Quantitative Ambient Imaging and Analysis at a Subcellular Level using Mass Spectrometry

在化学系化学测量和成像计划的支持下，以及分子和细胞生物科学系系统和合成生物学集群的部分共同资助下，普渡大学的Julia Laskin教授和她的团队正在开发强大的新化学成像功能，将能够使用质谱学、电化学和地形敏感剪切力显微镜的组合来精确绘制细胞中高丰度和低丰度生物分子的空间图谱。虽然大多数化学成像技术仅限于特定的分子或分子群，但质谱学成像可以在一次实验中绘制数百个单独的生物分子的图谱。通过提高质谱学成像技术的空间分辨率、分析速度和定量能力，拉斯金团队寻求在理解和控制生物系统中发生的过程方面取得进展。这些进展将通过研究参与细胞信号传递的分子的定位和运输，为动态生物过程提供独特的见解。与仪器供应商和国家实验室的合作既增加了相关本科生和研究生的跨学科研究机会，也增加了该方法的商业化前景。该项目解决了与准确测量生物系统中的化学梯度以及对生物过程中涉及的众多化合物进行自信的鉴定和结构表征相关的几个分析挑战。特别是，Laskin团队正在开发使用环境电离质谱仪对生物样品进行高空间分辨率的稳健成像、使用离子迁移率光谱和串联质谱仪对每个像素中的分子进行即时结构表征以及使用电化学显微镜识别氧化还原活性信号分子的方法。这些新能力将广泛适用于研究不同生物系统中的新陈代谢过程，包括活细胞、多细胞聚集体和组织。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, and partial co-funding from the Systems and Synthetic Biology Cluster in the Division of Molecular and Cellular Biosciences, Professor Julia Laskin and her group at Purdue University are developing powerful new chemical imaging capabilities that will enable accurate spatial mapping of both high- and low-abundance biomolecules in cells using a combination of mass spectrometry, electrochemistry, and topography-sensitive shear force microscopy. Whereas most chemical imaging techniques are limited to specific molecules or groups of molecules, mass spectrometric imaging enables mapping of hundreds of individual biomolecules in one experiment. By improving the spatial resolution, speed of analysis, and quantitation capabilities of mass spectrometry imaging techniques, the Laskin group seeks to enable advances in understanding and controlling processes occurring in biological systems. These developments will provide unique insights into dynamic biological processes by examining both the localization and transport of molecules involved in cellular signaling. Collaborations with an instrument vendor and a National Laboratory enhance both the interdisciplinary research opportunities of involved undergraduate and graduate students, and the prospects for commercialization of the approach.This project addresses several analytical challenges associated with accurate measurement of chemical gradients in biological systems along with confident identification and structural characterization of numerous compounds involved in biological processes. In particular, the Laskin group is developing approaches for robust imaging of biological samples with high spatial resolution using ambient ionization mass spectrometry, on-the-fly structural characterization of molecules in each pixel using ion mobility spectrometry and tandem mass spectrometry, and identification of redox-active signaling molecules using electrochemical microscopy. These new capabilities will be broadly applicable to studying metabolic processes in diverse biological systems including living cells, multicellular aggregates, and tissues.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.