Dual-Nanopipettes for the Detection of Single Nanoparticles and Small Molecules.

Nanopore sensing is blooming due to its label-free and high sensitivity features. As a novel nanopore, a droplet is formed at the orifice of a dual-nanopipette, which allows for the translocation of analytes through the two channels at a relatively low speed and the promotion of signal-to-noise ratio. However, nanopore sensing based on the principle of current blockage requires the pore size to be comparable to that of the single entity, which poses a huge challenge for the direct detection of small molecules. In this work, gold nanoparticles (Au NPs) modified with sulfhydryl poly(ethylene glycol) (PEG-SH) or aptamers were detected successfully. The size difference of Au NPs and the interaction between Au NPs and dual-nanopipettes could be distinguished sensitively. Furthermore, Au NPs modified with designed aptamers will produce different blocking current after capturing the corresponding small molecules (e.g., dopamine and serotonin). Even non-electroactive ions, such as potassium ions, can also be detected, which is difficult to sense based on redox reactions, and further illustrates that the change of surface properties of nanoparticles is responsible for the detection. This work expands the application of nanopipette sensing for Au NPs and provides a universal platform for the small-molecule detection, which has the potential application in biosensing.