臺灣博碩士論文加值系統

摘要
近幾年來表面電漿生物感測器受到極大的關注，主因是它提供了免標定與具有極佳的表面靈敏度。但如何降低其製作成本、高通量與提升靈敏度為目前大家所追逐的目標。本論文，吾人利用電子束微影術及反應式離子蝕刻技術製作週期性奈米結構於矽基板上，藉由奈米壓印技術將此週期性結構複製到玻璃基板上，降其製程時間及成本。並將藉由測量不同重量百分比的甘油水混和溶液比較其波長與光強度之靈敏度，且由結果顯示分析光強度(8.5×10-5)與分析波長(3.1×10-5)對環境折射率改變之靈敏度並不會有太大的差異，但分析光強度變化的方式，適時地提供了高通量量測的優點。
因此吾人更進一步的在蛋白質微陣列的檢測實驗中，使用7nM的BSA與 2.5nM的anti-BSA進行蛋白質與蛋白質交互作用動力學測量
，並以波長(846nm)的LED燈源當入射光，利用一CCD相機（SBIG, ST-10XME）來記錄影像，最後利用程式分析影像中週期性奈米金屬狹縫陣列光強度的變化，在此實驗中，我們可以同時得到三個狹縫陣列中的蛋白質動力學反應。假設光源的穩定度為0.2%，此原件可以偵測到anti-BSA的濃度極限為35pM。

Abstract
Surface Plasmon Resonance has got lots of attention in last few years. It provides label-free and high surface sensitivity. However, decreasing the cost, high-throughput detection, and improving sensitivity are the main trends for everyone wants to achieve.
In this the thesis, I fabricate the period nanostructure on silicon subtract by E-beam lithography and RIE etching and then using the nanoinprint technology to replcate the nanostructure to glass subtract. In this way, it can not only decrease the time for fabricating the nanostructure sample but also the cost. The sensitivity of nanostructure base chip is done by glycerol solution in diffirent concentration. The result shows the sensitivity has no significant different performance between wavelength detection (3.1×10-5) and intensity detection (8.5×10-5) ,however, the intensity detection has the potential for high-throughput sensing development.
In the protein array sensing experiment, BSA and anti-BSA as the demonstration of molecular interaction dynamic detection, the BSA concentration is 7 nM and anti-BSA is 2.5 nM. The wavelength in 846 nm of LED as the light source in this experiment setup. The CCD records the image and analysising the image to get the intensity changing during the experiment. In the end, I perform the three slit array detection result. The anti-BSA detecting limitation is 35pM in assuming the light stability is 0.2%.

目錄
誌謝 i
中文摘要 ii
英文摘要 iii
目錄 iv
圖目錄 v
表目錄 v
第一章 緒論 1
1-1前言 1
1-2文獻回顧 3
1-2.1表面電漿子共振作用在生物感測器之發展 3
1-2.2奈米壓印技術發展[18] 5
1-2.3表面電漿子共振生物感測器之量測方式 7
1-3研究動機 9
1-4論文架構 10
第二章 金屬表面電漿子共振與激發 11
2-1簡介表面電漿子 11
2-2金屬介面與介質間表面電漿共振關係 11
2-3侷域性表面電漿共振關係[23] 18
2-4激發表面電漿的方式 21
2-4.1稜鏡耦合（prism coupling） 21
2-4.2光柵耦合（grating coupling） 23
2-5表面電漿耦合共振模型 24
第三章 奈米金屬狹縫製程與光學特性 26
3-1電子束微影技術簡介 26
3-2反應式離子蝕刻技術簡介 29
3-3母模奈米結構之製作 31
3-4紫外光固化奈米壓印 37
第四章 奈米金屬狹縫在生醫感測之應用 48
4-1奈米金屬狹縫表面電漿子共振生物感測器 48
4-2量測系統 49
4-3週期性奈米金屬狹縫環境折射率之靈敏度 53
4-4 週期性奈米金屬狹縫生物感測器 60
第五章 總結與未來展望 66
參考文獻 68

參考文獻
1. R. Narayanaswamy, O.S.W., Optical Sensors,Springer,New York,. 2004.
2. Rowe-Taitt, C.A., et al., Simultaneous detection of six biohazardous agents using a planar waveguide array biosensor. Biosensors & Bioelectronics, 2000. 15(11-12): p. 579-589.
3. Cowan, J.J., R.H. Ritchie, and E.T. Arakawa, SURFACE PLASMON RESONANCE EFFECT IN GRATING DIFFRACTION. Bulletin of the American Physical Society, 1968. 13(11): p. 1413-&.
4. Homola, J., S.S. Yee, and G. Gauglitz, Surface plasmon resonance sensors: review. Sensors and Actuators B-Chemical, 1999. 54(1-2): p. 3-15.
5. Piehler, J., A. Brecht, and G. Gauglitz, Affinity detection of low molecular weight analytes. Analytical Chemistry, 1996. 68(1): p. 139-143.
6. Goddard, N.J., D. Pollardknight, and C.H. Maule. REAL-TIME BIOMOLECULAR INTERACTION ANALYSIS USING THE RESONANT MIRROR SENSOR. 1994: Royal Soc Chemistry.
7. Clerc, D. and W. Lukosz. INTEGRATED OPTICAL OUTPUT GRATING COUPLER AS BIOCHEMICAL SENSOR. 1994: Elsevier Science Sa Lausanne.
8. G Boisde, A.H., Chemical and biochemical sensing with optical fibers and waveguides, Artech House, . 1996
9. B Liedberg, C.N., I Lundstrom, Surface plasmon resonance for gas detection and biosensing, Sens. Actuators. 1983.
10. Homola, J., Present and future of surface plasmon resonance biosensors. Analytical and Bioanalytical Chemistry, 2003. 377(3): p. 528-539.
11. MacBeath, G. and S.L. Schreiber, Printing proteins as microarrays for high-throughput function determination. Science, 2000. 289(5485): p. 1760-1763.
12. Hoa, X.D., A.G. Kirk, and M. Tabrizian, Towards integrated and sensitive surface plasmon resonance biosensors: A review of recent progress. Biosensors & Bioelectronics, 2007. 23(2): p. 151-160.
13. Ebbesen, T.W., et al., Extraordinary optical transmission through sub-wavelength hole arrays. Nature, 1998. 391(6668): p. 667-669.
14. Lezec, H.J., et al., Beaming light from a subwavelength aperture. Science, 2002. 297(5582): p. 820-822.
15. Boozer, C., et al., DNA directed protein immobilization on mixed ssDNA/oligo(ethylene glycol) self-assembled monolayers for sensitive biosensors. Analytical Chemistry, 2004. 76(23): p. 6967-6972.
16. Rindzevicius, T., et al., Long-range refractive index sensing using plasmonic nanostructures. Journal of Physical Chemistry C, 2007. 111(32): p. 11806-11810.
17. Chou, S.Y., Krauss, P. R. and Renstrom, P. J., Appl. Phys. Lett., 67, 3114 1995.
18. 蔡宏營, 奈米轉印技術介紹, 工研院機械所奈米工程技術部專欄. 2004.
19. Willson, C.G., et al., Proc. SPIE, 3676(I): 379, 1999.
20. Lin, H.-Y., Direct Detection of C-reactive Proteins in Human Serum Using Surface Plasmon Resonance Biosensing 2006, 06, 15.
21. Lee, K.L., et al., Sensitive biosensor array using surface plasmon resonance on metallic nanoslits. Journal of Biomedical Optics, 2007. 12(4): p. 5.
22. Wood, R.W., On a remarkable case of uneven distribution of light in a diffraction grating spectrum. Philosophical Magazine, 1902. 4(19-24): p. 396-402.
23. Fano, U., The theory of anomalous diffraction gratings and of quasi-stationary waves on metallic surface, Journal of the Optical Society of America. 1941.
24. 邱國斌、蔡定平, 金屬表面電漿簡介,物理雙月刊(二十八卷二期). 2006.
25. 吳民耀、劉威志, 表面電漿子理論與模擬,物理雙月刊(二十八卷二期). 2006.
26. Kottmann, J.P., et al., Plasmon resonances of silver nanowires with a nonregular cross section. Physical Review B, 2001. 64(23): p. 10.
27. Gordon, R., Light in a subwavelength slit in a metal: Propagation and reflection. Physical Review B, 2006. 73(15): p. 3.
28. Beck, M., et al. Improving stamps for 10 nm level wafer scale nanoimprint lithography. 2002: Elsevier Science Bv.
29. Koo, N., et al., The fabrication of a flexible mold for high resolution soft ultraviolet nanoimprint lithography. Nanotechnology, 2008. 19(22): p. 4.