International Journal of Nanomedicine (Sep 2021)
A Novel Silicon Platform for Selective Isolation, Quantification, and Molecular Analysis of Small Extracellular Vesicles
Abstract
Antonio Alessio Leonardi,1– 3 Rosalia Battaglia,4 Dario Morganti,1,2 Maria Josè Lo Faro,1,3 Barbara Fazio,2 Chiara De Pascali,5 Luca Francioso,5 Gerardo Palazzo,6,7 Antonia Mallardi,8 Michele Purrello,4 Francesco Priolo,1 Paolo Musumeci,1,* Cinzia Di Pietro,4,* Alessia Irrera2,* 1Dipartimento di Fisica e Astronomia, Università di Catania, Catania, 95123, Italy; 2CNR-IPCF, Istituto per i Processi Chimico-Fisici, Messina, 98158, Italy; 3CNR-IMM UoS Catania, Istituto per la Microelettronica e Microsistemi, Catania, 95123, Italy; 4Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy; 5CNR-IMM, Institute for Microelectronics and Microsystems, Via Monteroni, University Campus, Lecce, 73100, Italy; 6Chemistry Department, University of Bari ‘Aldo Moro’, Bari, 70125, Italy; 7CSGI, Center for Colloid and Surface Science c/o Chemistry Department, Bari, 70125, Italy; 8CNR-IPCF, Institute for Chemical-Physical Processes, c/o Chemistry Department, Bari, 70125, Italy*These authors contributed equally to this workCorrespondence: Paolo Musumeci; Cinzia Di Pietro Email [email protected]; [email protected]: 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, neurodegenerative and cardiovascular diseases, and as potential targets for therapeutic intervention. 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× 105 sEVs/mL and was tested with follicular fluid and blastocoel samples. Moreover, the possibility to detach the selectively 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.Keywords: silicon nanowires, biosensor, small extracellular vesicles, label-free, luminescence