簡易檢索 / 詳目顯示

研究生: 洪家緯
Hung, Chia-Wei
論文名稱: 利用鎳鈀合金微孔洞薄膜過濾晶片收集血漿之研究
Study of Blood Plasma Collection by Using Ni-Pd Alloy Micro-porous Membrane Filtration Chips
指導教授: 林裕城
Lin, Yu-Cheng
學位類別: 碩士
Master
系所名稱: 工學院 - 工程科學系
Department of Engineering Science
論文出版年: 2011
畢業學年度: 100
語文別: 中文
論文頁數: 127
中文關鍵詞: 微電鑄技術鎳鈀合金微孔洞薄膜過濾晶片過濾率
外文關鍵詞: micro-electroforming technology, Ni-Pd alloy micro-porous membrane, filtration chip, filtration rate
相關次數: 點閱:78下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 本研究成功開發鎳鈀合金微孔洞薄膜過濾晶片,並以此晶片將血球(Blood cells)與血漿(Plasma)分離。研究策略是利用掃流過濾(Cross flow filtration)來分離血液中的血球細胞,掃流過濾的原理是當流體平行流經過濾薄膜平面,而產生平行剪應力來掃除堆積於過濾薄膜表面的粒子,使得小於濾膜孔徑的分子隨著時間仍能維持高濾速穿過濾膜,而不增加操作阻力。本實驗利用微機電製程技術 (Micro electro mechanical systems, MEMS)製作出聚二甲基矽氧烷(Polydimethylsiloxane, PDMS)掃流區晶片及收集區晶片,而鎳鈀合金微孔洞薄膜則使用微電鑄技術(Micro-electroforming)製作,最後將鎳鈀合金微孔洞薄膜與PDMS晶片結合,即完成鎳鈀合金微孔洞薄膜過濾晶片。本研究將對不同全血稀釋倍數(10倍、5倍、3倍、2倍及未稀釋)、不同薄膜孔徑(1 µm、2 µm、4 µm、7 µm及10 µm)及不同流量(1 mL/min、3 mL/min、5 mL/min、7 mL/min及10 mL/min)去進行血球過濾率的探討。由實驗結果發現,當薄膜孔徑為2 µm且流量達到10 mL/min的情況下,則血球過濾率則可達最佳過濾率96.2%,所以鎳鈀合金微孔洞薄膜孔徑及流量大小對於血球過濾率有影響性。最後,本鎳鈀合金微孔洞薄膜過濾晶片以免疫球蛋白E(Immunoglobulin E, IgE)過敏患者血液作為臨床檢測分析目標,以酵素免疫分析方法(Enzyme-linked immunosorbent assay, ELISA)分別對傳統離心機與過濾晶片分離出的血漿進行呈色分析,結果顯示上述兩種血液分離方法所分離出的患者血漿具有相同的檢測趨勢。本研究所開發的過濾晶片有別於一般傳統離心機與過濾晶片,用於分離血球與血漿有著良好的過濾效果,可在短時間完成過濾,並具備不易阻塞、不易溶血(Hemolysis)、低成本及容易操作等優點。

    This study successfully develops the nickel-palladium alloy micro-porous membrane filtration chip and utilizes the chip to separate blood cells and blood plasma. The filtration chip is based on the cross flow filtration, and the fluid flows parallel to the membrane, and it generates parallel shear stress to remove the clogging microparticles on the membrane. The Ni-Pd alloy micro-porous membrane filtration chip uses MEMS process and casting molding to manufacture polydimethylsiloxane (PDMS) cross flow chip and reservoir chip. Then, combined Ni-Pd alloy micro-porous membrane with PDMS chips, in addition, the membrane is manufactured by micro-electroforming process. This study was discussed the filtration rate under different blood dilution times(original, 2X, 3X, 5X and 10X), different membrane pore sizes(1 µm, 2 µm, 4 µm, 7 µm and 10 µm) and different flow rates(1 mL/min, 3 mL/min, 5 mL/min, 7 mL/min and 10 mL/min). When the flow rate is 10 mL/min and pore size is 2 µm, the filtration rate is up to 96.2%. Finally, this study is focused on IgE allergy blood sample separation, and is compared centrifuge with filtration chip by ELISA, and the results of filtration chip have the same trend with centrifuge. This study is different to other filtration chip that it can rapidly finish separation, and avoid clogging and hemolysis, and has great effect on blood cells and plasma separation from the experimental results.

    摘要 I ABSTRACT III 縮寫表 V 符號表 VII 致謝 VIII 目錄 IX 表目錄 XIII 圖目錄 XV 第一章 緒論 1 1-1 血球與血漿分離晶片的重要性 2 1-2 微流體晶片的發展與應用 4 1-2-1 微機電系統技術與微流體晶片 4 1-2-2 微流體晶片之製程技術 6 1-3 文獻回顧 9 1-3-1 人類血液組成 9 1-3-2 微型分選過濾機制 11 1-3-3 薄膜過濾系統 19 1-3-3-1 過濾薄膜分類 19 1-3-3-2 多層過濾 20 1-3-3-3 掃流過濾 22 1-4 研究動機與目的 24 1-5 研究架構 25 第二章 過濾晶片之設計與製作 27 2-1 鎳鈀合金微孔洞薄膜設計與製作 27 2-2 多層過濾晶片設計 32 2-3 多層過濾晶片製作 34 2-4 掃流過濾晶片光罩設計與母模製作 42 2-4-1 掃流區及收集區晶片光罩設計 42 2-4-2 掃流區及收集區晶片母模製作 45 2-5 PDMS灌注成形與翻製流程 53 2-6 掃流過濾晶片接合與封裝 57 第三章 實驗與研究方法 60 3-1 實驗儀器與設備 60 3-1-1 倒立式螢光光學顯微鏡 60 3-1-2 正立式光學顯微鏡 61 3-1-3 微量注射幫浦 62 3-1-4 真空抽氣系統 63 3-1-5 流式細胞儀 64 3-1-5-1 流式細胞儀原理 64 3-1-5-2 流式細胞儀資料分析 66 3-1-6 細胞計數盤 68 3-2 實驗藥品 71 3-3 實驗方法 71 3-3-1 多層過濾分離實驗 72 3-3-2 掃流過濾分離實驗 73 3-3-2-1 影響掃流過濾的因素 74 3-3-2-2 不同全血稀釋倍數對血球過濾率之實驗 76 3-3-2-3不同薄膜孔徑對血球過濾率之實驗 76 3-3-2-4不同過濾流量對血球過濾率之實驗 77 3-3-2-5 IgE過敏血液檢測實驗 78 第四章 結果與討論 80 4-1 利用多層過濾晶片於膠體微粒溶液過濾 80 4-1-1 過濾實驗定性分析 81 4-1-2 流式細胞儀定量分析 83 4-1-3 多層過濾晶片於全血分離之結果討論 87 4-2 利用掃流過濾晶片於膠體微粒溶液過濾 88 4-2-1 流式細胞儀定量分析 88 4-3 利用掃流過濾晶片於血球與血漿分離 90 4-3-1 不同全血稀釋倍數與血球過濾率之探討 91 4-3-2 不同微孔洞薄膜孔徑與血球過濾率之探討 96 4-3-3 不同流量與血球過濾率之探討 101 4-3-4 不同全血稀釋倍數與血漿收集量之探討 104 4-3-5 不同微孔洞薄膜孔徑與血漿收集量之探討 107 4-3-6 不同流量與血漿收集量之探討 111 4-4 傳統離心法與晶片分離之比較 113 第五章 結論與建議 116 5-1 結論 116 5-2 建議 119 參考文獻 120 自述 127

    [1] J. B. Lee, J. English, C. H. Ahn, and M. G. Allen, “Planarization techniques for vertically integrated metallic MEMS on silicon foundry circuits,” Journal of Micromechanics and Microengineering, vol. 7, pp. 44-54, 1997.
    [2] M. Yano, F. Yamagishi, and T. Tsuda, “Optical MEMS for photonic switching-compact and stable optical crossconnect switches for simple, fast, and flexible wavelength applications in recent photonic networks,” IEEE Journal of Selected Topics in Quantum Electronics, vol. 11, pp. 383-394, 2005.
    [3] C. L. Goldsmith, Z. M. Yao, S. Eshelman, and D. Denniston, “Performance of low-loss RF MEMS capacitive switches,” IEEE Microwave and Guided Wave Letters, vol. 8, pp. 269-271, 1998.
    [4] A. C. R. Grayson, R. S. Shawgo, A. M. Johnson, N. T. Flynn, Y. W. Li, M. J. Cima, and R. Langer, “A BioMEMS review: MEMS technology for physiologically integrated devices,” Proceedings of the IEEE, vol. 92, pp. 6-21, 2004.
    [5] P. Hernández, L. Cortina, H. Artaza, N. Pol, R. M. Lam, E. Dorticós, C. Macías, C. Hernández, L. del Vall, A. Blanco, A. Martínez, and F. Díaz, “Autologous bone-marrow mononuclear cell implantation in patients with severe lower limb ischaemia: A comparison of using blood cell separator and Ficoll density gradient centrifugation,” Atherosclerosis, vol. 194, pp. 52-56, 2007.
    [6] K. Seiler, D. J. Harrison and A. Manz, “Planar chips technology for miniaturization and integration of separation techniques into monition systems,” Journal of Chromatography, vol. 593, pp. 253-258, 1992.
    [7] Y. N. Xia and G. M. Whitesides, “Soft lithography,” Angewandte Chemie-International Edition, vol. 37, pp. 551-575, 1998.
    [8] L. Martynova, L. E. Locascio, M. Gaitan, G. W. Kramer, R. G. Christensen, and W. A. MacCrehan, “Fabrication of plastic microfluid channels by imprinting methods,” Analytical Chemistry, vol. 69, pp. 4783-4789, 1997.
    [9] H. Becker and U. Heim, “Polymer hot embossing with silicon master structures,” Sensors and Materials, vol. 11, pp. 297-304, 1999.
    [10] M. Heckele, W. Bacher, and K. D. Muller, “Hot embossing - The molding technique for plastic microstructures,” Microsystem Technologies, vol. 4, pp. 122-124, 1998.
    [11] H. Becker and U. Heim, “Hot embossing as a method for the fabrication of polymer high aspect ratio structures,” Sensors and Actuators A-Physical, vol. 83, pp. 130-135, 2000.
    [12] D. Snakenborg, H. Klank and J. P. Kutter, “Microstructure fabrication with a CO2 laser system,” Journal of Micromechanics and Microengineering, vol. 14, pp. 182-189, 2004.
    [13] K. S. Huang, T. H. Lai and Y. C. Lin, “Manipulating the generation of ca-alginate microspheres using microfluidic channels as a carrier of gold nanoparticles,” Lab on a Chip, vol. 6, pp. 954-957, 2006.
    [14] K. S. Huang, T. H. Lai, Y. C. Lin, “Using a microfluidic chip and internal gelation reaction for monodisperse calcium alginate microparticles generation,” Frontiers in Bioscience, vol. 12, pp. 3061-3067, 2006.
    [15] R. M. McCormick, R. J. Nelson, M. G. AlonsoAmigo, J. Benvegnu, and H. Hooper, “Microchannel electrophoretic separations of DNA in injection-molded plastic substrates,” Analytical Chemistry, vol. 69, pp. 2626-2630, 1997.
    [16] H. Arjomandi, S. Barcelona, S. Gallocher, M. Vallejo, “Biofluid dynamics of the human circulatory system,” Congress on Biofluid Dynamics of Human Body Systems at Biomedical Engineering, 2003.
    [17] S. Metz, C. Trautmann, A. Bertsch, and P. Renaud, “Flexible microchannels with integrated nanoporous membranes for filtration and separation of moleculles and particles,” Proc. IEEE 17th International MEMS Conference (IEEE MEMS 2004), pp. 81-84, 2002.
    [18] X. Chen, D. F. Cui, C. C. Liu, H. Li, “Microfluidic chip for blood cell separation and collection based on crossflow filtration,” Sensors and Actuators B-Chemical, vol. 130, pp. 216–221, 2008.
    [19] C. Blattert, R. Jurischka, I. Tahhan, A. Schoth, P. Kerth, and W. Menz, “Separation of blood in microchannel bends,” Proceedings of the 26th Annual International Conference of the IEEE EMBS, CA, USA, 2004.
    [20] M. J. Madou, L. J. Lee, S. Daunert, S. Lai, and C. H. Shih, “Design and fabrication of CD-like microfluidic platforms for diagnostic: microfluidic functions,” Biomedical Microdevices, vol. 3, pp. 245-254, 2001.
    [21] M. H. Moon, S. G. Yang, J. Y. Lee, and S. Lee, “Combination of gravitational SPLITT fractionation and field-flow fractionation for size-sorting and characterization of sea sediment,” Analytical and Bioanalytical Chemistry, vol. 381, pp. 1299-1304, 2005.
    [22] R. Rong, J. W. Choi, and C. H. Ahn, “A functional magnetic bead biocell sorter using fully integrated magnetic micro nano tips,” Proc. IEEE 16th International MEMS Conference (IEEE MEMS 2003), pp. 530-533, 2003.
    [23] C. B. Fuh, H. Y. Tsai, and J. Z. Lai, “Development of magnetic split-flow thin fractionation for continuous particle separation,” Analytica Chimica Acta, vol. 497, pp. 115-122, 2003.
    [24] I. Doh and Y. H. Cho, “A continuous cell separation chip using hydrodynamic dielectrophoresis (DEP) process,” Sensors and Actuators A-Physical, vol. 121, pp. 59-65, 2005.
    [25] M. Ozkan, M. Wang, C. Ozkan, R. Flynn, A. Birkbeck, and S. Esener, “Optical manipulation of objects and biological cells in microfluidic devices,” Biomedical Microdevices, vol. 5, pp. 61-67, 2003.
    [26] M. Yamada, M. Nakashima, and M. Seki, “Pinched flow fractionation: Continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel,” Analytical Chemistry, vol. 76, pp. 5465-5471, 2004.
    [27] 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.
    [28] W. J. Webe, Jr. and E. J. LeBoeuf, “ Processes for advanced treatment of water,” Water Science and Technology, vol. 40, No. 4-5, pp. 11-19, 1999.
    [29] 盧文章、楊子岳,薄膜程序回收石化產業放流水之應用,環保月刊,七月號(第一期廢水專輯),第195-205 頁,民國90年。
    [30] C. Piotr, L. Francisco and G. Carme, “Membrane fouling during microfiltraion of fermented beverages,” Journal of Membrane Science, vol. 166, No.2, pp. 199-212, 2000.
    [31] D. J. Chang and S. J. Huang, “Unsteady-state permeate flux of crossflow microfiltration,” Separation Science Technology, vol. 29, No.12, pp. 1593-1608, 1994.
    [32] S. Elmaleh, L. Vera, R. Villarroel-Lopez, L. Adbelmoumni, N. Ghaffor and S. Delgado, “Dimensional analysis of steady state flux for microfiltration and ultrafiltration membranes,” Journal of Membrane Science, vol. 139, pp. 37-45, 1998.
    [33] E. L. Brainerd, “Caught in the crossflow,” Nature, vol. 412, pp. 387-388, 2001.
    [34] MEMOS Membranes Modules Systems GmbH, “Membrane filtration - crossflow-systems”, http://www.memos-filtration.de/cms/en/crossflow.php
    [35] 趙毅、林文江,利用微過濾技術處理研磨廢水半導體洗淨節水及環境技術國際研討會,新竹市,第72-99 頁,民國88年。
    [36] G. Belfort, R. H. Davis and A. L. Zydney, “The behaviour of suspensions and macromolecular solutions in crossflow microfiltration, ” Journal of Membrane Science, vol. 96, pp. 1-58, 1994.
    [37] I. H. Huisman, E. Vellenga, G. Tragardh, C. Tragardh, “The influence of the membrane zeta potential on the critical flux for crossflow microfiltration of particle suspensions,” Journal of Membrane Science, vol. 156, pp. 153-158, 1999.
    [38] N. Xu, Y. Zhao, J. Zhong, J. Shi, “Crossflow microfiltration of micro-sized mineral suspensions using ceramic membranes,” Institution of Chemical Engineers, Trans IChemE., vol. 80, part A, pp. 215-221, 2002.
    [39] D. J. Chang, F. C. Hsu, S. J. Hwang, “Steady-state permeate flux of cross-flow microfiltration,” Journal of Membrane Science, vol. 98, pp. 97-106, 1995.

    無法下載圖示 校內:2021-12-31公開
    校外:不公開
    電子論文尚未授權公開,紙本請查館藏目錄
    QR CODE