臺灣博碩士論文加值系統

黃麴毒素（Aflatoxin）主要是由黃麴菌（Aspergillus Flavus）二次代謝產生的黴菌毒素（Mycotoxin），為一級人體致癌物。
目前官方公告的穀物中黃麴毒素檢測分析方法需要一次性免疫親和管柱（成本高）進行萃取，但此方法對於未被污染的農作物樣品仍需要支出同樣高的成本，並不符合綠色環保的概念，本篇利用MALDI-TOF 質譜法所具有的靈敏度高、偵測時間短以及可快速進行大量樣品篩檢的優點，建立實用可行的快篩方法，先行篩檢出未被污染的穀物，減少高成本定量分析所需要的資源支出。以2005年Ramos R.C.中提出以離子液體基質幫助黃麴毒素進行游離的分析方法中，其偵測極限無法達到符合法規的要求及前處理有使用到氯仿對環境並不友善，本篇對文獻中前處理步驟進行簡化，包括省略硫酸銅、矽藻土、氯仿的部分來達到省時（從 30 分鐘縮短至 10 分鐘）和綠色環保的概念，以及使用十八烷基三氯矽烷（OTS）修飾的鋁箔作為樣品承載表面，將偵測極限由100 ppb降低為0.1 ppb符合了法規的要求。

Aflatoxin, one of mycotoxin, is a secondary metabolite of Aspergillus Flavus and recognized as a primary human carcinogen.
The official method for aflatoxin analysis required a single-use immunoaffinity column for extraction. However, this high cost column cannot be waived for uncontaminated samples. It does not comply with the concept of green chemistry. A fast screening method may solve this problem and is interested. MALDI analysis offers the advantages of simple pretreatment procedure, high throughput and is a good candidate of fast screening. In 2005, ionic liquid matrix was first applied in the analysis of aflatoxin by MALDI-TOF MS, however, chloroform used in the sample pretreatment is not friendly to the environment and the detection limit is too high to reach the official standard in our tests. In this research, we simplified the pretreatment steps, including waived the copper sulfate, diatomaceous earth and chloroform to save time (from 30 minutes to 10 minutes) and more friendly to environment. Moreover, the using of octadecyltrichlorosilane coating aluminum foil surface for sample target reduced the detection limit from 100 ppb to 0.1 ppb and reach the official standard.

目錄
中文摘要..................................................I
英文摘要.................................................II
誌謝....................................................III
目錄.....................................................IV
表目錄..................................................VII
圖目錄.................................................VIII
第一章 緒論...............................................1
1.2.1 黃麴毒素（Aflatoxin）...............................4
1.2.2 黃麴毒素（Aflatoxin）檢測方法比較....................7
1.3.1 MALDI的發展........................................10
1.3.2 MALDI樣品配置......................................12
1.3.3 基質的特性.........................................14
1.3.4 離子液體基質（Ionic liquid martrices,ILMs）的簡介...18
1.3.5 MALDI 離子形成的機制...............................22
1.3.6 飛行時間質量分析儀的原理............................23
1.3.7 MA LDI-TOF MS的特點...............................30
1.3.8 影響分析物在M ALDI-TOF MS中的因素..................31
第二章 材料與方法........................................36
2.1.1 實驗藥品..........................................36
2.1.2 實驗樣品..........................................38
2.1.3 儀器設備...................... ...................38
2.2.1 基質溶液的配製............... .....................40
2.2.2 鹽類溶液的配製.....................................41
2.2.3 標準品的配製.......................................42
2.3.1 穀物樣品的毒素添加.................................43
2.3.2 穀物樣品的毒素萃取（DON、ZEA）......................43
2.3.3 穀物樣品的毒素萃取（AFS）...........................43
2.3.4 穀物樣品的毒素萃取（FB1）...........................44
2.4.1 MALDI 樣品的配製..................................44
2.4.2 MALDI-TOF MS的操作條件............................46
第三章 結果與討論........................................47
第四章 結論.............................................76
參考文獻................................................78
表目錄
表一、各國常見食品中真菌毒素的含量限制.......................3
表二、台灣食品中黃麴毒素（Aflatoxin）的含量限制..............3
表三、黃麴毒素異構物精確分子量及光學特性.....................5
表四、AFB1與DON精確分子量..................................6
表五、黃麴毒素(AFBS)的質譜檢測方法..........................9
表六、常用的基質結構與適用的分析物和有效的雷射波長............16
表七、MALDI離子液體(固體)基質的結構式與分子量................21
表八、MALDI-TOF MS 之各種毒素檢測條件統整表.................35
表九、MALDI-TOF MS操作參數設定.............................46
表十、毒素檢測條件統整(加入黃麴毒素).........................74
表十一、本實驗檢驗方法與衛生署公告檢驗方法的結果比較...........75

圖目錄
圖一、黃麴毒素（Aflatoxin）的化學結構式......................5
圖二、脫氧雪腐鐮刀菌烯醇（Deoxynivalenol）的化學結構式........6
圖三、MALDI-TOF MS的簡圖：(a) linear (b) reflectron......29
圖四、離子液體基質Et3N-α-CHCA於一般鋼盤之結晶狀態............48
圖五、離子液體基質Et3N-α-CHCA於OTS修飾鋁箔之結晶狀態.........48
圖六、離子液體基質Et3N-α-CHCA於一般鋼盤之MALDI-TOF質譜圖.....49
圖七、10 ppm的AFB1標準品與離子液體基質Et3N-α-CHCA與不同濃度NaCl混和後於一般鋼盤之MALDI-TOF質譜圖：（a）無添加NaCl；（b）1×10-1 M NaCl；（c）1×10-2 M NaCl；（d）1×10-3 M NaCl...........................................50
圖八、離子液體基質Et3N-α-CHCA與1×10-1 M NaCl與不同濃度的AFB1標準品混和後於一般鋼盤之MALDI-TOF質譜圖：（a）1 ppm；（b）100 ppb；（c）10 ppb；（d）1 ppb......53
圖九、10 ppm之AFB1標準品與離子液體基質Et3N-α-CHCA於OTS修飾鋁箔之MALDI-TOF質譜圖：（a）blank；（b）10 ppm...................................55
圖十、離子液體基質Et3N-α-CHCA與1×10-1 M NaCl與不同濃度的AFB1標準品混和後於OTS修飾鋁箔之MALDI-TOF質譜圖：（a）blank；（b）10 ppm；（c）1 ppm；（d）100 ppb；（e）10 ppb；（f）1 ppb（g）0.1 ppb...............................57
圖十一、10 ppm之DON標準品與離子液體基質Et3N-α-CHCA與 1×10-8 M KCl 混和後於一般鋼盤之MALDI-TOF質譜圖：（a）blank；（b）10 ppm...............61
圖十二、10 ppm的DON標準品與離子液體基質Et3N-α-CHCA與 1×10-1 M NaCl 混和後於OTS修飾鋁箔之MALDI-TOF質譜圖：（a）blank；（b）10 ppm............62
圖十三、不同濃度的AFB1標準品與離子液體基質Et3N-α-CHCA與 1×10-8 M KCl 於一般鋼盤之MALDI-TOF質譜圖：（a）10 ppm；（b）1 ppm；（c）100 ppb；（d）10 ppb.......63
圖十四、AFB1與DON各0.1 ppb標準品與離子液體基質Et3N-α-CHCA與鹽類混和後於一般鋼盤及OTS修飾鋁箔之MALDI-TOF質譜圖：（a）一般鋼盤；（b）OTS修飾鋁箔......65
圖十五、AFB1、DON、、FB1、ZEA毒素各0.1 ppb標準品與離子液體基質Et3N-α-CHCA與鹽類混和後於一般鋼盤及OTS修飾鋁箔之MALDI-TOF質譜圖：（a）OTS修飾鋁箔；（b）一般鋼盤...66
圖十六、真實穀物樣品添加測試（使穀物中含有各種濃度之AFB1）之MALDI-TOF質譜圖：（a）blank；（b）100ppb；（c）10ppb...................................67
圖十七、測試經不同材質之濾膜過濾AFB1標準品0.1 ppb之MALDI-TOF質譜圖：（a）blank - 0.22 μm Nylon；（b）0.1 ppb - 0.22 μm Nylon（c）blank - 0.22 μm PVDF；（d）0.1 ppb - 0.22 μm PVDF；（e）blank - 0.45 μm PVDF；（f）0.1 ppb - 0.45 μm PVDF ....................................................68
圖十八、測試經不同孔徑的PVDF濾膜過濾的真實樣品（使穀物中含有10 ppb AFB1）之MALDI-TOF質譜圖：（a）blank - 0.22 μm；（b）10 ppb - 0.22 μm；（c）blank - 0.45 μm；（d）10 ppb - 0.45 μm.....................................71
圖十九、實際樣品添加測試（使穀物中含有0.1 ppb之毒素）之MALDI-TOF質譜圖：（a）AFB1 0.1 ppb；（b）AFBS 0.1 ppb................................73

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