本研究提出利用低成本的濾紙片以及3D列印技術，製作一個整合式的卡匣系統，將二維紙層析分離濃縮與紙電噴灑游離法進行整合，將樣本經過第一維紙層析的簡易分離後，再透過第二維紙層析凝縮提升分離後的樣本濃度，最後再經由紙電噴灑游離法透過質譜進行偵測、分析，並將其應用於食品安全以及生物樣本的檢測。本研究選用市售的定性濾紙，做為二維紙層析分離濃縮以及紙電噴灑質譜法的基材，並且使用ABS以及基於ABS改質的導電高分子做為卡匣的材料，其成本相當低廉，且取得容易。卡匣主體是使用雙噴頭的3D列印機製造，由於卡匣使用的兩種材料皆是以ABS做為基底，因此可以在單一次的3D列印程序中，藉由兩個噴頭製造出含有內嵌高分子電極的卡匣，大幅降低製造的成本以及複雜度，並且使用二氧化碳雷射加工機切割紙片，定義出二維紙層析以及紙電噴灑游離法所需要的功能區域，因此，本實驗所需的製造及加工方式，可完全自動化進行，大幅降低人力成本以及社會資源的浪費。而本研究將二維紙層析及紙電噴灑游離整合，不需任何設備輔助即可在單一卡匣內完成，因此大幅提升檢測的自由度、方便性及易用性，使得普羅大眾可以輕易使用，大幅降低以往進行各項檢測的高門檻，間接提升社會安全。透過卡匣及紙片設計上的優化，解決了第一維層析分離時容易產生的拖尾現象，並且使樣本殘留降低了10倍，且透過節流閥以及犧牲翼的設計，使第一維層析時的理論板數分別提升了3.9倍以及1.6倍。樣本經過第二維層析濃縮後，質譜所偵測到的訊號強度相較於濃縮前，大幅提升了100倍，證實二維紙層析確實能將樣本濃縮於紙片尖端，提升質譜檢測的靈敏度。研究結果表明，本卡匣不僅可以量測到市售植物樣本中的微量農藥殘留，也能量測到人體體液(唾液、尿液)中的藥物殘留及藥物代謝，證明本卡匣系統於食品安全及生醫檢測的領域有著極大的潛力。

This paper presents a novel paper-based microfluidic cassette integrated two-dimensional paper chromatography and paper spray mass spectrometry (PS-MS) detection in bioanalysis and food-safety applications. The cassette can be fabricated in a single-process through a dual-extrusion 3D printer equipped with ABS and ABS conductive polymers such that delicate fabrication processes can be excluded for producing the cassette. The sample injection, separation, concentration and electrospray ionization could be completed in the single microfluidic cassette through the specially designed cassette, paper-based microfluidic and the embedded polymer electrode. The liquid sample is directly applied to the sample trench and then separated and concentrated using a 2D paper chromatography technique. To further improve the performance of the paper-based microfluidic system, several special designs including a tip contact for uniform developing solution dispersion, several sacrificial wings for sample smear elimination and sculpted holes for electrical isolation during paper spray ionization. Results shows that the sacrificial wing and throttle valve can increase the number of theoretical plate to about 3.9 and 1.6 times respectively in the first-dimensional chromatography, and greatly reduce the sample residue on the paper tip. The second-dimensional chromatography has increased the signal strength by nearly a hundred times. The developed system can detect the residual pesticides in fresh grape, and the residual drug in body fluid.

目錄
論文審定書 i
論文授權書 ii
誌謝 iii
中文摘要 iv
Abstract v
目錄 vi
圖目錄 viii
符號表 x
簡寫表 i
第一章 緒論 1
1.1 研究背景 1
1.2 微流體晶片系統 2
1.2.1 微流體晶片 2
1.2.2 紙基微流體晶片 3
1.2.3 側流式微流體卡匣 5
1.3 質譜檢測 6
1.3.1 質譜分析系統簡介 7
1.3.2 傳統質譜檢測方法 8
1.3.3 新興質譜檢測方法 8
1.4 電噴灑游離法 9
1.4.1 電噴灑游離法之發展 9
1.4.2 紙電噴灑質譜法 10
1.4.3 3D列印輔助紙電噴灑游離法 12
1.5 研究動機與目的 15
1.6 論文架構 16
第二章 實驗原理與材料特性 17
2.1 毛細現象 17
2.2 層析法 18
2.3 紙電噴灑游離法 22
第三章 實驗設計與架構 25
3.1 新型卡匣檢測系統的設計與製作 25
3.1.1 新型卡匣設計與製作 26
3.1.2 紙片設計與製作 29
3.1.3 卡匣與紙片的特殊設計 31
3.2 新型整合式二維紙層析卡匣系統 33
3.3 紙電噴灑游離質譜檢測系統 35
3.4 實驗系統架構 36
3.5 實驗設計與檢測目標 38
3.6 實驗溶液配製 40
第四章 實驗結果與討論 41
4.1 樣本進樣口寬度分析 41
4.2 卡匣系統分離效能分析 42
4.2.1 犧牲翼效能分析 42
4.2.2 節流閥效能分析 44
4.3 卡匣系統濃縮效能分析 45
4.4 卡匣系統偵測極限分析 47
4.5 市售植物樣本檢測 48
4.6 生物樣本檢測 50
4.6.1 人體尿液中的藥物殘留分析 51
4.6.2 人體唾液中的藥物殘留分析 54
第五章 結論與未來展望 57
5.1 結論 57
5.2 未來展望 58
參考文獻 59
自述 64
圖目錄
圖 1-1 改良型鈉玻璃微流體晶片製程示意圖。 3
圖 1-2 3D堆疊紙微流體裝置示意圖。 4
圖 1-3 LFIA應用三明治法檢測示意圖。 6
圖 1-4 紙電噴灑質譜法架構示意圖。 11
圖 1-5 葉片電噴灑質譜法式架構示意圖。 12
圖 1-6 3D列印輔助紙電噴灑游離法架構示意圖。 13
圖 1-7 新型紙微流體電噴灑卡匣系統示意圖。 14
圖 1-8 論文架構圖。 16
圖 2-1 二維紙層析分離濃縮流程示意圖。 19
圖 2-2 電噴灑游離法之原理示意圖。 24
圖 3-1 本研究所使用的雙噴頭3D列印機。 27
圖 3-2 新型檢測卡匣設計圖。 28
圖 3-3 新型卡匣系統的紙片設計圖。 30
圖 3-4 新型卡匣系統的特殊設計。 32
圖 3-5 本研究之二維紙層析分離濃縮流程圖及實際影像。 34
圖 3-6 本實驗所使用的LCQ Deca XP Plus離子阱式質譜儀。 36
圖 3-7 本實驗之架構示意圖。 38
圖 4-1 樣本進樣口寬度分析。 41
圖 4-2 犧牲翼設計層析效能影像分析。 43
圖 4-3 犧牲翼設計層析效能理論板數分析。 44
圖 4-4 節流閥效能理論板數分析。 45
圖 4-5 第二維紙層析濃縮效能分析。 46
圖 4-6 卡匣系統與傳統紙電噴灑效能分析。 48
圖 4-7 市售葡萄量測質譜圖。 50
圖 4-8 攝取市售黑咖啡後的人體尿液樣本量測質譜圖。 52
圖 4-9 攝取複合藥物的人體尿液樣本質譜圖。 53
圖 4-10 吸菸者的唾液樣本量測質譜圖。 55
圖 4-11 攝取市售喉糖的人體唾液樣本質譜圖。 56

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