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研究生: 陳英傑
Chen, Ying-Chieh
論文名稱: 應用微流體晶片同時生成不同濃度褐藻酸鈣微膠囊之研究
Simultaneous Generation of Ca-alginate Microcapsules with Different Concentrations in a Microfluidic Chip
指導教授: 林裕城
Lin, Yu-Cheng
學位類別: 碩士
Master
系所名稱: 工學院 - 工程科學系
Department of Engineering Science
論文出版年: 2010
畢業學年度: 99
語文別: 中文
論文頁數: 112
中文關鍵詞: 微機電系統微流體晶片均一粒徑褐藻酸鈣微膠囊牛血清蛋白
外文關鍵詞: MEMS, Microfluidic chip, Uniform size, Ca-alginate, Microcapsules, BSA
相關次數: 點閱:162下載:3
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  • 本研究利用微機電系統製程技術之灌注成形法,完成聚二甲基矽氧烷(Polydimethylsiloxane, PDMS)微流體晶片之製備,以應用於同時生成四種不同濃度且均一粒徑的微膠囊之研究。研究策略為利用計算流體力學軟體來模擬微流道晶片內四個微流管道的流速分佈情形,並改變樹狀分流管道寬度設計,以達到微流體晶片於後端產生四管一樣的流速分佈,並藉由微機電製程技術製作實驗所需的微流體晶片。實驗上,在微流體晶片前端分別注入台盼藍水溶液和去離子水,利用微混合器與樹狀分流的設計,均勻混合出四種不同的濃度,並在微流體晶片後端利用鞘流原理來產出四管均一粒徑且具有不同濃度的微乳化球,粒徑分佈範圍介於50.8 ~ 100.5 m之間。之後,將此微流體晶片應用於生成均一粒徑且包覆不同牛血清蛋白(Bovine serum albumin, BSA)濃度之褐藻酸鈣(Ca-alginate)微膠囊的生成上,實驗結果在粒徑分佈範圍可介於59.9 ~ 105.2 m之間。將微流體晶片所生成四種不同BSA濃度的微膠囊置於磷酸鹽緩衝溶液中進行BSA釋放,在經過長時間的紫外光-可見光吸收光譜儀量測,發現此微流體晶片所生成的Ca-alginate,可成功釋放出具有不同濃度分佈的BSA,證明本研究所設計的微流體晶片可應用於同時生成均一粒徑且不同濃度的微膠囊。

    In this study, the polydimethylsilcoxane (PDMS) microfluidic chip is fabricated by using MEMS, casting molding, and microimprinting technology. The chip is used to study microcapsules of different concentrations. Our strategy is to simulate the velocity distribution of fluids in different microfluidic channels by using computational fluid dynamic (CFD) software. The results of simulation give us insight on how to design the wide of bifurcate channels and fabricate the microfludic chip by MEMS. The solution is mixed by using the microfluidic network, and via the sheath focusing effect to form uniform water-in-oil (w/o) emulsions with different concentrations. We demonstrate that the size of emulsions can be controlled from 50.8 µm to 100.5 µm in diameter, simply by altering the relative continuous/dispersed phase flow rate ratio. However, the manipulation of Ca-alginate microcapsules, using a microfluidic chip, for the encapsulation of Bovine serum albumin (BSA) with different concentrations is by external gelation methods. The size can be controlled from 59.9 µm to 105.2 µm in diameter, and then the microcapsules are placed in the phosphate buffer saline (PBS) for drug release. Through the UV-Vis spetrophotometry at 280 nm, we demonstrate that the different concentrations of BSA are encapsulated in the microcapsules.

    摘要 I ABSTRACT III 致謝 V 目錄 VI 圖目錄 IX 表目錄 XIV 第一章 緒論 1 1-1 前言 1 1-2 藥物控制與釋放的重要性 3 1-3 藥物載體褐藻酸鈉之介紹 6 1-4 微流體晶片的發展與應用 9 1-4-1 微機電系統技術與微流體晶片 9 1-4-2 微流體晶片之製程技術 11 1-4-3 微流體晶片之應用 14 1-5 研究動機與目的 20 1-6 研究架構 21 第二章 微流體晶片之設計與製作 23 2-1 微流體數值模擬 23 2-1-1 模型及網格建立 24 2-1-2 模擬環境設定與介紹 27 2-2 光罩設計與母模製作 29 2-2-1 光罩設計 29 2-2-2 母模製作 31 2-3 PDMS灌注成形技術及翻製流程 39 2-3-1 晶片接合與組裝技術 44 第三章 實驗與研究方法 47 3-1 實驗儀器與設備 47 3-1-1倒立式螢光光學顯微鏡 47 3-1-2 微量注射幫浦 48 3-1-3 真空抽氣系統 49 3-1-4 表面粗度儀 49 3-1-5 場放射-掃描式電子顯微鏡 50 3-1-6 紫外光-可見光吸收光譜儀 51 3-2 實驗藥品與配置方法 53 3-2-1 實驗藥品 53 3-2-2 藥品配置 53 3-3 實驗方法 55 3-3-1 生成不同濃度之W/O乳化球實驗 55 3-3-2 不同濃度之褐藻酸鈣微膠囊實驗 57 3-3-3 牛血清蛋白釋放實驗 60 第四章 結果與討論 61 4-1-1 相同分流管道寬度設計之實驗分析 61 4-1-2 模擬結果分析 62 4-2 微流體晶片製程 75 4-3 生成不同濃度之W/O乳化球實驗結果 77 4-3-1 各管道濃度分佈之探討 77 4-3-2 不同濃度乳化球之粒徑分析 81 4-4 不同濃度牛血清蛋白褐藻酸鈉乳化球之粒徑分析 87 4-5 BSA濃度釋放之分析 94 第五章 結論與建議 98 5.1 結論 98 5.2 建議 101 參考文獻 102 自述 112

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