有鑑於 Point of care testing (POCT) 是現今醫療發展的新趨勢，期待滿足臨床治療或家用看護所進行的準確、快速、及時的診斷需求。但現今許多生物感測器仍然笨重昂貴且檢測靈敏度未達需求，故本研究開發全新生物感測方法以滿足此需求。
在本研究中利用共振波導光柵(Resonant Waveguide Grating , RGW)結構所產生的電場增強粒子電漿共振(Particle Plasmon Resonance ,PPR)效應，並透過三明治法來提升感測靈敏度。在此選用前降鈣素 (Procalcitonin , PCT)為目標分析物，PCT為敗血症生物指標之一，因此對檢測靈敏度需求較高，若能成功偵測才能滿足現今醫療機構所需。
在晶片與金奈米分別使用葡聚糖與自組裝單層，以減少非特異性吸附的發生，最佳化條件並使用三明治法後可成功於15分鐘內偵測PCT，線性範圍為10-17－10-13 g/mL；相關係數為0.99；偵測極限為10-19g/mL 水平。除此之外也探討了不同製程的晶片與配體金奈米濃度對檢測上的影響，因晶片本身使用環烯烴共聚物(Cyclic Olefin Copolymer , COC)價格較低易大量製造，故此感測平台在未來極具商品化的潛力。

In this work, a novel biosensing method based on enhancement of particle plasmon resonance (PPR) phenomenon by resonant waveguide grating (RWG) using a sandwich assay is illustrated. The sandwich approach is utilized to improve the sensitivity of the RWG-PPR biosensor platform for ultrasensitive detection of procalcitonin (PCT), a biomarker of severe bacterial and fungal infections.
We use Dextran and Self-assembled monolayer (SAM). Its molecular property allows the chip sensing region to form an anti-nonspecific adsorption layer. Experimental results demonstrate that the RWG-PPR biosensor platform has an excellent ability for rapid (15 min), sensitive (10-19g mL-1 level) and quantitative analysis of PCT.. Moreover, since the sensing chip is constructed by cycle olefin copolymer (COC) using a low-cost and easy mass production process, there is a high potential to commercialize the biosensor platform.

摘要 1
Abstract 2
總目錄 3
第一章 緒論 5
1-1前言 5
1-2生物感測器 (Biosensor) 6
1-2.1生物感測器簡介 6
1-2.2生物感測器近年發展與挑戰 8
1.3波導模態共振 (Guide mode resonance , GMR) 9
1-3.1光柵異常繞射現象介紹 9
1-3.2波導模態共振結構與效應 11
1-3.3波導層原理與漸逝波介紹 13
1.4粒子電漿共振 (Particle Plasmon Resonance , PPR) 15
1-4.1金屬奈米粒子 15
1-4.2金奈米粒子 16
1.5前降鈣素元 (Procalcitonin , PCT) 19
1.6檢測降鈣素元 (PCT) 文獻回顧 21
第二章 實驗設備、藥品及方法 24
2.1實驗設備 24
2.2藥品 25
2.3晶片製程 27
2-3.1晶片製作 27
2-3.2晶片封裝 28
2-4金奈米粒子合成 29
2-5穿透光譜儀架設 30
2-6反射式即時偵測系統架設 31
2-7波導模態共振波長最佳化策略 33
2-8反射式即時偵測系統感測能力測試 34
2-9生化分子檢測策略 34
2-10檢測生化分子修飾方法 35
2-10.1晶片修飾捕獲抗體 35
2-10.2配體金奈米修飾方法 37
2-11三明治法之配體金濃度條件優化 40
2-12背景吸附測試 41
2-13 PCT標準品檢測 42
第三章 結果與討論 44
3-1晶片製作與修飾後鑑定 44
3-2金奈米合成與修飾鑑定 45
3-3波導模態共振波長最佳化 47
3-4反射式即時偵測系統感測測試 50
3.5濺鍍有孔洞晶片即時偵測 51
3-6濺鍍無孔洞晶片即時偵測 52
3-7蒸鍍晶片即時偵測 54
3-8配體金奈米濃度最佳化 56
3-9背景吸附測試 58
3-10 PCT標準品檢測 59
第四章 結論與未來展望 61
第五章 參考文獻 62

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