Separation of Microvesicles from Serological Samples Using Deterministic Lateral Displacement Effect

Abstract

Label-free isolation and detection of extracellular vesicles are essential in many diagnostic and therapeutic approaches. Recently, there has been an interest in methods that avoid the use of biochemical labels, intrinsic biomarkers, or electrical polarizability to identify microvesicles (also referred to as microparticles) from serological samples. Here, we report a microfluidic device to separate circulating extracellular vesicles from serological samples using the deterministic lateral displacement principle. The device continuously fractionates label-free extracellular vesicles and cells according to size and membrane flexibility by displacing them perpendicularly to the fluid flow direction in a micro-fabricated array of posts. Experimental data and computational fluid dynamic simulations are presented to create a compelling argument that microvesicles from serological samples could be separated by deterministic lateral displacement arrays. Direct separation of different-sized micro- and nanospheres were demonstrated using a multi-stage separation strategy thus offering a potential route for novel cancer diagnostic approaches where microvesicles can be targeted and intercepted during cell-to-cell communication.