A century after British writer HG Wells proposed the possibility of altering the refractive index of a person’s body to make them invisible, a team of researchers has used the same theoretical approach to achieve similar results, at a superficial scale, on the skin of a mouse.
In a study published this Thursday in the journal ScienceThe team led by Zihao Ou of the University of Texas describes how they managed to make the skin on the skull and abdomen of living mice transparent by applying a mixture of water and a common yellow food coloring called tartrazine to these areas. “For those who understand the basic physics behind it, it makes sense; but if you’re not familiar with it, it seems like a magic trick,” Ou cautions.
He trick consists of find the liquid that can penetrate the tissues and change the refractive index of the cells to match that of some of their components such as lipids. In other words, light scatters much less on the skin and passes through it, allowing us to see what is underneath.
“We combined the yellow dye, which is a molecule that absorbs most light, especially blue and ultraviolet light, with the skin, which is a scattering medium,” explains the lead author. “Individually, these two elements block most of the light from passing through them. But when we combined them, we were able to achieve the transparency of the mouse skin.
Light without obstacles
Drawing on fundamental knowledge in the field of optics, the researchers realized that the dyes most efficient at absorbing light can also be very efficient at directing light uniformly over a wide range of refractive indices.
One dye that the researchers thought would be particularly effective was tartrazine, more commonly known as FD&C Yellow 5, which is used in candy, alcoholic beverages, and even to color paella. And it turns out they were right: When dissolved in water and absorbed into tissues, tartrazine molecules are perfectly structured to match refractive indices and prevent light from traveling unimpeded, resulting in transparency.
For those who understand the fundamental physics behind it, it makes sense; but if you’re not familiar with it, it seems like a magic trick.
Zihao Ou
— University of Texas researcher and lead author of the study
The first tests were conducted on thin slices of chicken breast. The authors then gently applied a temporary solution of tartrazine to the scalps of living mice, making the skin transparent and revealing blood vessels. They then applied the solution to the abdomen, which faded within minutes to reveal contractions of the intestine and movements caused by heartbeat and breathing.
The authors of the work also verified that when the dye was washed off with water, the fabrics quickly returned to their normal opacity. Tartrazine does not appear to have long-term effects and any excess is excreted within 48 hours in the urine. “It takes a few minutes for the transparency to appear,” Ou explains. “It works similarly to a cream or a face mask: the time it takes depends on how quickly the molecules diffuse into the skin.”
Application in humans
The researchers believe that injecting the dye should lead to a better understanding of organisms, with implications for both biology and medicine. “Optical equipment, such as microscopes, are not used directly to study living humans or animals because light cannot pass through living tissue,” Ou says. “But now that we can make the tissue transparent, it will allow us to observe more detailed dynamics. “This will completely revolutionize existing optical research in biology.”
The dye has the advantage of being cheap and not requiring a large amount to work, at least in mice, which have very thin skin. The researchers now want to test the technique on humans, whose skin is about ten times thicker than that of a mouse. So it’s not clear what dose of dye or method of administration would be needed.
This doesn’t mean that one day we’ll be able to apply a cream to a person’s skin and see their internal organs without the need for a scanner, but scientists believe that if it proves safe and effective in humans, it could perhaps be applied to a wide range of medical diagnoses, from locating lesions to monitoring digestive disorders or identifying cancers.
In the future, this technology could make veins more visible for blood sampling.
Guosong Hong
— Stanford University researcher and co-author of the article
“In the future, this technology could make veins more visible for blood sampling, facilitate laser tattoo removal, or aid in the early detection and treatment of cancers,” said Guosong Hong, assistant professor of materials science and technology at Stanford University. “For example, some therapies use lasers to eliminate cancer and precancerous cells, but are limited to areas near the surface of the skin. “This technique can improve the penetration of light.”
A breakthrough for biotechnology
Pablo Artal, an optics specialist and professor at the University of Murcia (UMU), considers this to be an interesting work, although the approach is certainly counterintuitive, as the authors themselves acknowledge. “What they do is add absorbent particles to the fabric that seem they command the fabric in some way and reduce the level of diffusion and make the fabric more transparent,” he explains to elDiario.es.
In Artal’s opinion, the image results are very good and the approach seems to work. “Another issue is its possible usefulness beyond mere curiosity and questions about reversibility and possible tissue damage, because the scattering is reduced, but the tissue remains stained, as shown in some images,” he says.
Tartrazine appears to be an ideal compound for “cleaning” tissues in vivo
Conchi Lillo
— Neurobiologist and vision specialist at the University of Salamanca (USAL)
Conchi Lillo, a neurobiologist and vision specialist at the University of Salamanca (USAL), points out that compounds such as acrylamide are already used to “eliminate” lipids that allow brain tissue to be better observed under a microscope. “It is now possible to analyze blocks of brain tissue with this technique because whitening makes the fabric transparent, but allows it to be done only on fixed fabric, not on fabric in vivobecause these compounds are not harmless to cells,” he explains. “So tartrazine seems to be an ideal compound for clearing fabric in vivo“.
However, Lillo warns, this method has some limitations, because it relies on adapting the refractive index of the aqueous medium to that of lipids and proteins. “The refractive index of these compounds is heterogeneous, so it remains difficult to find a single, optimal concentration of the dye solution to obtain a perfect adjustment of the refractive index in a given tissue,” he points out. On the other hand, he points out, the thickness of the skull of the mice with which they are doing the experiments is only a few millimeters, which allows them to see the blood vessels of the brain. With the thickness of human skin and bones, remember, everything would be very different.
For María Victoria Gómez Gaviro, principal researcher at the Gregorio Marañón Health Research Institute, the novelty lies in the substance used and its use. in vivo. “This brings advantages for preclinical experimentation and surgical models, as it can facilitate the localization of vessels and muscles, which would reduce the invasiveness of some surgical procedures; invasive procedures such as cutting the skin and manipulating muscles, vessels and organs would be avoided,” he explains in statements to the SMC. On the limitations side, he believes that the toxicity of this compound in vivo, side effects and medium and long-term effects should be ignored. “More complete studies on possible damage to organs located under the optical window created and on skin recovery are lacking,” he says.
