The first iSCAT-type of measurements were performed in the biophysics community in the 1990s. A systematic development of the method for the detection of nano-objects started in the early 2000s as a general effort to explore fluorescence-free options for studying single molecules and nano-objects. In particular, gold nanoparticles down to a size of 5 nm were imaged via the interference of their scattered light with a reflected beam from the cover-slip supporting them. Using a supercontinuum laser additionally allowed for recording the particles’ plasmon spectra. The early measurements were limited by residual speckle-like background. A new approach to background subtraction and the acronym iSCAT were introduced in 2009. Since then, a series of important works has been reported by various groups. Notably, further innovations in background and noise suppression have led to the development of new quantification methods such as mass photometry (originally introduced as iSCAMS), in which ultrasensitive and accurate interferometric detection is converted into a quantitative means for measuring the molecular mass of single biomolecules.
