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  1. NTU Theses and Dissertations Repository
  2. 理學院
  3. 化學系
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73141
完整後設資料紀錄
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dc.contributor.advisor徐丞志(Cheng-Chih Hsu)
dc.contributor.authorYi-Ling Gaoen
dc.contributor.author高鐿綾zh_TW
dc.date.accessioned2021-06-17T07:19:21Z-
dc.date.available2024-07-25
dc.date.copyright2019-07-25
dc.date.issued2019
dc.date.submitted2019-07-09
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73141-
dc.description.abstract因為環境中的汙染物或特定生活習慣而造成的長期慢性暴露,往往帶來不良的身體健康影響。然而,人體、周遭環境及生活習慣間的關係是相當複雜且難以運用單一技術或儀器進行分析探討的。因此,我們將透過不同技術的整合探討三者間之關聯性。
生活環境會受到個人的行為及健康狀態影響。因此,分析室內灰塵的化學組成能讓我們更進一步了解人體健康與環境的關係。同時,為了瞭解人體與生活習慣之關聯,我們探討了嚼食檳榔及攝取保健食品之議題。我們應用了質譜儀分析多樣化的樣品並收集多樣且高質量的資訊。更利用液相層析質譜儀來獲得時間解析的化學資訊。除此之外,結合GNPS及機器學習等高通量數據處理方法,我們得以在短暫且有限的時間內分析龐大數據,並應用於其他型態的樣品上。
在本論文中,我們使用質譜儀並結合多樣分析數據方法,來探討以下兩大類的議題: (1) 利用紙片即時直接分析質譜儀顯著提升分析速度及定量之準確性;(2) 結合串聯式質譜儀及分析數據平台,如GNPS與監督式機器學習,了解人體、周遭環境及生活型態之關係。
zh_TW
dc.description.abstractThere is a high chance for a human to have adverse health outcomes because of the long term chronic exposure under a polluted environment or having improper lifestyles. However, the interactions between the human, surrounding environment and the lifestyles are complicated and hard to fathom with only one single technique. Therefore, we demonstrated examples of clarifying these interactions by combining multiple techniques.
The behaviors and conditions of individuals influence the environment. As a result, screening the composition of the chemicals of indoor dust allows us to get a deeper insight into the relationships between individuals and the environment. On the other hand, to understand the human health-habit interaction, we investigated the effect of chewing betel quid and intaking functional food. In our approach, we apply mass spectrometry (MS) to obtain diverse and high-quality information from various samples. Time-resolved chemical information was also obtained by tandem mass spectrometry technique. Furthermore, combining the MS data with high-throughput data processing strategies, such as GNPS and machine learning, we were able to analyze tremendous data within a little amount of time and to use the same framework in different samples.
In this thesis, we used mass spectrometry combining analysis strategies to demonstrate that (1) the relationship between human, surrounding environment and the lifestyles can be understood by the combination of tandem mass spectrometry and data analysis platforms, including GNPS and supervised machine learning; (2) applying pDART significantly increase the analysis throughput while maintaining the quantitative accuracy compared to the traditional LC-MS approach.
en
dc.description.provenanceMade available in DSpace on 2021-06-17T07:19:21Z (GMT). No. of bitstreams: 1
ntu-108-R06223116-1.pdf: 6990089 bytes, checksum: 9ae29b8debf7ee87411dde9133973de5 (MD5)
Previous issue date: 2019
en
dc.description.tableofcontents目錄
謝誌 i
摘要 v
Abstract vii
圖目錄 xiii
表目錄 xvi
Chapter 1. Introduction 1
1-1 The Linking of Environment and Lifestyle to Human 1
1-1-1 The Connection of Environment to Human 2
1-1-2 The Connection of Lifestyle to Human 3
1-1-3 Study and Analysis Approach by Mass Spectrometry 4
1-1-4 Motivation 4
1-2 Mass Spectrometry Analysis 5
1-2-1 High Performance Liquid Chromatography Tandem Mass Spectrometry (HPLC-MS) 6
1-2-2 Direct Analysis in Real Time Mass Spectrometry (DART-MS) 7
1-2-3 Ion Mobility Spectrometry (IMS)49 8
1-3 Data Analysis Platform 9
1-3-1 Global Natural Products Social Molecular Networking (GNPS) 9
1-3-2 Supervised Machine Learning 10
1-4 Conclusion 11
Chapter 2. Using pDART-MS for Rapid Quantification of Arecoline for Betel Quids in Eastern Taiwan 13
2-1 Introduction 13
2-2 Materials and Methods 15
2-2-1 Sample Collection 15
2-2-2 Preparation of Betel Quid Water Extract 16
2-2-3 Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UHPLC-MS/MS) 16
2-2-4 Paper-loaded Direct Analysis in Real Time Mass Spectrometry (pDART-MS) 17
2-3 Results and Discussion 18
2-3-1 Quantification Model Construction: Data Collection and Data Processing 18
2-3-2 Validation for pDART-MS Quantification by UHPLC-MS/MS 22
2-3-3 Betel Quid Containing Different Ingredients 26
2-3-4 Arecoline Release after Chewing 28
2-4 Conclusion 30
Chapter 3. Rapid Quantification of Phthalate with the Separation of Isomer Using pDART Coupling with Ion Mobility Spectrometry Mass Spectrometry (TWIMS-MS) 33
3-1 Introduction 33
3-2 Materials and Methods 36
3-2-1 Materials 36
3-2-2 Sample Collection 37
3-2-3 Preparation of Dust Extract 37
3-2-4 Paper-loaded Direct Analysis in Real Time Mass Spectrometry (pDART-MS) 38
3-2-5 Mass Spectrometry Analysis: Ion Mobility Spectrometry (TWIMS) 38
3-2-6 High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS) 39
3-3 Results and Discussion 40
3-3-1 Calibration Curves Construction and Comparison of LOQ Between pDART-MS and LC-MS/MS 40
3-3-2 Isomer Identification by pDART-IMS 44
3-4 Conclusion 45
Chapter 4. Linking Chemo-environmental Fingerprints of Dust with Health Status of Household Members 47
4-1 Introduction 47
4-2 Materials and Methods 51
4-2-1 Sample Collection 51
4-2-2 Preparation of Household Dust Extract 52
4-2-3 Method Validation: Extraction Recovery Rate Estimation 53
4-2-4 Ultra High Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS/MS) 54
4-2-5 Household Grouping: Health Examinations and Questionnaires 55
4-2-6 Supervised Machine Learning (ElasticNet Regularization) 55
4-2-7 Compounds Identification by GNPS Molecular Networking 58
4-3 Results and Discussion 59
4-3-1 Extraction Efficiency Evaluation by Targeted Compounds 59
4-3-2 MS/MS Molecular Networking 60
4-3-3 Labels Prediction and Compounds Elucidation 66
4-4 Conclusion 77
Chapter 5. Molecular Networking as a Dereplication Strategy for Monitoring Metabolites of Natural Product Treated Cancer Cells 79
5-1 Introduction 79
5-2 Materials and Methods 83
5-2-1 Preparation of C. militaris Extract 83
5-2-2 Cell Culture 83
5-2-3 High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS) 84
5-2-4 Molecular Networking 85
5-2-5 Time-dependent Molecular Networking 87
5-3 Results and Discussion 88
5-3-1 Elucidation of Cordycepin Relative Compounds by Molecular Networking 88
5-3-2 C. militaris Extract-induced Metabolites Changes in Cells 95
5-4 Conclusion 101
Chapter 6. Conclusion 103
Appendix A: Table of Abbreviation 105
References 107
dc.language.isoen
dc.subjectGNPSzh_TW
dc.subject人體健康生活及環境zh_TW
dc.subject環境化學zh_TW
dc.subject紙片即時直接分析質譜儀zh_TW
dc.subject天然產物zh_TW
dc.subject液相層析質譜儀zh_TW
dc.subject機器學習zh_TW
dc.subjectHuman health interactionen
dc.subjectpDART-MSen
dc.subjectGNPSen
dc.subjectMachine learningen
dc.subjectNatural productsen
dc.subjectEnvironmental chemistryen
dc.subjectLC-MS/MSen
dc.title基於質譜代謝體分析技術探討環境及生活習慣與人體健康之關聯性zh_TW
dc.titleInvestigate the linking of environment and lifestyle to human health by analyzing metabolites using mass spectrometry techniquesen
dc.typeThesis
dc.date.schoolyear107-2
dc.description.degree碩士
dc.contributor.oralexamcommittee蘇大成(Ta-Chen Su),何佳安(Ja-an Ho),陳玟伶(Wen-Ling Chen)
dc.subject.keyword液相層析質譜儀,紙片即時直接分析質譜儀,GNPS,機器學習,天然產物,環境化學,人體健康生活及環境,zh_TW
dc.subject.keywordLC-MS/MS,pDART-MS,GNPS,Machine learning,Natural products,Environmental chemistry,Human health interaction,en
dc.relation.page118
dc.identifier.doi10.6342/NTU201901305
dc.rights.note有償授權
dc.date.accepted2019-07-09
dc.contributor.author-college理學院zh_TW
dc.contributor.author-dept化學研究所zh_TW
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