臺灣博碩士論文加值系統

波導干涉術(Waveguide Interferometry)是指在波導內全反射傳遞的光，會因波導邊界之折射率或厚度不同造成相位的變化，配合干涉術產生干涉條紋，並利用相移法求出干涉條紋的相位值的一種光學檢測技術。由於此檢測技術可以TE和TM兩種偏極光進行量測，故能提供較多資訊推導出波導上樣本的折射率與厚度等參數值，故可應用於生物分子反應檢測上。本論文提出一具有雙偏極光量測的波導干涉儀架構，以馬赫-曾德干涉術(Mach-Zehnder Interferometry)光路架構為基礎，其中包含自行設計製作的波導晶片、可切換偏極態的樣本光路和參考光路、四分之ㄧ波板和分析板進行相位調制，並使用CCD、IMAQ1409影像擷取卡、LabVIEW程式完成訊號擷取與分析，另外加入溫度控制模組於系統中，可有效降低環境溫度擾動對干涉訊號漂移的誤差。
本研究主要目的是為了解決表面電漿共振術和橢偏術應用於生醫檢測領域所面臨的困難，表面電漿共振術由於檢測原理的限制只能使用TM偏極態量測，所得資訊較無法直接進行複雜的生物反應研究分析；而橢偏術因入射光正向打入樣本時須在水溶液內全反射，會有折射現象造成判讀角度上的困難。雙偏極光之波導干涉術一方面因同時使用TE和TM偏極態可得到較多訊號進行生物參數反解，另一方面由於入射光在波導內傳遞，不會有入射介質折射率改變的問題，同時解決上述兩種檢測技術遭遇的困難。此外由於波導干涉術入射光在波導內多次全反射其訊號為疊加，和上述兩種技術僅為單點量測方式相比具有較高的解析度。
目前所架設雙偏極光之波導干涉儀已完成相關的生物反應檢測驗證。在ELISA生化反應和重現性實驗，成功的量測出Anti-IgG與不同濃度的IgG反應結果，所得訊號將可提供生物醫學領域人員進行複雜生化反應的分析研究。為增進系統的精確度和應用面，已就光機架構、訊號偵測、波導晶片、流道系統等方面做更進一步的研究，使本論文研發之創新生醫檢測技術－雙偏極光波導干涉儀功能更為完備。

When light beam propagates in the waveguide, the optical phase is influenced by the boundary index and thickness variations. Applying the phase modulation method in the configuration, the optical phase can be retrieved from the interference fringes. This technique combining the waveguide and the interferometry is so called “waveguide interfermetry”. It offers more information to resolve bio-sample parameters because both TE and TM polarizations are available. Therefore, it is very suitable to being applied to bio-molecules interactions measurement. In this thesis, a newly developed dual-polarization waveguide interferometry system is developed. The Mach-Zehnder Interferometry based optical configuration includes the newly developed waveguide chip, the sample and the reference light beams equipped with different polarizations, the phase modulation mechanism by combining quarter wave plate and analyzer, CCD, IMAQ card, and LabVIEW program to acquire the signal. Moreover, integrating the analog temperature control system in this optical biochip system further reduces the influence of the environmental disturbance.
The motivation of this dissertation is to solve some problems faced by SPR and ellipsometry detection techniques in bio-tech analysis. Due to generic optical configuration limitations, SPR technique can only adopt TM polarization detection and thus may have less information to retrieve parameters needed to explore the complex bio-reactions. In ellipsometry detection, the incident light path through the bio-sample layer changes due to the bio-sample index variations, which makes it hard to determine the exact incident angle needed for inverse calculations. In order to improve shortcomings of these techniques, the dual-polarization waveguide interferometry system is developed and built during the course of this research. The incident light beam in this method can sense the bio-sample by using both TE and TM polarizations and is propagated in the waveguide without suffering variable indices when light beam penetrates across bio-sample and chip layers. Furthermore, the resolution of waveguide interferomerty is increased due to the multi-reflections exist the waveguide.
The dual-polarized waveguide interferometry system has bee proved the ability to detect the bio-molecules interactions. Some ELISA interaction and regeneration experiments were completed. The Anti-IgG and IgG reaction was successfully measured. These experimental results can be converted into the complex bio-reaction information sought after by biomedical researchers. To further improve the resolution and to expand the application regime of this system, several work items were proposed, which include minimizing the optical system size, simplifying the signal detection part, reducing the waveguide chip cost, and integrating the flow injection system. With these suggested potential improvements implemented, the dual-polarization waveguide interferometry system is expected to become even more accurate and more versatile.

第 1 章 緒論 1
1-1 研究背景 1
1-2 文獻回顧 2
1-2-1 生醫晶片檢測技術 2
1-2-2 波導干涉術之研究與應用 4
1-3 研究動機 8
1-4 論文架構 9
第 2 章 波導干涉儀之光學原理 10
2-1 幾何光學分析 10
2-1-1 漸逝波理論 12
2-1-2 傳播方程式分析 13
2-2 波動光學分析 15
2-2-1 電磁波原理 15
2-2-2 電磁波傳播形式 18
2-2-3 TE偏極態之三層波導 18
2-2-4 TM偏極態之三層波導 20
2-2-5 TE偏極態之四層以上波導 21
2-2-6 TM偏極態之四層以上波導 22
2-3 波導耦合方式 23
2-3-1 透鏡耦合 23
2-3-2 稜鏡耦合 24
2-3-3 光柵耦合 24
2-4 干涉術原理 25
2-4-1 五步相移法 27
2-4-2 步進相移法種類介紹 31
2-4-3 旋轉分析板解相位 34
2-4-4 波導干涉術原理與架構 35
2-5 光學參數對應生物樣本參數關係 37
2-5-1 生化反應之尺寸-密度圖 38
2-5-2 折射率和厚度推算樣本尺寸和濃度關係 40
第 3 章 波導晶片設計與製作 42
3-1 波導晶片介紹 42
3-2 波導晶片材料介紹 44
3-3 晶片製程 45
3-3-1 波導晶片清洗與沉積薄膜 46
3-3-2 波導晶片結構製作 47
3-3-3 波導晶片切割與拋光 48
第 4 章 波導干涉儀系統之設計與研製 51
4-1 光路系統佈局 51
4-2 系統分析 56
4-2-1 系統檢測流程圖 56
4-3 系統光路調校 58
4-3-1 整體光路調校流程 60
4-3-2 偏極元件調校流程 61
4-3-3 入射光導入波導晶片調校流程 62
4-4 溫度控制系統 63
第 5 章 實驗模擬 65
5-1 Film Wizard參數模擬 65
5-2 正算模態解分析軟體 68
5-2-1 單披覆層折射率變化分析 69
5-2-2 多披覆層折射率和厚度變化分析 73
5-3 反算模態解分析軟體 76
5-4 有限差分時域法(FDTD)模擬 77
5-4-1 TE偏極態模擬 78
5-4-2 TM偏極態模擬 80
第 6 章 實驗結果與討論 85
6-1 波導晶片導光性測試 85
6-2 旋轉分析板相位變化測試 87
6-3 不同濃度之純溶液量測 88
6-3-1 訊號重複性實驗 88
6-3-2 純溶液樣本製備 89
6-3-3 大濃度酒精水溶液實驗 91
6-3-4 小濃度酒精水溶液實驗 93
6-3-5 反算純溶液折射率 95
6-4 ELISA生醫鍵結反應量測 96
6-4-1 波導晶片活化及生物架接層製備步驟 96
6-4-2 生物樣本製備步驟 97
6-4-3 TE偏極態量測結果 97
6-4-4 TM偏極態量測結果 98
6-4-5 反算生物樣本折射率和厚度 99
6-4-6 重現性量測結果 100
第 7 章 結論與未來展望 102
7-1 結論 102
7-2 未來展望 103
參考文獻 106

Alayo, M. I., Pereyra, I., Carreno, M. N. P. (1998), “Thick SiOxNy and SiO2 films obtained by PECVD technique at low temperatures,” Thin Solid Films 332, 40-45.
Aust, E. F., and Knoll, W. (1993), “Electro-optical waveguide microscopy,” J. Appl. Phys., 73(6), 2705-2708.
Bearinger, J. P., Voros, J., Hubbell, J. A., and Textor M. (2002), “Electrochemical optical waveguide lightmode spectroscopy (EC-OWLS): A pilot study using evanescent-field optical sensing under voltage control to monitor polycationic polymer adsorption onto indium tin oxide (ITO)-coated waveguide chips,” Oberflachentechnik Laboratory for Surface Science and Technology, Institute for biomedical Engineering.
Brecht, A., Klotz, A., Barzen, C., Gauglitz, G., Harris, R.D., Quigley, G. R., Wilkinson, J.S., Sztajnbok, P., Abuknesha, R., Gascon, J., Oubina, A., and Barcelo, D. (1998), “Optical immunoprobe development for multiresidue monitoring in water,” Analytica Chimica Acta, 362, 67-79.
Chiu, M. H., Lee, J. Y., and Su, D. C. (1997), “Refractive-index measurement based on the effects of total internal reflection and the uses of heterodyne interferometry,” APPLIED OPTICS, 36(13), 2936-2939.
Choo, A. G., Chudgar, M. H., Jackson, H. E., De Brabander, G. N., Kumarm, M., and Boyd, J. T. (1995), “Photon scanning tunneling microscopy of optical channel waveguides,” Ultramicroscopy, 57, 124-129.
Cross G. H., and Freeman, N. J. “Commercialization of optical waveguide biosensor technology,” Farfield Sensors Ltd.
Cross, G. H., Reeves, A. A., Brand, S., Popplewell, J.F., Peel, L. L., Swann, M. J., Freeman, N. J. (2003), “A new quantitative optical biosensor for protein characterisation,” Sensors and Actuators B, 19, 383-390.
Cross, G. H., Reeves, A., Brand, S., Popplewell, J. F., Peel, L. L., Swann, M. J., Freeman, N. J., and Jian R Lu (2004), “The metrics of surface absorbed small molecules on the Young’s fringe dual-slab waveguide interferometer,” J. Phys. D: Appl. Phys, 37, 74-80.
Cross, G. H., Ren, Y., and Freeman, N. J. (1999), “Young’s fringes from vertically integrated slab waveguide: Applications to humidity sensing,” J. Appl. Phys., 86(11), 6483-6488.
Cross, G. H., and Strachan, E. E. (2002), “Diode Laser Wavelength Tracking Using an Integrated Dual Slab Waveguide Interferometer,” IEEE PHOTONICS TECHNOLOGY LETER, 14(7), 950-952.
Freeman, N. J., Peel, L. L., Swann, M. J., Cross, G. H., Reeves, A. A., Brand, S., and Lu, J. R. (2004), “Real time, high resolution studies of protein adsorption and structure at the solid-liquid interface using dual polarization interferometry,” J. Phys.: Condens. Matter, 16, S2493-S2496.
Frins, E. M., Dultz, W., Ferrari. J. A. (1998), “Polarization-shifting method for step interferometry,” Pure Appl. Opt., 7, 53-60.
Goldberg, K. A., and Bokor, J. (2001), “Fourier-transform method of phase-shift determination,” Applied optics, 40(17), 2886-2894.
Han, Y. T., Shin, J. U., Kim, D. J., Park, S. H., Park, Y. J., and Sung, H. K. (2003), “A Rigorous 2D Approximation Technique for 3D Waveguide Structures for BPM Calculations,” ETRI Journal, Volume 25, 535-537.
Harris, R.D., and Wilkinson, J.S., ”Waveguide surface plasmon resonance sensors,” Sensors and Actuators B, 29, 261-267.
Hickel, W., and Knoll, W. (1990), “Optical waveguide microscopy,” Appl. Phys. Lett., 57(13), 1286-1288.
Horvath, R., Voros, J., Graf, R., Fricsovszky, G., Textor, M., Lindvold, L. R., Spencer, N. D., and Papp E. (2001), “Effect of pattern and inhomogeneities on the surface of waveguides used for optical waveguide lightmode spectroscopy applications,” Appl. Phys. B, 72, 441-447.
Horvath, R., Pedersen, H. C., Skivesen, N., Selmeczi, D., and Larsen, N. B. (2003), “Optical waveguide sensor for on-line monitoring of bacteria,” Optics Letters, 28(14), 1233-1235.
http://wwwhome.math.utwente.nl/~hammer/oms.html
http://www.kyoto-kem.com/english/products/refract/ra130.php
http://www.ni.com
http://www.optiwave.com
http://www.teamwavelength.com
Klotz, A., Brecht, A., Barzen, C., Gauglitz, G., Harris, R. D., Quigley, G. R., Wilkinson, J. S., and Abuknesha, R. A. (1998), “Immunofluorescence sensor for water analysis,” Sensors and Actuators B, 51, 181-187.
Klotz, A., Brecht, A., and Gauglitz, G. (1997), “Channel waveguide mode beat interferometer,” Sensors and Actuators B, 38, 310-315.
Kurrat, R., Textor, M., Ramsden, J. J., Boni, P., and Spencer, N. D. (1997), “Instrumental improvements in optical waveguide light mode spectroscopy for the study of biomolecule adsorption,” Rev. Sci. Instrum., 68(5), 2172-2176
Kurrat, R., Walivaara, B., Marti, A., Textor, M., Tengvall, P., Ramsden, J. J., and Spencer N. D. (1998), “Plasma protein adsorption on titanium: comparative in situ studies using optical waveguide lightmode spectroscopy and ellipsometry,” Colloids and surface B: Biointerfaces, 11, 187-201.
Lehr, H. P., Brandenbrurg, A., and Sulz, G. (2003), “Modeling and experimental verification of the performance of TIRF-sensing systems for oligonucleotide microarrays based on bulk and integrated optical planar waveguides,” Sensors and Actuators B, 92, 303-314.
Li, Y. F., and Lit, J. W. Y. (1987), “General formulas for the guiding properties of a multilayer slab waveguide,” J. Opt. Soc. Am. A, 4(4), 671-677.
Ligler, F. S., and Taitt, C. A. R. (2002), Optical Biosensors : Present and Future, Elsevier Science, 277-304.
Lin, S. F., Hou, J. P., Chiu, C. H., Lin, J. Y., Tsai, D. P., and Chu, A. K. ”Fabrication of slilca-on-silicon waveguide devices by PECVD,” National Taiwan University, National Sun Yat-Sen University.
Liu, X., Clegg, W., Liu, B. (2000), “Ultra low head-disk spacing measurement using dual beam polarisation interferometry,” Optics & Laser Technology, 32, 287-291.
Lu, J. R., Swann, M. J., Peel, L. L., and Freeman N. J. (2003), “Lysozyme Adsorption Studies at the Silica/Water Interface Using Dual Polarization Interfrometry,” Farfield Sensors Ltd.
Luff, B. J., Wilkinson, J. S., Piehler, J., Hollenbach, U., Ingenhoff, J., and Fabricius, N. (1998), “Integrated Optical Mach-Zehnder Biosensor,” JOURNAL OF LIGHTWAVE TECHNOLOGY, VOL. 16, NO. 4.
Lukosz, W., (1995) “Integrated optical chemical and direct biochemical sensors,” Sensors and Actuators B, 29, 37-50.
Lukosz, W., Stamm, C., Moser, H.R. Ryf R., Dübendorfer J. (1997), “Differenceinterferometer with new phase-measurement method as integrated-opticalrefractometer, humidity sensor and biosensor,” Sensors and Actuators B, 38-39, 316-323.
Nakadate, S. (1988), “Phase detection of equidistant fringes for highly sensitive optical sensing. I. Principle and error analyses,” J. Opt. Soc. Am. A, 5(8), 1258-1264.
Nakadate, S. (1988), “Phase detection of equidistant fringes for highly sensitive optical sensing. II. Experiments,” J. Opt. Soc. Am. A, 5(8), 1265-1269.
Pandraud, G., and Parriaux, O. (1999), “Zero Dispersion in Step Index Slab Waveguides,” Journal of lightwave technology, 17(11), 2336-2341.
Plowman, T. E., Saavedra, S. S., and Reichert, W. M. (1998), “Planar integrated optical methods for examining thin films and their surface adlayers,” Biomaterials 19, 341-355.
Prieto, F., Sepúlveda B., Calle, A., Llobera, A., Dominguez, C., Lechuga, L.M. (2003), “Integrated Mach-Zehnder interferometer based on ARROW structures for biosensor applications,” Sensors and Actuators B, 92, 151-158.
Reeves, A., Brand, S., Cross, G., “Use of vertically intergrated dual slab waveguide for bio-sensor applications,” Farfield Sensors Ltd.
Ronan, G. (2004), “Dual Polarization interferometry determines protein structure and function,” SPIE’s oemagazine, 17-20.
Sarkisov, S. S., Diggs, D. E., Adamovsky, G., and Curley, M. J. (2001), “Single-arm double-mode double-order planar waveguide interferometric sensor,” Applied Optics, 40(3), 349-359.
SCI (1994), Film WizardTM – Optical Thin Film Software: Getting Started Manual, Professional Version, Scientific Computing International, CA, USA.
Sheridan, A. K., Harris, R. D., Bartlett, P. N., Wilkinson, J. S. (2004), ”Phase interrogation of an integrated optical SPR sensor,” Sensors and Actuators B, 97, 114-121.
Swann, M. J., Peel, L. L., Carrington, S., and Freeman N. J. (2004), “Dual-polarization interferometry: an analytical technique to measure changes in protein structure in real time, to determine the stoichiometry of binding events, and to differentiate between specific and nonspecific interactions,” Analytical Biochemistry, 329, 190-198.
Veldhuis, G.J., Parriaux, O., and Lambeck, P.V. (1999), “Normalized analysis for the optimization of geometric wavelength dispersion in three-layer slab waveguides,” Optics Communications, 163, 278-284.
Voros, J., Graf, R., Kenausis, G. L., Bruinink, A., Mayer, J., Textor, M., Wintermantel, E., and Spencer, N.D. (2000), “Feasibility study of an online toxicological sensor based on the optical waveguide technique,” Biosensor & Bioelectronics, 15, 423-429.
Vo-Dinh, T., and Cullum, B. (2000), “Biosensors and biochips: advances in biological and medical diagnostics,” Fresenius J Anal Chem, 366, 540-551.
Ymeti, A., Kanger, J. S., Greve, J., Lambeck, P. V., Wijn, R., and Heideman, R. G. (2003), “Realization of a multichannel integrated Young interferometer chemical sensor,” APPLIED OPTICS, 42(28), 5649-5660.
Ymeti, A., Kanger, J. S., Wijn, R., Lambeck, P. V., Greve, J. (2002), “Development of a multichannel integrated interferometer immunosensor,” Sensors and Actuators B, 83, 1-7.
朱福海（1997），多功光學顯微系統：設計與研製共焦及光子穿隧顯微鏡，國立台灣大學應用力學研究所碩士論文。
李政隆（2004），掺鍺二氧化矽光波導表面電漿共振生物感測晶片之研發，國立台灣大學醫學工程研究所碩士論文。
李世光，林啟萬，林世明（2003），光生化型晶片系統於流行性疾病檢測與藥物篩選之研發，製藥與生物技術國家型計畫。
李正中（1999），薄膜光學與鍍膜技術，藝軒圖書出版社。
李舒昇（2004），以拋物面鏡為基礎之表面電漿共振儀研究生物晶片上分子反應介面親和力，國立台灣大學應用力學研究所博士論文。
徐維良（2004），光學與電子生醫檢測技術之開發：多功光電生醫晶片儀與新式電化學量測方式，國立台灣大學應用力學研究所碩士論文。
陳怡君（2000），全域波傳量測系統之理論與實驗：以穩頻雙共振腔脈衝雷射為電子斑點干涉即全像紀錄/重建光源之架構開發，國立台灣大學應用力學研究所碩士論文。
陳志豪（2005），以旋轉偏極法突破顯微鏡空間繞射極限之研究，行政院國家科學委員會大專學生參與專題研究計畫研究成果報告。
章鑫（1998），多功光學顯微系統：設計與研製全域非均質表面輪廓量測顯微鏡，國立台灣大學應用力學研究所博士論文。
薛順成（2003），多功光電生醫晶片儀之研製：橢偏術與表面電漿共振偵測之系統整合與應用，國立台灣大學應用力學研究所博士論文。