Researchers have peered into the brains and bodies of living animals after discovering that a common food dye can make skin, muscle and connective tissues temporarily transparent.
Applying the dye to the belly of a mouse made its liver, intestines and bladder clearly visible through the abdominal skin, while smearing it on the rodent’s scalp allowed scientists to see blood vessels in the animal’s brain.
Treated skin regained its normal colour when the dye was washed off, according to researchers at Stanford University, who believe the procedure opens up a host of applications in humans, from locating injuries and finding veins for drawing blood to monitoring digestive disorders and spotting tumours.
“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumours by simply examining a person’s tissue without the need for invasive surgical removal,” said Dr Guosong Hong, a senior researcher on the project. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin.”
The trick has echoes of the approach taken by Griffin in HG Wells’s 1897 novel, The Invisible Man, in which the brilliant but doomed scientist discovers that the secret to invisibility lies in matching an object’s refractive index, or ability to bend light, to that of the surrounding air.
When light penetrates biological tissue, much of it is scattered because the structures inside, such as fatty membranes and cell nuclei, have different refractive indices. As light moves from one refractive index to another, it bends, making tissue opaque. The same effect makes a pencil look bent when dropped in a glass of water.
Dr Zihao Ou and his colleagues at Stanford theorised, counterintuitively, that particular dyes could make certain wavelengths of light pass more easily through skin and other tissues. Strongly absorbing dyes alter the refractive index of tissues that absorb them, allowing scientists to match the refractive indices of different tissues and suppress any scattering.
In a series of experiments described in Science, the researchers show how a fresh chicken breast became transparent to red light minutes after being immersed in tartrazine solution, a yellow food dye used in US Doritos, SunnyD drink and other products. The dye reduced light scattering inside the tissue, allowing the rays to penetrate more deeply.
The team then smeared the yellow dye on a mouse’s underbelly, making the abdominal skin see-through and revealing the rodent’s intestines and organs. In another experiment, they applied dye to a mouse’s shaved head and, with a technique called laser speckle contrast imaging, saw blood vessels in the animal’s brain.
“The most surprising part of this study is that we usually expect dye molecules to make things less transparent. For example, if you mix blue pen ink in water, the more ink you add, the less light can pass through the water,” Hong said. “In our experiment, when we dissolve tartrazine in an opaque material like muscle or skin, which normally scatters light, the more tartrazine we add, the clearer the material becomes. But only in the red part of the light spectrum. This goes against what we typically expect with dyes.”
The researchers describe the process as “reversible and repeatable”, with skin reverting to its natural colour once the dye is washed away. At the moment, transparency is limited to the depth the dye penetrates, but Hong said microneedle patches or injections could deliver the dye more deeply.
The procedure has not yet been tested on humans and researchers will need to show it is safe to use, particularly if the dye is injected beneath the skin.
Others stand to benefit from the breakthrough. Many scientists study naturally transparent animals, such as zebrafish, to see how organs and features of disease, such as cancer, develop in living creatures. With transparency dyes, a much wider range of animals could be studied in this way.
In an accompanying article, Christopher Rowlands and Jon Gorecki, of Imperial College London, say there will be “extremely broad interest” in the procedure, which, when combined with modern imaging techniques, could allow scientists to image an entire mouse brain or spot tumours beneath centimetre-thick tissues. “HG Wells, who studied biology under TH Huxley, as a student would surely approve,” they write.
