A cascaded microfluidic system by integrating deterministic lateral displacement with cyclic tangential flow filtration for efficient sorting of exosomes from whole blood samples

Exosomes are a type of extracellular vesicle ranging from 30 to 150 nm in diameter that contain constituents of the cells that secrete them. The initial challenge in utilizing exosomes lies in their effective sorting from body fluids. However, traditional methods for exosome sorting are often time-consuming and costly. In this work, a cascaded microfluidic system was proposed for sorting exosomes from whole blood samples by integrating a deterministic lateral displacement (DLD) module with a circulation tangential flow filtration (CTFF) module. The DLD module, featuring multiple critical diameters, served as the first stage to remove blood cells from the sample. The CTFF module functioned as the second stage for exosome sorting. Sorting parameters were optimized including the sample flux, dilution factor of the blood sample, and transmembrane pressure. Exosomes were efficiently sorted from the plasma samples using the CTFF chip, achieving a recovery rate of 89.64% and a recovery purity of 84.27%. When employed to directly sort exosomes from whole blood samples, this cascaded system achieved a recovery purity of 70.21% and a recovery rate of 28.64%. The proposed sorting system presents a promising approach for the efficient sorting of micro/nanoparticles in complex biological samples.