Researchers at Stanford University have created a powerful new imaging system that reveals the inner workings of living cells with remarkable clarity. Known as Interferometric Image Scanning Microscopy (iISM), the technology combines two advanced microscopy techniques to achieve a resolution of about 120 nanometers, an unprecedented level of detail for an approach that does not require fluorescent labels.
The system makes it possible to observe multiple cellular structures simultaneously while they move, change, and respond to their surroundings. Scientists can also investigate what happens when cells encounter drugs or disease-causing organisms, potentially uncovering biological processes that have been difficult to study.
One of the most important advantages of the new microscope is its ability to reveal cellular activity without relying on fluorescent markers. Many existing microscopy techniques use fluorescent substances to highlight specific structures inside cells, but these methods come with limitations. Researchers can generally label only a small number of structures at once, and fluorescent signals can fade during observation through a process known as photobleaching. Introducing the labels can also be challenging, and some markers may alter the behavior of the very structures scientists want to study.
The Stanford system avoids these problems by imaging cells without fluorescent labels. This allows researchers to follow numerous cellular components over extended periods while observing their activity in a more natural setting. Additionally, iISM requires substantially less illumination power than comparable label-free methods, reducing the possibility of photodamage.
“This new microscope provides a fantastic new view into the cell, where you can see the tiny structures and machines in the cell moving, changing, and interacting without having to add fluorescence to observe them,” said senior author W.E. Moerner, the Harry S. Mosher Professor of Chemistry in Stanford’s School of Humanities and Sciences. “It’s a wonderful look into these complex little cellular boxes that drive our life.”