簡易檢索 / 詳目顯示

研究生: 李瑞中
Lee, Jui-Chung
論文名稱: 利用三維電極結合微孔洞結構於單一子宮頸癌細胞之捕捉與阻抗量測
Trapping and Impedance Measurement of Single HeLa Cells Using Three-Dimensional Electrodes In-tegrated with Micro-Cavity Structures
指導教授: 張凌昇
Jang, Ling-Sheng
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2015
畢業學年度: 103
語文別: 英文
論文頁數: 67
中文關鍵詞: 微流道技術微孔洞微粒子捕捉三維電極非標記子宮頸癌細胞阻抗量測
外文關鍵詞: microfluidics, micro-cavities, micro-beads trapping, three dimensional electrodes, label-free, HeLa cells, impedance measurement
相關次數: 點閱:251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
  • 中文摘要

    微流道晶片具有可微小型化、大量製造、與低成本等特性,相較於傳統的晶片裝置,可以運作的更有效率。
    本論文結合數種微機電製程技術,包含黃光製程技術、電鍍技術,實現出一組可以捕捉微米等級粒子的微流道晶片。此晶片將微電極結合於微孔洞,形成一立體的捕捉量測結構。如果微粒子被捕捉,便可立即對微粒子進行阻抗量測。阻抗量測是一種可以用來區分且分析不同待測物電特性的技術。本研究利用研製出的微流道晶片,可以百分之百地捕捉到單一微粒子與單一子宮頸癌細胞。此組微流道晶片有五組電極,可同時量測五組阻抗值。經過比較和分析,五組量測值相對誤差在4%以下。由捕捉前後阻抗變化以及相角的差異,此裝置可以不用標記待測物下成功地區分微粒子與細胞。因此,本捕捉量測晶片未來可運用於生物醫學檢測上的應用,具備可量測、非標記、多筆資料的優勢。

    ABSTRACT

    Microfluidic chips have the advantages of mass production, minia-turization, and low cost. Compared to conventional devices, these chips are more efficient to operate.
    This study combines several processing techniques, including photolithography process and electroplating to fabricate a microfluidic device which can capture micro-scale particles. This device integrates microelectrodes with micro-cavities to perform a three dimensional trapping and measurement structures. If a micro-bead is trapped in the structure, the device can make impedance measurement immediately. EIS (Electrical impedance spectroscopy) technique is used to differentiate and analyze the electrical properties of different objects under measurement. In this study, single micro-bead and single HeLa cell can be captured by one hundred percent by using developed microfluidic device. The device consists of five groups of electrodes which can take measurement simultaneously. Through comparison and analysis, the relative error is under 4%. According to the variation of the impedance magnitude and phase, this device can distinguish label-free single micro-bead and single HeLa cell successfully. Therefore, this device has the potential to be applied in biomedical detection in the future for holding the advantages of being measureable, label-free, and simultaneous multiple measurements.

    CONTENTS 中文摘要 I ABSTRACT II ACKNOWLEDGEMENT III CONTENTS IV LIST OF FIGURES VII CHAPTER 1 INTRODUCTION 1 1-1 Background and Motivation 1 1-1-1 Background 1 1-1-2 Motivation 2 1-2 Literature Review 3 1-2-1 Introduction to Particles Trapping 3 1-2-2 Mechanical and Hydrodynamic Trapping Mechanism 4 1-2-3 Introduction to Electrical Impedance Spectroscopy 6 1-3 Organization of the Dissertation 6 CHAPTER 2 METHOD AND PRINCIPLE 8 2-1 Photoresist AZ P4620 Photolithography Process 8 2-2 Micro-cavity Manufacture 12 2-3 Electroplating 12 CHAPTER 3 MATERIALS AND FABRICATION 18 3-1 Introduction to Instruments 19 3-1-1 Other Instruments 19 3-2 Chip Fabrication 21 3-2-1 Simulation to Measurement Electrodes 22 3-2-2 Introduction to Micro-cavity Structures Fabrication 25 3-2-3 Introduction to Microelectrodes Fabrication 25 3-2-4 Microfluidic Channel and Chamber Fabrication 31 CHAPTER 4 EXPERIMENTAL SETUP AND MEASUREMENT RESULT 35 4-1 Experimental Setup 35 4-1-1 Impedance Measurement System 35 4-1-2 Calibration and Error Caused by Contact Resistance 37 4-1-3 Micro-beads Preparation 42 4-1-4 Cell culture 43 4-1-5 Experimental Setup 43 4-2 Measurement Result 45 4-2-1 The Influence of different length of Electrodes on Impedance Measurement 46 4-2-2 The Impedance Measurement And Analysis of DMEM 46 4-2-3 Analysis of Micro-beads Trapping and Impedance Measurement 49 4-2-4 Analysis of the HeLa cells Trapping and Impedance Measurement 53 4-2-5 Analysis of the Micro-bead and HeLa cells Trapping and Impedance Measurement 58 4-2-6 Analysis of Mixed Trapping and Impedance Measurement 59 CHAPTER 5 CONCLUSIONS AND FUTURE WORK 63 REFERENCES 65

    REFERENCES

    [1] B. W. Stewart, P. Kleihues, and I. A. f. R. o. Cancer, World cancer report vol. 57: IARC press Lyon, 2003.
    [2] 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.
    [3] A. Z. Wang, R. Langer, and O. C. Farokhzad, "Nanoparticle delivery of cancer drugs," Annual review of medicine, vol. 63, pp. 185-198, 2012.
    [4] S. L. Tsai, J. L. Hong, M. K. Chen, and L. S. Jang, "Experimental study of dielectrophoresis and liquid dielectrophoresis mechanisms for particle capture in a droplet," Electrophoresis, vol. 32, pp. 1337-1347, 2011.
    [5] Y. Yamaguchi, T. Arakawa, N. Takeda, Y. Edagawa, and S. Shoji, "Development of a poly-dimethylsiloxane microfluidic device for single cell isolation and incubation," Sensors and Actuators B: Chemical, vol. 136, pp. 555-561, 2009.
    [6] M. Hosokawa, T. Hayata, Y. Fukuda, A. Arakaki, T. Yoshino, T. Tanaka, et al., "Size-selective microcavity array for rapid and efficient detection of circulating tumor cells," Analytical chemistry, vol. 82, pp. 6629-6635, 2010.
    [7] M. Hosokawa, T. Yoshikawa, R. Negishi, T. Yoshino, Y. Koh, H. Kenmotsu, et al., "Microcavity array system for size-based enrichment of circulating tumor cells from the blood of patients with small-cell lung cancer," Analytical chemistry, vol. 85, pp. 5692-5698, 2013.
    [8] J. Chen, J. Li, and Y. Sun, "Microfluidic approaches for cancer cell detection, characterization, and separation," Lab on a Chip, vol. 12, pp. 1753-1767, 2012.
    [9] S. Lindström and H. Andersson-Svahn, "Overview of single-cell analyses: microdevices and applications," Lab on a Chip, vol. 10, pp. 3363-3372, 2010.
    [10] S. Zheng, H. Lin, J.-Q. Liu, M. Balic, R. Datar, R. J. Cote, et al., "Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells," Journal of Chromatography A, vol. 1162, pp. 154-161, 2007.
    [11] G. Kang, Y.-j. Kim, H.-s. Moon, J.-W. Lee, T.-K. Yoo, K. Park, et al., "Discrimination between the human prostate normal cell and cancer cell by using a novel electrical impedance spectroscopy controlling the cross-sectional area of a microfluidic channel," Biomicrofluidics, vol. 7, p. 044126, 2013.
    [12] K. F. Lei, M.-H. Wu, C.-W. Hsu, and Y. Chen, "Electrical impendance determination of cancer cell viability in a 3-dimensional cell culture microfluidic chip," Int J Electrochem Sci, vol. 7, pp. 12817-12828, 2012.
    [13] S. Pecorelli, G. Favalli, L. Zigliani, and F. Odicino, "Cancer in women," International Journal of Gynecology & Obstetrics, vol. 82, pp. 369-379, 2003.
    [14] M. Schlesinger and M. Paunovic, Modern electroplating vol. 55: John Wiley & Sons, 2011.
    [15] 陳冠廷, "應用雙層電極結合微孔洞結構於微粒子捕捉及阻抗量測," 碩士, 電機工程學系, 國立成功大學, 台南市, 2014.
    [16] J. Luo, D. Chu, A. Flewitt, S. Spearing, N. Fleck, and W. Milne, "Uniformity control of Ni thin-film microstructures deposited by through-mask plating," Journal of The Electrochemical Society, vol. 152, pp. C36-C41, 2005.
    [17] H. Yang and S.-W. Kang, "Improvement of thickness uniformity in nickel electroforming for the LIGA process," International Journal of Machine Tools and Manufacture, vol. 40, pp. 1065-1072, 2000.
    [18] I. Kim and P. F. Mentone, "Electroformed nickel stamper for light guide panel in LCD back light unit," Electrochimica Acta, vol. 52, pp. 1805-1809, 2006.
    [19] J.-d. Li, P. Zhang, Y.-h. Wu, Y.-s. Liu, and M. Xuan, "Uniformity study of nickel thin-film microstructure deposited by electroplating," Microsystem Technologies, vol. 15, pp. 505-510, 2009.
    [20] Y. Guo, G. Liu, and Y. Tian, "Investigation on overplating high-aspect-ratio microstructure," in MOEMS-MEMS 2006 Micro and Nanofabrication, 2006, pp. 61090M-61090M-8.
    [21] T. A. Nguyen, T.-I. Yin, and G. Urban, "A cell impedance sensor chip for cancer cells detection with single cell resolution," in SENSORS, 2013 IEEE, 2013, pp. 1-4.
    [22] Y. Cho, H. S. Kim, Z. G. Chen, D. M. Shin, and A. Han, "Whole-cell impedance analysis for highly and poorly metastatic cancer cells," Microelectromechanical Systems, Journal of, vol. 18, pp. 808-817, 2009.
    [23] A. Comsol, "COMSOL multiphysics user’s guide," Version: September, 2005.
    [24] S. Chisca, I. Sava, V.-E. Musteata, and M. Bruma, "Dielectric and conduction properties of polyimide films," in CAS 2011 Proceedings (2011 International Semiconductor Conference), 2011.
    [25] M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, et al., "Gold nanostructures: engineering their plasmonic properties for biomedical applications," Chemical Society Reviews, vol. 35, pp. 1084-1094, 2006.
    [26] S. Terry, "HeLa Herself," The Scientist, vol. 20, p. 22, 2006.
    [27] M.-H. Wang and W.-H. Chang, "Effect of Electrode Shape on Impedance of Single HeLa Cell: A COMSOL Simulation," BioMed research international, vol. 2015, 2015.


    無法下載圖示 校內:2020-08-27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