In order to take a look inside the body, complex imaging techniques – or a scalpel – were previously required. Now researchers have found a simple and reversible method to make the skin of living organisms transparent: the commercially available food coloring tartrazine changes the refractive index of the tissue so that it becomes permeable to visible light. When the researchers rubbed mice with the dye dissolved in water, their blood vessels and internal organs became visible. The method could open up new possibilities for biological research and medicine.
Whether a material is permeable to visible light, i.e. appears transparent to us, depends, among other things, on its refractive index. Light is scattered at the interface between substances with different refractive indices. The lower the scattering, the more transparent the material. This effect can be observed, for example, when you mix anise liquor such as ouzo or raki with water. Individually, both liquids are transparent, but together they become milky because the light is scattered at the interface between the water and the tiny anise oil droplets dissolved in the alcohol. It is similar with our skin: water and fat molecules are mixed here and ensure that the incoming light is strongly scattered.
Light refraction adjusted
A team led by Zihao Ou from Stanford University in California has now found a way to adjust the refractive index of the watery parts of the skin to that of the fatty components so that the skin becomes transparent. To do this, the team used the commercially available food coloring tartrazine (E102). The azo dye is used in the food industry, for example, to give lemonade, pudding or processed cheese a yellow-orange color.
The dye molecules are highly light-absorbing, especially in the blue-violet spectrum. “We made the counterintuitive observation that highly absorbing molecules can achieve optical transparency in living tissues,” the researchers report. “The physical background of this observation is that when the light-absorbing molecules dissolve in water, they change the refractive index of the aqueous medium so that it corresponds to that of tissue components with a high refractive index, such as lipids.”
Insights into the interior of the body
To test the effects of the dye on the light transmission of tissues, the researchers first used a thin slice of chicken breast, which they placed in an aqueous solution of the dye. And indeed: As the tartrazine concentration increased, the refractive index of the aqueous components increased to such an extent that the slice became transparent. In the next step, the team tested the method on living mice. They carefully rubbed the animals’ heads, stomachs or hind legs with an aqueous tartrazine solution.
As hoped, the structures beneath the skin were actually visible. The individual blood vessels could be seen on the head, the muscles on the hind leg, and the internal organs on the stomach, including the intestinal movements and the beating heart. The method also proved to be very successful in combination with other imaging techniques. It was also completely reversible: when the researchers washed off the dye, the skin soon looked the same as before.
Perspectives for future use
“This approach offers a new way to visualize the structure and activity of deep tissues and organs in vivo in a safe, temporary and non-invasive way,” write Christopher Rowlands and Jon Gorecki of Imperial College London, who were not involved in the study, in an accompanying commentary also published in the journal Science. “One of the benefits of being able to make tissue optically transparent is the synergy with other techniques that enable deeper imaging than either could achieve on its own.”
“Looking ahead, this technology could make veins more visible for blood sampling, simplify tattoo removal using lasers, or help with early detection and treatment of cancer,” says Ou’s colleague Guosong Hong. “For example, certain therapies use lasers to eliminate cancer and precancerous cells, but these are confined to areas close to the surface of the skin. This technique may be able to improve the penetration of light.”
The current study did not investigate whether the method is also suitable for use in humans. However, the fact that tartrazine is already approved for use in food speaks for its safety. The mice also tolerated the dye well. When it was administered systemically, the animals excreted excess amounts in their feces within 48 hours. The study also provides the basis for the discovery of other potentially suitable dyes. “Our calculations suggest that the search for powerful optical clarifiers should focus on strongly absorbing molecules,” say the researchers.
Source: Zihao Ou (Standford University, CA, USA) et al., Science, doi: 10.1126/science.adm6869