研究生: |
石庭禎 Ting-Chen Shih |
---|---|
論文名稱: |
陣列式介電泳細胞操控元件之設計與分析 Design and analysis of bio-molecular manipulating array by dielectrophoresis |
指導教授: |
劉承賢
Cheng-Hsien Liu |
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
工學院 - 動力機械工程學系 Department of Power Mechanical Engineering |
論文出版年: | 2005 |
畢業學年度: | 93 |
語文別: | 英文 |
論文頁數: | 58 |
中文關鍵詞: | 操控 、分離 、可程式化 、矩陣式介電泳多重分類晶片 |
外文關鍵詞: | Manipulation, Separation, Programmable, Multi-sorting DEP array |
相關次數: | 點閱:3 下載:0 |
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近年來,由於微機電系統(MEMS)快速的成熟發展,且其尺寸相近於細胞分子,因此微機電系統(MEMS)在生物分子及細胞組成學上成為一個很好的工具。而在生醫及藥學的應用上,發展單一細胞的特徵修飾技術,不只可用來診斷檢驗帶有不同修飾基的細胞,還可生產特殊有價值的細胞,因此要在低濃度的樣本裡,分離、分類、純化和檢測特定的生物分子,像是DNA、蛋白質、病毒和細胞,變得相當的重要。過去以來,研究工作者發表了一些技術,如光學鑷子、磁鑷子、微夾子…等等,來操控及分離細胞、蛋白質和DNA,但即使擁有如此先進的技術和亮眼的實驗結果,其在實際應用面上,要從低樣品濃度的溶液中以高效率萃取純化出想要的生物分子仍是一項挑戰。因此本論文介紹一個新穎的理論”介電泳(DEP)”,並藉由可程式化的矩陣式介電泳晶片來產生非接觸的力量去操控及分離細胞。
本論文首先介紹一些過去的文獻探討,並經由理論公式計算及CFD-RC軟體的數值模擬來驗證此晶片的可能性,接著利用微機電系統的製程來規劃實現此可程式化的矩陣式介電泳多重分類晶片,最後,我們提出了一個整合性的生物晶片,其利用矩陣式介電泳理論而有效率的應用在蛋白質的捕捉及分離上。
Recently, MEMS has been a good tool in application of molecular and cellular biotechnology researches because the scale fit to the size of the molecule and cell. For medical and pharmaceutical purposes, development of new and modified single cell characterization techniques could allow individual cell-based diagnostic assays and product a lot of highly specialized cells. Therefore, to separate, sort out, purify and detect target biological particles/molecules like DNA, proteins, viruses, and cells from very low-concentration sample solution has been important. In the past, research workers publish some technology such as optical tweezers, magnetic tweezers, microgripper, and etc. to manipulate and separate cells, proteins, and DNA. Even with such technology advances and impressive technology demonstration, the high effective separation, sorting, and purification for target bio-molecules in a very low-concentration sample solution are still a big challenge for practical applications and attractive research topics. Hence, this thesis introduce a novel theory, dielectrophoresis, (DEP) to manipulate and separate cells with non-concact force by the programmable DEP array.
Firstly, this thesis first introduces the survey of literatures, and prove the feasibility of the design concepts via theoretical and numerical analysis with CFD-RC. Through the MEMS fabrication processes, a device with programmable DEP array is realized to demonstrate the function of manipulation and separation. Furthermore, we address a integrated biochip for the applications of trapping and adaptive multi-sorting proteins using DEP array.
[1] G. H. Patterson, and J. Lippincott-Schwartz, “A photoactivatable GFP for selective photolabeling of proteins and cells”, Science, 2002, 297, 1873.
[2] D. A. Zacharias, J. D. Violin, A. C. Newton, and R. Y. Tsien, “Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells”, Science, 2002, 296, 913.
[3] B. J. Bevis, and B. S. Glick, “Rapidly maturing variants of the Discosoma red fluorescent protein (DsRed)”, Nature Biotechnol, 2002, 20, 83.
[4] J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology”, Nature, 2002, 3, 906.
[5] R. A. Reynolds III, C. A. Mirkin, and R. L. Letsinger, “Creating new fluorescent probes for cell biology”, Pure Appl. Chem., 2000, 72, 229.
[6] W. Robert, Jr. Applegate, S. Jeff, V. Tor, O. John, W. David, and M. Marr, “Optical trapping, manipulation, and sorting of cells and colloids in microfluidic systems with diode laser bars”, OPTICS EXPRESS, 2004, 12, 4390.
[7] H. Lee, T. P. Hunt, and R. M. Westervelt, “Magnetic and Electric Manipulation of a Single Cell in Fluid”, Mat. Res. Soc. Symp. Proc., 2004, 820,
[8] C. J. Kim, A. P. Pisano, R. S. Muller, “Silicon-Processed Overhanging Microgripper,” J. MEMS, 1992, 1, 31-36.
[9] A. P. Lee, D. R. Ciarlo, P. A. Krulevitch, S. Lehew, J. Trevino, M. A. Northrup, “A Practical Microgripper by Fine Alignment, Eutectic Bonding and SMA Actuation”, Tech. Dig., Transducers’ 95, 1995, 368-371.
[10] N. G. Green, and H. Morgan, “Dielectrophoresis of submicrometer latex spheres. I. Experimental results”, J. Phys. Chem., 1999, 103, 41.
[11] M. P. Hughes, H. Morgan, and F. J. Rixon, “Measurements of the properties of herpes simplex virus type 1 virons with dielectrophoresis”, Biochim. Biophys. Acta, 2002, 1751, 1.
[12] M. P. Hughes, and H. Morgan, “Dielectrophoretic manipulation of protein molecules in solution”, Proc. 1st Eur. Worksh. Electrokinetics Electrohydr -dynamics Microsyst., 2001.
[13] P. R. C. Gascoyne, R. Pethig, J. P. H. Burt, and F. F. Becker, “Membrane changes accompanying the induced differentiation of Friend murine try throleulcemia cells studied by dielectrophoresis”, Biochim. Biophys. Acta, 1993, 1149, 119.
[14] H. Morgan, M. P. Hughes, and N. G. Green, “Separation of Submicron bio particles by dielectrophoresis”, Biophys. J., 1999, 77, 516.
[15] M. P. Hughes, H. Morgan, and M. F. Flynn, “Surface conductance in the diffuse double-layer observed by dielectrophoresis of latex nanospheres”, J. Coll. Int. Sci., 1999, 220, 454.
[16] M. P. Hughes, “Nanoelectromechanics in Engineering and Biology”, LRC press, 2003.
[17] A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, and S. Chu, “Observation of a single-beam gradient force optical trap for dielectric particles”, Opt. Lett., 1986, 11, 288.
[18] A. Ashkin, “History of optical trapping and manipulation of small-neutral particle, atoms, and molecules, Selected Topics in Quantum Electronics”, IEEE Journal, 2000, 6, 841.
[19] G. Medoro, N. Manaresi, A. Leonardi, L. Altomare, M. Tartagni, R. Guerrieri, “A Lab-on-a-chip For Cell Detection And Manipulation”, SiBio_IEEE Sensors 2002 section 26.4.
[20] Doneun Huh, H.-H. Wei, O. Kripfgans, B. Fowlkes, J.B. Grotberg, S. Takayama, “Gravity-Driven-Microhydrodynamics-Based Cell Sorter (microHYCS) for Rapid, Inexpensive, and Efficient Cell Separation and Size-Profiling”, IEEE MEMS, 2002, 180, 466-469.
[21] C.C. Chen, and S. Zappe, “Microfluidic Switch for Embryo and Cell Sorting”, Transducers, 2003, 65, 659-662.
[22] K.L. Chan, N.G. Green, M.P. Hughes and H. Morgan, “Cellular characterization and separation: Dielectrophoretically Activated Cell Sorting (DACS)”, IEEE Conf. on Engineering in Medicine and Biology (Hong Kong), 1998, 2953-2956.
[23] H. Sano, H. Kabata, O. Kurosawa, and M. Washizu, “Dielectrophoretic chromatography with cross-flow injection”, IEEE MEMS, 2002, 11-14.
[24] M. J. Madou, “Fundamentals of MICRO FABRICATION, The Science of Miniaturization”, Second Edition, 560-570.
[25] J. Voldman, R. A. Braff, M. Toner, M. L. Gray, and M. A. Schmidt, “Holding Forces of Single-Particle Dielectrophoretic Traps”, Biophysical J., 2001, 80, 531.
[26] J. Voldman, M. L. Gray, M. Toner and M. A. Schmidt, “A Microfabrication -Based Dynamic Array Cytometer”, Anal. Chem, 2002, 74, 3984-3990.
[27] Tom Hunt, “Gradient traps for bioparticle manipulation: optical tweezers, magnetic tweezers, and dielectrophoresis”, AP 298r term paper 5-12-03
[28] J. Voldman, R. A. Braff, M. Toner, M. L. Gray, and M. A. Schmidt, “QUANTITATIVE DESIGN AND ANALYSIS OF SINGLE-PARTICLE DIELECTROPHORETIC TRAPS”, A. van den berg et al.(eds.)Micro Total analysis Systems 2000,431-434.
[29] R. Fuhr Guënter, Reichle Christoph “Living cells in opto-electrical cages” trends in analytical chemistry, 2000, 19, 402-409.
[30] P. A. Baeuerle, D. Baltimore, “IkB: A Specific Inhibitor of the NF-kB Transcription Factor”, Science, 1988, 242, 540.
[31] Gavin MacBeath, and Stuart L. Schreiber, “Printing proteins as microarrays for high-throughput function determination”, Science, 2000, 289,1760.
[32] Zheng Lifeng, P. Brody James, and J. Burke. Peter, “Electronic manipulation of DNA, proteins, and nanoparticles for potential circuit assembly”, Biosensors and Bioelectronics, 2004, 20, 606-619.
[33] J. Voldman, M. Toner, M.L. Gray, and M.A. Schmidt, “A Dielectrophoresis -Based Array Cytometer”, Proc. Int. Conf. on Solid-State Sensors and Actuators, Transducers '01, 2001, 322.
[34] R. M. Bruce, F. Y. Donald, H. Okiishi. Theodore, “Fundamentals of fluid mechanics”, 4th edition, 2002, 589.
[35] L.-M. Fu, G.-B. Lee, Y.-H. Lin, and R.-J. Yang, “Manipulation of microparticles using new modes of traveling-wave-dielectrophoretic forces: numerical simulation and experiments”, IEEE/ASME Transactions on mechatronics, 2004, 9.
[36] T. Muller, A. Gerardino, T. Schnelle, S. G. Shirley, F. Bordoni, G. DeGasperis, R. Leoni, and G. Fuhr, “Trapping of micrometre and sub-micrometre particles by high-frequency electric fields and hydrodynamic forces”, J. Phys. D: Appl. Phys., 1996, 29, 340.