以蒸氣誘導相分離技術製備含甲基丙烯酸聚乙二醇酯之聚氟化乙二烯薄膜與其低生物結垢性及生物相容性之探討

In-situ Modification of PVDF Membrane Prepared by VIPS Process Using PS-b-PEGMA Copolymer, for Biofouling Resistance and Improved Hemocompatibility

吳佳儒(Jia-Ru Wu)

指導教授 ： 張雍 ； 費安東

中原大學/工學院/化學工程研究所/碩士(2014年)

https://doi.org/10.6840/cycu201400597

摘要

薄膜已被廣泛應用於各個領域當中，基於其材料特性及膜孔大小而應用於不同範圍，其中以微過濾膜(0.1 μm-10μm)之應用最為廣泛，微過濾膜可用於微生物及懸浮顆粒之過濾分離，常見應用有廢水處理、血液透析…等。微過濾膜也普遍應用於RO逆滲透前處理系統，以微過濾膜做為前處理之逆滲透系統可增加RO薄膜分離效能及使用壽命，而以壓力為驅動力之過濾系統而言，機械強度為首要需求，因此擁有良好耐熱性、抗化學腐蝕性、生物相容性及高度機械強度之聚氟化乙二烯高分子為首要製膜考量，然而，其低表面能特性使之置放於生物環境時易與微生物產生生物分子沾黏，生物分子沾黏行為常會於薄膜的內外部產生，長久下來易造成生物分子聚集而使薄膜孔洞堵塞，導致薄膜過濾及分離效能下降，而文獻指出若表面具有高親水性，即可於表面形成水層，進而有效抵抗生物分子沾黏。為此含有甲基丙烯酸聚乙二醇酯之結構為表面改質親水化之良好選擇，因此本研究以苯乙烯（styrene）以及聚(乙二醇)甲醚甲基丙烯酸酯（poly(ethylene glycol) methyl ether methacrylate, PEGMA）進行原子轉移自由基聚合反應，合成聚苯乙烯及聚(乙二醇)甲醚甲基丙烯酸酯之雙嵌段共聚高分子（Polystyrene60-block-PEGMA108, PS60-b-PEGMA108），藉由混摻方式製備PVDF/ PS60-b-PEGMA108/ NMP鑄膜液及利用蒸氣誘導相分離程序製備微過濾膜。
薄膜製備完成後首先對於添加共聚高分子之薄膜進行物性及化性方面檢測，再以微米及奈米等級之生物分子對於親水化之薄膜抗沾黏程度進行觀察，最後測量其血液相容性及血球貼附情形。由實驗結果發現，隨著共聚高分子的添加量提高，薄膜內部結構由球狀結構轉為雙連續結構，此結構上之改變證明相轉換過程中結晶凝膠化與非結晶凝膠化(crystallization-gelling vs. non-crystallization gelling)為成膜結構之主導因素，其結晶構形經由PVDF內部存在之結晶物改變(β-polymorph vs. α-polymorph)來決定高分子結晶排列情形進而影響最終膜結構分布。此外，經由平均孔徑分布測試發現改質後薄膜之平均孔徑由0.197 µm 轉為 0.102 µm，但其孔隙度分布依然能維持在70 %。隨著添加共聚高分子成分增加，其成膜後之整體機械強度有增強的效果，而膜材整體水和能力有明顯的提升。
由以上薄膜特性分析得知，藉由共聚高分子的添加能有效於原位修飾疏水PVDF膜材，同時達到機械強度增強及薄膜親水化效果。
生物檢測以微米及以及奈米級生物分子進行檢測，分別進行蛋白質吸附測試、細菌貼附測試，血球貼附測試以及血液相容性測試，蛋白質吸附測試方面以牛血清白蛋白，溶菌酶，纖維蛋白原，人血清白蛋白及球蛋白進行檢測，由實驗結果得知改質後膜材能有效抵抗以上非特定蛋白質吸附，儘管原位修飾過後共聚高分子均勻突出於界面使表面仍具有一定粗糙度，但在此相對粗糙的膜面下，其親水化效果卻依然能提供極佳抗蛋白吸附性質，於大型生物分子貼附測試亦可發現相同結果，改質後薄膜能有效抑制非特定細菌貼附。以上測試皆指出改質薄膜能具有良好抗生物分子沾黏之特性，最後進行血液貼附測試及血液相容性測試，於血液貼附測試發現，改質薄膜於紅血球、白血球、血小板及全血中都有具有良好的抵抗結果。此外，含有重量百分比5 wt% 共聚物添加之膜材相較於原始PVDF薄膜具有極低溶血特性（1％）及延遲血漿凝固時間之效果，以上實驗結果指出改質薄膜具有良好血液相容性質。總體而言，本研究成功利用原位修飾蒸氣誘導相分離法有效製備出低生物沾黏及良好血液相容性之PVDF薄膜。

關鍵字

生物相容性 ； 成膜機制 ； 抗生物結垢 ； 甲基丙烯酸聚乙二醇酯之聚氟化乙二烯薄膜 ； 蒸氣誘導相分離

並列摘要

Biofouling by proteins, contamination by micro-organisms and lack of knowledge on their hemocompatibility limit the use of PVDF membranes in biomedical applications. As these membranes offer excellent bulk properties, we investigated their facile in-situ modification by a PEGylated copolymer (PS60-b-PEGMA108). Membranes were formed by vapor-induced phase separation. Efforts were first oriented toward the characterization of the effect of copolymer on membrane formation, membranes surface chemistry and membranes physical properties. Then, biofouling at nano-scale and micro-scale were investigated, before moving onto the hemocompatibility of membranes. Membranes structure evolved from nodular to bi-continuous with PS60-b-PEGMA108 content, evidencing a change of dominating phenomena during phase inversion (crystallization-gelling vs. non-crystallization gelling), supported by a change of prevailing crystalline polymorph (β-polymorph vs. α-polymorph). Further, mean pore flow diameter was slightly decreased (0.20 µm to 0.10 µm), while porosity remained about constant (70%) and stiffness of matrices was improved with copolymer content. Hydration of membranes was importantly enhanced, severely affecting nano-biofouling: bovine serum albumin, lysozyme, fibrinogen, Human Serum Albumin, γ-globulin adsorption were drastically reduced, despite rough surfaces, highlighting the efficiency of the copolymer and that of the in-situ modification process. Bacterial attachment tests revealed that macro-biofouling was inhibited. Results of erythrocytes, leukocytes, and thrombocytes adhesion indicated that membranes prepared from a casting solution containing 5 wt% of copolymer are highly hemocompatible, result supported by low hemolysis (1%) ratio and delay of plasma clotting time compared with virgin membrane. Overall, this study unveils that in-situ modification coupled to the VIPS method can be efficient to readily prepare hemocompatible PVDF membranes.

並列關鍵字

PEGylated PVDF membrane ； hemocompatibility ； formation mechanisms ； VIPS process ； antibiofouling

參考文獻

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