臺灣博碩士論文加值系統

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。

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 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.

Contents
摘要................................................................................................................................ I
Abstract..................................................................................................................... III
Acknowledgment V
Contents......................................................................................................................VI
List of Tables VIII
List of Figures IX
Chapter 1 Introduction 1
1.1 Motivation 1
1.2 Thesis Organization 2
Chapter 2 Introduction of Implantable Device and Stimulation Therapy 3
2.1 Introduction of Implantable SoC 3
2.2 Introduction of Neuromodulation 4
2.3 Introduction of Electrode-Tissue Impedance Model 6
2.4 Introduction of Stimulation Patterns 8
Chapter 3 Design of Monopolar Biphasic Voltage Stimulator 11
3.1 Prior Works of Stimulator 11
3.1.1 Bipolar Configuration 11
3.1.2 Monopolar Configuration 13
3.2 Specifications and Design Considerations of Stimulator 15
3.2.1 Negative Voltage Operation Analysis 16
3.3 Design of Stimulator 18
3.3.1 Stimulus Driver 19
3.3.2 Driver Switch Control 21
3.3.3 Voltage Reference DAC 23
3.3.4 Folded Cascode Op-amp 25
Chapter 4 Simulation Results and Measurement Results 28
4.1 Simulation Results 28
4.2 Measurement Results 32
4.3 Animal Experiment Results 40
4.4 Measurement Results of Other Applications 44
4.4.1 Modified for Bipolar Stimulator 44
4.4.2 8-Channel Monopolar Stimulator System 48
4.5 Summary 53
Chapter 5 Conclusions and Future Works 54
5.1 Conclusions 54
5.2 Future Works 55
5.2.1 Parkinson’s Disease Application 55
5.2.2 Stimulator with Output Capacitor 56
5.2.3 Design of Dual-Configuration and Dual-Mode Stimulator 60
References 62
Vita............................................................................................................................... 66

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