Looking into living cells without dye: Stanford unveils new microscope
A team led by Nobel laureate W.E. Moerner observes structures in living cells at 120-nanometer resolution, with no fluorescent labels that fade or can disturb the cell.
Archive image · Photo: Christopher Michel / Wikimedia Commons, CC BY-SA 4.0 (cropped and resized)
Researchers at Stanford University have developed a microscope that can track processes in living cells in real time without first labeling them with fluorescent dyes. The technique is called interferometric image scanning microscopy (iISM) and, according to the team, achieves a lateral resolution of about 120 nanometers. The study by Michelle Küppers and W.E. Moerner was published in the journal Light: Science & Applications. Moerner received the 2014 Nobel Prize in Chemistry for super-resolved fluorescence microscopy.
The principle: a laser illuminates the cell, and the scattered light is amplified by superimposing it with a second laser beam. A detector array, like those found in modern confocal microscopes, captures dozens to hundreds of views, which a computational method combines into sharper images with more contrast and depth information. Fluorescent labels, by contrast, can usually show only a few structures at once, fade over time and can alter the behavior of the labeled molecules. According to Stanford, iISM also requires significantly less light than comparable label-free methods, which helps prevent cell damage.
The team sees the method not as a replacement for fluorescence but as a complement. "This is not a niche technique," Küppers said. Planned studies will examine how plant cells, fungi and bacteria interact and how a cancer drug enters the cell; studies on the deformation of red blood cells in malaria are in preparation. The researchers are working to make the device available to many fields of biology.