Detection
of small amounts of biological compounds is of ever-increasing
importance but also remains an experimental challenge. In this context,
plasmonic nanoparticles have emerged as strong contenders enabling
label-free optical sensing with single-molecule resolution. However,
the performance of a plasmonic single-molecule biosensor is not only
dependent on its ability to detect a molecule but equally importantly
on its efficiency to transport it to the binding site. Here, we present
a theoretical study of the impact of downscaling fluidic structures
decorated with plasmonic nanoparticles from conventional microfluidics
to nanofluidics. We find that for ultrasmall picolitre sample volumes,
nanofluidics enables unprecedented binding characteristics inaccessible
with conventional microfluidic devices, and that both detection times
and number of detected binding events can be improved by several orders
of magnitude. Therefore, we propose nanoplasmonic–nanofluidic
biosensing platforms as an efficient tool that paves the way for label-free
single-molecule detection from ultrasmall volumes, such as single
cells.