Deep Learning-Enabled Rapid Metabolic Decoding of Small Extracellular Vesicles via Dual-Use Mass Spectroscopy Chip Array

The increasing focus of small extracellular vesicles (sEVs) in liquid biopsy has created a significant demand for streamlined improvements in sEV isolation methods, efficient collection of high-quality sEV data, and powerful rapid analysis of large data sets. Herein, we develop a high-throughput dual-use mass spectroscopic chip array (DUMSCA) for the rapid isolation and detection of plasma sEVs. The DUMSCA realizes more than a 50% increase in speed compared to traditional method and confirms proficiency in robust storage, reuse, high-efficiency desorption/ionization, and metabolite quantification. With the collected metabolic data matrix of sEVs, a deep learning model achieves high-performance diagnosis of Crohn's disease. Furthermore, discovered biomarkers by feature sparsification and tandem mass spectrometry experiments also exhibited remarkable performance in diagnosis. This work demonstrates the rapidity and validity of DUMSCA for disease diagnosis, enabling the diagnosis of diseases without the necessity for prior knowledge and providing a high-throughput technology for sEV-based liquid biopsy that will empower its vigorous development.