We present a comprehensive
computational study on the optimization
of the size of gold nanorods for single-molecule plasmonic sensing
in terms of optical refractive index sensitivity. We construct an
experimentally relevant model of single-molecule–single-nanoparticle
sensor based on spherically capped gold nanorods, tip-specific functionalization
and passivation layers, and biotin-streptavidin affinity system. We
introduce a universal figure of merit for the sensitivity, termed
contrast-to-noise ratio (CNR), which relates the change of measurable
signal caused by the discrete molecule binding events to the inherent
measurement noise. We investigate three distinct sensing modalities
relying on direct spectral measurements, monitoring of scattering
intensity at fixed wavelength and photothermal effect. By considering
a shot-noise-limited performance of an experimental setup, we demonstrate
the existence of an optimum nanorod size providing the highest sensitivity
for each sensing technique. The optimization at constant illumination
intensity (i.e., low-power applications) yields similar values of
approximately 20 × 80 nm2 for each considered sensing
technique. Second, we investigate the impact of geometrical and material
parameters of the molecule and the functionalization layer on the
sensitivity. Finally, we discuss the variable illumination intensity
for each nanorod size with the steady-state temperature increase as
its limiting factor (i.e., high-power applications).