Researchers discovered that common food colorings could temporarily make skin, muscle and connective tissue transparent, allowing them to closely examine the brains and bodies of living animals.
When the dye was applied to the abdomen of a rat, the liver, intestines and bladder were clearly visible through the abdominal skin, and when the dye was applied to the scalp of a rat, the scientists were able to see the blood vessels in the rat’s brain.
Once the dye was washed off, the treated skin returned to its normal color, according to the Stanford researchers, who believe the procedure could have a variety of human applications, from locating injuries and finding veins for blood draws to monitoring gastrointestinal diseases and detecting tumors.
“Instead of relying on invasive biopsies, doctors may be able to diagnose deep-seated tumors simply by examining a person’s tissue without the need for invasive surgical removal,” said Dr. Guosong Hong, a senior investigator on the project. “This technology could potentially reduce the pain of blood draws by making it easier for phlebotomists to find veins under the skin.”
The trick is reminiscent of a technique employed by Griffin in H.G. Wells’ 1897 novel, The Invisible Man, in which a brilliant but doomed scientist discovers that the secret to invisibility lies in matching an object’s refractive index – its ability to bend light – to the refractive index of the air around it.
When light penetrates biological tissue, much of it is scattered due to the different refractive indices of internal structures such as fatty membranes and cell nuclei. As the light travels to areas with a different refractive index, it bends, making the tissue opaque. The same effect causes a pencil to appear bent when you drop it into a glass of water.
Dr. Zhihao Ou of Stanford University and his colleagues theorized that, counterintuitively, certain dyes can make it easier for certain wavelengths of light to pass through skin and other tissues. Highly absorbing dyes change the refractive index of the tissues that absorb them, allowing scientists to match the refractive indices of different tissues and reduce scattering.
In a series of experiments published in the journal Science, the researchers showed that fresh chicken breasts became transparent to red light after a few minutes of being immersed in a solution of tartrazine – a yellow food colouring used in US products such as Doritos and Sunny-D drinks. The dye reduced light scattering inside the tissue, allowing the rays to penetrate deeper.
The team then smeared a yellow dye on the mice’s undersides, allowing the skin to be penetrated to expose the intestines and other organs. In another experiment, they applied the dye to the shaved heads of the mice and used a technique called laser speckle contrast imaging to view blood vessels in the mice’s brains.
“What’s most surprising about this study is that dye molecules are typically expected to decrease transparency — for example, if you mix blue pen ink with water, the more ink you add, the less light passes through the water,” says Hong. “In our experiments, when we dissolved tartrazine in opaque materials that normally scatter light, like muscle or skin, the more tartrazine we added, the more transparent the material became — but only in the red part of the light spectrum. This is the opposite of what is typically expected for dyes.”
The researchers explain that the process is “reversible and repeatable,” and that once the dye is washed off, the skin’s natural color reverts. At present, transparency is limited to the depth to which the dye has penetrated, but Hong said that the dye could be delivered deeper with microneedle patches or injections.
The procedure has not yet been tested in humans, and researchers need to prove it is safe to use, especially when the dye is injected under the skin.
Others stand to benefit from this breakthrough: Many scientists study naturally transparent animals, such as zebrafish, to learn how organs and disease traits like cancer develop in organisms. Using transparent dyes could make it possible to study a much wider range of animals in this way.
In an accompanying article, Christopher Rowlands and John Gorecki of Imperial College London say the technique will be of “enormous wide interest” because, when combined with modern imaging techniques, it could enable scientists to image entire mouse brains and find tumours beneath centimetres of tissue. “HG Wells, as a student of biology under TH Huxley, would surely have been a fan of this technique,” they write.
