Label-Free Nanoparticle Characterization via Electrical Impedance-Based Submicrofluidic Analysis

Accurate characterization of nanoparticles and extracellular vesicles is essential for nanotechnology, biomedical research, and diagnostic applications. Here, we present an impedance-based submicrofluidic analysis (ISMA) system that integrates a submicrochannel with a double differential electrode configuration to enable label-free, high-resolution nanoscale particle measurement. The double differential design, combined with wavelet filtering, significantly reduces electrical noise and produces a clear, analyzable signal waveform. The ISMA system was validated by using polystyrene nanoparticles, achieving a 50 nm detection limit with results that closely matched scanning electron microscopy (SEM) measurements. Compared with nanoparticle tracking analysis (NTA), ISMA exhibited higher measurement accuracy. The ISMA can also characterize exosomes from MDA-MB-231 cells and distinguish them from similar-sized synthetic particles in mixtures. These findings indicate that the ISMA system provides a powerful and scalable approach for precise size and concentration analysis of nanoparticles and extracellular vesicles, with broad potential in biomedical research and nanodiagnostics.