Coordination of Ligand-Protected Metal Nanoclusters and Glass Nanopipettes: Conversion of a Liquid-Phase Fluorometric Assay into an Enhanced Nanopore Analysis

We propose a unique concept for transforming the liquid-phase fluorometric assay into an enhanced nanopore analysis, which is based on the analyte binding-mediated changes in the surface chemistry of noble metal nanostructures in a confined space. In a proof-of-concept trial, the bovine serum albumin-protected gold nanoclusters (BSA-Au NCs) were designed as the sensing unit for biothiol determination. Through the specific interaction between biothiols and BSA-Au NCs, the validation system not only performed well in aqueous fluorescent detection but also can be developed into a more selective and sensitive nanopore sensor. In the confined space of the nanopore, the BSA-Au NC film with high density formed, and the addition of biothiols triggered the fluorescence enhancement as well as the ionic current response, hence leading to the construction of the dual-signal-output (fluorescence/ion current signal) system. The fluorescence signal proved that the ionic current change corresponded to the specific recognition process, improving the reliability of our nanopore method. Moreover, the ionic current response from the BSA-Au NC film can be used to quantify cysteine in a broad dynamic range of 0.001-1 pM with a detection limit as low as 1 fM. Such a strategy can be used to detect biothiols in complex biological fluids such as human serum. Therefore, the present work provided a new design strategy for a glass nanopipette sensor inspired by the principles of numerous and diverse fluorometric assays. It also sheds light on how the coupling of electrical and optical signals improves the accuracy, sensitivity, and selectivity of the glass nanopipette platform.

Automated summary

This study introduces a unique concept for transforming liquid-phase fluorometric assay into enhanced nanopore analysis, utilizing bovine serum albumin-protected gold nanoclusters for biothiol determination as a proof of concept. The system showed potential in detecting and quantifying biothiols, enhancing sensitivity and selectivity in the glass nanopipette platform by coupling electrical and optical signals.