用於植入式生醫應用之多通道單端雙相電壓刺激器設計 Design of Multi-Channel Monopolar Biphasic Voltage Stimulator for Implantable Biomedical Applications 研究生 : 謝佳琪指導教授 : 柯明道教授

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1 國立交通大學電子研究所碩士論文用於植入式生醫應用之多通道單端雙相電壓刺激器設計 Design of Multi-Channel Monopolar Biphasic Voltage Stimulator for Implantable Biomedical Applications 研究生 : 謝佳琪 (Chia-Chi Hsieh) 指導教授 : 柯明道教授 (Prof. Ming-Dou Ker) 中華民國一 O 七年六月

2 用於植入式生醫應用之多通道單端雙相電壓刺激器設計 Design of Multi-Channel Monopolar Biphasic Voltage Stimulator for Implantable Biomedical Applications 研究生 : 謝佳琪指導教授 : 柯明道教授 Student:Chia-Chi Hsieh Advisor:Prof. Ming-Dou Ker 國立交通大學電子研究所碩士論文 A Thesis Submitted to Institute of Electronics College of Electrical and Computer Engineering National Chiao Tung University in Partial Fulfillment of the Requirements for the Degree of Master of Science in Electronics Engineering June 2018 Hsinchu, Taiwan, Republic of China 中華民國一 O 七年六月

3 用於植入式生醫應用之多通道單端雙相電壓刺激器設計學生 : 謝佳琪指導教授 : 柯明道教授國立交通大學電子研究所摘要腦中神經系統的不正常放電現象, 可能會進一步影響運動神經, 讓身體發生無法控制的抖動, 像是帕金森氏症及癲癇等疾病, 而世界上約有七千萬人口患有此類症狀近年來, 電刺激技術漸漸取代藥物治療, 被用於醫療方面, 透過在異常的神經部位給予電刺激的方式, 可以使身體恢復部分機能並且, 隨著積體電路與生醫電子的發展, 在單晶片上整合智慧型仿生系統的目標可被實現, 結合微電子技術醫學以及生物化學, 能夠發展出應用於不同治療的生物晶片, 例如 : 閉迴路深層腦部刺激 (Deep brain stimulation) 系統植入式單晶片癲癇抑制系統以及電子耳的應用根據本生醫研究團隊為治療帕金森氏症的前提, 本篇提出一多通道的電壓刺 I

4 激器, 藉由單一輸出對植入式起搏器 (Implantable pulse generator) 機殼送出雙相位的定電壓, 來完成每次的電壓刺激為因應電極與人體組織阻抗的變動, 考慮負載適應性, 此刺激器設計了 0.5V~ 8V 的大範圍電壓輸出, 搭配 4 位元的控制訊號, 有 16 種電壓大小可以調整, 因此系統可根據不同的應用輸出適當的刺激電壓像是帕金森氏症的治療, 通常使用不超過 3.5V 的電壓刺激, 但在電子耳的動物實驗中, 卻可能需要大於 5V 的電壓刺激對於植入式單晶片的整合而言, 設計時需考量安全性功率消耗與可靠度, 而刺激器的電源供應, 會由前級的電荷幫浦系統提供 10V 的高電壓來維持整體電路的正常操作刺激器電路在 0.25-μm 2.5-V/5-V/12-V 的高電壓製程下實現, 即使在必須承受 20V 耐壓的狀況下與負電壓的操作中, 電路也不會有 p-n 接面的崩潰 p-n 接面的順向導通或元件過壓等問題 II

5 Design of Multi-Channel Monopolar Biphasic Voltage Stimulator for Implantable Biomedical Applications Student: Chia-Chi Hsieh Advisor: Prof. Ming-Dou Ker Institute of Electronics National Chiao-Tung University Abstract Neurological disorder causes unusual electrical activity in the brain that further affects the motor system, such as Parkinson s disease and epilepsy, and there are seventy million population around the world suffer from these symptoms. Instead of drugs, electrical stimulation therapy has been proven to effectively restore some physical functions of patients by stimulating the abnormal nerve sites. With the development of CMOS process and bioelectronics, an implantable system-on-chip (SoC) device is able to be realized. Combing with microelectronics, medicine and biochemistry, the biomedical chip is made for different therapeutic applications. For example, closed-loop deep brain stimulation (DBS) system, implantable SoC for seizure control, and cochlear implant. According to the research of our biomedical group, a multi-channel voltage stimulator is proposed for Parkinson s disease treatment. It completes every III

6 stimulation by delivering biphasic stimulus voltage to implantable pulse generator (IPG) case from one of the stimulator outputs. Considering of loading adaptation due to electrode-tissue impedance variation, a wide-range of stimulus voltage from 0.5V to 8V is designed. The adjustable output voltage is controlled by 4-bit binary code, which allows the system to generate 16 different amplitudes. Therefore, the proposed stimulator can be used in many biomedical applications through providing a proper stimulus voltage. In the treatment of Parkinson s disease, voltage stimulation under 3.5V is often used. However, a voltage that is larger than 5V might be needed in the animal experiment of cochlear. For implantable SoC integration, safety, power consumption, and reliability have to be taken into consideration. A multi-charge-pump (MCP) system, which serves as power supply to stimulator and provides 10V to support the circuit operation. The whole stimulator circuit has been fabricated in TSMC 0.25-μm HV USG 2.5-V/5-V/12-V CMOS process without device overstress, p-n junction breakdown issue, or p-n junction forward-leakage problem under 20V compliance voltage and negative voltage operation. IV

苗栗三山國王信仰及其地方社會意涵 The Influences and Implications of Local Societies to Three Mountain Kings Belief, in Taiwan Miaoli 研究生 : 林永恩指導

苗栗三山國王信仰及其地方社會意涵 The Influences and Implications of Local Societies to Three Mountain Kings Belief, in Taiwan Miaoli 研究生 : 林永恩指導國立交通大學客家文化學院客家社會與文化學程碩士論文苗栗三山國王信仰及其地方社會意涵 The Influences and Implications of Local Societies to Three Mountain Kings Belief, in Taiwan Miaoli 研究生 : 林永恩指導教

用於植入式生醫應用之 多通道單端雙相電壓刺激器設計 Design of Multi-Channel Monopolar Biphasic Voltage Stimulator for Implantable Biomedical Applications 研究生 : 謝佳琪 指導教授 : 柯明道教授

用於植入式生醫應用之多通道單端雙相電壓刺激器設計 Design of Multi-Channel Monopolar Biphasic Voltage Stimulator for Implantable Biomedical Applications 研究生 : 謝佳琪指導教授 : 柯明道教授