癌症一直以來都備受全球關注。儘管研究人員不斷努力尋找治療方法並持續進行發展，但仍然沒有完全根治癌症的方法。癌細胞轉移是使癌症難以治療的主要原因之一，其中腹膜轉移是最複雜以及最難處理的類型。腹膜轉移多發生在晚期癌症患者，涉及一種以上的癌細胞在患者的腹膜腔內擴散，主要源自胃癌、結直腸癌和卵巢癌等。為了治療這類患者，腹腔溫熱化療（Hyperthermic Intraperitoneal Chemotherapy, HIPEC）是一種新興的治療方法，通常在腹腔腫瘤減積手術（Cytoreductive Surgery, CRS）之後進行。手術過程中，溫度保持在42-43℃之間。同時，需要在腹腔內持續注入藥物60至90分鐘，利用熱和化療藥物來殺死癌細胞。
在本研究中，我們將開發一個藥物篩選的平台，使用微機電技術製造出晶片。在晶片中，藥物可以自動形成組合並直接流入腔室。此外，基於介電泳技術將癌細胞和纖維母細胞排列成特定的圖案並以特定比例組成，以模仿實際的腫瘤微環境。實驗過程中，將系統溫度保持在42～43℃，模擬出腹腔溫熱化學療法的治療過程。最後使用細胞死活螢光測定對細胞進行染色，以螢光共定位分析癌細胞之存活率。由實驗結果可以知道Cisplatin+Docetaxel的組合對癌細胞有最高的抑制效果，並且我們發現癌細胞會隨著纖維母細胞比例增加而有更強的抗藥性。

Cancer metastasis, particularly peritoneal metastasis, poses a significant challenge in cancer treatment. Despite ongoing research, no complete cure for cancer has been found. One emerging option for treating peritoneal metastasis is Hyperthermic Intraperitoneal Chemotherapy (HIPEC). HIPEC involves maintaining the surgical temperature at 42 to 43 ℃ while injecting chemotherapy drugs into the peritoneal cavity for 90 minutes. This combined approach utilizes heat and chemotherapy to eliminate cancer cells effectively.
This research aims to develop a drug screening platform for HIPEC. We employed the Microelectromechanical Systems (MEMS) technique to fabricate our microfluidic chips. This chip enables automatic drug combination formation and direct flow to the cell culture chamber. Moreover, we utilized the dielectrophoresis technique to arrange cancer cells and fibroblasts in specific patterns and compositions, mimicking the tumor microenvironment. Finally, we assessed cell viability using a fluorescence-based assay, analyzing cancer cell survival through colocalization analysis. The experimental results revealed that the combination of Cisplatin and Docetaxel exhibited the highest inhibitory effect on cancer cells. We also found that cancer cells exhibited increased resistance to the treatment with the escalation of fibroblast cell proportions.

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 癌症 3
1.3.1 簡介 3
1.3.2 腹膜腫瘤轉移 4
1.3.3 腹腔溫熱化療 5
1.4 生醫微機電與實驗室晶片 7
第二章 系統理論與文獻回顧 9
2.1 微流體晶片設計理論 9
2.2 微型混合理論 12
2.3 液體組合微流道設計 15
2.3.1 單層幾何設計 15
2.3.2 立體結構設計 17
2.4 被動式微型混合器 18
2.5 粒子操縱技術 21
2.5.1 粒子介電泳理論 (Dielectrophoresis, DEP) 22
2.5.2 細胞操縱技術 27
2.6 腫瘤-基質細胞交互作用(cancer-stromal cell interaction) 30
第三章 晶片設計與製程 35
3.1 微流體晶片設計 35
3.1.1 詳細設計與功能介紹 35
3.1.1.1 上層PDMS晶片：藥物注入導向與模擬 36
3.1.1.2 下層PDMS晶片：藥物組合及細胞培養 37
3.1.1.3 ITO電極晶片：細胞排列與模擬 39
3.1.2 運作流程 42
3.2 晶片製作流程 43
3.2.1 微流道母模製作流程 43
3.2.2 介電泳電極晶片製程 46
3.2.3 系統晶片整合製作 48
3.2.4 製程結果 49
第四章 實驗材料與方法 50
4.1 細胞培養 50
4.2 膠原蛋白 51
4.3 多孔隙水膠(Gelatin Methacryloyl, GelMA) 51
4.4 DEP緩衝溶液 53
4.5 熱化療藥物 53
4.5.1 Cisplatin (CDDP) 53
4.5.2 Docetaxel (DOCX) 54
4.5.3 Mitomycin C (MMC) 54
4.6 細胞存活率分析 (CCK-8 assay) 55
4.7 細胞螢光染劑 57
4.8 細胞死活螢光染劑 57
4.9 實驗設備 58
第五章 實驗結果與討論 60
5.1 藥物組合測試 60
5.2 CCK-8試驗及IC50量測 61
5.3 GELMA曝光時間測試 63
5.4 細胞排列及比例測試 64
5.5 晶片功能測試 66
5.6 熱化療藥物測試 68
5.6.1 晶片藥物測試實驗 68
5.6.2 共定位分析 78
第六章 結論與未來展望 86
第七章 參考文獻 88

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