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

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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.