Light microscopy has been a mainstay of neuroscience and many areas of biology for more than a century. But the resolution limit of light, based on immutable physical principles, has kept the fine details of many structures out of view. Scientists can’t change the laws of physics—but NIH-supported researchers recently devised a highly creative way to see images that were previously out of reach, by expanding the contents of tissue sections up to five times their normal size, while maintaining the anatomic arrangements. The new approach takes advantage of a compound used in—get this—disposable diapers!
By harnessing the super-absorbent properties of sodium polyacrylate, a polymer commonly used in diapers, a team from the Massachusetts Institute of Technology (MIT) developed a new technique that makes it possible for conventional microscopes to produce super high-resolution images of brain cells. The name of the new technique? Expansion microscopy.
To create such images, MIT neuroscientist Ed Boyden, along with graduate students Fei Chen and Paul Tillberg, start by labeling proteins of interest with fluorescent antibodies. The sample is then embedded within a 3D mesh of sodium polyacrylate, with the fluorescent molecules on the antibodies connecting to the sodium polyacrylate. The proteins are dissolved, leaving the fluorescent labels attached to the expandable polymer. The researchers then add water, and the polymer matrix swells evenly in three dimensions just as it does in a diaper. The final product is a neural landscape with greatly enlarged cell structures that also appear transparent, making them perfect for microscopy.
Expansion microscopy can be used to scan whole brain structures and show entire neural networks in 3D. To date, Boyden, who is a recipient of both the NIH Director’s Pioneer and Transformative Research awards, has tested expansion microscopy on brain cells cultured in the lab and on slices of neural tissue from mice. Who knows where he’ll take it from here?
 Optical imaging. Expansion microscopy. Chen F, Tillberg PW, Boyden ES. Science. 2015 Jan 30;347(6221):543-8.
 Microscopy. The superresolved brain. Dodt HU. Science. 2015 Jan 30;347(6221):474-5.
Video: Superabsorbent Diaper Compound May Soup Up Brain Cell Imaging (National Institute of Neurological Disorders and Stroke/NIH and McGovern Institute for Brain Research at MIT)
Synthetic Neurobiology Group, Ed Boyden, MIT, Cambridge, MA
NIH Director’s Pioneer Award Program (Common Fund/NIH)
NIH Director’s Transformative Research Award Program (Common Fund/NIH)
NIH Support: Common Fund; National Institute of Neurological Disorders and Stroke; National Institute of Mental Health