Bioprobes-regulated precision biosensing of exosomes: From the nanovesicle surface to the inside

Exosomes are becoming the surrogates of their parental cells by inheriting cell surface and inner molecular information, thereby emerging as biomarkers in diseases diagnosis and treatment monitoring. However, their inherent nanosize and 'biocolloid'-like distribution in biofluids pose formidable challenges in exosome-oriented precision analysis. In particular, exosomal heterogeneity demands highly specific and sensitive approaches to reveal their subpopulations. To address these challenges, we here propose a review to summarize recent progress in bioprobes-mediated exosomal biosensing from extravesicular to intravesicular, from solid sensor (gold and non-gold) surface to solution phase and from simplex to multiplexing. We highlight the involved bioprobes from one dimensional (1D) to 3D, from antibodies to functional nucleic acids as well as their nanocomplexes in recognition, capture and detection of exosomal biomarkers. Finally, we provide insights into the current challenges and future opportunities in ultrasensitive, specific and multiplexed detection outside and/or inside exosomes, and envision the next-generation smart bioprobes to enable more precise exosome-based diagnostics.(c) 2022 Elsevier B.V. All rights reserved.