臺灣博碩士論文加值系統

本研究開發出一整合於液相層析串聯質譜儀(Liquid chromatography-tandem mass spectrometry, LC-MS/MS)系統之微流體晶片，並用於毒品檢測。在利用LC-MS/MS系統分析待測物之成份時，需使用層析管柱來分離待測物中的不同成份，形成不同成份間的時間差，使我們在獲得質譜圖時之訊號更為清晰可見，但目前市面上的層析管柱大多只能針對某一種成份的物質有比較高的分析效率；因此，本研究欲利用微流體之優勢，來開發一拋棄式微流體晶片之製程，以達到層析管柱微小化為目標、且於未來可發展對不同成份間皆有較高分離效率的多流道微流體晶片，解決目前毒品檢驗工具在檢測速度上之侷限。
針對拋棄式微流體晶片之製程，本研究提出兩種解決方法，來改善粒子封裝製程會產生的溢膠現象及封裝效果之問題，由實驗結果得知：(1)利用些許酒精可降低粒子在黏合表面的擴散情形；(2)利用微流體晶片上之圍牆結構設計，並搭配UV膠黏合技術，使粒子確實有效封裝於微流體晶片之粒子填充區。

How to rapidly analyze the drug compound is an emerging demand and this study intends to integrate a microfluidic chip with a LC-MS/MS system to address this issue. Since the operation pressure of compound separation in a microchannel is relatively high and how to completely seal the separation particle inside the microchannel is quite difficult, chip manufacturing is quite challenging. Two approaches were used, (1) ethanol solution and wall structure with UV glue were used to bond the chip with securing the particles inside the microchannel; (2) C-type fixture was used to increase the bonding strength. Initial experiment result showed that this chip with filled particles can be potentially used as a commercial separation column for analyzing the drug compound with connecting to a LC-MS/MS system.

摘要 I
Abstract II
誌謝 III
目錄 IV
圖目錄 VIII
表目錄 XIII
第一章 緒論 1
1.1 研究背景 1
1.1.1 微流體生醫晶片 1
1.1.2 液相層析串聯式質譜儀 4
1.2 研究動機與目的 6
1.3 研究方法 10
1.4 論文架構 11
第二章 文獻回顧 13
2.1 LC-MS/MS檢測及整合微流體系統相關文獻 13
2.1.1 利用微流體晶片輔助質譜儀之電噴霧電離 14
2.1.2 利用微流體晶片輔助質譜儀分析，應用於蛋白質組學 19
2.1.3 利用微流體晶片輔助質譜儀分析，其他應用 21
2.2 微流體封裝黏合技術相關文獻 24
2.2.1 熱黏接(Thermal bonding) 24
2.2.2 化學溶劑溶解黏接(Solvent bonding) 26
2.2.3 膠著劑黏接(Adhesive bonding) 28
第三章 微流體晶片製程 30
3.1 微銑削簡介 31
3.1.1 微銑削機加工介紹 34
3.1.2 操作方式與使用說明 35
3.2 單流道晶片初步設計及結果 38
3.2.1 連接頭滲漏 39
3.2.2 乙醇黏合技術無法有效封裝層析粒子 40
3.2.3 UV膠封裝技術溢膠 40
3.2.4 濾膜造成系統流速不穩定 41
3.2.5 填充層析粒子之緻密程度 42
3.3 改良後單流道晶片結構設計 43
3.3.1 微流道粒子填充區下層 44
3.3.2 微流道粒子填充區上層 47
3.3.3 粒子篩版固定層 51
3.3.4 連接管固定層 53
3.3.5 連接頭固定層 56
3.3.6 輔助實驗器具 59
3.4 粒子填充與晶片黏合製程 61
第四章 研究設備介紹 64
4.1 製程設備與軟體 64
4.2 量測設備與軟體 71
第五章 實驗方法 78
5.1 UV膠黏合強度測試 78
5.2 單流道微流體晶片功能評估 79
5.2.1 單一藥物之測試 79
5.2.2 混合藥物之測試 80
第六章 實驗結果與討論 81
6.1 UV膠黏合強度測試 81
6.2 單流道微流體晶片功能評估 82
6.2.1 單一藥物之測試結果 82
6.2.2 混合藥物之測試結果 84
第七章 結論與未來展望 86
7.1 結論 86
7.2 未來展望 87
參考文獻 89
附錄A 黏合強度實驗數據 101
附錄B 市售Column上機測試之數據 102

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