  Optical detection of individual nanometer-sized analytes, virus particles,
and protein molecules holds great promise for understanding and control of
biological samples and healthcare applications. As fluorescent labels impose
restrictions on detection bandwidth and require lengthy and invasive processes,
label-free optical techniques are highly desirable. Powerful label-free optical
methods have recently emerged, such as interferometric scattering microscopy,
plasmonic nanoparticle-based assays and microcavity-based assays. Although
highly sensitive, these methods are so far restricted to integration times in
excess of microseconds. This often imposes a requirement to impede analyte
motion during these periods via specific molecular tethers, unspecific
adsorption or confining arrangements. Here we introduce an optical technique
capable of transforming gold nanorods commonly used as photostable labels into
highly localized high-speed probes. Our method provides a time resolution well
below microseconds. This mitigates the requirement for molecular tethers and
allows us to detect single untethered nanoparticles in Brownian motion
traversing sub atto-liter sensing volumes. Our method opens a novel gateway for
the investigation of highly localized and highly dynamic nanoscale systems and
constitutes a first step towards the label-free recognition of single
untethered proteins.
