王大銘臺灣大學：化學工程學研究所蕭嘉賢Shiau, Jia-ShyanJia-ShyanShiau2007-11-262018-06-282007-11-262018-06-282004http://ntur.lib.ntu.edu.tw//handle/246246/52369蛋白質微過濾程序中的過濾阻力成長，與蛋白質聚集體在膜面發生的堵塞、堆積及壓縮等現象有十分密切關聯性。本研究發展出結合粒子堵塞與濾餅過濾的理論模式，藉以探討蛋白質溶液在不同操作型式與條件下之過濾阻力成長。此外，也引入濾餅壓縮模式，來探討在蛋白質聚集體會被壓縮的情況下，過濾阻力成長的過程。 研究中基於濾液總流率為流體流經膜面上堵塞區與未堵塞區之和的概念，發展出可描述由膜孔堵塞至濾餅堆積過程的dead-end恆壓與恆率微過濾理論模式；然後也配合由粒子在膜面上所受水平力與垂直力平衡的概念所推衍而得之粒子附著機率模式，發展出適用於掃流(cross-flow)恆壓微過濾之理論模式。此外，在考慮蛋白質聚集體會被壓縮的情況下，本研究也在粒子堵塞與堆積之結合模式中加入濾餅壓縮模式，來探討濾餅壓縮對過濾阻力成長的影響。 為了證明所發展理論模式之適用性，研究中亦進行實驗，與理論模式作比較。本研究在不同過濾方式及不同操作條件下，進行蛋白質過濾實驗，量測過濾阻力隨時間之變化。由理論模式與實驗數據的比較發現，無論恆壓或是恆率微過濾，理論模式與實驗結果均十分吻合。也發現可用完全堵塞與濾餅過濾之結合模式來描述直孔型態濾膜的阻力成長，但必須用中間堵塞與濾餅過濾機制之結合模式來描述網狀型態濾膜的阻力成長。 此外也發現理論模式所調整的參數(孔洞堵塞參數β)，在初始阻力成長方面：網狀膜(β=1500∼2400 m2/kg)大於直孔膜(β=600 m2/kg)；疏水膜(β=2400 m2/kg)大於親水膜(β=1700 m2/kg)，參數所表示之物理意義十分符合實驗所觀察到的結果。因此顯示膜材的結構與親疏水性，會影響初期的堵塞機制及後續的過濾行為。The growth of filtration resistance during protein microfiltration is strongly related to the associated phenomena of pore blocking, particle deposition and cake compression, caused by the protein aggregates deposited on membrane surface. Models combining pore blocking and cake filtration were developed to describe the growth of filtration resistance during protein microfiltration under different operation conditions. In addition, a model of cake compression was introduced to take into account the effect of the compressibility of protein aggregates. Theoretical models, combining pore blocking and cake filtration, were derived for constant-pressure and constant-rate dead-end microfiltrations to provide a smooth transition from the pore blockage to cake formation regimes based on the concepts that the total flow rate is the sum of the flow rates through the open and blocked pores. Moreover, the probability of particle adhesion, which can be obtained from estimations of the forces on particles along the flow and permeation directions, was introduced into the combined models of pore blocking and cake filtration to take into account the effect of particle sweep due to cross flow for constant-pressure and constant-rate cross-flow microfiltrations. When the effect of the compressibility of protein aggregates is not negligible, a cake compression model was incorporated to make the combined models complete. In order to verify the applicability of the developed models, experiments of BSA microfiltration were performed. The obtained data were in good agreement with the combined models for all the studied cases. It was also found that the combined model of complete pore blockage and cake filtration, was suitable for describing the resistance growth for membranes with straight-through pore. On the other hand, for membranes with interconnected structure, the combined model of intermediate pore blockage and cake filtration is more adequate. The physical meanings of the model parameters were examined and the results indicate that the membrane structure and hydrophilicity have strong effect on the initial blocking mechanism and the following filtration behavior. For initial resistance growth, the comparison of pore blocking parameters was listed as follow that the interconnected membranes (β=1500∼2400 m2/kg) were larger than straight-through membrane (β=600 m2/kg) while the hydrophobic membrane (β=2400 m2/kg) was higher than hydrophilic membrane (β=1700 m2/kg).中文摘要 …………………………………………………………. I 英文摘要 …………………………………………………………. Ⅲ 目 錄 …………………………………………………………. V 圖 目 錄 …………………………………………………………. IX 表 目 錄 …………………………………………………………. XV 第一章 緒論……………………………………………………... 1 1-1 薄膜過濾程序……………………………………….. 1 1-2 微過濾程序之應用………………………………….. 2 1-3 薄膜結垢…………………………………………….. 3 1-4 dead-end過濾與掃流過濾操作…………………….. 5 1-5 研究動機與目的…………………………………….. 7 1-6 論文內容…………………………………………….. 8 第二章 文獻回顧………………………………………………... 11 2-1 蛋白質吸附………………………………………….. 11 2-2 蛋白質沉積………………………………………….. 15 2-2-1 結垢機制……………………………………….. 16 2-2-2 操作變數對結垢行為的影響………………….. 19 2-3 蛋白質聚集與結垢關係…………………………….. 22 2-3-1 自身聚集反應………………………………….. 22 2-3-2 操作環境的影響……………………………….. 25 2-4 濾膜結構與結垢之關係…………………………….. 31 2-5 蛋白質掃流過濾…………………………………….. 34 2-6 基本過濾理論……………………………………….. 37 2-6-1 固體壓縮壓力………………………………….. 38 2-6-2 Kozeny 方程式………………………………… 38 2-6-3 Darcy 定律……………………………………... 40 2-6-4 傳統的過濾方程式…………………………….. 40 2-7 濾速衰退之理論模式……………………………….. 42 2-7-1 完全阻塞模式………………………………….. 42 2-7-2 中間阻塞模式………………………………….. 44 2-7-3 標準阻塞模式………………………………….. 45 2-7-4 濾餅過濾模式………………………………….. 46 2-7-5 其他結垢模式………………………………….. 47 2-8 結合膜孔堵塞與濾餅過濾之理論模式…………….. 49 第三章 蛋白質微過濾之阻力成長理論模式…………………... 51 3-1 dead-end恆壓過濾…………………………….…….. 52 3-2 掃流恆壓過濾……………………………………….. 59 3-3 dead-end恆率過濾…………………………….…….. 69 第四章 實驗方法………………………………………………... 73 4-1 實驗材料…………………………………………….. 73 4-2 實驗儀器…………………………………………….. 75 4-3 dead-end恆壓過濾實驗裝置與步驟………………... 77 4-3-1 dead-end恆壓過濾裝置………………………... 77 4-3-2 dead-end恆壓過濾實驗步驟…………………... 78 4-3-3 蛋白質濾餅層厚度之同步量測……………….. 79 4-4 dead-end恆率過濾實驗裝置與步驟………………... 82 4-4-1 dead-end恆率過濾裝置………………………... 82 4-4-2 dead-end恆率過濾實驗步驟…………………... 83 4-5 掃流恆壓過濾實驗裝置與步驟…………………….. 84 4-5-1 掃流恆壓過濾裝置…………………………….. 84 4-5-2 掃流恆壓過濾實驗步驟……………………….. 85 4-6 CF4/C2H2電漿處理方式…………………………….. 85 4-7 以掃描式電子顯微鏡分析濾膜表面結垢現象…….. 87 4-8 以光散射與光繞射之雷射粒徑分析儀分析蛋白質溶液之粒徑分佈…………………………………….. 88 4-8-1 光散射分析…………………………………….. 88 4-8-2 光繞射分析…………………………………….. 89 4-9 實驗數據分析……………………………………….. 90 4-9-1 掃流過濾中濾餅平均過濾比阻之求法……….. 90 4-9-2 結垢機制判定………………………………….. 90 4-9-3 以實驗方式決定蛋白質溶液中聚集體的比率.. 91 4-9-4 結垢層壓縮性之分析………………………….. 92 第五章 蛋白質dead-end微過濾之阻力成長…………………… 93 5-1en-US濾餅過濾膜孔堵塞阻力成長微過濾蛋白質Pore BlockingCake FiltrationResistance GrowthProteinMicrofiltrationthesis