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研究生: 鄭雅云
Ya-Yun Zheng
論文名稱: 磺甜菜鹼氮矽三環雙離子自組裝抗污塗層
Silatrane-Based Zwitterionic Self-Assembled Coating for Antifouling Properties
指導教授: 黃俊仁
Chun-Jen Huang
口試委員:
學位類別: 碩士
Master
系所名稱: 生醫理工學院 - 生物醫學工程研究所
Graduate Institute of Biomedical Engineering
論文出版年: 2017
畢業學年度: 105
語文別: 中文
論文頁數: 78
中文關鍵詞: 抗非特異性吸附兩性雙離子材料自組裝材料生物界面氮矽三環材料
外文關鍵詞: Antifouling properties, zwitterionic material, silatrane, biointerfaces, self-assembly
相關次數: 點閱:21下載:0
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  • 植入性醫療器材因長時間與血液及組織接觸,易引發生物分子的非特異性吸附,引發血栓、凝血反應、細菌感染等問題。目前解決之方法為,於材料表面修飾一層抗非特異性吸附之塗層。矽烷 (silane) 官能基常用於修飾氧化矽之自組裝塗層鍵結,然而矽烷易被水解,使得接枝官能基失活,因此增加保存以及修飾上的困難。而氮矽三環 (silatrane) 為以氮矽鍵為軸組成的三環籠狀對稱結構,已被證實於結構上較矽烷穩定。本研究以帶有氧矽三環的磺甜菜鹼兩性雙離子(sulfobetainesilatrane, SBSiT)於氧化矽材料上修飾自組裝抗汙塗層。將以 (1) 核磁共振光譜儀及傅里葉轉換紅外光譜驗證分子結構和水解速度;(2) MTT細胞毒性測試材料生物相容性;(3) 水接觸角測量儀觀察修飾後表面之親水性質;(4) X射線光電子能譜分析表面元素成分;(5)原子力顯微鏡觀察修飾表面粗糙度;(6) 橢圓儀測試表面厚度;(7) 細菌貼附、蛋白質貼附實驗證明此材料具抗非特異性吸附之特性。SBSiT材料不僅突破矽烷官能基容易水解,所造成表面聚集、不均勻之問題,更保有兩性雙離子良好抗非特異性吸附之特性,乃極具潛力之兩性雙離子抗汙塗層,是為生物醫學工程領域上的重大發展。


    Zwitterionic coatings are a new class of antifouling materials for high biocompatibility. Development of the antifouling film has been of great interest over the last decades, particularly for silicon surface modification due to their potential biomedical applications. The most commonly used chemical functionalization of silicon surface is silane. However, silane is very sensitive to moisture which leads to polymerization on the silicon surface. Therefore, silatranes have received attention from the structures features. Because of a strong intramolecular donor-acceptor interaction between nitrogen and silicon atom, silatrane are chemically more stable to hydrolysis than silane. Thus, the formation of large polymer clusters and roughness on silica surface is minimized. In this study, we have developed a superhydrophilic zwitterionic surface by sulfobetaine silatrane ( SBSiT ) coating as an alternative to sulfobetaine silane ( SBSi ) coating. The performance of sulfobetaine silatrane was less sensitive to moisture and more difficult to hydrolyze. SBSiT films offer a significant advantage over SBSi due to its smooth, aggregate free, film formation and also solve homogeneity and reproducibility problems caused by silane. SBSiT suggests its potential role in anti-fouling coatings on silica surface and benefits the development of devices and sonsors based on biomedical applications.

    中文摘要------------------------------------------------------------------------------------------V Abstract-------------------------------------------------------------------------------------------VI 致謝----------------------------------------------------------------------------------------------VII 目錄---------------------------------------------------------------------------------------------VIII 圖目錄-------------------------------------------------------------------------------------------XI 表目錄------------------------------------------------------------------------------------------XIII 第一章 文獻回顧-------------------------------------------------------------------------------01 1-1生物汙染-------------------------------------------------------------------------------------01 1-1-1 生物膜的形成------------------------------------------------------------------02 1-1-2 抵抗生物汙染之機制---------------------------------------------------------03 1-2 抗生物沾黏材料--------------------------------------------------------------------------05 1-2-1 聚乙二醇材料------------------------------------------------------------------06 1-2-2 兩性雙離子材料---------------------------------------------------------------08 1-2-2-1 兩性雙離子材料抗非特異性吸附機制----------------------------10 1-3 自組裝抗汙塗層---------------------------------------------------------------------------11 1-4 矽烷官能基---------------------------------------------------------------------------------12 1-4-1矽烷官能基修飾原理----------------------------------------------------------13 1-4-2矽烷官能基修飾衍生之問題------------------------------------------------15 1-5氮矽三環類化合物------------------------------------------------------------------------18 1-5-1氮矽三環類化合物修飾機制-------------------------------------------------19 1-5-2氮矽三環類化合物修飾優勢-------------------------------------------------21 第二章、研究目的-----------------------------------------------------------------------------23 第三章、材料與方法--------------------------------------------------------------------------24 3-1實驗藥品-------------------------------------------------------------------------------------24 3-2實驗儀器-------------------------------------------------------------------------------------25 3-3材料合成-------------------------------------------------------------------------------------26 3-3-1磺甜菜鹼氮矽三環兩性雙離子 (SBSiT) ----------------------------------26 3-3-2帶矽烷官能基磺甜菜鹼兩性雙離子 (SBSi) ------------------------------27 3-3-3無水乙醇製備-------------------------------------------------------------------27 3-4實驗方法-------------------------------------------------------------------------------------28 3-4-1 SBSi、SBSiT自組裝抗汙塗層製備----------------------------------------28 3-4-2 接觸角測量---------------------------------------------------------------------29 3-4-3 橢圓偏振儀厚度量測---------------------------------------------------------29 3-4-4 高解析電子能譜儀 (XPS) --------------------------------------------------29 3-4-5 傅立葉轉換紅外光譜 (FTIR) ----------------------------------------------30 3-4-6 SBSi、SBSiT對於酸鹼值不同的UV-VIS吸收光譜分析------------30 3-4-7 SBSi、SBSiT對於酸鹼值不同的粒徑分析 (DLS) ---------------------30 3-4-8 SBSi、SBSiT與不同酸鹼值的粗糙度分析 (AFM) --------------------31 3-4-9 細菌貼附實驗------------------------------------------------------------------31 3-4-10 石英晶體微天平對牛血清蛋白吸附試驗 (QCM-D) -----------------32 3-4-10 毒性試驗 (MTT) ------------------------------------------------------------32 第四章、結果與討論------------------------------------------------------------------33 4-1 SBSi以及SBSiT材料分析-------------------------------------------------------------33 4-1-1 磺甜菜鹼氮矽三環兩性雙離子 (SBSiT) 之NMR頻譜分析--------33 4-1-2 利用 NMR頻譜分析比較SBSi以及SBSiT水解速度---------------34 4-1-3 利用FTIR分析比較SBSi以及SBSiT水解----------------------------36 4-1-4 SBSi以及SBSiT材料之保存性-------------------------------------------37 4-1-5 SBSi以及SBSiT材料之生物相容性 (MTT) --------------------------38 4-2 SBSi以及SBSiT表面修飾--------------------------------------------------------------39 4-2-1 SBSiT自組裝抗汙塗層對於不同修飾方法以及溶劑之選擇--------39 4-2-2 SBSiT 自組裝抗汙塗層對於不同修飾時間之水接觸角-------------41 4-2-3 SBSiT 自組裝抗汙塗層表面元素分析 (XPS) ------------------------43 4-2-4 SBSiT 自組裝抗汙塗層粗糙度測試 (AFM) --------------------------46 4-2-5 SBSiT 自組裝抗汙塗層厚度測試 (Ellipsometry) --------------------48 4-2-6 SBSiT 自組裝抗汙塗層之抗細菌貼附----------------------------------49 4-2-7 SBSiT 自組裝抗汙塗層之抗蛋白質貼附 (QCM-D) -----------------51 第五章、討論-------------------------------------------------------------------------------------52 5-1 SBSiT於酸性條件之水解開環--------------------------------------------------------52 5-2 SBSiT表面修飾機制--------------------------------------------------------------------53 5-3 SBSi以及SBSiT之溶膠凝膠化 (Sol-gel) ------------------------------------------55 第六章、結論------------------------------------------------------------------------------------58 第七章、未來展望-------------------------------------------------------------------------------59 第八章、參考文獻------------------------------------------------------------------------------60

    1. Ye, B. L. a. Q., Antifouling Surfaces of Self-assembled Thin Layer. 2015.
    2. Donlan, R. M., Biofilm Formation: A Clinically Relevant Microbiological Process. Clinical Infectious Diseases 2001, 33 (8), 1387-1392.
    3. Van Houdt, R.; Michiels, C. W., Role of bacterial cell surface structures in Escherichia coli biofilm formation. Research in microbiology 2005, 156 (5-6), 626-33.
    4. Runnan Zhang, Y. L., ab Mingrui He, Yanlei Su,ab Xueting Zhao,; Jiang, M. E. a. Z., Antifouling membranes for sustainable water purification: strategies and mechanisms. Chem. Soc. Rev 2016, 45, 5888--5924.
    5. Whitesides, G. M., A Survey of Structure−Property Relationships of Surfaces that Resist the Adsorption of Protein. Langmuir : the ACS journal of surfaces and colloids 2001, 17 (18), pp 5605–5620.
    6. Chen, S.; Li, L.; Zhao, C.; Zheng, J., Surface hydration: Principles and applications toward low-fouling/nonfouling biomaterials. Polymer 2010, 51 (23), 5283-5293.
    7. (a) Yeh, S. B.; Chen, C. S.; Chen, W. Y.; Huang, C. J., Modification of silicone elastomer with zwitterionic silane for durable antifouling properties. Langmuir : the ACS journal of surfaces and colloids 2014, 30 (38), 11386-93; (b) JOHNSON, D., On the Aging of Oxygen Plasma-Treated Polydimethylsiloxane Surfaces. Journal of Colloid and lnterface Science 1989, 137.
    8. Pombo Garcia, K.; Zarschler, K.; Barbaro, L.; Barreto, J. A.; O'Malley, W.; Spiccia, L.; Stephan, H.; Graham, B., Zwitterionic-coated "stealth" nanoparticles for biomedical applications: recent advances in countering biomolecular corona formation and uptake by the mononuclear phagocyte system. Small 2014, 10 (13), 2516-29.
    9. Jiang, S., Poly(zwitterionic)protein conjugates offer increased stability without sacrificing binding affinity or bioactivity. NATURE CHEMISTRY 2012, 4.
    10. Lu, C.; Liu, N.; Gu, X.; Li, B.; Wang, Y.; Gao, H.; Ma, J.; Wu, G., Synthesis and characterization of biocompatible zwitterionic sulfobetaine polypeptides and their resistance to protein adsorption. Journal of Polymer Research 2014, 21 (11).
    11. RF, Z., Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 1997, 15 (89), 1121-1132.
    12. Schlenoff, J. B., Zwitteration: coating surfaces with zwitterionic functionality to reduce nonspecific adsorption. Langmuir : the ACS journal of surfaces and colloids 2014, 30 (32), 9625-36.
    13. Whitesides, G. M., Zwitterionic SAMs that Resist Nonspecific Adsorption of
    Protein from Aqueous Buffer. Langmuir : the ACS journal of surfaces and colloids 2001, 17, 2841-2850.
    14. Jiang, S., Highly Protein-Resistant Coatings from Well-Defined Diblock
    Copolymers Containing Sulfobetaines. Langmuir : the ACS journal of surfaces and colloids 2006, 22, 2222-2226.
    15. Sin, M.-C.; Chen, S.-H.; Chang, Y., Hemocompatibility of zwitterionic interfaces and membranes. Polymer Journal 2014, 46 (8), 436-443.
    16. Estephan, Z. G.; Schlenoff, P. S.; Schlenoff, J. B., Zwitteration as an alternative to PEGylation. Langmuir : the ACS journal of surfaces and colloids 2011, 27 (11), 6794-800.
    17. (a) Whitesides, G. M., Self-Assembled Monolayers of Thiolates on Metals as a Form of Nanotechnology. Chem. Rev. 2005, 105, 1103-1169; (b) Jadhav, S. A., Self-assembled monolayers (SAMs) of carboxylic acids: an overview. Central European Journal of Chemistry 2011, 9 (3), 369-378; (c) Jiang, S., Strong Resistance of Phosphorylcholine Self-Assembled Monolayers to Protein Adsorption: Insights into Nonfouling Properties of Zwitterionic Materials. J. Am. Chem. Soc. 2005, 127, 14473-14478.
    18. Estephan, Z. G.; Jaber, J. A.; Schlenoff, J. B., Zwitterion-stabilized silica nanoparticles: toward nonstick nano. Langmuir : the ACS journal of surfaces and colloids 2010, 26 (22), 16884-9.
    19. Hu, F.; Chen, K.; Xu, H.; Gu, H., Functional short-chain zwitterion coated silica nanoparticles with antifouling property in protein solutions. Colloids and surfaces. B, Biointerfaces 2015, 126, 251-6.
    20. Witucki, G. L., A Silane Primer: Chemistry andApplications of AIkoxy Silanes. 1992.
    21. QIAO Bing, G. H., WANG Tingjie, JIN Yong, Process and mechanism of surface modification of silica with silane coupling agent APTS. CIESC Journal 2014, 65.
    22. Díaz-Benito, B.; Velasco, F.; Martínez, F. J.; Encinas, N., Hydrolysis study of bis-1,2-(triethoxysilyl)ethane silane by NMR. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2010, 369 (1-3), 53-56.
    23. Shlyakhtenko, L. S.; Gall, A. A.; Filonov, A.; Cerovac, Z.; Lushnikov, A.; Lyubchenko, Y. L., Silatrane-based surface chemistry for immobilization of DNA, protein-DNA complexes and other biological materials. Ultramicroscopy 2003, 97 (1-4), 279-287.
    24. Balas, M. V.-R. a. F., Silica Materials for Medical Applications. The Open Biomedical Engineering Journal 2008, 2, 1-9.
    25. Tsai, M.-F.; Lee, Y.-D.; Chen, K.-N., NMR spectroscopic studies of dimethyldiethoxy silane hydrolysis and polysiloxane conversion. Journal of Applied Polymer Science 2002, 86 (2), 468-477.
    26. Zhu, M.; Lerum, M. Z.; Chen, W., How to prepare reproducible, homogeneous, and hydrolytically stable aminosilane-derived layers on silica. Langmuir : the ACS journal of surfaces and colloids 2012, 28 (1), 416-23.
    27. Dumitriu, A. M.-C.; Cazacu, M.; Shova, S.; Turta, C.; Simionescu, B. C., Synthesis and structural characterization of 1-(3-aminopropyl)silatrane and some new derivatives. Polyhedron 2012, 33 (1), 119-126.
    28. (a) Michael W. Schmidt, T. L. W., t and MarkS. Gordon, Structural Trends in Silicon Atranes. J. Am. Chem. Soc. 1995, 117, 7480-7486; (b) Puri, J. K.; Singh, R.; Chahal, V. K., Silatranes: a review on their synthesis, structure, reactivity and applications. Chemical Society reviews 2011, 40 (3), 1791-840.
    29. Frye, Triptych-siloxazolidines: pentacoordinate bridgehead silanes resulting from transannular interaction of nitrogen and silicon. J Am Chem SOC 1961 (93), 996.
    30. voronkov, Biochemistry of silicon and related problems. 1978.
    31. Voronkov, KINETICS OF HYDROLYSIS OF SILATRANES IN A NEUTRAL MEDIL. 1985.
    32. Tseng, Y. T.; Lu, H. Y.; Li, J. R.; Tung, W. J.; Chen, W. H.; Chau, L. K., Facile Functionalization of Polymer Surfaces in Aqueous and Polar Organic Solvents via 3-Mercaptopropylsilatrane. ACS applied materials & interfaces 2016, 8 (49), 34159-34169.
    33. Kim, D.; Zuidema, J. M.; Kang, J.; Pan, Y.; Wu, L.; Warther, D.; Arkles, B.; Sailor, M. J., Facile Surface Modification of Hydroxylated Silicon Nanostructures Using Heterocyclic Silanes. J Am Chem Soc 2016, 138 (46), 15106-15109.
    34. Huang, K.-W.; Hsieh, C.-W.; Kan, H.-C.; Hsieh, M.-L.; Hsieh, S.; Chau, L.-K.; Cheng, T.-E.; Lin, W.-T., Improved performance of aminopropylsilatrane over aminopropyltriethoxysilane as a linker for nanoparticle-based plasmon resonance sensors. Sensors and Actuators B: Chemical 2012, 163 (1), 207-215.
    35. Wenwen Zhao, Q. Y., Haiyuan Hu,aXiaolong Wang and Feng Zhou, Grafting zwitterionic polymer brushes via electrochemical surface-initiated atomic-transfer
    radical polymerization for anti-fouling applications. J. Mater. Chem. B, 2014, 2, 5352–5357.
    36. Schott, P. G. a. H., Fourier-Transform Midinfrared Spectroscopy for Analysis and Screening of Liquid Protein Formulations. BioProcess International 2006.
    37. Huang, C.-J.; Chang, Y.-C., In Situ Surface Tailoring with Zwitterionic Carboxybetaine Moieties on Self-Assembled Thin Film for Antifouling Biointerfaces. Materials 2013, 7 (1), 130-142.
    38. Alothman, Z., A Review: Fundamental Aspects of Silicate Mesoporous Materials. Materials 2012, 5 (12), 2874-2902.
    39. Schubert, U., Sol–Gel Chemistry and Methods,2012.

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