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

在化学系化学测量和成像项目的支持下，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型化学成像能力，通过结合质谱、电化学、和地形敏感剪切力显微镜。虽然大多数化学成像技术仅限于特定的分子或分子群，但质谱成像可以在一次实验中绘制数百个单个生物分子。通过提高空间分辨率、分析速度和质谱成像技术的定量能力，拉斯金小组寻求在理解和控制生物系统中发生的过程方面取得进展。这些发展将通过检查参与细胞信号传导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增加了本科生和研究生的跨学科研究机会，以及该方法商业化的前景。该项目解决了与生物系统中化学梯度的精确测量相关的几个分析挑战，以及对生物过程中涉及的许多化合物的自信鉴定和结构表征。特别是，Laskin小组正在开发高空间分辨率的生物样品鲁棒成像方法，使用环境电离质谱法，使用离子迁移谱法和串联质谱法对每个像素中的分子进行动态结构表征，以及使用电化学显微镜识别氧化还原活性信号分子。这些新功能将广泛适用于研究各种生物系统的代谢过程，包括活细胞、多细胞聚集体和组织。该奖项反映了美国国家科学基金会的法定使命，并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，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.