Label-Free Tracking of Proteins through Plasmon-Enhanced Interference

Single unmodified
biomolecules in solution can be observed and
characterized by interferometric imaging approaches; however, Rayleigh
scattering limits this to larger proteins (typically >30 kDa).
We
observe real-time image tracking of unmodified proteins down to 14
kDa using interference imaging enhanced by surface plasmons launched
at an aperture in a metal film. The larger proteins show slower diffusion,
quantified by tracking. When the diffusing protein is finally trapped
by the nanoaperture, we perform complementary power spectral density
and noise amplitude analysis, which gives information about the protein.
This approach allows for rapid protein characterization with minimal
sample preparation and opens the door to characterizing protein interactions
in real time.