A new laboratory technique enables researchers to see minuscule biological features, such as individual neurons and synapses, at a nearly molecular scale through conventional optical microscopes. In a paper published in the journal Science, researchers at MIT said they were able to increase the physical size of cultured cells and tissue by as much as five times while still preserving their structure. The scientists call the new technique expansion microscopy.
The idea of making objects larger to make them more visible is a radical solution to a vexing challenge. By extending the resolving power of conventional microscopes, scientists are able to glimpse such biological mysteries as the protein structures that form ion channels and the outline of the membrane that holds the genome within a cell. The researchers have examined minute neural circuits, gaining new insights into local connections in the brain and a better understanding of larger networks.
The maximum resolving power of conventional optical microscopes is about 200 nanometers, about half the wavelength of visible light. (By contrast, a human hair is about 500 times wider.) In recent decades, scientists have struggled to push past these limits. Last year, three scientists received a Nobel Prize for a technique in which fluorescent molecules are used to extend the resolving power of optical microscopes. But the technique requires specialised equipment and is costly.
With expansion microscopy, Edward S. Boyden, a co-director of the MIT Centre for Neurobiological Engineering, and his colleagues were able to observe objects originally measuring just 70 nanometres in cultured cells and brain tissue through an optical microscope. They were also able to produce super-resolution animations in which the viewer “flies” through a detailed three-dimensional image of a mouse hippocampus. “We hope we have a technology that will allow you to scan the nervous system of entire animals,” Boyden said.
The idea began as a joke during a brainstorming session several years ago, according to Boyden. But he and the graduate students Fei Chen and Paul W. Tillberg realised it might be feasible after exploring the work of the MIT physicist Toyoichi Tanaka, who in the 1970s discovered a class of “intelligent” gels that respond to stimuli such as water. One of those materials is a polymer widely used today in diapers, which absorbs 200 to 300 times its mass in water. The researchers realised it was perfect for forcing biological tissue to swell.