You may have caught a glance of yesterday’s Nobel Prize in chemistry — the science community was awash with the news. Three scientists won the award for pushing the limits of microscope resolution far beyond what was ever thought possible. But you may not know that one of the winners, American physicist Eric Betzig, has continued to push the boundaries of biological imaging by incorporating elements from astronomy.
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| The Very Large Telescope in Chile using a laser guide star. Credit: Yuri Beletsky (ESO) via Wikimedia Commons |
Both molecular biologists and astronomers rely critically on boosting the resolution of their images. Molecular biologists study objects on small scales that challenge all but the most powerful of microscopes, and astronomers study extremely distant objects that make them appear incredibly small. Astronomers constantly battle against resolution limits in order to probe the furthest and most compact exotic objects in the Universe such as black holes, neutron stars, and the nursery regions of stars and planets.
The Earth’s atmosphere presents a particular challenge, creating a blurry effect akin to looking up from the bottom of a swimming pool. To overcome this obstacle, astronomers use a technique called adaptive optics to cancel out distortions caused by light passing through a wobbly atmosphere.
Similarly, biologists encounter the same problem when they peer through layers of tissue in order to image an internal structure. By applying traditional astronomical techniques, Betzig and his colleagues at HHMI Janelia Farm Research Campus have managed to greatly enhance the power of their microscopes.
Adaptive Optics in Astronomy
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| Compilation of 8 images showing the effect of Earth’s atmosphere on our view of the Moon. Credit: Philipp Salzgeber |
Atmospheric distortions are evident as the twinkling and blurring of stars when you look up into a clear dark sky and are caused by temperature and wind fluctuations within the atmosphere. These distortions severely limit the practical resolution of Earth-based optical telescopes such that, at best, they can resolve something like the Lower Mississippi river flowing on the surface of the moon.
By selecting a nearby, bright ‘guide star’ and measuring how this star’s incoming light wavefront changes with time and position in the sky, astronomers can subtract off distortions from the atmosphere and create a much more focused image of their target. In practice, this subtraction is usually achieved by rapidly adjusting sections of a deformable mirror to cancel out the distortions.
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| Perturbed light caused by passing through the atmosphere or a biological membrane. Credit: 2pem via Wikimedia Commons |
Biology
Very similar light distortions also vex biologists trying to resolve cellular structures because biological samples can bend the light from the microscope in complex and unpredictable ways. In the past few years, Betzig and colleagues at Janelia have used the same principles of astronomical adaptive optics to shine a guide star of focused light through a biological sample and then correct for the resulting bumpy wavefront.
This works well with transparent samples (think organisms like jelly fish) where the light is distorted but not significantly scattered as it passes through the sample. The analogy with the transparent atmosphere of Earth then allows for a straightforward transfer of the adaptive optics technique to the realm of microscopy.
The nature of biological samples, however, varies a lot over small scales; thus, the correction to a bumpy wavefront at one point in the sample does not apply to light from a different point in the sample. By scanning the guide star across the sample and determining an average correction, a much higher quality image results.
An added bonus of this technique is that it is largely non-invasive, allowing the working processes of living organisms to be observed. This past April, Betzig’s group demonstrated the high-resolution imaging of neurons within the brain of a living zebrafish in a report in Nature Methods, as shown in this video (no commentary).
In the future, it should be possible to use adaptive optics to readily give ordinary microscopes the power to see things in a much sharper focus. The work of Betzig and colleagues highlights just how invaluable emerging image resolution techniques can be, regardless of astronomical or biological scale.
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By Tamela Maciel, also known as “pendulum”