研究生: |
簡婕安 Jean, Chieh-An |
---|---|
論文名稱: |
肺癌免疫療法用於藥物測試平台 Lung Cancer On Chip for Testing Immunotherapy |
指導教授: |
劉承賢
Liu, Cheng-Hsien |
口試委員: |
盧向成
徐琅 |
學位類別: |
碩士 Master |
系所名稱: |
工學院 - 動力機械工程學系 Department of Power Mechanical Engineering |
論文出版年: | 2019 |
畢業學年度: | 108 |
語文別: | 中文 |
論文頁數: | 78 |
中文關鍵詞: | 肺癌 、免疫治療 、微流體 、立體培養 、水膠 、遷移 |
外文關鍵詞: | lung cancer, Immunotherapy, microfluidic, 3D culture, hydrogel, migration |
相關次數: | 點閱:3 下載:0 |
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現階段免疫治療為癌症的研究重要方向之一,主要都是利用人體自身的細胞來對抗癌症。免疫檢查點抑制劑屬於藥物型的免疫治療,目前在黑色素瘤及肺癌已經可以看到治療的成效,當藥物成功時,T細包不會被抑制生長,可以有效攻擊癌症細胞。在本研究中,藉由免疫細胞是能增生及遷移至癌症細胞內部,建立一個測試藥物的模型。且一改過去生物微流體晶片大多是利用平面二維的細胞培養作為基準進行藥物測試,為了更符合實際上人體內的三圍組織結構,本研究結合了組織工程上更接近真實人體的三維組織結構和微流體的全方位系統晶片,此兩種概念與技術的結合創造一個三維組織藥物檢測模型的微系統晶片。
利用微機電技術製作一微流體晶片,結合具有生物相容性的多孔隙光固化水膠材料:gelatin methacrylate(GelMA)作為細胞的支架。將肺癌細胞培養在支架上,模擬人體內的肺癌腫瘤,成功觀察免疫細胞遷移至立體的肺癌組織內部,並將遷移結果用亮度與距離關係進行分析。微流體晶片上亦有設計微柱體的結構,使水膠可以固定在晶片中。除此之外也設計濃度梯度產生器,使微流體晶片能產生0%、50%及100%三種濃度的藥物測試,藉三者的相對結果來測試藥物的成效。
Cancer immunotherapy is the artificial stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight cancer. Checkpoints inhibitors become one of the most promising ways to activate therapeutic anti-tumor immunity and have made significant breakthroughs in melanoma and lung cancer.
In this research, we established a predictive model based on T cell expression at the invasive margin to test checkpoint inhibitors. In addition, the most recent research studies taking advantage of bio-microfluidics for drug testing focus on two-dimensional (2D) cell cultures. In reality, tissue and organs are three-dimensional (3D) structures in our bodies. To approach the biomimetic situation in vitro, this study takes advantage of microfluidic techniques and tissue engineering to build a 3D drug-testing microsystem. We used MEMS technology to fabricated a microfluidic chip model and combined with highly biocompatible porous photo-initiated cross-linked hydrogel, gelatin methacrylate (GelMA), was used as a scaffold material. The lung cancer cells are cultured on a scaffold to simulate lung cancer tumors in the human body. Therefore, we can build an immunoassay system and observe the T cell migration on the three-dimensional structure. We fabricated a series of micro-pillar to allow hydrogels forming a diffusion scaffold and fixing to chamber. Also, the microfluidic chip can produce three different concentrations of drug by using the concentration gradient generator
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