Nanophotonic approaches for nanoscale imaging and single-molecule detection at ultrahigh concentrations

Over the last decade, we have witnessed an outburst of many different optical techniques aimed at breaking the diffraction limit of light, providing super-resolution imaging on intact fixed cells. In parallel, single-molecule detection by means of fluorescence has become a common tool to investigate biological interactions at the molecular level both in vitro and in living cells. Despite these advances, visualization of dynamic events at relevant physiological concentrations at the nanometer scale remains challenging. In this review, we focus on recent advancements in the field of nanophotonics toward nanoimaging and single-molecule detection at ultrahigh sample concentrations. These approaches rely on the use of metal nanostructures known as optical antennas to localize and manipulate optical fields at the nanometer scale. We highlight examples on how different optical antenna geometries are being implemented for nanoscale imaging of cell membrane components. We also discuss different implementations of self-standing and two-dimensional antenna arrays for studying nanoscale dynamics in living cell membranes as well as detection of individual biomolecular interactions in the µM range for sensing applications.