A yellow dye makes living animals transparent

By applying a food additive dissolved in water, US scientists have managed to make the skin of the skull and abdomen of mice become translucent in a safe and reversible way. This advance could revolutionize optical research in biology and help in medical diagnosis if it is applied to humans in the future.

By topical application to a live mouse of a common food coloring –the tartrazine–, which strongly absorbs light, researchers at Stanford University (USA) have managed to make their tissues transparent.

This is how they have been able to observe the blood vessels of the scalp and brain surface, the movement of the organs located under the skin of the abdomen and the tiny contractile units of the working muscle. Details are published this week in the magazine Science.

Through the mouse's transparent skin, the blood vessels of the scalp and the movement of the abdominal organs could be seen.

The colorant used dissolved in water (known as FD&C Yellow 5 in the United States, yellow 5 in Latin America and additive E 102 in the European Union) is often used in chips as an appetizer, the toppings of candies and other orange or yellowish foods. 

The authors have combined this dye, which absorbs most of the blue and ultraviolet light, with a light-dispersing medium such as the skin. Separately, these two components block most of the light rays, but when they are put together, the transparency of the external tissue that covers the animal is achieved.

«Biological tissue is a complex combination of water (with low refractive index) and biomolecules such as lipids y proteins (which have a high refractive index); and as with a mixture of water and oil, the light is scattered in all directions as it travels through the tissue, causing optical opacity.”, the main author explains to SINC, Zihao Ou, who has just joined the University of Texas at Dallas as a professor of Physics from Stanford.

«By introducing strongly light-absorbing molecules, such as tartrazine, into this aqueous medium, the refractive index of the solution at certain wavelengths increases (according to mathematical equations called Kramers-Kronig relationships) and the differences in refractive index in biological tissues decrease considerably. This reduces light scattering in tissue biological and becomes visually transparent”

Zihao Ou (Stanford/UT Dallas)

In essence, the dye molecules reduce the degree of light scattering in the skin tissue, as if dissipating a bank of fog.

Researchers discovered the advantages of tartrazine and other absorbent molecules to achieve transparency from Basic knowledge of the field of optics and doing predictions on how light interacts with stained biological tissues.

Transparent chicken breast

They first tested their predictions on thin slices of chicken breast. As the concentrations of the dye increased, the refractive index of the fluid inside the muscle cells increased, until it matched the refractive index of the muscle proteins. As a result, the slice became transparent.

Then, in their experiments with mice, the authors rubbed the water-tartrazine solution onto the skin of their skulls and abdomens. Once the dye had fully diffused into that tissue, in a few minutes, this became transparent, although with an orange tone.

Temporary and reversible effect

The transparency effect is temporary and reversible, since can be removed with a quick wash of the dye. The amount that has penetrated the skin It is metabolized and eliminated through urine.Unlike other methods used to increase transparency, these substances do not harm living animals.

Thus, through the transparent skin of the mouse skull, the researchers were able to directly see the blood vessels on the surface of the brain. In the abdomen, they observed the internal organs and the peristalsis, the muscle contractions that move contents through the digestive tract.

“It is important that the colorant is biocompatible, that is, safe for living organisms,” says Ou, who highlights that, in addition, “it is very cheap and effective: we do not need a lot of it for it to work.”

Future application in humans

The authors have not yet tested the process in the human skin, which is about 10 times thicker than that of a mouse, but this could be done in the future. It is not yet clear what dose of dye or method of administration would be needed to penetrate the entire thickness.

" fundamental physics “The underlying optical opacity is the same between human and mouse skin,” the professor stresses, “and we foresee that there are no essential limits to the application of our invention to people. What is required is a drug delivery strategy and a recipe design more efficient and precise to achieve optimal imaging conditions with minimal adverse effects.”

"The fundamental physics underlying optical opacity is the same between human and mouse skin, and we foresee no fundamental limits on the application of our invention to people."

Zihao Ou (Stanford/UT Dallas)

The researcher anticipates that one of the first applications of the technique will probably be to improve the current ones. research methods in optical imaging“When we saw the results of our experiments, we immediately thought about how this could improve biomedical research. Optical equipment, such as microscopes, is not directly used to study living humans or animals because light cannot pass through living tissue. But now that we can make tissue transparent, it will allow us to observe more detailed dynamics. It will completely revolutionize current optical research in biology.”

"This technique will completely revolutionize current optical research in biology"

Zihao Ou (Stanford/UT Dallas)

“Apart from that – he continues – due to its character non-invasive unique, it will also allow investigations of chronic biological questions that span a relatively long time, such as cancer metastasis and the Alzheimer disease. Furthermore, we foresee the possible clinical application of this invention for the early diagnosis of other pathologies and health monitoring in people.”

He also points out that many medical diagnostic platforms are expensive and inaccessible to a wide audience, “but those based on our technology should not be.”

Next Steps

The next steps of the investigation will consist of determine what dose of the dye molecule may work better in human tissues. Moreover, the authors are already experimenting with other molecules, including artificial materials, which may be more effective than tartrazine.

This study was supported by U.S. federal agencies including the National Institutes of Health (NIH), the National Science Foundation (NSF), and the Air Force Office of Scientific Research. The authors have already applied for license of this technology.

Reference: Zihao Ou et al. “Achieving optical transparency in live animals “with absorbing molecules”. Science, 2024

Source: SINC

Rights: Creative Commons