Tangential Flow Microfluidics for the Capture and Release of Nanoparticles and Extracellular Vesicles on Conventional and Ultrathin Membranes

Membranes have been used extensively for the purification and separation of biological species. A persistent challenge is the purification of species from concentrated feed solutions such as extracellular vesicles (EVs) from biological fluids. Investigated is a new method to isolate micro‐ and nanoscale species termed tangential flow for analyte capture (TFAC), which is an extension of traditional tangential flow filtration. Initially, EV purification from plasma on ultrathin nanomembranes is compared between both normal flow filtration (NFF) and TFAC. NFF results in rapid formation of a protein cake which completely obscures any captured EVs and also prevents further transport across the membrane. On the other hand, TFAC shows capture of CD63 positive small EVs with minimal contamination. The use of TFAC to capture target species over membrane pores, wash, and then release in a physical process that does not rely upon affinity or chemical interactions is explored. This process is studied with model particles on both ultrathin and conventional thickness membranes. Successful capture and release of model particles is observed using both membranes. Ultrathin nanomembranes show higher efficiency of capture and release with significantly lower pressures indicating that ultrathin nanomembranes are well‐suited for TFAC of delicate nanoscale particles such as EVs. Extracellular vesicles are captured using a new method called tangential flow for analyte capture (TFAC), which is an extension of traditional tangential flow filtration. TFAC resembles bind and elute purification strategies, although it distinguishes itself from affinity chromatography because the binding is purely physical. Experiments and theory confirm that ultrathin nanomembranes enable improved capture and release of target species.