臺灣博碩士論文加值系統

高度生物相容性為發展先進醫材與進階醫療器材的重要需求功能之ㄧ，隨著近年來高分子材料的快速發展，拓展新應用方向也扮演研發功能性醫材的關鍵角色。隨著日益增長的慢性疾病與病毒疫情帶來的影響，發展用於注射液過濾裝置的微過濾薄膜系統也逐漸受到重視。本研究擬探討的問題為如何提高微過濾薄膜系統抵抗生物分子沾黏的性質，同時也需克服經高溫濕式滅菌程序處理後，膜材各項性質的穩定度。本研究擬設計一新型雙離子高分子，合成製備聚(4-乙烯基吡啶丙基磺基甜菜鹼)來強化高分子的耐熱性質，並導入聚(乙二醇單甲醚甲基丙烯酸酯)與聚(苯乙烯)分子鏈段來提升與泛用型濾膜材料聚偏二氟乙烯(poly(vinylidene difluoride), PVDF)的相容性。在PVDF微過濾薄膜系統的製備方面，採用非溶劑誘導相轉換法來控制薄膜的雙連續孔洞結構，並建立相圖來分析薄膜成形的可能機制。由於薄膜表面對於水分子作用所產生的水合現象與其生物惰性有重要的關聯性，因此本研究導入水氣吸脫附實驗來探討不同含量的雙離子高分子於PVDF薄膜中對於水合性質變化的影響，並進一步建立分析模型與關聯性指標。在薄膜物化性質分析方面，採用場發射掃描式電子顯微鏡、X射線光電子能譜儀、傅立葉轉換紅外線光譜儀、原子力顯微鏡、拉力機、與表面界達電位儀對於所製備的膜材進行定性檢測與量化分析。本研究的重要成果歸納如下：(1) 透過導入聚(乙二醇單甲醚甲基丙烯酸酯)分子鏈段成功解決雙離子共聚物之溶解度問題； (2) 成功合成出聚(苯乙烯)-r-聚(乙二醇單甲醚甲基丙烯酸酯)-r-聚(4-乙烯基吡啶丙基磺基甜菜鹼)的雙離子共聚物，並可製備出可抵抗121℃濕熱滅菌處理的生物惰性PVDF微過濾薄膜，實現濾膜具熱穩定性功能; (3) 新型雙離子共聚物可展現高度水合性質，在37℃與相對溼度90%下能保有高於自身重量48%的水合含量; (4) 在含雙離子共聚物 5wt%的最佳混摻比例，PVDF膜面可抵抗大於98%的細菌(大腸桿菌與嗜麥芽窄食單胞菌)貼附量，展現高度抗細菌污垢沾黏的功能； (5) 此種薄膜經比較不具熱穩定性之聚(苯乙烯)-r-聚(乙二醇單甲醚甲基丙烯酸酯)-r-聚(4-乙烯基吡啶丙基磺基甜菜鹼)雙離子共聚物薄膜後發現其水合性質與高溫滅菌前後的抗細菌貼附效果都更加顯著； (6) 將薄膜置於去離子水及磷酸鹽緩衝溶液環境中歷時一個月仍能展現其優異的改質穩定性。

Biocompatibility is one of the important functions that required for the development of advanced biomaterials and medical equipment. Recently, the rapid development of outstanding polymer materials and expanding various applications have also played a key role in the development of functional biomaterials. The development of the microfiltration membrane systems for the injection devices has gradually attracted attention with an increasing impact of chronic diseases and the virus epidemics. The problem to be discussed in this study is how to improve the resistance of the bio-foulant adhesion using the microfiltration membrane system and also necessary to overcome the stability of various properties of the prepared membranes after being treated by the high-temperature and wet sterilization procedures. In this study, an innovative zwitterionic random copolymer was designed, and the existence of the 4-vinylpyridine propylsulfobetaine, 4VPPS) was used to enhance thermal stability of the copolymer as well as the membranes. Poly(ethylene glycol) methyl ether methacrylate (PEGMA) and poly(styrene) chain segments were introduced to improve the material compatibility with polyvinylidene fluoride (PVDF). The prepared PVDF microfiltration membrane via non-solvent induced phase separation method was used to control the bi-continuous membrane structure, and the ternary phase diagram was analyzed to confirm the possible mechanism of membrane formation. The water vapor adsorption and desorption experiments were introduced to investigate the effect of the different contents of zwitterionic copolymer on the PVDF membranes. In the analysis of the physical and chemical properties of the membranes, the prepared membranes were successfully characterized qualitatively and quantitatively. The important results of this study were summarized as follows: (1) The solubility problem of the zwitterionic copolymer was successfully solved by the addition of PEGMA segments; (2) Zwitterionic PVDF microfiltration membranes was successfully synthesized, and effectively applicable for bio-inert that could resist 121℃ steam sterilization treatment to realize the thermal stability of the membraneproperties; (3) The innovative zwitterionic copolymer exhibited highly hydratable properties, retaining 48% hydration content at 37°C and 90% relative humidity; (4) Finally, 5 wt% zwitterionic copolymer (M5.0) resisted more than 97% attachment of bacteria (Escherichia coli and Stenotrophomonas maltophilia), showed high degree of resistance to the bacterial fouling; (6) M5.0 membrane exhibited excellent stability after being immersed into deionized water and Phosphate buffered saline for one month.

目次
摘要 I
Abstract II
致謝 III
目次 V
圖目次 VIII
表目次 XI
第一章 緒論 1
第二章 文獻回顧與研究動機 3
2.1 薄膜改質技術 3
2.1.1 薄膜改質方法與其優劣比較 3
2.1.2 薄膜高分子設計 8
2.2 生物惰性材料 10
2.2.1 生物惰性材料發展進程 10
2.2.2 生物惰性材料之設計準則 13
2.2.3 雙離子系統材料研究 14
2.3 熱穩定型材料 18
2.3.1 熱穩定型材料簡介 18
2.3.2 具熱穩定性質之生物惰性材料研究 20
2.4 研究動機與實驗假設 22
2.5 需解決問題 24
第三章 實驗藥品、儀器與實驗方法 25
3.1 實驗藥品 25
3.1.1 單體 25
3.1.2 起始劑 28
3.1.3 溶劑 29
3.1.4 重溶劑 34
3.1.5 鹽類 35
3.1.6 檢測試劑與染劑 38
3.1.7 菌種培養 40
3.1.8 細胞培養 43
3.2 實驗設備與儀器 46
3.3 實驗方法 48
3.3.1 單體、高分子合成方法 48
3.3.2 薄膜製程方法 55
3.3.3 材料鑑定與檢測 59
3.3.4 薄膜物化性質檢測 66
3.3.5 成膜機制實驗 79
3.3.6 薄膜長期穩定性測試 81
3.3.7 生物性檢測 83
3.3.8 薄膜過濾應用 95
第四章 結果與討論 99
4.1 材料合成結果與分析 99
4.1.1 單體合成 99
4.1.2 共聚高分子合成 102
4.2 材料之熱穩定性質與水合性質分析 108
4.2.1 材料熱穩定性 108
4.2.2 材料水合能力 110
4.3 最優化薄膜製程條件選定 115
4.3.1 鑄膜液配方 115
4.3.2 薄膜表面結構確定 117
4.3.3 抗細菌貼附測試 119
4.4 薄膜表面物理化學性質分析 122
4.4.1 薄膜孔徑大小與孔隙率 122
4.4.2 薄膜機械強度 124
4.4.3 薄膜表面與截面結構 125
4.4.4 薄膜表面粗糙度 127
4.4.5 薄膜表面親水性與表面電性 129
4.4.6 薄膜表面功能性官能基含量及分布 132
4.4.7 薄膜表面元素含量與化學鍵 134
4.5 成膜機制分析 138
4.6 薄膜長期穩定性 142
4.7 薄膜經高溫滅菌前後之抗生物污垢沾黏比較 144
4.7.1 抗細菌貼附結果 144
4.7.2 抗人體細胞貼附結果 150
4.7.3 抗人體全血細胞吸附結果 152
4.8 薄膜經高溫滅菌前後之大腸桿菌過濾的應用 155
第五章 結論 160
5.1 研究結論 160
5.2 未來發展性 163
參考文獻 164
圖目次
圖1 2016~2018美國醫療器材市場規模 2
圖2 近十年生物相容性相關研究發表數 2
圖3 薄膜改質方法示意圖27 6
圖4 第一代至第三代抗沾黏材料設計演進40 11
圖5 雙離子界面的分子設計示意圖27 12
圖6 細胞膜結構示意圖50 14
圖7 MPC化學結構 15
圖8 SBMA化學結構 15
圖9 CBMA化學結構 16
圖10 近十年雙離子系統相關研究發表數 17
圖11 近十年熱穩定型高分子相關研究發表數 18
圖12 研究假設圖 23
圖13 4VPPS單體合成化學反應 48
圖14 4VPPS單體產物 49
圖15 合成poly(Styrene-r-PEGMA)之無規共聚反應 50
圖16 合成poly(Styrene-r-PEGMA-r-SBMA)之無規共聚反應 52
圖17 合成poly(Styrene-r-PEGMA-r-4VPPS)之無規共聚反應 53
圖18 無規共聚物poly(Styrene-r-PEGMA-r-4VPPS)產物 54
圖19 鑄膜液配製結果圖 55
圖20 製膜程序圖 57
圖21 薄膜製程完之結果圖 58
圖22 細胞計數盤 90
圖23 單體4VPPS之1H-NMR圖譜 100
圖24 單體4VPPS之FTIR圖譜 101
圖25 共聚高分子P(Styrene-r-PEGMA-r-4VPPS)之1H-NMR圖譜 103
圖26 共聚高分子P(Styrene-r-PEGMA-r-4VPPS)與其單體之1H-NMR圖譜 103
圖27 不同共聚高分子之TGA結果圖 109
圖28 不同共聚高分子之動態水蒸氣吸附曲線 111
圖29 不同共聚高分子之不同濕度下抓水能力表現 114
圖30 不同共聚高分子之不同濕度下抓水能力表現 114
圖31 鑄膜液配製結果圖 116
圖32 FE-SEM拍攝之薄膜表面形貌圖 118
圖33 FE-SEM拍攝之薄膜截面結構圖 118
圖34 展開條件薄膜之E. coli, G細菌貼附結果 120
圖35 CLSM對展開條件薄膜拍攝之E. coli, G細菌貼附圖 120
圖36 FE-SEM拍攝之滅菌前後M0.0~M5.0薄膜表面形貌圖 126
圖37 FE-SEM拍攝之滅菌前後M0.0~M5.0薄膜截面結構圖 126
圖38 M0.0~M5.0之薄膜表面粗糙度 128
圖39 M0.0~M5.0之薄膜表面粗糙度三維圖 128
圖40 M0.0~M5.0之薄膜表面動態水接觸角測量結果 131
圖41 M0.0~M5.0之薄膜表面靜態水接觸角測量與表面電位測量結果 131
圖42 M0.0~M5.0之薄膜表面FTIR圖譜 133
圖43 M0.0~M5.0之薄膜表面FTIR官能基含量分佈圖 133
圖44 M0.0~M5.0之薄膜表面XPS (Survey)全圖譜 134
圖45 M0.0薄膜表面XPS之碳、氮、硫窄譜分峰圖 136
圖46 M5.0薄膜表面XPS之碳、氮、硫窄譜分峰圖 136
圖47 M0.0與M5.0成膜動力學之動態光穿透結果圖 139
圖48 成膜熱力學之霧點三相圖 141
圖49 成膜三相圖示意圖 141
圖50 M5.0薄膜泡於DI-water一個月之穩定性測試 142
圖51 M5.0薄膜泡於PBS水溶液一個月之穩定性測試 142
圖52 滅菌前後M0.0~M5.0薄膜之E. coli, G負電菌貼附結果 145
圖53 CLSM對滅菌前後M0.0~M5.0薄膜拍攝之E. coli, G負電菌貼附圖 145
圖54 不同混摻材料的滅菌前後薄膜之E. coli, G負電菌貼附結果 147
圖55 CLSM對不同混摻材料的滅菌前後薄膜之E. coli, G負電菌貼附圖 147
圖56 滅菌前後M0.0~M5.0薄膜之S. maltophilia正電菌貼附結果 149
圖57 CLSM對滅菌前後M0.0~M5.0薄膜拍攝之S. maltophilia正電菌貼附圖 149
圖58 滅菌前後M0.0~M5.0薄膜之HT1080 fibroblast cell貼附結果 151
圖59 CLSM對滅菌前後M0.0~M5.0薄膜拍攝之HT1080 fibroblast cell貼附圖 151
圖60 滅菌前後M0.0~M5.0薄膜之全血球細胞吸附結果 153
圖61 CLSM對滅菌前後M0.0~M5.0薄膜拍攝之全血球細胞吸附圖 153
圖62 FE-SEM對滅菌前後M0.0~M1.0薄膜拍攝之全血球細胞表面吸附圖 154
圖63 滅菌前後之M5.0與M0.0與商業親水膜Commercial細菌過濾通量圖 158
圖64 滅菌前後之M5.0與M0.0與商業親水膜Commercial細菌過濾通量圖(無因次) 158
圖65 進料細菌溶液定量檢量線 159
圖66 經滅菌前後之多種生物分子抗沾黏測試結果圖 161
圖67 研究結果圖片摘要 162
表目次
表1 鑄模液配方表 56
表2 霧點相圖實驗之鑄膜液配方表 80
表3 單體4VPPS之1H-NMR峰值 100
表4 共聚高分子P(Styrene-r-PEGMA-r-4VPPS)特徵峰之 1H-NMR峰值 104
表5 共聚高分子P(Styrene-r-PEGMA-r-4VPPS)各鏈段組成比例 104
表6 共聚高分子P(Styrene-r-PEGMA-r-4VPPS)之合成條件與分子量測量結果 105
表7 溶解度測試表 107
表8 不同共聚高分子之熱裂解溫度 109
表9 不同共聚高分子之水合能力定量分析表 111
表10 鑄膜液配方表 116
表11 條件選定後之鑄膜液配方表 121
表12 M0.0~M5.0之薄膜孔徑與孔隙率 123
表13 M0.0~M5.0之薄膜機械強度 124
表14 M0.0~M5.0之薄膜表面元素組成比例 135
表15 M0.0與M5.0薄膜表面之不同鍵結訊號位置 137
表16 滅菌前後之M5.0與M0.0與商業親水膜Commercial細菌過濾效能比較 159
表17 重要實驗結果歸納 162

1.Medical Device Manufacturers Market Size from: https://www.grandviewresearch.com/industry-analysis/us-medical-device-manufacturers-market.
2.Ogbonna, C. N.; Nwoba, E. G., Bio-based flocculants for sustainable harvesting of microalgae for biofuel production. A review. Renew. Sust. Energ. Rev. 2021, 139, 16.
3.Rashid, T.; Sher, F.; Hazafa, A.; Hashmi, R. Q.; Zafar, A.; Rasheed, T.; Hussain, S., Design and feasibility study of novel paraboloid graphite based microbial fuel cell for bioelectrogenesis and pharmaceutical wastewater treatment. J. Environ. Chem. Eng. 2021, 9 (1), 8.
4.Fahimirad, S.; Fahimirad, Z.; Sillanpaa, M., Efficient removal of water bacteria and viruses using electrospun nanofibers. Sci. Total Environ. 2021, 751, 18.
5.Ghosal, K.; Agatemor, C.; Spitalsky, Z.; Thomas, S.; Kny, E., Electrospinning tissue engineering and wound dressing scaffolds from polymer-titanium dioxide nanocomposites. Chemical Engineering Journal 2019, 358, 1262-1278.
6.Musah, S.; Mammoto, A.; Ferrante, T. C.; Jeanty, S. S. F.; Hirano-Kobayashi, M.; Mammoto, T.; Roberts, K.; Chung, S.; Novak, R.; Ingram, M.; Fatanat-Didar, T.; Koshy, S.; Weaver, J. C.; Church, G. M.; Ingber, D. E., Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nat. Biomed. Eng 2017, 1 (5), 12.
7.Moretro, T.; Langsrud, S., Residential Bacteria on Surfaces in the Food Industry and Their Implications for Food Safety and Quality. Compr. Rev. Food. Sci. Food Saf. 2017, 16 (5), 1022-1041.
8.Chou, Y. N.; Venault, A.; Wang, Y. H.; Chinnathambi, A.; Higuchi, A.; Chang, Y., Surface zwitterionization on versatile hydrophobic interfaces via a combined copolymerization/self-assembling process. J. Mat. Chem. B 2018, 6 (30), 4909-4919.
9.Miller, D. J.; Dreyer, D. R.; Bielawski, C. W.; Paul, D. R.; Freeman, B. D., Surface Modification of Water Purification Membranes. Angew. Chem.-Int. Edit. 2017, 56 (17), 4662-4711.
10.Ahmad, A. L.; Abdulkarim, A. A.; Ooi, B. S.; Ismail, S., Recent development in additives modifications of polyethersulfone membrane for flux enhancement. Chemical Engineering Journal 2013, 223, 246-267.
11.Shi, H.; He, Y.; Pan, Y.; Di, H. H.; Zeng, G. Y.; Zhang, L.; Zhang, C. L., A modified mussel-inspired method to fabricate TiO2 decorated superhydrophilic PVDF membrane for oil/water separation. Journal of Membrane Science 2016, 506, 60-70.
12.Louie, J. S.; Pinnau, I.; Ciobanu, I.; Ishida, K. P.; Ng, A.; Reinhard, M., Effects of polyether-polyamide block copolymer coating on performance and fouling of reverse osmosis membranes. Journal of Membrane Science 2006, 280 (1-2), 762-770.
13.Kochkodan, V.; Hilal, N., A comprehensive review on surface modified polymer membranes for biofouling mitigation. Desalination 2015, 356, 187-207.
14.Huang, S. L.; Ras, R. H. A.; Tian, X. L., Antifouling membranes for oily wastewater treatment: Interplay between wetting and membrane fouling. Curr. Opin. Colloid Interface Sci. 2018, 36, 90-109.
15.Lien, C. C.; Yeh, L. C.; Venault, A.; Tsai, S. C.; Hsu, C. H.; Dizon, G. V.; Huang, Y. T.; Higuchi, A.; Chang, Y., Controlling the zwitterionization degree of alternate copolymers for minimizing biofouling on PVDF membranes. Journal of Membrane Science 2018, 565, 119-130.
16.Shi, Q.; Su, Y. L.; Zhao, W.; Li, C.; Hu, Y. H.; Jiang, Z. Y.; Zhu, S. P., Zwitterionic polyethersulfone ultrafiltration membrane with superior antifouling property. Journal of Membrane Science 2008, 319 (1-2), 271-278.
17.Zhu, Y. Z.; Wang, J. L.; Zhang, F.; Gao, S. J.; Wang, A. Q.; Fang, W. X.; Jin, J., Zwitterionic Nanohydrogel Grafted PVDF Membranes with Comprehensive Antifouling Property and Superior Cycle Stability for Oil-in-Water Emulsion Separation. Adv. Funct. Mater. 2018, 28 (40), 10.
18.Liu, C. H.; Lee, J.; Ma, J.; Elimelech, M., Antifouling Thin-Film Composite Membranes by Controlled Architecture of Zwitterionic Polymer Brush Layer. Environ. Sci. Technol. 2017, 51 (4), 2161-2169.
19.Li, Q.; Imbrogno, J.; Belfort, G.; Wang, X. L., Making polymeric membranes antifouling via "grafting from" polymerization of zwitterions. J. Appl. Polym. Sci. 2015, 132 (21), 14.
20.Ma, W.; Rahaman, M. S.; Therien-Aubin, H., Controlling biofouling of reverse osmosis membranes through surface modification via grafting patterned polymer brushes. J. Water Reuse Desalin. 2015, 5 (3), 326-334.
21.Zhang, Q. F.; Zhang, S. B.; Dai, L.; Chen, X. S., Novel zwitterionic poly(arylene ether sulfone)s as antifouling membrane material. Journal of Membrane Science 2010, 349 (1-2), 217-224.
22.Khongnakorn, W.; Bootluck, W.; Jutaporn, P., Surface modification of FO membrane by plasma-grafting polymerization to minimize protein fouling. J. Water Process. Eng. 2020, 38, 11.
23.Venault, A.; Liou, C. S.; Yeh, L. C.; Jhong, J. F.; Huang, J.; Chang, Y., Turning Expanded Poly(tetrafluoroethylene) Membranes into Potential Skin Wound Dressings by Grafting a Bioinert Epoxylated PEGMA Copolymer. ACS Biomater. Sci. Eng. 2017, 3 (12), 3338-3350.
24.Huang, C. J.; Chang, Y. C., In Situ Surface Tailoring with Zwitterionic Carboxybetaine Moieties on Self-Assembled Thin Film for Antifouling Biointerfaces. Materials 2014, 7 (1), 130-142.
25.Venault, A.; Chou, Y. N.; Wang, Y. H.; Hsu, C. H.; Chou, C. J.; Bouyer, D.; Lee, K. R.; Chang, Y., A combined polymerization and self-assembling process for the fouling mitigation of PVDF membranes. Journal of Membrane Science 2018, 547, 134-145.
26.Dizon, G. V.; Venault, A., Direct in-situ modification of PVDF membranes with a zwitterionic copolymer to form bi-continuous and fouling resistant membranes. Journal of Membrane Science 2018, 550, 45-58.
27.Venault, A.; Chang, Y., Designs of Zwitterionic Interfaces and Membranes. Langmuir 2019, 35 (5), 1714-1726.
28.Chapman, R. G.; Ostuni, E.; Takayama, S.; Holmlin, R. E.; Yan, L.; Whitesides, G. M., Surveying for surfaces that resist the adsorption of proteins. J. Am. Chem. Soc. 2000, 122 (34), 8303-8304.
29.Wu, J.; Lin, W. F.; Wang, Z.; Chen, S. F.; Chang, Y., Investigation of the Hydration of Nonfouling Material Poly(sulfobetaine methacrylate) by Low-Field Nuclear Magnetic Resonance. Langmuir 2012, 28 (19), 7436-7441.
30.Faghihnejad, A.; Zeng, H. B., Hydrophobic interactions between polymer surfaces: using polystyrene as a model system. Soft Matter 2012, 8 (9), 2746-2759.
31.Lin, N. J.; Yang, H. S.; Chang, Y.; Tung, K. L.; Chen, W. H.; Cheng, H. W.; Hsiao, S. W.; Aimar, P.; Yamamoto, K.; Lai, J. Y., Surface Self-Assembled PEGylation of Fluoro-Based PVDF Membranes via Hydrophobic-Driven Copolymer Anchoring for Ultra-Stable Biofouling Resistance. Langmuir 2013, 29 (32), 10183-10193.
32.Lin, W. H.; Lin, C. Y.; Tsai, C. C.; Yu, J. S.; Tsai, W. B., Spheroid Formation of Human Adipose-Derived Stem Cells on Environmentally Friendly BMA/SBMA/HEMA Copolymer-Coated Anti-Adhesive Surface. Bull. Chem. Soc. Jpn. 2018, 91 (9), 1457-1464.
33.Leduc , E. H.; Holt , S. J., HYDROXYPROPYL METHACRYLATE, A NEW WATER-MISCIBLE EMBEDDING MEDIUM FOR ELECTRON MICROSCOPY. Journal of Cell Biology 1965, 26 (1), 137-155.
34.Chou, Y. N.; Chang, Y.; Wen, T. C., Applying Thermosettable Zwitterionic Copolymers as General Fouling-Resistant and Thermal-Tolerant Biomaterial Interfaces. ACS Appl. Mater. Interfaces 2015, 7 (19), 10096-10107.
35.Hsu, C. H.; Venault, A.; Zheng, H. Z.; Lo, C. T.; Yang, C. C.; Chang, Y., Failure of sulfobetaine methacrylate as antifouling material for steam-sterilized membranes and a potential alternative. Journal of Membrane Science 2021, 620, 14.
36.Dizon, G. V.; Lee, Y. S.; Venault, A.; Maggay, I. V.; Chang, Y., Zwitterionic PMMA-r-PEGMA-r-PSBMA copolymers for the formation of anti-biofouling bicontinuous membranes by the VIPS process. Journal of Membrane Science 2021, 618, 15.
37.Apple, D. J.; Sims, J., Harold Ridley and the invention of the intraocular lens. Surv. Ophthalmol. 1996, 40 (4), 279-292.
38.Apple, D. J.; Trivedi, R. H., Sir Nicholas Harold Ridley, Kt, MD, FRCS, FRS - Contributions in addition to the Intraocular lens. Arch. Ophthalmol. 2002, 120 (9), 1198-1202.
39.Zhang, Z.; Chao, T.; Chen, S. F.; Jiang, S. Y., Superlow fouling sulfobetaine and carboxybetaine polymers on glass slides. Langmuir 2006, 22 (24), 10072-10077.
40.Sin, M. C.; Chen, S. H.; Chang, Y., Hemocompatibility of zwitterionic interfaces and membranes. Polym. J. 2014, 46 (8), 436-443.
41.Mrabet, B.; Nguyen, M. N.; Majbri, A.; Mahouche, S.; Turmine, M.; Bakhrouf, A.; Chehimi, M. M., Anti-fouling poly(2-hydoxyethyl methacrylate) surface coatings with specific bacteria recognition capabilities. Surf. Sci. 2009, 603 (16), 2422-2429.
42.Yoshikawa, C.; Goto, A.; Tsujii, Y.; Fukuda, T.; Kimura, T.; Yamamoto, K.; Kishida, A., Protein repellency of well-defined, concentrated poly(2-hydroxyethyl methacrylate) brushes by the size-exclusion effect. Macromolecules 2006, 39 (6), 2284-2290.
43.Ma, H. W.; Hyun, J. H.; Stiller, P.; Chilkoti, A., "Non-fouling" oligo(ethylene glycol)-functionalized polymer brushes synthesized by surface-initiated atom transfer radical polymerization. Adv. Mater. 2004, 16 (4), 338-+.
44.Zheng, J.; Li, L. Y.; Tsao, H. K.; Sheng, Y. J.; Chen, S. F.; Jiang, S. Y., Strong repulsive forces between protein and oligo (ethylene glycol) self-assembled monolayers: A molecular simulation study. Biophys. J. 2005, 89 (1), 158-166.
45.Ray, S. S.; Dangayach, R.; Kwon, Y. N., Surface engineering for anti-wetting and antibacterial membrane for enhanced and fouling resistant membrane distillation performance. Chemical Engineering Journal 2021, 405, 17.
46.Shen, M. C.; Martinson, L.; Wagner, M. S.; Castner, D. G.; Ratner, B. D.; Horbett, T. A., PEO-like plasma polymerized tetraglyme surface interactions with leukocytes and proteins: in vitro and in vivo studies. J. Biomater. Sci.-Polym. Ed. 2002, 13 (4), 367-390.
47.Luk, Y. Y.; Kato, M.; Mrksich, M., Self-assembled monolayers of alkanethiolates presenting mannitol groups are inert to protein adsorption and cell attachment. Langmuir 2000, 16 (24), 9604-9608.
48.Ostuni, E.; Chapman, R. G.; Holmlin, R. E.; Takayama, S.; Whitesides, G. M., A survey of structure-property relationships of surfaces that resist the adsorption of protein. Langmuir 2001, 17 (18), 5605-5620.
49.Caurie, M., Bound water: its definition, estimation and characteristics. Int. J. Food Sci. Technol. 2011, 46 (5), 930-934.
50.Cell membrane structure from: https://zhtw.eferrit.com/%E7%B4%B0%E8%83%9E%E8%86%9C%E5%8A%9F%E8%83%BD%E5%92%8C%E7%B5%90%E6%A7%8B/.
51.Kadoma, Y.; Nakabayashi, N.; Masuhara, E.; Yamauchi, J., Synthesis and Hemolysis Test of the Polymer Containing Phosphorylcholine Groups. KOBUNSHI RONBUNSHU 1978, 35 (7), 423-427.
52.Chang, Y.; Shu, S.-H.; Shih, Y.-J.; Chu, C.-W.; Ruaan, R.-C.; Chen, W.-Y., Hemocompatible Mixed-Charge Copolymer Brushes of Pseudozwitterionic Surfaces Resistant to Nonspecific Plasma Protein Fouling. Langmuir 2010, 26 (5), 3522-3530.
53.Chang, Y.; Chang, W. J.; Shih, Y. J.; Wei, T. C.; Hsiue, G. H., Zwitterionic sulfobetaine-grafted poly(vinylidene fluoride) membrane with highly effective blood compatibility via atmospheric plasma-induced surface copolymerization. ACS Appl Mater Interfaces 2011, 3 (4), 1228-37.
54.Ladd, J.; Zhang, Z.; Chen, S.; Hower, J. C.; Jiang, S., Zwitterionic Polymers Exhibiting High Resistance to Nonspecific Protein Adsorption from Human Serum and Plasma. Biomacromolecules 2008, 9 (5), 1357-1361.
55.Vaisocherová, H.; Yang, W.; Zhang, Z.; Cao, Z.; Cheng, G.; Piliarik, M.; Homola, J.; Jiang, S., Ultralow fouling and functionalizable surface chemistry based on a zwitterionic polymer enabling sensitive and specific protein detection in undiluted blood plasma. Anal Chem 2008, 80 (20), 7894-901.
56.Chiu, C. Y.; Chang, Y.; Liu, T. H.; Chou, Y. N.; Yen, T. J., Convergent charge interval spacing of zwitterionic 4-vinylpyridine carboxybetaine structures for superior blood-inert regulation in amphiphilic phases. J. Mat. Chem. B 2021, 9 (40), 8437-8450.
57.Arrhenius equation from: http://www.laohuajiance.com/h-nd-21.html.
58.Laidler, K. J., The development of the Arrhenius equation. Journal of Chemical Education 1984, 61 (6), 494.
59.Higuchi, A.; Shirano, K.; Harashima, M.; Yoon, B. O.; Hara, M.; Hattori, M.; Imamura, K., Chemically modified polysulfone hollow fibers with vinylpyrrolidone having improved blood compatibility. Biomaterials 2002, 23 (13), 2659-2666.
60.Marchant, R. E.; Johnson, S. D.; Schneider, B. H.; Agger, M. P.; Anderson, J. M., A hydrophilic plasma polymerized film composite with potential application as an interface for biomaterials. Journal of Biomedical Materials Research 1990, 24 (11), 1521-1537.
61.Wetzels, G. M. R.; Koole, L. H., Photoimmobilisation of poly(N-vinylpyrrolidinone) as a means to improve haemocompatibility of polyurethane biomaterials. Biomaterials 1999, 20 (20), 1879-1887.
62.Robinson, S.; Williams, P. A., Inhibition of Protein Adsorption onto Silica by Polyvinylpyrrolidone. Langmuir 2002, 18 (23), 8743-8748.
63.Davies, W. L.; Gloor Jr., W. T., Batch production of pharmaceutical granulations in a fluidized bed II: Effects of various binders and their concentrations on granulations and compressed tablets. Journal of Pharmaceutical Sciences 1972, 61 (4), 618-622.
64.Hoang, T.; Jorgensen, M. G.; Keim, R. G.; Pattison, A. M.; Slots, J., Povidone-iodine as a periodontal pocket disinfectant. Journal of Periodontal Research 2003, 38 (3), 311-317.
65.Reimer, K.; Vogt, P. M.; Broegmann, B.; Hauser, J.; Rossbach, O.; Kramer, A.; Rudolph, P.; Bosse, B.; Schreier, H.; Fleischer, W., An Innovative Topical Drug Formulation for Wound Healing and Infection Treatment: In vitro and in vivo Investigations of a Povidone-Iodine Liposome Hydrogel. Dermatology 2000, 201 (3), 235-241.
66.Telford, A. M.; James, M.; Meagher, L.; Neto, C., Thermally Cross-Linked PNVP Films As Antifouling Coatings for Biomedical Applications. ACS Appl. Mater. Interfaces 2010, 2 (8), 2399-2408.
67.Chou, Y.-N.; Chang, Y.; Wen, T.-C., Applying Thermosettable Zwitterionic Copolymers as General Fouling-Resistant and Thermal-Tolerant Biomaterial Interfaces. ACS Appl. Mater. Interfaces 2015, 7 (19), 10096-10107.
68.Yang, C. C.; Lo, C. T.; Luo, Y. L.; Venault, A.; Chang, Y., Thermally Stable Bioinert Zwitterionic Sulfobetaine Interfaces Tolerated in the Medical Sterilization Process. ACS Biomater. Sci. Eng. 2021, 7 (3), 1031-1045.
69.Chang, J.; Tao, Y.; Wang, B.; Guo, B. H.; Xu, H.; Jiang, Y. R.; Huang, Y. B., An in situ-forming zwitterionic hydrogel as vitreous substitute. J. Mat. Chem. B 2015, 3 (6), 1097-1105.
70.Liu, Q. S.; Li, W. C.; Singh, A.; Cheng, G.; Liu, L. Y., Two amino acid-based superlow fouling polymers: Poly(lysine methacrylamide) and poly(ornithine methacrylamide). Acta Biomater. 2014, 10 (7), 2956-2964.
71.Hirasawa, M.; Tsutsumi-Arai, C.; Takakusaki, K.; Oya, T.; Fueki, K.; Wakabayashi, N., Superhydrophilic co-polymer coatings on denture surfaces reduce Candida albicans adhesion-An in vitro study. Arch. Oral Biol. 2018, 87, 143-150.
72.Chen, S.-H.; Chang, Y.; Ishihara, K., Reduced Blood Cell Adhesion on Polypropylene Substrates through a Simple Surface Zwitterionization. Langmuir 2017, 33 (2), 611-621.
73.Venault, A.; Chen, S. J.; Lin, H. T.; Maggay, I.; Chang, Y., Bi-continuous positively-charged PVDF membranes formed by a dual-bath procedure with bacteria killing/release ability. Chemical Engineering Journal 2021, 417, 20.
74.Mukherjee, M.; De, S., Antibacterial polymeric membranes: a short review. Environmental Science: Water Research & Technology 2018, 4 (8), 1078-1104.
75.Maggay, I. V.; Suba, M.; Aini, H. N.; Wu, C. J.; Tang, S. H.; Aquino, R. B.; Chang, Y.; Venault, A., Thermostable antifouling zwitterionic vapor-induced phase separation membranes. Journal of Membrane Science 2021, 627, 15.
76.Tang, S.-H.; Venault, A.; Hsieh, C.; Dizon, G. V.; Lo, C.-T.; Chang, Y., A bio-inert and thermostable zwitterionic copolymer for the surface modification of PVDF membranes. Journal of Membrane Science 2020, 598, 117655.
77.Song, L. X.; Lam, Y. M., Selective betainization of PS-P4VP and solution properties. Langmuir 2006, 22 (1), 319-324.
78.Venault, A.; Lin, K.-H.; Tang, S.-H.; Dizon, G. V.; Hsu, C.-H.; Maggay, I. V. B.; Chang, Y., Zwitterionic electrospun PVDF fibrous membranes with a well-controlled hydration for diabetic wound recovery. Journal of Membrane Science 2020, 598, 117648.
79.Hsu, C.-H.; Venault, A.; Chang, Y., Facile zwitterionization of polyvinylidene fluoride microfiltration membranes for biofouling mitigation. Journal of Membrane Science 2022, 648, 120348.
80.Venault, A.; Lai, M. W.; Jhong, J. F.; Yeh, C. C.; Yeh, L. C.; Chang, Y., Superior Bioinert Capability of Zwitterionic Poly(4-vinylpyridine propylsulfobetaine) Withstanding Clinical Sterilization for Extended Medical Applications. ACS Appl. Mater. Interfaces 2018, 10 (21), 17771-17783.
81.Venault, A.; Liu, Y.-H.; Wu, J.-R.; Yang, H.-S.; Chang, Y.; Lai, J.-Y.; Aimar, P., Low-biofouling membranes prepared by liquid-induced phase separation of the PVDF/polystyrene-b-poly (ethylene glycol) methacrylate blend. Journal of Membrane Science 2014, 450, 340-350.
82.Wijmans, J. G.; Smolders, C. A., Preparation of Asymmetric Membranes by the Phase Inversion Process. In Synthetic Membranes: Science, Engineering and Applications, Bungay, P. M.; Lonsdale, H. K.; de Pinho, M. N., Eds. Springer Netherlands: Dordrecht, 1986; pp 39-56.
83.Wang, J.; Pan, G.; Li, Y.; Zhang, Y.; Shi, H.; Liu, X.; Yu, H.; Zhao, M.; Liu, Y.; Wu, C., Bicontinuous porous membranes with micro-nano composite structure using a facile atomization-assisted nonsolvent induced phase separation method. Frontiers of Chemical Science and Engineering 2022.
84.Song, W. L.; Li, Z. P.; Li, Y. Z.; You, H.; Qi, P. S.; Liu, F.; Loy, D. A., Facile sol-gel coating process for anti-biofouling modification of poly (vinylidene fluoride) microfiltration membrane based on novel zwitterionic organosilica. Journal of Membrane Science 2018, 550, 266-277.
85.Kuo, C. Y.; Lin, H. N.; Tsai, H. A.; Wang, D. M.; Lai, J. Y., Fabrication of a high hydrophobic PVDF membrane via nonsolvent induced phase separation. Desalination 2008, 233 (1-3), 40-47.
86.Venault, A.; Chin, Y.-T.; Maggay, I.; Yeh, C.-C.; Chang, Y., Poly(vinylidene fluoride)/poly(styrene-co-acrylic acid) nanofibers as potential materials for blood separation. Journal of Membrane Science 2022, 641, 119881.
87.Juang, R. S.; Lin, K. H., Flux recovery in the ultrafiltration of suspended solutions with ultrasound. Journal of Membrane Science 2004, 243 (1-2), 115-124.
88.Kim, J. O.; Somiya, I., Effective combination of microfiltration and intermittent ozonation for high permeation flux and VFAs recovery from coagulated raw sludge. Environ. Technol. 2001, 22 (1), 7-15.
89.Song, L. X.; Lam, Y. M., Nanopattern formation using a chemically modified PS-P4VP diblock copolymer. Nanotechnology 2007, 18 (7), 6.
90.Venault, A.; Hsu, C. H.; Ishihara, K.; Chang, Y., Zwitterionic bi-continuous membranes from a phosphobetaine copolymer/poly(vinylidene fluoride) blend via VIPS for biofouling mitigation. Journal of Membrane Science 2018, 550, 377-388.
91.Bormashenko, E., Progress in understanding wetting transitions on rough surfaces. Adv. Colloid Interface Sci. 2015, 222, 92-103.
92.O'Hanley, H.; Coyle, C.; Buongiorno, J.; McKrell, T.; Hu, L. W.; Rubner, M.; Cohen, R., Separate effects of surface roughness, wettability, and porosity on the boiling critical heat flux. Appl. Phys. Lett. 2013, 103 (2), 5.
93.Rupp, F.; Liang, L.; Geis-Gerstorfer, J.; Scheideler, L.; Huttig, F., Surface characteristics of dental implants: A review. Dent. Mater. 2018, 34 (1), 40-57.
94.Wang, D. H.; Sun, Q. Q.; Hokkanen, M. J.; Zhang, C. L.; Lin, F. Y.; Liu, Q.; Zhu, S. P.; Zhou, T. F.; Chang, Q.; He, B.; Zhou, Q.; Chen, L. Q.; Wang, Z. K.; Ras, R. H. A.; Deng, X., Design of robust superhydrophobic surfaces. Nature 2020, 582 (7810), 55-+.
95.Ismail, N. H.; Salleh, W. N. W.; Ismail, A. F.; Hasbullah, H.; Yusof, N.; Aziz, F.; Jaafar, J., Hydrophilic polymer-based membrane for oily wastewater treatment: A review. Sep. Purif. Technol. 2020, 233, 18.
96.Rahimpour, A.; Madaeni, S. S.; Jahanshahi, M.; Mansourpanah, Y.; Mortazavian, N., Development of high performance nano-porous polyethersulfone ultrafiltration membranes with hydrophilic surface and superior antifouling properties. Appl. Surf. Sci. 2009, 255 (22), 9166-9173.
97.Tripathi, B. P.; Dubey, N. C.; Choudhury, S.; Simon, F.; Stamm, M., Antifouling and antibiofouling pH responsive block copolymer based membranes by selective surface modification. J. Mat. Chem. B 2013, 1 (27), 3397-3409.
98.Chang, Y.; Ko, C. Y.; Shih, Y. J.; Quemener, D.; Deratani, A.; Wei, T. C.; Wang, D. M.; Lai, J. Y., Surface grafting control of PEGylated poly(vinylidene fluoride) antifouling membrane via surface-initiated radical graft copolymerization. Journal of Membrane Science 2009, 345 (1-2), 160-169.
99.Chiu, C.-Y.; Yen, T.-J.; Chang, Y., Intelligent sterilizable self-cleaning membranes triggered by sustainable counterion-induced bacteria killing/releasing procedure. Chemical Engineering Journal 2022, 440, 135798.
100.Lien, C.-C.; Chen, P.-J.; Venault, A.; Tang, S.-H.; Fu, Y.; Dizon, G. V.; Aimar, P.; Chang, Y., A zwitterionic interpenetrating network for improving the blood compatibility of polypropylene membranes applied to leukodepletion. Journal of Membrane Science 2019, 584, 148-160.
101.Beard, B. C.; Hare, J., Surface interaction of quaternary amines with hair. J. Surfactants Deterg. 2002, 5 (2), 145-150.
102.Shafi, H. Z.; Wang, M.; Gleason, K. K.; Khan, Z., Synthesis of surface-anchored stable zwitterionic films for inhibition of biofouling. Mater. Chem. Phys. 2020, 239, 12.
103.Machado, P. S. T.; Habert, A. C.; Borges, C. P., Membrane formation mechanism based on precipitation kinetics and membrane morphology: flat and hollow fiber polysulfone membranes. Journal of Membrane Science 1999, 155 (2), 171-183.
104.Lin, D. J.; Beltsios, K.; Young, T. H.; Jeng, Y. S.; Cheng, L. P., Strong effect of precursor preparation on the morphology of semicrystalline phase inversion poly(vinylidene fluoride) membranes. Journal of Membrane Science 2006, 274 (1-2), 64-72.
105.Li, C. L.; Wang, D. M.; Deratani, A.; Quemener, D.; Bouyer, D.; Lai, J. Y., Insight into the preparation of poly(vinylidene fluoride) membranes by vapor-induced phase separation. Journal of Membrane Science 2010, 361 (1-2), 154-166.
106.Tsai, H. A.; Ruaan, R. C.; Wang, D. M.; Lai, J. Y., Effect of temperature and span series surfactant on the structure of polysulfone membranes. J. Appl. Polym. Sci. 2002, 86 (1), 166-173.
107.Zhao, S.; Wang, Z.; Wei, X.; Tian, X. X.; Wang, J. X.; Yang, S. B.; Wang, S. C., Comparison study of the effect of PVP and PANI nanofibers additives on membrane formation mechanism, structure and performance. Journal of Membrane Science 2011, 385 (1-2), 110-122.
108.Djadoun, S.; Karasz, F. E.; Hamou, A. S. H., Blends of poly(isobutyl methacrylate) with poly(styrene-co-acrylic acid) and of poly(isobutyl methacrylate-co-acrylic acid) with poly(styrene-co-N,N-dimethyl aminoethyl methacrylate). Thermochim. Acta 1996, 283, 399-410.
109.Wang, X. Y.; Zhang, L.; Sun, D. H.; An, Q. F.; Chen, H. L., Formation mechanism and crystallization of poly(vinylidene fluoride) membrane via immersion precipitation method. Desalination 2009, 236 (1-3), 170-178.
110.Lin, Y. C.; Chao, C. M.; Wang, D. K.; Liu, K. M.; Tseng, H. H., Enhancing the antifouling properties of a PVDF membrane for protein separation by grafting branch-like zwitterions via a novel amphiphilic SMA-HEA linker. Journal of Membrane Science 2021, 624, 13.