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姓名	李穎昌(Ying-Chang Li)  查詢紙本館藏	畢業系所	光電科學與工程學系
論文名稱	成對表面電漿波生物感知器應用在去氧核糖核酸及微型核糖核酸 雜交反應檢測 (DNA and miRNA analysis by Paired Surface Plasma-based biosensor )
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摘要(中)	表面電漿共振 (Surface Plasmon Resonance, SPR) 可以直接檢測偵測晶片上生物反應的特殊技術。SPR 因可監控偵測晶片上折射率的微量變化，在生化量測上排除了螢光標定過程，且能達到即時地分析生物分子之間交互作用的能力，縮短量測所需的時間。近年來，SPR技術已廣泛利用於生物分子診斷的許多相關領域，諸如抗原-抗體反應、蛋白質的非特異性吸附、去氧核糖核酸分子雜交等。 本次研究中，我們自行研發了相敏式表面電漿共振生物感知器(DP-SPRB)及成對表面電漿波生物感知器(PSPWB)，它們具有相較於傳統SPR感知器，達到更高靈敏度且更好的雜訊抑制能力。其後我們利用成對表面電漿波生物感知器進行去氧核糖核酸分子雜交的量測，也成功區分單股核苷酸在互補配對及單點突變條件下雜交反應的差異，以及單股核苷酸序列長度不同時雜交反應的區別。我們也結合Langmuir isotherm equation 將高濃度去氧核糖核酸分子溶液的雜交結果的進行動力學分析。最後，我們利用表面電漿波生物感知器量測具有21個鹼基的微型核糖核酸 (miRNA) 雜交反應，並使用Langmuir isotherm方程式算出其结合速率常数。未來目標以金膜表面處理為優先，使系統能在血清或血漿作微量miRNA檢測。並將系統優化，使其維持高穩定性，以達到定量分析之能力，以期能讓系統在miRNA濃度分析上進行臨床檢驗，協助參與癌症預估及診斷分析。
摘要(英)	Surface plasmon resonance spectroscopy is a surface characteristerization technique that can direct detect the biological interaction on the chip surface. The sensitivity to the refractive index of a substance is much higher than other detection methods and the feature of label-free detection can rule out some participations of the labeling process. It is particularly important to execute the biomolecular interaction analysis (BIA) with real-time monitoring, which is greatly shortened the detection period to avoid denaturation of surface-adsorbed antigens. In recent years, SPR spectroscopy has been widely applied in many areas of biomolecular diagnostics, such as receptor-ligand or antigen-antibody interactions, non-specific adsorption (NSA) of biomolecules, DNA hybridization, etc. In this investigation, the development of differential phase surface plasmon resonance biosensor (DP-SPRB) and paired surface plasma waves biosensor (PSPWB) is to extend the detection limit and decrease the background fluctuation in biomaterial interactions. The discrimination between perfect-matched and single-base-pair-mismatched nucleic acid duplexes was performed by using PSPWB. An in vitro culture model was developed to make comparisons by using different sequence length of oligonucleotides for hybridization test on the platform of PSPWB, too. Finally, the kinetics information of short DNA oligonucleotides was obtained from PSPWB, and the hybridization detection of a 21-base-pair microRNA (miRNA) were proposed and discussed. In the future, we try to change the surface chemistry in blocking process to avoid the unwanted biomolecules and optimize the stability of our optical system to reach to quantitative detection of specific miRNA for the purpose of being used in cancer prognosis and diagnosis.
關鍵字(中)	★ 去氧核糖核酸 ★ 表面電漿共振 ★ 微型核糖核酸 ★ 雜交	關鍵字(英)	★ microRNA ★ surface plasmon resonance ★ DNA ★ hybridization
論文目次	摘要 vi ABSTRACT vii ACKNOWLEDGEMENTS viii LIST OF FIGURES xii LIST OF TABLES xv EXPLANATION OF SYMBOLS xvi 1 INTRODUCTION - 1 - 2 THEORY - 4 - 2.1 DNA and miRNA in general - 4 - 2.1.1 DNA - 4 - 2.1.2 MicroRNA - 7 - 2.2 SURFACE PLASMON RESONANCE - 9 - 2.2.1 Description of the SPR phenomenon - 10 - 2.2.2 The twe-interfaces system and its dispersion curves - 14 - 2.2.3 SPR profile including the resonance angle - 19 - 2.3 Langmuir Isotherm - 21 - 3 RESEARCH CONTENTS AND METHODS - 23 - 3.1 Interrogations of SPR-based sensor - 23 - 3.2 Experimental Methods - 33 - 3.2.1 Differential-phase surface plasmon resonance biosensor (DP-SPRB) setup ………………………………………………………………………...- 33 - 3.2.2 Paired Surface Plasma waves biosensor setup - 38 - 4 EXPERIMENTAL RESULTS IN DP-SPRB - 40 - 4-1 Detection Limit - 41 - 4-2 IgG/antimouse IgG interaction - 47 - 5 PSPWB OF DNA-RNA AND DNA-DNA HYBRIDIZATIONS - 51 - 5.1 Deteceion limit in short sequence length oligonucleotide hybridization - 52 - 5.1.1 Materials - 52 - 5.1.2 Immobilization of oligonucleotide probes - 54 - 5.1.3 The preparation of target oligonucleotide - 56 - 5.1.4 Measurement of affinity between oligonucleotides - 56 - 5.1.5 Construction of sensor chip - 57 - 5.1.6 Results and discussion - 60 - 5.2 Validation of the oligonucleotide binding specificity - 64 - 5.3 Length dependence of oligonucleotide target sequences - 66 - 5.4 Sequence dependence of oligonucleotide target - 68 - 5.5 Kinetics analysis - 70 - 5.6 DNA-RNA hybridization - 72 - 6 CONCLUSION - 75 - 6.1 DP-SPRB - 75 - 6.2 PSPWB detection and hybridizations of oligonucleotide or miRNA - 77 - REFERENCE - 79 -
參考文獻	[1] Raether, H. 1988, Surface Plasmons on Smooth and Rough Surfaces and on Gratings, New York, Springer-Verlag: 118-119. [2] Homola, J. 2003, “Present and future of surface plasmon resonance biosensors,” Analytical and Bioanalytical Chemistry 377: 528–539. [3] Ekgasit, S.; Thammacharoen, C.; Knoll, W. 2004, “Surface Plasmon Resonance Spectroscopy Based on Evanescent Field Treatment,” Analytical Chemistry 76: 561-568 [4] Lokate, A.M.C.; Beusink, J.B.; Besselink, G.A.C.; Pruijn, G.J.M.; Schasfoort, R.B.M. 2007, “Biomolecular Interaction Monitoring of Autoantibodies by Scanning Surface Plasmon Resonance Microarray Imaging,” Journal of American Chemical Society 129: 14013–14018. [5] Kuo, W. C., Chou, C., Wu, H. T., 2003, “Optical heterodyne surface-plasmon resonance biosensor,” Optics Letters 28: 1329-1331. [6] Homola, J.; Yee, S.S.; Gauglitz, G. 1999, “Surface plasmon resonance sensors: review,” Sensors and Actuators B: Chemical 54: 3-15. [7] Wu, S.Y.; Ho, H.P.; Law, W.C.; Lin, C. 2004, “Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach–Zehnder configurationin,” Optics Lettters 29: 2378–2380. [8] Šipova, H.; Zhang, S.; Dudley, A.M.; Galas, D.; Wang, K.; Homola, J. 2010, “Surface Plasmon Resonance Biosensor for Rapid Label-Free Detection of Microribonucleic Acid at Subfemtomole Level,” Analytical Chemistry 82: 10110-10115. [9] Wark, A.W.; Lee, H.J.; Qavi, A.J.; Corn, R.M. 2007, “Surface Plasmon Resonance Biosensor for Rapid Label-Free Detection of Microribonucleic Acid at Subfemtomole Level,” Analytical Chemistry 79: 6697-6701. [10] Storhoff, J.J.; Marla, S.S.; Bao, P.; Hagenow, S.; Mehta, H.; Lucas, A.; Garimella, V.; Patno, T.; Buckingham, W.; Cork, W.; Muller, U. R. 2004, “Gold nanoparticle-based detection of genomic DNA targets on microarrays using a novel optical detection system,” Biosensors and Bioelectronics 19: 875-883. [11] D’’Agata,R.; Corradini, R.; Ferretti, C.; Zanoli, L.; Gatti, M.; Marchelli, R.; Spoto, G. 2010, “Ultrasensitive detection of non-amplified genomic DNA by nanoparticle-enhanced surface plasmon resonance imaging,” Biosensors and Bioelectronics 25: 2095-2100. [12] Gifford, L.K.; Sendroiu, I.E.; Corn, R.M.; Luptak, A. 2010, “Attomole Detection of Mesophilic DNA Polymerase Products by Nanoparticle-Enhanced Surface Plasmon Resonance Imaging on Glassified Gold Surfaces,” Journal of American Chemical Society 132: 9265–9267. [13] Huang, Y.C.; Chen, Y.L.; Kuo, W.C. 2006, “Characteristics of a paired surface plasma waves biosensor,” Optics Express 14: 4307-4315. [14] Su, L. C.; Chen, R. C.; Li, Y. C.; Chang, Y. F.; Lee, Y. J.; Lee, C. C.; Chou, C.; 2010, “Detection of Prostate-Specific Antigen with a Paired Surface Plasma Wave Biosensor,” Analytical Chemistry 82: 3714–3718. [15] Iguchi, H.; Kosaka, N.; Ochiya, T. 2010, “Versatile Applications of microRNA in Anti-Cancer Drug Discovery: From Therapeutics to Biomarkers” Current Drug Discovery Technologies 7: 95-105. [16] George, G.P.; Mittal, R.D. 2010, “MicroRNAs: Potential Biomarkers in Cancer” Indian Journal of Clinical Biochemistry 25: 4-14. [17] Watson J.D. and Crick F.H.C. 1953, “A Structure for Deoxyribose Nucleic Acid” Nature 171: 737–738. [18] Isaksson, J., Acharya, S., Barman, J., Cheruku, P., Chattopadhyaya, J. 2004, “Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern” Biochemistry 43: 15996–16010. [19] Ahn, S.; Walt, D.R. 2005, “Detection of Salmonella spp. Using microsphere-based, fiber-optic DNA array,” Analytical Chemistry 77: 5041-5047. [20] Ricci, F.; Plaxco, K.W. 2008, “E-DNA sensors for convenient, label-free electrochemical detection of hybridization,” Microchim Acta 163: 149-155. [21] Burbulis, I.; Yamaguchi, K.; Gordon, A.; Carlson, R.; Brent, R. 2005, “Using protein-DNA chimeras to detect and count small numbers of molecules,” Nature Methods 2, 31-37. [22] Vaisocherova, H.; Snašel, J.; Špringer, T.; Špringer H.; Rosenberg, I.; Štěpanek, J.; Homola, J. 2009, “Surface plasmon resonance study on HIV-1 integrase strand transfer activity,” Analytical and Bioanalytical Chemistry 393:1165. [23] Bartel, D.P. 2004, “MicroRNAs: genomics, biogenesis, mechanism, and function” Cell 116: 281–297. [24] He, L.; Thomson, J.M.; Hemann, M.T.; Hernando-Monge, E.; Mu, D.; Goodson, S.; Powers, S.; Cordon-Cardo, C.; Lowe, S.W.; Hannon, G.J.; Hammond, S.M. 2005, “A microRNA polycistron as a potential human oncogene, ” Nature 435: 828–833. [25] Mraz, M., Pospisilova, S., Malinova, K., et al. 2009, “MicroRNAs in chronic lymphocytic leukemia pathogenesis and disease subtypes” Leukumia & Lymphoma 50: 506–509. [26] Lu, J., Getz, G., Miska, E.A. et al. 2005, “MicroRNA expression profiles classify human cancers” Nature 435: 834–838. [27] Kosaka, N., Iguchi, H., Ochiya, T. 2010, “Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis” Cancer Science 101: 2087–2092. [28] Lawrie, C.H., Gal, S., Dunlop, H.M. et al. 2008, “Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma.” British Journal of Haematology 141: 672–675. [29] Ritchie, R.H. 1957, “Plasma Losses by Fast Electrons in Thin Films.” Physical Review 106: 874–881. [30] Liedberg, B., Nylander, C., Lunstrom, I. 1983, “Surface plasmon resonance for gas detection and biosensing.” Sensors and Actuators 4: 299–304. [31] Flanagan, M.T. and Pantell, R.H. 1984, “Surface plasmon resonance and immunosensors.” Electronics Letters 20: 968–970. [32] Schasfoort, R.B.M.; Tudos, A.J. 2008, Hankbook of Surface Plasmon Resonance, Rolyal Society of Chemistry. [28] Boardman , A.D. 1982, Electromagnetic surface modes, Wiley, Chichester. [29] Born, M.; Wolf, E. 1999, Principles of optics: electromagnetic theory of propagation, interference and diffraction of light, Cambridge University Press, Cambridge. [30] Atkins, P.W. 1998, Physical Chemistry, 6th edition, Oxford University Press, 858-859. [31] Liu, J.; Tiefenauer, L.; Tian, S.J.; Nielsen, P.E.; Knoll, W. 2006, “PNA-DNA Hybridization Study Using Labeled Streptavidin by Voltammetry and Surface Plasmon Fluorescence Spectroscopy,” Analytical Chemistry 78: 470-476. [32] Schasfoort, R.B.M.; Tudos, A.J. 2008, Hankbook of Surface Plasmon Resonance, Rolyal Society of Chemistry. [33] Innes, R.A.; Welford, K.R. 1987, Surface Plasmon-Polaritons, Proceeding of a one-day workshop of the Thin Films and Surface Group of The Institute of Physics, London. [34] Neumann, T. 2001, Strategies for Detecting DNA Hybridisation Using Surface Plasmon Fluorescence Spectroscopy, Mainz, p.15. [35] Park, H.; Germini, A.; Sforza, S.; Corradini, R.; Marchelli, R.; Knoll, W. 2006, “Kinetic and affinity analyses of hybridization reactions between peptide nucleic acid probes and DNA targets using surface plasmon field-enhanced fluorescence spectroscopy” Biointerphases 1: 113-122. [36] Yu, F.; Yao, D.; Knoll, W. 2004, “Oligonucleotide hybridization studied by a surface plasmon diffraction sensor (SPDS)” Nucleic Acids Research 32: e75. [37] Boozer, C.; Ladd, J.; Chen, S.F.; Jiang, S.Y. 2006, “DNA-Directed Protein Immobilization for Simultaneous Detection of Multiple Analytes by Surface Plasmon Resonance Biosensor, ” Analytical Chemistry 78: 1515-1519. [38] Kolomenskii, A.A.; Gershon, P.D.; Schuessler, H.A. 1997, “Sensitivity and detection limit of concentration and adsorption measurements by laser-induced surface-plasmon resonance,” Applied Optics 36: 6539–6547. [39] Brandenburg, A.; Krauter, R.; Ku ‥nzel, C.; Stefan, M.; Schulte, H. 2000, “ Interferometric Sensor for Detection of Surface-Bound Bioreactions,” Applied Optics 39: 6396–6405. [40] Chou, C.; Hsu, H.Y.; Wu, H.T.; Tseng, K.Y.; Chiou, A.; Yu, C.J.; Lee, Z.Y.; Chan, T.S. 2007, “Fiber optic biosensor for the detection of C-reactive protein and the study of protein binding kinetics, ” Journal of Biomedical Optics 12: 24025. [41] Zhang, J.; Fu, Y.; Chowdhury, M. H.; Lakowicz, J. R. 2007, “Metal-Enhanced Single-Molecule Fluorescence on Silver Particle Monomer and Dimer:  Coupling Effect between Metal Particles,” Nano Letters 7: 2101–2107. [42]http://www.biacore.com/lifesciences/products/systems_overview/t100/system_information/index.html/, Biacore T100 Product Information.pdf.; Biacore Inc., (May 2007) [43] Chou,C.; Lyu, C.W.; Peng, L.C. 2001, “Polarized Differential-Phase Laser Scanning Microscope,” Applied Optics 40: 95–99. [44] Wu, S. Y.; Ho, H. P.; Law, W. C.; Lin, C. 2004, “Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach–Zehnder configuration,” Optics Letters 29: 2378–2380. [45] Schreiner, S.M.; Shudy, D.F.; Hatch, A.L.; Opdahl, L. 2010, “Controlled and Efficient Hybridization Achieved with DNA Probes Immobilized Solely through Preferential DNA-Substrate Interactions” Analytical Chemistry 82: 2803-2810. [46] Pan, S.; Rothberg, L. 2005, “Chemical Control of Electrode Functionalization for Detection of DNA Hybridization by Electrochemical Impedance Spectroscopy,” Langmuir 21: 1022-1027. [47] Pris, A. D., Ostrowski, S. G., Garaas, S. D., 2010, “Simultaneous Optimization of Monolayer Formation Factors, Including Temperature, To Significantly Improve Nucleic Acid Hybridization Efficiency on Gold Substrates, ” Langmuir 26: 5655-5660. [48] Milkani, E., Morais, S., Lambert, C. R., McGimpsey, W. G., 2010, “Detection of oligonucleotide systematic mismatches with a surface plasmon resonance sensor, ” Biosensors and Bioelectronics 25: 1217-1220. [49] Jiang, T., Minunni, M., Wilson, P., Zhang, J., Turner, A. P. F., Mascini, M., 2005 , “Detection of TP53 mutation using a portable surface plasmon resonance DNA-based biosensor, ” Biosensors and Bioelectronics 20: 1939-1945. [50] Whelan, R. J., Wohland, T., Neumann, L., Huang, B., Kobilka, B. K., Zare, R. N., 2002, “Analysis of Biomolecular Interactions Using a Miniaturized Surface Plasmon Resonance Sensor, ”Analytical Chemistry 74: 4570-4576. [51] Carrascosa, L. G., Calle, A., Lechuga, L. M. 2009, “Label-free detection of DNA mutations by SPR: application to the early detection of inherited breast cancer,” Analytical and Bioanalytical Chemistry 393: 1173-1182. [52] Cotton, R. G. H. 1997, Mutation, Oxford University Press: Oxford, U.K. [53] Zhao, X.J.; Tapec-Dytioco, R.; Wang, K.M.; Tan, W.H. 2003, “Collection of Trace Amounts of DNA/mRNA Molecules Using Genomagnetic Nanocapturers,” Analytical Chemistry 75: 3476-3483. [54] Casey, J.; Davidson, N. 1977, “Rates of formation and thermal stabilities of RNA:DNA and DNA:DNA duplexes at high concentrations of formamide” Nuclear Acid Research 4:1539-1552. [55] Kankia, B.I.; Marky, L.A. 1999, “DNA, RNA, and DNA/RNA Oligomer Duplexes: A Comparative Study of Their Stability, Heat, Hydration, and Mg2+ Binding Properties,” the Journal of Physical Chemistry B 103:8759-8767. [56] Lee, H.J.; Wark, A.W.; Corn, R.M. 2006, “Creating Advanced Multifunctional Biosensors with Surface Enzymatic Transformations,” Langmuir 22: 5241-5250. [57] Wu, S. Y.; Ho, H. P.; Law, W. C.; Lin, C. 2004, “Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach–Zehnder configuration,” Optics Letters 29: 2378–2380. [58] Kabashin, A.V.; Patskovsky, S.; Grigorenko, A.N. 2009, “Phase and amplitude sensitivities in surface plasmon resonance bio and chemical sensing,” Optics Express 17: 21191-21204. [59] Milkani, E., Morais, S., Lambert, C. R., McGimpsey, W. G., 2010, “Detection of oligonucleotide systematic mismatches with a surface plasmon resonance sensor, ” Biosensors and Bioelectronics 25: 1217-1220. [60] Nagrath, S.; Sequist, L.V.; Maheswaran, S.; Bell, D.W.; Irimia, D.; Ulkus, L.; Smith, M.R.; Kwak, E.K.; Digumarthy, S.; Muzikansky, A.; Ryan, P.; Balis, U.J.; Tompkins, R.G.; Haber, D.A.; Toner, M. 2007, “Isolation of rare circulating tumour cells in cancer patients by microchip technology” Nature 450: 1235-1241. [61] Skoog, D.A.; Holler, F.J.; West, D.M., Analytical Chemistry: An Introduction, 5th ed.; Saunders College Publishing: Philadelphia, PA, 1990; Chapter 2. [62] Biacore, A. B. Biacore Sensor Surface Handbook, BR-1005-71, Uppsala, 2003. [63] Garrett, R.H.; Grisham, C.M. 2008, Biochemistry 4rd Edition. Cengage Learning, p.322.
指導教授	李正中、周晟 (Cheng-Chung Lee、Chien Chou)	審核日期	2012-7-26
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