Professor David Cooper Honored at CVPR Conference

David Cooper, Professor Emeritus of Engineering and Professor of Engineering (Research), was honored at the 25th International IEEE (Institute of Electrical and Electronics Engineers) Conference on Computer Vision and Pattern Recognition (CVPR) which was held in Providence from June 18-20. This is the major annual meeting on CVPR. Professor Cooper was honored “In appreciation of his outstanding and pioneering contributions to Unsupervised Learning and Bayesian Inference in Computer Vision.” The international conference was held this year at the Convention Center with over 1800 attendees. Brown University Professor Benjamin Kimia served as one of three general co-chairs of the conference.

Ben Kimia, David Cooper, Rama Chellappa

Professor Cooper’s current research focuses on the development and application of new geometric, algebraic, and probabilistic approaches, models, and algorithms for recognizing and estimating 2D and 3D geometric information and functioning in 3D scenes from images, video, and range data.

Professor Cooper received both his Sc.B. and Sc.M. degrees from MIT in electrical engineering, and his Ph.D. from Columbia University in applied mathematics. After graduation, he joined the Brown faculty in September of 1966 as an assistant professor. He became an associate professor in 1969, and was promoted to full professor in 1978. During his more than 45 years at Brown, Cooper has also served as cofounder and associate director of the Laboratory for Engineering Man/Machine Systems (LEMS) for more than 15 years, and the head of electrical engineering for two years. He is a fellow of the IEEE and has published roughly 140 papers in refereed journals or as book chapters.

For more information on the CVPR awards, please go to: http://www.cvpr2012.org/program-details/awards

Fei Guo Ph.D. ’12 Receives Brian Kelly Award

Brown University School of Engineering postdoctoral researcher Fei Guo Ph.D. ’12 was presented the Brian Kelly Award at Carbon 2012, the annual world conference on carbon in Krakow, Poland, on June 21. Guo, who was advised by Professor Bob Hurt at Brown, delivered a 30-minute award lecture, “Graphene-Based Environmental Barriers,” to the conference participants.

In his presentation, Guo demonstrated the potential for graphene oxide films to act as high-performance barriers for environmental toxicants. Applying elemental mercury (considered a neurotoxic) as a model, he showed that just 20 nm graphene oxide films, which were deposited onto surface treated polymers, reduced mercury permeability by 90%.

This prestigious annual award was established in 1996 by the British Carbon Group in memory of Brian Kelly, a leading authority on the physics of graphite to reward excellence in carbon science and technology. The award is currently five hundred pounds sterling (£500) and was presented at the time of the conference with a certificate. The award is intended as a travel grant for students and early career researchers with up to ten years postdoctoral experience to attend the annual World Carbon Conference.

Selenium controls staph on implant material

A coating of selenium nanoparticles significantly reduces the growth of Staphylococcus aureus on polycarbonate, a material common in implanted devices such as catheters and endotracheal tubes, engineers at Brown University report in a new study.

PROVIDENCE, R.I. [Brown University] — Selenium is an inexpensive element that naturally belongs in the body. It is also known to combat bacteria. Still, it had not been tried as an antibiotic coating on a medical device material. In a new study, Brown University engineers report that when they used selenium nanoparticles to coat polycarbonate, the material of catheters and endotracheal tubes, the results were significant reductions in cultured populations of Staphylococcus aureus bacteria, sometimes by as much as 90 percent.

Selenium solutionQi Wang swirls a solution of selenium nanoparticles in the lab.
Coatings of the nanoparticles appear effective in fighting staph
bacteria in medical device materials, according to a new study.
Credit: Webster Lab/Brown University

“We want to keep the bacteria from generating a biofilm,” said Thomas Webster, professor of engineering and orthopaedics, who studies how nanotechnology can improve medical implants. He is the senior author of the paper, published online this week in the Journal of Biomedical Materials Research A.

Biofilms are notoriously tough colonies of bacteria to treat because they are often able to resist antibiotic drugs.

“The longer we can delay or inhibit completely the formation of these colonies, the more likely your immune system will clear them,” Webster said. “Putting selenium on there could buy more time to keep an endotracheal tube in a patient.”

Meanwhile, Webster said, because selenium is actually a recommended nutrient, it should be harmless in the body at the concentrations found in the coatings. Also, it is much less expensive than silver, a less biocompatible material that is the current state of the art for antibacterial medical device coatings.

Webster has been investigating selenium nanoparticles for years, mostly for their possible anticancer effects. As he began to look at their antibiotic properties, he consulted with Hasbro Children’s Hospital pediatrician Keiko Tarquinio, assistant professor of pediatrics, who has been eager to find ways to reduce biofilms on implants.

Studying selenium

For this study, Webster and first author Qi Wang grew selenium nanoparticles of two different size ranges and then used solutions of them to coat pieces of polycarbonate using a quick, simple process. On some of the polycarbonate, they then applied and ripped off tape not only to test the durability of the coatings but also to see how a degraded concentration of selenium would perform against bacteria.

On coated polycarbonate — both the originally coated and the tape-tested pieces — Wang and Webster used electron and atomic force microscopes to measure the concentration of nanoparticles and how much surface area of selenium was exposed to interact with bacteria.

One of their findings was that after the tape test, smaller nanoparticles adhered better to the polycarbonate than larger ones.

Then they were ready for the key step: experiments that exposed cultured staph bacteria to polycarbonate pieces, some of which were left uncoated as controls. Among the coated pieces, some had the larger nanoparticles and some had the smaller ones. Some from each of those groups had been degraded by the tape, and others had not.

All four types of selenium coatings proved effective in reducing staph populations after 24, 48, and 72 hours compared to the uncoated controls. The most potent effects — reductions larger than 90 percent after 24 hours and as much as 85 percent after 72 hours — came from coatings of either particle size range that had not been degraded by the tape. Among those coatings that had been subjected to the tape test, the smaller nanoparticle coatings proved more effective.

Staph populations exposed to any of the coated polycarbonate pieces peaked at the 48-hour timeframe, perhaps because that is when the bacteria could take fullest advantage of the in vitro culture medium. But levels always fell back dramatically by 72 hours.

The next step, Webster said, is to begin testing in animals. Such in vivo experiments, he said, will test the selenium coatings in a context where the bacteria have more available food but will also face an immune system response.

The results may ultimately have commercial relevance. Former graduate students developed a business plan for the selenium nanoparticle coatings while in school and have since licensed the technology from Brown for their company, Axena Technologies.

Small Wonder

Partnering with an engineer, a pathologist goes in a new direction.

The yellow-and-black signs outside Dr. Agnes Kane’s pathology laboratory read “CAUTION: Cancer hazard.” Nodding at the ominous-looking postings, Kane explains, “because of their toxicity similar to asbestos, we handle these materials as if they were carcinogens.” Meanwhile, across the Providence River, at the School of Engineering, Professor Robert Hurt is hard at work creating the very materials that Kane is so gingerly studying: nanoparticles.

Smaller than 1,000th the width of a human hair—so small that you need an electron microscope to see them— nanoparticles’ practical applications may be enormous: making implants more biocompatible; diagnosing and treating cancers; cleaning up oil spills. That said, the history of science is filled with promising solutions that create additional unforeseen problems of their own. No one is more aware of this than Kane, chair of Brown’s Department of Pathology and Laboratory Medicine. She has spent her career on, and helped guide the Department’s focus on, the human health effects of environmental and occupational exposures. She and Hurt tick off some examples demonstrating this law of unintended consequences:

“Corn ethanol,” says Hurt, referring to the fact that 40 percent of the corn grown in America is used to create this alternative fuel. “Then you raise the corn prices for food.”

Kane nods. “Use more fertilizer? Contaminate our water supplies. There’s always these trade-offs.”

One of modern history’s most devastating trade-offs was of a common mineral that makes an excellent flameretardant building material. Its usefulness notwithstanding, asbestos can cause devastating cancers and fatal lung problems both for those who mine it and for those who live and work in buildings that contain it.

Small, Novel...but Safe

Selenium-carbon nanocomposite particles
synthesized as a novel chemotherapy agent

From the time Kane joined Brown’s pathology department as a founding member in 1982, she has studied the mechanisms by which asbestos injures cells and causes cancer. When, in 2004, she gave a talk about this research to a group of colleagues, Hurt approached her afterward. The asbestos fibers that Kane showed in her talk reminded Hurt of the carbon nanofibers he had been developing. “We were not working on health effects at the time,” Hurt says. “We were doing traditional nanoscience, trying to make new things that had never been made before.”

But when Hurt told Kane about his carbon nanofibers, “I immediately asked him if I could have some,” Kane recalls. Her worrisome discovery—that the particles were similar to asbestos in several key ways—has changed the direction of both her own and Hurt’s careers and of the pathology department’s research and teaching.

Now Kane and Hunt work side-by-side to create innovative nanotechnology and, simultaneously, assess the materials’ safety and toxicity. “It’s a new paradigm to try to consider the implications of the technology as you develop the technology,” says Hurt. “We haven’t done a lot of that in the past. We just develop technology and we field it and then we worry about what its implications might be. So it’s kind of fun to do these things together.”

In 2007, their collaboration gave rise to the Institute for Molecular and Nanoscale Innovation (IMNI), an interdisciplinary organization comprising more than 60 faculty in nine departments. Kane heads IMNI’s NanoHealth Initiative, which studies the environmental and health effects of nanotechnology.

Training the Next Interdisciplinarians

With curly chin-length gray hair and blue eyes, Kane—known to friends and colleagues as “Aggie”—smiles often and laughs readily. Her unassuming manner and commitment to collaboration, teaching, and mentorship have won her numerous teaching awards and devotees.

“If it weren’t for Aggie, I wouldn’t be doing what I’m doing,” says Luba Dumenco, a lecturer in pathology and director of the Medical School’s preclinical curriculum. “She’s always valued teaching incredibly highly.” Just recently, Dumenco struck up a conversation with another mom at the local skating rink.The woman happened to be a neonatologist who had trained at Brown’s medical school. “I told her I was teaching at the med school, and she said, ‘Do you know Dr. Aggie Kane? She was our favorite! We loved her!’” Dumenco says with a laugh. “She cares a lot about the students.She does a wonderful job and they’re very lucky to have her.”

The breadth of students that Kane reaches each year has grown as a result of her partnership with Hurt. In 2009, they secured a grant from GAANN, or Graduate Assistance in Areas of National Need, to fund interdisciplinary training in nanotechnology. Between six and eight doctoral students study nanotoxicology and nanomedicine with co-mentors in engineering or physical sciences and biological science. Kane and Hurt also co-teach an undergraduate and graduate course called “Small Wonders: Science, Technology, and Human Health Impacts of Nanomaterials.” For their final projects, students working together in interdisciplinary teams are required both to use nanotechnology to solve some real-world problem and to address—and minimize—their solution’s potential environmental and health impacts. “I look at this as training the next generation of environmental scientists and engineers,” Kane says.

But first they have to learn how to talk to each other. When Kane and Hurt began collaborating, “it took us a while to learn each other’s languages,” says Kane, “because medicine has its own vocabulary, as well as engineering.” Kane might, for example, say “mitochondria,” or “epigenetics,” and get a blank stare in return. “And so we would just keep asking each other questions, any time we didn’t understand something,” she recalls. “It took us quite some time to learn enough to communicate effectively.”

Their newest collaboration is funded by the Gulf of Mexico Research Initiative, which was established in the wake of the Deepwater Horizon disaster. Hurt has set out to design nanoparticles called nanosorbents, which by capturing and sequestering pollutants like oil, may be safer and more effective than existing methods of cleaning up oil spills. The Deepwater Horizon cleanup team—like the Exxon Valdez team before it—relied on Corexit, a dispersant which causes oil to suspend in the water as tiny particles rather than accumulate on the surface as oil slicks.

“They used it in enormous amounts in the Deepwater Horizon cleanup,” says Hurt, but “it’s not clear if it’s a good idea to use very large amounts of chemicals in a marine environment.”

But it’s not clear whether nanosorbents are a good idea, either. As Hurt designs the particles, Kane and her team set out to answer two questions. “First, will they work?” she asks. “And then, will they be toxic to the organisms?”

“They might be worse,” Hurt acknowledges. “We don’t know.”

Engineering Prevention

To begin to answer these questions, Kane has a small steel tank in her lab. Like a miniature wave pool, the open-air tank bubbles with seawater maintained at exactly 72 degrees. Soon this will be home to a small colony of brine shrimp, tiny marine organisms that, as larvae in the wild, are eaten by small fish, which, in turn, are used as bait to catch larger fish, which are eaten by people. As such, the brine shrimp are a good “indicator species” for study.

“We don’t want to have these kinds of dispersants accumulate up the food chain,” says Kane, peeking at the churning water.

A tube runs from a beaker into the basin, helping to aerate the water. As the shrimp grow in the lab, Kane and her colleagues will release oil and Hurt’s nanoparticles into the water with them to see what happens. Will they stop swimming? Will they die? Will their RNA reflect toxicity or injury? If so, Kane says, she is confident that her colleagues can alter the nanoparticles to reflect her findings.

“Engineers are very clever,” she says with a smile. “If we can identify the specific properties that are associated with the toxic effects, they can design [the nanoparticles] or process them to eliminate those properties or reduce those properties and reduce their toxicity.” And part of the excitement of studying nanoparticles is the ability to intervene now, in the very early stages—to prevent environmental and health disasters, rather than clean them up after the fact.

“When you think about what happened with the widespread use of asbestos throughout the 20th century— and we’re still suffering the consequences because of the long latent period of those diseases—the fact that those fibers persist in the buildings and in the environment and we’re still being exposed,” says Kane, “that’s a very expensive lesson. We do not want to repeat that tragedy again.”

by Beth Schwartzapfel ’01
Photographs by Karen Philippi
Courtesy of Brown Medicine Magazine

A SMART(er) way to track influenza

Brown University researchers have created a reliable and fast flu-detection test that can be carried in a first-aid kit. The novel prototype device isolates influenza RNA using a combination of magnetics and microfluidics, then amplifies and detects probes bound to the RNA. The technology could lead to real-time tracking of influenza. Results are published in the Journal of Molecular Diagnostics.

PROVIDENCE, R.I. [Brown University] — In April 2009, the world took notice as reports surfaced of a virus in Mexico that had mutated from pigs and was being passed from human to human. The H1N1 “swine flu,” as the virus was named, circulated worldwide, killing more than 18,000 people, according to the World Health Organization. The Centers for Disease Control and Prevention in the United States said it was the first global pandemic in more than four decades.

Swine flu will not be the last viral mutation to cause a worldwide stir. One way to contain the next outbreak is by administering tests at the infection’s source, pinpointing and tracking the pathogen’s spread in real time. But such efforts have been stymied by devices that are costly, unwieldy and unreliable. Now, biomedical engineers at Brown University and Memorial Hospital in Rhode Island have developed a biochip that can detect the presence of influenza by zeroing in on the specific RNA sequence and then using tiny magnets in a tube to separate the flu-ridden sequence from the rest of the RNA strand. The result: A reliable, fast prototype of a flu-detection test that potentially can be carried in a first-aid kit and used as easily as an iPhone.

“We wanted to make something simple,” said Anubhav Tripathi, associate professor of engineering at Brown and the corresponding author on the paper, published in the Journal of Molecular Diagnostics. “It’s a low-cost device for active, on-site detection, whether it’s influenza, HIV, or TB (tuberculosis).”

The Brown assay is called SMART, which stands for “A Simple Method for Amplifying RNA Targets.” Physically, it is essentially a series of tubes, with bulbs on the ends of each, etched like channels into the biochip.

There are other pathogen-diagnostic detectors, notably the Polymerase Chain Reaction device (which targets DNA) and the Nucleic Acid Sequence Based Amplification (which also targets RNA). The SMART detector is unique in that the engineers use a DNA probe with base letters that match the code in the targeted sequence. This ensures the probe will latch on only to the specific RNA strand being assayed. The team inundates the sample with probes, to ensure that all RNA molecules bind to a probe.

“The device allows us to design probes that are both sensitive and specific," Tripathi said.

Anubhav Tripathi
“We wanted to make something simple. (This is) a low-cost device
for active, on-site detection, whether it’s influenza, HIV, or TB.”
Credit: Mike Cohea/Brown University

This approach creates excess — that is, probes with no RNA partners. That’s OK, because the Brown-led team then attached the probes to 2.8 micron magnetic beads that carry the genetic sequence for the influenza RNA sequence. The engineers then use a magnet to slowly drag the RNA-probe pairs collected in the bulb through a tube that narrows to 50 microns and then deposit the probes at a bulb at the other end. This convergence of magnetism (the magnetized probes and the dragging magnets) and microfluidics (the probes’ movement through the narrowing channel and the bulbs) serves to separate the RNA-probe pairs from the surrounding biological debris, allowing clinicians to isolate the influenza strains readily and rapidly for analysis. The team reports that it tracks the RNA-probe beads flawlessly at speeds up to 0.75 millimeters per second.

“When we amplify the probes, we have disease detection,” Tripathi said. “If there is no influenza, there will be no probes (at the end bulb). This separation part is crucial.”

Once separated, or amplified, the RNA can be analyzed using conventional techniques, such as nucleic acid sequence-based amplification (NASBA).

The chips created in Tripathi’s lab are less than two inches across and can fit four tube-and-bulb channels. Tripathi said the chips could be commercially manufactured and made so more channels could be etched on each.

The team is working on separate technologies for biohazard detection.

Stephanie McCalla, who earned her doctorate at Brown last year and is now at the California Institute of Technology, is the first author on the paper. Brown professors of medicine Steven Opal and Andrew Artenstein, with Carmichael Ong and Aartik Sarma, who earned their undergraduate degrees at Brown, are contributing authors.

The U.S. National Institutes of Health and the National Science Foundation funded the research.

- by David Orenstein