簡易檢索 / 詳目顯示

回結果列表
研究生： 黃騰毅
Teng-Yi Huang
論文名稱： 石墨烯氧化物薄膜於表面電漿子共振生物感測器之研發
Development of Graphene Oxide Sheets for Surface Plasmon Resonance Biosensors
指導教授： 邱南福
Chiu, Nan-Fu
學位類別： 碩士
Master
系所名稱： 光電工程研究所
Graduate Institute of Electro-Optical Engineering
論文出版年： 2013
畢業學年度： 101
語文別： 中文
論文頁數： 106
中文關鍵詞： 表面電漿子共振 、分子自組裝單層膜 、石墨烯氧化物 、動力學分析 、肺結核桿菌
英文關鍵詞： Surface plasmon resonance, Self-assembled monolayer, Graphene oxide, Kinetic analysis, Mycobacterium tuberculosis
論文種類： 學術論文
相關次數： 點閱：153  下載：11 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • 表面電漿子共振(Surface plasmon resonance, SPR)生物感測器為利用金膜表面與生物分子交互作用所造成的微量折射率變化，進而達到免標記且高靈敏度之檢測技術，為目前光學式生物感測技術中的重要方法之一。

    本論文將石墨烯氧化物(Graphene oxide, GO)鍵結於黃金薄膜上，所得到的薄膜稱為石墨烯氧化物薄膜，並透過表面電漿子共振生物感測技術，將此薄膜應用於生物感測上。石墨烯氧化物薄膜的製作首先將胱胺二鹽酸(Cystamine, Cys)作為連接劑，並透過分子自組裝單層膜(Self-assembled monolayer, SAM)技術，將胱胺鍵結於金膜上，形成胱胺薄膜。接著將石墨烯氧化物以共價鍵結的方式固定於胱胺薄膜表面，形成石墨烯氧化物薄膜(GO sheets)。論文中利用本實驗室之SPR量測系統並透過牛血清白蛋白與肺結核桿菌等生物分子進行檢測，並比較石墨烯氧化物薄膜與傳統金膜之靈敏度、檢測極限以及動力學分析之差異。

    本論文發展之石墨烯氧化物薄膜表面電漿子共振生物感測器，與傳統金膜比較後，石墨烯氧化物薄膜之靈敏度約可提升12倍，檢測極限與動力學分析後之結果亦皆優於傳統金膜。最重要的是，石墨烯氧化物薄膜可直接透過官能基與生物分子鍵結，不必再透過抗原抗體的交互作用來執行，因此可有效地降低檢測成本。未來本系統除了可供醫學與疾病檢測外，亦可應用於製藥工業、環境檢測、農業科技等領域之分析應用，以造福人群。

    The advantage of surface plasmon resonance (SPR) biosensors includes high sensitivity, label-free, and real-time detection. These advantage leading SPR biosensors to identified as one of the most important optical detection methods for biomolecules.

    The goal of this thesis is to develop graphene oxide (GO) sheets SPR biosensor that used GO as sensing layer for biomolecules detection. First, we used cystamine as linker layer, forming Cys film by self-assembled monolayer (SAM) technique. Then, GO solution was immobilized on the surface of Cys film through covalent attachment, forming GO sheets. The GO sheets SPR biosensor was used to detect the dynamic interactions of biomolecules and antibody-antigen. For experimental verification of this system, bovine serum albumin (BSA) and LAMP DNA products were used to demonstrate by GO sheets and conventional Au films. We also compared these two films by sensitivity, detection limits and kinetic analysis.

    The sensitivity of GO sheets that can be determined by this thesis is about 12-fold higher than that obtained with the sensor based on conventional Au films. The detection limits and the results of kinetic analysis of GO sheets were also better than conventional Au films. Most important of all, GO sheets have the ability for directly detect biomolecules, skipped the immunization interactions, leading to a low cost experiment. We anticipate that graphene oxide sheet SPR biosensors will not only enable for possible applications for biomedicine and diseases but also have wide spectrum of application in pharmaceutical industry, environmental monitoring, and agriculture in the near future.

    致謝.....................................................i 中文摘要................................................iii Abstract................................................iv 目錄....................................................vi 圖目錄..................................................xii 表目錄...................................................xv 第一章 緒論...............................................1 1.1 前言...............................................1 1.2 研究動機與目標.......................................1 1.3 論文架構............................................2 第二章 基本原理與文獻回顧....................................4 2.1 表面電漿子共振原理....................................4 2.1.1 表面電漿波......................................4 2.1.2 表面電漿子共振...................................5 2.1.3 表面電漿子共振之激發..............................7 2.1.4 表面電漿子共振之光學感測...........................8 2.1.5 表面電漿子共振生物感測器..........................10 2.2 表面電漿子共振金膜之固定化............................11 2.2.1 金膜之表面修飾..................................11 2.2.2 分子固定化技術..................................14 2.3 石墨烯衍生物與生物感測器上之應用........................18 2.3.1 石墨烯(Graphene)...............................18 2.3.2 石墨烯氧化物(Graphene Oxide, GO)................20 2.3.3 還原石墨烯氧化物(reduced Graphene Oxide, rGO)....22 2.3.4 以石墨烯氧化物為基礎之表面電漿子共振生物感測器........24 2.4 肺結核的診斷與恆溫環狀擴增法...........................26 2.4.1 肺結核的診斷....................................26 2.4.2 恆溫環狀擴增法..................................26 2.4.3 肺結核桿菌增幅方法比較............................28 2.4.4 肺結核桿菌DNA序列IS6110.........................30 2.5 分子動力學分析......................................30 2.5.1 分子動力學方程式.................................30 2.5.2 質傳效應.......................................34 第三章 實驗材料、儀器設備與研究方法...........................36 3.1 實驗材料...........................................36 3.2 儀器設備...........................................38 3.3 多功能電漿量測系統架構................................40 3.4 表面電漿子共振感測晶片製作............................43 第四章 石墨烯氧化物薄膜透過表面電漿子共振技術檢測生物樣本.........45 4.1 實驗目的...........................................45 4.2 實驗方法...........................................45 4.2.1 實驗溶液配製....................................45 4.2.2 金膜固定化之檢測.................................46 4.2.2.1 穿透光譜系統實驗.............................46 4.2.2.2 數位顯微鏡系統實驗...........................46 4.2.2.3 掃描電子顯微鏡(SEM)系統實驗...................47 4.2.3 多功能電漿量測系統(MPS)實驗.......................47 4.2.4 表面電漿子共振(SPR)微流道系統實驗..................47 4.2.4.1 分子自組裝單層膜(SAM)時間最佳化...............48 4.2.4.2 胱胺與石墨烯氧化物之濃度最佳化.................49 4.2.4.3 石墨烯氧化物薄膜表面官能基之影響................49 4.2.4.4 表面電漿子共振系統流速最佳化...................50 4.2.4.5 表面電漿子共振即時檢測........................50 4.2.4.6 動力學分析.................................51 4.2.4.7 牛血清白蛋白免疫反應分析......................51 4.3 實驗結果與討論......................................52 4.3.1 金膜固定化之檢測結果.............................52 4.3.1.1 穿透光譜系統實驗結果.........................52 4.3.1.2 數位顯微鏡系統實驗結果........................53 4.3.1.3 掃描電子顯微鏡(SEM)系統實驗結果...............53 4.3.2 多功能電漿量測系統(MPS)實驗結果...................54 4.3.3 表面電漿子共振(SPR)微流道系統實驗結果...............56 4.3.3.1 分子自組裝單層膜(SAM)時間最佳化結果............56 4.3.3.2 胱胺與石墨烯氧化物之濃度最佳化結果..............57 4.3.3.3 石墨烯氧化物薄膜表面官能基之影響結果............58 4.3.3.4 表面電漿子共振系統流速最佳化結果................61 4.3.3.5 表面電漿子共振即時檢測結果....................63 4.3.3.6 動力學分析結果..............................67 4.3.3.7 牛血清白蛋白免疫反應分析結果...................69 第五章 石墨烯氧化物薄膜透過表面電漿子共振技術檢測肺結核桿菌.......72 5.1 肺結核桿菌簡介......................................72 5.2 實驗目的...........................................72 5.3 實驗方法...........................................73 5.3.1 實驗溶液配製....................................73 5.3.2 實驗樣品設計條件.................................74 5.3.3 凝膠電泳對TB-DNA樣本之檢測.......................75 5.3.4圓漬點墨法對地高辛精(Dig)之免疫反應檢測..............76 5.3.5 表面電漿子共振(SPR)微流道系統實驗..................77 5.3.5.1 透過Digoxigenin抗體進行免疫分析法.............77 5.3.5.2 設計不同LAMP產物與GO薄膜交互作用..............80 5.4 實驗結果與討論......................................82 5.4.1 凝膠電泳對TB-DNA樣本之檢測結果....................82 5.4.2圓漬點墨法對地高辛精(Dig)之免疫反應檢測結果...........85 5.4.3 表面電漿子共振(SPR)微流道系統實驗結果...............86 5.4.3.1 透過Digoxigenin抗體進行免疫分析法之結果........86 5.4.3.2 設計不同LAMP產物與GO薄膜交互作用之結果..........90 第六章 結論與未來展望......................................93 6.1 結論..............................................93 6.2 未來展望...........................................94 參考文獻.................................................95

    [1]R. W. Wood, “XLII. On a remarkable case of uneven distribution of light in a diffraction grating spectrum,” Phil. Mag., 4, 396 (1902).
    [2]A. Sommerfeld, “Über die Ausbreitung der Wellen in der drahtlosen Telegraphie,” Annalen der Physik, 333, 665 (1909).
    [3]A. Otto, “Excitation of Nonradiative Surface Plasma Waves in Silver by the Method of Frustrated Total Reflection,” Z. Phys., 216, 398 (1968).
    [4]E. Kretschmann, “Die bestimmung optischer Konstanten von Metallen durch Anregung von Oberflachen plasmaschwingungen,” Z. Phys., 241, 313 (1971).
    [5]J. Homola, S. S. Yee, and G. Gauglitz, “Surface plasmon resonance sensors: review,” Sensors and Actuators B., 54, 3 (1999).
    [6]W. L. Barnes, A. Dereux, and T. W. Ebbesen, “Surface plasmon subwavelength optics,” Nature, 424, 824 (2003).
    [7]S. G. Nelson, K. S. Johnston, and S. S. Yee, “High sensitivity surface plasmon resonance sensor based on phase detection,” Sensors and Actuators B: Chemical, 35, 187 (1996).
    [8]J. Homola, “Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species,” Chem. Rev., 108, 462 (2008).
    [9]E. Stenberg, B. Persson, H. Roos, and C. Urbaniczky, “Quantitative determination of surface concentration of protein with surface plasmon resonance using radiolabeled proteins”, Journal of colloid and interface science, 143, 513 (1991).
    [10]E. Hutter, J. H. Fendler, and D. Roy, “Surface Plasmon Resonance Studies of Gold and Silver Substrates by 2-Aminoethanethiol and 1,6-Hexanedithiol,” J. Phys. Chem. B., 105, 11159 (2001).
    [11]B. Liedberg, C. Nylander, and I. Lunström, “Surface plasmon resonance for gas detection and biosensing,” Sensors and Actuators, 4, 299 (1983).
    [12]I. Langmuir, “The constitution and fundamental properties of solids and liquids. II. Liquids,” J. Am. Chem. Soc., 39, 1848 (1917).
    [13]W. C. Bigelow, D. L Pickett, and W. A. Zisman, “Oleophobic monolayers: I. Films adsorbed from solution in non-polar liquids,” Journal of Colloid Science., 1, 513 (1946).
    [14]R. G. Nuzzo and D. L. Allara, “Adsorption of bifunctional organic disulfides on gold surfaces,” J. Am. Chem. Soc., 105, 4481 (1983).
    [15]H. Sellers, A. Ulman, Y. Shnidman, and J. E. Eilers, “Structure and binding of alkanethiolates on gold and silver surfaces: implications for self-assembled monolayers,” J. Am. Chem. Soc., 115, 9389 (1993).
    [16]A. Ulman, “Formation and Structure of Self-Assembled Monolayers,” Chem. Rev., 96, 1533 (1996).
    [17]S. Löfås and B. Johnsson, “A novel hydrogel matrix on gold surfaces in surface plasmon resonance sensors for fast and efficient covalent immobilization of ligands,” J. Chem. Soc., Chem. Commun., 21, 1526 (1990).
    [18]R. G. Nuzzo, F. A. Fosco, and D. L. Allara, “Spontaneously organized molecular assemblies. 3. Preparation and properties of solution adsorbed monolayers of organic disulfides on gold surfaces,” J. Am. Chem. Soc., 109, 2358 (1987).
    [19]M. D. Porter, T. B. Bright, D. L. Allara, and C. E. D. Chidsey, “Spontaneously organized molecular assemblies. 4. Structural characterization of n-alkyl thiol monolayers on gold by optical ellipsometry, infrared spectroscopy, and electrochemistry,” J. Am. Chem. Soc., 109, 3559 (1987).
    [20]B. Johnsson, S. Löfås, G. Lindquist, A. Edström, R. M. M. Hillgren, and A. Hansson, “Comparison of methods for immobilization to carboxymethyl dextran sensor surfaces by analysis of the specific activity of monoclonal antibodies,” J. Mol. Recognit., 8, 125 (1995).
    [21]B. Johnsson, S. Löfås, and G. Lindquist, “Immobilization of proteins to a carboxymethyldextran-modified gold surface for biospecific interaction analysis in surface plasmon resonance sensors,” Anal. Biochem., 198, 268 (1991).
    [22]A. K. Geim, “Graphene: Status and Prospects,” Science, 324, 1530 (2009).
    [23]A. Geim and K. Novoselov, “For groundbreaking experiments regarding the two-dimensional material graphene,” The Nobel Prize in Physics (2010). http://www.nobelprize.org/nobel_prizes/physics/laureates/2010/
    [24]C. S. Shan,　H. F. Yang,　J. F. Song,　D. X. Han,　A. Ivaska,　and L. Niu, “Direct Electrochemistry of Glucose Oxidase and Biosensing for Glucose Based on Graphene,” Anal. Chem., 81, 2378 (2009).
    [25]W. Lv, M. Guo, M. H. Liang, F. M. Jin, L. Cui, L. J. Zhi, and Q. H. Yang, “Graphene-DNA hybrids: self-assembly and electrochemical detection performance,” J. Mater. Chem., 20, 6668 (2010).
    [26]L. Wu, H. S. Chu, W. S. Koh, and E. P. Li, “Highly sensitive graphene biosensors based on surface plasmon resonance,” Optics Express, 18, 14395 (2010).
    [27]H. Raether, “Surface Plasmons on Smooth and Rough Surfaces and on Gratings,” Springer Tracts in Modern Physics., 111, ISBN: 978-3-540-17363-2 (1988).
    [28]R. R. Nair, P. Blake, A. N. Grigorenko, K. S. Novoselov, T. J. Booth, T. Stauber, N. M. R. Peres, and A. K. Geim, “Fine structure constant defines visual transparency of graphene,” Science, 320, 1308 (2008).
    [29]S. H. Choi, Y. L. Kim, and K. M. Byun, “Graphene-on-silver substrates for sensitive surface plasmon resonance imaging biosensors,” Optics Express, 19, 458 (2011).
    [30]O. Salihoglu, S. Balci, and C. Kocabas, “Plasmon-polaritons on graphene-metal surface and their use in biosensors,” Appl. Phys. Lett., 100, 213110 (2012).
    [31]X. S. Li, W. W. Cai, J. H. An, S. Y. Kim, J. H. Nah, D. X. Yang, R. Piner, A. Velamakanni, I. Jung, E. Tutuc, S. K. Banerjee, L. Colombo, and R. S. Ruoff, “Large-Area Synthesis of High-Quality and Uniform Graphene Films on Copper Foils,” Science, 324, 1312 (2009).
    [32]D. R. Dreyer, S. J. Park, C. W. Bielawski and R. S. Ruoff, “The chemistry of graphene oxide,” Chem. Soc. Rev., 39, 228 (2010).
    [33]X. Sun, Z. Liu, K. Welsher, J. T. Robinson, A. Goodwin, S. Zaric, and H. Dai, “Nano-graphene oxide for cellular imaging and drug delivery,” Nano Res., 1, 203 (2008).
    [34]Z. Liu, J. T. Robinson, X. Sun, and H. Dai, “PEGylated nano-graphene oxide for delivery of water insoluble cancer drugs,” J. Am. Chem. Soc., 130, 10876 (2008).
    [35]C. H. Lucas, A. J. L. Peinado, J. de D. L. González, M. L. R. Cervantes, and R. M. M. Aranda, “Study of oxygen-containing groups in a series of graphite oxides: Physical and chemical characterization,” Carbon, 33, 1585 (1995).
    [36]F. Liu, J. Y. Choi, and T. S. Seo, “Graphene oxide arrays for detecting specific DNA hybridization by fluorescence resonance energy transfer,” Biosens Bioelectron, 25, 2361 (2010).
    [37]Y. Hu, F. H. Li, X. X. Bai, D. Li, S. C. Hua, K. K. Wang, and L. Niu, “Label-free electrochemical impedance sensing of DNA hybridization based on functionalized graphene sheets,” Chem. Commun., 47, 1743 (2011).
    [38]M. R. Kagan and R. L. McCreery, “Reduction of fluorescence interference in Raman spectroscopy via analyte adsorption on graphitic carbon,” Anal. Chem., 66, 4159 (1994).
    [39]Z. Liu, Q. Liu, Y. Huang, Y. Ma, S. Yin, X. Zhang, W. Sun, and Y. Chen, “Organic photovoltaic devices based on a novel acceptor material: graphene,” Adv. Mater., 20, 3924 (2008).
    [40]S. He, B. Song, D. Li, C. Zhu, W. Qi, Y. Wen, L. Wang, S. Song, H. Fang, and C. Fan, “A graphene nanoprobe for rapid, sensitive, and multicolor fluorescent DNA analysis,” Adv. Funct. Mater., 20, 453 (2010).
    [41]C. H. Lu, H. H. Yang, C. L. Zhu, X. Chen, and G. N. Chen, “A graphene platform for sensing biomolecules,” Angew. Chem. Int. Ed., 48, 4785 (2009).
    [42]S. Myung, A. Solanki, C. Kim, J. Park, K. S. Kim, and K. B. Lee, “Graphene-Encapsulated Nanoparticle-Based Biosensor for　the Selective Detection of Cancer Biomarkers,” Adv. Mater., 23, 2221 (2011).
    [43]A. Citri and Y. Yarden, “EGF-ERBB signalling: towards the systems level,” Nat. Rev. Mol. Cell Biol., 7, 505 (2006).
    [44]F. Patolsky, G. F. Zheng, and C. M. Lieber, “Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species,” Nat. Protoc., 1, 1711 (2006).
    [45]World Health Organization (WHO), “Global Tuberculosis Report 2012.”
    http://apps.who.int/iris/bitstream/10665/75938/1/9789241564502_eng.pdf
    [46]K. N. Olivier, D. J. Weber, R. J. J. Wallace, A. R. Faiz, J. H. Lee, Y. Zhang, B. A. Brown-Elliot, A. Handler, R. W. Wilson, M. S. Schechter, L. J. Edwards, S. Chakraborti, and M. R. Knowles, “Nontuberculous mycobacteria. I: Multicenter prevalence study in cystic fibrosis,” Am. J. Respir. Crit. Care Med., 167, 828 (2003).
    [47]T. Notomi1, H. Okayama, H. Masubuchi1, T. Yonekawa, K. Watanabe1, N. Amino, and T. Hase, “Loop-mediated isothermal amplification of DNA,” Nucleic Acids Res., 28, e63 (2000).
    [48]T. Iwamoto, T. Sonobe1, and K. Hayashi, “Loop-mediated isothermal amplification for direct detection of mycobacterium tuberculosis complex, M. avium, and M. intracellulare in sputum samples,” J. Clin. Microbiol., 41, 2616 (2003).
    [49]M. Caws, S. M. Wilson, C. Clough, and F. Drobniewski, “Role of IS6110-targeted PCR, culture, biochemical, clinical, and immunological criteria for diagnosis of tuberculous meningitis,” J. Clin. Microbiol., 38, 3150 (2000).
    [50]L. Kohan, M. H. Shahhosseiny, M. R. Razavi, K. Parivar, E. Moslemi, and J. Werngren, “Evaluation of loop mediated isothermal amplification for diagnosis of Mycobacterium tuberculosis complex in clinical samples,” Afr. J. Biotech., 10, 5096 (2011).
    [51]I. K. Neonakis, D. A. Spandidos, and E. Petinaki, “Use of loop-mediated isothermal amplification of DNA for the rapid detection of Mycobacterium tuberculosis in clinical specimens,” Eur. J. Clin. Microbiol. Infect. Dis., 30, 937 (2011).
    [52]Y. M. Hale, G. E. Pfyffer, and M. Salfinger, “Laboratory diagnosis of mycobacterial infections: new tools and lessons learned,” Clin. Infect Dis., 33, 834 (2001).
    [53]H. Soini and J. M. Musser, “Molecular diagnosis of mycobacteria,” Clin Chem., 47, 809 (2001).
    [54]G. L. Woods, “Molecular methods in the detection and identification of mycobacterial infections,” Arch. Pathol. Lab Med., 123, 1002 (1999).
    [55]S. Y. Lee, J. G. Huang, T. L. Chuang, J. C. Sheu, Y. K. Chuang, M. Holl, D. R. Meldrum, C. N. Lee, and C. W. Lin, “Compact optical diagnostic device for isothermal nucleic acids amplification,” Sensors and Actuators B, 133, 493 (2008).
    [56]B. R. Eing, A. Becker, A. Sohns, and R. Ringelmann, “Comparison of roche cobas amplicor mycobacterium tuberculosis assay with in-house PCR and culture for detection of M. tuberculosis,” J. Clin. Microbiol., 36, 2023 (1998).
    [57]T. J. Hellyer, T. W. Fletcher, J. H. Bates, W. W. Stead, G. L. Templeton, M. D. Cave, and K. D. Eisenach, “Strand displacement amplification and the polymerase chain reaction for monitoring response to treatment in patients with pulmonary tuberculosis,” J. Infect. Dis., 173, 934 (1996).
    [58]E. Aryan, M. Makvandi, A. Farajzadeh, K. Huygen, P. Bifani, S. L. Mousavi, A. Fateh, A. Jelodar, M. M. Gouya, and M. Romano, “A novel and more sensitive loop-mediated isothermal amplification assay targeting IS6110 for detection of Mycobacterium tuberculosis complex,” Microbio. Res., 165, 211 (2010).
    [59]S. C. Hsieh, C. C. Chang, C. C. Lu, C. F. Wei, C. S. Lin, H. C. Lai, and C. W. Lin, “Rapid identification of Mycobacterium tuberculosis infection by a new array format-based surface plasmon resonance method,” Nanoscale Res. Lett., 7, 180 (2012).
    [60]C. C. Boehme, P. Nabeta, G. henostroza, R. Raqib, Z. Rahim, M. Gerhardt, E. Sanga, M. Hoelscher, T. Notomi, T. Hase, and M. D. Perkins, “Operational feasibility of using loop mediated isothermal amplification for diagnosis of pulmonary tuberculosis in microscopy center of developing countries,” J. Clin. Microbiol., 45, 1936 (2007).
    [61]B. D. Pandey , A. Poudel, T. Yoda, A. Tamaru, N. Oda, Y. Fukushima, B. Lekhak, B. Risal, B. Acharya, B. Sapkota, C. Nakajima, T. Taniguchi, B. Phetsuksiri, and Y. Suzuki, “Development of an in-house loopmediated isothermal amplification (LAMP) assay for detection of Mycobacterium tuberculosis and evaluation in sputum samples of Nepalese patients,” J. Med. Microbiol., 57, 439 (2008).
    [62]R. Y. Zhu, K. X. Zhang, M. Q. Zhao, Y. H. Liu, Y. Y. Xu, C. M. Ju, B. Li, and J. D. Chen, “Use of visual loop mediated isothermal amplification of rimM sequence for rapid detection of Mycobacterium tuberculosis and Mycobacterium bovis,” J. Microbiol. Methods., 78, 339 (2009).
    [63]D. G. Myszka, “Kinetic analysis of macromolecular interactions using surface plasmon resonance biosensors,” Current Opinion in Biotechnology, 8, 50, (1997).
    [64]R. J. Green, R. A. Frazier, K. M. Shakesheff, M. C. Davies, C. J. Roberts, and S. J. B. Tendler, “Surface plasmon resonance analysis of dynamic biological interactions with biomaterials,” Biomaterials, 21, 1823 (2000).
    [65]L. P. Lin, L. S. Huang, C. W. Lin, C. K. Lee, J. L. Chen, S. M. Hsu, and S. Lin, “Determination of binding constant of DNA-binding drug to target DNA by surface plasmon resonance biosensor technology,” Curr. Drug Targets Immune. Endocr. Metabol. Disord., 5, 61 (2005).
    [66]Biosensing Instrument Inc., “BI-3000 SPR System User’s Manual (Version 2.0.4),” (2009). http://www.BiosensingUSA.com/
    [67]D. G. Myszka, T. A. Morton, M. L. Doyle, and I. M. Chaiken, “Kinetic analysis of a protein antigen-antibody interaction limited by mass transport on an optical biosensor” Biophysical Chemistry, 64, 127 (1997).
    [68]D. A. Brevnov, H. O. Finklea, and H. V. Ryswyk, “Ac voltammetry studies of electron transfer kinetics for a redox couple attached via short alkanethiols to a gold electrode,” J. Electroanalytical Chem., 500, 100 (2001).
    [69]C. C. Chang, N. F. Chiu, D. S. Lin, Y. C. Su, Y. H. Liang, and C. W. Lin, “High-Sensitivity Detection of Carbohydrate Antigen 15-3 Using a Gold/Zinc Oxide Thin Film Surface Plasmon Resonance-Based Biosensor,” Anal. Chem., 82, 1207 (2010).
    [70]H. Zhou, X. Wang, P. Yu, X. Chen, and L. Mao, “Sensitive and selective voltammetric measurement of Hg2+ by rational covalent functionalization of graphene oxide with cysteamine,” Analyst, 137, 305 (2012).
    [71]H. Zhang, Y. Sun, S. Gao, J. Zhang, H. Zhang, and D. Song, “A Novel Graphene Oxide-Based Surface Plasmon Resonance Biosensor for Immunoassay,” Small, DOI: 10.1002/smll.201202958 (2013).
    [72]J. Zhang, Y. Sun, B. Xu, H. Zhang, Y. Gao, H. Zhang, and D. Song, “A novel surface plasmon resonance biosensor based on graphene oxide decorated with gold nanorod–antibody conjugates for determination of transferrin,” Biosens Bioelectron., 45, 230 (2013).
    [73]D. C. Carter and J. X. Ho, “Structure of serum albumin,” Adv. Protein Chem., 45, 153 (1994).
    [74]W. C. Tsai and I. C. Lin, “Development of a piezoelectric immunosensor for the detection of alpha-fetoprotein,” Sensors and Actuators B, 106, 455 (2005).
    [75]X. Su, F. T. Chew, and S. F. Y. Li, “Self-Assembled Monolayer-Based Piezoelectric Crystal Immunosensor for the Quantification of Total Human Immunoglobulin E,” Anal Biochem., 273, 66 (1999).
    [76]S. F. Chou, W. L. Hsu, J. M. Hwang, and C. Y. Chen, “Development of an immunosensor for human ferritin, a nonspecific tumor marker, based on surface plasmon resonance,” Biosens Bioelectron., 19, 999 (2004).
    [77]G. K. Ramesha and S. Sampath, “Electrochemical Reduction of Oriented Graphene Oxide Films: An in Situ Raman Spectroelectrochemical Study,” J. Phys. Chem. C., 113, 7985 (2009).
    [78]P. Wagner, M. Hegner, H. J. Guntherodt, and G. Semenza, “Formation and in Situ Modification of Monolayers Chemisorbed on Ultraflat Template-Stripped Gold Surfaces,” Langmuir, 11, 3867 (1995).
    [79]M. J. E. Fischer, “Amine coupling through EDC/NHS: a practical approach,” Methods Mol Biol., DOI: 10.1007/978-1-60761-670-2_3 (2010).
    [80]A. Kausaite, M. V. Dijk, J. Castrop, A. Ramanaviciene, J. P. Baltrus, J. Acaite, and A. Ramanavicius, “Surface Plasmon Resonance Label-free Monitoring of Antibody Antigen Interactions in Real Time,” Biochem Mol Biol Educ., 35, 57 (2007).
    [81]C. Q. Xiao, F. L. Jiang, B. Zhou, R. Li, and Y. Liu, “Interaction between a cationic porphyrin and bovine serum albumin studied by surface plasmon resonance, fluorescence spectroscopy and cyclic voltammetry,” Photochem Photobiol Sci., 10, 1110 (2011).
    [82]G. Eda and M. Chhowalla, “Chemically Derived Graphene Oxide, Towards Large-Area Thin-Film electronics and Optoelectronics,” Adv. Mater., 22, 2392 (2010).
    [83]Z. Wang, S. Wu, J. Zhang, P. Chen, G. Yang, X. Zhou, Q. Zhang, Q. Yan and H. Zhang, “Comparative studies on single-layer reduced graphene oxide films obtained by electrochemical reduction and hydrazine vapor reduction,” Nanoscale Res. Lett., 7, 161 (2012).
    [84]T. Kono, R. Savan, M. Sakai, and T. Itami, “Detection of white spot syndrome virus in shrimp by loop-mediated isothermal amplification,” J Virol Methods., 115, 59-65 (2004).
    [85]D. Thierry, M. D.Cave, K. D.Eisenach, J. T.Crawford, J. H.Bates, B. Gicquel, and J. L.Guesdon, “IS6110, an IS-like element of Mycobacterium tuberculosis complex,” Nucleic Acids Research., 18, 188 (1990).
    [86]A. P. Mortari and R. P. Bucy, “In situ hybridization with digoxigenin-labeled RNA probes: facts and artifacts,” Biotechniques., 18, 300 (1995).
    [87]J. Chevalier, J. Yi, O. Michel, and X. M. Tang, “Biotin and Digoxigenin as labels for light and electron microscopy in situ hybridization probe: Where do we stand?,” J. Histochem. Cytochem., 45, 481 (1997).
    [88]N. L. Ge, K. M. Kocan, G. L. Murphy, and E. F. Blouin, “Detection of anaplasma marginale DNA in bovine erythrocyte by slot-blot and in situ hybridization with a PCR-mediated digoxigenin-labeled DNA probe,” J. Vet. Diagn. Invest., 7, 465, (1995).
    [89]J. Zhang, Y. Sun, B. Xu, H. Zhang, Y. Gao, H. Zhang, and D. Song,　“A novel surface plasmon resonance biosensor based on graphene oxide decorated with gold nanorod-antibody conjugates for determination of transferrin,” Biosens Bioelectron., 45, 230 (2013).

    下載圖示
    QR CODE