A novel silicon platform for selective isolation, quantification, and molecular analysis of small extracellular vesicles

Introduction: Small extracellular vesicles (sEVs), thanks to their cargo, are involved in cellular communication and play important roles in cell proliferation, growth, differentiation, apoptosis, stemness and embryo development. Their contribution to human pathology has been widely demonstrated and they are emerging as strategic biomarkers of cancer, neuro-degenerative and cardiovascular diseases, and as potential targets for therapeutic interven-tion. However, the use of sEVs for medical applications is still limited due to the selectivity and sensitivity limits of the commonly applied approaches. Methods: Novel sensing solutions based on nanomaterials are arising as strategic tools able to surpass traditional sensor limits. Among these, Si nanowires (Si NWs), realized with cost-effective industrially compatible metal-assisted chemical etching, are perfect candidates for sEV detection. Results: In this paper, the realization of a selective sensor able to isolate, concentrate and quantify specific vesicle populations, from minimal volumes of biofluid, is presented. In particular, this Si NW platform has a detection limit of about 2×10 sEVs/mL and was tested with follicular fluid and blastocoel samples. Moreover, the possibility to detach the selec-tively isolated sEVs allowing further analyses with other approaches was demonstrated by SEM analysis and several PCRs performed on the RNA content of the detached sEVs. Discussion: This platform overcomes the limit of detection of traditional methods and, most importantly, preserves the biological content of sEVs, opening the route toward a reliable liquid biopsy analysis.