After applying it, the skin becomes transparent, and the blood vessels and muscles are clearly visible...

Produced by: Science Popularization China

Author: Guo Fei (Yantai University)

Producer: China Science Expo

Editor's note: In order to understand the latest developments in cutting-edge science and technology, the China Science Popularization Frontier Science Project has launched a series of articles titled "Understanding Top Science Journals", which selects outstanding papers from authoritative journals and interprets them in plain language as soon as possible. Let us broaden our scientific horizons and enjoy the fun of science through the window of top journals.

Not long ago, in a laboratory at Stanford University, scientists carefully applied a yellowish solution to the skin of experimental mice. After just a few minutes, an incredible scene occurred - the skin of the mice gradually became transparent, and the beating heart and moving intestines in the body were clearly visible. Even more amazing is that when they washed off the solution with water, the skin returned to its original state.

This groundbreaking discovery was published in the top academic journal Science on September 6, 2024, and immediately caused a sensation in the global scientific community. This discovery can't help but remind people of HG Wells' 1897 science fiction novel "The Invisible Man", and more importantly, it has opened up a whole new field for life science research.

The interaction between light and skin can make it "transparent"

(Image source: Reference 1)

Extraordinary discoveries in ordinary matter

This magical substance that can make biological tissues transparent is actually a food coloring that can be found everywhere in our daily lives - lemon yellow. This food additive brings bright colors to many foods, beverages, and even cosmetics and daily necessities. Who would have thought that this ordinary pigment molecule could hide such an extraordinary secret?

The scientists' first experimental subject was ordinary chicken breast. When they dripped lemon yellow solutions of different concentrations onto thin slices of chicken breast, a wonderful change began to occur: as the solution penetrated, the originally opaque slices of meat gradually became transparent, and the writing underneath was clearly visible. The initial success of the experiment gave the research team great confidence and laid the foundation for subsequent in vivo experiments.

Thinly sliced ​​chicken treated with dye

(Image source: Reference 1)

The following in vivo experiments were even more exciting. When the lemon yellow solution was applied to the head of mice, the crisscrossing blood vessel network on the surface of the brain was clearly visible, and scientists could directly observe the flow of blood in the blood vessels; when applied to the abdomen, the peristalsis of the internal organs was clearly visible, and even the contraction of the intestines could be seen; when applied to the limbs, even the fine structure of muscle fibers could be observed. This unprecedented way of observation gave scientists a pair of perspective eyes.

The abdominal skin of mice becomes transparent after solution treatment

(Image source: Reference 1)

The most surprising thing is that this transparency effect is completely reversible. After washing away the dye with water, the tissue will return to its original state in a short time. The study also found that the dye remaining in the tissue will be naturally excreted from the body through metabolism within 48 hours, which means that this technology has extremely high biosafety. This controllability and safety are unmatched by any previous tissue transparency technology.

Why does a tiny drop of lemon yellow have such magical power?

Why is the skin opaque? It all starts with the behavior of light. Our skin tissue is filled with different components, such as water, fat, and protein, which are like countless tiny lenses inlaid together, and each component refracts light to a different degree. When light tries to pass through the skin, it refracts and scatters at the junction of these different "lenses", ultimately making the skin appear opaque.

The magic of this new technology comes from the Kramers-Kronig relationship, a physical law discovered a hundred years ago: if a substance exhibits strong absorption at a certain wavelength of light, it can affect the refraction behavior of light of other wavelengths.

Scientists have discovered that lemon yellow molecules strongly absorb blue light and have the ability to adjust the refractive index of aqueous solutions. When lemon yellow dissolves in the water of tissues, it can cleverly adjust the refractive index of water to match the refractive index of surrounding fat and protein.

In this way, light can pass through the tissue unimpeded, just like passing through a piece of glass. This ingenious mechanism derived from physics has finally found revolutionary applications in the field of life sciences a hundred years later.

Schematic diagram of the principle of mouse skin becoming transparent

(Image source: Reference 1)

Groundbreaking technological breakthrough

The reason why this discovery is so important is that it completely changes the way we observe life. Before this, scientists who wanted to observe the inside of an organism either needed to perform surgery to cut open the tissue or rely on expensive medical equipment such as X-rays and MRIs. Even existing tissue clearing techniques often require the use of high concentrations of chemical reagents such as glycerol, sugars, or acidic solutions. These methods either cause cell dehydration and inflammation, or can only be used for dead samples, making it impossible to observe dynamic processes in living bodies.

This new technology based on lemon yellow is like a magic window for life. It is not only safe and reversible, but also simple to operate and low-cost. Most importantly, it allows us to directly observe the dynamic changes inside living organisms without affecting life activities. It is like we could only understand life through snapshots in the past, but now we can watch a vivid documentary. This technology does not require complex equipment, but only an ordinary food dye, which allows us to see life phenomena that were previously difficult to observe.

Unlimited possibilities for the future

The discovery of this technology is like opening a door to the future. In the field of basic research, it will help scientists better understand various processes in the body. For example, researchers can directly observe the activity of neurons to understand how the brain processes information; they can observe the formation and growth of blood vessels to study the metastasis mechanism of cancer; they can even track the movement of immune cells to reveal how the immune system fights disease.

If this new technology is proven to be effective in humans, it may also show similar effects in human hands.

(Image credit: Keyi 'Onyx' Li/US National Science Foundation)

In terms of medical applications, the technology has even more exciting prospects. It may help doctors perform intravenous injections more accurately because the location of blood vessels will be clearly visible; it may improve the precision of minimally invasive surgery because doctors will be able to directly see deep tissues; and it may even provide new methods for early diagnosis and treatment of cancer because it makes it easier for us to detect abnormal tissue changes.

In the field of drug development , this technology may also bring revolutionary changes. Researchers can directly observe the distribution and effects of drugs in living bodies and understand how drugs affect various organs, which will greatly speed up the development of new drugs. In addition, this technology may also be used in the field of bioengineering to help scientists develop better tissue engineering products.

The future is bright but the road may still be long

Of course, there are many challenges to overcome before this technology can be applied to humans. Human skin is much thicker than that of mice, about ten times thicker, which means that more effective dye penetration methods need to be studied. At the same time, although tartrazine has been proven to be safe as a food additive, its safety when used for skin transparency requires more research. In addition, the transparency effect of hard tissues such as bones and whether the transparency of deeper tissues can be achieved still need further exploration.

Just as the laws of physics from a century ago have found new applications today, the magic of science often manifests itself in unexpected places. In a sense, this technology realizes a dream in science fiction. Perhaps in the near future, doctors will be able to better understand and treat various diseases through this "window of life", and scientists will also be able to reveal more mysteries of life.

References:

1.ZIHAO OU et. al., Achieving optical transparency in live animals with absorbing molecules