本研究利用半導體製程技術研發製備植入型微電極陣列探針，其中所應用的半導體製程包括加熱、微影、薄膜、蝕刻等，並針對每個步驟進行最佳化，進而製備出精密、微型、高產量、低成本的微電極陣列探針。製程主要可分為三個階段，第一階段為探針金屬圖層之形成，包含電極端、電路及封裝端的形成，利用微影製程及電子束蒸鍍，將金屬圖案轉印至基材上。第二階段為探針表層的鈍化，除了電極端與封裝端以外的部分皆須沉積絕緣層，因此金屬圖案形成後我們使用電漿輔助化學氣相沉積將其表面覆蓋介電層作絕緣，並將電極端與封裝端進行局部的蝕刻以利後續研究。第三階段為探針邊界輪廓定義，利用微影製程定義出探針的輪廓後，進行不同材料的深蝕刻將探針從晶圓中取出。在整個流程中以微影製程的步驟最為困難及繁瑣，然而曝光所使用的光罩直接地影響光阻的圖案化，且圖樣的設計非常彈性，因此本研究同時針對光罩的設計部分進行修改與調整，盼能在微影製程中能夠有更好的效率及良率。本製程主要以成本作為考量，並著重探針生產的效率以及產量，比較不同方法對於製程的適性所建立的植入型微電極陣列製程。

In this research, the semiconductor manufacturing technology we used to fabricate implantable microelectrode array (MEA) probes. The manufacturing process that we used included thermal oxidation, photolithography, thin film deposition and etching. We optimized each processing step in order to make miniaturized and low-cost microelectrode array probes with good spatial resolution, high production rate, and high yield. The process can be divided into three parts. The first part is the formation of metal layer on the probes that defined electrode sites, channels and bonding pads. The photolithography technology and metal deposition technology by electron beam evaporator were used to transfer the metal pattern on the substrate. The second part is the passivation process of probe surface. The dielectric layer was deposited on the probe to prevent short circuit. Therefore, after the formation of metal layer, plasma enhanced chemical vapor deposition (PECVD) was used to deposit dielectric layer. Then the electrode sites and the bonding pads defined by the second photolithography process were etched to expose their metal surfaces. The third part is the definition of probe outline. The third photolithography process was used to define the pattern of probe outline and then, the etching process was used to etch the outline to the bottom of the substrate in order to make the probes releasable from the wafer. In the whole process, photolithography is the most difficult and complicated step; however, we can modify the pattern of the probe layout to improve the process conditions. In this research, we also focused on the layout design of MEA probes and hoped to improve the process efficiency and the yield of MEA probes. The cost of this manufacturing process is a major consideration; therefore, we compared different processing method and chose better processing parameters for our process in order to establish an optimized MEA manufacturing process for the production of probes with high production rate and yield.

[1] Wassum, K. M., Tolosa, V. M., Wang, J., Walker, E., Monbouquette, H. G., & Maidment, N. T. (2008). Silicon wafer-based platinum microelectrode array biosensor for near real-time measurement of glutamate in vivo. Sensors, 8(8), 5023-5036.
[2] Burmeister, J. J., Pomerleau, F., Palmer, M., Day, B. K., Huettl, P., & Gerhardt, G. A. (2002). Improved ceramic-based multisite microelectrode for rapid measurements of L-glutamate in the CNS. Journal of Neuroscience Methods, 119(2), 163-171.
[3] Wise, K. D., Sodagar, A. M., Yao, Y., Gulari, M. N., Perlin, G. E., & Najafi, K. (2008). Microelectrodes, microelectronics, and implantable neural Microsystems. Proceedings of the IEEE, 96(7), 1184-1202.
[4] Plummer, J. D., Deal, M. D., & Griffin, P. B. (2000). Silicon VLSI Technology: Fundamentals, Practice and Modeling, Upper Saddle River, New Jersey, MA: Prentice Hall.
[5] Xiao, H. 著. 羅正忠, 張鼎張 譯. (2002) 半導體製程技術導論 (Introduction to Semiconductor Manufacturing Technology), 台北, 台灣培生教育出版: 學銘圖書發行.
[6] Castillo, J., Gaspar, S., Letha, S., Niculescua, M., Mortari, A., Bontideana, I., Soukharevb, V., Dorneanu, S. A., Ryabovc A. D., & Csoregi E. (2004). Biosensors for life quality: Design, development and applications. Sensors and Actuators B: Chemical, 102(2), 179-194.
[7] Cunningham, A. J. (1998). Introduction to Bioanalytical Sensors(1st ed.)., New York: John Wiley & Sons, INC.
[8] Stulik, K., Amatore, C., Holub, K., Marecek, V., & Kunter, W. (2000). Microelectrodes. Definitions, characterization, and applications (Technical Report). Pure and Applied Chemistry, 72(8), 1483-1492.
[9] Frey, O., van der Wal, P., de Rooij, N., & Koudelka-Hep, M. (2007, August). Development and Characterization of Choline and L-Glutamate Biosensor Integrated on Silicon Microprobes for In-vivo Monitoring. Conference of the IEEE EMBS, Cite Internationale, Lyon, France.
[10] Hammerle, H., Kobuch, K., Kohler, K., Nisch, W., Sachs, H., & Stelzle, M. (2002). Biostability of micro-photodiode arrays for subretinal implantation. Biomaterials, 23(3), 797-804.
[11] Bai, Q., & Wise, K. D. (2001). Single-Unit Neural Recording with Active Microelectrode Arrays. IEEE Transactions on Biomedical Engineering, 48(8), 911-920.
[12] Campbell, P.K., Jones, K.E., Huber, R.J., Horch, K.W., & Normann, R. A. (1991). A Silicon-Based, Three-Dimensional Neural Interface: Manufacturing Processes for an Intracortical Electrode Array. IEEE Transactions on Biomedical Engineering, 38(8), 758-768.
[13] Csicsvari, J., Henze, D. A., Jamieson, B., Harris, K. D., Sirota, A., Bartho, P., Wise, K. D., & Buzsaki, G. (2003). Massively Parallel Recording of Unit and Local Field Potentials Wih Silicon-Based Electrodes. Journal of Neurophysiology, 90, 1314-1323.
[14] Wise, K.D., Anderson, D.J., Hetke, J.F., Kipke, D.R., & Najafi, K., (2004). Wireless Implantable Microsystems: High-Density Electronic Interfaces to the Nervous System. Proceedings of the IEEE, 92(1), 76-97.
[15] Zhong Y., Yu X., Gilbert R., & Bellamkonda R. V. (2001). Stabilizing electrode-host interfaces: a tissue engineering approach. Journal of Rehabilitation Research and Development, 38(6), 627-632.
[16] Cheung, K. C., Renaud, P., Tanila, H., & Djupsund, K. (2006). Flexible polyimide microelectrode array for in vivo recordings and current source density analysis. Biosensors and Bioelectronics, 22(8), 1783-1790.
[17] Richardson Jr., R. R., Miller, J. A., & Reichert, W. M. (1993). Polyimides as biomaterials: preliminary biocompatibility testing. Biomaterials, 14(8), 627-635.
[18] Seo, J. -M., Kim, S. J., Chung, H., Kim, E. T., Yu, H. G., & Yu, Y. S. (2004). Biocompatibility of polyimide microelectrode array for retinal stimulation. Materials Science and Engineering, 24(1-2), 185-189.