New microscope lets scientists see inside living cells without dyes
Nobel laureate W. E. Moerner's team at Stanford has built a microscope that reaches about 120 nanometres of detail in living cells without fluorescent labels, using less light so cells suffer less damage. It could help show how drugs work and how infections such as malaria take hold.
To see inside a living cell in detail, scientists usually stain it with fluorescent labels. It works, but there are drawbacks: the labels fade over time, are hard to get into cells and can change the very structures being studied. A team at Stanford University has built a microscope that skips that step. It described the instrument in Light: Science & Applications, a Nature portfolio journal.
The technique is called interferometric image scanning microscopy (iISM). It reaches a detail of about 120 nanometres, which its developers say is the finest yet achieved without labels. It comes from the lab of W. E. Moerner, who won the 2014 Nobel Prize in Chemistry, with postdoctoral researcher Michelle Kueppers as first author.
How it works
A laser lights up the cell, and its structures scatter a small amount of that light. A second beam amplifies the faint signal so it can be detected. Instead of a single detector, the instrument uses an array that captures tens to hundreds of views at once, and the team developed a way to combine them into sharper images. It also uses far less light than other high-contrast label-free methods, lowering the risk of damaging the cells. That means many structures can be watched at once, and for longer.
What it could be used for
The team is already working with collaborators to study how cancer drugs get into cells and how plants, fungi and bacteria interact in real time. It also plans to watch how red blood cells change shape during a malaria infection. ‘This is not a niche technique,’ says Kueppers.
Its limits
Its resolution is coarser than that of the most specialised high-resolution microscopes, and it is not meant to replace fluorescence microscopy – the researchers see the two as complementary. The work was first announced in March and was funded by the US National Institute of General Medical Sciences.
