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研究生： 陳俊諭
Jyun-Yu Chen
論文名稱： 開發腸道器官晶片-具生理蠕動之體外細胞培養模型
Development of Gut On a Chip - in Vitro Cell Culture Model with Physiological Peristalsis
指導教授： 陳品銓
Pin-Chuan Chen
口試委員: 劉承賢
Cheng-Hsien Liu
陳珮珊
Pai-Shan Chen
謝堅銘
Chien-Ming Hsieh
曾修暘
Hsiu-Yang Tseng
學位類別： 碩士
Master
系所名稱： 工程學院 - 機械工程系
Department of Mechanical Engineering
論文出版年： 2022
畢業學年度： 110
語文別： 中文
論文頁數： 12
中文關鍵詞： 微流體技術 、器官晶片 、腸道晶片 、體外細胞培養 、電漿黏合
外文關鍵詞： Microfluidic, Organ on a chip, Gut on a chip, in vitro cell, Plasma bonding
相關次數： 點閱：309  下載：5 
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  •  上一筆

    • 藥物開發是生醫科技發展中重要的一環，透過藥物開發，能夠為罹患不治之症的人看見一線生機，然而開發的過程中是複雜且冗長的，平均一款新藥從測試到上市需花費10～15年，故如何縮短藥物的開發時程是當前的首要目標。目前有許多團隊以體外細胞模型來取代動物實驗，其優勢在於能夠減少個體差異間所造成的結果誤差，並透過外在的機械循環應變，以達到與實際人體相仿的結果。
    小腸為人體器官中吸收營養與藥物的主要器官，故本研究與臺北醫學大學藥學系合作，透過將微流體技術與生醫領域結合，以小腸為主，選擇腸上皮細胞(Caco-2)做為模擬藥物測試之體外細胞培養模型，並透過產生機械循環應變，開發一具生理蠕動之腸道器官晶片(Gut on a chip, GOC)。以微銑削、澆鑄翻模、雷射加工和電漿黏合技術為主，製作出能夠向前蠕動之腸道器官模型，研究中以不同微環境對Caco-2的生長條件進行探討，並透過細胞螢光染色分析比較。相較於一般動物實驗，腸道器官晶片的結果能夠更近於真實人體，也能夠減少因個體因素產生的誤差，且具有大量同時進行的優勢，故能夠於短時間內取得大量的數據，進而減少藥物開發的時程。

    Drug development is an important part of the development of biomedical technology. People can see the chances to be cured with incurable diseases. However, the development process is complicated and lengthy, and it takes an average of 10～15years to go from test to market. Therefore, how to shorten the development time of drugs is the current primary goal. At present, many teams use in vitro cell models to replace animal experiments. The advantage is that it can reduce the error of results caused by individual differences, and achieve results similar to the actual human body through external mechanical cyclic strain.
    The small intestine is the main organ that absorbs nutrients and drugs in the human body. Therefore, we are in cooperation with the Department of Pharmacy, Taipei Medical University, and we combine microfluidics with the field of biomedical. We select intestinal epithelial cells (Caco-2) as an in vitro cell culture model for drug testing. And developed a gut on a chip (GOC) with physiological peristalsis by generating cyclic mechanical strain. Base on micro-milling, casting, laser processing and plasma bonding technique, the GOC that can perform peristalsis forward, and we discuss the growth conditions of Caco-2 in different microenvironments through fluorescence staining analysis. Compared with general animal experiments, the results of organ on a chip can be closer to the real human body, and it can also reduce the errors caused by individual factors. GOC has the advantage that a large number of operations can be performed at the same time, so a large amount of data can be obtained in a short period of time, and reduce the time of the drug development.

    摘要 I Abstract II 誌謝 III 目錄 IV 圖目錄 VIII 表目錄 XV 第1章 前言 1 1.1 研究背景 1 1.1.1 微流體生醫晶片 1 1.1.2 器官晶片 3 1.2 研究動機與目的 4 1.3 研究方法 6 1.4 論文架構 8 第2章 文獻回顧 11 2.1 各種製程之生醫微流體晶片 11 2.1.1 利用微銑削加工之生醫微流體晶片 11 2.1.2 利用3D列印技術之生醫微流體晶片 13 2.1.3 利用光刻法之生醫微流體晶片 14 2.2 器官晶片種類相關文獻 16 2.2.1 腸道晶片 17 2.2.2 心臟晶片 18 2.2.3 肝臟晶片 19 2.2.4 肺晶片 21 2.2.5 腎臟晶片 23 2.2.6 血管晶片 24 2.2.7 骨晶片 26 2.2.8 多重器官晶片 27 第3章 腸道器官晶片製程設計 30 3.1 PDMS晶片與PMMA模具之設計與製程 31 3.1.1 晶片設計 31 3.1.2 PMMA模具設計 34 3.1.3 加工與機台操作 35 3.1.4 PMMA模具製作 38 3.1.5 PDMS晶片製作 39 3.2 PDMS薄膜製程 41 3.3 腸道器官晶片黏合製程 44 3.4 晶片之周邊零件設計與製程 47 第4章 研究設備與實驗方法 51 4.1 研究設備、軟體與材料介紹 51 4.1.1 製程設備 51 4.1.2 量測設備 55 4.1.3 實驗設備 57 4.1.4 研究材料 60 4.2 實驗方法 62 4.2.1 多孔性PDMS薄膜雷射加工參數實驗 62 4.2.2 PDMS薄膜變形量實驗 65 4.2.3 膠原蛋白塗層成分實驗 67 4.2.4 腸道晶片微環境測試實驗 70 第5章 實驗結果與討論 76 5.1 多孔性PDMS薄膜雷射加工參數實驗 76 5.2 PDMS薄膜變形量實驗 80 5.3 膠原蛋白塗層實驗 84 5.4 細胞微環境實驗 88 5.4.1 靜態環境 88 5.4.2 流動態環境 90 5.4.3 蠕動態環境 92 第6章 結論與未來展望 96 6.1 結論 96 6.2 未來展望 98 參考文獻 101

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