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研究生:馬振華
研究生(外文):Cheng-Hua Ma
論文名稱:台灣冬季氣膠中棕炭成分之分析鑑定;利用微米液珠加速蛋白水解開發快速線上消化平台用於混合蛋白質樣品之即時由下而上鑑定分析
論文名稱(外文):Molecular Characterization of Brown Carbon in Wintertime Aerosol of Taiwan;Developing a Rapid Online Digestion Platform for Real-Time Bottom-Up Characterization of Protein Mixtures Utilizing Microdroplet-Accelerated Enzymatic Digestion
指導教授:徐丞志
指導教授(外文):Cheng-Chih Hsu
口試委員:陳玉如陳逸然丁育頡
口試委員(外文):Yu-Ju ChenYet-Ran ChenYu-Chieh Ting
口試日期:2023-06-29
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:化學系
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2023
畢業學年度:111
論文頁數:139
中文關鍵詞:氣膠棕炭紫外光與可見光吸收分子網路蛋白質體學質譜法分析微米液珠化學線上消化
外文關鍵詞:AerosolBrown carbonUV-Vis absorptionMolecular networkingMass spectrometry-based proteomicsMicrodroplet chemistryOnline digestion
DOI:10.6342/NTU202303844
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  • 被引用被引用:0
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氣膠為大氣中懸浮的粒子,大小範圍落於幾奈米至幾十微米之間。其來源可能源於多種排放源與反應途徑,使得內含的化合物在結構上差異極大。在氣膠液滴進行的液相反應中所觀察到的獨特性質也進一步推動名為「微米液珠化學」的研究領域。本篇論文中,我們展示了質譜用於微米尺度環境下產物之分析鑑定以及探索微米液珠化學的實際應用。
第一章節講述冬季氣膠中棕炭(brown carbon, BrC)成分的分析鑑定。BrC屬於有機碳,在紫外光以及可見光波段具吸收,且已被證明會對大氣、環境和健康產生重要的影響。分子之鑑定分析在追蹤BrC物種來源和評估光學性質上扮演重要角色。考量其吸光性質,我們首先結合紫外光-可見光吸收與質譜檢測來挑選BrC物種。與吸收峰滯留時間相互配對的質譜特徵被明確指認為BrC物種。為了對可能的BrC物種進行較大規模的篩選與鑑定,我們採用分子網路技術(Molecular networking)並成功尋找到代表硝基酚(Nitrophenol)衍生物的分子群(Cluster),其中大部分的化合物並未於先前的部分被鑑定。至此,我們提供BrC物種在分子組成的概貌,這將有助於後續鑑定的工作。
在第二章節,我們利用微米液珠加速化學反應的能力開發快速蛋白質分析平台。蛋白水解仍為傳統蛋白質分析流程之其中一項「速率決定步驟」,其中蛋白質的存在通常由串聯質譜技術所鑑定到的胜肽來推斷,這被稱為「由下而上(Bottom-up)」的策略。先前研究表明,在加速氣流電噴灑所產生的微米液珠中進行消化能將此反應加速至毫米以下的時間尺度。在此,我們提出一個簡單且快速的線上消化平台,該平台結合層析分離與微米液珠內消化,稱作線上微米液珠加速蛋白水解(Microdroplet-accelerated enzymatic digestion, MAED)。該平台以簡單的儀器架設將微米液珠內消化的應用範圍從單一蛋白質擴展至混合蛋白質樣品,且分析前無須進行耗時的蛋白水解。此平台能大大縮減耗時並經精簡蛋白質分析的流程。我們利用線上MAED針對不同複雜度的樣品進行測試,並且探討蛋白水解酶濃度對鑑定結果的影響。最後,我們比較了線上MAED與傳統蛋白質分析流程以探討該平台目前的限制與優勢。總而言之,透過微米液珠強大的催化活性,我們針對混合蛋白質樣品之鑑定分析提供一個簡單且快速的替代方案。
Aerosols refer to suspended particles in the atmosphere ranging in size between a few nanometers to tens of micrometers and may originate from various emission sources and reaction pathways, making its components structurally diverse. Extraordinary properties were observed in aqueous phase reactions of aerosol droplets, which later on drove the field of research termed “microdroplet chemistry”. In this thesis, we demonstrated two applications of mass spectrometry regarding the characterization of products in the microscale environment and investigating the utilization of microdroplet chemistry for practical use.
The first chapter involves the molecular characterization of brown carbon (BrC) species in aerosol samples collected in wintertime in Taiwan. BrC is a subset of organic carbon that has possess absorption at the UV and visible region and was proven to have a large impact on the atmosphere, environment, and human health. Molecular characterization is essential to trace the source and assess the optical properties of BrC species. Considering its light-absorbing property, we first demonstrated the identification of BrC chromophores by combining UV-Vis detection with mass spectrometric analysis. The features with retention times matched to absorption peaks were unambiguously identified as BrC species. To screen for potential BrC species on a larger scale, we employed molecular networking and successfully assigned a cluster representing nitrophenol derivatives, in which most of them were not identified in the previous sections. Up to this point, we provide an overview of the molecular landscape of BrC species which would facilitate identification in the following works.
In the second chapter, we harnessed the unique property of microdroplets, namely the acceleration of reaction rates, to develop a rapid analytical platform for protein analysis. Enzymatic proteolysis remains one of the “rate-determining steps” in the conventional protein analysis workflow, where the presence of protein is inferred from the peptides identified generally via tandem mass spectrometry, known as the “bottom-up” approach. It has been demonstrated that such reaction to a timescale lower than milliseconds by performing digestion in microdroplets generated from electrosonic spray. We describe a simple and rapid online digestion platform involving the integration of chromatographic separation with enzymatic digestion in microdroplets, termed online microdroplet-accelerated enzymatic digestion. Online MAED expands the scale of enzymatic digestion via microdroplet MS from single protein to protein mixtures and simultaneously eliminates the need for lengthy enzymatic digestion in sample preparation with minor modifications to conventional LC-MS setup, significantly reducing the time required and eventually streamlining the entire protein analysis process. Online MAED was tested on different samples in terms of complexity and the influence of pepsin concentration on the identification results was investigated. Lastly, we compared online MAED with the conventional protein analysis workflow to demonstrate its current limitations and advantages. Overall, we provide a simple and rapid method alternative to conventional approaches for characterizing protein mixtures through the immense catalytic activity of microdroplets.
謝誌 i
摘要 iii
Abstract v
目錄 viii
圖目錄 xi
表目錄 xvi
Chapter 1. Molecular Characterization of Brown Carbon in Wintertime Aerosol of Taiwan 1
1月1日 Introduction 1
2001/1/1 Brown carbon in atmospheric aerosol 1
2001/1/2 Molecular networking 5
2001/1/3 Study aim 7
1月2日 Materials and Methods 8
2001/2/1 Samples collection and preparation 8
2001/2/2 Sample analysis 8
2001/2/3 Data analysis 9
1月3日 Results and Discussion 10
2001/3/1 Direct assignment of BrC chromophores 10
2001/3/2 Molecular networking for BrC characterization 17
1月4日 Conclusion 20
1月5日 Future directions 20
1月6日 Reference 23
1月7日 Supporting information 30
Chapter 2. Developing a Rapid Online Digestion Platform for Real-Time Bottom-Up Characterization of Protein Mixtures Utilizing Microdroplet-Accelerated Enzymatic Digestion 42
2月1日 Introduction 42
2002/1/1 Mass spectrometry-based proteomics 42
2002/1/2 Accelerated digestion methods 45
2002/1/3 Accelerated reaction rates in microdroplets 47
2002/1/4 Microdroplet mass spectrometry 50
2002/1/5 Our concept and study aim 53
2月2日 Materials and Methods 54
2002/2/1 Chemicals and Reagents 54
2002/2/2 ESSI sprayer setup 55
2002/2/3 Instrument setup of direct infusion experiments 56
2002/2/4 Online MAED 57
2002/2/5 Conventional bottom-up and top-down analysis setup 59
2002/2/6 Bulk digestion 60
2002/2/7 Reduction and alkylation of BSA and MAb 60
2002/2/8 Mouse brain extract preparation 60
2002/2/9 Data processing 61
2月3日 Results and Discussion 64
2002/3/1 Feasibility assessment and optimization 64
2002/3/2 Demonstration on mixed protein standard 70
2002/3/3 Demonstration on proteins of larger molecular weight 72
2002/3/4 Application to mouse brain extract 77
2002/3/5 Comparison with the conventional bottom-up approach 82
2002/3/6 Features of online MAED and current limitations 94
2002/3/7 Future applications 99
2月4日 Conclusion 102
2月5日 References 103
2月6日 Supporting information 113
Appendix - Table of Abbreviations 138
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