融合微滴電噴灑游離質譜法（fused-droplet electrospray ionization mass spectrometry, FD-ES/MS）為一種新的游離技術，其操作原理是利用一霧化裝置（超音波霧化器）將分析物溶液霧化成微滴（aerosol）後，再與產自電噴灑游離源之帶電液滴融合，以達到游離的目的，因此分析物微滴的體積將會對於融合的過程有相當大的影響。由於在以超音波霧化器作為霧化裝置時，所產生的液滴其體積大小均相當一致，因此便無法使用此種裝置來探討當分析物微滴的體積產生變化時，其對於游離機制會造成何種影響。
本研究發現利用可控制溫度的加熱式霧化器（heated nebulizer）來當作融合微粒電噴灑游離質譜法的霧化裝置時，可以利用控制霧化器的溫度來改變分析物微滴之體積，也期望能藉由加溫的方式來探討此時融合微滴電噴灑游離質譜法中之游離機制。
研究中採用的方法是以加溫的方式（加熱範圍為25〜500℃）來控制由霧化裝置所產生之分析物（蛋白質、胜肽以及高分子聚合物）微滴中所含溶劑的量，藉此以改變液滴的體積。研究結果顯示隨著溫度的逐漸增加，分析物微滴中之溶劑分子會有不同程度的揮發，而質譜圖上所產生的分析物分子離子訊號會由原來的以帶多價電荷離子為主，轉變為以帶單一價數離子為主的分佈。也就是說將霧化器的溫度控制在較低溫度時，由於液滴的體積較大，分析物分子離子形成的機制會與電噴灑游離法所得的結果類似。但是在當霧化器的溫度控制在較高溫度時，導致液滴的體積減小，此時分析物分子離子形成的機制則與大氣壓力化學游離法所得的結果類似，而造成這些離子形成的原因顯然和分析物分子溶劑化（solvation）的程度有關。
使用加熱式霧化器當作融合微滴電噴灑游離法之霧化裝置時，其游離機制同時具備了電噴灑游離法與大氣壓力化學游離法之優點，以致於我們可以利用此種游離法以控制溫度的方式來改變分析物分子離子所帶的電荷數，進而可以使得分析物在不同溫度之下，以不同的帶電荷形式出現於融合微滴電噴灑游離質譜圖中。此外，這項研究也是在電噴灑游離法中首先能以物理（加溫）的方式來改變分析物所帶的電荷數。

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目 錄
摘 要………………………………………………………………Ⅰ
目 錄………………………………………………………………Ⅲ
圖 目 錄………………………………………………………………Ⅴ

壹、 緒論………………………………………………………………1
一、 質譜游離法的發展………………………………………….1
二、 電噴灑游離質譜法的發展歷史…………………………….4
三、 電噴灑游離質譜法中離子形成機制與原理……………….7
1、帶電液滴的生成………………………………………..7
2、溶劑的揮發與液滴的爆裂………………………….….8
3、氣相離子的生成原因探討……………………………..9
四、 融合微滴電噴灑游離質譜法的發展歷史…………………12
五、 融合微滴電噴灑游離質譜法之原理…………………..…..19
六、 論文目標……………………………………………….…...21

貳、 實驗……………………………………………………………...23
一、 儀器裝置…………………………………………………....23
二、 融合微滴電噴灑游離質譜法之游離源的組裝……………25
三、 實驗操作流程……………………………………………….30
四、 試劑及藥品的配製………………………………………….31

參、 結果與討論………………………………………………………34
一、 融合微滴電噴灑游離質譜法於蛋白質分子之分析…….…35
二、 融合微滴電噴灑游離質譜法於胜肽分子之分析……….…42
三、 融合微滴電噴灑游離質譜法於高分子聚合物之分析…….54
四、 融合微滴電噴灑游離質譜法於含鹽類（金屬離子）之PEG1000分子的分析……………………………………….66

肆、 結論…………………………………………………………...….75

伍、 參考文獻………………………………………………………....77

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