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Scientists invent a new kind of nanoscale imaging for living cells

Biology is messy, and this is a problem for imaging science. Living things are squishy and porous. They tend to be bathed in fluid. They also move, and all that motion makes it practically impossible to get good high-resolution images of cells and what’s inside them.

The best we’ve had to date has been electron microscopy, which can take images with stunning detail — once whatever’s being imaged has been fixed stiff with formaldehyde or smushed up against a glass plate to get a crisp focal plane. That’s fine, if you only want to image dead stuff. Worse, fixation permanently changes the physical properties of the sample, so microscopy can’t be used to accurately determine characteristics of tissue on the nanoscale.

To get around this, a team of scientists from the University of Texas at Austin have put their heads together and demonstrated a whole different way of imaging cells, called “thermal noise imaging.” It’s easiest to explain by analogy: Imagine you needed to take a three-dimensional image of a room in total darkness. If you were to throw a glowing rubber ball into the room and use a camera to collect a series of high-speed snapshots of the ball as it bounces around, you would see that as the ball moves around the room, it doesn’t move through solid objects such as tables and chairs. Combining millions of images taken so fast that they have “negligible motion blur,” you could build yourself a picture by mapping both positive space (wherever the ball couldn’t go) and negative space (where it could go).

So in a way, it’s like looking for a black cat in a dark room… by throwing a dozen glow-in-the-dark rubber balls. No, we are not throwing the glow-in-the-dark rubber balls at the cat. Yes, it is safe to assume a spherical cat. What is it with you physicists and your cats?

With thermal noise imaging, the equivalent of the glowing rubber ball is a nanosphere that moves around in a sample by natural Brownian motion. The nanospheres don’t light up, necessarily — but like ball bearings, they reflect back whatever light hits them, and the reflection makes a tiny specular highlight. Pin-pricks of light like this are easy to find, and because they’re so tiny and so numerous, they do a great job of literally bouncing off the walls. The UT researchers used their new technique to make images of a single, 25nm collagen microfibril like the ones that make up our cells’ internal cytoskeletons.

No longer daunted by needing a new microscopy technique, the researchers intend to forge ahead with their work on collagen — they’re moving toward creating better artificial skin. “This chaotic [Brownian] wiggling is a nuisance for most microscopy techniques because it makes everything blurry,” says Florin. “We’ve turned it to our advantage. We don’t need to build a complicated mechanism to move our probe around. We sit back and let nature do it for us.”

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