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研究生： 吳建宏
Jian-Hung Wu
論文名稱： 光學式生化反應即時偵測系統
指導教授： 楊宗勳
Tsung-Hsun Yang
口試委員:
學位類別： 碩士
Master
系所名稱： 理學院 - 光電科學與工程學系
Department of Optics and Photonics
畢業學年度： 94
語文別： 中文
論文頁數： 115
中文關鍵詞： 光學感測器 、導膜共振
外文關鍵詞： Biosensor, Guide-mode resonance, DNA hybridization
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    • 本文研製一新型光學生物感測器：導模共振(guided mode resonance, GMR)光學生物感測器。本元件利用半導體技術，製作一次波長光柵結構，並利用其產生的窄帶高反射率之效果，及其光柵表面區域之高敏感度，應用於共種生化反應，本元件具有以下優點：免標定、微小化、可高產量、即時偵測、易與其它半導體元件接合之優點。
    本研究已將GMR元件組裝至流體系統內，形成GMR流體晶片。除了方便將整個生化實驗於晶片內進行外，所使用到的檢體量也相對的減少，並發展出一套即時檢測平台，縮短了檢測所需時間。目前於晶片本身已能檢測出折射率變化量小於0.001，且偵側去氧核醣核酸之雜交行為，除了可即時觀察出有無雜交反應外，其有無雜交差異量更達9倍之多。對於胜肽合成，能成功偵測出每段長度約0.3nm之胺基酸接合反應及其反應之分子動力學行為。

    We report a novel method for detecting biomolecular interaction which utilizes the guided-mode resonance (GMR) phenomenon with narrow-band high reflection efficiency characteristics. The structure of GMR device generally consists of two stages — upper grating layer and waveguide layer. GMR device and flow cell are combined to from a GMR flow cell system. The system has several advantages such as label-free, minimizing, real time monitoring, high throughput, low cost, and the potential to become portable. We show the system experimentally with the ability to detect the refractive index variations <0.001,the amino acid thickness variations <0.3nm. It also can detect DNA hybridization and measure molecular interaction.

    第一章 緒論......................................................................1 1.1 生物晶片簡介..............................................................3 1.1.1 微陣列晶片...............................................................4 1.1.2 實驗室晶片...............................................................5 1.2 生物反應訊號之光學檢測方法..................................6 1.2.1 螢光共振能量轉移法...............................................7 1.2.2 表面電漿共振儀.......................................................9 1.2.3 MACH-ZEHNDER干涉儀生物感測法......................10 1.2.4全內反射螢光法......................................................11 1.3 研究動機.... ............................................................ 14 1.3.1 GMR發展................................................................15 1.3.2 GMR生物檢測流體晶片....................................... 17 第二章 GMR流體晶片之設計與模擬.............................19 2.1 GMR理論...................................................................19 2.1.1 GMR簡介................................................................19 2.1.2 GMR嚴格耦合波概論............................................20 2.2 GMR流體晶片之設計...............................................26 2.2.1 GMR元件設計........................................................26 2.2.2 GMR流道系統之設計............................................29 2.3 GMR流體晶片之模擬...............................................39 2.3.1 GMR元件之模擬....................................................40 2.3.2 GMR流體晶片之模擬............................................44 第三章 GMR流體晶片之製作與量測.............................48 3.1 GMR流體晶片之製作...............................................48 3.1.1 GMR元件之製作....................................................48 3.1.2 GMR流道之製作....................................................51 3.2 GMR流體晶片之特性量測.......................................54 3.2.1量測系統..................................................................54 3.2.2 GMR流體晶片之特性量測...................................55 3.3 即時監測軟體之開發............................................... 57 3.3.1多項式的曲線擬合..................................................59 3.3.2 系統操作說明.........................................................61 第四章 GMR即時生物檢測流體晶片.............................63 4.1 靈敏度之分析……………………………………….63 4.1.1不同溶液之偵測…………………………………...63 4.1.2 不同濃度已醇溶液偵測..................................................65 4.2 去氧核醣核酸之雜交偵測.................................................67 4.2.1 去氧核醣核酸之雜交......................................................70 4.2.2 DNA雜交實驗流程..........................................................71 4.2.3 去氧核醣核酸偵測訊號分析..........................................76 4.2.4 DNA雜交之重複性偵測..................................................77 4.3 胜肽合成.............................................................................81 4.3.1 胺基酸接合......................................................................82 4.3.2 胜肽合成實驗流程..........................................................86 4.3.3去氧核醣核酸偵測訊.......................................................88 4.3.4胜肽合成之反應動力曲線分析.......................................91 第五章 結論與未來展望............................................................. 93 參 考 文 獻........................................................................... 96

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