Researchers at Stanford University have found that an aqueous solution of a common food color approved by the U.S. Food and Drug Administration, tartrazine, has the effect of reversibly making the skin, muscle, and connective tissues transparent in live rodents.
Illustration of skin tissues rendered transparent following saturation by FD & C Yellow 5, including the paths of photons reflecting off un-dyed tissues. Image credit: Keyi ‘Onyx’ Li / U.S. National Science Foundation.
“We combined the yellow dye, which is a molecule that absorbs most light, especially blue and ultraviolet light, with skin, which is a scattering medium. Individually, these two things block most light from getting through them,” said study first author Dr. Zihao Ou, who, with colleagues, conducted the study while he was a postdoctoral researcher at Stanford University before joining the University of Texas at Dallas in August 2024.
“But when we put them together, we were able to achieve transparency of the mouse skin.”
To master the new technique, Dr. Ou and colleagues developed a way to predict how light interacts with dyed biological tissues.
Those predictions required a deep understanding of light scattering, as well as the process of refraction, where light changes speed and bends as it travels from one material into another.
Scattering is the reason we cannot see through our body: fats, fluids within cells, proteins, and other materials each have a different refractive index, a property that dictates how significantly an incoming light wave will bend.
In most tissues, those materials are closely compacted together, so the varied refractive indices cause light to scatter as it passes through. It is the scattering effect that our eyes interpret as opaque, colored, biological materials.
The researchers realized if they wanted to make biological material transparent, they had to find a way to match the different refractive indices so light could travel through unimpeded.
Building upon fundamental insights from the field of optics, the researchers realized dyes that are the most effective at absorbing light can also be highly effective at directing light uniformly through a wide range of refractive indices.
One dye the scientists predicted would be particularly effective was tartrazine, the food dye more commonly known as FD & C Yellow 5.
It turns out, they were correct: when dissolved into water and absorbed into tissues, tartrazine molecules are perfectly structured to match refractive indices and prevent light from scattering, resulting in transparency.
The authors first tested their predictions with thin slices of chicken breast.
As tartrazine concentrations increased, the refractive index of the fluid within the muscle cells rose until it matched the refractive index of the muscle proteins — the slice became transparent.
Then, they gently rubbed a temporary tartrazine solution on mice.
First, they applied the solution to the scalp, rendering the skin transparent to reveal blood vessels crisscrossing the brain.
Next, they applied the solution to the abdomen, which faded within minutes to show contractions of the intestine and movements caused by heartbeats and breathing.
The technique resolved features at the scale of microns, and even enhanced microscope observations.
When the dye was rinsed off, the tissues quickly returned to normal opacity.
The tartrazine did not appear to have long-term effects, and any excess was excreted in waste within 48 hours.
“It’s important that the dye is biocompatible — it’s safe for living organisms,” Dr. Ou said.
“In addition, it’s very inexpensive and efficient; we don’t need very much of it to work.”
The team has not yet tested the process on humans, whose skin is about 10 times thicker than a mouse’s.
“At this time it is not clear what dosage of the dye or delivery method would be necessary to penetrate the entire thickness,” Dr. Ou said.
“In human medicine, we currently have ultrasound to look deeper inside the living body.”
“Many medical diagnosis platforms are very expensive and inaccessible to a broad audience, but platforms based on our tech should not be.”
The study was published this week in the journal Science.
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Zihao Ou et al. 2024. Achieving optical transparency in live animals with absorbing molecules. Science 385 (6713); doi: 10.1126/science.adm6869
This article was adapted from original releases by U.S. National Science Foundation and the University of Texas at Dallas.
