Multispray Technology for Studying Biomolecular Interactions

Project Summary/Abstract Proteome reflects physiology and pathology of a person therefore proteomics is a powerful tool for early disease diagnosis, drug discovery, and therapeutic response monitoring. Mass spectrometry (MS) measures the mass- to-charge ratio of charged species and has become the enabling technology for proteomics. One of the most exciting developments in mass spectrometry in recent years is native spray mass spectrometry for studying biomolecular interactions under native or native-like physiological conditions. This was mainly due to the dramatic improvement in resolution and sensitivity of the new classes of high-resolution mass spectrometers. On the other hand, the mass spectrometry front-end solutions including sample processing and LC chromatography have not kept pace with the mass spectrometry back-end revolutions. Major technological advances are needed to achieve high sensitivity, robustness, throughput, and automation for diverse LC-MS analysis of biologically relevant samples. In this SBIR direct Phase II project, Newomics proposes to further develop and commercialize its differentiated, vendor-agnostic, UniESI system with M3 emitters and MEA chips, as an integrated imaging-mass spec front-end platform, for native spray mass spectrometry. We will validate the performance of the platform for native MS studies of biomolecular interactions predicted by AlphaFold 3 and demonstrate its utilities in studying conformational changes and ligand binding under native conditions. Once commercialized, our UniESI platform will facilitate high-throughput and high-sensitivity top- down proteomics and native mass spectrometry, for studying biomolecular interactions and discovery of new drugs and druggable targets, thereby contributing to precision medicine.