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 monitoring (QCM-D), to detect exosomes by exploiting their surface protein profile. Exosomes expressing the trans-membrane 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 in 75%v/v serum, exhibiting a limit-of detection of 2.9x10^8 and 1.4x10^8 exosome sized particles (ESPs)/ml for frequency and dissipation response respectively, i.e., clinically relevant concentrations. Our proof of concept findings...