隨著醫療的進步，各種疾病的治癒率越來越高，然而，癌症卻仍深深影響著現代人，其中肺癌更是高居死亡率與罹患率之冠。在肺癌的治療上，以目前最佳的因應對策─外科手術而言，雖然有約60%的五年存活率，但其有局部性的限制，因此在醫學上，相關研究仍占有相當重要的地位。
根據最新的研究，複合式治療被認為是癌症治療的希望，也就是透過傳統療法與標靶治療的結合來提高肺癌腫瘤的治癒率。文獻指出，當癌症腫瘤生長超過2 mm時，將會因缺氧釋放血管新生因子，使新血管朝腫瘤生長，因此，使用細胞分子抑制腫瘤血管生成，即是所謂的標靶治療，已成為癌症治療的新方向。
在醫學研究上，由於直接進行體內測試將會帶來許多限制，如費用過高、法律問題與道德爭議等等，因此近年來，相關研究多使用微機電技術。微機電技術，在生物學上，能在體外重建體內組織所處之微環境，以重現體內組織機能，使研究更方便且有意義，在臨床上，使我們能在藥物測試時，預期最佳的治療效果，同時降低體內測試的成本。
然而，在過去的血管新生研究中，多直接使用已知之生長因子VEGF，但實際上在不同的生長階段，腫瘤釋放的生長因子並不相同，且腫瘤的構成不只有癌症細胞，亦包含許多非實質性細胞，因此，本計畫預期設計一生醫晶片，同時整合濃度梯度產生器與DEP細胞排列技術，重建體內肺癌腫瘤組織所處之微環境，並將其應用在血管新生的研究，期望能重現腫瘤細胞釋放血管新生因子，誘使新血管朝腫瘤生長的過程，以探討癌症細胞與血管內皮細胞相互作用，希望能在腫瘤研究與臨床癌症標靶治療上提供相關資訊。

With the advance of the medical approach, the cure rate of many diseases has been improved. However, cancer still deeply affects human being. Among them, lung cancer is the one with the highest mortality and morbidity. There are so many treatments. The most effective one is surgery with about 60% of the five-year survival but it is locally restricted. Therefore, the related research still occupies a very important position. According to the latest research, the treatment combining traditional strategies and targeted therapy is considered the new hope to cure cancer. Literature indicates that when tumor grows over 2 mm in diameter, it would release the angiogenic factors, which would induce the new blood vessel growth toward the tumor due to hypoxia. Therefore, using a cell based systems to inhibit the angiogenesis of tumor had become the new strategy of cancer treatment.
In medical research, in vivo test has many restrictions, such like the high cost, legal issues and ethical controversies. MEMS technology, which not only can be used to reconstruct the micro environment around tissue to reappear the function of tissue in vitro, but also predict the improved treatment effect for medication tests to reduce the cost of clinical practice. However, the past researches most use VEGF to induce angiogenesis directly. In fact, at different stage of the tumor, the angiogenesis facts released by the tumor are different. Moreover, the composition of the tumor is not only tumor cells but also many nonparenchymal cells. Thus, a chip integrating gradient generator and DEP cell patterning technology is developed in this research to reconstruct the micro environment around tumor for the studies of angiogenesis. It is expected to provide pharmaceutical information and aid in drug discovery for cancer.

目錄
Abstract I
中文摘要 II
致謝 III
目錄 IV
圖目錄 VII
1. 緒論 1
1.1. 研究背景與動機 1
1.1.1. 微機電技術與實驗室晶片 1
1.1.2. 腫瘤血管新生 2
1.1.3. 血管新生與細胞外基質(extracellular matrix ,ECM) 4
1.2. 研究動機與目標 5
1.3. 文獻回顧 6
1.3.1. 微流體系統產生濃度梯度 6
1.3.2. 微流體系統產生濃度梯度在生物研究上之應用 6
1.3.3. 微流體濃度梯度產生裝置之血管新生生物應用 11
1.3.4. 三維空間基質 13
1.3.5. 細胞排列技術 15
1.4. 肺癌與腫瘤治療及其前瞻性 20
2. 研究方法、原因與元件設計 22
2.1. 理論背景 22
2.1.1. 介電泳 22
2.1.2. 擴散理論 25
2.1.3. 微尺度下的物質傳遞 28
2.2. 微流體分析 29
2.3. 肺癌組織模型 31
2.4. 設計概念 32
2.4.1. 肺癌組織模型電極設計 34
2.4.2. 肺癌組織模型圖案化定義工作原理 35
2.4.3. 肺癌組織模型電極之數值模擬 36
2.4.4. 載入細胞外基質微流道設計 37
2.4.5. 擴散效應濃度梯度產生裝置之設計 38
3. 晶片製程 41
3.1. 製作流程 41
3.1.1. A549 與 HUVEC 區域定義微流道製程 41
3.1.2. 肺癌組織圖形化定義電極製程 43
3.2. 製程結果 45
4. 實驗結果與討論 46
4.1. 材料準備 46
4.1.1. 細胞培養 46
4.1.2. 表面改質增加細胞貼附能力 47
4.2. 實驗架設 48
4.2.1. 儀器架設 48
4.2.2. 實驗參數設定 49
4.3. 實驗結果 50
4.3.1. 肺癌組織模型圖案化定義 50
4.3.2. 雙層 su-8 結構測試結果 51
4.3.2.1. 濃度梯度測試 51
4.3.2.2. 細胞遷移測試 52
4.3.3. 不同FBS濃度對A549釋放VEGF細胞之影響 53
4.3.4. 細胞排列對A549釋放VEGF細胞之影響 54
4.3.5. 人類臍帶血管內皮細胞遷移實驗 55
4.3.5.1. 實驗結論 56
5. 結論 57
6. 參考文獻 58

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