system
Given the following post, respond as if you're commenting on Reddit:
human
The Nobel Prize in Chemistry this year was awarded for super-resolution fluorescence microscopy. How does it work?
gpt
Normally, in samples you see a diffuse spread of thousands or millions of fluorescent molecules. You cannot resolve these individually because the light coming from each of these particles is "fuzzy" and gets blurred out because of the fundamental nature of photons. This fuzziness arises from a limit called the diffraction limit. It turns out that you can localize fluorescent particles better than this limit, but you need to do some tricks.

One way of seeing below this limit is to image the particles one at a time. If you want to see below this limit, you need a way of only imaging samples such that the particles you see are not so close together. It turns out that you can localize them individually much better than you can when they are all together, so you just need a way of randomly localizing them one at a time. One technique is called PALM (photo-activated localization microscopy).

Another way is to use some exotic properties of fluorescent materials that arise because of photophysical properties. These are properties that arise from the way the electrons transitions in these materials. If you are careful about the way you image, you can excite a super-small portion of the material, smaller than the diffraction limit mentioned above. If you do this and sweep over the entire sample, you can get resolution better than the diffraction limit. This is very simplified way of describing it, but this technique is called STED (stimulated emission depletion microscopy).

This technique is also similar in principle to something called "near field microscopy," where you only illuminate your sample with a tiny probe that is smaller than the wavelength of light you would ordinarily illuminate with. This probe is like a nanoscale flashlight. If you sweep this tiny probe over your sample, it will fluoresce only when your tiny probe is in a place where it can generate fluorescence. This is another trick to "beat" the diffraction limit.

**Summary**

A lot of this work has been slowly developed over the last 20 or more years. The diffraction limit remains a fundamental limit of light resolution, but it turns out that if you do the experiment with certain tricks in just the right way, you can get around some of the limitations it imposes. Basically these guys won the Nobel for these tricks.