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研究生: 蔡定璋
Ding-Zhang Tsai
論文名稱: 運用光通訊波段頻譜干涉表面電漿共振感測器之生醫檢測
Biomedical Sensor using Spectral Interferometry-Based Surface Plasmon Resonance through Telecommunication Wavelength
指導教授: 徐世祥
Shih-Hsiang Hsu
口試委員: 林保宏
Pao-hung Lin
劉信孚
Sin-Fu Liou
張哲菖
Che-Chang Chang
學位類別: 碩士
Master
系所名稱: 電資學院 - 電子工程系
Department of Electronic and Computer Engineering
論文出版年: 2016
畢業學年度: 104
語文別: 中文
論文頁數: 72
中文關鍵詞: 生醫檢測頻譜干涉相位調制去氧核醣核酸結核桿菌流行性感冒表面電漿共振
外文關鍵詞: surface plasmon resonance, biomedical sensing, spectral interferometry, phase interrogation, DNA, mycobacterium tuberculosis, influenza
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  • 生醫光電是一新興且成長迅速的研究領域,近年來已成為生物科技之重點發展項目之一。光電技術及電腦科技的應用與蓬勃發展,帶動了以電腦輔助生命科學的研究模式,更為未來生命科技的進展帶來新的方向。在生醫系統的各種感測原理中,隨著生化反應的進行,偵測其光學性質的改變,是頗為有效且廣受歡迎的方法。
    表面電漿共振是一種存在於金屬與非導電介質界面的物理現象。當一束偏極光進入玻璃稜鏡時,會產生全反射。光在行進的時候,會與稜鏡上所覆蓋的金屬薄膜的原子產生共振,並產生衰逝波進入介電質層。當光經由稜鏡反射之後,在某一特定角度或波長的光強度會因為共振作用而急速下降,而光之相位則是會發生劇烈的變化,此一角度稱為共振角度,而波長稱為共振波長。改變介電質層之折射率時,共振角度或是波長會產生位移,相位則會產生變化,將此特性應用於生物感測器,具有即時檢測、高靈敏度與不須標記等特性,因此廣泛應用於生物檢測與免疫組織化學上,可有效的分析檢測物質之微小濃度折射率變化。常見的表面電漿共振量測方式有四種,角度調制、波長調制、強度調制與相位調制,其中又以相位調制之靈敏度為最高,而為了取得反射光相位之資訊,必須使用干涉之方法來量測。
    在本論文中,我們利用通訊波段之寬頻譜光源作為入射光源,於相同的光路徑, 藉由P極化光產生表面電漿共振效應之相位差與S極化光進行干涉,完成了一頻譜干涉表面電漿共振感測器。我們成功的量測probe前後流感與結核桿菌DNA之干涉頻譜波長位移與相位之靈敏度, 並證明了固定化probe後之靈敏度較未使用probe高。


    Biophotonics is a new and rapidly growing field in prevailing researches. Moreover, it has become one of the major developed projects of biomedical technology in recent years. The booming technology from the photonics and computing has not only promoted the life science development but also led the biotechnology progress to a new direction. In various sensing principles of biomedical systems, the optical property variation detected from the biochemical reaction process is an efficient, accurate, and popular approach.
    Surface plasmon resonance (SPR) is a physical phenomenon that happens between the interface of metal and non-conductive material. When a polarized light wave is entering a glass prism and satisfying the total internal reflection, the incident light will resonate with the thin metal film which is covered on the prism and generate the evanescent wave that penetrates into the dielectric layer. When the light is reflected by the prism at a specific angle or wavelength, the optical power will rapidly drop to minimum because of the resonant effect. In the meantime, the reflected light phase will also change dramatically. This specific angle and wavelength are named resonant angle and resonant wavelength, respectively. When the refractive index of the dielectric layer is changed, the resonant angle or resonant wavelength will shift, same as the reflected light phase. By applying these features onto biosensors, the real-time, high sensitivity and label-free detection could be demonstrated. Therefore, it has been extensively utilized in biosensing and immunochemistry for its efficiency in analyzing the small refractive index variation of detected materials. Among four common SPR modulation approaches, angle modulation, wavelength modulation, Intensity modulation and phase modulation, the phase modulation demonstrates the highest sensitivity. In order to retrieve the reflected light phase, the optical interference system is considered as a good implementation.
    In this thesis, a superluminescent emitting diode with the optical fiber communication bandwidth is utilized as the incident light source to generate the s-polarized light and p-polarized light in a common path. The p-polarization will interact and experience an additional optical path from SPR. Finally, a linear polarizer is implemented to combine two polarizations to illustrate the interference and produces a spectral interferometry-based SPR sensor. We successfully demonstrate the sensitivity of wavelength modulation and phase modulation of influenza and Mycobacterium tuberculosis DNA before and after the DNA probing. The sensitivity from DNA probes increases higher with the phase and wavelength modulations without immobilization.

    摘要 I Abstract II 誌謝 IV 圖目錄 VII 表目錄 IX 第一章 緒論 1 1.1 研究背景 1 1.2 研究目的 2 1.2.1 流行性感冒 2 1.2.2 結核桿菌 3 1.3 研究之重要性 4 1.4 論文架構 5 第二章 文獻探討 6 2.1 表面電漿波原理 6 2.1.1 表面電漿色散關係式 6 2.1.2 激發表面電漿波之條件 13 2.2表面電漿之耦合方式 14 2.2.1 稜鏡耦合 14 2.2.2 波導耦合 15 2.2.3 光柵耦合 16 2.3 表面電漿共振生物感測器 17 2.3.1 生物感測器簡介 17 2.3.2 表面電漿共振生物感測器 17 2.3.3 靈敏度與解析度 19 2.4 國內外研究比較 20 2.4.1 角度調制之研究比較 20 2.4.2 波長調制之研究比較 22 2.4.3 強度調制之研究比較 23 2.5 利用干涉之SPR感測器之研究 24 2.5.1 利用空間干涉之SPR感測器之研究 25 2.5.2 利用頻譜干涉之SPR感測器之研究 28 第三章 研究方法 31 3.1 金薄膜厚度設計 31 3.1.1 Kretschman組態下系統反射率 31 3.1.2 金薄膜厚度模擬 35 3.2 SPR金薄膜之製程 38 3.2.1 使用設備 38 3.2.2 製程步驟 39 3.3 頻譜干涉表面電漿共振感測器 41 第四章 實驗步驟與結果 44 4.1 實驗架構 44 4.2 實驗步驟 45 4.2.1 待測物濃度調配 45 4.2.2 DNA之固定化程序 47 4.2.3 入射角度之控制 48 4.2.4 頻譜干涉SPR實驗步驟 50 4.3 流感量測結果與分析 53 4.3.1 使用probe之量測結果與分析 53 4.3.2 未使用probe之量測結果與分析 57 4.4 結核桿菌量測結果與分析 61 4.4.1 使用probe之量測結果與分析 61 4.4.2 未使用probe之量測結果 65 第五章 結論與未來展望 70 5.1 結論 70 5.2 未來展望 72 參考文獻 73

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