Nanopore sensing-based technologies have made significant progress for single molecule and single nanoparticle detection and analysis. In recent years, multimode sensing by multifunctional nanopores shows the potential to greatly improve the sensitivity and selectivity of traditional resistive-pulse sensing methods. In this paper, we showed that two label-free electric sensing modes could work cooperatively to detect the motion of 40 nm diameter spherical gold nanoparticles (GNPs) in solution by a multifunctional nanopipette. The multifunctional nanopipettes containing both nanopore and nanoelectrode (pyrolytic carbon) at the tip were fabricated quickly and cheaply. We demonstrated that the ionic current and local electrical potential changes could be detected simultaneously during the translocation of individual GNPs. We also showed that the nanopore/CNE tip geometry enabled the CNE not only to detect the translocation of single GNP but also to collectively detect several GNPs outside the nanopore entrance. The dynamic accumulation of GNPs near the nanopore entrance resulted in no detectable current changes, but was detected by the potential changes at the CNE. We revealed the motions of GNPs both outside and inside the nanopore, individually and collectively, with the combination of ionic current and potential measurements.

In recent years, various single-entity electrochemical methods have been developed to study the dynamic events of single nanoparticles (NPs) in solution. It has been demonstrated that the assembly, transport, and translocation of metallic NPs near a nanopore entrance can be detected based on the open-circuit potential change of a floating nanoelectrode placed near the nanopore. In this study, we applied the nanopore-nanoelectrode-based method to study polystyrene (PS) NPs with various sizes, which were used as the model dielectric NPs. Furthermore, by utilizing dielectrophoretic (DEP) force applied through the nanoelectrode, PS NPs can be efficiently preconcentrated to form large assemblies outside the nanopipette tip, enabling high-throughput single NP analysis. We revealed how the interactions between NPs and between the NP and the nanopore surface affected the current and potential signals. We investigated the dynamic structures and motions of PS NPs inside the large assembly based on the complementary and correlated the ionic current and potential signals from both the nanopore and the nanoelectrode. We also compared the difference in the dynamic events between polarizable metallic NPs and non-polarizable dielectric NPs during multi-NP structure formation and individual NP transport and translocation motions.

In recent years, surface enhanced Raman spectroscopy (SERS) has emerged as a prominent tool for probing molecular interaction and reaction with single-molecule sensitivity. Here we use SERS to investigate the...