臺灣博碩士論文加值系統

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)生化感測元件於蛋白質激&;#37238;A活性之檢測。由於此生物感測元件有免標定、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，應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。生物感測實驗部分，進行蛋白質激&;#37238;A活性之檢測，實驗結果顯示此生物感測元件能有效地定性且定量檢測其反應。

In this study, 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-efficiency, 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 a symmetric cladding structure to prevent from being affected by environmental changes, and the sensing region is configured with a liquid flow channel which assists bioagents in attaching to the gold surface for reaction. For the bioassay experiments, the protein kinase A (PKA) activity has been detected. The measurement results have shown that the ARROW-B SPR biosensors with the circulating-flow system can be applied to detect the PKA interaction quantitatively and qualitatively.

1 Introduction 1
2 ARROW-B Waveguides 4
2.1 Two General Types: ARROW and ARROW-B . . . . . . . . . . . . . . . 5
2.2 Characteristics of an ARROW-B Structure . . . . . . . . . . . . . . . . . 7
3 Surface Plasmon Resonance 9
3.1 Principles of SPR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3.2 Derivation of SPW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
4 Methods for Analysis 15
4.1 Transfer Matrix Method . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
4.2 Normalization of Guided Modes . . . . . . . . . . . . . . . . . . . . . . . 19
4.3 Eigenmode Expansion Analysis . . . . . . . . . . . . . . . . . . . . . . . 21
5 Design of Au-Coated ARROW-B SPR Sensors 23
5.1 Design of ARROW-B Waveguide Structure . . . . . . . . . . . . . . . . . 23
5.2 Propagation Region in an ARROW-B Waveguide . . . . . . . . . . . . . 26
5.3 Au Sensing Region in ARROW-B Waveguide . . . . . . . . . . . . . . . . 29
5.3.1 Bu¤er layer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
5.3.2 Adjusting layer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
6 Fabrication Process of SPR Sensors 34
6.1 Layout of SPR Sensor . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
6.2 Fabrication Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
7 Detection of Protein Kinase A (PKA) Activity with ARROW-B SPR
Biosensors 44
7.1 Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
7.2 Optical Measurement Setup with a Fluid-Flow System . . . . . . . . . . 47
7.3 Measurement of NaCl Solutions . . . . . . . . . . . . . . . . . . . . . . . 48
7.4 Real-Time Measurement of 95% Ethanol . . . . . . . . . . . . . . . . . . 50
7.5 Detection of Protein Kinase A Activity . . . . . . . . . . . . . . . . . . . 52
8 Conclusion 56
Bibliography 58

[1] C. F. R. Mateus, M. C. Y. Huang, C. J. Chang-Hasnain, J. E. Foley, R. Beatty,P. Li, and B.T. Cunningham, "Ultra-sensitive immunoassay using VCSEL detection system," Electronics Letters, vol. 40, no. 11, 2004.
[2] D. L. Venton and C. P. Woodbury, "Screening combinatorial libraries,"Chemometrics and Intelligent Laboratory Systems, vol. 48, pp. 131-150, 1999.
[3] M. A. Cooper, "Optical biosensors in drug discovery," Nature Reviews - Drug Discovery, vol. 1, pp. 515-528, 2002.
[4] O. Hugon, P. Benech, and H. Gagnaire, "Surface plasmon chemical/biological sensor in integrated optics," Sensors and Actuators B, vol. 51, pp. 316-320, 1998.
[5] K. Nakatani, S. Sando, and I. Saito, "Scanning of guanine-guanine mismatches in DNA by synthetic ligands using surface plasmon resonance," Nature Biotechnology,vol. 19, pp. 51-55, 2001.
[6] J. M. McDonnell, "Surface plasmon resonance: towards an understanding of themechanisms of biological molecular recognition," Current Opinion in Chemical Biology, vol. 5, pp. 572-577, 2001.
[7] E. Kretschmann and H. Raether, "Radiative decay of nonradiative surface plasmons excited by light," Z. Naturforsch, vol. 23, pp. 2135-2136, 1968.
[8] J. Homola, S. S. Yee, and G. Gauglitz, "Surface plasmon resonance sensors: review," Sensors and Actuators B, vol. 54, pp. 3-15, 1999.[9] M. A. Duguay, Y. Kokubun, and T. L. Koch, "Antiresonant reflecting optical waveguides in SiO₂-Si multilayer structures," Applied Physics Letters, vol. 49, no.1, pp. 13-15, 1986.
[10] T. Baba and Y. Kokubun, "Dispersion and radiation loss characteristics of antiresonant reflecting optical waveguides numerical results and analytical expressions," IEEE Journal of Quantum Electronics, vol. 28, no. 7, pp. 1689-1700, July 1992.
[11] T. Baba and Y. Kokubun, "New polarization-insensitive antiresonant reflecting optical waveguide (ARROW-B),"IEEE Photonics Technology Letters, vol. 1, no. 8,pp. 232-234, 1989.
[12] J. Homola and S. S. Yee, "Novel polarization control scheme for spectral surface plasmon resonance sensors," Sensors and Actuators B, vol. 51, pp. 331-339, 1998.
[13] T. Baba and Y. Kokubun, "Scattering Loss of antiresonant reflecting optical waveguides," Journal of Lightwave Technology, vol. 9, no. 5, pp. 590-597, 1991.
[14] C. H. Chen, "Design of ARROW-B SPR sensors in aqueous environment with the spectral shift method," Master Thesis, Institute of Electronics, National Chiao Tung University, Hsinchu, Taiwan, R.O.C., 2003.
[15] J. J. Burke, G. I. Stegeman, and T. Tamir, "Surface-polariton-like waves waves guided by thin lossy metal films," Physical Review B, vol. 33, no. 8, pp. 5186-5201,1986.
[16] F. M. Mirabella and N. J. Harrick, "Internal Reflection Spectroscopy: Review and Supplement," Harrick Scientific Corporation, vol. 3, pp. 84?5, 1985.
[17] H. Raether, "Surface Plasmons on Smooth and Rough Surfaces and on Gratings," Springer Tverlag, 1988.
[18] C. C. Huang, "Real-Time Detection of α-Thrombin Binding to Single-Strand DNA Aptamers and Dengue Virus DNA Hybridization by ARROW-B SPR Biosensors," Master Thesis, Institute of Electronics, National Chiao Tung University, Hsinchu, Taiwan, R.O.C., 2006.
[19] T. Tamir (Ed.) et al., Guided-wave optoelectronics, Springer-Verlag, 1990.
[20] J. J. Deng, The analysis and design of antiresonant reflecting optical waveguide devices with discontinuities, Ph. D. Dissertation, National Chiao-Tung University, 2000.
[21] T. Baba and Y. Kokubun, "Scattering Loss of antiresonant reflecting optical waveguides," Journal of Lightwave Technology, vol. 9, no. 5, pp. 590-597, 1991.
[22] P.E. Laibinis, G.M. Whitesides, D.L. Allara, "Comparison of the structures and wetting properties of self-assembled monolayers of n-alkanethiols on the coinage metal surfaces, copper, silver, and gold," Journal of the American Chemical Society, vol. 113, pp. 7152, 1991.
[23] H. de Bruijn, R. Kooyman, and J. Greve, "Choice of metal and wavelength for surface plasmon resonance sensors: Some Considerations," Applied Optics, vol. 31, no. 4, pp. 440-442, 1992.[24] M. Mrksich, J. R. Grunwell, and G. M. Whitesides "Biospecific absorption of carbonic anhydrase to self-assembled monolayers of alkanethiolates that present benzenesulfonamide groups on gold," Journal of the American Chemical Society, vol. 117, pp. 12009-12010, 1995.117, pp. 12009-12010, 1995.
[25] C. D. Bain, E. B. Troughton,Y. T. Tao, J. Evall, and G. M. Whitesides, "Formation of monolayer films by the spontaneous assembly of organic thiols from solution onto gold," Journal of the American Chemical Society, vol. 111, pp. 321-335, 1989.
[26] F. Schreiber, "Structure and growth of self-assembling monolayers," Progress in Surface Science, vol. 65, pp. 151-256, 2000.[27] G. G. Nenninger, P. Tobiska, J. Homola, and S. S. Yee, "Long-range surface plasmons for high-resolution surface plasmon resonance sensors," Sensors and Actuators B, vol. 74, pp. 145-151, 2001.
[28] M. Iga, A. Sekib, K. Watanabea, "Gold thickness dependence of SPR-based heterocore structured optical fiber sensor," Sensors and Actuators B, vol. 106, pp. 363-368, 2005.
[29] J. Ctyroky, J. Homola, and M. Skalsky, "Tuning of spectral operation range of a waveguide surface plasmon resonance sensor," Electronics Letters, vol. 33, no. 14, pp. 1246-1248, 1997.
[30] J. L. Kadrmas, and M. C. Beckerle, "The LIM domain: from the cytoskeleton to the nucleus," Nature Reviews Molecular Cell Biology, vol. 5, pp. 920-931, 2004.
[31] K. Y. Tsai, "Design and fabrication of ARROW-B SPR biochemical sensors in aqueous environment," Master Thesis, Institute of Electronics, National Chiao Tung University, Hsinchu, Taiwan, R.O.C., 2002.
[32] Jing Wanga, Min Shenb, Ya Caoa, Genxi Li, "Switchable "On-Off" electrochemical technique for detection of phosphorylation," Biosensors and Bioelectronics 26 (2010) 638-642.