肝癌，長期以來是影響人們深遠的一種疾病，因為肝癌在早期階段不易發現，在末期才會出現較為明顯的症狀，並且高機率會夾帶著許多的併發症，因此患者的壽命已所剩不多。由上述可知，治療肝癌一直是一項很艱難的議題，也會因每個病人的生理機制不同，對於藥物的反應也不同，所以在選擇肝癌的藥物上也是一大挑戰。
本研究針對肝癌的治療提出了一項具有創新性的實驗室晶片，該晶片旨在仿肝癌微環境，以更深入地研究這一複雜的疾病。透過運用微機電技術，我們所設計之晶片，能使藥物能夠自動形成組合，並流入細胞培養室，提供了一個嶄新的晶片，以探索不同藥物組合對於肝癌細胞的治療效果。為了貼近真實情況，我們利用介電泳技術，使肝癌細胞和纖維母細胞能夠以不同的比例組成，並排列特定的圖案，以模擬出腫瘤微環境的情況，也使用生物相容水膠材料GelMA，給予細胞生長的支架，使環境能仿三維結構，以接近人體環境。透過實驗結果的分析，我們發現透過藥物組合相較於單一藥物能展現出更好的毒殺效果，特別是由Cisplatin和5FU組成的藥物組合表現最為優異，細胞的生存率僅剩33%，因此可做為最佳藥物推薦組合。此外，我們發現到隨著纖維母細胞比例的增加，肝癌細胞會產生抗藥性之現象。

Hepatocellular carcinoma (HCC) is a pervasive and challenging disease that has had a significant impact on global health for an extended period. The insidious nature of HCC lies in its often-asymptomatic progression, leading to late-stage diagnosis when treatment options become limited. Consequently, finding effective therapeutic strategies for managing HCC remains an urgent priority in the field of oncology.
This study endeavors to develop an innovative drug screening platform tailored specifically for hepatocellular carcinoma. Utilizing cutting-edge microelectromechanical systems (MEMS) technology, a sophisticated biomedical microchip will be meticulously crafted. Our chip can allowing the combination of three different drugs to be directly delivered into the cell culture chamber. Furthermore, we employ dielectrophoresis to arrange fibroblast and cancer cells into specific patterns, simulating the tumor microenvironment's architecture. The fluorescent analysis will be utilized to quantify cell viability. The experimental results indicate that the drug combination of Cisplatin and 5FU exhibits the highest cytotoxicity against HCC cells, the cell viability is reduced to 33%. Additionally, an observation of increased fibroblast proportion leading to cancer cell resistance to the treatment was made.

ABSTRACT I
摘要 II
致謝 III
目錄 V
圖表目錄 VII
第一章 緒論 1
1.1 前言 1
1.2 研究動機與目的 2
1.3 研究背景 3
1.3.1 生醫微機電與實驗室晶片 3
1.3.2 肝臟組織與功能 4
1.3.3 肝癌簡介與治療 7
第二章 系統理論與文獻回顧 11
2.1 微流體晶片設計理論 11
2.2 微型混合理論 15
2.3 液體組合微流道設計 17
2.3.1 濃度梯度產生器 18
2.3.2 組合式混合器 19
2.3.3 被動式微型混合器 23
2.4 粒子操縱技術 25
2.4.1 粒子介電泳理論 (Dielectrophoresis, DEP) 26
2.4.2 細胞操縱技術 31
2.4.3 腫瘤微環境(Tumor Microenvironment, TME) 34
2.4.4 癌化纖維母細胞 (Cancer-associated fibroblastse CAFs) 35
第三章 實驗材料與方法 37
3.1 微流體晶片設計 37
3.1.1 各層晶片之詳細設計與功能 38
3.1.2 運作流程 45
3.1.3 微流道晶片製程 47
3.1.4 介電泳電極晶片製程 49
3.1.5 系統晶片整合製作 51
3.2 細胞培養 53
3.3 化療藥物 54
3.3.1 Cisplatin 54
3.3.2 5-Fluorouracil 54
3.3.3 Mitoxantrone 54
3.4 多孔隙水膠GelMA (Gelatin Methacryloyl, GelMA) 55
3.5 DEP緩衝溶液 57
3.6 膠原蛋白 58
3.7 細胞存活率分析 (CCK-8 assay) 58
3.8 細胞螢光染劑 60
3.9 細胞死活染劑 61
3.10 實驗設備 61
第四章 實驗結果與討論 63
4.1 藥物組合測試 63
4.2 化療藥物半抑制濃度測試 64
4.3 GelMA曝光時間測試 66
4.4 細胞排列及比例測試 67
4.5 化療藥物測試 69
第五章 結論與未來展望 85
第六章 參考文獻 87

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