Engineering Solutions to Global Health Problems

Tuesday, Jan 24, 2012

 

Princeton researchers are developing health-related innovations at Princeton's School of Engineering and Applied Sciences. Here we present a snapshot of the research projects that have the potential to improve prevention, diagnosis, treatment and understanding of disease.

Avoiding hospital re-admissions

Mark Braverman, an assistant professor of computer science, is helping solve a pressing problem in health care: how to prevent patients from relapsing soon after being discharged from a hospital. During a previous stint at Microsoft Research, Braverman helped develop software that allows computers to “learn” based on actual patient data those patients that are most at risk so that hospitals can tailor their post-discharge care and avoid re-admissions. Microsoft released the software as part of its hospital-data management product in spring 2011.

 

Protecting blood to prevent neurological damage

Alexander Smits, chair and the Eugene Higgins Professor of mechanical and aerospace engineering, is working with students to understand the ways that sheer forces and turbulence damage blood cells. The work could lead to new designs for heart-lung bypass machines, which are commonly used in surgeries but are thought to cause neurological damage and other complications. The researchers have described the behavior of blood over a very wide range of conditions, more precisely than ever done before.

 

Printable sensors form basis for many tests

Princeton engineers are collaborating with Maryland-based Vorbeck Materials to develop printable sensors that greatly improve the performance of many basic medical tests.

The researchers in the laboratory of Ilhan Aksay, professor of chemical and biological engineering, are using “functionalized graphene” — a singleatom- thick sheet of carbon with certain structural and chemical modifications — that could form the basis for inexpensive, highly reliable tests for chemicals such as glucose and dopamine.

The technology is being commercialized by Vorbeck, which recently established a research lab in Princeton near the University to continue the collaboration.

 

Lasso-shaped proteins as drug candidates

Professor and student in lab
Assistant Professor James Link and graduate student Jessica (Si Jia) Pan are developing peptide drugs that could treat bacterial infections that have become resistant to antibiotics. (Photo by Frank Wojciechowski)

Bacteria secrete antimicrobial peptides — short chains of amino acids — for defense against other species. James Link, an assistant professor of chemical and biological engineering, is pioneering research on a class of such peptides that are lasso-shaped, which makes them resistant to the body’s defense mechanisms and hence good drug candidates. “We’re understanding how these amazing structures are made by bacteria,” Link said. “Thermodynamically they shouldn’t exist.”

Starting with one particular lasso peptide, Link and his graduate student Jessica (Si Jia) Pan have created a dozen variants with more antibiotic potency. The researchers use a method called directed evolution in which they create random mutations, test for desirable properties and repeat. They screened 20,000 variations of the peptide for the most promising molecules and found the most promising to be as potent as the antibacterial peptides used in the food industry to protect perishables.

The researchers are now trying to beat bacteria at their own game. “We’re trying to use directed evolution to find a peptide that can kill E. coli that are resistant to it,” Link said. “In the same way that a bacteria evolves resistance, we can try to evolve peptides that overcome that resistance.”

 

Drug Design

While Link’s approach to designing drugs is experimental, Christodoulos Floudas, the Stephen C. Macaleer Professor of Chemical and Biological Engineering, has spent more than a decade developing computational methods for the same purpose.

Floudas and his graduate students have found a way to calculate whether a peptide, based on its structure and amino-acid sequence, will bind to a specific protein. They have designed seven new peptides that bind to a human enzyme linked to cancer progression. Experiments by a Boston company have shown that the peptides inhibit the enzyme’s function. “There’s no currently available inhibitor for this enzyme,” Floudas said.

Lasers Allow Non-invasive Tests

 

What if a person with diabetes could measure blood sugar without a pinprick? What if a quick scan of a person’s breath could reveal how their kidneys are doing or whether they have asthma?

Behind the technologies is a device known as a quantum cascade laser, which offers a compact, inexpensive and easy-to-use method for producing and detecting mid-infrared light. Among the uses currently being developed is a device that scans a persons’ skin to reveal his or her blood glucose level — a project that is now supported by Princeton’s Eric and Wendy Schmidt Transformative Technology Fund. Compared to the current method of drawing and testing a drop of blood, the innovation could provide much more control over diabetes.

Another area of research involves sensing nitric oxide or ammonia in a person’s breath. Technology under development at Princeton could allow much more finely tuned detection of nitric oxide than was previously possible, allowing a more fundamental understanding of the role of the gas in the body and in disorders such as asthma. A similar scan for ammonia could give doctors critical information about the kidneys. More precise and frequent monitoring of these conditions might allow reduced use of steroids or dialysis, saving medical costs and avoiding potential complications.

 

Simulating brain damage

The membranes shown here combine electronics with stretchable material, enabling medical researchers to test the effects of trauma on brain cells.

Researchers in the lab of Professor of Electrical Engineering Sigurd Wagner are using their expertise in flexible electronics to give medical researchers an unprecedented view of brain damage.

Doctors would like to model brain damage in the lab by rapidly stretching nerve cells, but the electronics needed to monitor the effects typically are mounted on glass, which does not stretch. Wagner’s group, including graduate student Wenzhe Cao, has developed a flexible electronic array and is testing it with biomedical engineers at Columbia University.

Brain tissue cultures grown on this flexible material can be stretched to model traumatic injury, and the tissue's electrophysiology can be monitored before, during and after stretching.

 

Small packages: Nanoparticles improve drug delivery

A technique for encapsulating drug molecules in tiny plastic-like coatings shows promise for improving treatment of cancer and tuberculosis, while aiding the laboratory testing of new drugs.

Robert Prud’homme, professor of chemical and biological engineering, developed the fundamental method, called “flash nanoprecipitation,” and has numerous collaborations with companies, medical researchers and engineering colleagues to develop it into therapies and diagnostics.

In one project, Prud’homme is working with Howard Stone, the Donald R. Dixon ’69 and Elizabeth W. Dixon Professor of Mechanical and Aerospace Engineering, as well as Pat Sinko, a professor of pharmacy at Rutgers University, to develop nanosized, medicine-filled particles that accumulate in the lungs, where they deliver concentrated doses of cancer drugs.

Prud’homme also is working with Maryland-based biosciences company Sequella, Inc., and the University of Sydney in Australia to use nanoparticles to deliver anti-tuberculosis drugs to the lungs.

In a separate project, Prud’homme is collaborating with Pennsylvania-based company Optimeos Life Sciences to develop a method for using nanoparticles to track tumor growth in lab animals, which could provide better information throughout a drug trial and avoid the need to euthanize animals to gather data during the course of an experimental therapy.

 

Outsmarting bacteria

Bacteria are survival experts, but Mark Brynildsen, an assistant professor of chemical and biological engineering, is on to their tricks.

In one project, Brynildsen studies bacteria’s ability to enter and exit a quiescent state that makes them impervious to antibiotics. “You’re basically nuking them and they’re OK,” he said. “If we could figure out how they do that we could learn how to kill them” and avoid relapses of infections.

Other work involves understanding and predicting the formation of biofilms, structured colonies of bacteria that pose major problems for prosthetics and other implants. In a third area of work, Brynildsen is developing antibiotics called “anti-virulence therapies” that fight bacteria indirectly by disrupting their interactions with their host.

 

Body language: Low-power devices read signals to stave off health problems

Naveen Verma, an assistant professor of electrical engineering, is designing wearable or implantable electronic devices that monitor brain or heart signals to prevent acute problems and perform long-term assessments in patients with chronic illnesses such as heart disease and epilepsy.

 

Verma collaborates with medical researchers to create devices that analyze large databases accumulated by hospitals and provide information about what to look for in monitoring a patient’s heart and brain activity. He seeks to feed this information into lightweight, low-power devices that patients would wear daily.

The devices would use machinelearning techniques to identify the unique signals from a patient’s body and send a warning to clinicians in advance of a heart attack or seizure. The devices may also initiate treatments, such as electrical stimulation that wards off a seizure.

“The goal of these devices is to transform healthcare from a curative discipline to a preventative or preemptive discipline, yet in a low-cost and scalable way,” Verma said.

Read more articles from the Winter 2012 EQuad News, a publication of Princeton University's School of Engineering and Applied Sciences