Single-molecule microscopy and spectroscopy have revolutionized the real-time observation of molecular dynamics, yielding unprecedented insights into molecular interactions. Among these techniques, fluorescence correlation spectroscopy (FCS) has been instrumental in studying biological processes within live cells. However, conventional FCS is restricted to diffraction-limited detection volumes of around one femtoliter, which is sufficient for single-molecule studies at nanomolar concentrations but inadequate under physiological conditions, where concentrations typically reach the micromolar range and require detection volumes on the order of 100 zeptoliters. In this study, we present the fabrication of nanowaveguide devices consisting of a titania core with a plasmonic metal cladding in cylindrical or slit formats. This design surpasses the diffraction limit, achieving sampling volumes on the order of 200 zeptoliters. Furthermore, the near-field confinement of the transmitted light enables an illumination spot with dimensions of sub-50-nm laterally and about 20 nm longitudinally, rendering this system particularly suitable for investigating single-molecule dynamics in cell membranes under physiological conditions. Here, we investigate how variations in reactive ion etching parameters, such as RF power and chamber pressure, influence the etch rate and the anisotropic sidewall profiles of the titania dielectric core, and characterize the optical properties of these nanowaveguides with far-field transmission and FCS measurements.
Rodriguez et al. (2026) studied this question.