Using techniques borrowed from astronomy, biologists have developed a new microscopy technique that delivers extraordinary 3D video of cells moving around inside living tissue. It's a fascinating window into just how busy and complex life is at the cellular level.
Researchers at the Howard Hughes Medical Institute's Janelia Research Campus in Virginia combined two cutting-edge imaging techniques to produce moving images of life at the microscopic level in unprecedented definition.
The new microscope uses an adaptive optical system – similar to what astronomers use to unscramble the view of distant stars through Earth's swirling atmosphere – to create and maintain a thinly illuminating lattice light sheet that penetrates within an organism.
A second adaptive optics system looks down from another angle to create distortion-free images of the illuminated frame, while a third system fires a laser through either of these pathways, creating a super bright point of light that can be used to further correct any optical aberrations in the other two systems.
Different tissues give different amounts of distortion, allowing the researchers to classify and color them in a 3D model. The result is an extraordinarily high-definition set of 3D point clusters that can be used to create stunning video footage of cellular motion within living tissue.
Take a look at this incredible footage of immune cells worming their way through the tissue of a zebrafish's inner ear, gobbling up blue particles of sugar as they go.
Or this creepy shot of a cancer cell rolling its way around in a piece of zebrafish xenograft tissue, its sticky appendages trailing behind it. Or, travel up the middle of a spinal cord and watch the neural circuits forming connections as it develops.
The new technique also helps solve one of the main issues with current cellular imaging, which typically requires researchers to shine very high intensity light through the tissue to get a signal back out – light levels that physicist Eric Betzig describes as "thousands to millions of times more intense than the desert sun." These kinds of light intensities could easily put living cells under significant stress, causing them to exhibit behaviors they might not under normal conditions. The ultra-thin sheet of light this new technique uses is much gentler to the samples.
Clearly, it's a huge leap forward in microscopic imaging. The device used to film these videos is currently big enough to fill a 10-ft-long (3 m) table. Betzig and the research team are working on a next-gen version that should be much smaller.
The first machine they build will go to Janelia's Advanced Imaging Center, where scientists around the world will have the opportunity to use it, and the group is also planning to release the design in such a way that other scientists with the necessary equipment can build their own. There is also a move to commercialize it as a product. Betzig predicts that within 10 years, this will be a standard technique widely available to biologists.
The whole thing, to the casual observer, provides a mind-bending glimpse into the incredible complexity of life on a totally different scale. And it seems somehow fitting that tools and techniques used to map the universe on a cosmic scale are now giving us a window into life at the cellular level.
The team's work is described in a paper published in Science, and more incredible imaging examples can be seen in the 19-minute video below.
Source: Howard Hughes Medical Institute
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