Advanced Enrichment and Separation of Extracellular Vesicles through the Super Absorbent Polymer Nanosieves

Extracellular vesicles (EVs) are promising therapeutic biomaterials capable of transferring their cargo molecules and external drugs to other cells in vivo and contain various biomarkers that can be used in liquid biopsies. The clinical application of EVs requires an efficient EV enrichment system for the large-scale production or high-throughput isolation of EVs from liquid samples, such as culture media, plant juices, and body fluids. However, current EV enrichment methods, such as ultrafiltration and ultracentrifugation, have limited applicability owing to their associated costs, inefficiency, scalability, and centrifugation time. Herein, we describe the development of a nanosieve based on a superabsorbent polymer for selective EV enrichment. The nanosieve absorbs small molecules while expelling large molecules, such as EVs, through the nanosized channels. We successfully concentrated EVs from clinical samples, such as serum and plasma, with superior cost and time efficiencies. The nanosieves did not interact with the EVs during enrichment, allowing the retention of their therapeutic functions. In addition, the nanosieve surface was specifically engineered to provide multifunctionality to effectively promote EV capture from bulk solutions. Overall, our nanosieve-based EV enrichment method is effective, time- and cost-saving, versatile, scalable, and modulable, and is an excellent option for EV production.