Multiscale modeling and analysis for high-fidelity interferometric scattering microscopy

Abstract

Interferometric scattering microscopy (iSCAT), as an ultrasensitive fluorescence-free imaging modality, has recently gained enormous attention and has been rapidly developing from demonstration of principle to quantitative sensing and bioanalytics. Here we report on a theoretical framework of multiscale modeling and analysis for iSCAT with samples of arbitrary shapes under any types of illumination and detection schemes. We theoretically predict and experimentally confirm different evolution behaviors of the interference contrast as a function of the axial defocusing for dielectric and metallic nanoparticles. We provide a transparent understanding of the origin of the interference phenomenon in terms of plane wave components and explain how the interference contrast changes with the size and material of the nanoprobe and the numerical aperture of the microscope objective. Moreover, we investigate a sample system mimicking a gold nanoparticle in a simplified cell environment and show the position-dependent and asymmetric point spread function of the nanoparticle.