Nanoplasmonic–Nanofluidic Single-Molecule Biosensors for Ultrasmall Sample Volumes

[Image: see text] 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.