Why can’t light microscopes see inside cells?

A close-up view of a light microscope.
| Photo Credit: Indra Projects

A: The resolution of an instrument that uses light to see things can’t improve beyond a point. This is called the diffraction limit.

The resolving ability of, say, a telescope says how well it can distinguish between two distant objects that are close to each other. The higher the telescope’s resolution, the better its resolving ability.

In the late 1870s and early 1880s, a German engineer and physicist named Ernst Karl Abbe found a formula that connected the maximum resolution to the wavelength of light and a number called the numerical aperture:

d = w/2N

where w is the wavelength, N is the numerical aperture, and d is the maximum resolvable distance.

Thanks to the diffraction limit, scientists could use the light microscope to see cells but not the proteins inside them or a virus attacking them.

But there are optical microscopes today that can see inside cells and even things as small as atoms. This is because, from the 1980s onwards, scientists developed a new technique called super-resolution microscopy, and it wasn’t bound by the diffraction limit.

Instead of sending light through the microscope to illuminate the cells, it attached special molecules to the cells. These molecules — called fluorophores — glowed when hit with radiation, and when they did, the microscope could also understand their surroundings.

In 2014, the developers of super-resolution microscopy were awarded the chemistry Nobel Prize for their work.