Interferometric detection of scattering (iSCAT): from sensing to microscopy

While fluorescence labeling remains a powerful tool for many studies, it also poses fundamental limitations, which have motivated many groups to develop fluorescence-free measurement methods. Scattering offers many interesting opportunities for these efforts, but lack of spectral specificity makes the detection of small objects via scattering challenging. Nearly two decades ago, we showed that, nevertheless, single gold nanoparticles as small as 5 nm could be detected via interferometric detection, giving birth to a new detection scheme that was later coined iSCAT. Since then, it has been shown that small unlabeled proteins could be detected and counted, and transmembrane proteins tracked on living cells using gold nanoparticles as scattering label. In this presentation, I discuss the technical subtleties of iSCAT, its principal advantages and several new studies that have become possible by it.