Carnegie Mellon University
April 01, 2020

Using Chemistry as a Lens to Aid in Diagnosing Diseases

By Ben Panko

A team of researchers led by a Carnegie Mellon Biological Sciences researcher has improved a powerful cellular magnification technique, making it more practical for use in clinical settings.

"For almost 200 years, pathologists have used optical microscopes to examine biopsies from patients," said Assistant Professor of Biological Sciences Yongxin (Leon) Zhao. However, the diffraction limit of light means that minute, but important, details in tissue samples can't be seen with even the best conventional optical microscopes.

More powerful techniques and devices, such as super-resolution optical microscopes and electron microscopes, do exist; however, they are expensive and technically complex and therefore not available to most pathologists. To get around this issue, Zhao and collaborators have pioneered a technique known as Expansion Pathology, which can magnify the details of human tissues by physically making them larger. This allows normal microscopic equipment to see far more detail than ordinarily possible.

In a new collaborative paper published in the journal Nature Protocols, Zhao and his colleagues at the Massachusetts Institute of Technology and Harvard Medical School have laid out step-by-step how this new field of Expansion Pathology can enable pathologists to inexpensively and rapidly track even the subtlest changes in human tissue.

Zhao likens Expansion Pathology to looking at the Earth with an ordinary backyard telescope. You may be able to see some features of the planet but nothing in close detail. Now imagine if you were able to literally stretch the Earth and everything on it in all directions equally, expanding it in size. Suddenly, with that same ordinary telescope you would be able to see houses, trees and even people.

The technique works by chemically embedding the specimen in a hydrogel, which is a substance made of cross-linking polymer chains that expand when they come into contact with water. Perhaps best known for being used in baby diapers, these hydrogels tug on the tissue from all directions and stretch it to a larger size.

"We use chemistry as a lens to further magnify the details of the pathological samples," Zhao explained.

Previous iterations of this technique would take around 30 hours to properly expand and image samples, but in their newest paper Zhao and his collaborators introduce an improved version called Rapid Expansion Pathology that takes only four to eight hours to use, which significantly lowers the barrier for adaptation in the fast-paced clinical setting.

"This technique can be applicable to a wide range of tissues or questions that you want to work with, and it can be further empowered by machine learning," Zhao said. "Basically, now the limitation is what kind of questions do you want to ask that can benefit from this kind of technology. “

On that end, Zhao is now working with pathologists to conduct new clinical studies enabled by Expansion Pathology that may one day foster new diagnostics.

"It's not just a technique — it's a new possibility to open up the field," Zhao said.