Sniffing out cancer.
Hossam Haick, a senior lecturer in chemical engineering, has created an electronic “nose” that can diagnose cancer in just two or three minutes by analyzing a patient’s breath.
When a cancerous tumor develops in the body, its cells produce various chemicals that appear in the urine and blood. These biomarkers cross from the blood into the lungs, where they are exhaled in minuscule amounts. Haick’s device detects cancer by “sniffing out” those telltale molecules; the current version can even distinguish between lung, breast, and colon cancer. He has begun testing the nose in collaboration with the oncology division of the Rambam Medical Center in Haifa. The finished device should be portable and inexpensive, providing a faster, easier, and more sensitive way to screen for tumors. Such screening should help doctors detect cancer early, when it’s most treatable. Haick hopes the nose will eventually be as small as a cell phone and sophisticated enough to pinpoint a tumor’s location.
Superlenses for watching cells.
The resolution of the best conventional light microscopes–which, unlike higher-resolution electron microscopes, can magnify living cells–is about 400 nanometers. That’s good enough to let biologists tell cells apart, but it’s not good enough to let them observe the workings of organelles within the cell, such as metabolizing mitochondria, which are about 200 nanometers across. Nicholas Fang hopes that within the next few years, his technology will enable biologists to watch living cells at a resolution as fine as 15 nanometers (about the size of a protein molecule), revealing not only cell organelles but their molecular workings (see “Life Left in Light,” September/October 2008).
Objects smaller than the wavelength of the light being shined onto them–several hundred nanometers, in the case of visible light–scatter the light as so-called evanescent waves. These waves move in such a way that they can’t be collected and redirected by conventional lenses. But in 2005 Fang developed the first optical superlens–a device that can collect evanescent waves to soup up the performance of a light microscope.
At a small workbench in his lab, Fang stamps out nanoscale silver gratings that make it possible to convert conventional light-microscope parts into superlenses. To pattern his metal structures onto fragile glass slides and other microscope parts, he starts by coating a coverslip with a thin film of silver. Separately, he carves a pattern–the inverse of the final, desired one–into a reusable stamp. He places the stamp over the coverslip and applies an electrical voltage, causing a reaction in which the silver dissolves and is pulled into the crevices of the stamp. Once the stamp is removed, the silver coating of the coverslip is left with the grating pattern.
Using this method, Fang creates intricate nanoscale patterns in about five minutes. The stamping doesn’t break the delicate devices and doesn’t need to be done in a clean room. And Fang says the process should be amenable to mass production of superlenses that could turn every biologist’s microscope into a nanoscope.
Revealing how materials behave at the nanoscale.
Julia Greer has reinvented nanomechanics–the field that studies the mechanical properties, such as elasticity and strength, of materials at extremely small scales. These materials behave very differently from those at larger scales, and understanding the differences is essential for building reliable and durable ultrasmall devices.
Scientists have typically measured the mechanical properties of nanoscale materials by using a scanning electron microscope to capture images of an extremely sharp tip poking the surface of a thin film of the material. Greer, an assistant professor of materials science, greatly simplified and improved the process by introducing a technique that tests a nano pillar of the target material, compressing it and pulling on it in a single dimension instead of deforming an entire sheet.
Greer has used the method to confirm that metals and metal alloys are stronger at the nanoscale than at larger scales, something that researchers hadn’t been able to prove before. The findings are providing engineers with the information they need to build nanoscale devices.
Gecko-inspired surgical tape.
Bioengineer Jeffrey Karp may finally have found a noninvasive alternative to the sutures and staples that have long been a mainstay of surgery and emergency medicine. Using a biodegradable elastic polymer, Karp and his colleagues have created a surgical tape that is covered with nanoscale pillars akin to the gripping structures on geckos’ feet. Coated with a sugar-based glue, the tape securely closes a surgical incision and then degrades completely over time.
Karp can adapt the polymer to suit different applications: a patch for the heart, for example, would need to be more stretchable than one for the liver, while one to close cuts on the skin would need a different pattern of pillars. The polymer can also release drugs to help tissue heal. More than two dozen companies are interested in licensing the tape, which has shown promise in early animal tests. If all goes well, gecko tape could enter clinical trials within five years.
In 2004, Manchester University fellow Kostya Novoselov discovered graphene, a fundamentally new molecule that may revolutionize computing. Physicists had previously speculated about the material, theorizing that it could be made into transistors more than a hundred times as fast as today’s silicon devices. But until Novoselov found and tested it, some thought the essentially two-dimensional material would be unstable.
To make graphene, which is a mesh of carbon one atom thick, Novoselov shaves small flakes of graphite, similar to that found in pencils, onto adhesive tape. He then folds the tape over and pulls it apart, splitting the graphite into two thinner flakes. He repeats the process until he has a one-atom-thick sheet.
Since the discovery, Novoselov has made a fast, low-power graphene transistor using techniques from the semiconductor industry. Because they conduct electrons so rapidly, such transistors could lead to faster computers and to specialized communications and imaging technologies such as terahertz-wave imaging, which could be used for medical tests or security applications. A slew of academic and corporate labs have begun working on graphene, but Novoselov and other scientists are still researching practical techniques for making large sheets of it. For now, Novoselov’s pencil-and-tape method is standard.
Ultrasensitive detectors to sniff out explosives.
The detonation of a single pound of explosives hidden aboard an airliner flying over Lockerbie, Scotland, in 1988 was, for many, a turning point in understanding how vulnerable the public is to the actions of terrorists. The bombing of Pan Am Flight 103 and the deaths of its 259 passengers (and 11 people on the ground in Lockerbie) set off a behind-the-scenes, government-funded race to find better ways to detect explosives. That race acquired additional urgency after the September 11 attacks, and it became frantic when IEDs–improvised explosive devices–started killing U.S. soldiers in Afghanistan and Iraq. Now, 20 years after the Lockerbie bombing, Aimée Rose is playing a key role in creating and commercializing ultrasensitive detectors that help to protect us against explosives.
Largely because of Rose’s work as a scientist, engineer, and research manager, new types of portable chemical “sniffers” are now widely used to detect trace amounts of explosives in the air. These sensitive instruments are already detecting land mines, IEDs, liquid explosives in sealed containers, and even people who have been in contact with explosives. “You can pull aside as many passengers in security lines as you want, but if you don’t have the ability to detect explosives on them, it won’t do much good,” says Susan Martonosi, an operations researcher at Harvey Mudd College in Claremont, CA, who studies homeland security. “That has long been a weakness in the system.”
Rose’s chemical sniffers are part of a growing effort to develop explosives detectors that go beyond x-ray scanners, the large instruments commonly found in airports. Whereas x-ray scanners look for the characteristic shapes of bombs and can easily be fooled by tricks such as embedding explosives in electronic devices, the new kinds of detectors find explosives by picking out their distinctive chemical composition. But it’s a complex problem, because those chemical signatures are diverse and often extremely faint. (Trained dogs that sniff out the vapor given off by explosives are still the most reliable and sensitive bomb detectors, but they’re in short supply.) Airports have largely relied on ion-mobility spectrometers that examine the chemicals in either swabs from luggage or puffs of air blown at passengers in sealed chambers. Swabs can easily miss a well-hidden explosive, though, and analyses of air samples are frequently thrown off by dirt, dust, and other contaminants. Rose’s technology, on the other hand, is the first explosives detector that matches the sensitivity of dogs. What’s more, it’s handheld and easy to use, and it’s the only device capable of detecting the hidden liquid explosives that have become a serious security concern in the past few years.
Rose was in college when she first tackled the problem of detecting chemicals and toxic materials. “I wanted an opportunity to put something in people’s hands that could affect their lives and maybe make them safer,” she says. She was planning to do her graduate work in materials science at Harvard, until she was awakened at six one morning by a phone call from a stranger who spoke in long, enthusiastic rushes. “It was as if he couldn’t get the words out fast enough,” she recalls. “I was half asleep and very irritated.” After a few minutes she was able to make out that the man was a chemistry professor who had just set up shop at MIT, complete with a new grant from the U.S. Defense Advanced Research Projects Agency to develop a chemical sensor capable of detecting land mines. He had seen her application to MIT, an application that everyone else in the department had ignored; would she consider visiting?
She did visit–after all, she was going be in town anyway–and it didn’t take long for the professor, Timothy Swager, to persuade her to sign on as a graduate student in his lab. For one thing, land-mine detection seemed like exactly the sort of project she had been looking for. “The poorest countries in the world are littered with land mines, and that hurts some of the most needy people on the planet,” she says. “It’s a very motivating cause.”
When Rose joined Swager’s lab, he was synthesizing polymers that fluoresce when exposed to certain wavelengths of light. If a certain type of smaller molecule–say, one found in an explosive such as TNT–binds with one of these polymer chains at any location, the whole polymer stops glowing. The sudden loss of fluorescence is measurable even if just a single target molecule has bound to the chain, so the polymer can serve as the heart of an extremely sensitive detector. “The polymer acts like a string of Christmas tree lights, where if you knock one out, the whole string shuts down,” Rose explains. “The fact that you have a much larger molecule responding means you get a much larger signal, which means you have much greater sensitivities.” Tweaking the composition of a polymer could enable it to detect different sorts of molecules. For Swager, Rose, and the rest of the team, the goal was to get the polymers to detect the tiny amount of vaporized explosive drifting in the air immediately above a buried land mine.
Swager, now the head of the chemistry department at MIT, says Rose’s contributions were critical to the team’s success in using the polymers in ultrasensitive detectors. First, he says, Rose added to the researchers’ theoretical understanding of how the polymers respond to light. Then she figured out how to employ that insight to develop polymers that fluoresce more brightly and are thus more easily monitored in a working device.
Still, progress with the polymers came slowly. “We were trying to take what a chemist does with a lot of equipment and boiling beakers on a bench, and make it so it could be embedded in a handheld device that’s small, robust, and sensitive,” says Rose. But in 1999 the lab successfully tested early prototypes in mock land-mine fields. The potential applications would soon expand greatly in number and urgency. “I had been thinking only about making a contribution to land-mine safety, not the safety of U.S. soldiers and everyone who travels by plane,” Rose says. “We weren’t expecting September 11; we weren’t expecting Afghanistan or Iraq; we weren’t expecting terrorists to carry liquid explosives in bottles on planes.”
While still a graduate student at MIT, Rose had begun to collaborate with researchers at a startup called Nomadics, which had licensed the polymer technology and had government funding to develop explosives detectors for the U.S. military. Rose completed her PhD in 2003, and in 2004, she joined Nomadics as a research scientist, helping to commercialize the technology. (ICx Technologies acquired Nomadics in 2005.) After years working on basic scientific questions, she now faced an entirely new challenge: how to use the promising advances in chemistry to make a practical working device. The polymer worked well enough in liquid in a test tube, but for use in an actual detector, it would have to be deposited as a thin film and still fluoresce brightly enough for any interruption in light output to be reliably detected.
The first product to result from the efforts of Rose and her colleagues was a handheld military explosives detector called Fido XT. Unlike conventional detectors, Fido XT can detect a few trillionths of a gram of explosive in the air; it rarely gives out a false positive signal; and it resets almost instantly (some detectors require hours after a hit). Has the device saved lives? “There are definitely success stories,” says Rose. “But I can’t talk about them.” The military isn’t keen to let the world evaluate its bomb-sniffing capabilities.
Rose can say that the handheld detectors are frequently deployed at security checkpoints and during patrols in Iraq and Afghanistan. Because of its extreme sensitivity, Fido XT has been particularly useful in catching bomb makers themselves: telltale explosives residues often cling to their clothes and skin. By employing the technology at traffic stops, in public places, and when checking homes in neighborhoods suspected of harboring terrorists, the military hopes to identify and arrest those who have been preparing bombs. “Terrorist cells have a lot of people willing to go out and blow themselves up or plant a bomb, but they only have one or two people who are expert at making bombs,” Rose says. “If you can take that person out of the chain, you can prevent hundreds of bombings.”
After the release of Fido XT, Rose and ICx set their sights on airport security. Unfortunately, by 2006 the threat had changed. Terrorist plots broken up in the United Kingdom suggested that would-be airline bombers were turning to liquid explosives invisible to existing detectors–including the polymers in the company’s device. But Rose’s efforts to develop a thin film for the Fido XT provided another payoff: the same method proved useful in making thin films of other polymers, including those capable of detecting the new explosive threat. As a result, the company was able to rush out a new product. The Fido PaxPoint handheld detector is now deployed at airports, where it can instantly pick up molecules of the liquids wafting out of even hidden, sealed containers. “We had been looking at those substances for a few years, and when the threat came to the front burner we were able to move from first prototype to a working airport device in less than a year,” Rose says. The ability to tweak the polymers to detect new types of explosives is one of the technology’s biggest advantages, she adds.
That’s a good thing, because terrorists are likely to keep changing the game, notes Harvey Mudd’s Martonosi. “Just as our ability to detect explosives is evolving, the ability to create new explosives is evolving,” she says. “It’s a moving target.”