Label-Free Impedance Imaging of Single Extracellular Vesicles Using Interferometric Electrochemical Microscopy

Extracellular vesicles (EVs) are pivotal in various biological processes and diseases, yet their small size and heterogeneity pose challenges for single EV quantification. We introduce interferometric electrochemical microscopy (iECM), a sensitive label-free technique that combines interferometric scattering and electrochemical impedance imaging. This method enables the quantification of the impedance of single EVs, providing unique insights into their electrochemical properties, and allows for the simultaneous measurement of size and real-time monitoring of antibody binding. Notably, we discovered that the impedance spectra of EVs can serve as specific fingerprints to differentiate EVs from cancerous and healthy cells, establishing iECM as a unique platform for EV characterization and classification.