Imaging of interactions of biomolecules with nanomaterials with interferometric scattering microscopy

Interferometric scattering microscopy (iSCAT) is a label-free imaging technique that achieves single-molecule spatial and milli-second temporal resolution. In this technique, we use the combination of reflected and scattered light of the nanoparticle itself as our signal obviating the need of a label or tags as commonly used in fluorescence microscopy. With iSCAT, photobleaching is not an issue as the signal donor (the particle of interest) provides an infinite budget of scattered photons and hence indefinite imaging times. We apply this method to image and track biomolecules, such as DNA and proteins, without any fluorescent tags in their native state for upwards of seconds. We characterize and tracked the motion of DNA from the initial attachment, diffusion along the surface and finally detachment with single-molecule resolution. This allows us to image the nanoscopic interactions of native DNA with different 2D nanomaterials such as graphene and hBN. Together with other surface characterization techniques such as AFM, we identify sites of increased trapping potential and elucidate the nanoscopic mechanism behind the interaction between biomolecules and the 2D material surface. We envision that our studies allow us to inform on future biosensor design with engineered surface interactions.