Nanopore Trap for Label-Free Fingerprinting of Surface-modified Single Nanoparticles

Label-free characterization of nanoparticle surface functionalization at single-particle resolution is essential for a wide range of applications. Solid-state nanopore sensing provides a direct electrical readout that is intrinsically sensitive to the size, surface layer, and interfacial chemistry of single particles in liquid environments. The trapping-based nanopore sensing regime further enables probing surface-dependent particle-pore interactions with extended observation time. Here, a solid-state nanopore trap-based fingerprinting method is presented to differentiate single nanoparticles with distinct surface modifications. The method combines a "trap-release" measurement protocol with a multi-metric analysis workflow that extracts blockade distributions, sub-level statistics and frequency-domain signatures from trapping events, and constructs a unique fingerprint for each particle species. Applied to silica cores (≈25-30 nm) functionalized with APTES, NHS-PEG₄-Biotin and Tween-20, the approach generates distinct fingerprints that map to surface charge, coating conformation and configuration heterogeneity. Moreover, in situ detection of surface chemical transformation via specific streptavidin binding is demonstrated, with stoichiometry-dependent progression of the fingerprints. This platform provides a complementary tool to optical, spectral and ensemble assays for characterizing engineered nanoparticle surfaces and tracking interfacial molecular interactions in solution with label-free and single-particle sensitivity.