Characterization of vesicular stomatitis virus populations by tunable resistive pulse sensing

Although transmission electron microscopy (TEM) has historically been the method of choice to estimate concentrations of virus and virus-like particles, these measures can often be time-consuming and labor-intensive to perform. Tunable resistive pulse sensing (TRPS) is an emerging method that applies principles of Coulter counting to nanoscale particles and may provide a simpler and higher-throughput alternative to TEM for the quantitation of virus populations. To assess the performance of TRPS compared to TEM, the samples of polymer spheres at a diameter of 100 nm and vesicular stomatitis virus (VSV) were characterized using both techniques. TRPS was able to quantify concentrations down to 107 particles/ml, providing nearly 50-fold larger measurement range, and more reproducible counts than TEM. Total-to-infectious particle ratio of VSV populations as measured by TRPS and plaque assay suggested that each VSV particle is infectious. In addition to particle counts, TRPS successfully measured particle size distributions based on hundreds of particles. Such high throughput sustained by TRPS can assist quantitative characterization of virus populations.