Microdroplet On-tissue Chemical Reactions for Mass Spectrometric Imaging of the Untargeted Metabolome

在化学系化学测量和成像项目的支持下，爱荷华州州立大学的Young-Jin Lee教授和他的团队正在开发一种新的生物组织表面成像和表征方法，涉及表面微滴中的化学反应以提高检测代谢物的能力（细胞过程的产物）在表面上使用强大的分析探针被称为“质谱”。“这是第一次系统地研究表面衍生化微滴中的反应加速。对表面微滴反应的基本理解将导致通过质谱成像对小代谢物进行有效分析，否则这些代谢物是不可能检测到的。潜在的影响跨越许多科学学科和分析项目，包括生物标志物发现，植物代谢组学，食品安全，药物代谢和生物防御。该项目将通过不同的渠道招募不同的学生参与，包括美国化学学会为经济困难的高中生提供的项目SEED和为第一代和代表性不足的学生提供的McNair计划。该项目的目标是了解表面微滴反应，通过比较中性和电喷雾试剂液滴，找出主要的驱动力，并操纵反应条件以提高反应效率，同时使离子抑制和交叉反应性最小化。 一组选定的反应正在研究，以实现这些目标的衍生胺，羧酸，酮/醛，和邻二醇。 此外，正在开发新的表面氢氘交换，作为直接从组织表面辅助代谢物鉴定的一种方式。目前大多数代谢组学研究都没有认识到细胞特异性或组织特异性代谢。 随着这项研究的成功，质谱成像将使更好地了解多细胞生物体的代谢生物学。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Young-Jin Lee and his group at Iowa State University are developing a new approach to the imaging and characterization of the surface of biological tissue, involving chemical reactions in surface microdroplets to improve the ability to detect metabolites (products of cellular processes) on the surface using the powerful analytical probe know as "mass spectrometry." This is the first systematic study of reaction acceleration in microdroplets for on-surface derivatization. Fundamental understanding of on-surface microdroplet reactions will lead to the effective analysis of small metabolites by mass spectrometry imaging that are otherwise impossible to detect. The potential impact spans across many scientific disciplines and analytical projects, including biomarker discovery, plant metabolomics, food safety, drug metabolism, and biodefense. A diverse group of students will be recruited to participate in the project through various channels including the American Chemical Society's Project SEED for economically disadvantaged high-school students and the McNair Program for first generation and underrepresented students.The objective of this project is to understand on-surface microdroplet reactions, find out major driving forces by comparing neutral vs electrosprayed reagent droplets, and manipulate the reaction conditions to improve reaction efficiencies while minimizing ion suppression and cross-reactivity. A selected set of reactions is being studied to achieve these goals for the derivatization of amines, carboxylic acids, ketones/aldehydes, and vicinal diols. Furthermore, novel on-surface hydrogen deuterium exchange is being developed as a way to assist metabolite identification directly from the tissue surface. Most metabolomics studies are currently being performed without recognizing cell-specific or tissue-specific metabolism. With the success of this research, mass spectrometry imaging will allow better understanding of metabolic biology in multicellular organisms.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.