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作者(中文):游士弘
作者(外文):You, Shih-Hong
論文名稱(中文):整合奈米磁珠之微液滴操控平台 及其應用於細胞封裝
論文名稱(外文):Droplet-Based Microfluidic Platforms with Magnetic Beads for Encapsulation of Cells
指導教授(中文):洪健中
指導教授(外文):Hong, Chien-Chong
口試委員(中文):朱一民
黃效民
學位類別:碩士
校院名稱:國立清華大學
系所名稱:動力機械工程學系
學號:101033612
出版年(民國):103
畢業學年度:102
語文別:中文
論文頁數:146
中文關鍵詞:微液滴形成微液滴切割磁珠293T細胞兔子軟骨細胞
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本論文研究為發展微液滴操作平台,並達成微液滴操作與應用,內容主要可以分為四個部分,第一部分為微液滴晶片之設計、模擬與分析;第二部分是微液滴形成晶片製作與封裝,並完成整體微液滴操控平台系統架設;第三個部分進行微液滴形成的參數探討,包括微流道寬度、絕對微流量、兩相微流量比率以及表面活性濃度;最後第四個部分則是微液滴操作與應用。
在微液滴晶片設計上,以CFD-ACE套裝模擬軟體模擬與分析流量與微液滴形成位置與時間之關係。在微液滴實驗方面,使用微影製程製作微液滴晶片,並以真空氧電漿進行微晶片之黏合封裝,並以外接幫浦與攝影機進行微流體驅動及微液滴觀測。本論文針對微液滴形成進行相關參數探討,由結果得知在兩相等流量下,在絕對微流量50-600 μL/hr範圍內皆能穩定產生微液滴,而在此範圍內所產生微液滴之大小、速度及位置與絕對微流量有線性關係;另外,在固定乳化相微流量為100 μL/hr而連續相微流量為100-600 μL/hr下,微液滴皆能穩定產生,所產生之微液滴大小、速度及位置也與連續相微流量有線性關係;最後探討表面活性劑之影響,由結果發現7% Krytox 157 FSL添加於連續相中之微液滴穩定度效果最佳。本研究並設計不同微流道晶片對微液滴進行等份切割與不等份切割,不等份切割分為5個不同大小液滴輸出,可形成平均大小0.84 nL、0.37 nL、0.35 nL、0.37 nL及0.11 nL之微液滴。最後應用所設計之等份切割之微液滴晶片於磁珠與293T細胞之封裝,可於單一微液滴內封裝至最低只含2個293T細胞;使用不等份切割微液滴晶片於玻璃微珠及兔子軟骨細胞之封裝,可於單一微液滴內封裝至最低只含3個兔子軟骨細胞。
本論文所開發之微液滴晶片未來能夠提供高速細胞篩選與檢測、奈米材料合成及生化反應有用之工具,並進而研發為細胞操作與檢測相關之微全分析系統。
摘要 III
Abstract IV
誌謝 VI
目錄 VII
圖目錄 IX
表目錄 XV
第一章.緒論 1
1.1 研究背景 1
1.1.1 細胞篩選與封裝 1
1.1.2 微全分析系統 3
1.2 細胞篩選 4
1.2.1 被動式微結構 6
1.2.2 介電泳操控 8
1.2.3 光鉗操控 13
1.2.4 光誘發介電泳操控 14
1.2.5 聲波抓取 16
1.2.6 磁珠操控 18
1.3 微液滴封裝細胞 20
1.3.1 微液滴形成 20
1.3.2 微液滴的操縱與排列 23
1.3.3 微液滴封裝細胞 27
1.4 研究動機 31
1.5 研究目的與方法 31
1.6 論文架構 32
第二章. 微液滴形成原理與方法 34
2.1 微液滴形成原理 34
2.1.1 高原-瑞利不穩定性 34
2.1.2 雷諾數 35
2.1.3 毛細管數 36
2.1.4 兩相流體進口流率比 37
2.2 微液滴形成的方法 37
2.3 液體種類與化學性質的影響 40
2.3.1 表面活性劑分類 40
2.3.2 表面活性劑原理 43
2.3.3 表面活性劑之選擇 45
第三章. 微液滴晶片之設計、模擬與分析 47
3.1 微液滴晶片之設計 47
3.2 二維微液滴形成模擬與分析 49
3.2.1 網格收斂性 49
3.2.2 微流速比率影響 56
3.2.3 微流道寬度影響 60
3.3 三維微液滴形成模擬與分析 62
3.3.1 網格收斂性 62
3.3.2 微流量比率影響 68
3.3.3 微流道厚度之影響 70
3.4 結論 72
第四章. 微液滴形成晶片製作與參數探討 75
4.1 微液滴形成平台製作 75
4.1.1 微液滴形成晶片製程 75
4.1.2 微液滴形成晶片封裝 78
4.1.3 微液滴形成晶片平台架設 80
4.2 微液滴形成參數探討 83
4.2.1 微流道寬度及縮口影響 83
4.2.2 絕對微流量影響 90
4.2.3 微流量比率影響 94
4.2.4 表面活性劑影響 98
4.3 微液滴操作晶片之設計 101
4.4 結論 111
第五章. 微液滴晶片應用 114
5.1 微液滴封裝磁珠與細胞 ─ 文獻回顧114
5.2 微液滴封裝磁珠 118
5.3 微液滴封裝細胞 120
5.4 結論 125
第六章. 總結與研究成果 127
6.1 總結 127
6.2 研究成果 127
6.3 學術貢獻點 129
6.4 未來研究建議 131
參考資料 135
作者簡介 144
發表著作 145
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