血管新生在癌症的研究中，一直是一個很重大的議題。在癌症的病史過程中，最讓人感到害怕的便是癌症轉移。而血管新生做為癌症轉移的必經過程，在癌症治療中被視為是非常重要的目標。
然而，在人體所構成的複雜環境內，不同種類的細胞所分泌的生長物質不斷的影響著彼此，使得血管新生仍是一個布滿許多神秘面紗的機制。而在我們的研究中，我們展示一個為觀察多細胞相互作用所設計的微流體晶片。在大多數血管新生的研究中，都只單純使用單一生長物質作為建構體外模型的重點，但這樣的狀況離人體內的環境仍相去甚遠。而我們的設計可用於多細胞的觀察。透過流阻與濃度梯度的分析，我們的晶片可以分別將不同的細胞定位在三個不同的培養區中，並從設計的觀測區中觀測細胞相互作用的結果。在我們的生物實驗結果中，我們可以分別培養HUVEC、3T3及A549於三個個別的培養區域中，看到有部分的HUVEC因受到刺激而有遷移的現象，並透過Image J的分析，得到HUVEC的細胞數在三天從64個培養至129個。
此晶片設計提供了一種觀測多細胞相互作用的平台，且在多細胞的環境下，能貼切的建構血管新生體外模型。期望能在血管新生與癌症研究上提供更多有利的資訊。

In cancer research, angiogenesis is always an important issue. One of the well-known cancer growing procedures is metastasis which has been known as the most horrible stage of cancer. Then angiogenesis, the necessary procedure in metastasis, has been a quite important target for cancer treatment.
The angiogenesis is still a mysterious process because of the various growth factor that affect the cancer in human body. Here we propose a microfluidic chip that is designed for multi-cell interaction observation. For angiogenesis research, most of them show using only one kind of growth factor to construct the in vitro model. Our proposed chip was used to demonstrate and observe the angiogenesis induced by multi-cell interaction. By the analysis of flow resistance and diffusion gradient, we can separately place the cell to the three different culture areas. The cell interaction could be observed in the designed observation zone. In our experimental results, we can properly culture HUVEC, 3T3 and A549 in the chip and observe the number of HUVEC cells growing from 64 to 129 in 3 days by using Image J for the characterization.
We demonstrate a unique in vitro model for multi-cell interaction. This model is expected to mimic the angiogenesis conditions in vitro. We expect this on-chip model to provide helpful information for angiogenesis and cancer study.

Abstract I
中文摘要 II
誌謝 III
目錄 IV
圖目錄 VI
1. 緒論 1
1.1 前言 1
1.1.1 微流體技術與實驗室晶片 1
1.1.2 腫瘤血管新生與癌症轉移 1
1.2 研究動機 3
1.3 文獻回顧 5
1.3.1 濃度梯度 5
1.3.2 細胞定位 8
1.3.3 微流體閥 11
1.3.4 體外模型 13
1.3.5 細胞外基質 16
2. 研究方法 18
2.1 設計原理 18
2.1.1 流阻分析 18
2.1.2 擴散理論 22
2.2 設計概念 23
2.2.1 結構設計 25
2.2.1.1 晶片操作 25
2.2.1.2 設計分析 28
2.2.2 設計模擬 31
3. 晶片製程 34
3.1 製作流程 34
3.1.1 上層結構 34
3.1.2 下層結構 37
3.1.3 晶片製作 38
3.2 製作結果 42
4. 實驗結果與討論 43
4.1 實驗架設 43
4.1.1 細胞準備 43
4.1.2 晶片準備 43
4.1.3 凝膠準備 43
4.1.4 實驗步驟 44
4.2 實驗結果 45
5. 結論 52
6. 參考文獻 53

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