The detection of small nanoparticles and individual molecules has traditionally relied on fluorescence, however, this technique is usually limited by the photophysics and by the requirement of labeling. Interferometric scattering (iSCAT) microscopy, which leverages the Rayleigh scattering of nanoparticles, has proven to be a powerful label-free alternative for the detection of small nanoparticles and single molecules. In this presentation, I will highlight the recent advancements in iSCAT microscopy as a method for high spatio-temporal 3D tracking of nanoparticles and imaging in complex environments. Through a quantitative understanding of the iSCAT point spread function (iPSF) and modeling the experimental imaging apparatus, we have developed a novel algorithm for 3D tracking of single nanoparticles with µs temporal and sub-nanometer spatial resolution. Our technique also offers potential for precise sizing of nanoparticles in liquid suspensions, as well as investigation of molecular interactions at surfaces. Additionally, I will introduce a data analysis toolbox that allows us to model the speckle pattern and iPSF distortion on scattering surfaces, providing us with phase information and enabling us to track nanoparticles in highly speckled environments. Lastly, I will showcase a new iSCAT modality that reduces speckles and provides label-free visualization of cellular components such as the endoplasmic reticulum and vesicle transport.

Mahdi Mazaheri obtained his B.Sc. in Electrical Engineering at the University of Tehran. He furthered his education with an M.Sc. in Electrical Engineering, where his thesis focused on the design and fabrication of a device to enhance photon-induced current in plasmonic nanostructures. Building on his expertise in electrical engineering, Mahdi continued his academic journey with a second M.Sc. in Integrated Life Sciences awarded with distinction from Friedrich-Alexander-Universität Erlangen-Nürnberg and the Max Planck Institute for the Science of Light in Erlangen, Germany with a thesis focus on ultra-high-speed imaging of rotational diffusion of a gold nanorod on a supported lipid bilayer. Currently, Mahdi is a PhD student in the group of Prof. Vahid Sandoghdar at the Max Planck Institute for the Science of Light. Mahdi’s research is centered on development of microscopy techniques, with a specific emphasis on tracking and imaging in highly scattering media. By combining computational modeling of optical systems with experiments and developing signal processing toolboxes, Mahdi aims to tackle the challenges presented by tracking and imaging in scattering media, primarily via interferometric scattering microscopy.