Seeing the invisible

In the 1670s the Dutch cloth merchant Antonie van Leeuwenhoek ground tiny glass lenses and looked at pond water, scrapings from teeth and rainwater. He saw living "animalcules" that nobody had known existed. His single-lens microscopes magnified up to roughly 270 times. A modern school microscope can magnify 1,000 times, but there is a catch: bigger magnification is not the same as a clearer picture.

Magnification makes the image larger. Resolution is the smallest gap between two points that you can still see as two points. If the resolution is poor, magnifying more just gives a bigger blur. This is called empty magnification.

For a light microscope, resolution is limited by the wavelength of light. The Abbe limit says the smallest resolvable distance is about

d = λ ÷ (2 × NA)

where λ is the wavelength of light and NA is the numerical aperture of the lens, a number for how much light the lens gathers. Take green light with λ ≈ 550 nm and a very good lens with NA ≈ 1.4: d ≈ 550 ÷ 2.8 ≈ 200 nm.

So a bacterium of about 2,000 nm is ten times bigger than the limit and shows up clearly. An influenza virus of about 100 nm is smaller than the limit. A light microscope can show it only as a faint blur, if at all.

Electron microscopes use a beam of electrons instead of light. Fast electrons behave like waves with wavelengths far shorter than visible light, so they can resolve details of about a nanometre or even finer in the best instruments. The first electron microscope was built in the early 1930s. In 1939 researchers in Germany published electron micrographs of tobacco mosaic virus, among the first images of a virus particle. (Viruses had been known as "filterable agents" since the 1890s, because they passed through filters that stopped bacteria. Nobody had seen one until then.)