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研究生： 江咸徹
XIAN-CHE JIANG
論文名稱： 氧化石墨烯奈米帶/導電高分子奈米複合纖維膜於親蛋白尿毒素移除之應用研究
Graphene Oxide Nanoribbons/Conductive Polymer Composite Nanofiber Membranes for Efficient Removal of Protein-bound Uremic Toxin Applications
指導教授： 蕭育生
Yu-Sheng Hsiao
口試委員: 楊銘乾
Ming-Chien Yang
孫嘉良
Chia-Liang Sun
洪維松
Wei-Song Hung
學位類別： 碩士
Master
系所名稱： 工程學院 - 材料科學與工程系
Department of Materials Science and Engineering
論文出版年： 2022
畢業學年度： 110
語文別： 中文
論文頁數： 100
中文關鍵詞： 生物電子界面 、蛋白結合尿毒症毒素 、聚(3,4-乙烯二氧噻吩)：聚(苯乙烯磺酸鹽) 、氧化石墨烯奈米帶 、多壁奈米碳管 、血液透析
外文關鍵詞： bioelectronic interface, protein bound uremic toxic, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate), graphene oxide nanoribbon, multiwalled carbon nanotubes, hemodialysis
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    • 蛋白結合尿毒症毒素(protein bound uremic toxic, PBUTs)具有很強的蛋白質結合力，所以它很難經由標準血液透析(hemodialysis, HD)治療中去除，而PBUT長期在人身體中是非常有害的。此研究中我們首先以微波輔助合成方式通過不同微波功率(50、100、150、200和250W)對多壁碳奈米管(multiwalled carbon nanotubes, MWCNT)進行部分解鏈合成氧化石墨烯奈米帶(graphene oxide nanoribbon, GONR)。然後，搭配靜電紡絲製造工藝製備導電奈米複合纖維，將GONR、聚(3,4-乙烯二氧噻吩)：聚(苯乙烯磺酸鹽)(PEDOT：PSS)、(聚環氧乙烷)(PEO)和(3-環氧丙氧丙基)三甲氧基矽烷(GOPS)的四元混成材料均勻沉積在聚醚碸(PES)透析膜上作為移除(PBUT)應用。因為此導電奈米纖維具有以下特性:包括(i)其中GONR及PEDOT:PSS可提供優異電化學性能；(ii)其中GOPS作為交聯輔助劑及接著劑以表現極佳水相操作穩定性；(iii)優秀的細胞存活率和極低的紅血球溶血率。最後，我們將此導電透析膜作為一種生物電子界面(bioelectronic interface, BEI)以組裝成新型HD裝置，用於研究對三種PBUT[如:對甲酚(PC)、馬尿酸(HA)和硫酸吲哚酚(IS)及一種小分子尿毒素肌酐(CRT)]的去除能力。並探索電刺激效應對移除蛋白質與PBUT鍵結之效能與可行性。

    Protein bound uremic toxins (PBUTs) would cause noxious effects on the patients suffering from renal failure, which were difficult to be removed by the standard hemodialysis (HD) treatment due to their strong protein binding affinity. Herein we reported a microwave-assisted synthesis of graphene oxide nanoribbons (GONRs) by partial unzipping of multiwall carbon nanotubes (MWCNTs) under different microwaves powers (50, 100, 150, 200 and 250 W). Then, the electrospinning fabrication process of electrically conductive quaternary composite nanofibers, included the synthesized GONRs, poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS), poly(ethylene oxide) (PEO), and (3-glycidyloxypropyl) trimethoxysilane (GOPS) materials, was explored to deposit on the polyethersulfone (PES) dialysis membranes as the bioelectronics interface (BEI) platform for effective removal of PBUTs via the electrically triggered dissociation process of protein‒toxin binding, as well as PBUT adsorption process. This composite nanofibers platform possessed (i) GONR and PEDOT:PSS can provide excellent electrochemical performance; (ii) high adhesion strength on the PES membrane due to the GOPS as an adhesion promoter; (iii) good cell viability and negligible hemolysis to red blood cells. Finally, this organic BEI electronic system was demonstrated as the novel single membrane HD device to study the removal efficiency of four kinds of uremic toxins [p-cresol (PC), hippuric acid (HA), and indoxyl sulfate (IS); creatinine (CRT)], as well as the protein binding PC and IS removal efficiency under the electrical stimulation operation.

    第一章、緒論 1 1.1 社會現況 1 1.2 生物電子晶片 2 1.3 腎臟衰竭之治療方式 3 1.3.1 腎臟移植 3 1.3.2 血液透析 5 1.3.3 血液灌流 6 1.3.4 腹膜透析 7 1.4 尿毒素(Uremic toxins) 8 1.4.1 普遍親蛋白尿毒素移除方法 9 第二章、文獻探討 12 2.1 導電高分子 12 2.2 奈米碳管 13 2.3 氧化石墨烯奈米帶合成與特性 14 2.3.1 氧化石墨烯奈米帶吸附有機化合物機理 16 2.4 靜電紡絲技術 17 2.4.1 靜電紡絲製程機理 18 2.4.2 靜電紡絲參數影響 19 2.4.3 靜電紡絲應用領域 20 2.5 靜電紡絲技術於去除尿毒素應用 21 2.6 電化學用於控制蛋白質構型 22 2.7 研究動機與目的 24 第三章、實驗流程與方法 25 3.1 實驗流程 25 3.2 實驗藥品 26 3.3 實驗儀器 27 3.4 GONR合成與製備 28 3.5 GONR物化性測試 29 3.5.1 GONR TEM表面形貌 29 3.5.2 GONR拉曼光譜 29 3.5.3 GONR XPS紫外線電子表面元素光譜 30 3.6 GONR電性分析 30 3.6.1 GONR 電化學特性分析 31 3.6.2 GONR之質量擴散係數量測 32 3.6.2.1 離子擴散係數氧化還原指示劑製備 32 3.6.3 GONR之EIS電子阻抗量測 32 3.7 靜電紡絲製備與製程 33 3.7.1 靜電紡絲溶液製備 33 3.8 靜電紡絲物化性測試 37 3.8.1 紡絲表面形貌之TEM,FE-SEM分析 37 3.8.2 紡絲之拉曼光譜分析 37 3.8.3 紡絲之XPS紫外線電子光譜分析 38 3.9 靜電紡絲之電性測試 38 3.9.1 電容密度 38 3.9.2 基礎電性(四點探針與指叉式電極) 39 3.9.3 質量擴散係數 39 3.9.4 CV耐受度測試 39 3.10 紡絲生物相容性與對水穩定度 39 3.10.1 溶血分析 40 3.10.1.1 紅血球分散液製備 40 3.10.1.2 溶血測試步驟 40 3.10.2 凝血時間測試 41 3.10.3 細胞存活率 42 3.10.3.1 MTT Assay 42 3.10.3.2 Live/Dead assay 44 3.10.4 固體材料的表面電位分析 45 3.10.5 水相穩定性測試 45 3.10.6 水接觸角 45 3.11 HD生物電子元件的電極製備 46 3.11.1 熱蒸鍍製程 46 3.11.2 銀/氯化銀(Ag/AgCl)電極製備 48 3.12 透析實驗 48 3.12.1 透析溶液配製 49 3.12.1.1 磷酸鹽緩衝液 (Phosphate buffered saline, PBS) 49 3.12.1.2 尿毒素溶液 49 3.12.1.3 蛋白結合親蛋白尿毒素溶液 50 3.12.2 無蛋白尿毒素透析實驗 51 3.12.3 PSS影響蛋白質結合率實驗 51 3.12.4 電刺激蛋白結合之親蛋白尿毒素實驗 52 3.13 電刺激蛋白結合尿毒素串聯實驗 54 3.14 透析濃度分析 56 3.14.1 蛋白質定量分析 57 第四章、結果與討論 59 4.1 GONR之物化性分析 59 4.1.1 GONR拉曼光譜分析 59 4.1.2 表面形貌之TEM影像分析 60 4.1.3 表面元素之XPS光譜分析 61 4.2 GONR 電化學分析 63 4.2.1 CV 特徵峰譜掃描 63 4.2.2 EIS 電子阻抗測試 64 4.2.3 GONR 質量擴散係數 66 4.3 GONR測試總結 68 4.4 紡絲物化性分析 69 4.4.1 紡絲拉曼光譜分析 69 4.4.2 紡絲表面形貌分析 71 4.4.3 紡絲XPS表面元素分析 72 4.4.4 TGA 熱重分析結果 73 4.5 紡絲電分析 74 4.5.1 紡絲電容密度 74 4.5.2 紡絲質量擴散係數 76 4.5.3 紡絲電性量測 77 4.5.4 紡絲電耐久測試 78 4.6 生物相容性與水穩定性測試 79 4.6.1 溶血分析 79 4.6.2 凝血時間 79 4.6.3 細胞存活率分析 80 4.6.3.1 MTT assay測試結果 80 4.6.3.2 Live/Dead 結果 81 4.6.4 固態材料表面電位分析 83 4.6.5 水接觸角量測 84 4.6.6 水相穩定性結果 84 4.7 透析結果分析 86 4.7.1 尿毒素移除效率探討 86 4.7.2 尿毒素清除率數值校正 87 4.7.3 PSS影響蛋白質結合率結果 88 4.7.4 電刺激效應於親蛋白尿毒素移除之研究 89 4.7.5 串聯式元件電刺激比較 93 第五章、結論 95 參考文獻 96

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