Liposome purification from micromolar protein background using diffusiophoretic trapping

Abstract

Colloid purification from liquid biopsies is a promising route for early diagnostics of complex diseases based on extracellular vesicle biomarkers. We have previously demonstrated that colloids, such as liposomes and exosomes, can be concentrated in a fluidic device by the combined effects of diffusiophoresis and diffusioosmosis induced by a salt gradient. The salt gradient imposed on an open channel causes an osmotic flow opposing the particle diffusiophoresis, which traps particles. Diffusioosmosis depends on the surface charge density of the device's inner walls. This is adjusted with a coating that also ensures that particle stiction is suppressed. When proteins are present at concentrations typically found in liquid biopsies, both aspects are challenged. Surface passivation by Pluronic polymers remediates these effects. We show that Pluronic effectively prevents adsorption of bovine and human serum albumin, as well as negatively charged liposomes, while maintaining a sufficiently high surface zeta potential to induce an osmotic flow that traps liposomes. Liposomes with a zeta potential of −30 mV and a diameter of 120 nm are captured from a dilute solution in the presence of bovine or human serum albumin at micromolar concentrations. The proteins are removed from the trap through diffusion while the liposomes remain trapped, and finally, we demonstrate how liposomes can effectively be purified from 10% plasma. These experiments bring diffusiophoretic trapping closer to practical applications in liquid biopsies.