The Lemelson–M.I.T. Program recognized four student inventors Wednesday poised to make a profound impact in the areas of disease diagnostics, drug development, assistive devices such as wheelchairs, and security screening for explosives. Each of the winners—from the California Institute of Technology; Harvard University and the Massachusetts Institute of Technology; Rensselaer Polytechnic Institute (R.P.I.); and the University of Illinois at Urbana–Champaign (U.I.U.C.)—receives a $30,000 prize to help bring their emerging technologies to market.

This year, Lemelson–M.I.T. tipped its hat to a group of young entrepreneurs that includes Caltech's Guoan Zheng, Harvard–M.I.T.'s Alice Chen, R.P.I.'s Benjamin Clough and U.I.U.C.'s Scott Daigle.

Disease diagnostics
Zheng, a fourth-year electrical engineering PhD candidate at Caltech in Pasadena, is developing a low-cost, portable imaging device and software that can inexpensively turn a computer or smart phone into a high-resolution digital microscope. Such use of computers to enhance the quality of low-resolution images is familiar to fans of CSI and other TV police procedurals, where law enforcement lab technicians often crack a case by magnifying some small detail of a digital image pulled from grainy surveillance footage. "The trick they're using is the same trick I'm using, which is to use super-resolution technology to turn a sequence of low-resolution images into one high-resolution image," says the 26-year-old native of Guangzhou, China.

Zheng adapted super-resolution image-processing technology to create an on-chip microscope—a sub-pixel resolving optofluidic microscope (SROFM)—made up of a complementary metal-oxide semiconductor (CMOS) sensor connected via a USB port to a computer loaded with image-enhancing software. His primary objective is to provide doctors in developing countries with a means to scan residents for malaria at a cost of about 50 cents per blood sample. A SROFM device would use microfluidics channels (micrometer-size molded tubing and interconnects) to deliver a blood sample directly across the CMOS sensor, which would capture a series of low-resolution images for a mobile computer and reconstruct them as a single high-resolution image.

Last month, Zheng received a research grant from Qualcomm to develop a SROFM smart-phone application, which will make his on-chip microscope even more portable. He is hoping to have the application—which would enable the on-chip microscope to plug into an iPhone or a handset running Google's Android mobile operating system, for example—ready this summer and to begin field-testing the technology as soon as possible.

Zheng wants to wrap up his studies either late this year or in early 2012, at which time he hopes to focus on a start-up he formed with his advisor, Changhuei Yang, a Caltech professor of electrical engineering and bioengineering.

Faster, cheaper, safer drug development
Chen, a biomedical engineer and graduate student in the Harvard–M.I.T. Division of Health Sciences and Technology and the Harvard School of Engineering and Applied Sciences, was recognized for her work developing a new way to implant human cells in lab mice to better test the efficacy of new drug candidates. The result could shave time and money off of the process of developing new drugs, which can take a decade and cost tens of millions of dollars.

Drug developers often rely on in vitro cell-based microchips to test promising new chemical compounds. These chips are important for eliminating many early problematic amalgams, but animal tests are still needed to see how a drug is broken down by multiple organs in the body—the liver and gut, in particular—and how the broken-down metabolites circulate to other organs, the 29-year-old San Jose, Calif., native says.

Chen discovered a way to "humanize" a mouse with a tissue-engineered, humanlike liver to better determine how a real human liver might metabolize a particular chemical compound and respond to infectious disease. Differences between animal and human liver activity often result in under-reported human toxicities in preclinical animal testing of drug compounds. "Right now, we have this whole pipeline where drugs are developed, and animal toxicology models are a very important part of that," she says. "But they miss a lot of drug dangers and drug metabolites that then show up in clinical trials and can cause toxicities and adverse reactions and, in worst-case scenarios, deaths."

Chen's bioengineered liver does not actually resemble a human liver. It resembles a soft contact lens comprising a biomaterial matrix that encapsulates human cells in much the same way Jell-O can encapsulate fruit, she says. "It's tuned so that it connects to the mouse's circulatory system but will respond to drugs in a similar way to a human," she adds.

When Chen wraps up her studies at the end of this month, she plans to focus full time on Sienna Labs, a start-up she co-founded with fellow M.I.T. graduate Todd Harris. Although Sienna does not focus on humanized mice, it follows a similar thread in her career goal, which is to develop technologies that can improve existing medical treatments. Sienna's medical pigments designed to enhance microsurgeries for skin disease are expected to go into clinical trials this year, she says.

T-ray test
Clough, an R.P.I. doctoral student in electrical, computer and systems engineering who hopes to complete his PhD within a year, has demonstrated a cost-effective technique for using sound waves to boost the effective distance of terahertz spectroscopy from less than a meter to several meters.

Passing terahertz waves through an object renders a spectral fingerprint of its chemical composition. Because this frequency (which exists in the electromagnetic spectrum between the infrared and microwave bands) is able to penetrate many optically opaque barriers, terahertz waves effective at longer range hold potential for detecting hidden explosives, chemicals and other dangerous materials while allowing security personnel to keep their distance. Terahertz radiation is also low energy, so if they are used to scan people, the waves are less dangerous than x-rays or microwaves.

Unfortunately, terahertz waves do not propagate very well through the air, limiting their practical applications. "Even after a few feet you have quite a bit of your energy lost due to absorption by the water vapor in the air," says Clough, a 26-year-old native of Albuquerque, N.M. As a result, even though several airports already rely on a type of terahertz security scanners, they typically use low-frequency, continuous-wave energy at a single terahertz frequency, which enables them to create images of items carried in suitcases and pockets but not a spectral signature of those items that would indicate their composition.

Clough sees his sound-wave work having commercial and military applications. He is interested in postgraduate work at Sandia National Laboratories, where his father worked for years as a chemist and where Clough has had several internships. "I really enjoyed the environment there, and I know they are really security oriented, so I can envision possibly taking this tech there and hoping to further develop it," he says.

In gear
Daigle is a second-year graduate student in mechanical science and engineering at U.I.U.C. who plans to graduate in August. His mission over the past few years has been to make life easier for people who rely on manual wheelchairs for mobility. To that end, he co-founded IntelliWheels, Inc., in May 2010 with Marissa Siebel, a PhD candidate in community health and disability studies at U.I.U.C. and the athletic trainer for the Illinois wheelchair athletics team. The company's mission is to develop and commercialize an automatic gear shifter that can be installed on manual wheelchairs to reduce the amount of exertion required to operate them. "Gear shifting is in cars, it's in bikes, but for some reason it's not in wheelchairs right now," Daigle says.

The IntelliWheels device senses how fast the wheelchair is moving, whether it is on an incline or a decline, and how hard the chair's user is pushing. It uses that information to select the best gear and shift into that gear between pushes. Daigle says he was careful to not add too much weight to the wheelchair when designing the IntelliWheels device. "An ultralight wheelchair weighs about 10 pounds [4.5 kilograms]," he says. "Our system would add about 10 pounds of weight to the wheelchair, but you also end up with 95 percent mechanical efficiency when the gears are added." The device features a user interface that displays what gear the chair is in and offers a manual override button if the user would like to shift to a different gear.

Daigle has a working prototype of the device and has gotten approval to let wheelchair users begin testing it. "We're basically going to take about a month and run through about 20 wheelchair users to get them to test the chair in an everyday environment and get their feedback on the design," he says. "After that we are planning on life-cycle testing, where we put it through a simulated three years of life using a computer-controlled system. This should flush out all of the mechanical bugs."

The 24-year-old Westmont, Ill., native's plans after graduation are to devote as much time as possible to building IntelliWheels as a company. In order to support the flagship gear-shifting device, Daigle is also developing caster skis that clip onto a manual wheelchair's wheels to help them move more easily through snow. Another idea is to create snap-on snow chains for the winter months. "We're working to develop these and hope to get them for sale on our Web site in the next few months," he says.

View a slide show of the Lemelson-M.I.T. award-winning technology.