臺灣博碩士論文加值系統

本篇論文提出一電流模式且具備電荷補償架構之電刺激器(Functional Electrical Stimulator, FES)，在此雙通道系統之電刺激器中具備一六位元之電流數位類比轉換器以提供刺激電流，且為因應動物實驗及人體使用需求，其電流之調整幅度為50uA至3mA。此外，亦考量電刺激器之安全議題，因此使用雙相位電流模式(biphasic current mode)，藉由陰極電流達到抑制癲癇之效果，隨之以一個同樣大小的陽極電流進行第一階段之電荷補償，且所產生之刺激波形參數可以12位元進行調整，以增加使用彈性。然而由於製程非理想效應，累積電荷無法被雙相位電流完全抵銷，因此進一步以一創新之AB類放大器作為電荷補償機制，藉由AB類放大器之特點，可以達到低靜態電流，高補償效率之特點。並以此雙通道電刺激器系統結合實驗室發展之類比前端感測電路(analog front-end, AFE) 系統發展動物實驗平台並與台灣大學獸醫系張芳嘉教授團隊合作進行動物實驗，藉此驗證功能性電刺激器在使用上之安全性，並評估刺激之有效性。而為了進一步增加此電刺激器系統之使用彈性，亦將單一通道之電刺激器重新進行模組化設計，以利通道之擴增；同時，改良雙相電流架構，並新增脈衝(pulse)及指數衰減性(decaying exponential) 波形之選擇，用以衡量不同刺激波形對於刺激效率造成之影響。此設計以四通道之規格進行晶片下線，晶片之效能正在進行量測。

A current mode functional electrical stimulator(FES) with class-AB charge compensation mechanism is proposed. In the two-channel FES, a six-bit current DAC is equipped to provide the stimulation current, and the current intensity can be adjusted from 50 uA to 3 mA for animal experiments and human body use. In addition, the safety issue of the electric stimulator is also considered. Therefore, the biphasic current mode is applied to suppress the epileptic effect first by a cathodic current, and then an anodic current of the same intensity is performed for the first stage charge elimination. Besides, the generated stimulation waveform parameters can be adjusted in 12 bits to increase the application flexibility. However, due to the non-ideal effect of the process, the accumulated charge cannot be completely cancelled by the biphasic current. Therefore, an innovative class-AB based charge compensator is proposed. By the characteristics of the class AB OTA, low quiescent current and high compensation efficiency can be achieved. The two-channel FES system was combined with an analog front-end (AFE) system to develop an animal experimental platform and cooperated with the team of Professor Fang-Chia Chang of the Taiwan University Veterinary Department to conduct animal experiments to verify the safety issue and the effectiveness of the FES. In order to further increase the flexibility of the FES, a single channel FES is modularized to facilitate channel expansion. At the same time, the biphasic current architecture is improved, and the shape selection function between pulse and decaying exponential shape is added to further analysis the stimulation efficiency. This design is applied in a four-channel FES, and the performance of the chip is being measured.

Abstract in Chinese . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Abstract in English . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viii
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
List of Figures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv
List of Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxii
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Structure of The Functional Electrical Stimulation . . . . . . . . . . . . . 3
1.2.1 Constant Voltage Stimulator . . . . . . . . . . . . . . . . . . . . 4
1.2.2 Constant Current Stimulator . . . . . . . . . . . . . . . . . . . . 5
1.2.3 Dynamic Power Supply Stimulator . . . . . . . . . . . . . . . . 7
1.3 Charge Compensation Mechanism . . . . . . . . . . . . . . . . . . . . . 9
1.3.1 Introduction of Charge Balance . . . . . . . . . . . . . . . . . . 9
1.3.2 Sample and Hold Current Mirror Structure . . . . . . . . . . . . 11
1.3.3 Active Charge Balancing Based On Pulse Insertion . . . . . . . . 12
1.4 The Model of The Electrode and The Electrolyte . . . . . . . . . . . . . 13
1.5 Analysis of Stimulation Efficiency Between Different Stimulation Shapes 15
2 Design Consideration of The Proposed Functional Electrical Stimulator . . . . 17
2.1 Using Scenarios . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.2 Design Specification . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.3 System Architecture of The Two-Channel FES . . . . . . . . . . . . . . 20
2.3.1 Overall Structure of Two-Channel FES . . . . . . . . . . . . . . 20
2.3.2 The Digital Control Scheme . . . . . . . . . . . . . . . . . . . . 22
2.3.3 The Analog Circuit Architechture . . . . . . . . . . . . . . . . . 24
2.4 System Architecture of The Four-Channel FES . . . . . . . . . . . . . . 27
2.4.1 Introduction of The Multi-Channel Design . . . . . . . . . . . . 27
2.4.2 Overall Structure of The Four-Channel Design . . . . . . . . . . 28
2.4.3 The Main Digital Control Scheme . . . . . . . . . . . . . . . . . 29
2.4.4 The Analog Circuit Architechture . . . . . . . . . . . . . . . . . 32
3 Circuit Implementation and Measurement Results . . . . . . . . . . . . . . . . 34
3.1 Circuit Implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3.1.1 Biphasic Current Structure Evolution . . . . . . . . . . . . . . . 34
3.1.2 Design of Different Stimulation Shapes . . . . . . . . . . . . . . 37
3.1.3 Digital Control Scheme . . . . . . . . . . . . . . . . . . . . . . . 42
3.1.4 Class-AB Charge Compensation Mechanism . . . . . . . . . . . 50
3.1.5 Multi-Channel Scalability . . . . . . . . . . . . . . . . . . . . . 56
3.2 Measurement Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3.2.1 Current DAC Measurement . . . . . . . . . . . . . . . . . . . . 62
3.2.2 Biphasic Current Measurement . . . . . . . . . . . . . . . . . . . 65
3.2.3 Charge Compensation Measurement . . . . . . . . . . . . . . . . 68
3.2.4 Digital Controller Measurement . . . . . . . . . . . . . . . . . . 70
3.2.5 Stimulation Shapes Measurement . . . . . . . . . . . . . . . . . 72
3.2.6 Comparison Table . . . . . . . . . . . . . . . . . . . . . . . . . 74
3.3 Discussion and Future Work . . . . . . . . . . . . . . . . . . . . . . . . 76
4 Stimulation System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
4.1 First Version: The FES Chip with FPGA controller . . . . . . . . . . . . 80
4.2 Second Version: The FES and AFE System Integration Platform . . . . . 82
4.3 Third Version: The Miniaturization of FES and AFE System Integration
Platform . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
5 Animal Experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
5.1 Experimental Setup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
5.1.1 Setting of The Reference Voltage in The Brain Tissue . . . . . . . 86
5.1.2 Correctness of Electrical Stimulation Pattern Before and After Flowing
Through The Tissue . . . . . . . . . . . . . . . . . . . . . . 87
5.2 Experimental Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
5.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
5.3.1 Judgment of Effective Electrical Stimulation . . . . . . . . . . . 95
5.3.2 Stimulation Parameters Applied in Animal Experiment and The
Experimental Mode . . . . . . . . . . . . . . . . . . . . . . . . . 96
5.3.3 Future Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
6 Conclusion and Contribution . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
6.1 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
6.2 Contribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Letter of Authority . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

[1] M. L. Kringelbach, N. Jenkinson, S. L. Owen, and T. Z. Aziz, “Translational principles of deep brain stimulation,” Nature Reviews Neuroscience, vol. 8, no. 8, pp. 623–635, 2007.
[2] P. Gildenberg, “Evolution of neuromodulation,” Stereotactic and Functional Neurosurgery, vol. 83, no. 2, pp. 71–79, 2005.
[3] J. Niparko, Cochlear implants, principles and practices. Philadelphia: Lippincott Williams and Wilkins, 2009.
[4] G. Dagnelie, “Retinal implants –emergence of a multidisciplinary field,” Current Opinion In Neurology, vol. 25, no. 1, pp. 67–75, 2012.
[5] H.-W. Chiu, M.-L. Lin, C.-W. Lin, I.-H. Ho, W.-T. Lin, P.-H. Fang, Y.-C. Li, Y.-R. Wen, and S.-S. Lu, “Pain control on demand based on pulsed radio-frequency
stimulation of the dorsal root ganglion using a batteryless implantable CMOS SoC,”
IEEE Transactions on Biomedical Circuits and Systems, vol. 4, no. 6, pp. 350–359, 2010.
[6] M. Capogrosso, T. Milekovic, D. Borton, F. Wagner, E. Moraud, J. Mignardot, N. Buse, J. Gandar, Q. Barraud, D. Xing, E. Rey, S. Duis, J. Yang, W. Ko, Q. Li, P. Detemple, T. Denison, S. Micera, E. Bezard, J. Bloch, and G. Courtine, “A brain– spine interface alleviating gait deficits after spinal cord injury in primates,” Nature, vol. 539, pp. 284–288, 2016.
[7] V.-S. Polikova, P.-A. Trescob, and W.-M. Reicherta, “Response of brain tissue to chronically implanted neural electrodes,” Journal of Neuroscience Methods, vol. 148, pp. 1–18, 2005.
[8] C.-Y. Lin, W.-L. Chen, and M.-D. Ker, “Implantable stimulator for epileptic seizure suppression with loading impedance adaptability,” IEEE Transactions on Biomedical Circuits and Systems, vol. 7, no. 2, pp. 196–203, 2013.
[9] E. Noorsal, K. Sooksood, H. Xu, R. Hornig, J. Becker, and M. Ortmanns, “A neural stimulator frontend with high-voltage compliance and programmable pulse shape for epiretinal implants,” IEEE Journal of Solid-State Circuits, vol. 47, no. 1, pp. 244–256, 2012.
[10] H.-M. Lee, H. Park, and M. Ghovanloo, “A power-efficient wireless system with
adaptive supply control for deep brain stimulation,” IEEE Journal of Solid-State Circuits, vol. 48, no. 9, pp. 2203–2216, 2013.
[11] S. Arfin and R. Sarpeshkar, “An energy-efficient, adiabatic electrode stimulator with inductive energy recycling and feedback current regulation,” IEEE Transactions on Biomedical Circuits and Systems, vol. 6, no. 1, pp. 1–14, 2012.
[12] M.-N. van Dongen and W.-A. Serdijn, “A power-efficient multichannel neural stimulator using high-frequency pulsed excitation from an unfiltered dynamic supply,” IEEE Transactions on Biomedical Circuits and Systems, vol. 10, no. 1, pp. 61–71, 2016.
[13] Y.-K. Lo, K. Chen, P. Gad, and W. Liu, “A fully-integrated high-compliance voltage SoC for epi-retinal and neural prostheses,” IEEE Transactions on Biomedical
Circuits and Systems, vol. 7, no. 6, pp. 761–772, 2013.
[14] Z. Luo and M.-D. Ker, “A high-voltage-tolerant and precise charge-balanced neurostimulator in low voltage CMOS process,” IEEE Transactions on Biomedical Circuits and Systems, vol. 10, no. 6, pp. 1087–1099, 2016.
[15] P. J.-H. Lee, A. Bermak, M.-K. Law, and J. Ohta, “A multichannel power-supplymodulated microstimulator with energy recycling,” Design and Test, vol. 33, no. 4, pp. 61–73, 2016.
[16] R. Shepherd, N. Linahan, J. Xu, G. Clark, and S. Araki, “Chronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli,” Acta Oto- Laryngologica, vol. 6, pp. 674–684, 1999.
[17] K. Sooksood, T. Stieglitz, and M. Ortmanns, “An active approach for charge balancing in functional electrical stimulation,” IEEE Transactions on Biomedical Circuits and Systems, vol. 4, no. 3, pp. 162–170, 2010.
[18] A. Demosthenous, “Advances in microelectronics for implantable medical devices,” Advances in Electronics, vol. 2014, no. 981295, 2014.
[19] P. Cong, “Neural interfaces for implantable medical devices: Circuit design considerations for sensing, stimulation, and safety,” IEEE Solid-State Circuits Magazine, vol. 8, pp. 48–56, November 2016.
[20] D. R. Merrill, M. Bikson, and J. G. Jefferys, “Electrical stimulation of excitable tissue: design of efficacious and safe protocols,” Journal of Neuroscience Methods, vol. 141, pp. 171–198, February 2005.
[21] A. Wongsarnpigoon, J. P. Woock, and W. M. Grill, “Efficiency Analysis of Waveform Shape for Electrical Excitation of Nerve Fibers,” IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING, vol. 18, no. 3, pp. 319–328, 2010.
[22] L. Fenno, O. Yizhar, and K. Deisseroth, “The development and application of optogenetics,” Annual Review of Neuroscience, vol. 34, pp. 389–412, 2011.
[23] P.-M. Rossini and S. Rossi, “Transcranial magnetic stimulation: di agnostic, therapeutic and research potential,” Neurology, vol. 68, no. 7, pp. 484–488, 2007.
[24] M. Hallett, “Transcranial magnetic stimulation and the human brain,” Nature,
vol. 406, pp. 147–150, 2000.
[25] W.-J. Tyler, Y. Tufail, M. Finsterwald, M.-L. Taumann, E. J. Olson, and C. Majestic, “Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound,” PLoS One, vol. 3, 2008.
[26] M.-D. Menz, . Oralkan, P.-T. Khuri-Yakub, and S.-A. Baccus, “Precise neural stimulation in the retina using focused ultrasound,” Journal of Neuroscience, vol. 33, pp. 4550–4560, 2013.
[27] S. Kunnumpurath, R. Srinivasagopalan, and N. Vadivelu, “Spinal cord stimulation: principles of past, present and future practice: a review,” Journal of Clinical Monitoring and Computing, vol. 25, pp. 333–339, 2009.
[28] R. R. Harrison and C. Charles, “A low-power low-noise CMOS amplifier for neural recording applications,” IEEE Journal of Solid-State Circuits, vol. 38, pp. 958–965, June 2003.
[29] J. A. Galan, A. J. López-Martín, R. G. Carvajal, J. Ramírez-Angulo, and C. Rubia-Marcos, “Super Class-AB OTAs with adaptive biasing and dynamic output current
scaling,” IEEE Transactions on Circuits and Systems I: Fundamental Theory and Applications, vol. 54, pp. 449–457, March 2007.
[30] N. Butz, A. Taschwer, S. Nessler, Y. Manoli, and M. Kuhl, “A 22 V compliant 56
μW twin-track active charge balancing enabling 100even in monophasic and 36stimulators,” IEEE Journal of Solid-State Circuits, vol. 53, pp. 2298–2310, August 2018.
[31] K. Song, H. Lee, S. Hong, H. Cho, U. Ha, and H.-J. Yoo, “A sub-10 nA DC-balanced adaptive stimulator IC with multi-modal sensor for compact electroacupuncture stimulation,” IEEE Transactions on Biomedical Circuits and Systems, vol. 6, pp. 533–541, December 2012.
[32] H. M. Lee, K. Y. Kwon, W. Li, and M. Ghovanloo, “A power-efficient switched capacitor stimulating system for electrical/optical deep brain stimulation,” IEEE
Journal of Solid-State Circuits, vol. 50, pp. 360–374, January 2015.
[33] W. Y. Hsu and A. Schmid, “Compact, energy-efficient high-frequency switched
capacitor neural stimulator with active charge balancing,” IEEE Transactions on Biomedical Circuits and Systems, vol. 11, p. 878–888, August 2017.
[34] H. Kassiri, F. D. Chen, and R. Genov, “Arbitrary-waveform electro-optical intracranial neurostimulator with load-adaptive high-voltage compliance,” IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING, vol. 7, pp. 582 – 593, April 2019.
[35] H. C, E. FI, B. SM, B. G, M. LE, and L. AM, “Bilateral anterior thalamic nucleus lesions and highfrequency stimulation are protective against pilocarpine induced seizures and status epilepticus,” Neurosurgery, vol. 54, pp. 191–197, January 2004.