研究生: |
徐元峻 Yuan-Chun Hsu |
---|---|
論文名稱: |
運用低同調光源與雷射聯級之表面電漿共振空間相位感測 Spatial Phase Biosensing on Surface Plasmon Resonance through Cascaded Laser and Low Coherence Interferometry |
指導教授: |
徐世祥
Shih-Hsiang Hsu 林保宏 Pao-hung Lin |
口試委員: |
徐世祥
Shih-Hsiang Hsu 林保宏 Pao-hung Lin 張哲菖 Chang, Che-Chang 劉國辰 Kou-Chen Liu |
學位類別: |
碩士 Master |
系所名稱: |
電資學院 - 電子工程系 Department of Electronic and Computer Engineering |
論文出版年: | 2019 |
畢業學年度: | 107 |
語文別: | 中文 |
論文頁數: | 104 |
中文關鍵詞: | 表面電漿干涉 、低同調干涉 、空間相位感測 |
外文關鍵詞: | Surface Plasmon Resonance, Low Coherence Interferometry, Spatial Phase Biosensing |
相關次數: | 點閱:323 下載:0 |
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表面電漿共振(Suface Plasmon Resonance, SPR)現象,被發現已經有近一百年的歷史,而近幾年來隨著生物醫學的發展,這項技術更是被廣泛應用在生物檢測上。由於它對不同折射率待測物有高靈敏度的特性,因此常常被用來做生物醫學檢測。常見的表面電漿共振量測方式有四種,角度調製、波長調製、強度調製以及相位調製,其中以相位靈敏度最高,因最大的相位變化發生在SPR曲線最窄處,也是探測電場相量最大處,所以為了取得反射光相位資訊,本論文使用低同調與高同調的光源干涉的表面電漿感測器架構來檢測微小核醣核酸的濃度變化。
本論文提出新穎性的方法以增強表面電漿共振空間相位生醫感測系統。由於低同調干涉波包具有穩定及明顯性,因此我們利用寬頻光源做為參考基準點,同時並聯高同調性雷射光源作為感測端,用以量測低濃度微小的相位變化。我們成功量測固定化Capture DNA前後之相位靈敏度,同時證明經硫醇修飾與硫基還原反應後的Capture DNA可以鍵結於金膜表面,並抓取Target DNA。另外專一性實驗,則證明我們使用之Capture DNA與Target DNA之間具有高度專一性。本架構量測microRNA-21之相位靈敏度為0.49 rad/µM。另外成功驗證雙通道同步取樣時間上的誤差,進而推算出檢測極限為0.63µM。
With the biomedical technique development, surface plasmon resonance (SPR), which phenomenon has been found for nearly a hundred years, is widely utilized in biological detection due to its high sensitivity. There are four kinds of SPR characterizations - angle, wavelength, intensity and phase modulation. Among them, the phase modulation demonstrates the highest sensitivity because the maximum phase change occurs in the SPR curve dip where the largest electric field is happening. In order to retrieve the reflected light phase information, the low coherence interferometry based SPR sensor is utilized to detect various concentrations of microRNA in this thesis.
In this thesis, a novel approach to improve SPR spatial phase biosensing is demonstrated. Because of the stability and resolvability of low coherence interferograms, the broad band source is interrogated with the laser beam reference interferogram to detect various analyte concentrations through the cascaded optical fiber low coherence interferometry (OFLCI).
We successfully demonstrated the capture DNA phase sensitivity before and after immobilization. The capture DNA could bond with the gold film surface through Thiol-modified Oligonucleotide reduction and then capture target DNA. Moreover, the excellent specificity between capture DNA and target DNA is also experimentally illustrated. Finally, the sensitivity is shown 0.49 (rad/µM). Furthermore, the error in the simultaneous sampling time of the two channels is utilized to successfully analyze the detection limit as 0.63 µM.
參考文獻
[1] R.W. Wood,“On remarkable case uneven distribution of light in a diffraction gration spectrum,” Phil. Magm., vol. 4,pp. 396-402, 1905.
[2] U. Fano, "The Theory of Anomalous Diffraction Gratings and of Quasi-Stationary Waves on Metallic Surfaces (Sommerfeld’s Waves)", Journal of the Optical Society of America, vol. 31, no. 3, p. 213, 1941.
[3] E. Krestschmann,“The determination of the optical constants of metals by excitation of surface plasmons,”Z. Physik, vol. 241, pp. 313, 1971.
[4] R. Lee, J. Hench and G. Ruvkun, "Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway", Current Biology, vol. 11, no. 24, pp. 1950-1957, 2001.
[5] P. Xu, S. Vernooy, M. Guo and B. Hay, "The Drosophila MicroRNA Mir-14 Suppresses Cell Death and Is Required for Normal Fat Metabolism", Current Biology, vol. 13, no. 9, pp. 790-795, 2003.
[6] J. DOSTIE, "Numerous microRNPs in neuronal cells containing novel microRNAs", RNA, vol. 9, no. 2, pp. 180-186, 2003.
[7] F. Wahid, A. Shehzad, T. Khan, and Y. Y. Kim, "MicroRNAs: Synthesis, mechanism, function, and recent clinical trials," Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol. 1803, pp. 1231-1243, 2010.
[8] V. Ghai and K. Wang, "Recent progress toward the use of circulating microRNAs as clinical biomarkers," Archives of Toxicology, vol. 90, pp. 2959-2978, 2016.
[9] M. Kashif, A. A. A. Bakar, N. Arsad, and S. Shaari, "Development of Phase Detection Schemes Based on Surface Plasmon Resonance Using Interferometry," Sensors vol. 14, pp. 15914-15938, 2014.
[10] 吳民耀與劉威志, “表面電漿子理論與模擬” 物理雙月刊,廿八卷二期,pp. 486-496,2006
[11] J. Homola, "Surface Plasmon resonance sensors for detection of chemical and biological species," Chemical Reviews, vol. 108, no. 2, pp. 462–493, Feb. 2008.
[12] B. Kimbrough, J. Millerd, J. Wyant, and J. Hayes, "Low-coherence vibration insensitive Fizeau interferometer," SPIE Optics + Photonics, vol. 6292, p. 12, 2006.
[13] N. Brock, J. Hayes, B. Kimbrough, J. Millerd, M. North-Morris, M. Novak, et al., "Dynamic interferometry," Optics and Photonics vol. 5875, p. 10, 2005.
[14] C. Lawson and R. Michael, "Fiber optic low-coherence interferometry for non-invasive silicon wafer characterization", Journal of Crystal Growth, vol. 137, no. 1-2, pp. 37-40, 1994.
[15] 游輝智,”光學低同調干涉技術系統的建構與應用”,國立台灣科技大學電子工程所,2008。
[16] 吳宗正, “生物感測器,” 生物技術,九州出版社,第十八章,pp. 24-262,1996。
[17] A. Hulanicki, “Chemical sensors definitions and classification,” Pure and Applied Chemistry, vol. 63, no. 9, pp. 1247-1250, 1991.
[18] Andrei V. Kabashin, Sergiy Patskovsky, and Alexander N. Grigorenko, "Phase and amplitude sensitivities in surface plasmon resonance bio and chemical sensing," Opt. Express 17, 21191-21204 (2009)
[19] J. Homola, “Surface Plasmon Resonance Based Sensor”.
[20] Susana Campuzano, María Pedrero, and J. M. Pingarrón, "Electrochemical genosensors for the detection of cancer-related miRNAs," Analytical and Bioanalytical Chemistry, vol. 406, pp. 27-33, 2014.
[21] S.P. Ng, C.M. L. Wu, S.Y. Wu, H.P. Ho, and S. K. Kong, "Differential spectral phase interferometry for wide dynamic range surface plasmon resonance biosensing," Biosensors and Bioelectronics, vol. 26, pp. 1593-1598, 2010.
[22] H.P. Ho and W.W. Lam, "Application of differential phase measurement technique to surface plasmon resonance sensors," Sensors and Actuators B: Chemical, vol. 96, pp. 554–559, 2003.
[23] W. Yuan, H. P. Ho, C. L. Wong, S. K. Kong, and C. Lin, "Surface Plasmon Resonance Biosensor Incorporated in a Michelson Interferometer With Enhanced Sensitivity," IEEE Sensors Journal, vol. 7, pp. 70-73, 2007.
[24] 林萱,“利用相位式表面電漿共振系統 檢測免疫球蛋白鍵結之應用分析,” 國立中央大學光電科學與工程學系研究所碩士論文, 2012
[25] 王雅榕,“改善光相位解析式表面電漿共振生物感測器之靈敏度及表面電漿共振影像系統之發展,”國立陽明大學生醫光電研究所碩士論文, 2009
[26] Y. W. Zheng Zheng, Xin Zhao, and Jinsong Zhu, "Spectral interferometric measurement of wavelength-dependent phase response for surface plasmon resonance sensors," APPLIED-OPTICS, 2009.
[27] Y. Huang, H. Ho, S. Kong and A. Kabashin, "Phase-sensitive surface plasmon resonance biosensors: methodology, instrumentation and applications", Annalen der Physik, vol. 524, no. 11, pp. 637-662, 2012.
[28] J. Homola, “Springer series on chemical sensors and biosensors,” Springer, vol. 4, pp. 3-44, 2006.
[29] A. Rakić, A. Djurišić, J. Elazar and M. Majewski, "Optical properties of metallic films for vertical-cavity optoelectronic devices", Applied Optics, vol. 37, no. 22, p.p 5271, 1998.
[30] P. B. Johnson and R. W. Christy, “Optical Constants of the Noble Metals,” Physical Review B, vol. 6, pp. 4370-4379, 1972.
[31] SCHOTT Taiwan Ltd., optical glass data sheets, 2015.
[32] S. A. Kim, S. J. Kim, S. H. Lee, T. H. Park, K. M. Byun, S. G. Kim, et al., "Avian influenza-DNA hybridization detection using wavelength interrogation-based surface plasmon resonance biosensor," presented at the 2009 IEEE Sensors, 2009.
[33] H. Su and X. G. Huang, "Fresnel-reflection-based fiber sensor for on-line measurement of solute concentration in solutions," Sensors and Actuators B: Chemical, vol. 126, pp. 579-582, 2007.