Imaging Breakthrough: Researchers Develop a New Method That Makes Animal Tissue Transparent

A new technique from a team at Scripps Research (La Jolla) that makes human and animal tissues transparent will make it much easier to study many diseases in the body, such as COVID-19 infection. The method, reported in the journal Nature Methods, involves tissue clearing to make large biological samples transparent. The technique makes it easier for researchers to visualize and study the biological processes underlying many systems and organs, both healthy and diseased.

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Transparent Lung of a Mouse

Transparent Lung of a Mouse. Credit: Scripps Research

This new technique, called “HYBRiD”, combines elements from two existing tissue-clearing methods to examine large samples. Lead author Li Ye, a professor of neuroscience at Scripps Research, adds that the method makes it possible to study “large body systems or even whole animals.”

tissue-clearing uses solvents to remove molecules that make tissue opaque (e.g. fat). The goal is to make the tissue optically transparent while keeping it in place and preserving most of the proteins and structures. Researchers commonly use genetically encoded or antibody-linked fluorescent tags to mark active genes or other molecules of interest in a laboratory model animal, and the tags can then be “imaged” at once for the whole animal.

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Current procedures use organic or aqueous solvents. The former are generally faster and more powerful but tend to weaken fluorescent signals. Methods using water-based solvents are more effective at preserving fluorescence but are not very effective at removing non-brain tissue. In addition, both types of methods require cumbersome procedures that require both significant human resources and hazardous chemicals. In other words, these procedures cannot be performed routinely by all medical laboratories.

The new method uses a sequential combination of organic solvents and water-based detergents, as well as hydrogels that protect the tissue molecules to be preserved. The procedure is simplified: “In many cases, you can put it in a jar and store it in a shaker on the bench until analysis,” explains Victoria Nudell, co-author and researcher at Scripps. “It becomes possible to do routine analysis.”

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Proof of concept has already been achieved through a series of experiments, including for the first time capturing SARS-CoV-2 infected cells in the entire lung of a mouse. Scientists are also working on tracking nerve pathways throughout the body.


HYBRiD: hydrogel-reinforced DISCO for clearing mammalian bodies



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