Acoustic Immunosensing of Exosomes Using a Quartz Crystal Microbalance with Dissipation Monitoring

Exosomes are endocytic lipid-membrane bound bodies with potential to be used as biomarkers in cancer and neurodegenerative disease. The limitations and scarcity of current exosome characterisation approaches has led to a growing demand for translational techniques, capable of determining their molecular composition and physical properties in physiological fluids. Here, we investigate label-free immunosensing, using a quartz crystal microbalance with dissipation (QCM-D), to detect exosomes by exploiting their surface protein profile. Exosomes expressing the transmembrane protein CD63 were isolated by size-exclusion chromatography from cell culture media. QCM-D sensors functionalised with anti-CD63 antibodies formed a direct immunoassay towards CD63-positive exosomes, exhibiting a limit-of-detection of 1.7x10^8 and 1.1x10^8 exosome sized particles (ESPs) ml^-1 for frequency and dissipation response respectively, i.e., clinically relevant concentrations. Our proof-of-concept findings support the adoption of dual-mode acoustic analysis of exosomes, leveraging both frequency and dissipation monitoring for use in diagnostic assays.