Mice turned see-through by a dye that lets you watch their organs

Massaging a common food dye onto the skin of living mice turned their tissues transparent, allowing us to see their blood vessels and organs at work. The technique could one day help doctors look deeper into our bodies to diagnose conditions.

Monitoring the internal environment of a living animal isn’t easy. When it is dead, we can take slices of its tissues or use chemicals to remove proteins and fats from them to get a better view. With live animals, some things can be viewed via scans and endoscopies, but to monitor living tissue, it often has to be cut out.

Now, Zihao Ou at the University of Texas at Dallas and his colleagues have turned tissues transparent in living mice by rubbing the food dye tartrazine, also known as E102 or Yellow 5, onto their skin. When the skin absorbs the dye molecules, this modifies the tissue’s refractive index – the speed at which light travels through it.

The mice then became transparent, which enabled the researchers to see peristalsis, the muscle contractions that move food through the digestive tract, and to look into the blood vessels on the surface of their brains.

To understand how the technique works, think about fizzy water, says Ou. Light shining through the fluid changes direction every time it goes from water to a gas bubble or vice versa, he says. This means light scatters in all directions and can’t penetrate the fluid as easily as it can in just air or water that isn’t fizzy. Biological tissue behaves similarly because it contains a lot of water, but also other molecules like lipids and proteins, which usually have a higher refractive index than the water.

Adding the dye changes the refractive index of the water inside tissues to more closely match that of the lipids and other molecules, reducing how much the light scatters. “That means you can see deeper, you can probe deeper,” says Ou.

The dye can be washed off and didn’t seem to harm the mice.

The work strikes at the heart of one of the biggest problems in microscopy, says Christopher Rowlands at Imperial College London. “If you wanted to see anything more than a millimetre or so from the surface of the tissue, forget it, that wasn’t happening – and now suddenly that’s a possibility,” he says. “You’re seeing through a centimetre, whereas you could previously see a millimetre. That centimetre makes a difference for a lot of applications.”

Tartrazine could potentially be toxic if a lot of it is put on skin, says Rowlands, but neurobiologists routinely stick probes and lenses into the brain or remove chunks of the cortex. Using a dye on skin that is widely accepted as safe for consumption would probably still be less harmful, he says.

But although the technique makes skin more transparent, it won’t give doctors a totally clear of view of a person’s insides. “It’s not going to be Harry Potter’s invisibility cloak,” says Rowlands. “It’ll be a thing where it looks like the skin is more glassy than it should be.” Even if the effect happened throughout the body, you would still be seeing bones and specialised structures called organelles inside cells, he says.

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