臺灣博碩士論文加值系統

本篇論文提出及分析應用於下視網膜互補式金氧半太陽能電池256像素刺激晶片移植系統，晶片架構基於分區供電方式(DPSS)和主動式像素元件(APS)改良輸出刺激電流之效率。實驗之晶片八區分區供電為16x16的光二極體陣列以及控制訊號產生電路。而晶片採用台積電0.18um互補式金氧半CIS製程工藝。最終的晶片尺寸為3mm x 3mm，DPSS11在5mW/cm2 之訊號光以及80mW/cm2 之紅外線背景光照射下量測，負載為10-kΩ時控制訊號頻率為47.68赫茲，輸出的雙向刺激電流有19.9uA;負載為生物模型時控制訊號頻率為45.45赫茲，輸出的雙向刺激電流有19.52uA，累積電荷量為1.1nC。DPSS12在0.4 mW/cm2 之訊號光以及80mW/cm2 之紅外線背景光照射下量測，負載為10-kΩ時控制訊號頻率為30.2赫茲，輸出的雙向刺激電流有19.95uA;負載為生物模型時控制訊號頻率為30.2赫茲，輸出的雙向刺激電流有19.84uA，累積庫倫量為1.64nC，此量測結果驗證了晶片可以正常操作。

A photovoltaic-cell-powered CMOS 256-pixel implantable chip is proposed for subretinal prostheses. In the proposed chip, the divisional power supply scheme (DPSS) and the active pixel sensor (APS) are adopted to improve the efficiency of output stimulation currents and the image sensitivity. The proposed chip consists of a 16x16 photodiode array with 8 DPSS divisions, control signal generator circuits, and photovoltaic cells. It is designed and fabricated in 180-nm CMOS image sensor (CIS) technology. The chip size is 3mm x 3mm. The DPSS11 measured frequency of eight-phase control signals is 47.68 Hz under signal light intensity of 5 mW/cm2 and background IR intensity of 80 mW/cm2. The measured output stimulation current is 19.9 μA under 10-kΩ load. Under the equivalent electrode impedance load, the measured frequency of eight-phase control signals is 45.45 Hz. The measured peak output stimulation current is 19.52 μA and the amount of injected charges per pixel is 1.1 nC. The DPSS12 measured frequency of eight-phase control signals is 30.2 Hz under signal light intensity of 0.4 mW/cm2 and background IR intensity of 80 mW/cm2. The measured output stimulation current is 19.95 μA under 10-kΩ load. Under the equivalent electrode impedance load, the measured frequency of eight-phase control signals is 30.2 Hz. The measured peak output stimulation current is 19.84 μA and the amount of injected charges per pixel is 1.64 nC. The measurement results have verified the correct function of the proposed subretinal implant chip.

DPSS11—CMOS CIS 256-pixel subretinal chip version I
DPSS12-- CMOS CIS 256-pixel subretinal chip version II

CONTENTS
ABSTRACT (CHINESE) i
ABSTRACT (ENGLISH) ii
ACKNOWLEDGEMENTS iv
CONTENTS v
TABLE CAPTIONS vii
FIGURE CAPTIONS viii

CHAPTER 1 INTRODUCTION 1
1.1 Background 1
1.2 Review on the Subretinal Prostheses 4
1.3 Motivation 9
1.4 Main Results and Thesis Organization 10
CHAPTER 2 CHIP ARCHITECTURE AND CIRCUIT DESIGN 11
2.1 Chip Architecture and Operational Principle 11
2.2 Circuit Design 15
2.2.1 Divisional Power Supply Scheme …………………………………..15
2.2.2 Current-Cancellation Circuit ………………………………………..18
2.2.3 Control Signal Generation Curcuit………………………………..........19
2.2.4 Pixel Stimulation Circuit……………………………………………….25
2.3 Post Simulation Results 29
CHAPTER 3 EXPERIMENTAL RESULTS 32
3.1 Measurement Results of Photodiode Test-keys 32
3.2 Measurement Results of Subretinal Chips 39
3.2.1 Measurement Setup…………………………………………………….39
3.2.2 Measurement Results ………………………………………………….41
3.2.3 Discussion…………………………………………………………...53
CHAPTER 4 CONCLUSIONS AND FUTURE WORK 59
4.1 Conclusions 59
4.2 Future Work 61
REFERENCES 62
VITA 65

[1] C.Hamel,”Retinitis pigmentosa,” Orphanet Journal of Rare Diseases, vol. 1, no.1 , article no. 40 ,2006.

[2] D. S. Friedman, B. J. O'Colmain, B. Munoz, S. C. Tomany, C. McCarty et al., “Prevalence of age-related macular degeneration in the United States,” Arch Ophthalmol, vol. 122, no. 4, pp. 564-572, April 2004.

[3] G. Brindley, W. Lewin "The sensation produced by electrical stimulation of the visual cortex". Journal of Physiology 196, pp. 479–93,1968

[4] A. Majji, M. Humayun, J. Weiland, S. Suzuki, S. D’Anna, E. deJuan Jr. (1999). "Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs". Investigative Ophthalmology and Visual Science 40 (9): 2073–81.

[5] P. Walter, P. Szurman, M. Vobig, H. Berk, H. Ludtke-Handjery, H.Richter, et. al. (1999). "Successful long-term implantation of electrically inactive epiretinal microelectrode arrays in rabbits". Retina 19 (6): 546–52.
[6] K. Sooksood, E. Noorsal, J. Becker, and M. Ortmanns, " A neural stimulator front-end with arbitrary pulse shape, HV compliance and adaptive supply requiring 0.05mm2 in 0.35μm HVCMOS," IEEE International Solid-State Circuits Conference, pp. 306-308,2011.

[7] C.-C. Chiao, Y.-T. Yang, C. Wan, W.-C. Yang, L.-J. Lin, P.-K. Lin, and C.-Y. Wu,” Responses of rabbit retinal ganglion cells to subretinal electrical stimulation with a silicon-based microphotodiode array,” ARVO Abstract. Invest. Ophtha. Vis. Sci., vol. 33, no. 4, May 2010, pp. 1048-1992.

[8] K. Mathieson, J. Loudin, G. Goetz, P. Huie, L. Wang, T. I. Kamins, L. Galambos, R. Smith, J. S. Harris, A. Sher and D. Palanker, “Photovoltaic retinal prosthesis with high pixel density,” Nature Photonics, vol. 6, pp. 391-397, May. 2012.

[9] C.-L. Lee and C.-C. Hsieh, “A 0.8-V 4096-Pixel CMOS Sense-and-Stimulus Imager for Retinal Prosthesis,” IEEE Transactions on Electron Devices, vol. 60, pp. 1162-1168, 2013.

[10]P.-K. Lin, P.-H. Kuo, Y.-C. Tsai, M.-J. Sui, C.-C. Chiao, T. Noda, J. Ohta, and C.-Y. Wu, “The ex vivo and in vivo electrophysiological investigations of a subretinal photovoltaic prosthesis embedded with solar cells and divisional-power-supply-scheme,” in TEATC (World Research Congress: The Eye and The Chip), 2014.

[11] S. Oh, J.-H. Ahn, S. Lee, H. Ko, J. M. Seo, Y.-S. Goo, and D. Cho, “Light-Controlled Biphasic Current Stimulator IC Using CMOS Image Sensors for High-Resolution Retinal Prosthesis and In Vitro Experimental Results With rd1 Mouse,” IEEE Transactions on Biomedical Engineering, vol. 62, pp. 70-79, 2015.

[12] K. Chen, Z. Yang, L. Hoang, J. Weiland, M. Humayun, and W. Liu, “An integrated 256-channel epiretinal prosthesis,” IEEE J. Solid-State Circuits, vol. 45, pp. 1946-1956, Sept. 2010.

[13] K. Chen, Z. Yang, L. Hoang, J. Weiland, M. Humayun, and W. Liu, “A 37.6mm2 1024-Channel High-Compliance -Voltage SoC for Epiretinal Prostheses,” in IEEE ISSCC Dig. Tech. Papers, 2013, pp. 294-296.

[14] C.-Y. Wu, W.-J. Sung, P.-H. Kuo, C.-K. Tzeng, C.-C. Chiao, and Y.-C. Tsai, “The design of CMOS self-powered 256-pixel implantable chip with on-chip photovoltaic cells and active pixel sensors for subretinal prostheses, ” IEEE Biomedical Circuits and Systems Conference (BioCAS), 2015.

[15] E. Zrenner, V. P. Gabel, F. Gekeler, R. B. Graf et al., "From passive to active subretinal implants, serving as adapting electronic substitution of degenerated photoreceptors," IEEE Proc. neural network Int. Joint Conf., vol 1, 2004.

[16] D. Besch, H. Sachs, P. Szurman., “Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: feasibility and outcome in seven patients,” British Journal of Ophthalmology, vol. 92, no. 10, pp.1361–1368, 2008.

[17] E. Zrenner, R. Wilke., “Subretinal microelectrode arrays allow blind retinitis pigmentosa patients to recognize letters and combine them to words,” in Biomedical Eng. and Informatics, 2009.

[18] F. Gekeler, P. Szurman, D. Besch, E. Zrenner., "Implantation and explantation of active subretinal visual prostheses using a combined transcutaneous and transchoroidal approach," Nove Acta Leopoldina, vol. 379, pp. 205-216, 2010.

[19] A. Rothermel., “A 1600-pixel subretinal chip with DC-free terminals and ±2V supply optimized for long lifetime and high stimulation efficiency,” ISSCC Dig. Tech. Papers, pp. 144-602, Feb. 2008.

[20] Brandon Bosse, Eberhart Zrenner, Robert Wilk “Standard ERG Equipment Can Be Used to Monitor Functionality of Retinal Implants,” 33rd Annual International Conference of the IEEE EMBS Boston, Massachusetts USA, August 30 - September 3, 2011

[21] K. Mathieson, J. Loudin, G. Goetz, P. Huie, L. Wang, T. I. Kamins, L. Galambos, R. Smith, J. S. Harris, A. Sher and D. Palanker, “Photovoltaic retinal prosthesis with high pixel density,” Nature Photonics, vol. 6, pp. 391-397, May. 2012.

[22] C.-Y. Wu, P.-H. Kuo, P.-K. Lin, Y.-C. Huang, C.-K. Su, H. Li, C.-C. Chiao, Y.-T. Huang, Y.-C. Tsai, J.-W. Pan, T. Noda, and J. Ohta, “A Soar-Cell Powered CMOS Sensing and Stimulation Chip with Divisional Power Supply Scheme for Subretinal Prostheses,” in TEATC (World Research Congress: The Eye and The Chip), 2014.

[23] J. Ohta , T. Tokuda , K Kagawa . Laboratory investigation of microelectronics-based stimulators for large-scale suprachoroidal transretinal stimulation (STS). J Neural Eng. 2007;4:S85–S91.

[24] T. Tokuda, T. Ito, T. Kitao, T. Noda . “ CMOS-based smart-electrode-type retinal stimulator with bullet-shaped bulk Pt electrodes,” 33rd Annual International Conference of the IEEE EMBS Boston, Massachusetts USA, August 30 - September 3, 2011

[25] P. B. Matteucci, P. Byrnes-Preston, S. C. Chen, N. H. Lovell, and G. J. Suaning, "ARM-based visual processing system for prosthetic vision," IEEE Engineering in Medicine and Biology Society, pp. 3921-3924, 2011.

[26] C.-Y. Wu, P.-K. Lin, J. Lin, C. Yang, C. Wan, “Power controlling apparatus applied to biochip and operating method thereof.” U.S. Patent 7 622 702, Mar. 12, 2009.