製作B型抗諧振反射光波導表面電漿子共振生物感測器於蛋白質酶活性與加保扶之檢測

Abstract

本論文研究適用於水中環境的B型抗諧振反射光波導(ARROW-B)表面電漿子共振(SPR)生化感測元件。由於此生物感測器具有免標定、高效率以及對於金表面所固定的生物分子層之折射率變化具有高靈敏度等 特性，因此能夠應用在即時感測表面生物分子之交互作用。此生物感測元件的設計，使用模擬分析光場在元件中的傳播特性，使其在水環境下具有最佳化的感測靈敏度。在感測區前後的光場傳播區設計具上下對稱的光波導隔離層，使元件能穩定導光而不受外界環境影響，並於感測區附加液體流道設計，幫助生物分子附著於感測區表面進行反應。在製程中使用含氫的矽酸鹽類(HSQ)材料替代氟化鎂，避免氟化鎂容易龜裂及脫膜的缺點。生物感測實驗部分，進行蛋白質酶活性與加保扶之檢測，由實驗結果顯示此生物感測器能精確地定性且定量檢測反應。此感測器以直接偵測方式偵測加保扶可達約10 ppm濃度之偵測極限。

In this thesis, an antiresonant reflecting optical waveguide of type B (ARROW-B) surface plasmon resonance (SPR) biosensor operating in the aqueous environment with a circulating-flow system has been investigated. The ARROW-B SPR biosensor is proposed to provide a label-free, high-throughput and highly surface-sensitive platform to detect the bimolecular interactions. Modal characteristics of ARROW-B are analyzed with simulation and designed for obtaining optimum sensitivity in aqueous environment. The waveguides in the front and rear of the SPR sensing regions have symmetric cladding structure to prevent from being affected by environmental changes, and sensing region is configured with a liquid flow channel which assists bioagents in attaching to the gold surface for reaction. We replace MgF2 with HSQ to avoid the peeling and crack of MgF2 in fabrication process. For the bioassay experiments, the proteinase activity and carbofuran are detected. The measurement results have shown that the ARROW-B SPR biosensors with the circulating-flow system can be applied to detect the proteinase/protein and tyrosinase/carbofuran interaction quantitatively and qualitatively. The limit of carbofuran detection is about 10 ppm by direct detection format.