汗液分析為臨床診斷提供了一種可替代的非侵入性方法。然而，採樣並將汗液樣品轉移到分析儀器是具有一定的挑戰性。在本報告中，我們展示了一種利用扁平圓盤形採樣探針的方法，以及與萃取式電噴灑電離法 (EESI) 質譜 (MS) 在線耦合相容的二次萃取裝置。該探針可以從約 2.2 cm2 的皮膚區域採樣代謝物。隨後通過 EESI-MS 進行在線再萃取和分析進一步降低了由汗液成分引起的基質效應，從而消除了樣品製備步驟。總分析時間僅為 6 分鐘。我們對系統的關鍵參數進行了優化，包括：ESI中霧化氣體的流速、氣動樣品霧化器中的霧化氣體壓力、ESI中溶劑的流速、萃取劑的組成。標準溶液 (0.1 mL) 中添加了 0.04 M 氯化鈉以模擬汗液樣品中的基質效應。該方法進一步表徵為四種化學標準（正離子模式：組氨酸、亮氨酸、尿刊酸；負離子模式：乳酸）。檢測限範圍為 1.09 至 95.9 nmol。我們進一步從人體皮膚採樣證明了該方法對汗液分析的適用性。最後透過產物離子掃描和準確/精確質量匹配來識別一些已記錄的m/z訊號。

Sweat analysis provides an alternative and non-invasive way of clinical diagnostics. However, sampling and transferring sweat-derived samples to analytical instruments is challenging. In this report, we demonstrate a method utilizing a flat disc-shaped sampling probe, and a compatible re-extraction apparatus coupled on-line with extractive electrospray ionization (EESI) mass spectrometry (MS). The probe enables sampling of metabolites from a skin area of ~ 2.2 cm2. The subsequent on-line re-extraction and analysis by EESI-MS further mitigates matrix effects caused by sweat components, thus eliminating sample preparation steps. The total analysis time is only 6 min. We have optimized the key parameters of the system, including: flow rate of the nebulizing gas in ESI, pressure of the nebulizing gas in pneumatic sample nebulizer, flow rate of the solvent in ESI, and composition of extractant. The standard solutions (0.1 mL) were supplemented with 0.04 M sodium chloride to mimic the matrix effect in sweat samples. The methodology has further been characterized with four chemical standards (positive-ion mode: histidine, leucine, urocanic acid; negative-ion mode: lactic acid). The limits of detection range from 1.09 to 95.9 nmol. We have further demonstrated the suitability of the method for analysis of sweat. An attempt was made to identify some of the recorded signals by product-ion scan and accurate/exact mass matching.

中文摘要 i
Abstract ii
謝誌 iii
Table of Contents v
List of Tables vi
List of Figures vii
List of Acronyms x
Chapter 1: Introduction 1
1.1 Skin 1
1.1.1 Structure and function 2
1.1.2 Metabolites and metabolomics 3
1.1.3 Sweat 4
1.1.4 Biomarker in sweat 5
1.2 On-line and off-line analysis 6
1.3 Mass spectrometry 7
1.3.1 Ion source 8
1.3.2 Mass analyzer 11
1.3.3 Tandem mass spectrometry 14
1.4 Goals of the study 17
Chapter 2: Flat Disc-Shaped Sampling Probe and On-Line Re-Extraction Apparatus for Mass Spectrometric Analysis of Skin Metabolites 18
2.1 Introduction 18
2.2 Experimental section 20
2.2.1 Chemicals 20
2.2.2 Flat disc-shaped sampling probe 20
2.2.3 On-line re-extraction apparatus 22
2.2.4 Extractive electrospray ionization 23
2.2.5 Mass spectrometry 25
2.2.6 Data treatment 26
2.3 Results and discussions 27
2.3.1 Method optimization 27
2.3.2 Method characterization 30
2.3.3 Initial tests of the developed method using real specimens 32
2.3.4 Peak assignment by MS/MS with EESI-QqQ-MS and ESI-Q-ToF-MS 34
2.3.5 Final considerations 40
Chapter 3: Conclusions and Future Perspective 41
References 43
Appendix 1 62

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