Photodynamics of MALDI matrix molecules studied by velocity-map imaging

基质辅助激光解吸电离(MALDI)在质谱界被广泛用于产生完整生物分子和其他非挥发性分子的气相样品。将感兴趣的样品嵌入或涂覆适当的‘基质化合物’，通常是有机酸，在紫外线(UV)中具有很强的光学吸收。在紫外光照射下，基质优先吸收光，从而保护脆弱的生物分子免受辐射损伤。光子的吸收触发了能量和电荷从基质化合物向生物分子的转移，然后生物分子被从表面喷射出来，产生适合于质谱仪分析的气相生物分子。虽然MALDI过程的基本原理得到了广泛的理解，但详细的分子机制还没有被很好地理解。我们计划采用“自下而上”的方法来理解MALDI机制。首先，我们将研究分离的MALDI基质分子的气相光化学，以了解它们在紫外光吸收后的分解路径。我们将使用多质量速度图成像(VMI)来测量每个照片碎片的飞行时间质谱图和产物散射分布，以便对碎片进行识别和量化，并详细研究碎片动力学。我们将研究这一过程的波长依赖性，这将提供有关电子态特征的信息，还将通过对适当衍生的分子进行测量来研究分子结构的依赖性。在项目接近尾声时，我们计划对从表面制备的晶体MALDI基质中射出的光碎片进行速度图成像测量，并将结果与气相研究的数据进行比较。更好地理解MALDI的分子机理将有助于用户以逻辑和系统的方式控制和优化不同分析应用的过程。该项目是牛津大学化学系的克莱尔·瓦伦斯和国家物理实验室国家光谱成像卓越中心(NICE-MS)联席主任约瑟芬·邦奇的研究小组合作完成的。目的和目的：1)分离的MALDI基质分子在气相中的VMI，以了解其在紫外光吸收后的分解途径。2)研究了观察到的光动力学与光解波长的关系。3)研究了观测到的光动力学与分子结构的关系。4)如果时间允许，研究MALDI基质分子在表面固态样品中激发的光动力学，并与气相研究的结果进行比较。这项拟议的研究将受益于牛津大学开发的两项专利技术，这两项技术之前是由EPSRC资助的。像素成像质谱仪(PIMMS)使用事件触发的时间戳图像传感器来记录每个检测到的离子的位置和到达时间，精度为12.5 ns，允许在激光引发的实验中的每个飞行时间周期内记录每个质荷比离子的图像。第二种技术是快速闪烁体，它可以提高典型离子探测器阵列的时间分辨率。这两项技术使得在许多不同的实验条件下对各种MALDI基质分子的光动力学进行广泛的探索成为可能。该项目属于EPSRC化学反应动力学和机制组合，以及EPSRC物理科学主题的传感器和仪器组合。

Matrix assisted laser desorption ionization (MALDI) is widely used within the mass spectrometry community to generate gas-phase samples of intact biomolecules and other non-volatile molecules. The sample of interest is embedded in or coated with a suitable 'matrix compound', often an organic acid, with a strong optical absorption in the ultraviolet (UV). On irradiation with UV light, the matrix absorbs the light preferentially, thereby protecting the delicate biomolecule from radiation damage. Absorption of a photon triggers the transfer of energy and charge from the matrix compound to the biomolecule, which is then ejected from the surface, yielding gas-phase biomolecules suitable for analysis by mass spectrometry. While the basic principle of the MALDI process is widely appreciated, the detailed molecular mechanism is not well understood. We plan to adopt a 'bottom up' approach to understanding the MALDI mechanism. Initially, we will study the gas-phase photochemistry of isolated MALDI matrix molecules in order to understand their decomposition pathways following absorption of UV light. We will employ multimass velocity-map imaging (VMI) to measure time-of-flight mass spectra and product scattering distributions for each photofragment, allowing the fragments to be identified and quantified and the fragmentation dynamics to be investigated in detail. We will investigate the wavelength dependence of the process, which will provide information on the character of the electronic states involved, and will also study the dependence on molecular structure by performing measurements on appropriately derivatised molecules. Towards the end of the project, we plan to perform velocity-map imaging measurements on photofragments ejected from crystalline MALDI matrices prepared at a surface, and to compare the results with data from the gas-phase studies. Improved understanding of the molecular mechanism of MALDI will help users to control and optimize the process for different analytical applications in a logical and systematic way. The project is a collaboration between the research groups of Claire Vallance, based in the Department of Chemistry at the University of Oxford, and Josephine Bunch, co-director of the National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MS) based at the National Physical Laboratory. Aims and objectives: 1) VMI of isolated MALDI matrix molecules in the gas phase in order to understand their decomposition pathways following absorption of ultraviolet light. 2) Investigation into the dependence of the observed photodynamics on photolysis wavelength. 3) Investigation into the dependence of the observed photodynamics on molecular structure. 4) If time permits, investigation into the photodynamics of MALDI matrix molecules excited within a solid-state sample on a surface, and comparison with the results of the gas-phase studies. The proposed research will benefit from two patented technologies developed at Oxford and previously funded by the EPSRC. Pixel Imaging Mass Spectrometry (PImMS), uses an event-triggered, time-stamping image sensor to record the position and arrival time for each detected ion with a precision of 12.5 ns, allowing images to be recorded for ions of each mass-to-charge ratio during every time-of-flight cycle in a laser-initiated experiment. The second technology is a fast scintillator that enhances the time resolution of typical ion detector arrays. These two technologies make feasible a broad-ranging exploration into the photodynamics of a variety of MALDI matrix molecules under a number of different experimental conditions. This project falls within the EPSRC chemical reaction dynamics and mechanisms portfolio as well as the sensors and instrumentation portfolio of the EPSRC's Physical Sciences theme.