A dye that helps give Doritos their orange color may also add transparency to mouse tissues, researchers have found. Applying the dye to the skin of living mice allowed scientists to look through tissues to underlying structures, including blood vessels and internal organs. The one on September 6th inSciencedescribed method 1could provide a less invasive way to monitor live animals used in medical research.

“It's a major breakthrough,” says Philipp Keller, a biologist at the Howard Hughes Medical Institute's Janelia Research Campus in Ashburn, Virginia.

The technique works by changing how normally opaque parts of the body interact with light. The liquids, fats, and proteins that make up tissues like skin and muscle have different refractive indices (a measurement of how much a material bends light): aqueous components have low refractive indices, while lipids and proteins have high ones. Tissues appear opaque because the contrast between these refractive indices causes light to scatter. The researchers speculated that adding a dye that strongly absorbs light to such tissues would narrow the difference between the components' refractive indices enough to make them transparent.

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“If a material absorbs a lot of light in one color, it will bend light in other colors more,” says study author Guosong Hong, a materials scientist at Stanford University in California. The team used theoretical physics to predict how certain molecules would change how mouse tissues interact with light. Several candidates emerged, but the team focused on tartrazine, or FD&C Yellow 5, a commonly used colorant in many processed foods. “When tartrazine is dissolved in water, it makes the water more pliable, similar to fats,” says Hong. A tissue containing fluids and lipids becomes transparent when the dye is added because the refraction of light from the fluids is equal to that of the lipids.

Transparent skin

The researchers demonstrated the ability of tartrazine to render tissue transparent on thin slices of raw chicken breast. They then massaged the dye into different areas of a live mouse's skin. By applying the dye to the scalp, the team was able to study tiny zigzag patterns of blood vessels; applying it to the abdomen provided a clear view of the mouse's intestinal movement during digestion and revealed other movements related to breathing. The team also used the solution on the mouse's leg and was able to detect muscle tissue under the skin.

The technique can only make tissue transparent to a depth of about 3 millimeters, so it is currently of limited practical use only for thicker tissues and larger animals.

But because tartrazine is a food dye, it's safe for live mice and the method is reversible - when the dye is rinsed off, the skin simply returns opaque again. This offers a major advantage over existing methods of producing transparent tissue, which are typically not suitable for live animals and often require the use of chemicals to change the refractive index of certain tissue components or remove them entirely.

The fact that the method creates transparency, is reversible and can be used on live animals “makes it an obvious thing that a lot of people want to use,” says Keller. He believes it could be useful, among other things, in mouse models that want to understand the nervous system and neurodegenerative diseases.