Rapid Trapping and Label-free Characterization of Single Nanoscale Extracellular Vesicles and Nanoparticles in Solution

Abstract: Achieving high-throughput, comprehensive analysis of single nanoparticles to determine their size, shape, and composition is essential for understanding particle heterogeneity with applications ranging from drug delivery to environmental monitoring. Existing techniques are hindered by low throughput, lengthy trapping times, irreversible particle adsorption, or limited characterization capabilities. Here, we introduce Interferometric Electrohydrodynamic Tweezers (IET), an integrated platform that rapidly traps single nanoparticles in parallel within three seconds. IET enables label-free characterization of particle size and shape via interferometric imaging and identifies molecular composition through Raman spectroscopy, all without the need for fluorescent labeling. We demonstrate the platform's capabilities by trapping and imaging colloidal polymer beads, nanoscale extracellular vesicles (EVs), and newly discovered extracellular nanoparticles known as supermeres. By monitoring their interferometric contrast images while trapped, we accurately determine the sizes of EVs and supermeres. Our IET represents a powerful optofluidics platform for comprehensive characterization of nanoscale objects, opening new avenues in nanomedicine, environmental monitoring, and beyond.