Nanofluidic resistive pulse sensing for characterization of extracellular vesicles

This paper describes the development, design and characterization of a resistive pulse sensing (RPS) system for the analysis of size distributions of extracellular vesicles (EVs). The system is based on microfluidic chips fabricated using soft-lithography and operated in pressure-driven mode. This fabrication approach provided reproducible pore dimensions and the best performing chip design enabled, without calibration, sizing of both 252 nm and 460 nm test particles within 8% of theoretically calculated values, based on the size specifications provided by suppliers. The number concentration measurement had higher variations and without calibration provided estimates within an order of magnitude, for sample concentrations across 4 orders of magnitude. The RPS chips could also measure successfully EVs and other biological nanoparticles in purified samples from cell culture media and human serum. A compact, fast and inexpensive RPS system based on this design could be an attractive alternative to current gold-standard techniques for routine characterization of EV samples.