How Microscopy Expansion Helps ‘Blow Up’ Tiny Brain Tissue

Microscopes magnify minute wonders, allowing them to be seen. Though the resolution and cost of such optical equipment have improved over the last 400 years, there are always constraints in terms of resolution and cost. This makes researching objects at the nanoscale, such as neurons, the brain’s fundamental functional unit, difficult.

Dr. Kiryl Piatkevich, the assistant professor at Westlake University in Hangzhou, then decided to go in the opposite direction. They came up with an idea not to magnify the image of an object but to magnify the object itself, to blow it up.

The concept is so absurd that even Dr. Piatkevich doubted it could be accomplished. Until Dr. Ed Boyden’s team at MIT, where Kiryl Piatkevich was working at the time, discovered a sort of self-expandable hydrogel consisting mostly of water-absorbing polymers. This is the same type of hydrogel that is now used in newborn diapers.

The new substance can absorb many times its own weight in water. Each hydrogel polymer chain grows in the same way during the process, allowing the material to increase exponentially in size, up to 1,000 times larger. And how can this instrument assist us in better understanding our brain?

READ ALSO: How Fluorescent Probes Helps Visualize Live Brain Cells

To allow this idea to work, Dr. Piatkevich embeds a slice of brain tissue into the hydrogel. The gel is then fully immersed in water. On the nanoscale, the molecules of the brain tissue slice stretch with the hydrogel molecules attached to them. This method is known as “expansion microscopy.”

Though the gel itself can grow equally in all directions, how do we ensure that the gel’s sample tissue will expand proportionally to keep its structure from being distorted?

“The main reason for the expansion appearing to be entirely isotropic, or equal in all directions,” Dr. Piatkevich noted, “is that the hydrogel monomers we’d inject are just less than one nanometer in size, so all of these monomers may be evenly covered by molecules that surround them.

To put it another way, the nanometer-scaled hydrogel monomers act as tiny little hooks. They tightly grip onto each molecule of brain tissue, then tug them toward their own development directions without changing the original shape, ensuring that there are enough hooks dispersed as evenly as possible. And, perhaps most crucially, into a considerably greater size.

With this technique, which has been further developed in Dr. Piatkevich’s lab at Westlake University, a sample slice can expand up to eight times in length, or roughly 700 times in volume.

This technology is sweeping the biological sciences because it is so easy, inexpensive, and reliable. Expansion of clinical specimens to obtain a super-resolution image of specific human tissues to diagnosis some early-stage disorders that are not visible with a regular microscope is being tested in the United States.

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