Dual-Mode and Label-Free Detection of Exosomes from Plasma Using an Electrochemical Quartz Crystal Microbalance with Dissipation Monitoring

The biomolecular contents of extracellular vesicles, such as exosomes, have been shown to be crucial in intercellular communication and disease propagation. As a result, there has been a recent surge in the exploration of novel biosensing platforms that can sensitively and specifically detect exosomal content such as proteins and nucleic acids, with a view toward application in diagnostic assays. Here, we demonstrate dual-mode and label-free detection of plasma exosomes using an electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D). The platform adopts a direct immunosensing approach to effectively capture exosomes via their surface protein expression of CD63. By combining QCM-D with a tandem in situ electrochemical impedance spectroscopy measurement, we are able to demonstrate relationships between mass, viscoelasticity and impedance inducing properties of each functional layer and analyte. In addition to lowering the limit of detection (by a factor of 2-4) to 6.71 x 10(7) exosome-sized particles (ESP) per mL in 25% v/v serum, the synergy between dissipation and impedance response introduces improved sensing specificity by offering further distinction between soft and rigid analytes, thereby promoting EQCM-D as an important technique for exosome analysis.

Automated summary

Extracellular vesicles, particularly exosomes, play a crucial role in intercellular communication and disease propagation. A novel biosensing platform, electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D), is demonstrated for dual-mode and label-free detection of plasma exosomes. By combining QCM-D with in situ electrochemical impedance spectroscopy measurement, relationships between mass, viscoelasticity, and impedance properties of each functional layer and analyte are revealed. This platform offers improved sensing specificity and lower limit of detection, making it an important technique for exosome analysis.