Developing Laser Postionization to Enhance Mass Spectrometry Imaging

在化学系化学测量和成像计划的支持下，芝加哥伊利诺伊大学的Luke Hanley和Igor L.Bolotin教授及其团队正在改进基于激光的方法，以在动物或植物组织、细菌和真菌生物膜、有机电子设备或岩石等样品的表面成像目标化学物种。基于一种被称为质谱学(MS)的强大检测方法，这种化学图像正变得司空见惯，并在药物发现、生物工程、植物生物学、微生物学、消费电子和地质学方面取得了许多进展。然而，目前的方法往往缺乏提供详细的分子结构和高清晰度(空间分辨率)的能力。Hanley/Bolotin团队正在努力提高这项技术的灵敏度，从而提高空间分辨率。这项研究还为来自代表性不足群体的本科生提供了与团队合作并获得重要工作技能的机会。基质辅助激光解吸/电离(MALDI)和二次离子质谱仪(SIMS)是目前使用最广泛的亚微米分辨率MS成像策略。这两种方法都可能会受到以下问题的影响：探头尺寸减小时信号不足、未检测到某些分析物的差异离子形成、较高横向分辨率下的碎裂和/或使图像变形的样品充电效应。Hanley/Bolotin团队正致力于将激光正电子与MALDI相结合，作为一种有效电离大部分未带电的解吸材料的手段，从而提供提高横向分辨率所需的信号增强，并改进对否则电离较差或根本不电离的物种的检测。真空紫外光正电化(使用氟准分子激光)和解吸羽流中的气相碰撞去团是作为提高灵敏度的手段而被评估的。该团队还在评估，是否可以通过改变激光波长和/或去星团来利用已经展示的低于500飞秒脉冲的分辨率提高。这些策略都在用包括细菌生物膜的测试样本进行评估。与英国国家物理实验室的Ian Gilmore教授进行的平行合作研究正在评估这些成果是否可以扩展到二次离子质谱仪(SIMS)成像。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professors Luke Hanley and Igor L. Bolotin and their group at the University of Illinois at Chicago are improving laser-based methods to image targeted chemical species on the surfaces of samples such as animal or plant tissues, bacterial and fungal biofilms, organic electronic devices, or rocks. Based on a powerful detection approach know as mass spectrometry (MS), such chemical images are becoming routinely available, and have led to many advances in drug discovery, bioengineering, plant biology, microbiology, consumer electronics, and geology. However, current methods often lack the ability to provide both detailed molecular structures and high clarity (spatial resolution). The Hanley/Bolotin group is working to improve the sensitivity of the technique and therefore the spatial resolution. The research is also providing opportunities for undergraduate students from underrepresented groups to work with the team and acquire important job skills.Matrix assisted laser desorption/ionization (MALDI) and secondary ion mass spectrometry (SIMS) are currently the most widely used strategies for sub-micrometer resolution MS imaging. Both of these methods can suffer from insufficient signal as the probe size is reduced, differential ion formation that misses some analytes, fragmentation at higher lateral resolution, and/or sample charging effects that deform images. The Hanley/Bolotin group is working to couple laser postionization to MALDI as a means of efficiently ionizing the large fraction of the desorbed material that is uncharged, thereby providing signal enhancement needed to improve lateral resolution and improving detection of species that otherwise ionize poorly or not at all. Vacuum ultraviolet postionization (using a fluorine excimer laser) and declustering using gas-phase collisions in the desorption plume are being evaluated as means of enhancing sensitivity. The team is also assessing whether resolution gains already demonstrated with sub-500 femtosecond pulses can be leveraged with gains from changing the laser wavelength and/or declustering. These strategies are all being evaluated with test samples that include bacterial biofilms. Parallel collaborative studies with Professor Ian Gilmore at the United Kingdom's National Physical Laboratory are assessing whether these gains can be extended to secondary-ion mass spectrometry (SIMS) imaging.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.