# Nanopore Trap for Label‐Free Fingerprinting of Surface‐modified Single Nanoparticles

## TL;DR

A new method uses nanopores to detect and differentiate nanoparticles based on their surface chemistry without needing labels.

## Contribution

A label-free nanopore trapping method is introduced for fingerprinting surface-modified nanoparticles at single-particle resolution.

## Key findings

- The method can distinguish silica nanoparticles with different surface coatings like APTES, PEG4-Biotin, and Tween-20.
- It detects surface chemical transformations, such as streptavidin binding, in real-time with single-particle sensitivity.

## Abstract

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.

A solid‐state nanopore trapping‐based methodology combines “trap‐release” measurement protocol with multiple features extracted from ionic current of trapping events to generate unique electrical fingerprints of nanoparticles with distinct surface functional layers. Applying this methodology enables the differentiation between APTES, PEG4‐Biotin and Tween‐20‐coated silica nanoparticles, and to monitor in situ surface chemical transformation via specific streptavidin binding on biotinylated nanoparticles.