Dual-Selective Magnetic Analysis of Extracellular Vesicle Glycans

Extracellular vesicles (EVs) harbor a rich glycome-diverse sugar modifications-that mediates and reflects disease progression. Despite its clinical potential, the analysis of EV glycans remains challenging due to limitations of current glycomics technologies. Here, we develop a dedicated analytical platform to directly profile EV glycans in native biofluids. Termed integrated magnetic analysis of glycans in extracellular vesicles (iMAGE), the platform utilizes rationally designed polycore magnetic nanoparticles to transduce EV-bound glycans, but not that of free-floating glycoproteins, into magnetic signals; the resultant signals are readily quantified through a built-in magnetoresistance sensor. The iMAGE assay is thus fast (<30 min), sensitive (<10(4) EVs), and wash-free. Through multiplexed measurements of EV glycans in native clinical specimens, the technology not only revealed disease signatures against complex biological background but also differentiated patient prognosis. As a majority of current clinical biomarkers are glycosylated, the technology could expand their applications for EV-based noninvasive diagnostics and prognostics.