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研究生: 洪鼎祥
DING-SIANG HONG
論文名稱: 藉由頻譜干涉表面電漿共振之凝血因子感測
Spectral Interferometry-based Surface Plasmon Resonance Sensing for Blood Coagulation
指導教授: 徐世祥
Shih-Hsiang Hsu
口試委員: 徐世祥
Shih-Hsiang Hsu
何文章
Wen-Jeng Ho
莊敏宏
Miin-Horng Juang
葉秉慧
Pinghui Sophia Yeh
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: 2020
畢業學年度: 108
語文別: 中文
論文頁數: 78
中文關鍵詞: 表面電漿共振相位生醫感測
外文關鍵詞: Surface Plasmon Resonance, Phase, Biosensing
相關次數: 點閱:189下載:0
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血液凝血檢測分析仍是目前外科手術、心血管疾病、慢性病併發症及血友病的重要依據。傳統檢測血液凝血酶原時間,一般使用自動凝血分析儀來做檢測,但是儀器設備系統昂貴、體積龐大、成本較高且檢測時間過長。近年來,SPR干涉系統在生物醫學的檢測上面,逐漸取代傳統的方法,SPR更是被廣泛的應用在生物檢測的範圍內,因為它有著對不同折射率的待測物高靈敏度的特性。其中,頻譜干涉表面電漿共振的原理,就是當光源入射經過一極化分光器,使入射之P極化與S極化光強度相同。光在進入稜鏡後會使P極化與S極化之光之間產生一延遲。由於只有P極化之光會產生SPR現象,於是在稜鏡內P極化與S極化光之間又產生了一延遲,接著經由稜鏡後方的線性偏振片結合而干涉,再由光頻譜分析儀(OSA)接收,直接觀察其干涉結果。
在本論文中,我們利用頻譜干涉表面電漿共振感測器之生醫檢測進行凝血時間的量測,將凝血因子依序與5mM、25mM、50mM、150mM、200mM之CaCl2 溶液配置,並以OSA(Optical Spectrum Analyzer)記錄干涉頻譜,量測出相對應的凝血時間為364秒至260秒逐漸縮短。並且當CaCl2溶液每增加1mM時,所需的時間將減少0.56秒。本系統血液樣本需求量較少且血液樣本可使用全血樣本,而非接觸式檢測,如此一來將減少對凝血機制之影響,對生醫領域提供一快速、方便簡單及低成本的光學生物檢測技術。


The blood coagulation characterization is important for surgery, cardiovascular disease, chronic disease complications and hemophilia. It is traditionally to use the automatic coagulation analyzer to detect the blood prothrombin time, but it possesses high price, bulky size, and long detection time. In recent years, surface plasmon resonance (SPR) interference systems own the potential in high sensitivity. The principle of interferometry based SPR is that when the light source is incident to a polarization beam splitter, the incident P-polarized and S-polarized light are adjusted to the approximately equal intensity. When these two polarizations enter the SPR sensor, there is a delay between the P and S-polarized light due to the P-polarized light producing SPR phenomenon. Then a delay will be formed between the P- and S-polarized lights to form the interference after the linear polarizer. Then the optical spectrum analyzer (OSA) can be utilized to directly observe interferograms.
In this thesis, we use the spectral interferometry-based SPR to biosense blood coagulation for coagulation time. After mixing the blood with CaCl2 with the concentrations of 5 mM, 25 mM, 50 mM, 150 mM and 200 mM, the coagulation time demonstrates from 364 seconds to 260 seconds. When CaCl2 increases by 1 mM, the coagulation time will be reduced by 0.56 seconds. The shortest time we could characterize is 260 seconds, and the solution is 200 mM CaCl2 due to the system limitation. In conclusion, the SPR can provide a fast, convenient and low-cost optical bio-detection technology for blood coagulation.

摘要 I 誌謝 III 目錄 IV 圖目錄 VI 表目錄 VIII 第一章 緒論 1 研究背景 1 1.2研究目的 2 1.3論文架構 3 第二章 基本理論 5 2.1表面電漿波原理 5 2.1.1表面電漿色散關係式 5 2.1.2激發表面電漿波之產生條件 10 2.2 MAZH-ZEHNDER干涉儀 11 2.3光纖低同調光學干涉 13 2.4 血液凝血機制 16 2.5 血液相關時間定義 19 2.5.1凝血時間(Coagulation Time, CT) 19 2.5.2 活化凝血時間(Activated Clotting Time, ACT) 19 2.5.3凝血酶原時間(Prothrombin Time, PT) 20 2.6.1 稜鏡耦合 21 2.6.2 光柵耦合 22 2.6.3 波導耦合 23 2.7表面電漿共振生物感測器 24 2.7.1生物感測器簡介 24 2.7.2表面電漿共振生物感測器 24 2.8國內外研究比較 26 2.8.1利用干涉之SPR生物感測器之研究 26 2.8.2 利用空間干涉之SPR生物感測器之研究 27 2.8.3利用頻譜干涉之SPR生物感測器之研究 28 2.8.4凝血因子表面電漿共振之研究 30 2.9 AWG理論與設計 31 2.9.1色散關係與通道間距 32 2.9.3 AWG設計內容 34 2.10基礎光學原理 36 2.10.1光學像差 37 2.10.2像差消除 40 2.10.2 鏡頭規格介紹 40 2.10.3 透鏡設計起始 42 第三章 研究方法 45 3.1金薄膜厚度設計 45 3.1.1 Kretschman組態下系統反射率 45 3.1.2 SPR模擬 49 3.2 SPR金薄膜之製程 52 3.2.1使用設備 52 3.2.2製程步驟 53 第四章 實驗步驟與結果 55 4.1實驗架構 55 4.2實驗流程 56 4.2.1量測步驟 56 4.2.2 實驗結果與分析 58 第五章 結論與未來展望 64 5.1 結論 64 參考文獻 65

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