A biosensor-integrated filtration device for nanoparticle isolation and label-free imaging.

Rapid, efficient, simple approaches for biological nanoparticle recovery from bodily fluids are required for translating detection strategies from lab diagnostics to low-resource settings, where expensive sample processing instruments such as an ultracentrifuge are not accessible. In this work, we characterize an alternative approach in which intact nanoparticles are filtered from plasma with a nanoporous filtration device that separates particulates within a 100-200 nm diameter range followed by detection on a photonic crystal (PC) biosensor with a portable photonic resonator interferometric scattering microscopy (PRISM) instrument. The biosensor-integrated recovery device's (BIRD) collection efficiency is initially characterized using gold nanoparticles and fluorescent nanobeads suspended in buffer solution and plasma, followed by spiking intact HIV pseudovirus into the same media. We demonstrate a recovery rate of 55.0% for 100 nm diameter AuNP and HIV spiked into the buffer and 11.9% for 100 nm diameter FluoSpheres spiked in human plasma. Using PRISM, we observed the Brownian motion of filtered nanoparticles and virions eluted into the detection compartment, with concentration-dependent counting of transient contact events between the nanoparticles and the PC surface.