Information-Rich High-Throughput Cellular Assays using Acoustic Mist Ionisation Mass Spectrometry

Cellular metabolites and phospholipids contain a vast amount of information about the current state of a cell, and are a useful resource for understanding the effects of drug candidates in vitro. Typical human cell-based assays in early drug discovery rely on simple readouts such as cell viability, or focus on single end-points revealed by an antibody or other label-based technologies. We introduce a generic 384-well plate-based workflow for data-rich cellular assays using facile sample preparation and direct analysis by acoustic mist ionization mass spectrometry (AMI-MS). The assays are compatible with adherent and suspension cells, and provide simultaneous information about a number of cellular small-molecule components (e.g., amino acids, nucleotides, phospholipids), cellular processes (e.g., proliferation, glycolysis, oxidative stress), as well as compound uptake and metabolism. Thanks to the high-throughput and low cost of analysis, the workflow can be introduced very early into any drug discovery pipeline to help select optimal lead molecules.