研究生: |
黃啟航 Chi-Huang Huang |
---|---|
論文名稱: |
利用微流體晶片捕捉微顆粒機制於生醫應用之探討 Study on Machanism of Trapping Microparticles in Microfluidic Devices for Biomedical Applications |
指導教授: |
張天立
Chang, Tien-Li |
學位類別: |
碩士 Master |
系所名稱: |
機電工程學系 Department of Mechatronic Engineering |
論文出版年: | 2014 |
畢業學年度: | 102 |
語文別: | 中文 |
論文頁數: | 92 |
中文關鍵詞: | 微流體晶片 、捕捉流道結構設計 、微顆粒 、腫瘤細胞 、微影技術 |
英文關鍵詞: | Microfluidic devices, Design of trapping microchannels, Microparticles, Tumor cells, Lithography process |
論文種類: | 學術論文 |
相關次數: | 點閱:151 下載:3 |
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 |
在環境監測以及重點照護的關鍵技術會包含生物樣本的培養以及測試。然而,傳統技術需要大型設備來完成,難以達到廣泛且靈活的運用。過去十年中,生物晶片結合電子、機械和生物等技術,可於不同環境條件下執行生物樣本的快速分析,諸多科學的發展促使生物晶片愈趨成熟。鑑於此,本研究會使用模擬設計的方法進行,並分析壓力場、速度場和相關流體行為之變化,藉以提出可能影響捕捉效率的原因。同時,將採用光微影技術製作該設計的結構,以液珠和高分子球進行微顆粒測試之機制分析,再利用癌症循環腫瘤細胞進行粒子測試實驗。在本研究結果認為會影響微流體晶片中,該捕捉效率原因會為微流阻影響移動路徑和負壓區域造成堆積現象。
實驗結果顯示在設計之U型結構對於在50 mm以下之微粒子,其捕捉效果不佳,微粒子會被高速流體導引向通過流。同時,實驗中發現在負壓區尺寸過大時,會使單一捕捉結構易捕捉到一顆以上微粒子,造成堆積效應。因此,本研究提出新型三角設計,使整體流場均勻化,微粒子可有效的填滿結構,且三角結構可以有效的降低負壓區,達到單一結構捕捉單一粒子的目的。本實驗分別以液珠(100± 15 mm)以及高分子微球(25 ±5 mm)進行測試,其結果顯示設計之三角和U型結構捕捉液珠效率較為相近,該捕捉率皆達95%。此外,在捕捉高分子微球之效率,則分別為9 %(U型結構)以及42.9 %(三角結構)。
For environmental monitoring and point of care (POC), the biological specimen culture and testing are an important technology. However, the requirement of space conditions for its high specification and heavy equipment is difficult for a wide range of flexible use. Over the past decade, the biochips combined with electronic, mechanical and biological technology that can perform a rapid analysis of biological samples under different environmental conditions. The aim of study is to design microfluidic system device with the simulation method for trapping channel structures in the microfluidic transportation system. Based on the fluid simulation results, the distribution of the pressure fields, velocity fields and its flow behaviors are obtained that can be useful to fabricate the suitable devices. It can be seen the reasons that probably affect the trapping efficiency such as the influence of mciroflow resistance on the moving path and the influence the accumulation phenomenon on negative pressure zone.
The experimental simulation results show the trapping efficiency is not well when the microparticles (≦50 m) run through the U-type structures in the microfluidic device. Because of the high-speed flow, the microparticles are easily induced them to pass the design of structures. Simultaneously, the single capturing structure can easily capture over one microparticle to cause the accumulation phenomenon occurs at the higher negative pressure. Consequently, this study proposes new type design of triangular structures in order to make the uniform flow, fill in the structure with particles and reduce the negative pressure. And the single structure can achieve to capture and the single particle. The capture particles size including the droplet (100 15 m) and polymer microsphere (25 5 m) can be used in this study. The trapping efficiency of droplets for design of triangle and the U-shaped structures is close whose the capture rate is over 95%. Furthermore, the trapping efficiency of polymer microspheres for triangular structured and U-type structured devices are 42.9% and 9%, respectively.
[1] A. Manz, N. Graber, and H. á. Widmer, "Miniaturized total chemical analysis systems: a novel concept for chemical sensing," Sensors and actuators B: Chemical, vol. 1, pp. 244-248, 1990.
[2] F. R. C. S. Stephen Paget, "The distribution of secondary growths in cancer of the breast," Lancet vol. 1, pp. 571–573, 1889.
[3] P. S. Steeg, "Tumor metastasis: mechanistic insights and clinical challenges," Nat Med, vol. 12, pp. 895-904, 2006.
[4] S. J. M. Tannishtha Reya, Michael F. Clarke , and Irving L. Weissman*, "Stem cells, cancer, and cancer stem cells," NATURE vol. 414, pp. 105-111, 2001.
[5] M. D. Massimo Cristofanilli, G. Thomas Budd, M.D., Matthew J. Ellis, M.B., Ph.D., M. D. Alison Stopeck, Jeri Matera, B.S., R.Ph., M. Craig Miller, B.S., P. D. James M. Reuben, Gerald V. Doyle, D.D.S., W. Jeffrey Allard, Ph.D., M. D. Leon W.M.M. Terstappen, Ph.D., Daniel F. Hayes, M.D., "Circulating Tumor Cells, Disease Progression, and survival in metastatic breast cancer," The new england journal of medicine, vol. 351, pp. 781-791, 2004.
[6] G. P. Gupta and J. Massague, "Cancer metastasis: building a framework," Cell, vol. 127, pp. 679-695, 2006.
[7] S. Zheng, H. K. Lin, B. Lu, A. Williams, R. Datar, R. J. Cote, and Y. C. Tai, "3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood," Biomed Microdevices, vol. 13, pp. 203-213, 2011.
[8] M. Yu, S. Stott, M. Toner, S. Maheswaran, and D. A. Haber, "Circulating tumor cells: approaches to isolation and characterization," J Cell Biol, vol. 192, pp. 373-382, 2011.
[9] G. Attard, J. F. Swennenhuis, D. Olmos, A. H. Reid, E. Vickers, R. A'Hern, R. Levink, F. Coumans, J. Moreira, R. Riisnaes, N. B. Oommen, G. Hawche, C. Jameson, E. Thompson, R. Sipkema, C. P. Carden, C. Parker, D. Dearnaley, S. B. Kaye, C. S. Cooper, A. Molina, M. E. Cox, L. W. M. M. Terstappen, and J. S. de Bono, "Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer," Cancer Res, vol. 69, pp. 2912-2918, 2009.
[10] B. Alberts, A. Johnson, J. Lewis, P. Walter, M. Raff, and K. Roberts, Molecular Biology of the Cell 4th Edition: International Student Edition: Routledge, 2002.
[11] A. M. Skelley, O. Kirak, H. Suh, R. Jaenisch, and J. Voldman, "Microfluidic control of cell pairing and fusion," Nat Methods, vol. 6, pp. 147-152, 2009.
[12] A. Huebner, D. Bratton, G. Whyte, M. Yang, A. J. Demello, C. Abell, and and F. Hollfelder, "Static microdroplet arrays: a microfluidic device for droplet trapping, incubation and release for enzymatic and cell-based assays," Lab Chip, vol. 9, pp. 692-698, 2009.
[13] A. A. Bhagat, H. W. Hou, L. D. Li, C. T. Lim, and J. Han, "Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation," Lab Chip, vol. 11, pp. 1870-1878, 2011.
[14] M. C. Kim, B. C. Isenberg, J. Sutin, A. Meller, J. Y. Wong, and C. M. Klapperich, "Programmed trapping of individual bacteria using micrometre-size sieves," Lab Chip, vol. 11, pp. 1089-1095, 2011.
[15] X. Xu, Z. Li, and A. Nehorai, "Finite element simulations of hydrodynamic trapping in microfluidic particle-trap array systems," Biomicrofluidics, vol. 7, pp. 54108-54125, 2013.
[16] V. Sivagnanam, B. Song, C. Vandevyver, J. C. Bunzli, and M. A. Gijs, "Selective breast cancer cell capture, culture, and immunocytochemical analysis using self-assembled magnetic bead patterns in a microfluidic chip," Langmuir, vol. 26, pp. 6091-6096, 2010.
[17] 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 Chip, vol. 10, pp. 211-219, 2010.
[18] S. Kobel, A. Valero, J. Latt, P. Renaud, and M. Lutolf, "Optimization of microfluidic single cell trapping for long-term on-chip culture," Lab Chip, vol. 10, pp. 857-863, 2010.
[19] W. Liu, H. Wei, Z. Lin, S. Mao, and J. M. Lin, "Rare cell chemiluminescence detection based on aptamer-specific capture in microfluidic channels," Biosens Bioelectron, vol. 28, pp. 438-442, 2011.
[20] J. A. Viator and K. P. Rollins, "Photoacoustic Detection and Imaging of Cancer Using Nanoparticles as Optical Contrast Agents," Recent Patents on Nanomedicine, vol. 1, pp. 68-73, 2011.
[21] E. P. Dupont, E. Labonne, Y. Maruyama, C. Vandevyver, U. Lehmann, M. A. M. Gijs, and E. Charbon, "Fluorescent magnetic bead and cell differentiation/counting using a CMOS SPAD matrix," Sensors and Actuators B: Chemical, vol. 174, pp. 609-615, 2012.
[22] Y. K. Chung, J. Reboud, K. C. Lee, H. M. Lim, P. Y. Lim, K. Y. Wang, K. C. Tang, H. M. Ji, and Y. Chen, "An electrical biosensor for the detection of circulating tumor cells," Biosens Bioelectron, vol. 26, pp. 2520-2526, 2011.
[23] H. Bruus, Theoretical microfluidics vol. 18: Oxford University Press, 2008.
[24] A. F. Bower, Applied mechanics of solids: CRC press, 2011.
[25] W. H. Tan and S. Takeuchi, "A trap-and-release integrated microfluidic system for dynamic microarray applications," Proc Natl Acad Sci U S A, vol. 104, pp. 1146-1151, 2007.
[26] W. Kern, "Cleaning solutions based on hydrogen peroxide for use in silicon semiconductor technology," RCA review, vol. 31, pp. 187-206, 1970.
[27] MicroChem, "SU-8 2000 DataSheet," http://www.microchem.com/pdf/SU-82000DataSheet2025thru2075Ver4.pdf.