皮膚代謝物在臨床診斷中有著巨大的潛力。然而，皮膚的採樣和分析工作流程單調且耗時。此文中我們展示了基於水凝膠輔助採樣的皮膚代謝物採樣的自動販賣機式皮膚排泄物分析平台。此平台中，機器手臂操縱具有水凝膠的採樣探針並將之壓上受試者的前臂。由於水凝膠的高度親水性，皮膚釋放的水溶性代謝物會被水凝膠所收集。然後探針被放置在客製的開放採樣端口上，端口連接到串聯質譜儀的電噴灑離子源。水凝膠中的代謝物迅速透過端口中的溶劑接點被萃取並由質譜儀分析。目標分析物的離子電流會顯示在客制的圖形用戶界面上，其也可用於控制分析平台的關鍵組件。在使用者投入硬幣或插入健保卡、按下按鈕、並將手放至指定位置後，採樣和分析工作流程會自動啟動。為了使平台更加易用，系統會發出語音提示使用者目前系統的狀態。該平台由低成本的機械和電子模塊構成（包含機器手臂，單板電腦和兩個微控制器）。此系統對於瓊脂糖中的精氨酸，瓜氨酸和組氨酸的偵測極限分別為0.11，0.22和0.17 μM。此系統也成功串聯高解析度質譜儀來鑑定出所收集到的幾種低分子量代謝物。

Skin metabolites show huge potential for use in clinical diagnostics. However, skin sampling and analysis workflows are tedious and time-consuming. Here, we demonstrate a vending-machine-style skin excretion profiling platform based on hydrogel-assisted sampling of skin metabolites. In this platform, a sampling probe with hydrogel is held by a robotic arm. The robotic arm manoeuvres the probe to press it onto the forearm of human subject. Water-soluble metabolites—released by skin—are collected into the hydrogel due to its highly hydrophilic nature. The probe is then placed on a custom-made open port sampling interface coupled to an electrospray ion source of a tandem mass spectrometer. Metabolites in the hydrogel are immediately extracted by a solvent liquid junction in the interface, and analyzed by the mass spectrometer. The ion current of the target analyte is displayed on a customized graphical user interface, which can also be used to control the key components of the analytical platform. The automated sampling and analysis workflow starts after the user inserts coins or presents an insurance card, presses a button, and extends an arm on the sampling area. To make the platform user-friendly, voice messages are emitted to notify the users about the status of the system. The platform relies on low-cost mechanical and electronic modules (a robotic arm, a single-board computer, and two microcontroller boards). The limits of detection of arginine, citrulline, and histidine (in agarose) are 0.11, 0.22 and 0.17 μM, respectively. Various low-molecular-weight metabolites have been identified with a high-resolution mass spectrometer.

中文摘要 i
Abstract ii
謝誌 iii
Table of Contents iv
List of Tables v
List of Figures vi
List of Acronyms xi
Chapter 1: Introduction 1
1.1 Skin metabolites 1
1.1.1 Origin of skin metabolites 1
1.1.2 Chemicals present on skin 2
1.1.3 Sampling methods 3
1.2 Automation in chemistry 4
1.2.1 Robot 5
1.2.2 Microcontroller board 6
1.2.3 Single-board computer 7
1.3 Mass spectrometry 8
1.3.1 Ion sources 9
1.3.2 Mass analyzer 11
1.3.3 Tandem mass spectrometry 13
1.4 Goals of the study 15
Chapter 2: Vending-Machine-Style Skin Excretion Profiling: a Case of Robotization of Sampling and Analysis 17
2.1 Introduction 17
2.2 Experimental section 20
2.2.1 Preparation of hydrogel probes 20
2.2.2 Robotic arm for skin sampling 23
2.2.3 Open port sampling interface for mass spectrometry 25
2.2.4 System integration and electronic control 28
2.2.5 Mass spectrometry parameters 31
2.2.6 Data acquisition, transmission, and processing 31
2.2.7 Calculation of limit of detection and limit of quantitation 32
2.2.8 Chemicals 33
2.3 Results and discussions 33
2.3.1 Operation of the platform 33
2.3.2 Optimization of the platform 35
2.3.3 Characterization of the platform 39
2.3.4 Application of the platform in skin profiling 41
2.4 Conclusions 47
Chapter 3: Conclusions and Future Perspective 48
References 51
Appendix 1 64
Appendix 2 67

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