Developing Laser Postionization to Enhance Mass Spectrometry Imaging

在化学系化学测量和成像项目的支持下，卢克汉利和伊戈尔L。位于芝加哥的伊利诺伊大学的Bolotin和他们的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表面上对目标化学物质进行成像。 基于被称为质谱（MS）的强大检测方法，这样的化学图像正变得常规可用，并导致药物发现，生物工程，植物生物学，微生物学，消费电子和地质学的许多进步。 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。汉利/博洛廷小组正在努力提高该技术的灵敏度，从而提高空间分辨率。 这项研究也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（西姆斯）是目前应用最广泛的亚微米分辨率MS成像策略。 这两种方法都可能遭受由于探针尺寸减小而导致的信号不足、错过一些分析物的差分离子形成、较高横向分辨率下的碎片化和/或使图像变形的样品充电效应。汉利/Bolotin小组正致力于将激光定位与MALDI结合起来，作为一种有效电离大部分不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，并提高对否则识别不良或根本不识别的物质的检测。 目前正在评估真空紫外定位（使用氟准分子激光器）和利用解吸羽流中的气相碰撞进行去聚，作为提高灵敏度的手段。 该团队还在评估是否可以利用已经用亚500飞秒脉冲证明的分辨率增益来改变激光波长和/或去聚类。这些策略都是用包括细菌生物膜的测试样品进行评估的。与英国国家物理实验室的Ian Gilmore教授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（西姆斯）成像。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

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.