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研究生: 吳允開
Wu, Yun-Kai
論文名稱: 以流體力學分析微流道粒子運動
Hydrodynamic investigation of particle dynamics in microfluidics
指導教授: 陳嘉元
Chen, Chia-Yuan
學位類別: 碩士
Master
系所名稱: 工學院 - 機械工程學系
Department of Mechanical Engineering
論文出版年: 2019
畢業學年度: 107
語文別: 中文
論文頁數: 63
中文關鍵詞: 循環腫瘤細胞磁性人工纖毛微粒子影像測速儀細胞分類
外文關鍵詞: circulating tumor cells, magnetic artificial cilia, micro-particle image velocimetry (µPIV), cell separation
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  • 近年來在生物和醫學的研究領域中,如何從異質混合物分離出細胞一直是重要的目標,而細胞分離更是許多臨床診斷和治療的必要步驟,對於細胞分離的需求也正擴展到分離某些稀有的靶細胞群,例如循環腫瘤細胞等,然而許多研究團隊發現循環腫瘤細胞不僅與主要腫瘤細胞擁有相似的生物特徵,亦可用於監測癌症治療的成效。然而,在血液的組成中,白血球細胞的直徑與循環腫瘤細胞極為相近,因此增加分離出循環腫瘤細胞的難度,故本研究將利用特殊的流體動力學設計,透過控制磁性人工纖毛不同的擺動模式,精準的調控流場剪應力及壁面效應,搭配粒子在微流體環境的移動特性,透過模擬方法研究直徑15與20 µm的粒子在微流體裝置中因人工纖毛擺動而產生的移動差異,藉由量化粒子在通過人工纖毛後的位置分佈,可以得到粒子最終平衡位置與雷諾數以及斯特勞克數的趨勢關係,更進一步說明尺度相似的粒子可以產生10 %的軌跡差異,進而找出最佳的流體參數以實現高效率的細胞分類,再透過實驗觀測粒子在流場中受磁性人工纖毛擺動所產生的移動軌跡,並利用微粒子影像測速儀進行流體動力學分析,驗證不同大小粒子的軌跡差異與模擬結果趨勢相同。本研究成功透過人工纖毛轉動達到調控流場剪切梯度作用力之目標,未來期待將此技術運用在生物醫學等領域作為分離循環腫瘤細胞的基礎。

    Recent years have witnessed an unprecedented effort from the scientific society towards separating specific cells from the heterogeneous mixture of cells for various biological and medical purposes. Such an example is capturing circulating tumor cells (CTCs) from the other blood cells. However, separating CTCs from the whole blood is hydrodynamically a difficult task as the size of other blood cells such as leukocyte have a similar dimensional features. In this aspect, we are investigating the migrating behavior of leukocytes and circulating tumor cells induced by magnetic artificial cilia within microfluidic environment through the precise control of flow-induced shear gradient and wall surface effect via numerical analysis. By quantifying the position distribution of the particles after passing the artificial cilia, the relations between the final equilibrium position of the particles and two non-dimensional number (Reynolds number and Strouhal number) can be obtained, further indicating that the particles with similar dimensions can produce a trajectory difference over 10%. In the experimental section, the particle trajectory induced by different rotational modes of magnetic artificial cilia can also be observed by micro-particle image velocimetry to verify that the experimental results are consistent with the simulation results. This study shows that the equilibrium position of particles with similar dimensions still can be manipulated into different positions through the precise control of the flow shear gradient by changing the frequency and amplitude of artificial cilia rotation. It is expected that this technology will be applied in the biomedical fields as the basis for separating circulating tumor cells.

    中英文摘要 I 誌謝 VI 目錄 VII 圖目錄 X 表目錄 XII 第一章、緒論 1 1.1 研究動機 1 1.2 文獻回顧 3 1.2.1 循環腫瘤細胞相關技術 3 1.2.2 微流體相關技術 5 1.2.3 慣性升力 7 1.2.4 人工纖毛 11 1.2.5 數值模擬 13 1.3 研究目標 15 1.4 論文架構 18 第二章、模擬分析與結果 19 2.1 模擬方法 19 2.1.1 統御方程式 19 2.1.2 無因次參數 20 2.1.3 流道設計 21 2.1.4 慣性升力量測 23 2.1.5 升力係數 27 2.1.6 模擬設定 30 2.2 模擬結果 36 2.2.1 慣性升力對粒子軌跡之影響 36 2.2.2 人工纖毛對粒子軌跡之影響 37 2.2.3 轉動人工纖毛對粒子軌跡之影響 38 2.2.4 粒子平衡位置之差異比較 41 第三章、實驗設計與結果 43 3.1 實驗方法 43 3.1.1 流道設計 43 3.1.2 流道製程 44 3.1.3 電磁鐵平台 46 3.1.4 微粒子影像測速儀 (μPIV) 48 3.2 實驗結果 50 3.2.1 粒子軌跡追蹤 50 第四章、結論與未來展望 52 4.1 結論 52 4.2 未來展望 54 參考文獻 55 附錄 61 附錄1 程式碼 – 相對速度 61 附錄2 使用者自定函數 – 慣性升力 61 附錄3 使用者自定函數 – 纖毛轉動 62

    [1] T. J. A. M. J. Ashworth, "A case of cancer in which cells similar to those in the tumours were seen in the blood after death," vol. 14, p. 146, 1869.
    [2] T. R. Geiger and D. S. J. B. e. B. A.-R. o. C. Peeper, "Metastasis mechanisms," vol. 1796, no. 2, pp. 293-308, 2009.
    [3] E. C. Woodhouse, R. F. Chuaqui, and L. A. J. C. I. I. J. o. t. A. C. S. Liotta, "General mechanisms of metastasis," vol. 80, no. S8, pp. 1529-1537, 1997.
    [4] I. J. J. N. R. C. Fidler, "The pathogenesis of cancer metastasis: the'seed and soil'hypothesis revisited," vol. 3, no. 6, p. 453, 2003.
    [5] S. Nagrath et al., "Isolation of rare circulating tumour cells in cancer patients by microchip technology," vol. 450, no. 7173, p. 1235, 2007.
    [6] P. Paterlini-Brechot and N. L. J. C. l. Benali, "Circulating tumor cells (CTC) detection: clinical impact and future directions," vol. 253, no. 2, pp. 180-204, 2007.
    [7] D. F. Hayes et al., "Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival," vol. 12, no. 14, pp. 4218-4224, 2006.
    [8] A. H. Reid et al., "Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate," vol. 28, no. 9, p. 1489, 2010.
    [9] D. T. Miyamoto, L. V. Sequist, and R. J. J. N. r. C. o. Lee, "Circulating tumour cells—monitoring treatment response in prostate cancer," vol. 11, no. 7, p. 401, 2014.
    [10] G. vAN DAluM et al., "Importance of circulating tumor cells in newly diagnosed colorectal cancer," vol. 46, no. 3, pp. 1361-1368, 2015.
    [11] Z. Shen, A. Wu, and X. J. C. S. r. Chen, "Current detection technologies for circulating tumor cells," vol. 46, no. 8, pp. 2038-2056, 2017.
    [12] K. Pantel, R. H. Brakenhoff, and B. J. N. R. C. Brandt, "Detection, clinical relevance and specific biological properties of disseminating tumour cells," vol. 8, no. 5, p. 329, 2008.
    [13] M. C. Miller, G. V. Doyle, and L. W. J. J. o. o. Terstappen, "Significance of circulating tumor cells detected by the CellSearch system in patients with metastatic breast colorectal and prostate cancer," vol. 2010, 2010.
    [14] S. Maheswaran et al., "Detection of mutations in EGFR in circulating lung-cancer cells," vol. 359, no. 4, pp. 366-377, 2008.
    [15] J. M. Lang, B. P. Casavant, and D. J. J. S. t. m. Beebe, "Circulating tumor cells: getting more from less," vol. 4, no. 141, pp. 141ps13-141ps13, 2012.
    [16] E. A. Punnoose et al., "Molecular biomarker analyses using circulating tumor cells," vol. 5, no. 9, p. e12517, 2010.
    [17] P. Noble and J. J. T. C. V. J. Cutts, "Separation of blood leukocytes by Ficoll gradient," vol. 8, no. 5, p. 110, 1967.
    [18] R. Rosenberg et al., "Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood," vol. 49, no. 4, pp. 150-158, 2002.
    [19] S. Carroll and M. J. J. o. i. m. Al-Rubeai, "ACSD labelling and magnetic cell separation: a rapid method of separating antibody secreting cells from non-secreting cells," vol. 296, no. 1-2, pp. 171-178, 2005.
    [20] G. Vona et al., "Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells," vol. 156, no. 1, pp. 57-63, 2000.
    [21] S. J. Tan, L. Yobas, G. Y. H. Lee, C. N. Ong, and C. T. J. B. m. Lim, "Microdevice for the isolation and enumeration of cancer cells from blood," vol. 11, no. 4, pp. 883-892, 2009.
    [22] D. Marrinucci et al., "Case study of the morphologic variation of circulating tumor cells," vol. 38, no. 3, pp. 514-519, 2007.
    [23] M. Toner and D. J. A. R. B. E. Irimia, "Blood-on-a-chip," vol. 7, pp. 77-103, 2005.
    [24] S. Suresh et al., "Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria," vol. 1, no. 1, pp. 15-30, 2005.
    [25] M. Alshareef et al., "Separation of tumor cells with dielectrophoresis-based microfluidic chip," vol. 7, no. 1, p. 011803, 2013.
    [26] A. Vaziri and A. J. N. m. Gopinath, "Cell and biomolecular mechanics in silico," vol. 7, no. 1, p. 15, 2008.
    [27] H. A. Cranston, C. W. Boylan, G. L. Carroll, S. P. Sutera, I. Gluzman, and D. J. S. Krogstad, "Plasmodium falciparum maturation abolishes physiologic red cell deformability," vol. 223, no. 4634, pp. 400-403, 1984.
    [28] D. J. L. o. a. C. Di Carlo, "Inertial microfluidics," vol. 9, no. 21, pp. 3038-3046, 2009.
    [29] D. Di Carlo, D. Irimia, R. G. Tompkins, and M. J. P. o. t. N. A. o. S. Toner, "Continuous inertial focusing, ordering, and separation of particles in microchannels," vol. 104, no. 48, pp. 18892-18897, 2007.
    [30] E. Ozkumur et al., "Inertial focusing for tumor antigen–dependent and–independent sorting of rare circulating tumor cells," vol. 5, no. 179, pp. 179ra47-179ra47, 2013.
    [31] A. Russom, A. K. Gupta, S. Nagrath, D. Di Carlo, J. F. Edd, and M. J. N. j. o. p. Toner, "Differential inertial focusing of particles in curved low-aspect-ratio microchannels," vol. 11, no. 7, p. 075025, 2009.
    [32] S. S. Kuntaegowdanahalli, A. A. S. Bhagat, G. Kumar, and I. J. L. o. a. C. Papautsky, "Inertial microfluidics for continuous particle separation in spiral microchannels," vol. 9, no. 20, pp. 2973-2980, 2009.
    [33] M. E. Warkiani, L. Wu, A. K. P. Tay, and J. J. A. r. o. b. e. Han, "Large-volume microfluidic cell sorting for biomedical applications," vol. 17, pp. 1-34, 2015.
    [34] M. E. Warkiani et al., "Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells," vol. 14, no. 1, pp. 128-137, 2014.
    [35] A. J. Mach, O. B. Adeyiga, and D. J. L. o. a. C. Di Carlo, "Microfluidic sample preparation for diagnostic cytopathology," vol. 13, no. 6, pp. 1011-1026, 2013.
    [36] B. Çetin and D. J. E. Li, "Dielectrophoresis in microfluidics technology," vol. 32, no. 18, pp. 2410-2427, 2011.
    [37] T. P. Forbes and S. P. J. L. o. a. C. Forry, "Microfluidic magnetophoretic separations of immunomagnetically labeled rare mammalian cells," vol. 12, no. 8, pp. 1471-1479, 2012.
    [38] Z. Wang and J. J. L. o. a. C. Zhe, "Recent advances in particle and droplet manipulation for lab-on-a-chip devices based on surface acoustic waves," vol. 11, no. 7, pp. 1280-1285, 2011.
    [39] D. G. J. n. Grier, "A revolution in optical manipulation," vol. 424, no. 6950, p. 810, 2003.
    [40] M. Yamada, M. Nakashima, and M. J. A. c. Seki, "Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel," vol. 76, no. 18, pp. 5465-5471, 2004.
    [41] L. R. Huang, E. C. Cox, R. H. Austin, and J. C. J. S. Sturm, "Continuous particle separation through deterministic lateral displacement," vol. 304, no. 5673, pp. 987-990, 2004.
    [42] P. K. Das and A. T. Hasan, "Effects of flow properties on the performance of a diffuser-nozzle element of a valveless micropump," in AIP Conference Proceedings, 2016, vol. 1754, no. 1, p. 040027: AIP Publishing.
    [43] S. Gambhire, N. Patel, G. Gambhire, S. J. I. J. o. C. E. Kale, and Technology, "A review on different micromixers and its micromixing within microchannel," vol. 4, pp. 409-413, 2016.
    [44] C.-Y. Chen, C.-Y. Chen, C.-Y. Lin, and Y.-T. J. L. o. a. C. Hu, "Magnetically actuated artificial cilia for optimum mixing performance in microfluidics," vol. 13, no. 14, pp. 2834-2839, 2013.
    [45] C.-Y. Chen, C.-Y. Lin, Y.-T. Hu, L.-Y. Cheng, and C.-C. J. C. E. J. Hsu, "Efficient micromixing through artificial cilia actuation with fish-schooling configuration," vol. 259, pp. 391-396, 2015.
    [46] P.-Y. Huang, B. Panigrahi, C.-H. Lu, P.-F. Huang, C.-Y. J. S. Chen, and A. B. Chemical, "An artificial cilia-based micromixer towards the activation of zebrafish sperms," vol. 244, pp. 541-548, 2017.
    [47] "<Segre, G. and A. J. N. Silberberg (1961). Radial particle displacements in Poiseuille flow of suspensions. 189(4760) 209..pdf>."
    [48] G. Segré and A. Silberberg, "Behaviour of macroscopic rigid spheres in Poiseuille flow Part 2. Experimental results and interpretation," Journal of Fluid Mechanics, vol. 14, no. 1, pp. 136-157, 2006.
    [49] D. Di Carlo, "Inertial microfluidics," Lab Chip, vol. 9, no. 21, pp. 3038-46, Nov 7 2009.
    [50] C. Liu and G. J. M. Hu, "High-throughput particle manipulation based on hydrodynamic effects in microchannels," vol. 8, no. 3, p. 73, 2017.
    [51] H. Amini, W. Lee, and D. J. L. o. a. C. Di Carlo, "Inertial microfluidic physics," vol. 14, no. 15, pp. 2739-2761, 2014.
    [52] D. R. Gossett et al., "Inertial manipulation and transfer of microparticles across laminar fluid streams," vol. 8, no. 17, pp. 2757-2764, 2012.
    [53] W. Mao and A. J. P. o. F. Alexeev, "Hydrodynamic sorting of microparticles by size in ridged microchannels," vol. 23, no. 5, p. 051704, 2011.
    [54] K. Hood, S. Lee, and M. J. J. o. F. M. Roper, "Inertial migration of a rigid sphere in three-dimensional Poiseuille flow," vol. 765, pp. 452-479, 2015.
    [55] D. Di Carlo, J. F. Edd, K. J. Humphry, H. A. Stone, and M. J. P. r. l. Toner, "Particle segregation and dynamics in confined flows," vol. 102, no. 9, p. 094503, 2009.
    [56] Y.-S. Choi, K.-W. Seo, and S.-J. J. L. o. a. C. Lee, "Lateral and cross-lateral focusing of spherical particles in a square microchannel," vol. 11, no. 3, pp. 460-465, 2011.
    [57] S. C. Hur, H. T. K. Tse, and D. J. L. o. a. C. Di Carlo, "Sheathless inertial cell ordering for extreme throughput flow cytometry," vol. 10, no. 3, pp. 274-280, 2010.
    [58] A. J. Mach, D. J. B. Di Carlo, and bioengineering, "Continuous scalable blood filtration device using inertial microfluidics," vol. 107, no. 2, pp. 302-311, 2010.
    [59] "<Berger, S., et al. (1983). Flow in curved pipes. 15(1) 461-512..pdf>."
    [60] M. G. Lee, S. Choi, and J.-K. Park, "Rapid laminating mixer using a contraction-expansion array microchannel," Applied Physics Letters, vol. 95, no. 5, 2009.
    [61] J. Zhang, M. Li, W. H. Li, and G. Alici, "Inertial focusing in a straight channel with asymmetrical expansion–contraction cavity arrays using two secondary flows," Journal of Micromechanics and Microengineering, vol. 23, no. 8, 2013.
    [62] H. Amini et al., "Engineering fluid flow using sequenced microstructures," Nat Commun, vol. 4, p. 1826, 2013.
    [63] H. Amini et al., "Engineering fluid flow using sequenced microstructures," vol. 4, p. 1826, 2013.
    [64] E. M. Purcell, "Life at low Reynolds number," American Journal of Physics, vol. 45, no. 1, pp. 3-11, 1977.
    [65] J. Belardi, N. Schorr, O. Prucker, and J. Rühe, "Artificial Cilia: Generation of Magnetic Actuators in Microfluidic Systems," Advanced Functional Materials, vol. 21, no. 17, pp. 3314-3320, 2011.
    [66] S. Nonaka, H. Shiratori, Y. Saijoh, and H. J. N. Hamada, "Determination of left–right patterning of the mouse embryo by artificial nodal flow," vol. 418, no. 6893, p. 96, 2002.
    [67] C. Y. Chen, C. Y. Chen, C. Y. Lin, and Y. T. Hu, "Magnetically actuated artificial cilia for optimum mixing performance in microfluidics," Lab Chip, vol. 13, no. 14, pp. 2834-9, Jul 21 2013.
    [68] C.-Y. Chen, C.-Y. Lin, Y.-T. Hu, L.-Y. Cheng, and C.-C. Hsu, "Efficient micromixing through artificial cilia actuation with fish-schooling configuration," Chemical Engineering Journal, vol. 259, pp. 391-396, 2015.
    [69] P.-Y. Huang, B. Panigrahi, C.-H. Lu, P.-F. Huang, and C.-Y. Chen, "An artificial cilia-based micromixer towards the activation of zebrafish sperms," Sensors and Actuators B: Chemical, vol. 244, pp. 541-548, 2017.
    [70] Y.-A. Wu, B. Panigrahi, Y.-H. Lu, and C.-Y. Chen, "An Integrated Artificial Cilia Based Microfluidic Device for Micropumping and Micromixing Applications," Micromachines, vol. 8, no. 9, p. 260, 2017.
    [71] B. Evans, A. Shields, R. L. Carroll, S. Washburn, M. Falvo, and R. Superfine, "Magnetically actuated nanorod arrays as biomimetic cilia," Nano letters, vol. 7, no. 5, pp. 1428-1434, 2007.
    [72] A. Shields, B. Fiser, B. Evans, M. Falvo, S. Washburn, and R. Superfine, "Biomimetic cilia arrays generate simultaneous pumping and mixing regimes," Proceedings of the National Academy of Sciences, vol. 107, no. 36, pp. 15670-15675, 2010.
    [73] J. den Toonder et al., "Artificial cilia for active micro-fluidic mixing," Lab on a Chip, vol. 8, no. 4, pp. 533-541, 2008.
    [74] C. L. Van Oosten, C. W. Bastiaansen, and D. J. Broer, "Printed artificial cilia from liquid-crystal network actuators modularly driven by light," Nature materials, vol. 8, no. 8, p. 677, 2009.
    [75] H. H. J. I. J. o. M. F. Hu, "Direct simulation of flows of solid-liquid mixtures," vol. 22, no. 2, pp. 335-352, 1996.
    [76] D. A. Drew and S. L. Passman, Theory of multicomponent fluids. Springer Science & Business Media, 2006.
    [77] L.-S. Fan and C. Zhu, Principles of gas-solid flows. Cambridge University Press, 2005.
    [78] Q. Wang, D. Yuan, and W. J. M. Li, "Analysis of hydrodynamic mechanism on particles focusing in micro-channel flows," vol. 8, no. 7, p. 197, 2017.
    [79] B. N. G. Sajay, C.-P. Chang, H. Ahmad, W. C. Chung, P. D. Puiu, and A. R. A. J. B. m. Rahman, "Towards an optimal and unbiased approach for tumor cell isolation," vol. 15, no. 4, pp. 699-709, 2013.

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