Multiscale modeling and analysis for high-fidelity interferometric scattering microscopy

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 experimental study for iSCAT with samples having structural dimensions that differ by 4-5 orders magnitude. In particular, demonstrate intuitively explain the profound effects sub-nanometer surface roughness glass coverslip mica absolute signal shape point spread function gold nanoparticle. These quantities significantly affect accuracies determining target size position in all three dimensions. Moreover, investigate sample system mimicking nanoparticle simplified cell environment show position-dependent even asymmetric The multiscale will facilitate development high fidelity real applications.