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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張培仁(Pei-Zen Chang) | |
| dc.contributor.author | Yu Wang | en |
| dc.contributor.author | 王煜 | zh_TW |
| dc.date.accessioned | 2021-06-08T02:41:44Z | - |
| dc.date.copyright | 2018-03-05 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-02-08 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20184 | - |
| dc.description.abstract | 自然殺手細胞療法是近代癌症治療方法之一，相較於傳統化療、放射線治療等方法，其具備有治療副作用小，且可使患者維持較好的生活品質等優勢。自然殺手細胞為人體內先天免疫系統的細胞，會主動辨識癌細胞並進行攻擊，藉由分泌細胞因子或炎性物質，啟動癌細胞凋亡程序，進而達成消滅癌細胞之目的。
本研究使用微流體技術，開發一人類自然殺手細胞毒殺率快速檢測微型化仿生平台，將自然殺手細胞(NK-92MI)與標靶癌細胞(K562)接觸後，利用微流道出入口水頭壓力差的原理，將懸浮的細胞混合液導入晶片當中，並以微結構捕捉固定後，利用螢光染色法來判定 K562細胞是否存在早期細胞凋亡的現象，用以檢測NK-92MI對 K562細胞毒殺率。利用計算流體力學（computational fluid dynamics, CFD）來預估微流體中應力作用對細胞的影響，確認在此微系統環境下，流場剪應力對於細胞存活率並無顯著影響，以增加微型化仿生平台檢測可靠度。實驗方面針對傳統流式細胞儀與本平台，比較不同接觸時間與不同效應細胞對目標細胞比例(effector to target cell ratio, E:T ratio)混合之樣本，進行自然殺手細胞毒殺能力的檢測與分析。結果顯示使用微型化仿生平台所獲得的結果與流式細胞儀一致性極高，此外本平台能捕捉少量(約〖10〗^2)懸浮細胞樣本，提供自然殺手細胞療法一嶄新的毒殺率檢測方式。並實際抽取人體血樣，驗證人類自然殺手細胞毒殺率變化，證明此裝置於自然殺手細胞療法中對醫師有臨床檢測功效。未來可規劃循環式流動系統，以達模擬真實血管中自然殺手細胞毒殺癌細胞的作用進行觀察。 本微型化仿生平台成功且有效檢測出自然殺手細胞之細胞毒殺率，可應用於為患者尋找合適的自然殺手細胞捐贈來源，提高自然殺手細胞療法成功率，實現個人化醫療(personalized medicine)的目標。此外本平台尚擁有製造低成本和低樣品消耗量等特性，充分具備未來於醫療實務應用上的發展潛力。 | zh_TW |
| dc.description.abstract | Natural killer cell therapy is one of the most recent forms of cancer treatment. Natural killer cell therapy has fewer side effects and better quality of life than chemotherapy and radiotherapy. Natural killer cells are cells of the innate immune system in the human body. They actively attack cancer cells by secreting cytokines or inflammatory cell apoptosis programs.
Cytotoxicity assays were performed on natural killer cells and K562 cells. By manipulating microfluidics, the cell mixture was injected into the chip to detect cytotoxicity. In this study, computational fluid dynamics (CFD) software was used to study the effect of shear stress on microfluidic cells. It was confirmed that the shear stress had no significant effect on cell in the flow. Increase the reliability of the miniaturized biomimetic platform. The cells are mixed according to the effector to target cell ratio (E: T ratio). The cytotoxicity of natural killer cells was compared with traditional flow cytometry. The results show that the analytical results using a miniaturized biomimetic platform are highly consistent with flow cytometry. In addition, the miniaturized biomimetic platform can capture a small amount of suspended cell samples (about 10^2 cells) and improve the shortcomings that flow cytometry requires a large number of cells (about 5 × 10^5 ~10^6). Blood was drawn off from donors to verify changes in cytotoxicity. This device proved to be clinically effective for physicians in natural killer cell therapy. The miniaturized biomimetic platform successfully and effectively detects the cytotoxicity of natural killer cells. It can be used to find suitable natural killer cell donation sources for patients. Increase the success rate of natural killer cell therapy. In addition, this platform still has manufacturing features such as low cost and low sample consumption. This research has the potential for development in practical medical treatment. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T02:41:44Z (GMT). No. of bitstreams: 1 ntu-107-R04543094-1.pdf: 4138566 bytes, checksum: 185be5c05fceae5fa6cba2536f4c086e (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii 英文摘要 iii 第1章 緒論 1 1-1 前言 1 1-2 研究動機 4 1-3 文獻回顧 5 1-3.1 免疫細胞療法 5 1-3.2 自然殺手細胞療法 7 1-3.3 自然殺手細胞特性與毒殺機制 11 1-3.4 實驗室晶片 (Lab on chip) 13 1-3.5 生物晶片細胞操控技術 14 1-4 論文架構 18 第2章 研究方法 19 2-1 流微體晶片製作 19 2-1.1 微流體晶片流道設計 19 2-1.2 微流體晶片母模製程 20 2-1.3 微流體晶片製作整合 22 2-2 微流道流場理論分析 26 2-2.1 水力聚焦流場分析 26 2-2.2 微流道內細胞受力分析 28 2-3 微流道流場模擬分析 31 2-4 細胞生物技術介紹 35 2-4.1 細胞培養 35 2-4.2 細胞凋亡機制 37 2-4.3 初代細胞與細胞株 38 2-4.4 血癌細胞與自然殺手細胞培養 39 2-5 毒殺分析方法―細胞膜螢光染色 43 2-5.1 K562細胞膜螢光標定 43 2-5.2 K562凋亡螢光標定 43 2-6 流式細胞分析儀 44 第3章 實驗流程 47 3-1 實驗架構 47 3-2 實驗操作流程 48 3-2.1 CFD軟體基本設定 48 3-2.2 微流體晶片毒殺分析 49 3-2.3 流式細胞儀毒殺分析 51 第4章 實驗結果 53 4-1 微流道流場模擬結果 53 4-2 細胞毒殺率計算 57 4-2.1 K562細胞螢光標定測試 57 4-2.2 微流體晶片之毒殺率計算 58 4-2.3 流式細胞儀之毒殺率計算 58 4-3 細胞在晶片內受損傷實驗 59 4-4 細胞株毒殺檢測 61 4-5 臨床應用檢測 63 第5章 實驗討論 65 5-1 細胞株毒殺檢測 65 5-2 臨床應用檢測 65 第6章 結論與未來展望 66 6-1 結論 66 6-2 未來展望 67 參考文獻 68 | |
| dc.language.iso | zh-TW | |
| dc.title | 人類自然殺手細胞毒殺率快速檢測微型化仿生平台-以血癌細胞為例 | zh_TW |
| dc.title | A Rapid Cytotoxicity Detection Method for the Human Natural Killer Cell and Leukemia Cell in the Miniaturized Biomimetic Platform | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 蔣雅郁(Ya-Yu Chiang) | |
| dc.contributor.oralexamcommittee | 李雨(U Lei),沈弘俊(Horn-Jiunn Sheen),蔡博宇(Bor-Yu Tsai) | |
| dc.subject.keyword | 自然殺手細胞,微流體,細胞毒性,流式細胞儀,免疫細胞療法, | zh_TW |
| dc.subject.keyword | Natural killer cell,microfluidics,Cytotoxicity,Flow Cytometry,Immune cell therapy, | en |
| dc.relation.page | 71 | |
| dc.identifier.doi | 10.6342/NTU201601816 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2018-02-08 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 應用力學研究所 | zh_TW |
| 顯示於系所單位： | 應用力學研究所 | |
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