臺灣博碩士論文加值系統

本論文研究B型抗諧振反射光波導(ARROW-B)表面電漿子共振(SPR)生化感測元件於蛋白質激酶A活性之即時檢測。由於此生化感測元件具有免標定、高效率以及對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。此外，由於B型抗諧振反射光波導擁有較大的入射導光區，所以能夠有效和單模光纖相匹配。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。感測元件的所有設計與製程步驟都會詳細的討論。生物感測實驗部分，進行蛋白質激酶A活性之檢測。蛋白質激酶A是一種酵素，它的主要功能在於催化磷酸化反應，磷酸化反應在新陳代謝中是常見且不可或缺的。實驗結果顯示，此生物感測元件能精確定性且即時檢測蛋白質激酶A的活性。

In this study, surface plasmon resonance (SPR) biosensors with antiresonant reflecting optical waveguide of type B (ARROW-B) structure have been investigated. The ARROW-B SPR biosensors was proposed to provide label-free, high-throughput, and highly sensitivity characteristics to detect the biomolecular interaction for the aqueous environment in real time. Moreover, The ARROW-B waveguide with a thick guiding region provides efficient coupling with a single-mode fiber. Modal characteristics of ARROW-B are analyzed with simulation and designed for obtaining optimum sensitivity in aqueous environment. The design and fabrication process of the ARROW-B sensor chips are described and discussed. For the bioassay experiments, the protein kinase A (PKA) activity is detected. PKA is a kind of enzyme, and its function is to catalyze the phosphorylation. The phosphorylation is common and indispensable in metabolism. In summary, the measurement results have shown that the ARROW-B SPR biosensors can be applied to detect the PKA activity quantitatively in real time.

Contents
Contents 1
List of Tables 3
List of Figures 4
1 Introduction 1
2 ARROW Waveguides 6
2.1 Characteristics of ARROW-B Structures . . . . . . . . . . . . . . . . . . 8
3 Analytic Theories and Methods 10
3.1 Transfer Matrix Method . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3.2 Normalization of Guided Modes . . . . . . . . . . . . . . . . . . . . . . . 14
3.3 Eigenmode Expansion Analysis . . . . . . . . . . . . . . . . . . . . . . . 15
4 SPR Sensor Based on an ARROW-B structure 18
4.1 Surface Plasmon Wave . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.1.1 Theorem of TIR . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.1.2 Physical Properties of SPR . . . . . . . . . . . . . . . . . . . . . . 19
4.2 Design of an ARROW-B Structure in Sensing Region . . . . . . . . . . . 25
4.3 Design of an ARROW-B Structure in Propagation Region . . . . . . . . 29
4.4 Au-coated ARROW-B SPR Sensor in Sensing Region . . . . . . . . . . . 33
1
4.4.1 Au-coated ARROW-B SPR Sensor with HSQ Bu¤er Layer . . . . 35
4.4.2 Au-coated ARROW-B SPR Sensor with Si3N4 Adjusting Layer . . 37
4.5 Au-coated ARROW-B SPR Sensor in propagation region . . . . . . . . . 40
5 Fabrication Process of ARROW-B SPR Sensor Chips 42
5.1 Layout of ARROW-B SPR Sensor . . . . . . . . . . . . . . . . . . . . . . 42
5.2 Fabrication Process of the ARROW-B SPR Sensor Chips . . . . . . . . . 46
6 Real-Time Detection Using ARROW-B SPR Biosensors 54
6.1 Optical Measurement Setup with a Fluid-Flow System . . . . . . . . . . 55
6.2 Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
6.3 Feasibility Demonstration of Sensor Chips . . . . . . . . . . . . . . . . . 59
6.3.1 Measurement of NaCl Solutions . . . . . . . . . . . . . . . . . . . 60
6.3.2 Real-Time Measurement of 95% Ethanol . . . . . . . . . . . . . . 60
6.3.3 Reusable Sensor Chips . . . . . . . . . . . . . . . . . . . . . . . . 62
6.4 Introduction to Protein Kinase A . . . . . . . . . . . . . . . . . . . . . . 64
6.5 Detection of Protein Kinase A Activity . . . . . . . . . . . . . . . . . . . 66
6.6 Speci.c Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
7 Conclusion 73
Bibliography 75

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