Progress in science is often linked to better ways of seeing: Stronger telescopes bring more stars into view, microscopes made bacteria vivid, new genomic techniques tease out once-hidden forms of life.
Now a group of MIT engineers has created a new microscope that can generate close to real-time images of processes at nearly the atomic level. For human observers, microscopic worlds that had appeared static suddenly leap into motion.
“Imagine when the microscope was invented, you could only take snapshots of what’s happening,” says Iman Bozchalooi, a postdoctoral associate and lead engineer of the microscope. “In that case, you couldn’t see that bacteria could swim or how or why they do it.” Just as video allowed scientists to see bacteria in motion, this new microscope will give them a similarly dynamic perspective on chemical and biological processes that up until now have been only glimpsed.
The device Bozchalooi and his collaborators, including mechanical engineer Kamal Youcef-Toumi, created is a version of an atomic force microscope, or AFM. Unlike optical microscopes, which resolve samples using wavelengths of light, or electron microscopes, which depict objects using beams of electrons, AFMs have a kind of mechanical vision. They work by running a highly sensitive stylus over the surface of a material, creating an image from the revealed topography.
“It literally touches the surface like a blind person trying to read Braille. And by touching the surface, it tries to figure out what’s happening,” says Bozchalooi.
AFMs were invented in the 1980s by engineers at IBM, and they allow scientists to see objects down to Angstrom level, a dimension approximately one-1,000,000th the width of a human hair. They are a big advance over other kinds of microscopes but also carry their own limitations, namely that they work slowly and can only produce static snapshots of the underlying phenomena.
“Right now, it’s old-fashioned photography, you take a picture, then take another five minutes later, and assume you can go from one picture to the other,” says Mark Grinstaff, a bioengineer at Boston University who uses AFMs in his research. “But maybe lots of things happen in between.”
Previous efforts to increase the imaging speed of AFMs have tended to carry a cost — they increase speed, but also restrict scientists to observing very small areas of a sample.
“Some people have increased the speed but ended up with a small range,” says Youcef-Toumi. “Slow speed, of course, constrains applications and limits them to studying static things.”
The MIT team figured out how to get both — rapid imaging speed and the ability to observe a large area. Their machine, which exists at the moment as a single prototype, allows scientists to look at samples 130 microns on a side, relatively vast by the standards of AFMs. At the same time, it can create 8 to 10 frames per second, which is inching toward real-time video (30 frames per second). They achieve this through a number of techniques, most especially the way they engineer the actuators, which move the sample beneath the AFM’s stylus. Bozchalooi explains the approach with a metaphor involving cranes: The microscope is equipped with a “large crane,” which moves the sample slowly over long distances, and a small crane, which is carried by the large crane, and can be unloaded locally when it’s time to start taking high-speed images.
“We combined these two together and tried to sort of synchronize them in a way that from the perspective of scientists using the microscope, it’s as if we have both high-speed and large-range capability at the same time,” he says.
So far, the group has put together a few videos that demonstrate the possibilities of near real-time imaging on such a microscopic scale. One shows what happens at the molecular level when acid erodes the surface of a sample of the mineral calcite, either etching away the calcite layer by layer or eroding it by forming sub-nanometer pits. Another depicts the chemical process that occurs when copper is deposited on gold. On one level, it’s a well-understood reaction. On another, up close and in near real-time, it was surprising.
“We saw a certain arrangement we couldn’t explain,” Bozchalooi says. “We spoke with materials scientists, and they had no clue why this was happening because all of this is so new.”
Bozchalooi and his collaborators hope to make the microscope easier to use and eventually to commercialize it. They anticipate it would be immediately useful in the biological and materials sciences among other fields. Grinstaff imagines, for one, that this kind of microscope could be used to observe and study how material from the body — platelets, other types of cells, and proteins — adhere to metals, for example a metal stent used for unblocking arteries.
All of that and more may be possible, but when Youcef-Toumi considers the microscope’s potential, he imagines something even more fundamental as well. He recalls a class on fluid mechanics he took long ago, in which students where shown a video depicting how liquid behaves when moving through a pipe, flowing around the cylinder and creating vortices. Years later, the image is still fixed in his head.
“As soon as you see that, it sticks in your mind, you see it clearly and never forget it,” Youcef-Toumi says. “Someone can try to explain what you’d see if water were going around a cylinder, but no matter how they explain it, it’s not the same as if you can see it.”
Now more phenomena, on a much smaller scale, have the potential to be viewed just as vividly.
Kevin Hartnett is a writer in South Carolina. He can be reached at firstname.lastname@example.org.
Clarification: This article has been updated to clarify statements about the development of optical microscopes.