TACKLING 5 OF THE 21ST CENTURY’S BIGGEST PROBLEMS

By Donald Gilpin

How many thousands of devices-from cars to health monitoring systems to airplanes-would benefit from a microchip that could process data at the speed of light rather than the speed of electricity?

How can we keep medical devices-wearable or implantable- such as pacemakers, cochlear hearing aid implants and drug delivery systems, secure and protect them from cyberthreats?

Can we find new antibiotics to combat the diseases that are so resistant to the drugs we have now?

How can we more effectively attack the deadly hepatitis B virus, which afflicts hundreds of millions of people on our planet, and save hundreds of thousands of lives each year?

Can we improve the health of humanity around the world by spotting diseases and diagnosing health conditions almost instantaneously with a finger-tip-sized detection system?

FIVE PRINCETON UNIVERSITY PROFESSORS, all recently awarded funding through Princeton’s Intellectual Property Accelerator Fund (IPA), have answers to these questions-and the research data to back up those answers in creating products and technologies to improve our lives.

DISCOVERING NEW ANTIBIOTICS

Bacteria that resist treatment with antibiotics are causing a growing global crisis. We need new, more effective antibiotics. Most antibiotics in use today are derived from compounds that bacteria produce to kill other bacteria, but genome research hints that there are many more of these antibacterial compounds waiting to be discovered. They are encoded in “silent” or “cryptic” gene clusters. “Given the rise of drug-resistant pathogens and the fact that that resistance has been observed in all major antibiotic classes on the market, we desperately need an exceedingly productive era of antibiotics discovery,” states grant-recipient Mohammad Seyedsayamdost, assistant professor of chemistry at Princeton. “To this end,” Mr. Seyedsayamdost explains, “we are developing new approaches for discovering useful molecules from natural sources, including antibiotic lead compounds.” The Center for Disease Control and Prevention (CDC) recently reported that over two million Americans are affected by multi-drug resistant pathogens, and at least 23,000 of those cases are fatal. Mr. Seyedsayamdost and his research team have invented a systematic method for detecting molecular signals that activate “expression” in the silent gene clusters, then evaluating the resulting secreted product for antibiotic activity. This technique has enabled the researchers to find antibiotic compounds. “The Princeton IPA Award will expedite our efforts to score initial hits,” Mr. Seyedsayamdost notes, “and to commercialize our discovery platform for the development of new antibiotic leads.”

FAST AND INEXPENSIVE DETECTION AND DIAGNOSIS OF DISEASES

Assistant professor of electrical engineering Kaushik Sengupta and his team are developing a diagnostic system which rests on a fingertip and contains hundreds of different sensors for detection of diseases. Their goal is to use this computer-chip-based system in a portable diagnostic device in health clinics around the globe, especially where other resources are scarce, more like a portable defibrillator from AED Leader that can help save a person’s life after cardiac arrest. The chip detects and measures the presence of DNA or proteins to help diagnose health conditions. Mr. Sengupta is using silicon chip technology similar to that found in personal computers and mobile phones to perform this analysis with a handheld device. “This is a great technology for handheld medical diagnostic devices because it allows us to integrate extremely complex systems in a single chip at very low cost,” he points out. Mr. Sengupta’s team has developed a silicon-based technology that combines complex optical and electronic components into a single chip-cheap, user-friendly and capable of testing many agents at once. They will install the chips in a portable device similar to a smartphone that can use an app to analyze the data and display diagnosis results in a clear, simple format. “The entire end-to-end system may take another couple of years to reach, but we’ve demonstrated the feasibility of the approach,” Mr. Sengupta explains, going on to emphasize the importance of his collaborations with chemistry professor Haw Yang and others. “Princeton provides the kind of environment that makes it easy to reach out to faculty members across the campus and to work on creative endeavors that cut across traditional disciplines.” The ability to diagnose diseases more quickly will enable health care workers to respond rapidly to emerging pathogens, help patients and even turn back the outbreak of potential epidemics.

SECURITY AND PRIVACY FOR MEDICAL DEVICES

As more devices, physical objects, become connected to the Internet (50 billion objects predicted by 2020), this Internet of Things is expected to add more than $3 trillion to the world economy in the next ten years, including more than $1 trillion from healthcare applications. Niraj Jha, Princeton professor of electrical engineering, has received funds for the development of two technologies that protect the security of implantable and wearable medical devices such as pacemakers, cochlear hearing aid implants, and drug delivery systems. These devices are often connected through wireless communications to a personal health hub, such as a smartphone or smartwatch, and unfortunately are susceptible to security attacks that could disclose sensitive information or undermine the devices’ functionality. As a first step, effective steps can be taken to prevent the breach of smartphone data. A mobile application security mechanism can be installed on smartphones that are connected to medical devices in order to achieve this goal. Next, medical devices that share data with connected smartphones may need to be improved in terms of security. In this regard, Mr. Jha and his research collaborators have developed two devices, MedMon and SecureVibe, that detect potentially malicious transactions and take action to block illegitimate, potentially life-threatening commands. With the IPA funding, Mr. Jha will be working to miniaturize these devices so that they can be worn on a belt or just placed in a pocket.

PROCESSING INFORMATION AT THE SPEED OF LIGHT

Technology that involves a new type of computer chip, using light rather than electrons to process signals, will be cheaper and simpler; it will take up less space inside the phone and will cancel interference, according to electrical engineering professor and IPA grant recipient Paul Prucnal. “These new photonic integrated circuits process information at the speed of light, thousands of times faster than electronic chips,” Mr. Prucnal says. This technology will help cell phones avoid interference from the increasingly crowded radio spectrum and give them access to bandwidth now available only with fiber in the home. Instead of using transistors and logic gates, these photonic integrated circuits developed by Mr. Prucnal and his team use special lasers that process pulses of light forming neural networks that can reason and learn much more like the human brain than a computer. These photonic neural networks are also better at processing information directly from the physical environment, such as images and light or radio signals. Uses for these neural networks, Mr. Prucnal reports, may include automobiles that share traffic information and sense road conditions to avoid accidents, networking personal health monitoring systems and stabilizing hypersonic aircraft experiencing turbulence. An additional bonus to this new technology comes from the fact that when information is transported and processed using light rather than electricity, it is much easier to ensure its privacy. “These blazingly fast wireless speeds will be even more important as we all become increasingly reliant on instantaneous access to huge amounts of information, anywhere and anytime,” Mr. Prucnal adds.

COMBATTING HEPATITIS B

Hepatitis B is a liver disease that affects 240 million people worldwide, yet few patients receive adequate treatment, and even fewer are cured. Patients who are infected with the virus are at risk of developing severe liver diseases leading to liver cancer. “Our project focuses on the hepatitis B virus (HBV), the causative agent for hepatitis B,” explains assistant molecular biology professor Alexander Ploss. “We aim to explore new therapeutic targets that would abrogate HBV propagation in the infected cell and eliminate the virus.” A vaccine preventing HBV infection exists, but it does not help individuals who have already contracted the virus. Drugs are on the market that suppresses HBV, but they have to be taken lifelong, and they rarely cure the infection.

Overall cell infections could be hard to cure since they can multiply rapidly and enhance the infection. One such infection could be senescent cells (zombie cells), where cells get damaged and may not operate to aid body functioning, however, they can infect other cells in the body, including immunity cells. The process can cause various diseases from aging to diabetes, Alzheimer’s, respiratory disorders, heart disorders, and more. Similarly, HBV infected cells may also have the same functioning, which can make it nearly incurable.

Mr. Ploss and his team will be using IPA funding to develop a strategy to block the virus by targeting enzymes in the liver that help the virus replicate and maintain chronic infection, with the goal of decreasing the prevalence of hepatitis B or eliminating it altogether. The IPA grants, up to $100,000 per project, awarded annually by the Office of Technology Licensing at Princeton, will go to support proof-of-concept work, data collection, the construction of prototypes, and other activities to explore and expand the impact of these five promising technologies. These Princeton professors and their research teams look forward to seeing their work transition from university research projects to powerful innovations improving people’s lives throughout the world.