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研究生:賴彥邦
研究生(外文):Lai, Yen-Pang
論文名稱:CMOS離子感測電晶體用於即時偵測去氧核糖核酸的放大過程
論文名稱(外文):A CMOS-Compatible ISFET for Detecting DNA in the Amplification in Real-time
指導教授:陳新陳新引用關係
指導教授(外文):Chen, Hsin
學位類別:碩士
校院名稱:國立清華大學
系所名稱:電機工程學系
學門:工程學門
學類:電資工程學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:英文
論文頁數:101
中文關鍵詞:去氧核糖核酸固定式滾環擴增法CMOS製程延伸閘極電晶體讀值電路
外文關鍵詞:DNAImmobilized RCACMOS-compatibleEGFETReadout circuitry
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  • 被引用被引用:0
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DNA(去氧核糖核酸)分析被廣泛地應用在生物醫學測試以及許多日常生活中相關應用的生物鑑定。因為DNA本身具有專一性的特點,所以我們可以藉由DNA分析來檢驗樣本內是否含有目標DNA以及它在樣本中的含量。

滾環擴增法(Rolling Circle Amplification)是用於DNA定性和定量分析的新穎技術。不同於傳統的聚合酶鏈鎖反應(Polymers Chain Reaction),這種滾環式擴增法可以在室溫下針對從檢體中取出的微量目標DNA進行大量複製。此外,固定式滾環擴增法可以藉由3-氨基丙基三甲氧基甲矽烷(APTES)修飾矽化物表面進而讓該反應能在其上進行。在本論文中,我們將使用CMOS元件即時檢測目標DNA在進行固定式滾環擴增法時的濃度變化。不同於以往使用螢光標定法或是進行電泳實驗,我們使用一個具有氮化矽絕緣層的CMOS延伸閘極場效電晶體(CMOS-compatible Extended-Gate Field-Effect-Transistor)即時感測目標DNA在固定式滾環擴增法中的濃度變化。此外我們也使用另一種CMOS開閘極離子感測電晶體 (CMOS-compitable open-gate Ion-Sensitive Field-Effect-Transistor)來測試DNA的電性量測。 最後我們提出並量測三種用來直接讀取表面電位變化的嵌入式延伸閘極電晶體讀值電路。

It is well known that the DNA (Deoxyribonucleic Acid) assays have been used widely in bio-medical tests and in many applications of bio-identification. Because DNA has the specific property, we can use DNA assays to justify if the target DNA exists and how many it is in the samples.

Rolling Circle Amplification (RCA) is a novel technology in both quantitative and qualitative DNA assays. Unlike the conventional Polymerase Chain Reaction (PCR) process, the RCA process can be proceeded in the room temperature to amplify a few of target DNAs which are extracted from the samples. Besides, the immobilized RCA can occur on the surface of silicon-based material with the modification of 3-Aminopropyltriethoxysilane (APTES). In this work, we are devoted to real-time detecting the changes of DNA concentrations in the immobilized RCA process with the current CMOS devices. Instead of using the fluorescence-labeling or doing the electrophoresis, a CMOS-compatible Extended-Gate Field Effect Transistor (EGFET) with its native passivation (silicon nitride) is employed to monitor the concentration change of the target DNA in the immobilized RCA process. Besides, the other CMOS-compatible open-gate ISFET is also proposed to do the pilot test of the DNA detection. Finally, three types of readout circuits with embedded EGFETs are proposed to read the surface potential of the embedded EGFETs directly and characterized electrically.

Chapter 1 :Introduction
1.1 Motivation
1.2 Contribution to Knowledge
1.3 Chapter Layout
Chapter 2 :Literature Review
2.1 DNA Amplification Methods
2.1.1 The Polymerase Chain Reaction
2.1.2 The Rolling Circle Amplification
2.2 Label-Free DNA Detection
2.2.1 Detecting the Intrinsic Charge of DNAs
2.2.2 The Charge Redistribution within The Intermolecular Space of DNAs
2.3 Label-Free DNA Detection Devices
2.3.1 Electrical-Gap Devices
2.3.2 FETs
2.3.3 Impedance Measurement
Chapter 3 :Label-Free Detection of DNA with CMOS- Compatible ISFETs
3.1 Pilot experiments with Open-Gate ISFETs
3.1.1 Post-CMOS Micromachining Process of Open-Gate ISFETs
3.1.2 Electrical Tests
3.1.3 Methodology of ds-DNA Immobilization
3.2 Design of Extend-Gate ISFETs
3.3 Measurement Setup
3.4 Experimental Results with EGFETs
3.5 Discussion
3.6 Summary
Chapter 4 :Detecting the Rolling Circle Amplification with EGFETs
4.1 The Immobilization of RCA Primers
4.2 Measurement Setup
4.3 Experimental Results
4.4 Discussion
4.5 Summary
Chapter 5 :EGFETs Integrated with Detection Circuitry on a Single Chip
5.1 Design Considerations
5.1.1 Sensor Structure
5.1.2 Integrated Circuitry
5.2 Simulation & Layout
5.2.1 First Edition CVCC Readout Circuit
5.2.2 Second Edition CVCC Readout Circuit
5.2.3 Embedded EGFET OP Readout Circuit
5.2.4 The Tunable Resistor
5.2.5 The Whole Chip Layout
5.3 Characterization of EGFETs and Detection Circuitries 75
5.3.1 The Capacitance of CMOS Passivation Layer
5.3.2 The Input Dynamic Range and Noise Level of The Readout Circuits without The Extended Gate
5.3.3 The Input Dynamic Range of The Readout Circuits with EGFETs
5.3.4 The Long Term Measurement
5.4 Summary
Chapter 6 :Conclusion and Future Work
6.1 Conclusion
6.2 Future Work
Appendix
1. The coupling ratio measurement of EGFET sensors with the external CVCC circuit
2. Measurement results with the fluorescent photographs of the EGFET sensors which are used in the RCA process
3. The Atomic Force Microscopy (AFM) photographs of RCA
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