Label-free Plasmonic Detection of Untethered Nanometer-sized Brownian Particles

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.