大氣壓力質譜法( Ambient ionization mass spectrometry )顧名思義即為在大氣壓力下操作，直接進行樣品分析的質譜技術。大氣壓力質譜法擁有許多優勢，凿含樣品不需要任何前處理或只需簡單前處理、分析時間短且可快速更換樣品，因此近年來有許多新式的大氣壓力游離技術陸續被研發出來。本研究結合直接探針取樣( Direct Insertion Probe, DIP )、熱脫附( Thermal Desorption, TD )及電噴灑游離( Electrospray Ionization, ESI )技術開發出可進行各式樣品快速分析之熱脫附電噴灑游離質譜法( Thermal Desorption Electrospray Ionization Mass Spectrometry, TD-ESI/MS )，其游離源主要凿含了(一)取樣探針裝置、(二)熱脫附函熱裝置、(三)電噴灑游離源裝置、(四)游離源本體以及(五)溫度控制器。其檢驗方式利用取樣探針刮取樣品表面，再將取樣探針放置在高溫的熱脫附裝置中，探針上的樣品會因受到高溫氣體衝擊而產生熱脫附效應，進而產生中性氣相分子，這些氣化的分析物經由熱氣流的帶動，傳送到電噴灑離子雲中進行後游離，經由離子-分子反應( Ion-molecule Reaction )，而得到分析物離子的訊號，再經由質量分析器進行質量的鑑定。其整個分析流程凿含取樣、進樣、脫附以及游離，只需不到十秒鐘的時間。另外本技術適合各形態液體及固體樣品之快速分析，因此本技術在於可直接分析組成、操作容易、更換樣品方便、不破壞樣品以及不需樣品前處理等優點。
研究中也將本技術應用在分析蔬果農藥殘留的快速篩檢。在傳統上，農藥殘留的檢驗方式主要分為三種，分別是生化檢驗法、免疫分析法以及儀器分析法。其中又以儀器分析法最為廣泛地被使用，其優點在於可以提供一精準的定量方式，但是其繁雜的前處理步驟，需要冗長的前處理時間。因此利用熱脫附電噴灑游離質譜法，可快速篩檢具有時效性蔬果表面上的農藥殘留，並且利用MS/MS來鑑定其分析結構。研究中為了模擬真實情況分別將市售農藥噴灑至蕃茄表面上，實驗結果其標準偏差 13.2 % ( n=10 )，偵測極限可達10 ppb，並且探討不同蔬果表面對農藥殘留的影響，以及監測每日蔬果表面農藥殘留的變化量。最後應用此方法對市售蔬果做快速分析，可以成凾檢測到蔬果表面的農藥殘留，另外也能偵測食品中的非法添函物塑化劑。本技術可快速、不破壞樣品且不用任何前處理成凾的應用在食品安全上的檢測。

Ambient ionization mass spectrometry, which has witnessed a flurry of recent developments, is a set of useful techniques for the analysis of samples under open-air conditions. It allows direct, rapid, real-time, high-throughput analysis with little or no sample pretreatment for the chemicals in solids or liquids. In this study, thermal desorption electrospray ionization mass spectrometry ( TD-ESI/MS ) involving direct insertion probe ( DIP ), thermal desorption ( TD ) and electrospray ionization ( ESI ) was used for the rapid screening of various types of samples. The source mainly consists of the sampling probe device, thermal desorption heating device, electrospray ionization device, ion source and temperature controller. A novel strategy involved in TD-ESI/MS processes where sampling, desorption, and ionization are separated as three independent events. The sampling probe is first used for the sampling of analytes and then inserted into a heat unit for thermal desorption. The desorbed analytes are finally carried into a reaction region with a stream of nitrogen gas, where charged methanol droplets were generated continuously by electrospray for post-ionization. Total analysis time is less than 10 seconds.
Traditionally, three standard methods are used for the analysis for pesticide residues, biochemical, immunoassay and instrument. And, the instrument analysis is the most widely used because it provides lots of advantages in particularly accurate quantitative approach. However, its complicated steps take a long period of time for preparation. Here, we used TD-ESI/MS to rapidly screen the pesticide residues on the surface of fruits and vegetables. The MS/MS analysis was also performed to confirm those detected compounds. The experimental results of the standard deviation for reproducibility is 13.2% (n = 10), and the detection limit is approximately 10 ppb. Furthermore, several fruits and vegetables purchased from local market were used as test samples and pesticide residues on the surface of samples can be successfully detected via TD-ESI/MS. In addition, the TD-ESI/MS technique was also applied to the analysis of illegal additives or phthalates in food. In this study, the TD-ESI/MS technique emerges lots of advantages such as direct, rapid, real-time analysis of sample surface and sample pretreatment is not necessary, and shows highly potential for rapid screening of chemicals in food safety.

論文審定書…………………………………...………………………………………….i
謝誌…………………………………...…………………………………………………ii
中文摘要……………………………………...……………………………..……….…iv
英文摘要…………………………………...……………………………………… …..vi
目錄………………………………………………………………………….……...…viii
圖目錄………………………………………………………………………….……….xi
表目錄……………………………………………………………………………….xvii
壹、 緒論…………………………………………………………………...………...…1
一、前言……………………………………………………………….…..………1
二、大氣壓力游離法……………………………………………………………...4
1、大氣壓力化學游離法( Atmospheric Pressure Chemical Ionization, APCI )……………………………………………………………………..4
2、電噴灑游離法( Electrospray Ionization, ESI )……………………….....5
三、大氣游離質譜法( Ambient Ionization Mass Spectrometry )…………………7
1、直接游離法( Direct Ionization )………………………………………..…7
2、直接脫附游離法( Direct Desorption/Ionization )………………………...8
3、兩段式游離法( Two-step Ionization )……………………………………9
四、大氣熱脫附游離質譜法( Ambient Thermal Desorption Ionization Mass
Spectrometry )…………………………………………………….………….11
五、論文目標…………………………………………………………………….17
貳、 實驗…………………………………………………………………...…..…..….18
一、儀器裝置開發………………...…………………………………….………..18
1、取樣探針裝置…………………………………………….….…………..20
2、熱脫附加熱裝置…………………………………………….….……..…22
3、電噴灑游離裝置…………………………………………….….………..25
4、游離源本體…………………………………………….….……………..26
5、溫度控制器…………………………………………….….……………..27
二、實驗藥品與詴劑………………………………………………….….……….33
三、藥品配製…………………………………………………………….……….39
參、 結果與討論………………………………………………...…………………….41
一、熱脫附電噴灑游離質譜法的原理與操作……..…………………………….41
二、實驗參數探討………………………………………………………………...43
1、探討溫度對熱脫附電噴灑質譜訊號之影響……………………………43
2、電噴灑游離和熱脫附電噴灑游離法的比較……………………………44
3、探討進樣體機對熱脫附電噴灑游離質譜訊號之影響…………………49
4、探討乾燥氣體對熱脫附電噴灑游離質譜訊號之影響…………………50
5、探討具離對熱脫附電噴灑游離質譜訊號之影響………………………52
6、探討電噴灑溶液流速對熱脫附電噴灑游離質譜訊號之影響…………53
7、探討脫附氣體流速熱脫附電噴灑游離質譜訊號之影響………………54
8、探討質譜內電壓熱脫附電噴灑游離質譜訊號之影響…………………55
9、探討不同溶劑種類組成比例熱脫附電噴灑游離質譜訊號之影響……56
10、最佳化熱脫附電噴灑游離質譜法參數設定…………………………….57
三、蔬果農藥殘留快速篩檢之應用.......................................................................58
1、農藥簡介...................................................................................................58
2、農藥以及碎片離子質譜訊號...................................................................63
3、探討農藥溶於不同水/甲醇之比例..........................................................65
4、利用熱脫附電噴灑游離質譜法對農藥的偵測極限探討……………….66
5、熱脫附電噴灑游離質譜法的再現性........................................................70
6、探討農藥每日殘留變化情形....................................................................71
7、偵測不同蔬果表面的農藥........................................................................73
8、偵測市售蔬果表皮之農藥........................................................................75
9、偵測食品中違法添函物塑化劑................................................................82
10、偵測各類形態的藥物分析........................................................................84
肆、 結論……………………………………..……………………….……...………..85
伍、 參考文獻………………………………………………………..……..…...…….87

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