Imma Perfetto
Cosmos science journalist
Clinicians can’t spy the blood vessels, muscle, and organs that lie beneath the skin with the naked eye when treating their patients. But researchers may have just found a way to make it possible one day.
US scientists have turned living tissues transparent with the use of a common food dye found in the humble packet of Doritos. The treatment is reversible.
The researchers used tartrazine, also known as FD&C Yellow 5, to turn the skin, muscles, and connective tissues transparent in live rodents, and they believe it will completely revolutionise existing optical research in biology.
The work is documented in a new paper in Science.
“Biological tissues, like skin, are usually not see-through because light gets scattered as it passes through them,” Guosong Hong, assistant professor of materials science and engineering at Stanford University and senior author on the paper, told Cosmos.
“This scattering happens because different parts of the tissue, like water and fats, bend light differently. Water, in particular, bends light less than fats in the visible part of the spectrum.”
This property, which dictates how much an incoming wave of light will be bent by a material, is its refractive index.
Our eyes interpret the scattering that occurs due to the many different refractive indices of biological tissues as opaque, coloured material.
But when tartrazine is dissolved in water and absorbed into tissues it reduces this scattering effect.
Animation depicting how photons interact with tissues at the cellular level, both with and without FD & C Yellow 5 (tartrazine) saturation. Credit: Keyi “Onyx” Li/U.S. National Science Foundation
“Tartrazine, a common yellow dye, absorbs light very strongly at 428nm, which is in the blue part of the visible spectrum, but barely absorbs any light beyond 600nm, in the red part of the spectrum,” explains Hong.
“According to a physics principle called the Kramers-Kronig relations, when a material absorbs a lot of light at one colour (e.g., 428 nm), it will bend light more at other colours (e.g., 600 nm).
“So, when tartrazine is dissolved in water, it makes water bend light more like fats do, without absorbing much light in the red part of the spectrum. This makes the tissue more transparent, especially in the red region of the visible spectrum.”
This means red light can transmit much deeper through the tissue.
The researchers first tested the effect on thin slices of chicken breast. They found that as tartrazine concentrations increased, the refractive index of the fluid within the muscle cells increased until it matched the refractive index of the muscle proteins, and the slice became transparent.
Real-time imaging showing the dynamic process of a chicken breast tissue transitioning from opacity to transparency after immersion in a 0.6 M solution of tartrazine. Scale bar: 5 mm. Credit: Guosong Hong, Stanford University
“This technology could make veins more visible, easing the process of venipuncture – the procedure of drawing blood or administering fluids via a needle – especially for elderly patients with veins that are difficult to locate,” says Hong.
“Moreover, this innovation could assist in the early detection of skin cancer, improve light penetration for deep tissue treatments like photodynamic and photothermal therapies, and make laser-based tattoo removal more straightforward.”
Photodynamic and photothermal therapies can be used to treat various medical conditions, including cancer, by administering a drug known as a photosensitizer, which is activated by light to releases a form of oxygen, known as an oxygen radical, which kills abnormal cells.
But before this effect can be exploited in humans, they needed to determine whether it is safe and effective in a live animal model.
They rubbed the dye solution into the abdomen, head, and legs of mice. Once the dye had completely diffused into the skin, it took on an orange colour and became transparent.
This allowed them to look at the blood vessels of the scalp, the movement of organs laying under the skin of the abdomen, and tiny contractile units of muscle (sarcomeres) at work in the leg.
Importantly, the tartrazine did not appear to have long-term effects, and any excess dye was excreted in waste within 48 hours.
Conventional methods to turn tissues more transparent, such as the use of glycerol, almost always require high concentrations that can cause side effects like dehydration, swelling, and structural changes to the sample.
Tartrazine requires much lower concentrations, which are within its physiologically tolerable limit, and is fully reversible by washing it away with water.
“Our research group is mostly academics, so one of the first things we thought of when we saw the results of our experiments was how this might improve biomedical research,” says lead author of the study and assistant professor of physics at the University of Texas, Zihao Ou.
“Optical equipment, like the microscope, is not directly used to study live humans or animals because light can’t go through living tissue. But now that we can make tissue transparent, it will allow us to look at more detailed dynamics.”
Hong says human skin is significantly thicker than mouse skin, with the stratum corneum, the outermost layer of the epidermis, serving as a substantial barrier that prevents effective delivery of molecules into the dermis.
“A safe method for percutaneous delivery of light-absorbing molecules, following comprehensive evaluation of its potential effects on human skin, may lead to its clinical application in the future,” he says.
