Single-Cell Multiomic MALDI-MSI Analysis of Lipids and N-Glycans through Affinity Array Capture

This study presents a novel approach utilizing matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for rapid single-cell analysis, enabling multiomic data acquisition from the same cell. Previously, single-cell approaches by MALDI-MSI have focused on increasing resolution to differentiate the analyte signal from adjacent cells in complex tissue or cultured cells. Laser ablation can occur on two separate cells, mixing single-cell data and requiring statistical computation to discern one cell's spectra from the other. Here, we describe a targeted single-cell approach that enables single-cell capture and sampling, assisted by micro-contact printing. We developed an AI-based application, SoloCell, to facilitate the automated selection of captured single cells within printed arrays. This method successfully captures thousands of single cells in a grid format, allowing for rapid lipid and N-glycan profiling from the same cell at a rate of 6 cells per second. This innovative technology combines the power of single-cell capture, AI automation, and imaging mass spectrometry to provide researchers with an unprecedented tool for unraveling the complexity of cellular populations.