未來展望

我們目前已能利用簡化之模組去鑑別細胞貼附與分化的細胞型態，未來一方 面可運用阻抗量測來測量神經細胞與電極介面之電阻抗特性，另一方面也可利用 膜外電刺激的方式來了解細胞電生理特性。

本實驗的阻抗量測環境是採用封閉式的培養環境，然而近年來在微流道系統 中分析更複雜的活體細胞研究更是引起了人們的注意，它在細胞生物學、神經生 物學、藥理學及組織工程等都發揮了日益重要的作用，其主要優點為可以為細胞 設計微米尺度的培養環境並可精確控制流體流動使其接近在活體培養環境，並且 微米尺度的培養空間能夠減少細胞培養的時間和成本。

若能進一步將阻抗系統與微流道結合，將能進行更多應用與分析。單一細胞 的行為與特性在醫療上可以為其病理狀態提供重要資訊，因此也希望未來可以藉 由微流道系統捕捉單一細胞後再進行阻抗分析。

55

參考文獻

[1] L. Clark Jr and C. Lyons, "Electrode systems for continuous monitoring in cardiovascular surgery," Annals of the New York Academy of Sciences, vol. 102, pp.

29-45, 1962.

[2] R. Pethig, "Dielectric properties of biological materials: biophysical and medical applications," IEEE Transactions on Electrical Insulation, pp. 453-474, 1984.

[3] M. Cheney, et al., "Electrical impedance tomography," SIAM review, vol. 41, pp.

85-101, 1999.

[4] L. Greene and A. Tischler, "Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor," Proceedings of the National Academy of Sciences of the United States of America, vol. 73, p. 2424,

1976.

[5] D. McClay, et al., "Intercellular recognition: quantitation of initial binding events," Proceedings of the National Academy of Sciences of the United States of America, vol. 78, p. 4975, 1981.

[6] C. Galbraith and M. Sheetz, "A micromachined device provides a new bend on fibroblast traction forces," Proceedings of the National Academy of Sciences of the United States of America, vol. 94, p. 9114, 1997.

[7] G. Sagvolden, et al., "Cell adhesion force microscopy," Proceedings of the National Academy of Sciences, vol. 96, p. 471, 1999.

[8] I. Giaever and C. R. Keese, "Monitoring fibroblast behavior in tissue culture with an applied electric field," Proc Natl Acad Sci U S A, vol. 81, pp. 3761-4, Jun 1984.

[9] A. Dijkstra, et al., "Review clinical applications of electrical impedance

56

tomography," Journal of medical engineering & technology, vol. 17, pp. 89-98, 1993.

[10] K. Cole and H. Curtis, "Electric impedance of the squid giant axon during activity," Journal of general physiology, vol. 22, p. 649, 1939.

[11] H. Fricke and S. Morse, "The electric resistance and capacity of blood for frequencies between 800 and 4.5 million cycles," J. Gen. Physiol, vol. 9, p. 153¡V67, 1925.

[12] L. Hause, et al., "Electrode and electrolyte impedance in the detection of bacterial growth," IEEE Transactions on Biomedical Engineering, pp. 403-410, 1981.

[13] J. Wegener, et al., "Electric cell-substrate impedance sensing (ECIS) as a noninvasive means to monitor the kinetics of cell spreading to artificial surfaces,"

Experimental Cell Research, vol. 259, pp. 158-166, 2000.

[14] I. Giaever and C. Keese, "Use of electric fields to monitor the dynamical aspect of cell behavior in tissue culture," IEEE Transactions on Biomedical Engineering, pp.

242-247, 1986.

[15] I. Giaever, "A morphological biosensor for mammalian cells," Nature, vol. 366, pp. 591-592, 1993.

[16] I. Giaever and C. Keese, "Fractal motion of mammalian cells," Physica D:

Nonlinear Phenomena, vol. 38, pp. 128-133, 1989.

[17] C. Lo, et al., "Monitoring motion of confluent cells in tissue culture,"

Experimental Cell Research, vol. 204, pp. 102-109, 1993.

[18] C. Lo, et al., "Impedance analysis of MDCK cells measured by electric cell-substrate impedance sensing," Biophysical journal, vol. 69, pp. 2800-2807, 1995.

[19] I. Giaever and C. Keese, "Micromotion of mammalian cells measured electrically," Proceedings of the National Academy of Sciences of the United States of America, vol. 88, p. 7896, 1991.

57

[20] R. Hagedorn, et al., "Characterisation of cell movement by impedance measurement on fibroblasts grown on perforated Si-membranes," Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, vol. 1269, pp. 221-232, 1995.

[21] J. Wegener, et al., "Impedance analysis of epithelial and endothelial cell monolayers cultured on gold surfaces," Journal of biochemical and biophysical methods, vol. 32, pp. 151-170, 1996.

[22] R. Ehret, et al., "Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures," Biosensors and Bioelectronics, vol. 12, pp.

29-41, 1997.

[23] G. Slaughter, et al., "Improving neuron-to-electrode surface attachment via alkanethiol self-assembly: an alternating current impedance study," Langmuir, vol. 20, pp. 7189-7200, 2004.

[24] C. Keese, et al., "Real-time impedance assay to follow the invasive activities of metastatic cells in culture," Biotechniques, vol. 33, pp. 842-851, 2002.

[25] M. Chanana, et al., "Interaction of polyelectrolytes and their composites with living cells," Nano Lett, vol. 5, pp. 2605-2612, 2005.

[26] M. Lundien, et al., "Induction of MCP-1 expression in airway epithelial cells:

role of CCR2 receptor in airway epithelial injury," Journal of clinical immunology, vol. 22, pp. 144-152, 2002.

[27] J. Luong, et al., "Monitoring motility, spreading, and mortality of adherent insect cells using an impedance sensor," Anal. Chem, vol. 73, pp. 1844-1848, 2001.

[28] E. Zudaire, et al., "The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers," Journal of Clinical Investigation, vol.

118, pp. 640-650, 2008.

[29] L. Charrier, et al., "ADAM-15 inhibits wound healing in human intestinal

58

epithelial cell monolayers," American Journal of Physiology- Gastrointestinal and Liver Physiology, vol. 288, p. G346, 2005.

[30] A. van den Berg and T. Lammerink, "Micro total analysis systems: microfluidic aspects, integration concept and applications," Microsystem Technology in Chemistry and Life Science, pp. 21-49, 1998.

[31] D. Reyes, et al., "Micro total analysis systems. 1. Introduction, theory, and technology," Anal. Chem, vol. 74, pp. 2623-2636, 2002.

[32] H. Andersson and A. Van den Berg, "Microfluidic devices for cellomics: a review," Sensors and Actuators B: Chemical, vol. 92, pp. 315-325, 2003.

[33] J. El-Ali, et al., "Cells on chips," Nature, vol. 442, pp. 403-411, 2006.

[34] D. Carlo, et al., "Dynamic single cell culture array," Lab on a Chip, vol. 6, pp.

1445-1449, 2006.

[35] G. Markx, et al., "Dielectrophoretic characterization and separation of micro-organisms," Microbiology, vol. 140, p. 585, 1994.

[36] D. Grier, "A revolution in optical manipulation," Nature, vol. 424, pp. 810-816, 2003.

[37] M. Park, et al., "Pumpless, selective docking of yeast cells inside a microfluidic channel induced by receding meniscus," Lab on a Chip, vol. 6, pp. 988-994, 2006.

[38] A. Manbachi, et al., "Microcirculation within grooved substrates regulates cell positioning and cell docking inside microfluidic channels," Lab on a Chip, vol. 8, p.

747, 2008.

[39] L. Kim, et al., "A practical guide to microfluidic perfusion culture of adherent mammalian cells," Lab on a Chip, vol. 7, pp. 681-694, 2007.

[40] M. Yang, et al., "Cell docking and on-chip monitoring of cellular reactions with a controlled concentration gradient on a microfluidic device," Anal. Chem, vol. 74, pp.

59

3991-4001, 2002.

[41] W. Tan and S. Takeuchi, "A trap-and-release integrated microfluidic system for dynamic microarray applications," Proceedings of the National Academy of Sciences, vol. 104, p. 1146, 2007.

[42] T. Merkel, et al., "Gas sorption, diffusion, and permeation in poly (dimethylsiloxane)," Journal of Polymer Science Part B: Polymer Physics, vol. 38, pp.

415-434, 2000.

[43] A. Paguirigan and D. Beebe, "Gelatin based microfluidic devices for cell culture," Lab on a Chip, vol. 6, pp. 407-413, 2006.