PROJECT SUMMARY / ABSTRACT Exosomes, the small extracellular vesicles (30-200 nm), are highly heterogeneous in biofluids. However, traditional bulk-level analysis approaches fail to represent their individual variations. A technique for multi-omics profiling of exosomes at single-particle resolution is of great interest to the exosome research field, but has yet to be developed. WellSIM proposes to develop and validate a method for multi-omics profiling of individual exosomes based on our exosome isolation system (EXODUS), a droplet-based microfluidic device (EXOSeq), and next-generation sequencing (NGS). Our proposed technique will be the first integrative proteomic and transcriptomic profiling of exosomes at the single-particle level, offering high-resolution multi-dimensional biological insights for exosome study and application.