Super-Resolution Fluorescence Microscopy

The 2014 Nobel Prize in Chemistry went to Eric Betzig for his work on super-resolution fluorescence microscopy. Many people are excited about this because Betzig essentially built a microscope that is metaphorically comparable in caliber to the Hubble telescope. Here is a quick summary of what he did and why it is awesome.

In order to understand what Betzig did, we have to start by understanding what the problem he solved was. In Microscopy, the main problem had to do with Abbe’s resolution limit. This limit describes the point at which two objects that are close together can no longer be distinguished from each other. The objects, in this case, are molecules or even individual atoms. As two molecules get closer together, the beams of light that are emitted/reflect off of them into the microscope’s lens begin to overlap. When this happens, the overlapping portions of both light waves combine to create a larger wave. As a result, the gap between both molecules is impossible to see and they are indistinguishable in the final image. The figure below explains how this happens and was taken from this website:

Betzig overcame this problem by developing a system that collects light emitted first from one molecule and second from the other to produce two separate images, one image for each molecule, and then combines both images to make a third image of both objects together. Because the light collected from the objects in each of the original two images is in a slightly different location, they are distinguishable in the the third image. Below is a quick movie of the principle being applied to an image of the Eiffel Tower as it sparkles at night over Paris. This is very simplistic explanation of what Betzig did when he created his PALM system. There is a lot of math and chemistry involved in the full explanation on the wikipedia article about the subject which you can check out here: Photoactivated Localiztion Microscropy (PALM)


A cool story: on the day Betzig was awarded the Nobel Prize, researchers in his lab announced that they were able to use his techniques to produce groundbreaking images of T-cells fighting HIV infected cells. Below is an image of a T-cell (orange) interacting with a target cell (blue). This image represents a stunning advance compared with the simplistic pictures of complex biological processes available when I was a kid. Check it out:


Here are some cool images taken using this system.


<p><a href=”″>Movie S12 High Resolution</a> from <a href=”″>HHMI NEWS</a> on <a href=””>Vimeo</a&gt;.</p>


C. elegans embryo (roundworm commonly found in soil)

<p><a href=”″>Movie S15 High Resolution</a> from <a href=”″>HHMI NEWS</a> on <a href=””>Vimeo</a&gt;.</p>


T. thermophila (a common protozoan found in freshwater ponds)

<p><a href=”″>Movie S13 High Resolution</a> from <a href=”″>HHMI NEWS</a> on <a href=””>Vimeo</a&gt;.</p>


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