抗積垢為目前生醫材料最重要的改質之一，在眾多抗積垢材料中以雙電性離子的效果最佳，其結構為帶有一正一負官能基但整體為電中性的單體，因此可藉由靜電吸引力在材料表面形成一層水合層，對蛋白質形成能量障礙，有效降低積垢現象的發生，而本研究將利用自行合成的雙電性離子單體來修飾聚丙烯之表面，以達到抗積垢的效果應用在生醫材料上。
本研究首先合成雙電性離子單體，接著以核磁共振(NMR)鑑定其結構，再來開始對聚丙烯表面進行改質，因為聚丙烯的結構為三個碳原子的單體聚合而成，其表面不具有反應性的官能基，為了能在表面進行改質，將以氧氣電漿使其表面產生具有反應性的羥基，後續即可藉由羥基與起始劑產生鍵結，最後接上自行合成的雙電性離子單體，各階段的表面性質分別以衰減全反射式傅立葉轉換紅外線光譜儀(ATR-FTIR)、能量散射光譜儀(EDS)、X射線光電子能譜學(XPS)、接觸角測量(WCA)觀察其表面鍵結、表面元素組成、表面親疏水性、改質層穩定性，而抗積垢的部分則分別以細菌貼附與血液相容性來觀察其效果。
綜合各實驗結果分析可知接枝上自行合成的雙電性離子單體後，其表面性質都有觀察到變化，包括鍵結的改變、元素組成的比例，而雙電性離子能藉由靜電吸引力於材料表面形成一層水合層，故親水性上升，接觸角有明顯的下降，後續抗細菌貼附與血液相容性也可以發現改質過後的表面與未改質的表面相比，細菌與血小板貼附量都減少許多，成功達到抗積垢的效果。

Antifouling is one of the most important applications in biomaterials. The effect of zwitterionic polymers is the best among all of the antifouling materials. It’s an electrically neutral structure composed of cation and anion functional group, so it could induce electrostatic interactions with the surrounding water molecules and form a hydration layer as an energy barrier to reduce fouling. In this work, novel zwitterionic monomer was synthesized for surface modification of polypropylene to achieve antifouling application in biomaterials.
First, the zwitterionic monomer was synthesized and analyzed by NMR. Second, the surface modification of polypropylene began. The structure of polypropylene is composed of a three-carbon monomer, so there is no reactive functional group on the surface. In order to graft the zwitterionic polymer, it is necessary to have a reactive functional group on the surface of polypropylene. The use of oxygen plasma could make the surface reactive with hydroxyl group. Therefore, the initiator could be immobilized on the polypropylene surface and the zwitterionic polymer could also be grafted on it. The surface characterization was analyzed by ATR-FTIR, EDS, XPS and WCA. Furthermore, the antifouling effect was examined by antimicrobial adhesion and platelet adhesion.
According to the results, the surface characterization has changed after grafting zwitterionic polymer including element composition, bonding, hydrophilicity. It could be noticed that the amounts of bacteria and platelet adhesion reduced dramatically after modification. Thus, the modification was successful and the surface had a great antifouling effect.

[1] Cheng G, Zhang Z, Chen S, et al. Inhibition of bacterial adhesion and biofilm formation on zwitterionic surfaces. Biomaterials, 2007, 28: 4192-4199
[2] Castner DG, Ratner BD. Biomedical surface science: Foundations to frontiers. Surface Science, 2002, 500: 28-60
[3] Baier R, Meyer A, Natiella J, et al. Surface properties determine bioadhesive outcomes: Methods and results. Journal of biomedical materials research, 1984, 18: 337-355
[4] Liu Q, Li W, Singh A, et al. Two amino acid-based superlow fouling polymers: Poly(lysine methacrylamide) and poly(ornithine methacrylamide). Acta Biomater, 2014, 10: 2956-2964
[5] Liu C, Lee J, Ma J, et al. Antifouling thin-film composite membranes by controlled architecture of zwitterionic polymer brush layer. Environ Sci Technol, 2017, 51: 2161-2169
[6] Zhang S, Cao J, Ma N, et al. Fast and facile fabrication of antifouling and hemocompatible pvdf membrane tethered with amino-acid modified peg film. Applied Surface Science, 2018, 428: 41-53
[7] Venault A, Zheng YS, Chinnathambi A, et al. Stimuli-responsive and hemocompatible pseudozwitterionic interfaces. Langmuir, 2015, 31: 2861-2869
[8] Sin M-C, Chen S-H, Chang Y. Hemocompatibility of zwitterionic interfaces and membranes. Polymer Journal, 2014, 46: 436-443
[9] Sin MC, Sun YM, Chang Y. Zwitterionic-based stainless steel with well-defined polysulfobetaine brushes for general bioadhesive control. ACS Appl Mater Interfaces, 2014, 6: 861-873
[10] Chang Y, Shu SH, Shih YJ, et al. Hemocompatible mixed-charge copolymer brushes of pseudozwitterionic surfaces resistant to nonspecific plasma protein fouling. Langmuir, 2010, 26: 3522-3530
[11] Yang W, Xue H, Li W, et al. Pursuing "zero" protein adsorption of poly(carboxybetaine) from undiluted blood serum and plasma. Langmuir, 2009, 25: 11911-11916
[12] Chang Y, Liao S-C, Higuchi A, et al. A highly stable nonbiofouling surface with well-packed grafted zwitterionic polysulfobetaine for plasma protein repulsion. Langmuir, 2008, 24: 5453-5458
[13] Venault A, Ye CC, Lin YC, et al. Zwitterionic fibrous polypropylene assembled with amphiphatic carboxybetaine copolymers for hemocompatible blood filtration. Acta Biomater, 2016, 40: 130-141
[14] Ajili SH, Ebrahimi NG, Khorasani MT. Study on thermoplastic polyurethane/polypropylene (tpu/pp) blend as a blood bag material. Journal of Applied Polymer Science, 2003, 89: 2496-2501
[15] Comim LM, Gazolla PS, Santiago TVF, et al. Effect of the extrusion process on the bactericidal performance of biocidal polypropylene catheters. Polymer-Plastics Technology and Engineering, 2012, 51: 283-289
[16] Freitas AFDP, de Araujo MD, Zu WW, et al. Development of weft‐knitted and braided polypropylene stents for arterial implant. Journal of the Textile Institute, 2010, 101: 1027-1034
[17] Minko, S., Polymer Surfaces and Interfaces First ed.; Spinger2008.
[18] Mavis B, Taş AC. Dip coating of calcium hydroxyapatite on ti‐6al‐4v substrates. Journal of the American Ceramic Society, 2000, 83: 989-991
[19] Chu S, Hu X, Du C, et al. Open space for the physisorption of h2: Cointercalation of graphite with li, ti metal atoms and ethylene molecules. International Journal of Hydrogen Energy, 2010, 35: 1280-1284
[20] Rodriguez-Emmenegger C, Kylian O, Houska M, et al. Substrate-independent approach for the generation of functional protein resistant surfaces. Biomacromolecules, 2011, 12: 1058-1066
[21] Navaneetha Pandiyaraj K, Deshmukh RR, Arunkumar A, et al. Evaluation of mechanism of non-thermal plasma effect on the surface of polypropylene films for enhancement of adhesive and hemo compatible properties. Applied Surface Science, 2015, 347: 336-346
[22] Irie H, Miura S, Kamiya K, et al. Efficient visible light-sensitive photocatalysts: Grafting cu(ii) ions onto tio2 and wo3 photocatalysts. Chemical Physics Letters, 2008, 457: 202-205
[23] Wang Y, Kim J-H, Choo K-H, et al. Hydrophilic modification of polypropylene microfiltration membranes by ozone-induced graft polymerization. Journal of Membrane Science, 2000, 169: 269-276
[24] Li R, Wang H, Wang W, et al. Gamma-ray co-irradiation induced graft polymerization of nvp and sss onto polypropylene non-woven fabric and its blood compatibility. Radiation Physics and Chemistry, 2013, 91: 132-137
[25] Li R, Wang H, Wang W, et al. Simultaneous radiation induced graft polymerization of n-vinyl-2-pyrrolidone onto polypropylene non-woven fabric for improvement of blood compatibility. Radiation Physics and Chemistry, 2013, 88: 65-69
[26] Adden N, Gamble LJ, Castner DG, et al. Phosphonic acid monolayers for binding of bioactive molecules to titanium surfaces. Langmuir, 2006, 22: 8197-8204
[27] Gawalt ES, Avaltroni MJ, Koch N, et al. Self-assembly and bonding of alkanephosphonic acids on the native oxide surface of titanium. Langmuir, 2001, 17: 5736-5738
[28] Gawalt ES, Avaltroni MJ, Danahy MP, et al. Bonding organics to ti alloys: Facilitating human osteoblast attachment and spreading on surgical implant materials. Langmuir, 2003, 19: 200-204
[29] Zhao J, Shi Q, Luan S, et al. Improved biocompatibility and antifouling property of polypropylene non-woven fabric membrane by surface grafting zwitterionic polymer. Journal of Membrane Science, 2011, 369: 5-12
[30] Fux CA, Costerton JW, Stewart PS, et al. Survival strategies of infectious biofilms. Trends Microbiol, 2005, 13: 34-40
[31] Carpenter AW, Schoenfisch MH. Nitric oxide release: Part ii. Therapeutic applications. Chem Soc Rev, 2012, 41: 3742-3752
[32] Chen S, Li L, Zhao C, et al. Surface hydration: Principles and applications toward low-fouling/nonfouling biomaterials. Polymer, 2010, 51: 5283-5293
[33] Chinn JA, Posso SE, Horbett TA, et al. Postadsorptive transition in fibrinogen adsorbed to polyurethanes: Changes in antibody binding and sodium dodecy1 sulfate elutability. Journal of biomedical materials research, 1992, 26: 757-778
[34] Mrabet B, Nguyen MN, Majbri A, et al. Anti-fouling poly(2-hydoxyethyl methacrylate) surface coatings with specific bacteria recognition capabilities. Surface Science, 2009, 603: 2422-2429
[35] Desseaux S, Hinestrosa JP, Schüwer N, et al. Swelling behavior and nanomechanical properties of (peptide-modified) poly(2-hydroxyethyl methacrylate) and poly(poly(ethylene glycol) methacrylate) brushes. Macromolecules, 2016, 49: 4609-4618
[36] Yoshikawa C, Hattori S, Honda T, et al. Non-biofouling property of well-defined concentrated poly(2-hydroxyethyl methacrylate) brush. Materials Letters, 2012, 83: 140-143
[37] Yoshikawa C, Goto A, Tsujii Y, et al. Protein repellency of well-defined, concentrated poly (2-hydroxyethyl methacrylate) brushes by the size-exclusion effect. Macromolecules, 2006, 39: 2284-2290
[38] Shen M, Martinson L, Wagner MS, et al. Peo-like plasma polymerized tetraglyme surface interactions with leukocytes and proteins: In vitro and in vivo studies. Journal of Biomaterials Science, Polymer Edition, 2002, 13: 367-390
[39] Jeong SP, Hong D, Kang SM, et al. Polymeric functionalization of cyclic olefin copolymer surfaces with nonbiofouling poly(oligo(ethylene glycol) methacrylate). Asian Journal of Organic Chemistry, 2013, 2: 568-571
[40] Ma H, Hyun J, Stiller P, et al. “Non-fouling” oligo(ethylene glycol)- functionalized polymer brushes synthesized by surface-initiated atom transfer radical polymerization. Advanced Materials, 2004, 16: 338-341
[41] Tedjo C, Neoh KG, Kang ET, et al. Bacteria-surface interaction in the presence of proteins and surface attached poly(ethylene glycol) methacrylate chains. J Biomed Mater Res A, 2007, 82: 479-491
[42] Kim S-M, Han SS, Kim AY, et al. Anti-biofouling effect of peg-grafted block copolymer synthesized by raft polymerization. Journal of Nanoscience and Nanotechnology, 2015, 15: 7866-7870
[43] Zhao J, Shi Q, Luan S, et al. Polypropylene non-woven fabric membrane via surface modification with biomimetic phosphorylcholine in ce(iv)/hno3 redox system. Materials Science and Engineering: C, 2012, 32: 1785-1789
[44] Chantasirichot S, Ishihara K. Electrospun phospholipid polymer substrate for enhanced performance in immunoassay system. Biosens Bioelectron, 2012, 38: 209-214
[45] Chen X, Chen T, Lin Z, et al. Choline phosphate functionalized surface: Protein-resistant but cell-adhesive zwitterionic surface potential for tissue engineering. Chem Commun (Camb), 2015, 51: 487-490
[46] Ishihara K, Ueda T, Nakabayashi N. Preparation of phospholipid polylners and their properties as polymer hydrogel membranes. Polymer Journal, 1990, 22: 355
[47] Zhao Y-H, Wee K-H, Bai R. Highly hydrophilic and low-protein-fouling polypropylene membrane prepared by surface modification with sulfobetaine-based zwitterionic polymer through a combined surface polymerization method. Journal of Membrane Science, 2010, 362: 326-333
[48] Kwon HJ, Lee Y, Phuong LT, et al. Zwitterionic sulfobetaine polymer-immobilized surface by simple tyrosinase-mediated grafting for enhanced antifouling property. Acta Biomater, 2017, 61: 169-179
[49] Sakuragi M, Tsuzuki S, Obuse S, et al. A photoimmobilizable sulfobetaine-based polymer for a nonbiofouling surface. Mater Sci Eng C Mater Biol Appl, 2010, 30: 316-322
[50] Smith RS, Zhang Z, Bouchard M, et al. Vascular catheters with a nonleaching poly-sulfobetaine surface modification reduce thrombus formation and microbial attachment. Science translational medicine, 2012, 4: 153ra132-153ra132
[51] Cheng G, Li G, Xue H, et al. Zwitterionic carboxybetaine polymer surfaces and their resistance to long-term biofilm formation. Biomaterials, 2009, 30: 5234-5240
[52] Sun F, Wu K, Hung HC, et al. Paper sensor coated with a poly(carboxybetaine)-multiple dopa conjugate via dip-coating for biosensing in complex media. Anal Chem, 2017, 89: 10999-11004
[53] Yu WN, Manik DHN, Huang CJ, et al. Effect of elimination on antifouling and ph-responsive properties of carboxybetaine materials. Chem Commun (Camb), 2017, 53: 9143-9146
[54] Vaisocherova H, Yang W, Zhang Z, et al. Ultralow fouling and functionalizable surface chemistry based on a zwitterionic polymer enabling sensitive and specific protein detection in undiluted blood plasma. Analytical chemistry, 2008, 80: 7894-7901
[55] Zhang Z, Chen S, Jiang S. Dual-functional biomimetic materials: Nonfouling poly (carboxybetaine) with active functional groups for protein immobilization. Biomacromolecules, 2006, 7: 3311-3315
[56] Venault A, Wei T-C, Shih H-L, et al. Antifouling pseudo-zwitterionic poly(vinylidene fluoride) membranes with efficient mixed-charge surface grafting via glow dielectric barrier discharge plasma-induced copolymerization. Journal of Membrane Science, 2016, 516: 13-25
[57] Liu D, Zhu J, Qiu M, et al. Antifouling performance of poly(lysine methacrylamide)-grafted pvdf microfiltration membrane for solute separation. Separation and Purification Technology, 2016, 171: 1-10
[58] Ishii T, Wada A, Tsuzuki S, et al. Copolymers including l-histidine and hydrophobic moiety for preparation of nonbiofouling surface. Biomacromolecules, 2007, 8: 3340-3344
[59] Zhang L, Tang M, Zhang J, et al. One simple and stable coating of mixed-charge copolymers on poly(vinyl chloride) films to improve antifouling efficiency. Journal of Applied Polymer Science, 2017, 134
[60] 王建國編著, 高分子成新技術, 化學工業出版社
[61] L.G. Wade Organic Chemistry 5th Ed, Mechanism supplements original, 319
[62] 蔡文城博士. 微生物學: 藝軒圖書出版社; 2002
[63] 何敏夫, 血液學, 合記出版社, 1993
[64] Ko, T. M.; Lin, J. C.; Cooper, S. L. Surface characterization and platelet-adhesion studies of plasma-sulfonated polyethylene, Biomaterials, 1993, 14, 657-664
[65] Graaff KMVD and Fox SI, Circulatory System: Blood, Concepts of Human Anatomy and Physiology, Chap 20, 531-542
[66] Chappuis, J. Edited by Hewitt, G. F.; Delhaye, J. M.; Zuber, N. Contact Angles, Multiphase Science and Technology, 1982, Chapter4, 47-505
[67] Skoog, D. A.; Holler, F. J.; Crouch, S. R. Principles of Instrumental Analysis. 6 ed. 2007, Thomson
[68] Ratner, B. D.; Castner, D. G. Edited by Vickerman, J. C.; Wiely, J.; Sons Electron Spectroscopy for Chemical Analysis, Surface Analysis-The Principal Technique, 1997,Chapter3, 43-98
[69] Briggs, D.; Seah, M. P.; Wiely, J.; Sons. Quantification of AES and XPS, Practical Surface Analysis Vol.1, 1990, Chapter5, 201-256
[70] 邱正宇, 掃描式電子顯微鏡簡介. 國立成功大學奈米中心
[71] Daniel C. Harris. Quantitative Chemical Analysis, Sixth edition, 2003
[72] L. H. Sperling. Introduction to Physical Polymer Science, Fourth edition, 2006
[73] Alswieleh AM, Cheng N, Canton I, et al. Zwitterionic poly(amino acid methacrylate) brushes. J Am Chem Soc, 2014, 136: 9404-9413
[74] Al-Jaf O, Alswieleh A, Armes SP, et al. Nanotribological properties of nanostructured poly(cysteine methacrylate) brushes. Soft Matter, 2017, 13: 2075-2084
[75] Ladmiral V, Charlot A, Semsarilar M, et al. Synthesis and characterization of poly(amino acid methacrylate)-stabilized diblock copolymer nano-objects. Polymer Chemistry, 2015, 6: 1805-1816
[76] Liu P, Huang T, Liu P, et al. Zwitterionic modification of polyurethane membranes for enhancing the anti-fouling property. J Colloid Interface Sci, 2016, 480: 91-101
[77] Wang X, Yuan S, Shi D, et al. Integrated antifouling and bactericidal polymer membranes through bioinspired polydopamine/poly(n-vinyl pyrrolidone) coating. Applied Surface Science, 2016, 375: 9-18