摘要
神經電刺激在神經功能失調治療和神經損傷康復中具有極其重要的作用。隨著微電子控制技術，電腦技術以及神經科學的發展，神經電刺激已經從傳統的經由皮層電刺激逐漸發展到植入式電刺激階段，目前植入式神經電刺激在治療和控制帕金森病，癲癇，慢性疼痛，聽視覺障礙等多個方面已經取得了較大進展。
本論文的設計為一個控制植入式生理電刺激器的控制器以及電刺激器。電刺激器必須透過電極作為介面才能對神經或肌肉進行電刺激的動作，然而電極－組織介面阻抗可能因電極本體受刺激電流、環境等因素而產生變化，或者受接觸不良、電極大小與材質的影響，例如視網膜是一個弧狀的面，所以不同位置的電極，接觸到組織形成的阻抗值亦會不同，其變異範圍在10KΩ– 100KΩ，所以對於不同的介面阻抗值，必須調整刺激週期使得刺激電荷量可以達到有效的電刺激，此時如果沒有依照阻抗的變化量予以控制增減刺激的電荷量，會導致所需要的刺激量和施予細胞的刺激量出現不相等的現象，並且當刺激量超過某一定程度之後，便有可能產生永久性的細胞傷害。
為了讓電刺激器能滿足阻抗變異的需求，根據阻抗變異與電刺激參數的設定，論文中提出了一個可以根據介面阻抗不同而自動調整刺激時間的控制器，此控制器能依照每次的刺激阻抗不同而自動調整所需要的刺激時間週期，一方面使得刺激的組織得到需要的刺激量，另一方面保護刺激過量導致組織損壞。
電刺激器則是利用產生三倍供應電壓輸出的高電壓輸出級驅動電路，並以台積電0.18μm互補式金氧半導體的標準製程實現，其好處是不需花費其他昂貴的特殊製程，又可以與其他電路整合於同一晶片。

Abstract
Functional Neuromuscular Stimulation plays an important role in the treatment of nervous diseases and rehabilitation of nerve injury. With the rapid development of microelectronic technology, bio-technology and Neuroscience, Functional Neuromuscular Stimulation has been transformed from a traditional electrical stimulation to implantable electrical stimulation, and got great progress in Parkinson, Epilepsy, Chronic Pain and others visual diseases.
This thesis aims to design an electrical stimulator controller for implanted visual prosthesis. The designed electrical stimulator stimulates nerves or muscles using electrodes as the interface. Generally the impedance of electrode-tissue interface may change in the rage of 10KΩ – 100KΩ due to electrode itself such as poor contact, the electrode size, material differences, and stimulus current and environmental factors. It is necessary to adjust the stimulus period to get correct electrical charge, otherwise, will induce the difference between theoretical electrical charge and real electrical charge, and sometimes will damage the cell permanently.
This thesis proposes a new impedance measurement circuit called PWM-based auto-tuning electrical charge timing controller, ahead of the stimulation circuit, to prevent inaccurate electrical charge and protect histiocyte. The width of the digital pulse width modulator can be varied automatically, based on different interface impedances. That means the stimulus period can be auto-adjusted with dynamic impedance to get required electrical charge and best effect.
Besides, the electrical stimulator is designed by a high voltage output driver which can generate three times supply voltage output. The whole design is implemented in TSMC 0.18-μm standard CMOS technology to demonstrate the feasibility of the proposed electrical stimulator. An advantage is that it can be fully integrated with other circuits without extra processing costs.

參考文獻
[1] W. T. Liberson, H. J. Holmquest, D. Scot, and M. Dow, “Functional electrotherapy: stimulation of peroneal nerve synchronized with the swing phase of the gait of hemiplegic patients,” Arch. Phys. Med. Rehabil., vol. 42, pp. 101-105, Feb. 1961.
[2] A. Kralj, T. Bajd, R. Turk, J. Krajnik, and H. Benko, “Gait restoration in paraplegic patients: a feasibility demonstration using multichannel surface electrode FES,” J. Rehabil. R&D, vol. 20, pp. 3-20, Jul. 1983.
[3] C. Sauer, M. Stanacevic, G. Cauwenberghs, and N. Thakor, “Power harvesting and telemetry in CMOS for implanted devices,” IEEE Journal of Solid-State Circuits, vol. 52, no. 12, pp. 2605 -2613, Dec. 2005.
[4] M. Sivapralasam, W. Liu, G. Wang, J. D. Weiland, and M. S. Humayun, “Architecture tradeoffs in high-density microstimulators for retinal prosthesis,” IEEE Transactions on Circuits and Systems, vol. 52, no. 12, pp. 2629-2641, Dec. 2005.
[5] D. R. McNeal, R. J. Nakai, P. Meadows, and W. Tu, “Open-loop control of the freely-swinging paralyzed leg,” IEEE Trans. Biomed. Eng., vol. 36, no. 9, pp.895-905, Sep. 1989.
[6] A. P. Chu, K. Morris, R. J. Greenberg, and D. M. Zhou, “Stimulus induced PH changes in retinal implants,” IEEE Engineering in Medicine and Biology Society Conference, vol. 2, pp. 4160-4162, Sep. 2004.
[7] M. Mahadevappa, J. D. Weiland, D. Yanai, I Fine, R. J. Greenberg, and M. S. Humayun, “Perceptual thresholds and electrode impedance in three retinal prosthesis subjects,” IEEE Trans. Neural Syst. Rehabil. Eng., vol. 13, no. 2, pp. 201-206, Jun. 2005.
[8] M. Sivaprakasam, W. Liu, M. S. Humayun, and J. D. Weiland, “A variable range bi-phasic current stimulus driver circuitry for an implantable retinal prosthetic device,” IEEE Journal of Solid-State Circuits, vol. 40, no. 3, pp. 763-771, Mar. 2005.
[9] L. S. Y. Wong, S. Hossain, A. Ta, J. Edvinsson, D. H. Rivas, and H. Naas, “A very low-power CMOS mixed-signal IC for implantable pacemaker applications,” IEEE J. Solid-State Circuits, vol. 39, no. 12, pp. 2446-2456, Dec. 2004.
[10] J. Georgiou and C. Toumazou, “A 126-μW cochlear chip for a totally implantable system,” IEEE J. Solid-State Circuits, vol. 40, no. 2, pp. 430-443, Feb. 2005.
[11] S. K. Kelly and J. Wyatt, “A power-efficient voltage-based neural tissue stimulator with energy recovery,” ISSCC Dig. Tech. Papers, pp. 228-230, Feb. 2004.
[12] M. Ghovanloo, “Switched-capacitor based implantable low-power wireless microstimulating systems,” Proc. ISCAS, pp. 2197-2200, May 2006.
[13] https://www.blindness.org
[14] http://webvision.med.utah.edu
[15] J. D. Weiland and M. S. Humayun, “Intraocular retinal prosthesis,” IEEE Eng. Med. Biol. Mag., vol. 25, pp. 60-66, Sep. 2006.
[16] J. D. Weiland, D. Yanai, M. Mahadevappa, R. Williamson, B. V. Mech, G. Y. Fujii, J. Little, R. J. Greenberg, E. de Juan Jr., and M. S. Humayun, “Electrical stimulation of retina in blind humans,” Proc. 25th Annu. Int. Conf. IEEE EMBS, Cancun, Mexico, vol. 3, pp. 2021-2022, Sep. 2003.
[17] P. Hossain, I. W. Seetho, A. C. Browning, and W. M. Amoaku, “Artificial means for restoring vision,” BMJ, vol. 330, pp. 30-33, Jan. 2005.
[18] K. Cha, K. W. Horch, R. A. Normann, and D. K. Boman, “Reading speed with a pixelized vision system,” J. Opt. Soc. Am. A, vol. 9, no. 5, pp. 673-677, May 1992.
[19] R. W Thompson, G. D. Barnett, M. S. Humayun, and G. Dagnelie, “Facial recognition using simulated prosthetic pixelized vision,” Invest. Ophthalmol. Vis. Sci., vol. 44, no. 11, pp. 5035-5042, Nov. 2003.
[20] J. D. Weiland and M. S. Humayun, “A biomimetic retinal stimulating array: design considerations,” IEEE Eng. Med. Biol. Mag., vol. 24, no. 12, pp. 14-21, Sep. 2005.
[21] Bin He, “Neural Engineering,” vol. 1, no. 1.5.1, Figure 1.22, pp. 29, 2005.
[22] J. J. Sit and R. Sarpeshkar, “A low-power blocking-capacitor-free charge-balanced electrode-stimulator chip with less than 6nA dc error for 1-mA full scale stimulation,” IEEE Transactions on Biomedical Circuits and System, vol. 1, no. 3, pp. 172-183, Sep. 2007.
[23] S. Franco, “Electric circuits fundamentals,” 1st ed. New York: Oxford, Aug. 1994.
[24] D. Seo, H. Dabag, Y. Guo, M. Mishra, and G. H. McAllister, “High-voltage-tolerant analog circuits design in deep-submicrometer CMOS technologies,” IEEE Transactions on Circuits and Systems, vol. 54, no. 10, pp. 2159-2166, Oct. 2007.
[25] B. Serneels, T. Piessens, M. Steyaert, and W. Dehaene, “A high-voltage output driver in a 2.5-V 0.25-μm CMOS technology,” IEEE Journal of Solid-State Circuits, vol. 40, no. 3, pp. 576-583, Mar. 2005.
[26] P. Swaroop, A. J. Vasani, and M. Ghovanloo, “A high-voltage output driver for implantable biomedical stimulators and I/O applications,” IEEE International Midwest Symposium on Circuits and Systems, pp. 566-569, Aug. 2006.
[27] S. Rajapandian, K. Shepard, P. Hazucha, and T. Karnik, “High-tension power delivery: Operating 0.18μm CMOS digital logic at 5.4V,” IEEE Solid-State Circuits Conference, vol. 16, no. 4, pp. 298-599, Feb. 2005.
[28] A. J. Annema, G. J. G. M. Geelen, and P. C. de Jong, “5.5-V I/O in a 2.5-V 0.25-μm CMOS technology,” IEEE Journal of Solid-State Circuits, vol. 36, no. 3, pp. 528-538, Mar. 2001.
[29] LINEAR TECHNOLOGY, LT1466L variable current Source circuit
[30] Li-Jen Liu, Yeong-Chau Kuo, and Wen-Chieh Cheng, “Analog PWM and Digital PWM Controller IC for DC/DC Converters” , IEEE 2009 Fourth International Conference on Innovative Computing, Information and Control, pp. 904-907, 2009
[31] Juing-Huei Su, Chien-Ming Wang, Jiann-Jong Chen, Jing-Da Lee and Tzu-Ling Chen,“Interactive Simulation and Verification SIMULINK Models for DC-DC Switching Converter Circuits using PWM Control ICs,” IEEE Power Electronics and Drives Systems, pp.1256-1261, Nov. 2005
[32] P. E. Allen and D. R. Holberg, “CMOS analog circuit design,” 2nd ed. New York: Oxford, Jan. 2002.
[33] D. Seo, H. Dabag, Y. Guo, M. Mishra, and G. H. McAllister, “High-voltage-tolerant analog circuit design in deep-submicrometer CMOS technologies,” IEEE Trans. Circuits Syst., vol. 54, no. 10, pp. 2159-2166, Oct. 2007.
[34] B. Serneels, T. Piessens, M. Steyaert, and W. Dehaene, “A high-voltage output driver in a 2.5-V 0.25-μm CMOS technology,” IEEE J. Solid-State Circuits, vol. 40, no. 3, pp. 576-583, Mar. 2005.
[35] http://www.tsmc.com/download/enliterature/html-newsletter/April04/Quality &Reliability /index.html
[36] N. Dommel, Y. T. Wong, P. J. Preston, T. Lehmann, N. H. Lovell, and G. J. Suaning, “The design and testing of an epi-retinal vision prosthesis neurostimulator capable of concurrent parallel stimulation,” Proc. 28th Annu. Int. Conf. IEEE EMBS, New York, USA, vol. 12, pp. 4700-4709, Sep. 2006.
[37] M. Ortmanns, N. Unger, A. Rocke, M. Gehrke, and H. J. Tietdke, “A 0.1mm2, digitally programmable nerve stimulation pad cell with high-voltage capability for a retinal implant,” ISSCC Dig. Tech. Papers, pp. 89-91, Feb. 2006.
[38] S. Ethier, M. Sawan, E. M. Aboulhamid, and M. E. Gamal, “A ±9V fully integrated CMOS electrode driver for high-impedance microstimulation,” Proc. 52nd IEEE Int. Midwest Symp. Circuits Syst., Cancun, Mexico, pp. 192-195, Aug. 2009.
[39] P. Nadeau and M. Sawan, “A flexible high voltage biphasic current-controlled stimulator,” Proc. IEEE BioCAS, London, UK, pp. 206-209, Nov. 2006.
[40] Y. Yao, M. N. Gulari, J. A. Wiler, and K. D. Wise, “A microassembled low-profile three-dimensional microelectrode array for neural prosthesis applications,” IEEE J. Microelectromech. Syst., vol. 6, no. 4, pp. 977-988, Aug. 2008.
[41] W. Qu, S. K. Islam, M. R. Mahfouz, M. R. Haider, G. To, and S. Mostafa, “Microcantilever array pressure measurement system for biomedical instrumentation,” IEEE Sensors Journal, vol. 10, no. 2, pp. 321-330, Feb. 2010.