Saturday, September 07, 2024

WAIT, WHAT?!

Common food dye turns live mice transparent

By Michael Franco
September 05, 2024


The dye that gives foods, drugs, and cosmetics a lemon yellow color can also make mice transparent, as illustrated in this generative image

In an effort to enhance the research abilities of biologists, Stanford University researchers have discovered that applying a popular food coloring to the skin of mice allowed them to see through to the rodents' internal organs and other structures.

While scientists have ways to peer deeply into the tissues and bodies of humans and other animals, most of those techniques can only be carried out through biopsy procedures or after the subject being studied is dead. Being able to look inside a creature that is alive offers scientists another tool to analyze biological functions and advance their research. It can also be a more humane way to carry out research that doesn't involve the pain or death of animal subjects.

One of the issues with trying to look through the skin of a living animal is that the protein and fat-based components of its skin are very good at scattering light. This effectively makes their skin opaque. However, the Stamford researchers discovered that the application of tartrazine, a food dye more popularly known as FD&C Yellow 5, tamed this scattering effect. Specifically, the dye was found to absorb light in the near ultraviolet and blue part of the spectrum, which allowed red and orange light to penetrate deeper into the tissue of mice. This basically turned their skin transparent, an effect that easily reversed once the dye was washed away.

The researchers applied the dye to the abdomen of mice and were able to watch neurons that they had tagged with fluorescent markers working in real time to reveal the gut motility in the rodents. Such a technique could help gain better insights into digestive issues such as IBS. The team also applied the dye to skulls of the mice, which allowed them to see the workings of cerebral blood vessels, and to the hindlimbs of the rodents, which made the operation of their musculature visible.

"Our approach … presents opportunities for visualizing the structure, activity, and functions of deep-seated tissues and organs without the need for surgical removal or the replacement of overlying tissues with transparent windows," write the researchers about their findings.

The discovery may also expand the types of animals that scientists use to conduct research. Writing about the study in the journal Science, Christopher J. Rowlands and Jon Gorecki – two researchers not involved in the study – point out that zebrafish and nematodes are often selected for studies because they already have transparent skin that allows researchers to view their internal processes. However, with the new dye-based procedures, nearly any animal can become temporarily transparent to give researchers a peek inside.

Rowlands and Gorecki also point out the significance of the finding.

"On the basis of (these) results," they write, "it is reasonable to expect 10-fold imaging-depth improvement given adequate dye penetration. With this, feats such as multiphoton imaging across a whole mouse brain or locating tumors around blood vessels beneath centimeter-thick tissues with optical coherence tomography catheters may become possible."

The study has been published in the journal Science.

Source: American Association for the Advancement of Science via EurekAlert


Live Mouse Turned Temporarily Transparent Thanks To Yellow Food Dye And Clever Physics

“If you aren’t familiar with it, it looks like a magic trick.”

Laura Simmons
Editor and Staff Writer
EditedbyMaddy Chapman


As the tartrazine dye is applied, the blood vessels in the mouse's brain become visible through the skin!
Image credit: Stanford University/Gail Rupert/USNSF

We at IFLScience are lucky enough to explore the weird, the wacky, the downright out of this world – sometimes literally! – every single day. And yet sometimes, a study hits our desks that leaves us with little to say but… “Wow!” That was pretty much our reaction when we learned that scientists had used food dye to turn a living mouse temporarily transparent

Making an “invisible mouse” might not sound like a pressing scientific priority at first glance – surely there’s cancer to be cured and pandemics to prevent? But the benefits of making skin transparent to visible light quickly become clearer when you consider that without that, the only way to look inside the body is with scans, even the best of which can only achieve a limited view, or surgery.

“Looking forward, this technology could make veins more visible for the drawing of blood, make laser-based tattoo removal more straightforward, or assist in the early detection and treatment of cancers,” said Dr Guosong Hong, a Stanford University assistant professor who helped lead the project, in a statement.

So, how did they do it? Surprisingly, the team used an ingredient you might even have lurking in a kitchen cupboard: the yellow food dye tartrazine. Combining this with a hypothesis born out of studying old optics textbooks, they thought of a way of applying well-known physics concepts to entirely new biomedical applications.

“We combined the yellow dye, which is a molecule that absorbs most light, especially blue and ultraviolet light, with skin, which is a scattering medium,” first author Dr Zihao Ou explained in another statement. “Individually, these two things block most light from getting through them. But when we put them together, we were able to achieve transparency of the mouse skin.”

Ou added, “For those who understand the fundamental physics behind this, it makes sense; but if you aren’t familiar with it, it looks like a magic trick.”

The magic, or physics – however you choose to look at it – lies in how dissolving the tartrazine in water alters its refractive index in such a way that it happens to match the refractive index of the lipid molecules in bodily tissues. As the tartrazine solution is rubbed into the skin, the light scatter within the tissue is gradually reduced, like the mist disappearing from your windscreen on a cold morning.

As this example using raw chicken meat shows, the text sitting behind the tissue gradually becomes more visible as the transparency increases.

Photographs illustrating the difference in the transparency of chicken breast tissue after soaking in tartrazine solutions with an increasing concentration. Scale bars: 1 cm.
Image credit: Guosong Hong/Stanford University


Doing this on a slab of meat is one thing – what about a living mouse? The team applied the tartrazine to the skulls and abdomens of mice, and waited a few minutes for the dye to fully diffuse into the skin. Then, they were able to visualize the blood vessels of the brain and the workings of the digestive system through the skin – no scalpels or scanners required.


Time-lapse images of blood vessels in the brain just beneath the skull of a sedated mouse, revealed without any surgery, incisions, or damage to the mouse’s bone or skin.
Image credit: Stanford University/Gail Rupert/NSF

Any excess dye can simply be washed off, while the dye that has been absorbed is harmlessly processed and excreted in urine within about 48 hours.

“It’s important that the dye is biocompatible – it’s safe for living organisms. In addition, it’s very inexpensive and efficient; we don’t need very much of it to work,” Ou said.

But please don’t take this as license to go rummaging in your kitchen and rubbing food dye on your skin. This hasn’t been tested in humans yet, and our skin is about 10 times thicker than a mouse’s, so some more experimentation is going to be needed to figure out how to make it work. But if the team can do it, the possibilities are exciting.

“Many medical diagnosis platforms are very expensive and inaccessible to a broad audience, but platforms based on our tech should not be,” Ou said, adding that using this method to open up the body to exploration with a light microscope could “completely revolutionize existing optical research in biology.”

Who would have thought adding yellow dye to skin could make it see-through? We know, we know – it’s physics. But we’re going to choose to call it magic for just a little bit longer.

The study is published in the journal Science.



Scientists make tissue of living animals see-through

Date:September 5, 2024

Source: University of Texas at Dallas

Summary:

In a pioneering new study, researchers made the skin on the skulls and abdomens of live mice transparent by applying to the areas a mixture of water and a common yellow food coloring called tartrazine.


FULL STORY

In a pioneering new study, researchers made the skin on the skulls and abdomens of live mice transparent by applying to the areas a mixture of water and a common yellow food coloring called tartrazine.

Dr. Zihao Ou, assistant professor of physics at The University of Texas at Dallas, is lead author of the study, published in the Sept. 6 print issue of the journal Science.

Living skin is a scattering medium. Like fog, it scatters light, which is why it cannot be seen through.

"We combined the yellow dye, which is a molecule that absorbs most light, especially blue and ultraviolet light, with skin, which is a scattering medium. Individually, these two things block most light from getting through them. But when we put them together, we were able to achieve transparency of the mouse skin," said Ou, who, with colleagues, conducted the study while he was a postdoctoral researcher at Stanford University before joining the UT Dallas faculty in the School of Natural Sciences and Mathematics in August.

"For those who understand the fundamental physics behind this, it makes sense; but if you aren't familiar with it, it looks like a magic trick," Ou said.

The "magic" happens because dissolving the light-absorbing molecules in water changes the solution's refractive index -- a measure of the way a substance bends light -- in a way that matches the refractive index of tissue components like lipids. In essence, the dye molecules reduce the degree to which light scatters in the skin tissue, like dissipating a fog bank.

In their experiments with mice, the researchers rubbed the water and dye solution onto the skin of the animals' skulls and abdomens. Once the dye had completely diffused into the skin, the skin became transparent. The process is reversible by washing off any remaining dye. The dye that has diffused into the skin is metabolized and excreted through urine.

"It takes a few minutes for the transparency to appear," Ou said. "It's similar to the way a facial cream or mask works: The time needed depends on how fast the molecules diffuse into the skin."

Through the transparent skin of the skull, researchers directly observed blood vessels on the surface of the brain. In the abdomen, they observed internal organs and peristalsis, the muscle contractions that move contents through the digestive tract.

The transparent areas take on an orangish color, Ou said. The dye used in the solution is commonly known as FD&C Yellow #5 and is frequently used in orange- or yellow-colored snack chips, candy coating and other foods. The Food and Drug Administration certifies nine color additives -- tartrazine is one -- for use in foods.

"It's important that the dye is biocompatible -- it's safe for living organisms," Ou said. "In addition, it's very inexpensive and efficient; we don't need very much of it to work."

The researchers have not yet tested the process on humans, whose skin is about 10 times thicker than a mouse's. At this time it is not clear what dosage of the dye or delivery method would be necessary to penetrate the entire thickness, Ou said.

"In human medicine, we currently have ultrasound to look deeper inside the living body," Ou said. "Many medical diagnosis platforms are very expensive and inaccessible to a broad audience, but platforms based on our tech should not be."

Ou said one of the first applications of the technique will likely be to improve existing research methods in optical imaging.

"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," he said. "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. It will completely revolutionize existing optical research in biology."

In his new Dynamic Bio-imaging Lab at UTD, Ou will continue the research he started with Dr. Guosong Hong, assistant professor of materials science and engineering at Stanford and a corresponding author of the study. Ou said the next steps in the research will include understanding what dosage of the dye molecule might work best in human tissue. In addition, the researchers are experimenting with other molecules, including engineered materials, that could perform more efficiently than tartrazine.

Study authors from Stanford, including co-corresponding author Dr. Mark Brongersma, the Stephen Harris Professor in the Department of Materials Science and Engineering, were funded by grants from federal agencies including the National Institutes of Health, the National Science Foundation and the Air Force Office of Scientific Research. As an interdisciplinary postdoctoral scholar, Ou was supported by the Wu Tsai Neuroscience Institute at Stanford. The researchers have applied for a patent on the technology.

Story Source:

Materials provided by University of Texas at Dallas. Original written by Amanda Siegfried. Note: Content may be edited for style and length.

Related Multimedia:Scientists made skin of live mice transparent by applying a mixture of water and a common yellow food coloring called tartrazine

Journal Reference:Zihao Ou, Yi-Shiou Duh, Nicholas J. Rommelfanger, Carl H. C. Keck, Shan Jiang, Kenneth Brinson, Su Zhao, Elizabeth L. Schmidt, Xiang Wu, Fan Yang, Betty Cai, Han Cui, Wei Qi, Shifu Wu, Adarsh Tantry, Richard Roth, Jun Ding, Xiaoke Chen, Julia A. Kaltschmidt, Mark L. Brongersma, Guosong Hong. Achieving optical transparency in live animals with absorbing molecules. Science, 2024; 385 (6713) DOI: 10.1126/science.adm6869

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University of Texas at Dallas. "Scientists make tissue of living animals see-through." ScienceDaily. ScienceDaily, 5 September 2024. <www.sciencedaily.com/releases/2024/09/240905143615.htm>.


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