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Microscopes are good, but not that good. The view through them gets prohibitively fuzzy when you try to look at things smaller than half the wavelength of the light used for imaging; for visible light, that is anything below a few hundred nanometres. Many things we would like to see in intimate detail, such as the processes that sustain life, are at far smaller scales than that.
We used to think of this “diffraction limit” as a fundamental physical barrier, caused by the bending and spreading out of light waves whenever they encounter an obstacle such as the lens of a microscope. Not any more. The rot started with electron microscopes, which exploit the tiny wavelengths of electrons to image objects just a few nanometres across. Unfortunately, living cells cannot survive being bombarded by electrons. So to expose life’s little secrets, we need to break light’s diffraction limit using light itself.
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The near-field scanning optical microscope, invented in 1984, does just that. It harnesses short-lived light waves that form along a material’s surface when it is illuminated. These “evanescent waves” do not have a chance to diffract, and capturing them before they disappear brings the size of the object that can be viewed down to about 50 nanometres. The downside is that to do that, the microscope’s aperture must stick very close to the sample, so you can only see a bit of it at any one time.
A far zippier solution is stimulated emission depletion (STED) microscopy. Laser beams are shot at a sample to produce distinctive patterns of fluorescence with a resolution of just 5 nanometres – only twice the width of a DNA molecule. That works whether the sample is living or dead. “The beauty is you can image anything with STED,” says of Purdue University in West Lafayette, Indiana.
The cutting edge now is diffraction-busting superlenses made from nano-engineered “metamaterials”, which could exploit evanescent waves while allowing a variable focus over a larger area. But even as we leave the diffraction limit behind, a more formidable barrier comes into view. As we enter the quantum realm, the notorious uncertainty principle, which limits any measurement’s accuracy, threatens to irrevocably blur our sight.
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