3748, 2004.
[38] P. Vulto, T. Huesgen, B. Albrecht, G. A. Urban, "A full-wafer fabrication process for glass microfluidic chips with integrated electroplated electrodes by direct bonding of dry film resist, " J. Micromech. Microeng., 19, 077001, 2009.
[39] B.J. Polk, A. Stelzenmuller, G. Mijares,W. MacCrehanb, M. Gaitan, "Ag/AgCl microelectrodes with improved stability for microfluidics," Sensors and Actuators B, 114, pp.239-247, 2006.
[40] E.T. Enikov, J.G. Boyd, "Electroplated electro-fluidic interconnects for chemical sensors," Sensors and Actuators, 84, pp.161-164, 2000.
[41] J.Y. Cheng, M.H. Yen, C.W. Wei, Y.C. Chuang ,T.H. Young," Crack-free direct-writing on glass using a low-power UV laser in the manufacture of a microfluidic chip," J. Micromech. Microeng, 15, pp.1147-1156, 2005.
[42] C.G.K. Malek, "Laser processing for bio-microfluidics applications (part II), " Anal Bioanal Chem, 385, pp.1362-1369, 2006.
[43] W.C. Jung, Y.M. Heo, G.S. Yoon, K.H. Shin, S.H. Chang, G.H. Kim, M.W. Cho," Micro Machining of Injection Mold Inserts for Fluidic Channel of Polymeric Biochips, " Sensors, 7, pp.1643-1654, 2007.
[44] D.S. Zhao, B. Roy, M.T. McCormick, W.G. Kuhr, S.A. Brazill, "Rapid fabrication of a poly(dimethylsiloxane) microfluidic capillary gel electrophoresis system utilizing high precision machining, " Lab chip, 3, pp.93-99, 2003.
[45] J.S. Mecombera, D. Hurdb, P.A. Limbach, "Enhanced machining of micron-scale features in microchip molding masters by CNC milling, " International Journal of Machine Tools & Manufacture, 45, pp.1542-1550, 2005.
[46] M.L. Huperta, W.J. Guya, S.D. Llopisa, C. Situmaa, S. Rania, D.E. Nikitopoulosa, S. A. Soper, "High-Precision Micromilling for Low-Cost Fabrication of Metal Mold Masters," Proc. of SPIE, 6112, pp.61120B1-12, 2005.
[47] M. Schilling, W. Nigge, A. Rudzinski, A. Neyerb, R. Hergenrödera, "A new on-chip ESI nozzle for coupling of MS with microfluidic devices, " Lab chip, 4, pp.220-224, 2004.
[48] G.S. Fiorini, D.T. Chiu, "Disposable microfluidic devices: fabrication, function, and application, " BioTechniques, 38, pp. 429-446, 2005.
[49] H. D. Rowland and W. P. King, "Polymer deformation and filling modes during microembossing", Journal of Micromechanics and Microengineering, 14, 1625, 2004.
[50] S. K. Sia and G. M. Whitesides,"Microfluidic devices fabricated in poly (dimethylsiloxane) for biological studies", Electrophoresis ,24,3563-3576, 2003.
[51] Y.-C. Su, J. Shah, and L. Lin, "Implementation and analysis of polymeric microstructure replication by micro injection molding", Journal of Micromechanics and Microengineering,14, 415, 2004.
[52] P.C. Chen, C.W. Pan, W.C. Lee, and K.M. Li, "An experimental study of micromilling parameters to manufacture microchannels on a PMMA substrate", The International Journal of Advanced Manufacturing Technology, 71, 1623-1630, 2014.
[53] M.L. Huperta, W.J. Guya, S.D. Llopisa, C. Situmaa, S. Rania, D.E. Nikitopoulosa, S. A. Soper,"High-Precision Micromilling for Low-Cost Fabrication of Metal Mold Masters", Proc. of SPIE, 6112, 61120B1-61120B 12, 2005.
[54] L. Tang and N. Y. Lee, "A facile route for irreversible bonding of plastic-PDMS hybrid microdevices at room temperature", Lab Chip, 10, 1274–1280,2010.
[55] 黃立政, 流體力學原理與應用. 台北市: 全華科技圖書股份有限公司, 2001.
[56] V. Liu, M. Patel and A. Lee, "A microfludic device for blood cell sorting and morphology analysis", 978-0-9798064-6-9/μTAS 2013.
[57] S. Tripathi, Y. V. Bala Varun Kumarl, A. Prabhakar, S. S. Joshi and A. Agrawal, "Performance study of microfluidic devices for blood plasma separation-a designer’s perspective", J. Micromech. Microeng. 25 , 2015.

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