The University of Pennsylvania is participating in two National Science Foundation projects designed to advance cyber­physical systems with medical applications. Cyber­physical systems are built from and depend upon the seamless integration of computation and physical components.

One project will combine teams of microrobots with synthetic cells to perform functions that may one day lead to tissue and organ regeneration. The other project will develop a “Cyberheart,” a virtual, patient­specific human heart model that can be used to improve and accelerate medical-device testing.

NSF will support the projects with two five-year awards totaling $8.75 million.

“NSF has been a leader in supporting research in cyber­physical systems, which has provided a foundation for putting the ‘smart’ in health, transportation, energy and infrastructure systems,” said Jim Kurose, head of NSF’s Computer & Information Science & Engineering directorate. “We look forward to the results of these two new awards, which paint a new and compelling vision for what’s possible for smart health.”

Penn is an international leader in embedded and cyber-physical systems research. During the past five years, the Penn Research in Embedded Computing and Integrated Systems Engineering, or PRECISE, Center has received funding totaling more than $30 million from NSF and other sources.

The Penn contingent of the microrobot project will be led by Vijay Kumar, the UPS Foundation Professor with appointments in the departments of Mechanical Engineering and Applied Mechanics, Computer and Information Science and Electrical and Systems Engineering in Penn’s School of Engineering and Applied Science.

Kumar, a former director of Penn’s main robotics laboratory and the GRASP Lab and the incoming dean of Penn Engineering, will join computer scientists, roboticists and biologists from Boston University and the Massachusetts Institute of Technology to develop a system that combines the capabilities of nano­scale robots with specially designed synthetic organisms. Together, they believe this hybrid “bio­-CPS” will be capable of performing heretofore impossible functions, from microscopic assembly to cell sensing within the body.

“The GRASP lab is not just about swarms of flying robots, propelled by batteries and rotors,” Kumar said. “We can apply some of the same principles to swarms of microrobots for applications in biology and medicine.”     

He joins Calin Belta, professor of mechanical engineering, systems engineering and bioinformatics at BU and the project’s lead principal investigator, as well as MIT professor Ron Weiss, who directs the Institute’s Synthetic Biology Center.

"We bring together synthetic biology and micron­scale robotics to engineer the emergence of desired behaviors in populations of bacterial and mammalian cells,” said Belta. “This project will impact several application areas ranging from tissue engineering to drug development."

The project builds on previous research by each team member in diverse disciplines and early proof-­of-­concept designs of bio­CPS systems. According to the team, the research is also driven by recent advances in the emerging field of synthetic biology, in particular the ability to rapidly incorporate new capabilities into simple cells. Researchers so far have not been able to control and coordinate the behavior of synthetic cells in isolation, but the introduction of microrobots that can be externally controlled may be transformative.

In this new project, the team will focus on bio-CPS systems with the ability to sense, transport and work together. As a demonstration of their idea, they will develop teams of synthetic cell/microrobot hybrids capable of constructing a complex, fabric­like surface.

Rahul Mangharam, an associate professor in the Department of Electrical and Systems Engineering and Department of Computer and Information Sciences will co-lead Penn’s contingent in the “Cyberheart” project with Sanjay Dixit, who is an associate professor of medicine at the Hospital of the University of Pennsylvania and director of the Philadelphia VA Medical Center's Cardiac Electrophysiology Laboratories. 

Mangharam is a founding member of Penn Engineering’s embedded-systems-focused PRECISE Center, which conducts research on cyber­physical systems with a variety of applications. Health-related cyber-physical systems, such as wearable sensors and implantable devices, are already being used to provide safer, more cost­effective care and could potentially speed­ up disease diagnosis and aid prevention.

Extending these efforts, Mangharam will join researchers from six universities and centers to develop far more realistic cardiac models than currently exist. Such models are critical to improving the software that governs implantable devices, such as pacemakers, defibrillators and cardiac rhythm therapy devices.

“There is no formal design methodology or open experimental platforms to ensure the correct operation of medical devices within a closed-loop context,” Mangharam said. “The FDA also does not review the safety of the software in medical devices. This effectively prevents software-controlled medical devices from reaching the full potential in providing the best possible patient care and reducing soaring healthcare costs.”

The team’s “Cyberheart” can be used to test and validate medical devices faster and at a far lower cost than existing methods. The models also can be used to design optimal procedures on a patient­-specific heart with fewer risks to the patient.

“Innovative ‘virtual’ design methodologies for implantable cardiac medical devices will speed device development and yield safer, more effective devices, and device-­based therapies, than is currently possible,” said Scott Smolka, professor of computer science at Stony Brook University and one of the principal investigators on the project.

The group’s approach combines patient­-specific computational models of heart dynamics with advanced mathematical techniques for analyzing how these models interact with medical devices. The analytical techniques can be used to detect potential flaws in device behavior early on during the device design phase, before animal and human trials begin. They can also be used in a clinical setting, to optimize device settings on a patient-­by­-patient basis before devices are implanted.

Other co­investigators on the project are Edmund Clarke of Carnegie Mellon University, Elizabeth Cherry of the Rochester Institute of Technology, W. Rance Cleavelan of the University of Maryland, Flavio Fenton of the Georgia Institute of Technology and Arnab Ray of the Fraunhofer Center for Experimental Software Engineering.