X-Ray specs and invisibility cloaks are the stuff of sci-fi and fantasy, but sometimes science is just stranger than fiction. A food dye that helps give certain sodas and snacks their hallmark orange hue renders mouse skin almost completely see-through in a reversible, potentially non-toxic research method that could transform medical and scientific imaging. Because of a counterintuitive fundamental physics principle, Tartrazine, also known as Yellow 5, can temporarily turn biological tissue transparent to the naked eye, as described in a study published September 5 in the journal Science.
So far, the scientists behind the new discovery have used the method to see the organs in a mouse’s intact abdomen, glimpse the pulsing vessels surrounding a rodent skull, and to get an exceptionally clear view of muscle tissue through a microscope. With further safety and efficacy research, the method may spur new scientific findings, boost microscopy advances, and improve medical diagnostic strategies and treatments.
“I instantly looked at it and went, ‘my god, this is revolutionary,’” says Christopher Rowlands, a senior lecturer and biophotonics researcher at Imperial College London. Rowlands wasn’t involved in the study, but wrote an accompanying perspective article on it after he acted as a reviewer for the research. “In optics, we spend an awful lot of time trying to increase [how well we can see into tissue] by 20 percent or 50 percent. These guys come along and they annihilate the boundary by a factor of 10.” The most advanced current optical imaging (i.e. non-invasive, and not reliant on radiation) techniques might allow a scientist to see a couple of millimeters into live tissue, but the new method could make detail more than a centimeter deep visible to the naked eye, says Rowlands. “It’s not magic, but it’s still very powerful,” he adds.
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The method is simple. In short, massaging tartrazine solution into hairless mouse skin over the course of a few minutes or using microneedling achieves “complete optical transparency in the red region of the visible spectrum,” per the study. Wash the dye away, and the skin returns to its natural, opaque state.
“Biological tissues, like skin, are usually not see-through because light gets scattered as it passes through them,” says Guosong Hong, co-senior study author and a bioengineer at Stanford University. Animal flesh is a matrix of different materials, mostly water and fats, and these two types of compounds refract light at different angles, he explains. A light particle, or photon, traveling through tissue under normal circumstances moves from water particle to lipid particle, being bounced around, taking a long, winding path, and oftentimes being absorbed by one of the many molecules it collides with along the way.
But tartrazine dye, through its powerful absorption of blue wavelengths of light, changes the refractive index of water to be much closer to that of fat, Hong says. This happens through a basic physical principle called the Kramers-Kronig relations, which dictates that waves (like those of light–which is both a particle and a wave) are the result of predictable signals. As a result, a photon can pass through skin almost as if the tissue were homogenous. It takes a shorter path, avoiding all of the bouncing and angle changes that increase the likelihood of light absorption, ultimately illuminating the inside of a mouse.
The physics concepts involved in the process are so fundamental that, “I was kicking myself that I hadn’t thought of it,” Rowlands tells Popular Science. “It’s one of these moments where it’s blindingly obvious, but you need somebody else to tell you it first. It makes so much sense in retrospect.” It’s a “triumph of fundamental understanding,” he adds, which demonstrates what happens when a deep understanding of a theory comes together with real-world experimentation.
Hong and his colleagues came to their precise method through modeling how different dyes would shift the way light travels in tissue. They homed in on Yellow 5 and a handful of other pigments as candidates for improving transparency. Then, they tested it out in liquid mixed with silica particles, raw chicken breast, live mice, and other mouse tissue samples–measuring how quickly and deeply the dye dispersed. They further combined the dye with other optical microscopy techniques, showing that tartrazine can be used to improve existing tech. Finally, they conducted an initial toxicity analysis, looking for short and long term effects in their rodent test subjects and tracking how quickly the mice seemed to clear the dye from their systems via urine and feces. The scientists determined that Yellow 5 passes through the body within 24 hours, causes little inflammation or irritation, and shows “minimal systemic toxicity.”
However, the method isn’t yet perfect and can’t, for instance, make an entire living mouse invisible or immediately enable us to see the inner-workings of a human abdomen. For one, Yellow 5 can only penetrate so far into tissue, so it won’t be as useful for imaging through thicker, less permeable flesh (like that of a human) without a targeted delivery strategy and a fine-tuned understanding of what concentration works best. Plus, though the dye reduces photon scattering, it doesn’t entirely eliminate it, notes Rowlands. The thicker the tissue you use it on, the darker and less clear the resulting image will be. Finally, though initial toxicity assessments bode well, Rowlands isn’t so sure tartrazine will prove totally harmless in the long term, with additional tests. “I would suspect that dumping that amount of anything into a live organism is going to have some substantial effect,” he says.
Hong, too, notes that more safety research is needed. “We strongly discourage attempting this on human skin, as the toxicology of dye molecules in humans, particularly when applied topically, has not been fully evaluated,” he tells Popular Science.
If Yellow 5 dye does prove safe in topical applications for humans, it might eventually be used for purposes as varied as early skin cancer detection, easing the process of routine blood draws for those with hard-to spot veins, speeding up laser tattoo removal, or supercharging photothermal cancer treatments, says Hong. Yet even if the snack-dye technique remains relegated to lab mice, it offers a better window into one of the most commonly used model organisms than we’ve ever had before. “In the short term, it’s a research tool,” says Rowlands, who envisions great strides coming from the finding soon: Optical imaging of a complete mouse brain, for instance. “If that’s not a paper [within a year], I’ll eat my hat.”