Nanofluidic Device for Measuring the Surface Charge of Extracellular Vesicles via a Tunable Electrostatic Landscape

Extracellular vesicles (EVs) play an essential role in intercellular communication. EV surface charge can be used to probe EV surface chemistry and bioconjugation, including surface proteins and sialic acid groups. Surface charge influences different biological processes associated with the EVs, such as cellular uptake and cytotoxicity [1]. Here, we propose a nanofluidic device to perform simultaneous size and charge measurement of EVs. Our device consists of a lattice of electrostatic potential wells embedded in a nanoslit. The nanoslit is interfaced to a thin membrane lid that can be deflected via applied pressure, varying the degree of confinement experienced by the EVs. Using the single molecule electrometry approach developed by the Krishnan group [2], we can use quantification of the EV diffusive dynamics in the lattice, as a function of confinement, to obtain EV size and charge. We apply our device to demonstrate that EVs generated from glioblastoma multiforme (GBM) cells have a lower surface charge compared to EVs generated from GBM normal counterparts (Normal Human Astrocyte, NHA) cells.