In an innovative research project, scientists successfully made the skin on live mice’s skulls and abdomens transparent using a combination of water and a well-known yellow food dye, known as tartrazine.
In an innovative research project, scientists successfully made the skin on live mice’s skulls and abdomens transparent using a combination of water and a well-known yellow food dye, known as tartrazine.
Dr. Zihao Ou, who is an assistant professor of physics at The University of Texas at Dallas, is the lead author of this study published in the September 6 issue of the journal Science.
Skin in its natural state acts like a barrier for light, similar to how fog obscures vision, which is why it’s usually not transparent.
“By combining the yellow dye, which absorbs most light, especially blue and ultraviolet wavelengths, with skin, which scatters light, we were able to create transparency. Alone, these substances block light, but together they allowed us to illuminate the mouse skin,” explained Ou, who conducted this research while he was a postdoctoral researcher at Stanford University before joining the faculty of UT Dallas in August.
“For those familiar with the underlying physics, this makes intuitive sense; for others, it might appear to be magic,” Ou remarked.
The “magic” emerges because dissolving the light-absorbing molecules in water adjusts the solution’s refractive index—indicating how much a substance bends light—so it aligns with that of bodily tissues like fats. Essentially, the dye molecules minimize the scattering of light, akin to clearing up fog.
During the experiments, the team applied the water and dye mixture onto the skin of the mice’s skulls and bellies, and once the dye permeated the skin, transparency was achieved. This process can be reversed simply by washing away the dye, as the absorbed dye is naturally metabolized and expelled through urine.
“It takes only a few minutes for the clarity to develop,” Ou said. “It’s similar to how a facial cream works: the duration depends on how quickly the molecules are absorbed by the skin.”
Through the now-transparent skull skin, researchers could see the blood vessels directly on the brain’s surface, while inside the abdomen, they observed internal organs and the contractions that propel food through the digestive system.
The transparent skin takes on an orangish hue, due to the dye known as FD&C Yellow #5, which is commonly found in yellow or orange snacks, candies, and various foods. The Food and Drug Administration has approved nine color additives, including tartrazine, for food use.
“It’s crucial that the dye is biocompatible, meaning it’s safe for living organisms,” Ou noted. “Moreover, it’s very affordable and effective; we don’t require a large amount for it to be effective.”
Currently, the researchers have not tested this technique on humans, whose skin is significantly thicker than that of mice—approximately ten times more. Ou cautioned that it’s unclear what dosage or method would be needed to penetrate human skin effectively.
“In human medicine, we usually rely on ultrasound for deeper imaging of live bodies,” Ou said. “Many diagnostic technologies are costly and not available to a wide audience, but methods rooted in our findings may be more accessible.”
According to Ou, one of the initial applications of this technique is likely to enhance existing research methodologies in optical imaging.
“Our team is primarily academic, so right away, we considered how these results might benefit biomedical research,” he mentioned. “Optical instruments like microscopes aren’t typically used on living humans or animals due to light being unable to penetrate living tissue. However, now that we can render tissue transparent, it will enable us to explore intricate biological dynamics, effectively transforming optical biology research.”
In his newly established Dynamic Bio-imaging Lab at UT Dallas, Ou aims to further the research he began with Dr. Guosong Hong, an assistant professor of materials science and engineering at Stanford, and one of the study’s co-authors. Ou indicated that future research steps will involve determining the most effective dosage of the dye for human tissues. Additionally, the team is exploring various other molecules, including engineered materials, that might outperform tartrazine.
Dr. Mark Brongersma from Stanford, a co-corresponding author of the study, along with other authors, received funding from various federal grants, including those from the National Institutes of Health, the National Science Foundation, and the Air Force Office of Scientific Research. Ou participated as an interdisciplinary postdoctoral scholar funded by the Wu Tsai Neuroscience Institute at Stanford. The team has filed for a patent for this technology.
