基于铝箔的固相基底电喷雾电离质谱的进一步发展研究

Development of electrospray ionization on solid substrates (solid-substrate ESI) facilitates mass spectrometric analysis by avoiding the clogging problem encountered in conventional capillary-based ESI, allowing more convenient sampling and permitting new applications. Our recent study demonstrated that ESI with household aluminum foil as solid substrate (Al-foil ESI) is a versatile mass spectrometric method allowing various applications, including on-surface cleanup of samples, direct analysis of complex samples and monitoring of thermal reactions. These new features significantly facilitate mass spectrometric analysis in various research fields, e.g. protein studies, food analysis, therapeutic monitoring, environmental analysis….etc. ..In solid-substrate ESI, the properties of substrate surface are critical factors influencing the effectiveness of these techniques in different applications, e.g., on-surface sample pretreatment and direct analysis of complex samples. In the present, we are going to further improve the applicability of Al-foil ESI in these applications by on-surface modifications, which is an effective approach in further improving the applicability of solid-substrate ESI. Al-foil has a planar surface that allows more convenient and flexible surface modification when comparing with other solid substrates, e.g., wooden-tip and metal needles, which have been used for ESI. We will attempt to incorporate different materials of particle coating, e.g., C18, C8, C4, silica, TiO2….etc, onto the Al foil surface and investigate the effect of these materials on the efficiency of sample cleanup, i.e., removal of salts and detergents from proteins and peptides and the analytical performance, i.e., sensitivity and specificity, in direct analysis of complex samples, i.e., analysis of glycopeptides and phosphopeptides in peptide mixtures and determination of 1-hydroxypyrene, a biomarker for exposure to environmental polycyclic aromatic hydrocarbons, in human urine. Different coating parameters, e.g., amount of particle materials, particles sizes, methods of coating…etc, will be explored to achieve desired applicability and analytical performance. Besides, the present study also aims to develop a robust instrumental prototype for study of thermal reactions with Al-foil ESI. The optimized prototype can be applied is different research areas, e.g., study of structural stability of proteins and monitoring of thermal chemical reactions.

电喷雾电离质谱在化学、生物及临床医药等领域具有广泛的应用。常规的电喷雾电离采用毛细管引导液体样品，容易引起堵塞问题，且不能分析粘稠和固态样品。我们在前期工作中发展了以铝箔为固体基底的电喷雾电离质谱新方法，该方法具有灵敏度高、背景干扰低、分析速度快的特点，可以在铝箔上实现对复杂样品的直接分析和样品的原位处理以及热反应。本项目拟在前期工作的基础上，进一步发展铝箔电喷雾电离技术，对铝箔进行表面修饰和改性，提高目标化合物在复杂样品中处理的选择性及检测的灵敏度；并建立加热系统，实现铝箔上热反应的监测。本项目的开展将为食品、环境、药品及生物临床等样品的分析提供新方法，并为其他新型质谱技术的发展提供新思路。

本项目采用了合成树脂黏合剂法修饰铝箔表面。将不同的材料均匀涂覆在铝箔表面，并对修饰的表面采用电镜进行表征，建立了操作便捷、重复性好、通用性的表面修饰方法。研究了铝箔表面不同的修饰对多肽/蛋白质溶液中金属盐和去污剂的去除作用，实现多肽/蛋白质溶液原位预处理和电喷雾离子化同时在表面修饰铝箔上完成。研究了TiO2纳米颗粒修饰的铝箔，对蛋白酶解液中磷酸肽的选择性吸附作用。通过优化富集、冲洗和洗脱条件，提高了磷酸肽的检测灵敏度和选择性，鉴定了磷酸化位点。本项目还研究了铝箔表面不同的修饰对尿液中1-OHP的选择性富集，提高复杂的真实样品中痕量物质检测的灵敏度，特异的定性、定量分析尿液中的1-OHP，定量检出限达到0.1 ng/mL，定性检出限达到0.01 ng/mL。通过精确控制和测量铝箔的温度，搭建高适用性及可靠的基于铝箔的热化学反应监控系统，研究影响温度对生物化学反应如蛋白质的热致变性，药物的热分解，以及生物小分子的热反应，本研究还发展了基于铝箔表面修饰的薄层色谱用于电喷雾电离及其应用。这些研究结果揭示了铝箔具有广泛的应用前景。本项目的结果将为食品、环境、药品及生物临床等样品的分析提供新方法，并为其他新型质谱技术的发展提供新思路。

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