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研究生: 鍾岳霖
Chung, Yueh-Lin
論文名稱: 應用於DNA感測之積體電路系統設計
An Integrated Circuit System for DNA Detection Application
指導教授: 陳新
Chen, Hsin
口試委員: 林致廷
Lin, Chih-Ting
金雅琴
King, Ya-Chin
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2017
畢業學年度: 105
語文別: 英文
論文頁數: 107
中文關鍵詞: DNA感測電荷感測阻抗感測奈米線
外文關鍵詞: DNA detection, Charge detection, Impedance detection, Nanowire
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  • DNA(去氧核醣核酸)是掌管生物體中遺傳訊息的重要物質,而DNA檢驗的技術也廣泛被應用在生醫相關領域上。與螢光標定法相比,利用DNA本身電性所開發出的電性感測系統可以在相對較低的成本及技術需求下完成DNA即時檢測的工作。然而,DNA電性檢測系統之靈敏度與解析度受限於反應環境、DNA感測元件特性、電路架構等因素,無法達到實務應用的需求。若能改善以上問題,則可以省去DNA檢測前所需的化學反應,進而達到實務上應用的可能。
    本論文嘗試利用各種不同的手法提升DNA電性檢測系統的靈敏度。於本論文中,一版電荷感測電路以及一版阻抗感測電路被設計以感測水溶液中之DNA含量。於感測電路中,本論文使用經過親水性處理之金電極EGFET增強DNA訊號,同時利用內部雜訊較低的感測電路降低其對靈敏度的限制。此外,由於DNA感測元件之靈敏度為決定整體系統靈敏度之最大要素,本論文嘗試利用台積電90奈米標準製成製作奈米線元件,並嵌入於感測晶片內,藉此達到較高之解析度及解析度,同時設計一版導電度感測電路以測量奈米線元件導電度之變化。
    量測及實驗結果顯示本次設計之兩版電路皆可量測到DNA反應所產生的訊號,而DNA反應之訊號之大小與EGFET表面電極之大小有關。奈米線元件之量測部分由於結構問題並無法表現正確的特性,而感測電路部分以電阻取代奈米線元件進行量測,量測結果顯示導電度感測電路則可以偵測到元件之導電度變化。


    DNA sequences store the genetic information of creatures, and DNA detection technique is employed for biochemical applications. Compared with fluorescent labeling, the detection system based on electrical characteristic of DNA can achieve DNA detection utility with lower cost and lower technical requirement. However, the sensitivity and the resolution of DNA detection system are restricted by the reaction environment, the characteristic of sensing devices, and the structure of readout circuits. If these issues can be solved, the chemical treatment before DNA detection can be omitted to reach practical application.
    Different DNA detection mechanism is employed in this thesis to improve the sensitivity of an electrical DNA detection system. In this thesis, a charge detection circuit and an impedance detection circuit is designed to sense DNA concentration in a solution. A gold electrode EGFETs with hydrophilic treatment are employed in this thesis to enhance the DNA signal, and the low-noise detection circuits are employed to improve the sensitivity of the detection system. Moreover, since the sensitivity of DNA sensing device dominates the performance of the detection system, a nanowire device made in TSMC 90nm process is designed and embedded in sensor chip to reach higher sensitivity and resolution. A conductance detection circuit is design with the nanowire to detect the conductance change of nanowire.
    The measurement results and experiment results show that both charge detection circuit and impedance detection circuits can detect signals of DNA reaction. The size of gold electrodes affects the amplitude of DNA signals. The electrical characteristic of

    Table of Contents 致謝 i 摘要 ii Abstract iii Table of Contents iv List of Figures vii List of Tables xii Chapter 1 Introduction 1 1.1 Motivation 1 1.2 Contribute to Knowledge 2 1.3 Chapter Layout 3 Chapter 2 Theory Description and Literature Review 3 2.1 Characteristics of DNA 4 2.2 DNA Replication 6 2.2.1 DNA Replication Mechanism 6 2.2.2 Polymerase Chain Reaction 7 2.2.3 Rolling Circle Amplification 9 2.3 Electrolyte-Electrode Interface 10 2.3.1 Charge-potential relation of electrolyte-electrode interface 10 2.3.2 Impedance Model of Electrolyte-electrode Interface 14 2.3.3 Effects of DNA Binding on the Electrode 16 2.3.3.1 Charge-potential effect 16 2.3.3.2 Impedance effect 17 2.3.4 Hydrophilic Issue of Electrolyte-electrode Interface 19 2.4 DNA Detection Mechanisms 20 2.4.1 Chemical Mechanism 20 2.4.2 Electrical Mechanism 21 2.5 Electrical DNA Concentration Detection 21 2.5.1 Field Effect Transistors System 22 2.5.1.1 Charge Detection Biosensors 23 2.5.1.2 Impedance Detection Biosensors 25 2.5.2 Nanowire 27 Chapter 3 Integrated Circuit with Gold Microelectrode 28 3.1 Gold Microelectrodes 28 3.2 Charge Detection DNA Sensor 31 3.2.1 System Architecture 32 3.2.2 Subtractor with Gold Microelectrodes 33 3.2.3 Low Pass Filter 34 3.2.4 Simulation Results 37 3.3 Impedance Detection DNA Sensor 42 3.3.1 System Architecture 43 3.3.2 Impedance Sensing Circuit with Gold Microelectrodes 45 3.3.3 Demodulator 49 3.3.4 Low-Pass Filter 51 3.3.5 Simulation Results 55 Chapter 4 Nanowire in TSMC CMOS 90nm Process 64 4.1 Nanowire in CMOS Process 64 4.2 Nanowire Device Design 66 4.3 Conductance Detection Circuit Design 67 4.4 Simulation Result 70 Chapter 5 Experimental Results 73 5.1 Gold Electrolyte-electrode Interface 73 5.1.1 Potential Measurement 73 5.1.2 Impedance Measurement 74 5.2 Charge Detection Sensor 75 5.2.1 Environment Setup 75 5.2.2 Electrical Characteristic Measurement 76 5.2.3 RCA Experiments 77 5.2.4 DNA Removal Experiments 81 5.2.5 Issue Discussion 86 5.3 Impedance Detection Sensor 86 5.3.1 Environment Setup 87 5.3.2 Electrical Characteristic Measurement 87 5.3.3 Ion Concentration Measurement 92 5.3.4 Issue Discussion 93 5.4 Nanowire 94 5.4.1 Measurement Result of Nanowire 95 5.4.2 Measurement Result of Conductance Detection Circuit 98 5.4.3 Issue Discussion 99 Chapter 6 Conclusion and Future Work 101 6.1 Conclusion 101 6.2 Future Work 102 Reference 103 Appendix 105

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