Multiscale Modeling and Analysis for High-fidelity Interferometric Scattering Microscopy

Abstract

Interferometric scattering microscopy (iSCAT), as an ultrasensitive fluorescence-free imaging modality, has recently gain enormous attention and been rapidly developing from demonstration of principle to quantitative sensing. Here we report on a theoretical and experimental study for iSCAT with samples having structural dimensions that differ by 4-5 orders of magnitude. In particular, we demonstrate and intuitively explain the profound effects of sub-nanometer surface roughness of a glass coverslip and of a mica surface on the absolute signal and the shape of the point spread function of a gold nanoparticle. These quantities significantly affect the accuracies for determining the target size and position in all three dimensions. Moreover, we investigate a sample system mimicking a gold nanoparticle in a simplified cell environment and show position-dependent and even asymmetric point spread function of the nanoparticle. The multiscale study will facilitate the development of high fidelity iSCAT in real applications.

arXiv commentExpanded the discussion on the effect of surface roughness

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