  More than twenty years ago, scientists succeeded in pushing the limits of
optical detection to single molecules using fluorescence. This breakthrough has
revolutionized biophysical measurements, but restrictions in photophysics and
labeling protocols have motivated many efforts to achieve fluorescence-free
single-molecule sensitivity in biological studies. Although several interesting
mechanisms using vibrational spectroscopy, photothermal detection, plasmonics
or microcavities have been proposed for biosensing at the single-protein level,
no method has succeeded in direct label-free detection of single proteins.
Here, we present the first results using interferometric detection of
scattering (iSCAT) from single proteins without the need for any label, optical
nanostructure or microcavity. Furthermore, we demonstrate super-resolution
imaging of protein binding with nanometer localization precision. The ease of
iSCAT instrumentation promises a breakthrough for industrial usage as well as
fundamental laboratory experiments.
