HYBRiD technology makes tissue transparent: Accelerating future disease research

The HYBRiD technique of making transparent tissue from the Scripps Research Institute (USA) is recognized as being able to easily analyze biological processes in the human body and diseases such as Covid-19….

Scientists from the Scripps Institute have announced a new tissue cleaning method that can make large biological samples transparent. This method makes it easier than ever for scientists to see and study the biological processes involved in disease and what goes on across multiple organ systems in the body.

Using the HYBRiD method to observe the whole chest of mice after SARS-CoV-2 infection showed that viral proteins are red and tissue structures (lungs, blood vessels, bones) are blue.

The method, dubbed HYBRiD, combines elements of two previous major approaches to tissue cleaning technology. HYBRiD was introduced in the journal Nature Method on March 28.

Study author Dr. Li Ye, professor of neuroscience at Scripps Research Institute, said: "This is a simple and common tissue-cleaning technique for large-body or even large-body studies. even the whole body".

Tissue cleansing involves using a solvent to remove molecules that make tissue opaque (such as fat), making the tissue optically transparent - while leaving most of it intact. proteins and structures. Scientists often use fluorescent beacons that are genetically encoded or bound to antibodies to mark active genes or other molecules of animal tissue. And the tissue erasure process makes it possible, in principle, to image these beacons all at once across the entire animal.

Scientists began developing methods of tissue deletion about 15 years ago, primarily aimed at tracing neural connections throughout the brain. While these methods work for the brain, they are not as effective when applied to other body parts or to the entire body, where structures are more difficult to dissolve.

Tissue erasure methods to date have used organic solvents or water-based solvents, which are better at preserving fluorescence but weak in removing non-brain tissues. In addition, these methods all require laborious processes, often using hazardous chemicals.

"A normal laboratory usually cannot use these methods on a regular and large scale," said Yu Wang, a doctoral student at the Ye lab who was also involved in the study.

The new method devised by Ye and his team uses a sequential combination of organic solvents and water-based detergents, while also using water-based hydrogels to protect those molecules in the tissue that needs to be preserved. .

The researchers demonstrated the ease and utility of this new method. Dr. John Teijaro - associate professor of immunology and microbiology used this method to visualize SARS-CoV-2 infected cells in the whole chest of mice.

Ye and his team are currently working with their scientific collaborators on many applications of the new method, including monitoring nerve pathways in the body.