癌症，又稱為惡性腫瘤，泛指人體內細胞不正常的增生，且這些增生的細胞可能侵犯身體的其他部分。其中造成癌症高死亡率的原因為轉移。在轉移過程中，循環腫瘤細胞會從原生腫瘤脫離並流入至人體血液循環並且在其他地方著陸並繼續侵害。這使得癌症治療變的越發困難。因此，本論文主要致力於研究癌症治療中的循環腫瘤細胞。本研究開發整合兩個部份的微流體晶片系統:確定性側向位移結構與細胞抓取結構。藉由將人類癌症肺泡上皮細胞(A549)混入人血中的樣本，經過第一部分兩階段的確定性側向位移結構，可有效地將大團塊的目標細胞A549從樣本中分離出來流入第二階段，由不同大小的微柱將其抓取，以利後續的細胞培養以及藥物測試。
實驗結果顯示，確定性側向位移結構可以成功地將人體癌症肺泡上皮細胞(A549)從血液樣本中分離出來，並且有著高達90%的循環腫瘤細胞回收率。經過篩選後並在細胞培養模組內進行培養，經過72小時的培養，細胞有著86%的存活率，因此證明了晶片的可行性。下一階段並進行了病人的人血樣本，從雙和醫院孫偉倫博士那取得，並通過IRB認證。在此晶片下測試並透過染色，可以觀察到癌細胞成功地被篩選出來並捕捉。

Cancer, known as a Malignant tumor, is the abnormal hyperplasia of the cells in the human body, which may infringe on any part of a person. One of the reasons that cause the high death rate is called metastasis. During the process, Circulating Tumor Cells (CTCs) can break away from the primary tumor, flow into the blood circulation, and find another location to invade, making the cancer treatment more difficult. Therefore, the research on CTCs plays a vital role in cancer therapy. This study integrates the microfluidic chip, including the Deterministic Lateral Displacement (DLD) module and the cell-capturing and cell-cultivation module. During the first DLD part, the Human lung epithelial carcinoma cell line_(A549) mixed with the human blood was separated from other cells in the two-stage DLD separation device. Then the sorted-out cells were captured in the second part (the cell-capturing and cell-cultivation module). The CTCs were captured well by these micropillar structures and cultivated drug testing.
The experimental results show that A549 cells can be separated from human blood and have a high recovery rate of up to 90% in the Deterministic Lateral Displacement (DLD) module. After sorting out the cells, A549 can be captured in the chip and cultured with good cell viability of up to 86%. After testing the feasibility of the chip, we took the patient's blood sample from Shuanghe Hospital. The results show that under the whole blood sample, the chip can still carry out the separation of CTCs from the blood.

ABSTRACT I
摘要 II
致謝 III
目錄 1
圖表目錄 3
第一章 緒論 6
1.1 前言 6
1.2 研究動機與目的 7
1.3 研究背景 9
1.3.1 生醫微機電系統與實驗室晶片 9
1.3.2 癌症 10
1.4 文獻回顧 13
1.4.1 被動性循環腫瘤細胞分離技術 14
1.4.2 細胞捕捉培養分析平台 20
第二章 系統理論與晶片設計 23
2.1 系統理論 23
2.1.1 微流體晶片設計理論 23
2.1.2 確定性側向位移理論（Deterministic lateral displacement） 27
2.2 微流體晶片設計 31
3.1.1 詳細設計及功能介紹 31
3.1.2 晶片預處理(膠原蛋白貼附) 39
3.1.3 運作流程 39
3.1.4 與前人文獻比較 40
第三章 微流道晶片製成 42
3.1 製作流程 42
3.1.1 微流道母模製程 42
3.1.2 系統晶片製程 44
3.2 製程結果 46
第四章 實驗材料與方法 47
4.1 實驗材料 47
4.1.1 人類癌症肺泡上皮細胞（Human lung epithelial carcinoma cell line, A549）培養 47
4.1.2 人T淋巴細胞 (Human T lymphocyte cell line, Jurkat)培養 48
4.1.3 膠原蛋白(Collagen)稀釋 49
4.1.4 細胞螢光染劑 50
4.2 實驗設備 51
第五章 實驗結果與討論 52
5.1 細胞大小與分佈分析 52
5.2 前端晶片:DLD細胞分選模組 53
5.2.1 DLD參數設計 53
5.2.2 細胞分選效率 55
5.3 後段晶片:晶片捕捉與培養模組 60
5.3.1 細胞捕捉結果 60
5.3.2 細胞捕捉後培養結果 61
5.3.3 細胞培養死亡率 62
5.3.4 全血晶片測試 62
第六章 結論與未來展望 64
6.1 結論 64
6.2 未來展望 65
第七章 參考文獻 66

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