Single molecule characterisation of metal nanoparticles using nanopore-based stochastic detection methods

Single-molecule techniques are revolutionising analytical chemistry methods by observing one molecule at a time, the specific dynamics of populations can be revealed, and the averaging of signals from many molecules, typically obtained in bulk analysis techniques, is avoided. Nanopores have emerged as sensors par excellence for the label-free analysis of single molecules. Nanopore applications are expanding, helped by the fact that biological nanopores can be engineered to improve their suitability for a particular application, and also due to the recent advances in nanofabrication techniques used in the production of solid-state nanopores. Nanopores have demonstrated a suitability for single-molecule analysis that has proven to be useful in systems designed to detect, identify, characterise and quantify a wide range of molecules. This review focuses on the analysis of monolayer-protected gold nanoparticles (NPs). An extraordinary variety of structures, properties, and applications are available for NPs, which has motivated interdisciplinary research efforts incorporating scientists from the fields of chemistry, physics, biology, medicine, electronics and engineering. However, the absence of a technique capable of fully characterising these structures is hampering progress. In the present review, special focus will be given to our pioneering study using the biological nanopore, α-hemolysin (αHL), for the single-molecule analysis of surface-modified gold NPs.