雙離子性(zwiiterionic)材料為依同時具有正電荷及負電荷官能基於同一單體而成一電中性之結構，其已被證實具有良好的抗生物積垢能力，但由於其具極佳之親水性，因此不易改質製疏水性材料表面。因此本篇研究擬合成一同時具有疏水性長鏈與雙離子性結構片段的共聚物，使其疏水性長鏈可以利用疏水性作用力附著於疏水性聚碸(Polysulfone, PSf)濾膜上，而暴露在外的雙離子性結構可用以對抗生物分子之沾黏。在本研究中選用2,5呋喃二酮與1-十八烯的共聚物(poly(maleic anhydride-alt-1-octadecene), MAO)與N,N-二甲基-1,3-二氨基丙烷(3-(dimethylamino)-1-propylamine, DMAPA)進行開環反應得到一同時具有疏水性長鏈與雙離子性結構片段的兩性共聚物MAO-DMAPA，並藉由核磁共振光譜儀(1H-NMR)分析其化學結構。
接著將MAO-DMAPA與PSf進行摻合(Blending)，再利用濕式相轉換法(Non-solvent induced phase separation, NIPS)製備出不同環境成膜之改質過後的薄膜，並且量測在不同pH值環境下，不同摻合量的PSf膜對於牛血清蛋白(Bovine serum albumin, BSA)與溶解酶(Lysozyme)的吸附量變化，同時由蛋白質靜態吸附實驗結果中挑選具有較佳抗蛋白質吸附能力的薄膜進行蛋白質過濾實驗與大腸桿菌E.coli.的貼附實驗。由各項測試的結果可得知，在70% EtOH環境下成膜，3.6wt%MAO-DMAPA摻合量的PSf膜具有良好的抗蛋白質吸附能力。

In recent years, the zwitterionic copolymers were paid much attention to use for modifying the membranes for the purpose of antifouling. In our study, we have designed an amphiphilic and zwitterionic copolymer MAO-DMAPA synthesized from poly(maleic anhydride-alt-1-octadecene) (MAO) and 3-(dimethylamino)-1-propylamine (DMAPA), then we used different MAO-DMAPA content to blend with polysulfone (PSf) and fabricate the ultrafiltration (UF) membrane by the non-solvent induced phase separation (NIPS) method under 0% and 70% EtOH/H2O mixture surrounding. After membrane preparation, we use the bovine serum albumin(BSA) and lysozyme to measure the protein adsorption resistance of membranes. For these two proteins, we found that the maximum of protein binding capacity and dissociation constant were decreased with elevating the blended MAO-DMAPA content. Finally, we found that the membrane formed under 70% EtOH has superior protein resistance. Then we did the MAO-DMPA titration curve to distinguish the pKa value of the tertiary amine and carboxyl group on MAO-DMAPA. According to the titration curve, we conducted the protein resistance of blended MAO-DMAPA membranes at different pH value surroundings by protein filtration. We got that 70% M-3.6 has higher flux and the best low-protein adsorption ability of those membranes. After protein adsorption experiment, we choose the 70% M-3.6 to carry out E.coli. adhesion. From the result, we can find that 70% M-3.6 has lower amount of E.coli. colonies than M-0. Therefore, we verify blending MAO-DMAPA contributed to improve the low-biofouling ability.

[1] H.-L. Huang, S. Yang, Filtration characteristics of polysulfone membrane filters, Journal of Aerosol Science, 37 (2006) 1198-1208.
[2] B. Kaeselev, J. Pieracci, G. Belfort, Photoinduced grafting of ultrafiltration membranes: comparison of poly(ether sulfone) and poly(sulfone), J Membrane Sci, 194 (2001) 245-261.
[3] L. Liu, A. Chakma, X. Feng, Preparation of hollow fiber poly(ether block amide)/polysulfone composite membranes for separation of carbon dioxide from nitrogen, Chem Eng J, 105 (2004) 43-51.
[4] M.D. Guiver, G.P. Robertson, S. Rowe, S. Foley, Y.S. Kang, H.C. Park, J. Won, H.N.L. Thi, Modified polysulfones. IV. Synthesis and characterization of polymers with silicon substituents for a comparative study of gas-transport properties, J Polym Sci Pol Chem, 39 (2001) 2103-2124.
[5] A. Grill, Cold Plasma in Materials Fabrication., IEEE Press, (1994).
[6] J.D. Andrade, Surface and interfacial Aspects of Biomedical Polymers., Plenum Press, (1985).
[7] G. Belfort, R.H. Davis, A.L. Zydney, The behavior of suspensions and macromolecular solutions in crossflow microfiltration, Journal of Membrane Science, 96 (1994) 1-58.
[8] M. Wahl, Marine epibiosis. I. Fouling and antifouling: some basic aspects, Marine ecology progress series. Oldendorf, 58 (1989) 175-189.
[9] A. Suki, A.G. Fane, C.J.D. Fell, Flux decline in protein ultrafiltration, J Membrane Sci, 21 (1984) 269-283.
[10] P. aimar, S. baklouti, V. sanchez, Membrane— solute interactions: influence on pure solvent transfer during ultrafiltration, J Membrane Sci, 29 (1986) 207-224.
[11] K.L. Jones, C.R. O'Melia, Protein and humic acid adsorption onto hydrophilic membrane surfaces: effects of pH and ionic strength, J Membrane Sci, 165 (2000) 31-46.
[12] R.A. Hartvig, M. van de Weert, J. Ostergaard, L. Jorgensen, H. Jensen, Protein Adsorption at Charged Surfaces: The Role of Electrostatic Interactions and Interfacial Charge Regulation, Langmuir, 27 (2011) 2634-2643.
[13] G. Cheng, Z. Zhang, S.F. Chen, J.D. Bryers, S.Y. Jiang, Inhibition of bacterial adhesion and biofilm formation on zwitterionic surfaces, Biomaterials, 28 (2007) 4192-4199.
[14] N. Cheng, A.A. Brown, O. Azzaroni, W.T.S. Huck, Thickness-dependent properties of polyzwitterionic brushes, Macromolecules, 41 (2008) 6317-6321.
[15] W. Feng, S.P. Zhu, K. Ishihara, J.L. Brash, Adsorption of fibrinogen and lysozyme on silicon grafted with poly(2-methacryloyloxyethyl phosphorylcholine) via surface-initiated atom transfer radical polymerization, Langmuir, 21 (2005) 5980-5987.
[16] J.H. Dankert, A. H.; Feijen, J., Biomedical polymers: bacterial adhesion, colonization, and infection, CRC Crit. Rev. Biocompat, 2 (1986) 219-301.
[17] K.C.S. Marshall, D. C.; Fletcher, M., Eds, Mechanisms of bacterial adhesion at solid-water interfaces, Bacterial Adhesion. Mechanisms and Physiological Significance,New York: Plenum Press, (1985) 133-161.
[18] K.C.S. Marshall, R.; Mitchell, R, Mechanism of initial events in the sorption of marine bacteria to surfaces, J. Gen. Microbiol, 68 (1971) 337-348.
[19] C.E. Zobell, The effect of solid surfaces upon bacterial activity, J. Bacteriol. , 46 (1943) 39-56.
[20] B. Gottenbos, H.J. Busscher, H.C. van der Mei, P. Nieuwenhuis, Pathogenesis and prevention of biomaterial centered infections, Journal of Materials Science: Materials in Medicine, 13 (2002) 717-722.
[21] C. Vuong, M. Otto, Staphylococcus epidermidis infections, Microbes and Infection, 4 (2002) 481-489.
[22] C.L.C. B. R. F. GERARD J. TORTORA, Microbiology : An Introduction, Benjamin-Cummings Publishing Company,United States, (1998).
[23] Y.H. An, R.J. Friedman, Concise review of mechanisms of bacterial adhesion to biomaterial surfaces, J Biomed Mater Res, 43 (1998) 338-348.
[24] V.A. Tegoulia, S.L. Cooper, Staphylococcus aureus adhesion to self-assembled monolayers: effect of surface chemistry and fibrinogen presence, Colloids and Surfaces B: Biointerfaces, 24 (2002) 217-228.
[25] M. Kiremitçi-Gümüşderelioǧlu, A. Peşmen, Microbial adhesion to ionogenic PHEMA, PU and PP implants, Biomaterials, 17 (1996) 443-449.
[26] A. Filimon, E. Avram, S. Dunca, I. Stoica, S. Ioan, Surface properties and antibacterial activity of quaternized polysulfones, Journal of Applied Polymer Science, 112 (2009) 1808-1816.
[27] J.M. Harris, Poly(Ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications, (1992).
[28] M.J. Roberts, M.D. Bentley, J.M. Harris, Chemistry for peptide and protein PEGylation, Adv Drug Deliver Rev, 54 (2002) 459-476.
[29] S.I. Jeon, J.D. Andrade, Protein Surface Interactions in the Presence of Polyethylene Oxide .2. Effect of Protein Size, J Colloid Interf Sci, 142 (1991) 159-166.
[30] S.I. Jeon, J.H. Lee, J.D. Andrade, P.G. Degennes, Protein Surface Interactions in the Presence of Polyethylene Oxide .1. Simplified Theory, J Colloid Interf Sci, 142 (1991) 149-158.
[31] E.F. Murphy, J.R. Lu, J. Brewer, J. Russell, J. Penfold, The Reduced Adsorption of Proteins at the Phosphoryl Choline Incorporated Polymer−Water Interface, Langmuir, 15 (1999) 1313-1322.
[32] J.H. Lee, H.B. Lee, J.D. Andrade, Blood compatibility of polyethylene oxide surfaces, Progress in Polymer Science, 20 (1995) 1043-1079.
[33] J.A. Hayward, D. Chapman, Biomembrane surfaces as models for polymer design: the potential for haemocompatibility, Biomaterials, 5 (1984) 135-142.
[34] A.A. Durrani, J.A. Hayward, D. Chapman, Biomembranes as models for polymer surfaces. II. The syntheses of reactive species for covalent coupling of phosphorylcholine to polymer surfaces, Biomaterials, 7 (1986) 121-125.
[35] T. Umeda, T. Nakaya, M. Imoto, Polymeric phospholipid analogues, 14. The convenient preparation of a vinyl monomer containing a phospholipid analogue, Die Makromolekulare Chemie, Rapid Communications, 3 (1982) 457-459.
[36] K.U. Ishihara, Tomoko; Nakabayashi, Nobuo, Preparation of phospholipid polymers and their properties as polymer hydrogel membranes, Polymer Journal, 5 (1990) 355-360.
[37] Y. Ma, Y. Tang, N.C. Billingham, S.P. Armes, A.L. Lewis, Synthesis of Biocompatible, Stimuli-Responsive, Physical Gels Based on ABA Triblock Copolymers, Biomacromolecules, 4 (2003) 864-868.
[38] J.S.H. Aaron L. Mills, George M. Hornberger, Todd H. deJesús, Effect of Solution Ionic Strength and Iron Coatings on Mineral Grains on the Sorption of Bacterial Cells to Quartz Sand, Appl Environ Microbiol., 60 (1994) 3300-3306.
[39] R.E. Holmlin, X. Chen, R.G. Chapman, S. Takayama, G.M. Whitesides, Zwitterionic SAMs that Resist Nonspecific Adsorption of Protein from Aqueous Buffer, Langmuir, 17 (2001) 2841-2850.
[40] Y. Chang, S. Chen, Z. Zhang, S. Jiang, Highly protein-resistant coatings from well-defined diblock copolymers containing sulfobetaines, Langmuir, 22 (2006) 2222-2226.
[41] Z. Zhang, S. Chen, Y. Chang, S. Jiang, Surface grafted sulfobetaine polymers via atom transfer radical polymerization as superlow fouling coatings, J Phys Chem B, 110 (2006) 10799-10804.
[42] Z. Zhang, T. Chao, S. Chen, S. Jiang, Superlow fouling sulfobetaine and carboxybetaine polymers on glass slides, Langmuir, 22 (2006) 10072-10077.
[43] G. Cheng, Z. Zhang, S. Chen, J.D. Bryers, S. Jiang, Inhibition of bacterial adhesion and biofilm formation on zwitterionic surfaces, Biomaterials, 28 (2007) 4192-4199.
[44] O. Azzaroni, A.A. Brown, W.T. Huck, UCST wetting transitions of polyzwitterionic brushes driven by self-association, Angew Chem Int Ed Engl, 45 (2006) 1770-1774.
[45] W. Yang, S. Chen, G. Cheng, H. Vaisocherova, H. Xue, W. Li, J. Zhang, S. Jiang, Film thickness dependence of protein adsorption from blood serum and plasma onto poly(sulfobetaine)-grafted surfaces, Langmuir, 24 (2008) 9211-9214.
[46] Y. Chang, S.C. Liao, A. Higuchi, R.C. Ruaan, C.W. Chu, W.Y. Chen, A highly stable nonbiofouling surface with well-packed grafted zwitterionic polysulfobetaine for plasma protein repulsion, Langmuir, 24 (2008) 5453-5458.
[47] J.K. Nagy, A.K. Hoffmann, M.H. Keyes, D.N. Gray, K. Oxenoid, C.R. Sanders, Use of amphipathic polymers to deliver a membrane protein to lipid bilayers, Febs Letters, 501 (2001) 115-120.
[48] R.S. Kane, P. Deschatelets, G.M. Whitesides, Kosmotropes form the basis of protein-resistant surfaces, Langmuir, 19 (2003) 2388-2391.
[49] Z. Zhang, S. Chen, S. Jiang, Dual-functional biomimetic materials: nonfouling poly(carboxybetaine) with active functional groups for protein immobilization, Biomacromolecules, 7 (2006) 3311-3315.
[50] Z. Zhang, H. Vaisocherova, G. Cheng, W. Yang, H. Xue, S. Jiang, Nonfouling behavior of polycarboxybetaine-grafted surfaces: structural and environmental effects, Biomacromolecules, 9 (2008) 2686-2692.
[51] M. Sivakumar, R. Malaisamy, C.J. Sajitha, D. Mohan, V. Mohan, R. Rangarajan, Preparation and performance of cellulose acetate–polyurethane blend membranes and their applications – II, J Membrane Sci, 169 (2000) 215-228.
[52] S.H. Yoo, J.H. Kim, J.Y. Jho, J. Won, Y.S. Kang, Influence of the addition of PVP on the morphology of asymmetric polyimide phase inversion membranes: effect of PVP molecular weight, J Membrane Sci, 236 (2004) 203-207.
[53] J.H. Kim, B.R. Min, H.C. Park, J. Won, Y.S. Kang, Phase behavior and morphological studies of polyimide/PVP/solvent/water systems by phase inversion, Journal of Applied Polymer Science, 81 (2001) 3481-3488.
[54] W. Zhao, Y.L. Su, C. Li, Q. Shi, X. Ning, Z.Y. Jiang, Fabrication of antifouling polyethersulfone ultrafiltration membranes using Pluronic F127 as both surface modifier and pore-forming agent, J Membrane Sci, 318 (2008) 405-412.
[55] Z.A. Yi, L.P. Zhu, Y.Y. Xu, Y.F. Zhao, X.T. Ma, B.K. Zhu, Polysulfone-based amphiphilic polymer for hydrophilicity and fouling-resistant modification of polyethersulfone membranes, J Membrane Sci, 365 (2010) 25-33.
[56] Y.H. Zhao, B.K. Zhu, L. Kong, Y.Y. Xu, Improving hydrophilicity and protein resistance of poly(vinylidene fluoride) membranes by blending with amphiphilic hyperbranched-star polymer, Langmuir, 23 (2007) 5779-5786.
[57] F.A. Ştefan Ioan VOICU, Marin RĂDUŢ, Gheorghe Nechifor, Nanostructure Polysulfone Composite Membranes, U.P.B. Sci. Bull., Series B, 70 (2008).
[58] M.A. Aroon, A.F. Ismail, M.M. Montazer-Rahmati, T. Matsuura, Morphology and permeation properties of polysulfone membranes for gas separation: Effects of non-solvent additives and co-solvent, Sep Purif Technol, 72 (2010) 194-202.
[59] D.L. Wang, K. Li, W.K. Teo, Polyethersulfone hollow fiber gas separation membranes prepared from NMP/alcohol solvent systems, J Membrane Sci, 115 (1996) 85-108.