食物為維持人體健康必需的營養品，除了含豐富的營養成分，在人體生長發育、更新細胞、修復組織及調節生理機能中扮演著不可或缺的角色。近年來，由於食品安全問題在臺灣可謂層出不窮，舉凡食品仿冒及難以即時得知食品品質的資訊等問題，均是目前食品品質監控工作上的困境。食品中的特定成分的檢測一直都是檢視食品安全的重要工作，透過檢測食品中指標成分之含量，除了可以作為食品銷售市場上鑑別真偽的工具，亦可藉以評估食物的新鮮度。然而，在現行食品分析工作中，面臨數以千計的待驗產品，勢必將付出極為可觀的時間及經濟成本。有鑑於此，為滿足現今食品分析工作的需求，分析化學家除了致力於開發具高通量分析效能、操作簡便且適用性高的分析平台外，也逐漸將目光轉向現場即時檢測甚至是居家監控分析裝置的開發。根據文獻報導，現今的食品品質監控分析技術業已逐漸朝向微型化及自動化的方向發展。
爰此，本研究旨在以多層微流體裝置的技術為基礎，開發出價格低廉、適用性高且快速分析的檢測平台。研究最初，係利用市面上常見的壓克力材料製作出未活化型高通量固相萃取晶片，並藉由可程式控制的閥及管路，有效將此晶片與感應耦合電漿質譜儀 (ICP-MS) 結合，建立自動化連線分析系統，並藉此進行不同年份威士忌酒質成分中微量金屬含量的分析，根據所獲致的實驗結果，本研究所建立的分析方法確實可用以鑑定不同年份的威士忌酒；本研究後續的研究主題則是進一步將裝置材料精簡化，援引近十年來興起的微流體紙基材分析裝置 (μPADs) 技術，達成僅需利用濾紙和噴蠟印表機就能輕鬆製作裝置的目標，另外亦透由摺紙藝術的巧思和功能化的設計，簡化流道對位的問題及改善樣品中分析物濃度過低之窘境。最後，並整合比色法與數位相機檢測系統，並藉以開發出適用於即時監測蜂蜜中新鮮度指標成分的檢測分析平台。

Food is essential for the well-being of human. With its plentiful nutrients, it plays an indispensable role in growth of human body, renewal of cells, repair of tissue and physiological function. For the past few years, food safety issues have always caused panic in the society. Thus the examination works of food have been widely noticed. Because specific components in the food is an important indicator of food safety issues, by detecting the content of the indicator components in the food, we can not only realize the authenticity of food, but also we can assess the freshness of food. Recently, Analytical Chemists are committed to develop an analytical platform with high-throughput analysis, easy-operation and high-adaptable, in order to fulfill the needs of modern food analysis. Furthermore, the idea of on-site or even home determinations start to stand out and contribute to parts of analytical technologies developing towards miniaturization and automation.
In this study, based on the concept of multi-layer microfluidic devices, we developed two low-cost, high-adaptable and rapid-analysis platforms. In the first work, the non-functionalized high-throughput solid-phase extraction microchip was fabricated through the use of poly(methyl methacrylate). Then, a programmable valves and manifolds were used to interface the developed microchip and inductively coupled plasma-mass spectrometry (ICP-MS) instrumentation to fully automate the hyphenated system. Based on the experimental results, we have successfully utilized the contents of different trace metals as an indicator for distinguishing age of whisky. In second work, we further applied the concept of microfluidic paper-based analytical devices (μPADs) to fabricate simpler and cheaper microfluidic device. Only by using a piece of paper and the solid-ink printer, we can easily complete the fabrication of μPADs. By way of origami artistry and special design of the device, we achieved a complicated fabrication process and solves the problem of determining low concentration analytes in the use of μPADs. Finally, by coupling to colorimetric method and the detection of digital single-lens reflex camera, we successfully built up a platform for on-site monitoring of honey freshness.

摘要 I
ABSTRACT II
謝誌 IV
目錄 V
圖目錄 VIII
表目錄 XI
第一章 緒論 1
1.1 食品安全的重要性 1
1.2 現行食品分析中遭遇困境 2
1.3 微流體分析裝置之技術演進 5
1.4 研究目的與因應策略 7
1.5 參考文獻 9
第二章 未活化型高通量固相萃取晶片搭配感應耦合電漿質譜儀之連線分析系統開發及其於威士忌酒中快速鑑定年份之應用 12
2.1 前言 12
2.2 實驗部分 19
2.2.1 試劑與材料 19
2.2.2 儀器設備 20
2.2.3 未活化型高通量固相萃取晶片製程 22
2.2.4 混合效率評估 25
2.2.5 未活化型高通量型固相萃取晶片−感應耦合電漿質譜儀連線系統之建立 27
2.2.6 真實樣品製備 31
2.3 結果與討論 32
2.3.1 未活化型高通量固相萃取晶片之設計理念 32
2.3.2 未活化型高通量固相萃取晶片混合效率評估 37
2.3.3 未活化型高通量固相萃取晶片穩定性評估 39
2.3.4 未活化型高通量固相萃取晶片操作條件最適化探討 40
2.3.4.1 萃取流速對萃取效率的影響 41
2.3.4.2 樣品pH值對萃取效率的影響 42
2.3.4.3 乙醇基質對訊號增強的影響 43
2.3.5 連線系統分析系統特性與效能評估 45
2.3.5.1 連線分析系統特性與分析方法確效 46
2.3.5.2 威士忌酒樣品分析 49
2.3.5.3 方法比較 51
2.4 小結 53
2.5 參考文獻 54
第三章 摺疊式紙基分析裝置搭配比色法之檢測系統開發及其於蜂蜜新鮮度指標評鑑之應用 57
3.1 前言 57
3.2 實驗部分 62
3.2.1 試劑與材料 62
3.2.2 儀器設備 62
3.2.3 摺疊式紙基分析裝置製程 63
3.2.4 真實樣品分析程序 65
3.3 結果與討論 67
3.3.1 摺疊式紙基分析裝置之設計理念 67
3.3.2 紙基材分析裝置製程之探討 70
3.3.3 顯色試劑於紙基平台上適用性之評估 74
3.3.3.1 紙基平台上顯色試劑濃度對於顯色靈敏度之影響 75
3.3.3.2 紙基平台上顯色試劑安定性對於顯色靈敏度之影響 77
3.3.3.3 紙基平台上潛在干擾物對於顯色靈敏度之影響 79
3.3.4 數位單眼相機及影像分析軟體之檢測系統整合 80
3.3.5 摺疊式紙基分析裝置操作條件最適化探討 83
3.3.5.1 裝置平衡時間對影像分析靈敏度之影響 83
3.3.5.2 檢測區域直徑大小對影像分析靈敏度之影響 84
3.3.5.3 反應流道長度對影像分析靈敏度之影響 85
3.3.5.4 樣品體積對影像分析靈敏度之影響 87
3.3.6 摺疊式紙基分析裝置效能評估 89
3.3.6.1 摺疊式紙基分析裝置特性與分析方法確效 90
3.3.6.2 真實樣品中指標成分分析 95
3.4 小結 97
3.5 參考文獻 98
第四章 結語 101
附錄、論文口試審查委員意見修正情形一覽 104

(1) Which destination has the world's best food?, http://edition.cnn.com/travel/article/world-best-food-culinary-journeys/index.html, (accessed September, 2017).
(2) 歷年食品中毒資料，衛生福利部食品藥物管理署，https://www.fda.gov.tw/TC/siteContent.aspx?sid=323，(2017年9月).
(3) United States, US 7,718,441 B2, 2010.
(4) 重金屬檢驗方法總則，衛生福利部食品藥物管理署，https://www.fda.gov.tw/TC/siteListContent.aspx?sid=103&id=9533，(2017年9月).
(5) 熊同銘、劉鎮山，環境分析－原理與應用，光譜分析法，環境分析學會，台灣，2012.
(6) Armenta, S.; Garrigues, S.; de la Guardia, M. TrAC, Trends Anal. Chem. 2008, 27, 497–511.
(7) SGS檢驗項目，台灣檢驗科技股份有限公司，http://www.sgs.com.tw/zh-TW/Local/Taiwan/Solutions/Taiwan-Safety-Information-Platform.aspx，(2017年9月).
(8) Lee, F. Lab-on-a-Chip: A Revolution in Instrumentation, John Wiley & Sons. New York, USA, 1996.
(9) Manz, A.; Graber, N.; Widmer, H. M. Sens. Actuators, B: Chem. 1990, 1, 244–248.
(10) Terry, S. C.; Jerman, J. H.; Angell, J. B. IEEE Trans. Electron Devices 1979, 26, 1880–1886.
(11) Harrison, D. J.; Manz, A.; Fan, Z.; Luedi, H.; Widmer, H. M. Anal. Chem. 1992, 64, 1926–1932.
(12) Harrison, D. J.; Fluri, K.; Seiler, K.; Fan, Z.; Effenhauser, C. S.; Manz, A. Science 1993, 261, 895–897.
(13) Ramsey, R. S.; Ramsey, J. M. Anal. Chem. 1997, 69, 1174–1178.
(14) He, B.; Tait, N.; Regnier, F. Anal. Chem. 1998, 70, 3790–3797.
(15) Boone, T. D.; Fan, Z. H.; Hooper, H. H.; Ricco, A. J.; Tan, H.; Williams, S. J. Anal. Chem. 2002, 74, 78 A–86 A.
(16) Martynova, L.; Locascio, L. E.; Gaitan, M.; Kramer, G. W.; Christensen, R. G.; MacCrehan, W. A. Anal. Chem. 1997, 69, 4783–4789.
(17) Klank, H.; Kutter, J. P.; Geschke, O. Lab Chip 2002, 2, 242–246.
(18) Cheng, J.-Y.; Wei, C.-W.; Hsu, K.-H.; Young, T.-H. Sens. Actuators, B: Chem. 2004, 99, 186–196.
(19) McCormick, R. M.; Nelson, R. J.; Alonso-Amigo, M. G.; Benvegnu, D. J.; Hooper, H. H. Anal. Chem. 1997, 69, 2626–2630.
(20) Ebara, M.; Hoffman, J. M.; Hoffman, A. S.; Stayton, P. S. Lab Chip 2006, 6, 843–848.
(21) Fogarty, B. A.; Heppert, K. E.; Cory, T. J.; Hulbutta, K. R.; Martin, R. S.; Lunte, S. M. Analyst 2005, 130, 924–930.
(22) Wu, D.; Qin, J.; Lin, B. Lab Chip 2007, 7, 1490–1496.
(23) Mecker, L. C.; Martin, R. S. Anal. Chem. 2008, 80, 9257–9264.
(24) Roberts, M. A.; Rossier, J. S.; Bercier, P.; Girault, H. Anal. Chem. 1997, 69, 2035–2042.
(25) Locascio, L. E.; Perso, C. E.; Lee, C. S. J. Chromatogr. A 1999, 857, 275–284.
(26) Martinez, A. W.; Phillips, S. T.; Whitesides, G. M.; Carrilho, E. Anal. Chem. 2010, 82, 3–10.
(27) Neethirajan, S.; Kobayashi, I.; Nakajima, M.; Wu, D.; Nandagopal, S.; Lin, F. Lab Chip 2011, 11, 1574–1586.
(28) Jokerst, J. C.; Emory, J. M.; Henry, C. S. Analyst 2012, 137, 24–34.
(29) Jenkins, G.; Wang, Y.; Xie, Y. L.; Wu, Q.; Huang, W.; Wang, L.; Yang, X. Microfluid. Nanofluid. 2015, 19, 251–261.
(30) Cate, D. M.; Adkins, J. A.; Mettakoonpitak, J.; Henry, C. S. Anal. Chem. 2015, 87, 19–41.
(1) International Wine & Spirit Research, https://www.theiwsr.com/index.aspx, (accessed September, 2017).
(2) Whisky Invest Direct, https://www.whiskyinvestdirect.com/about-whisky/Scotch-exports-major-markets-differences-201608241, (accessed September, 2017).
(3) The Scotch Whisky Association, http://www.scotch-whisky.org.uk/, (accessed September, 2017).
(4) Wiśniewska, P.; Dymerski, T.; Wardencki, W.; Namieśnik, J. J. Sci. Food Agric. 2015, 95, 2159–2166.
(5) Bonic, M.; Tesevic, V.; Nikicevic, N.; Cvejic, J.; Milosavljevic, S.; Vajs, V.; Mandic, B.; Urosevic, I.; Velickovic, M.; Jovanic, S. J. Serb. Chem. Soc. 2013, 78, 933–945.
(6) Saxberg, B. E. H.; Duewer, D. L.; Booker, J. L.; Kowalski, B. R. Anal. Chim. Acta 1978, 103, 201–212.
(7) Parker, I. G.; Kelly, S. D.; Sharman, M.; Dennis, M. J.; Howie, D. Food Chem. 1998, 63, 423–428.
(8) Heller, M.; Vitali, L.; Oliveira, M. A. L.; Costa, A. C. O.; Micke, G. A. J. Agric. Food Chem. 2011, 59, 6882–6888.
(9) Soufleros, E. H.; Mygdalia, A. S.; Natskoulis, P. Food Chem. 2004, 86, 625–636.
(10) Cameán, A. M.; Moreno, I.; López-Artı́guez, M.; Repetto, M.; González, A. G. Talanta 2001, 54, 53–59.
(11) Barbeira, P. J. S.; Stradiotto, N. R. Talanta 1997, 44, 185–188.
(12) Ijeri, V. S.; Srivastava, A. K. Anal. Sci. 2001, 17, 605–608.
(13) Sampaio, O. M.; Reche, R. V.; Franco, D. W. J. Agric. Food Chem. 2008, 56, 1661–1668.
(14) Lachenmeier, D. W.; Nathan-Maister, D.; Breaux, T. A.; Sohnius, E.-M.; Schoeberl, K.; Kuballa, T. J. Agric. Food Chem. 2008, 56, 3073–3081.
(15) Shih, T.-T.; Chen, W.-Y.; Sun, Y.-C. J. Chromatogr. A 2011, 1218, 2342–2348.
(16) Papadoyannis, I. N. S., V.F. in Encyclopedia of Chromatography, ed. J. Cazes, CRC, Boca Raton, Fl, 2004, 250–266.
(17) Armenta, S.; Garrigues, S.; de la Guardia, M. TrAC, Trends Anal. Chem. 2008, 27, 497–511.
(18) Kong, M. C. R.; Salin, E. D. Anal. Chem. 2012, 84, 10038–10043.
(19) Xi, Y.; Duford, D. A.; Salin, E. D. Talanta 2010, 82, 1072–1076.
(20) Shih, T.-T.; Hsieh, C.-C.; Luo, Y.-T.; Su, Y.-A.; Chen, P.-H.; Chuang, Y.-C.; Sun, Y.-C. Anal. Chim. Acta 2016, 916, 24–32.
(21) Paulson, A. J. Anal. Chem. 1986, 58, 183–187.
(22) Straßburg, S.; Wollenweber, D.; Wünsch, G. Fresenius J. Anal. Chem. 1998, 360, 792–794.
(23) Yuan, D.; Das, S. J. Appl. Phys. 2007, 101, 024901.
(24) Fu, X.; Liu, S.; Ruan, X.; Yang, H. Sens. Actuators, B: Chem. 2006, 114, 618–624.
(25) Stroock, A. D.; Dertinger, S. K. W.; Ajdari, A.; Mezić, I.; Stone, H. A.; Whitesides, G. M. Science 2002, 295, 647–651.
(26) Nam-Trung, N.; Zhigang, W. J. Micromech. Microeng. 2005, 15, R1–R16.
(27) Glasgow, I.; Aubry, N. Lab Chip 2003, 3, 114–120.
(28) Liang-Hsuan, L.; Kee Suk, R.; Chang, L. J. Microelectromech. Syst. 2002, 11, 462–469.
(29) G. Bessoth, F.; J. deMello, A.; Manz, A. Anal. Commun. 1999, 36, 213–215.
(30) He, B.; Burke, B. J.; Zhang, X.; Zhang, R.; Regnier, F. E. Anal. Chem. 2001, 73, 1942–1947.
(31) Hengzi, W.; Pio, I.; Erol, H.; Syed, M. Smart Mater. Struct. 2002, 11, 662–667.
(32) He, B.; Tait, N.; Regnier, F. Anal. Chem. 1998, 70, 3790–3797.
(33) Lim, T.-K.; Ohta, H.; Matsunaga, T. Anal. Chem. 2003, 75, 3316–3321.
(34) Eboatu, A. N.; Diete-Spiff, S. T.; Ezenweke, L. O.; Omalu, F. J. Appl. Polym. Sci. 2002, 85, 2781–2786.
(35) Watts, J. F.; Chehimi, M. M. J. Adhesion 1993, 41, 81–91.
(36) Su, C. K.; Li, T. W.; Sun, Y. C. Anal. Chem. 2008, 80, 6959–6967.
(37) Losey, M. W.; Schmidt, M. A.; Jensen, K. F. Ind. Eng. Chem. Res. 2001, 40, 2555–2562.
(38) Barciela, J.; Vilar, M.; García-Martín, S.; Peña, R. M.; Herrero, C. Anal. Chim. Acta 2008, 628, 33–40.
(39) Cheng, H.; Liu, J.; Xu, Z.; Yin, X. Spectroc. Acta Pt. B-Atom. Spectr. 2012, 73, 55–61.
(40) Hu, Z.; Hu, S.; Gao, S.; Liu, Y.; Lin, S. Spectroc. Acta Pt. B-Atom. Spectr. 2004, 59, 1463–1470.
(41) Rodushkin, I.; Ödman, F.; Appelblad, P. K. J. Food Compos. Anal. 1999, 12, 243–257.
(42) Chen, B.; Heng, S.; Peng, H.; Hu, B.; Yu, X.; Zhang, Z.; Pang, D.; Yue, X.; Zhu, Y. J. Anal. At. Spectrom. 2010, 25, 1931–1938.
(43) Xue, S.; Liu, Y.; Li, H.-F.; Uchiyama, K.; Lin, J.-M. Talanta 2013, 116, 1005–1009.
(44) Do Van, K.; Tamotsu, Y.; Yoshiaki, U.; Yuzuru, T. Jpn. J. Appl. Phys. 2014, 53, 05FS01-01–05FS01-05.
(45) Shih, T.-T.; Hsu, I. H.; Chen, S.-N.; Chen, P.-H.; Deng, M.-J.; Chen, Y.; Lin, Y.-W.; Sun, Y.-C. Analyst 2015, 140, 600–608.

(1) Ajibola, A.; Chamunorwa, J. P.; Erlwanger, K. H. Nutr. Metab. 2012, 9, 61.
(2) 王元元、張德芹，蜂蜜的外用功能主治研究進展，天津中醫藥大學學報，中國，2013.
(3) J.M. Ames, The Maillard reaction, Elsevier, London, 1992.
(4) Murkovic, M.; Pichler, N. Mol. Nutr. Food Res. 2006, 50, 842–846.
(5) Teixidó, E.; Santos, F. J.; Puignou, L.; Galceran, M. T. J. Chromatogr. A 2006, 1135, 85–90.
(6) Durling, L. J. K.; Busk, L.; Hellman, B. E. Food Chem. Toxicol. 2009, 47, 880–884.
(7) The Codex Alimentarius of the World Health Organisation, http://www.who.int/foodsafety/areas_work/food-standard/en/, (accessed September, 2017).
(8) Council Directive 2001/110/EC of 20 December 2001 relating to honey, http://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX%3A32001L0110, (accessed September, 2017).
(9) Spano, N.; Ciulu, M.; Floris, I.; Panzanelli, A.; Pilo, M. I.; Piu, P. C.; Scanu, R.; Sanna, G. Food Chem. 2008, 108, 81–85.
(10) Winkler, O. Zeitschrift für Lebensmittel-Untersuchung und Forschung 1955, 102, 161–167.
(11) White, J. W. J. Assoc. Off. Anal. Chem. 1979, 62, 509–514.
(12) Spano, N.; Ciulu, M.; Floris, I.; Panzanelli, A.; Pilo, M. I.; Piu, P. C.; Salis, S.; Sanna, G. Talanta 2009, 78, 310–314.
(13) Xu, H.; Templeton, A. C.; Reed, R. A. J. Pharm. Biomed. Anal. 2003, 32, 451–459.
(14) Teixidó, E.; Moyano, E.; Santos, F. J.; Galceran, M. T. J. Chromatogr. A 2008, 1185, 102–108.
(15) Alonso Lomillo, M. A.; Lomillo, M. A. A.; Munoz Pascual, F. J.; Lomillo, M. A.; del-Campo, F. J.; Pascual, F. J. Electroanalysis 2006, 18, 2435–2440.
(16) Terry, S. C.; Jerman, J. H.; Angell, J. B. IEEE Trans. Electron Devices 1979, 26, 1880–1886.
(17) Yamada, K.; Henares, T. G.; Suzuki, K.; Citterio, D. Angew. Chem.-Int. Edit. 2015, 54, 5294–5310.
(18) Liu, B.; Du, D.; Hua, X.; Yu, X.-Y.; Lin, Y. Electroanalysis 2014, 26, 1214–1223.
(19) Jones, G.; Kraft, A. Bus. Hist. 2004, 46, 100–122.
(20) Martinez, A. W.; Phillips, S. T.; Butte, M. J.; Whitesides, G. M. Angew. Chem.-Int. Edit. 2007, 46, 1318–1320.
(21) Martinez, A. W.; Phillips, S. T.; Wiley, B. J.; Gupta, M.; Whitesides, G. M. Lab Chip 2008, 8, 2146–2150.
(22) Willis, R. C. Anal. Chem. 2006, 78, 5261–5265.
(23) Wong, S. Y.; Cabodi, M.; Rolland, J.; Klapperich, C. M. Anal. Chem. 2014, 86, 11981–11985.
(24) United States, US 7,718,441 B2, 2010.
(25) Hostalkova, A.; Klingelhofer, I.; Morlock, G. E. Anal. Bioanal. Chem. 2013, 405, 9207–9218.
(26) Chin, C. D.; Linder, V.; Sia, S. K. Lab Chip 2007, 7, 41–57.
(27) Martinez, A. W.; Phillips, S. T.; Whitesides, G. M. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 19606–19611.
(28) Neethirajan, S.; Kobayashi, I.; Nakajima, M.; Wu, D.; Nandagopal, S.; Lin, F. Lab Chip 2011, 11, 1574–1586.
(29) Jokerst, J. C.; Emory, J. M.; Henry, C. S. Analyst 2012, 137, 24–34.
(30) Martinez, A. W.; Phillips, S. T.; Whitesides, G. M.; Carrilho, E. Anal. Chem. 2010, 82, 3–10.
(31) Liu, H.; Crooks, R. M. J. Am. Chem. Soc. 2011, 133, 17564–17566.
(32) Hull, T. C. Math. Intell. 2005, 27, 92–95.
(33) Carrilho, E.; Martinez, A. W.; Whitesides, G. M. Anal. Chem. 2009, 81, 7091–7095.
(34) Foley, W. M.; Sanford, G. E.; Mckennis, H. J. Am. Chem. Soc. 1952, 74, 5489–5491.
(35) Risner, C. H.; Kiser, M. J.; Dube, M. F. J. Food Sci. 2006, 71, C179–C184.
(36) Gaspar, E. M. S. M.; Lucena, A. F. F. Food Chem. 2009, 114, 1576–1582.
(37) Gaspar, E. M. S. M.; Lopes, J. F. J. Chromatogr. A 2009, 1216, 2762–2767.
(38) Foo Wong, Y.; Makahleh, A.; Al Azzam, K. M.; Yahaya, N.; Saad, B.; Amrah Sulaiman, S. Talanta 2012, 97, 23–31.
(39) 食品公告檢驗方法，衛生福利部食品藥物管理署，https://www.fda.gov.tw/TC/siteList.aspx?sid=103，(accessed September, 2017).
(40) Lu, Y.; Shi, W.; Qin, J.; Lin, B. Electrophoresis 2009, 30, 579–582.
(41) Silva, T. G.; de Araujo, W. R.; Muñoz, R. A. A.; Richter, E. M.; Santana, M. H. P.; Coltro, W. K. T.; Paixão, T. R. L. C. Anal. Chem. 2016, 88, 5145–5151.
(42) Wang, C.-C.; Hennek, J. W.; Ainla, A.; Kumar, A. A.; Lan, W.-J.; Im, J.; Smith, B. S.; Zhao, M.; Whitesides, G. M. Anal. Chem. 2016, 88, 6326–6333.
(43) 蜂蜜國家標準 (CNS 1305)，經濟部標準檢驗局，https://www.cnsonline.com.tw/?node=detail&generalno=1305&locale=zh_TW，(accessed September, 2017).