Modulation of ionic current signatures and transport dynamics of proteins in quartz nanopipettes via gold nanoparticle-assisted antigen binding.

Solid-state nanopore sensing provides a powerful platform for probing single-molecule translocation through the analysis of ionic current fluctuations; however, for protein analytes, rapid translocation and structural complexity often result in limited signal resolution. In this work, we systematically investigate the translocation behavior of proteins and nanoparticles in quartz nanopipettes under low ionic strength conditions, with a focus on the modulation of ionic current signatures by applied voltage and molecular structure. Chicken immunoglobulin exhibits both resistive and conductive events during translocation, reflecting the competition between excluded-volume effects and ion transport asymmetry, whereas gold nanoparticles display a clear voltage-dependent transition from resistive to conductive signals, highlighting the role of field-enhanced ion flux and Debye layer coupling. Furthermore, by constructing gold nanoparticle-antibody conjugates and introducing specific antigen binding, we demonstrate that the resulting composite structures exhibit prolonged dwell times and enhanced current modulation, indicating significantly altered translocation dynamics. Finite element simulations further reveal that particle size, surface charge, and local ion distribution collectively govern the observed ionic current responses. These findings provide new insights into the mechanisms of nanopipette translocation and offer a framework for understanding nanoparticle-assisted modulation of single-molecule transport in confined nanofluidic systems.