根據研究發現，HER1及HER2在很多種類的癌症常有過度表達(over-expression)情形產生。因此，檢測her1及 her2基因為目前廣泛應用於臨床上癌症病變預測的指標，特別是指乳癌與胃癌細胞。例如研究發現胃癌約有5-10%是由於her2基因過度表現進而引發癌變。最新研究發現此類病人可使用標靶藥物Herceptin治療，以提高其長期存活率，而標靶藥物所需要的費用相當高昂，因此需要一個準確度高的檢測方法。目前偵測HER2過度表現之標準方法是使用螢光原位雜交法(FISH)，不過此方法試劑過於昂貴且過程繁複耗時更需要專業人員的操作。更甚者，一位專業人員完成整個FISH的檢測得花上一到兩天的時間。因此，我們發展出一個新型整合性的微流體FISH晶片可以於自動化完成整個FISH流程。本研究的微流體FISH晶片結合了用於傳輸少量流體的流體控制模組和溫控模組以及穩定的雜交平台。藉由整合這幾個系統，這次研究中的新型微流體晶片可以在二十個小時內完成檢測。我們使用四種不同的cell line和兩種臨床組織來驗證整個系統與晶片的穩定性，四種cell line裡分別為兩種陰性反應與兩種陽性反應，兩種臨床組織則是一種陰性檢體與一種陽性檢體。實驗結果顯示晶片上與傳統的檢測並無顯著差異。再者，利用微流體的優點減少了大約70%的試劑用量特別是探針試劑的大幅減少至2-3 μl。整個系統僅用微量的試劑和樣本即能快速且自動化診斷her2基因的相關疾病，並在未來可優化延伸至不同的病理應用。

誌謝……………………………………………………………….…..I
Abstract……………………………………………………………..III
摘要...…………………………….……………………...…………….V
Table of Contents…………………………………………………..…VI
List of Figures...........................VIII
List of Tables………..………..……………….………..……………XII
Abbreviations……………….…...…..…………….……………...XIII
Nomenclature..............................XIV
Chapter 1. Introduction............................
1.1MEMS and microfluidic technology……………………………………………..1
1.2 Genetic diseases and detection methods………………….3
1.3 HER2 over-expression and cancer.………..…………..…...4
1.4 Fluorescence in situ hybridization (FISH)…………….5
1.5 Motivations and objectives…...…………………………………………………..6
Chapter 2. Theory……………………………………………...….…….9
2.1 Suction-type and compression-type micropumps………………9
2.2 Membrane deformation theory………………………….10
Chapter 3. Materials and Methods…………………….……………..13
3.1 FISH microfluidic chip design………………………………………..………13
3.2 Chip fabrication………………………………………………………………14
3.3 Experimental procedures (FISH protocol).…………………………15
3.3.1 Cell lines ……………………………………..……………..………..15
3.3.2 Tissue samples ……………………………………………..……………18
3.4 Statistical analysis…………………………………………………………….…..18
Chapter 4. Results and Discussion…....…………………………...….24
4.1 Characterization of the micropump………………………….……..24
4.2 FISH analysis using cell lines and tissue samples……25
Chapter 5. Conclusions and Future Perspectives….…..38
References………………………………………………………..……..39

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