Researchers at Stanford University have developed a microscope that can image the interior of living cells at roughly 120-nanometer resolution without using fluorescent labels. The instrument, called interferometric image scanning microscopy (iISM), combines interferometric scattering microscopy with an approach adapted from confocal microscopy. This lets scientists watch organelles and other structures move and interact in real time, while avoiding the photobleaching and labeling constraints of conventional fluorescence techniques.
Because iISM relies on scattered light rather than added markers, it can track many cellular components simultaneously and requires less illumination power than comparable label-free methods. That gentler illumination reduces photodamage, allowing longer observation periods. The researchers note that other specialized microscopes can achieve finer resolution, but the combination of detail, low light exposure, and extended imaging makes iISM particularly useful for studying living systems.
The team sees iISM as a complement to fluorescence microscopy rather than a replacement. As first author Michelle Kueppers explains, fluorescence provides molecular specificity while iISM supplies label-free context and dynamics, which together could address questions that have been difficult to tackle. Potential applications include cancer research, drug development, infectious disease studies, and plant-microbe interactions.