本論文利用加熱熔化光纖並且將其拉伸的方法拉細光纖，目的是為了使光纖內傳導的光不滿足全反射而溢散至光纖表面，以製作一利用激發光激發外部待測物之光學感測平台，而感測機制可利用光激螢光或是表面增強拉曼訊號。本論文之光纖感測平台是以全光纖式的架構所組成，有別於許多光纖感測器之研究大多收訊與激發架構是分開的並且需要配合濾鏡及放大訊號及過濾訊號之光電元件，本實驗將激發與收訊整合於全光纖平台，有架構簡潔及成本低廉之優點。本論文首先探討製作熱熔拉光纖的方法以及對於拉伸後光源溢散程度的分析，再以R6G螢光染料做測試，驗證了光纖平台之激發及收訊的可行性，並且測試本平台使用於光激螢光及激發表面增強拉曼訊號的效果。

Using fiber sensor has the advantages of compact、high environmental resistance and high signal-to-noise ratio. The optical fiber with tapered region was well fabricated by pulling and heating it. The incident light would leak out from the fiber so that we could use it to excite the analytes outside the fiber. By utilizing this feature, optical-sensing mechanism like fluorescence sensing or SERS signal detection could be achieved. Unlike many studies, the fiber sensing system we built has the advantages of simpler structure and lower cost without using filters and optoelectronics.
In this thesis, we demonstrated the experimental configuration and showed how much the leaking power was. Moreover, we confirmed the feasibility of the tapered fiber is available to excite the analytes and receive the signals. And we successfully received the R6G dye fluorescence. The last part of this thesis is the SERS signal excitation, the SERS signal is not observed might cause by low power density of the excitation light and the distance between particles is not close enough.

[1] http://web.ornl.gov/sci/techresources/Human_Genome/
[2] P.N. Prasad, Introduction to Biophotonics, Wiley-Interscience, New Jersey, Chapter 9. (2003)
[3] Clark, L.C.; Jr.; Lyons, C. “Electrode Systems for Continuous Monitoring in Cardiovascular Surgery,” Ann. N. Y. Acad. Sci. 102, 29-45. (1962)
[4] K. Hammarling, Jöns Hilborn, Hans-Erik Nilssonc, Anatoliy Manuilskiya, “Blood Ph Optrode Based on Evanescent Waves and Refractive Index Change,” Proceedings of the SPIE - Progress in Biomedical Optics and Imaging, 89381F ,7 pp. (2014)
[5] Xia Xin, Yinglang Wan, Wenjun Wang, Guangkun Yin, Eric S. McLamore & Xinxiong Lu, “A Real-Time, Non-Invasive, Micro-Optrode Technique for Detecting Seed Viability by Using Oxygen Influx,” SCIENTIFIC REPORTS, 3, 3057. (2012)
[6] Suzie Dufour, Guillaume Lavertu, Sophie Dufour-Beause´ jour, Alexandre Juneau-Fecteau, Nicole Calakos, Martin Descheˆnes, Re´ al Valle´e, Yves De Koninck , “A Multimodal Micro-Optrode Combining Field and Single Unit Recording, Multispectral Detection and Photolabeling Capabilities,” Plos One. 8, 2. (2013)
[7] F. Long, M. He, H.C. Shi, A.N. Zhu, “Development of Evanescent Wave All-Fiber Immunosensor for Environmental Water Analysis,” Biosensors and Bioelectronics. 23,952–958. (2008)
[8] Michael Shortreed, Raoul Kopelman, Michael Kuhn, and Brian Hoyland, “Fluorescent Fiber Optic Calcium Sensor for Physiological Measurements,” Anal. Chem. 68, 1414-1418. (1996)
[9] Katrin Kneipp, Yang Wang, Harald Kneipp, Lev T. Perelman, Irving Itzkan, Ramachandra R. Dasari, and Michael S. Feld, “Single Molecule Detection Using Surface-Enhanced Raman Scattering (SERS),” Physical Review Letters. 78, 9. (1997)
[10] Hongxing Xu, Erik J. Bjerneld, Mikael Käll, and Lars Börjesson, “Spectroscopy of Single Hemoglobin Molecules by Surface Enhanced Raman Scattering,” Physical Review Letters. 83, 21. (1999)
[11] Ximei Qian, Xiang-Hong Peng, Dominic O Ansari1, Qiqin Yin-Goen, Georgia Z Chen, Dong M Shin, Lily Yang, Andrew N Young, May D Wang & Shuming Nie, “In Vivo Tumor Targeting and Spectroscopic Detection with Surface-Enhanced Raman Nanoparticle Tags,” Nature Biotechnology. 26,1. (2007)
[12] J. Kneipp, H. Kneipp, B. Wittig and K. Kneipp, “One- and Two-Photon Excited Optical pH Probing for Cells Using Surface-Enhanced Raman and Hyper-Raman Nanosensors,” Nano Lett. 7, 9. (2007)
[13] Jiri Homola, Sinclair S. Yee, Gunter Gauglitz, “ Surface Plasmon Resonance Sensors: Review,” Sensors And Actuators B-chemical. 54,1-2. (1999)
[14] Ivan H. El-Sayed, Xiaohua Huang, and Mostafa A. El-Sayed, “Surface Plasmon Resonance Scattering and Absorption of anti-EGFR Antibody Conjugated Gold Nanoparticles in Cancer Diagnostics: Applications in Oral Cancer,” Nano Letters. 5,5. (2005)
[15] Kenzo Maehashi, Taiji Katsura, Kagan Kerman, Yuzuru Takamura, Kazuhiko Matsumoto, and Eiichi Tamiya, “Label-Free Protein Biosensor Based on Aptamer-Modified Carbon Nanotube Field-Effect Transistors,” Anal. Chem. 79, 782-787. (2007)
[16] Ying-Chung Chen, Wei-Tsai Chang, Chien-Chuan Cheng, Jing-Yi Shen, Kuo-Sheng Kao, “Development of Human Ige Biosensor Using Sezawa-Mode SAW Devices,” Current Applied Physics. 14, 4, 608-613. (2014)
[17] Jeong Hoon Lee, Ki Hyun Yoon b, Kyo Seon Hwang, Jaebum Park, Saeyoung Ahn, Tae Song Kim, “Label Free Novel Electrical Detection Using Micromachined PZT Monolithic Thin film Cantilever for The Detection of C-Reactive Protein,” Biosensors and Bioelectronics. 20, 2, 269–275. (2004)
[18] Andreas P. Abel, Michael G. Weller, Gert L. Duveneck, Markus Ehrat, and H. Michael Widmer, “Fiber-Optic Evanescent Wave Biosensor for the Detection of Oligonucleotides,” Anal. Chem. 68, 17, 2905-2912. (1996)
[19] Jane A. Ferguson, T. Christian Boles, Christopher P. Adams, and David R. Walt, “ A fiber-Optic Dna Biosensor Microarray for The Analysis of Gene Expression,” Nature Biotechnology. 14, 13, 1681-1684. (1996)
[20] Xiaojing Liu and Weihong Tan, “A Fiber-Optic Evanescent Wave DNA Biosensor, ” A Fiber-Optic Evanescent Wave DNA Biosensor” Anal. Chem. 71, 22, 5054-5059. (1999)
[21] Claudia Preinlnger, Ingo Kllmant, and Otto S. Wolfbels, “Optical Fiber Sensor for Biological Oxygen Demand,” Anal. Chem. 66, 11, 1841-1846. (1994)
[22] Paul A.E. Piunno, Uh-ich J. Krull, Robert H.E. Hudson, Masad J. Damha, Huguette Cohen “Fiber Optic Biosensor for Fluorimetric Detection of DNA Hybridization,” Analytica Chimica Acta. 288, 3, 205-214. (1994)
[23] Ursula E. Spichiger-Keller, “Chemical Sensors and Biosensors for Medical And Biological Applications,” Wiley-VCH. (1994)
[24] 鄭佩绮, ITRI-IEK, “全球生物感測市場發展概況” (2013)
[25] Brian D. MacCraith, Colette M. McDonagh, Gerard O'Keeffe, Emmetine T. Keyes Johannes G. Vos, Brendan O'Kelly and John F. McGilp, “Fibre Optic Oxygen Sensor Based on Fluorescence Quenching of Evanescent-wave Excited Ruthenium Complexes in Sol-Gel Derived Porous Coatings,” Analyst. 118, 4 , 385-388. (1993)
[26] Ravi A. Vijayendran and Deborah E. Leckband, “A Quantitative Assessment of Heterogeneity for Surface-Immobilized Proteins,” Anal. Chem. 73, 3 ,471-480. (2001)
[27] Yuhki Yanasea, Atsunori Arakib, Hidenori Suzukia, Tomoko Tsutsuia, Tatsuo Kimurab, Keishi Okamotob, Tatsuyuki Nakatanib, Takaaki Hiraguna, Michihiro Hide, “Development of An Optical Fiber SPR Sensor for Living Cell Activation,” Biosensors and Bioelectronics. 25, 5, 1244–1247. (2010)
[28] N. Cennamoa, A. Varrialeb, A. Pennacchiob, M Staianob, D. Massarottic, L. Zenia, Sabato D’Auria, “An Innovative Plastic Optical Fiber-Based Biosensor for New Bio/Applications. The Case of Celiac Disease,” Sensors and Actuators B, 176,1008– 1014. (2013)
[29] Mel N. Kronick, William A. Little, ” A New Immunoassay Based on Fluorescence Excitation by Internal Reflection Spectroscopy,” Journal of Immunological Methods. 8, 3, 235-240 (1975)
[30] L. L. Blyler, JR., R. A. Lieberman, L. G. Cohen, J. A.Ferrara*, and J. B. Macchesney, “Optical Fiber Chemical Sensors Utilizing Dye-Doped Silicone Polymer Claddings”, 29, 17, 1215–1218. (1989)
[31] M. S. John, A. Kishen, L. C. Sing, and A.Asundi,”Determination of Bacterial Activity by Use of An Evanescent-Wav Fiber-Optic Sensor,” Appl. Opt 41,7334-7338. (2002)
[32] H. S. Haddock, P. M. Shankar, and R. Mutharasan, “Evanescent Sensing of Biomolecules and Cells,” Sensors and Actuators B 88. (2003)
[33] Marcuse, D. J. Light wave Technol. 6, 1273-1279. (1988)
[34] Joel P. Golden, George P. Anderson, Sina Y. Rabbany and Frances S. Ligler, “An Evanescent Wave Biosensor- PartⅡ: Fluorescent Signal Acquisition from Tapered Fiber Optic Probes,” IEEE Eng. In Med and Bio, 358-363. (1994)
[34] E. Snitzer, L. Tumminelli, F. HAkimi, N.M. Chu, and T.Haw, ”Doubly Clad High Brightness Nd Fiber Laser Pumped by Gaalas Phased Array,” Optical Fiber Communication Conference. PD7. (1989)
[35] Michael Bass, “Fiber Optics Hhandbook,” McGRAW-HILL. (2002)
[36] J.dakin, B.culshaw, “Optical Fiber Sensors: Principles and Components,” Chapter 6. (1994).
[37] J.R. Lakowicz, “Principles of Fluorescence Spectroscopy 2nd edition,” Springer, New York, Chapter 1-2. (1999).
[38] http://omlc.ogi.edu/spectra/PhotochemCAD/html/083.html
[39] C. V. Raman & K. S. Krishnan “A New Type of Secondary Radiation,” Nature. 121, 501-502. (1928)
[40] Fleischmann, M., Hendra and AJ McQuillan "Raman Spectra of Pyridine Adsorbed at a Silver Electrode," Chemical Physics Letters 26 (2), 163–166. (1974)
[41] Jeanmaire, David L.; Richard P. van Duyne, "Surface Raman Electrochemistry Part I. Heterocyclic, Aromatic and Aliphatic Amines Adsorbed on the Anodized Silver Electrode,” Journal of Electroanalytical Chemistry 84: 1–20. (1977)
[42] Albrecht, M. Grant; J. Alan Creighton, “Anomalously Intense Raman Spectra of Pyridine at a Silver Electrode,” Journal of the American Chemical Society 99 (15): 5215–5217. (1977)
[43] Katrin Kneipp, Harald Kneipp, Irving Itzkan, Ramachandra R Dasari, and Michael S Feld, “Surface-enhanced Raman Sattering and Biophysics,” J. Phys.: Condens. Matter 14 R597–R624. (2002)
[44] A. Otto, “Theory of First Layer and Single Molecule Surface Enhanced Raman Scattering (SERS),” Phys. Status Solidi. 188,1455. (2001)
[45] Kneipp K., Kneipp H., Itzkan I., Dasari R. R. and Feld M. S. "Surface-Enhanced Non-Linear Raman Scattering At The Single- Molecule Level," Chemical Physics. 247, 155-162. (1999)
[46] Kneipp K, Kneipp H, Itzkan I, Dasari R R and Feld M. S., “Near-Infrared Surface-Enhanced Raman Spectroscopy of Biomedically Relevant Single Molecules on Colloidal Silver and Gold Clusters,” Scanning and force microscopies for biomedical applications II Proc. SPIE 3922 49. (2000)
[47] Hua Lu, Yujie Zhao, Jianmin Ma, Wenyou Li, ZuHong Lu, “Characterization of DNA hybridization on the Optical Fiber Surface,” A: Physicochemical and Engineering Aspects . 175, 147–152. (2000)
[48] Peter Hildebrandt and Manfred Stockburger, “Surface-Enhanced Resonance Raman Spectroscopy of Rhodamine 6G Adsorbed on Colloidal Silver,” J. Phys. Chem. 88, 5935-5944. (1984)