MIT team enlarges brain samples, making them easier to image

Beginning with the invention of the first microscope in the late 1500s, scientists have been trying to peer into preserved cells and tissues with ever-greater magnification. The latest generation of so-called “super-resolution” microscopes can see inside cells with resolution better than 250 nanometers.

A team of MIT researchers has now taken a novel approach to gaining such high-resolution images: Instead of making their microscopes more powerful, they have discovered a method that enlarges tissue samples by embedding them in a polymer that swells when water is added. This allows specimens to be physically magnified, and then imaged at a much higher resolution. This technique, which uses inexpensive, commercially available chemicals and microscopes commonly found in research labs, should give many more scientists access to super-resolution imaging, the researchers say.

“Instead of acquiring a new microscope to take images with nanoscale resolution, you can take the images on a regular microscope. You physically make the sample bigger, rather than trying to magnify the rays of light that are emitted by the sample,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT. Boyden is the senior author of a paper describing the new method in a recent online edition of Science.

Before enlarging the tissue, researchers first label the cell components or proteins that they want to examine, using an antibody that binds to the chosen targets. This antibody is linked to a fluorescent dye, as well as a chemical anchor that can attach the dye to the polyacrylate chain.

Once the tissue is labeled, the researchers add the precursor to the polyacrylate gel and heat it to form the gel. They then digest the proteins that hold the specimen together, allowing it to expand uniformly. The specimen is then washed in salt-free water to induce a 100-fold expansion in volume. Even though the proteins have been broken apart, the original location of each fluorescent label stays the same relative to the overall structure of the tissue because it is anchored to the polyacrylate gel.