近年來生醫材料被廣泛的應用於再生醫學及組織工程，但當生醫材料植入體內或與人體接觸時可能引起一些併發症，例如：蛋白質或生物分子會沾黏於材料表面，而使傷者感到不適，更嚴重可能引起發炎反應。為了解決上述問題，本論文目標為利用丙烯胺 (allylamine)、吡咯 (pyrrole)、及丙烯酸 (acrylic acid) 做為為前驅物，藉由真空電漿系統製備含有胺基及羧基電漿聚合沉積薄膜，並利用物理化學分析方法探討電漿功率與沉積時間等電漿參數、以及前驅物沉積順序，以改變電漿聚合薄膜厚度、表面化學官能基與元素組成，提升生物相容性、及抗沾黏效果。
本論文第一部分，為了提升硬式隱形眼鏡表面潤濕性以及降低蛋白質貼附性質，利用電漿聚合丙烯酸與丙烯胺混成薄膜 (pp(AAc+AAm))，而玻璃表面的水接觸角由46˚下降至10˚，隨著沉積時間增加，水接觸角呈現穩定。當利用溶菌酶 (LYS) 及牛血清蛋白質 (BSA) 作為蛋白質貼附測試時，pp(AAc+AAm) 薄膜在沉積30分鐘後，與未經改質的硬式隱形眼鏡相比分別減少52.3 %和26.9 %。經過24小時培養L-929老鼠纖維母細胞於硬式隱形眼鏡上，由乳酸脫氫脢試驗 (LDH assay) 結果可以得知，電漿沉積pp(AAc+AAm) 薄膜於硬式隱形眼鏡，細胞貼附量為69,165 cell/cm2，與未經處理的硬式隱形眼鏡相比有相近的細胞貼附量 (70,072 cell/cm2)，因此經由電漿沉積pp(AAc+AAm) 薄膜後，並不會影響隱形眼鏡的生物相容性。
本論文第二部分，為探討電漿沉積導電薄膜的最適化參數，因此利用電漿在施加功率為5 W、10 W、及20 W下沉積電漿聚合吡咯薄膜 (pp(Py))，藉由水接觸角量測結果觀察水接觸角由46˚上升至60˚，隨著沉積時間增加，水接觸角呈現穩定。經培養L-929老鼠纖維母細胞進行生物相容性測試，由LDH分析方法定量，由結果顯示經沉積pp(Py) 薄膜於玻璃基材上後，當施加功率為5 W、10 W、及20 W時，細胞貼附量與玻璃相比增加155 %、106 %、及170 %，而利用光學顯微鏡觀察細胞型態，細胞具有優異的延展性及貼附性。當電漿施加功率為20 W時，藉由控制pp(Py) 薄膜厚度為10 nm，經碘摻雜6小時後有最佳的電流響應 (982 A/cm2)。利用，化學分析電子能譜儀 (ECSA) 分析結果顯示，在沉積pp(Py) 薄膜後可以測量到N1s訊號，經碘摻雜後同時測量到I3d訊號，由此可證實pp(Py) 膜薄可成功地藉由電漿聚合方式沉積於基材上。
最後，為了製備具含有胺基及羧基雙官能基薄膜，利用電漿聚合沉積pyrrole及acrylic acid兩種前驅物，製備雙層及混成薄膜，由水接觸角量測結果觀察，當以電漿聚合沉積丙烯酸為上層薄膜時 (pp(AAc))，水接觸角從46˚下降至10˚，當以pp(Py) 為上層薄膜時，水接觸角為53˚，在沉積pp(AAc+Py) 混成薄膜時，水接觸角為30˚，因此能藉由通入不同前驅物於電漿系統，有效地改變基材表面親疏水性質。當以LYS為蛋白質貼附測試時，製備雙層薄膜並以pp(Py) 為上層薄膜時，pp(Py/AAc) 雙層薄膜與玻璃相比，LYS貼附量漸少44 %，而當以BSA進行蛋白質貼附測試時，製備雙層薄膜並以pp(AAc) 為上層薄膜時，pp(AAc/Py) 雙層薄膜的BSA貼附量減少71 %，而在pp(Py/AAc) 及pp(AAc+Py) 薄膜BSA貼附量分別減少41 % 及40 %，因此當電漿聚合胺基及羧基雙官能基薄膜於玻璃表面上，具有降低蛋白質貼附的效果。而由表面界達電位結果可得，經電漿聚合沉積pp(AAc/Py) 薄膜於玻璃上時，表面電位由-43.2 mV上升至-41.9 mV，而當沉積pp(Py/AAc) 及pp(AAc+Py) 薄膜於玻璃上時，表面電位由-43.2 mV上升至-28.9 mV和-11.2 mV。經培養L-929老鼠纖維母細胞於pp(AAc/Py) 薄膜上，由LDH測量結果，與未經處理的玻璃相比細胞量增加40 %，pp(Py/AAc) 細胞量增加50 %，而pp(AAc+Py) 細胞量增加107 %，藉由電漿沉積雙官能基薄膜有助於提升生物相容性，因此電漿聚合沉積含有胺基與羧基雙官能基薄膜具有應用於生醫材料之潛力。

The applications of biomaterials have drawn increasingly attention in fields of regenerative medicine and tissue engineering although some complications might occur. For example, the deposition of proteins or different biomolecules on the surface of the biomaterials which are in contact with personnel might lead to discomfort of patients. In order to overcome the aforementioned problems, the coatings of thin films on the surface of the biomaterials became an important issue for the applications in the fields of biomedicine. The research goal of this thesis is to prepare plasma polymerized thin films containing amine and carboxylic functional groups by introducing allylamine (AAm), pyrrole (Py) and acrylic acid (AAc) as precursors. By adjusting different applied power, plasma deposition time, and the orders of introducing precursors, the thickness of the plasma deposited thin films, surface wettability and functional groups, biocompatibility, and the antifouling properties of the resultant thin films will be discussed.
At the first part of the thesis, in order to promote the surface wettability and to decrease the biofouling problems of contact lens, pp(AAc+AAm) thin film was prepared. The surface wettability of pp(AAc+AAm) thin film was 10˚, comparing with the water contact angle (WCA) of 46˚ on untreated glass. The deposition of pp(AAc+AAm) for 30 mins for glass allowed to reduce 52.3 % and 26.9 % adsorption for lysozyme (LYS) and bovine serum albumin (BSA), comparing with pristine contact lens, respectively. The cell density of L-929 mouse fibroblast on pp(AAc+AAm) thin films after 24 h incubation time showed the similar result when compared with the pristine contact lens, which indicated that pp(AAc+AAm) thin film shows good biocompatibility.
At the second part of the thesis, in order to optimize the parameters for the deposition of conductive thin films, pyrrole was chosen as the precursor. Plasma-polymerized pyrrole (pp(Py)) thin films were deposited on glass with the applied power at 5 W, 10 W, and 20 W. The surface wettability was carried out by measuring the water contact angle which increased from 46˚ to 60˚ after the deposition of pp(Py) on glass. The WCA stayed unaltered water with longer deposition time. LDH assay results revealed that the cell density for L-929 mouse fibroblast on pp(Py) thin films decorated glass increased 155 %, 106 % and 170 %, when compared with the pristine glass at the applied power for 5 W, 10 W and 20 W, respectively. In addition, from optical microscope image revealed that the cell morphology was in fibroblast shape. When the applied power and the film thickness of pp(Py) thin films were controlled at 20 W and 10 nm, the pp(Py) thin film showed the highest current density (982 A/cm2) by iodine doping for 6 h. ESCA analyses showed that the N1s signal appeared after pp(Py) thin film was deposited on Si wafer. Moreover, I3d signal was found after iodine doping, which confirmed that pp(Py) thin film was successfully deposited on Si wafer by plasma polymerization and can be iodine doped.
For the third part of the thesis, in order to prepare thin films containing both amine and carboxylic functional groups, pyrrole and acrylic acid were chosen as the precursors. The surface wettability can be modulated by depositing different thin films as the top layer. When pp(AAc) was deposited as the top layer, the WCA decreased from 46˚ (pristine glass) to 10˚. Alternatively, when pp(Py) was deposited as the top layer, the WCA increased to 53˚. By depositing pp(AAc+Py) on glass, the WCA was 30˚, showing the potential hybrid properties of pp(AAc+Py), comparing with pp(Py) and pp(AAc). The antifouling property was carried out by using LYS and BSA as protein models. Compared with pristine glass, the LYS adsorption on pp(Py/AAc)/glass decreased 44 %, comparing with the prisitnie glass. The BSA adsorption on pp(AAc/Py)/glass, pp(Py/AAc)/glass and pp(AAc+Py)/glass decreased to 71 %, 41 % and 40 %, respectively, which showed that plasma polymerized amine and carboxylic functional groups on glass demonstrated the antifouling property. Moreover, the surface charge of pristine glass was -43.2 mV and increased to -41.9 mV after the depositing pp(AAc/Py) on glass. For pp(Py/AAc)/glass and pp(AAc+Py)/glass, the surface charge were -28.9 mV and -11.2 mV. The biocompatibility tests for pp(AAc/Py)/glass, pp(Py/AAc)/glass, and pp(AAc+Py)/glass showed that the L-929 mouse fibroblast cell density increased 40 %, 50 % and 107 % comparing with pristine glass, which concluded plasma polymerized amine and carboxylic functional groups possess the potential for the biomaterial applications.

[1] A. Ohl, W. Schleinitz, A. Meyer-Sievers, A. Becker, D. Keller, K. Schröder, "Design of an UHV reactor system for plasma surface treatment of polymer materials," Surface and Coatings Technology, vol. 116, pp. 1006-1010, 1999.
[2] C. Mandolfino, E. Lertora, S. Genna, C. Leone, and C. Gambaro, "Effect of laser and plasma surface cleaning on mechanical properties of adhesive bonded joints," Procedia Cirp, vol. 33, pp. 458-463, 2015.
[3] L. Latu-Romain, M. Ollivier, V. Thiney, O. Chaix-Pluchery, and M. Martin, "Silicon carbide nanotubes growth: an original approach," Journal of Physics D: Applied Physics, vol. 46, p. 092001, 2013.
[4] Z. Jiang, Z.-j. Jiang, Y. Shi, and Y. Meng, "Preparation and characteristics of acrylic acid/styrene composite plasma polymerized membranes," Applied Surface Science, vol. 256, pp. 6473-6479, 2010.
[5] P. K. Chu, J. Chen, L. Wang, and N. Huang, "Plasma-surface modification of biomaterials," Materials Science and Engineering: R: Reports, vol. 36, pp. 143-206, 2002.
[6] T. Lu, Y. Qiao, and X. Liu, "Surface modification of biomaterials using plasma immersion ion implantation and deposition," Interface focus, vol. 2, pp. 325-336, 2012.
[7] N. K. Guimard, N. Gomez, and C. E. Schmidt, "Conducting polymers in biomedical engineering," Progress in polymer science, vol. 32, pp. 876-921, 2007.
[8] M. M. Pérez-Madrigal, M. I. Giannotti, L. J. del Valle, L. Franco, E. Armelin, J. Puiggalı́, "Thermoplastic polyurethane: polythiophene nanomembranes for biomedical and biotechnological applications," ACS applied materials & interfaces, vol. 6, pp. 9719-9732, 2014.
[9] H. D. Tran, K. Shin, W. G. Hong, J. M. D'Arcy, R. W. Kojima, B. H. Weiller, "A template‐free route to polypyrrole nanofibers," Macromolecular Rapid Communications, vol. 28, pp. 2289-2293, 2007.
[10] Z. Yang, Q. Tu, J. Wang, X. Lei, T. He, H. Sun, "Bioactive plasma‐polymerized bipolar films for enhanced endothelial cell mobility," Macromolecular bioscience, vol. 11, pp. 797-805, 2011.
[11] R. Bitar, P. Cools, N. De Geyter, and R. Morent, "Acrylic acid plasma polymerization for biomedical use," Applied Surface Science, vol. 448, pp. 168-185, 2018.
[12] B.-S. Lou, S.-B. Wang, S.-B. Hung, C.-J. Wang, and J.-W. Lee, "Characterization of plasma polymerized organosilicon thin films deposited on 316L stainless steel," Thin Solid Films, 2018.
[13] R. J. Goldston and P. H. Rutherford, Introduction to plasma physics: CRC Press, 1995.
[14] J. A. Bittencourt, Fundamentals of plasma physics: Springer Science & Business Media, 2013.
[15] R. d'Agostino, P. Favia, C. Oehr, and M. R. Wertheimer, "Low‐temperature plasma processing of materials: past, present, and future," Plasma Processes and Polymers, vol. 2, pp. 7-15, 2005.
[16] R. Fitzpatrick, "Introduction to plasma physics," The University of Texas at Austin, p. 242, 2008.
[17] P. Bourke, D. Ziuzina, D. Boehm, P. J. Cullen, and K. Keener, "The potential of cold plasma for safe and sustainable food production," Trends in biotechnology, vol. 36, pp. 615-626, 2018.
[18] M. E. Vlachopoulou, G. Kokkoris, C. Cardinaud, E. Gogolides, and A. Tserepi, "Plasma etching of poly (dimethylsiloxane): roughness formation, mechanism, control, and application in the fabrication of microfluidic structures," Plasma Processes and Polymers, vol. 10, pp. 29-40, 2013.
[19] T. S. Williams, H. Yu, and R. F. Hicks, "Atmospheric pressure plasma activation as a surface pre-treatment for the adhesive bonding of aluminum 2024," Journal of Adhesion Science and Technology, vol. 28, pp. 653-674, 2014.
[20] S. K. Pankaj, C. Bueno-Ferrer, N. Misra, V. Milosavljević, C. O'donnell, P. Bourke, "Applications of cold plasma technology in food packaging," Trends in Food Science & Technology, vol. 35, pp. 5-17, 2014.
[21] K. J. Kanarik, T. Lill, E. A. Hudson, S. Sriraman, S. Tan, J. Marks, "Overview of atomic layer etching in the semiconductor industry," Journal of Vacuum Science & Technology A: Vacuum, Surfaces, and Films, vol. 33, p. 020802, 2015.
[22] A. Zille, M. M. Fernandes, A. Francesko, T. Tzanov, M. Fernandes, F. R. Oliveira, "Size and aging effects on antimicrobial efficiency of silver nanoparticles coated on polyamide fabrics activated by atmospheric DBD plasma," ACS applied materials & interfaces, vol. 7, pp. 13731-13744, 2015.
[23] M. Jubber, J. Wilson, I. Drummond, P. John, and D. Milne, "Design of a UHV reactor for microwave plasma deposition of diamond films," Vacuum, vol. 45, pp. 499-506, 1994.
[24] R. Ravichandran, S. Sundarrajan, J. R. Venugopal, S. Mukherjee, and S. Ramakrishna, "Applications of conducting polymers and their issues in biomedical engineering," Journal of the Royal Society Interface, vol. 7, pp. S559-S579, 2010.
[25] P. Pluta, P. Roversi, G. Bernardo-Seisdedos, A. L. Rojas, J. B. Cooper, S. Gu, "Structural basis of pyrrole polymerization in human porphobilinogen deaminase," Biochimica et Biophysica Acta (BBA)-General Subjects, vol. 1862, pp. 1948-1955, 2018.
[26] L.-X. Wang, X.-G. Li, and Y.-L. Yang, "Preparation, properties and applications of polypyrroles," Reactive and Functional Polymers, vol. 47, pp. 125-139, 2001.
[27] T. Nezakati, A. Seifalian, A. Tan, and A. M. Seifalian, "Conductive polymers: opportunities and challenges in biomedical applications," Chemical reviews, vol. 118, pp. 6766-6843, 2018.
[28] H. K. Koduru, L. Marino, J. Vallivedu, C. J. Choi, and N. Scaramuzza, "Microstructural, wetting, and dielectric properties of plasma polymerized polypyrrole thin films," Journal of Applied Polymer Science, vol. 133, 2016.
[29] C. Li, J. Hsieh, and Y. Lee, "Effects of radio frequency power on the microstructures and properties of plasma polymerized polypyrrole thin films," Vacuum, vol. 140, pp. 132-138, 2017.
[30] C. Li, J. Hsieh, and Y. Lee, "Fabrication and structural characterization of plasma polymerized polypyrrole thin film," Surface and Coatings Technology, vol. 320, pp. 206-212, 2017.
[31] S. Zhang, M. Xing, and B. Li, "Biomimetic Layer-by-Layer Self-Assembly of Nanofilms, Nanocoatings, and 3D Scaffolds for Tissue Engineering," International journal of molecular sciences, vol. 19, p. 1641, 2018.
[32] A. Ulman, An Introduction to Ultrathin Organic Films: From Langmuir--Blodgett to Self--Assembly: Academic press, 2013.
[33] G. Decher, J. Hong, and J. Schmitt, "Buildup of ultrathin multilayer films by a self-assembly process: III. Consecutively alternating adsorption of anionic and cationic polyelectrolytes on charged surfaces," Thin solid films, vol. 210, pp. 831-835, 1992.
[34] Z. Yang, X. Lei, J. Wang, R. Luo, T. He, H. Sun, "A novel technique toward bipolar films containing alternating nano–layers of allylamine and acrylic acid plasma polymers for biomedical application," Plasma Processes and Polymers, vol. 8, pp. 208-214, 2011.
[35] P. Li, X. Cai, D. Wang, S. Chen, J. Yuan, L. Li, "Hemocompatibility and anti-biofouling property improvement of poly (ethylene terephthalate) via self-polymerization of dopamine and covalent graft of zwitterionic cysteine," Colloids and Surfaces B: Biointerfaces, vol. 110, pp. 327-332, 2013.
[36] D. Rao, N. Meyyappan, and S. Feroz, "Treatment of effluent waters in food processing industries," Wastewater Treatment: Advanced Processes and Technologies, p. 239, 2012.
[37] M. Liu, Q. Chen, K. Lu, W. Huang, Z. Lü, C. Zhou, "High efficient removal of dyes from aqueous solution through nanofiltration using diethanolamine-modified polyamide thin-film composite membrane," Separation and Purification Technology, vol. 173, pp. 135-143, 2017.
[38] A. P. GmbH, The ZETA Guide Principles of the streaming potential technique, 2014.
[39] K. Cai, M. Frant, J. Bossert, G. Hildebrand, K. Liefeith, and K. D. Jandt, "Surface functionalized titanium thin films: zeta-potential, protein adsorption and cell proliferation," Colloids and Surfaces B: Biointerfaces, vol. 50, pp. 1-8, 2006.
[40] C. Bellmann, A. Caspari, V. Albrecht, T. L. Doan, E. Mäder, T. Luxbacher, "Electrokinetic properties of natural fibres," Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 267, pp. 19-23, 2005.
[41] F. S. Key, The Influence of pH on Zeta Potential, 2012.
[42] M. Elimelech, W. H. Chen, and J. J. Waypa, "Measuring the zeta (electrokinetic) potential of reverse osmosis membranes by a streaming potential analyzer," Desalination, vol. 95, pp. 269-286, 1994.
[43] L. Tušek, M. Nitschke, C. Werner, K. Stana-Kleinschek, and V. Ribitsch, "Surface characterisation of NH3 plasma treated polyamide 6 foils," Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 195, pp. 81-95, 2001.
[44] Y. Nitta, K. Okamoto, T. Nakatani, H. Hoshi, A. Homma, E. Tatsumi, "Diamond-like carbon thin film with controlled zeta potential for medical material application," Diamond and Related Materials, vol. 17, pp. 1972-1976, 2008.
[45] G. Altankov, K. Richau, and T. Groth, "The role of surface zeta potential and substratum chemistry for regulation of dermal fibroblasts interaction," Materialwissenschaft und Werkstofftechnik: Entwicklung, Fertigung, Prüfung, Eigenschaften und Anwendungen technischer Werkstoffe, vol. 34, pp. 1120-1128, 2003.
[46] C. Liu, J. Lee, J. Ma, and M. Elimelech, "Antifouling thin-film composite membranes by controlled architecture of zwitterionic polymer brush layer," Environmental science & technology, vol. 51, pp. 2161-2169, 2017.
[47] K. Hosono, I. Matsubara, N. Murayama, W. Shin, and N. Izu, "Effects of discharge power on the structure and electrical properties of plasma polymerized polypyrrole films," Materials Letters, vol. 58, pp. 1371-1374, 2004.
[48] J. L. Yagüe and S. Borrós, "Conducting plasma polymerized polypyrrole thin films as carbon dioxide gas sensors," Plasma Processes and Polymers, vol. 9, pp. 485-490, 2012.
[49] J. Wang, K. Neoh, and E. Kang, "Comparative study of chemically synthesized and plasma polymerized pyrrole and thiophene thin films," Thin Solid Films, vol. 446, pp. 205-217, 2004.
[50] S. Cetiner, H. Karakas, R. Ciobanu, M. Olariu, N. U. Kaya, C. Unsal, "Polymerization of pyrrole derivatives on polyacrylonitrile matrix, FTIR–ATR and dielectric spectroscopic characterization of composite thin films," Synthetic Metals, vol. 160, pp. 1189-1196, 2010.
[51] J. G. Steele, G. Johnson, C. McFarland, B. Dalton, T. Gengenbach, R. Chatelie, "Roles of serum vitronectin and fibronectin in initial attachment of human vein endothelial cells and dermal fibroblasts on oxygen-and nitrogen-containing surfaces made by radiofrequency plasmas," Journal of Biomaterials Science, Polymer Edition, vol. 6, pp. 511-532, 1995.
[52] G. Kaklamani, N. Mehrban, J. Bowen, H. Dong, L. Grover, and A. Stamboulis, "Nitrogen plasma surface modification enhances cellular compatibility of aluminosilicate glass," Materials Letters, vol. 111, pp. 225-229, 2013.
[53] B. Paosawatyanyong, K. Tapaneeyakorn, and W. Bhanthumnavin, "AC plasma polymerization of pyrrole," Surface and Coatings Technology, vol. 204, pp. 3069-3072, 2010.
[54] O. Fabela-Sánchez, H. Salgado–Ceballos, L. Medina-Torres, L. Álvarez-Mejía, S. Sánchez-Torres, R. Mondragón-Lozano, "Effect of the combined treatment of albumin with plasma synthesised pyrrole polymers on motor recovery after traumatic spinal cord injury in rats," Journal of Materials Science: Materials in Medicine, vol. 29, p. 13, 2018.
[55] L. Detomaso, R. Gristina, G. S. Senesi, R. d’Agostino, and P. Favia, "Stable plasma-deposited acrylic acid surfaces for cell culture applications," Biomaterials, vol. 26, pp. 3831-3841, 2005.
[56] S. W. Lee, B.-S. Kim, S. Chen, Y. Shao-Horn, and P. T. Hammond, "Layer-by-layer assembly of all carbon nanotube ultrathin films for electrochemical applications," Journal of the American Chemical Society, vol. 131, pp. 671-679, 2008.
[57] B. Gupta, C. Plummer, I. Bisson, P. Frey, and J. Hilborn, "Plasma-induced graft polymerization of acrylic acid onto poly (ethylene terephthalate) films: characterization and human smooth muscle cell growth on grafted films," Biomaterials, vol. 23, pp. 863-871, 2002.
[58] E. D. Giglio, C. Calvano, I. Losito, L. Sabbatini, P. Zambonin, A. Torrisi, "Surface (XPS, SIMS) chemical investigation on poly (pyrrole‐3‐acetic acid) films electrosynthesized on Ti and TiAlV substrates for the development of new bioactive substrates," Surface and Interface Analysis: An International Journal devoted to the development and application of techniques for the analysis of surfaces, interfaces and thin films, vol. 37, pp. 580-586, 2005.
[59] D. H. Kim, C.-S. Park, E. Y. Jung, D. S. Kum, J. Y. Kim, D. Kim, "Experimental study on atmospheric pressure plasma polymerized conducting polymer under coupling and remote conditions," Molecular Crystals and Liquid Crystals, vol. 663, pp. 108-114, 2018.
[60] G. Socrates, Infrared and Raman characteristic group frequencies: tables and charts: John Wiley & Sons, 2004.