December 1, 1998

Engineer's Miniature Heart Sensors Aid Cardiac Research

Dr. Troy Nagle, right, and Jason Fiering, left, have developed a sensor array for mouse hearts that is much smaller than this array created for dog hearts. The new mouse heart arrays will aid cardiac research.

What could a heart smaller than a pencil eraser have to do with preventing human heart problems? At NC State University and the University of North Carolina at Chapel Hill (UNC-CH), tiny hearts could mean a big improvement in the time it takes to study treatments for heart defects and disease.

NC State researchers, Dr. Troy Nagle, professor of electrical and computer engineering, and Jason Fiering, research associate, are creating very small flexible heart sensor arrays for use on mouse hearts. The arrays are carefully arranged electrical sensors that measure electrical wave fronts on the surface of the heart.

The tiny sensor arrays from NC State will help Dr. Timothy Johnson, associate professor of biomedical engineering and medicine at UNC-CH, and Dr. Wayne Cascio, associate professor of medicine at UNC-CH, study how the electrical impulses of the heartbeat spread through the heart and how the electrical activity is changed by medications and disease.

The researchers use a miniature heart-lung machine to supply blood to the tiny, isolated mouse hearts. The machine allows researchers complete access to the heart for study and maintains the working heart in excellent condition for long periods of time.

"Traditionally, cardiac research has been conducted on dog or pig hearts," says Nagle, who also holds a degree in medicine. "We have worked with researchers at Duke University to develop large sensor arrays for the study of the larger hearts. The sensor arrays designed for pig hearts are typically 120 microns thick--a human hair is about 100 microns thick. The arrays we are designing for the mouse hearts are much thinner--around 20 microns, about one-fifth the diameter of a human hair. At this thickness, the material that supports the sensor array is about the consistency of plastic wrap."

Nagle explains that the challenge is to create a sensor array that is tiny enough to fit the small hearts, flexible enough to withstand the rapid beating of mouse hearts--about 350 beats per minute--and strong enough to carry the numerous cables and wires that deliver the information from the sensors to the computers. In the beginning, the research team used rubber castings of mouse and rat hearts to approximate the size and shape of the hearts. Some are no larger than a water droplet. Recently, they have been using real hearts and have found handling the delicate tissues to be quite a challenge.

The challenge may well be worth the effort. Molecular biologists are now able to engineer mice and rats with specific genetic traits or conditions, giving researchers a new and powerful tool to study mechanisms of disease. The NC State and UNC-CH researchers are hopeful that the use of these new genetic models in conjunction with their experimental technique will provide new insights into the cause of disease and treatment strategies that will benefit humans.

"The advantage to creating sensor arrays for mouse hearts is the ability to manipulate the genetic makeup to create a specific condition for study," says Johnson. "In the larger hearts, this is not possible because transgenic or knockout animals are not available in larger species.

"The genetically engineered mouse hearts would significantly reduce research time since mice reproduce more quickly than dogs or pigs. Using mice, a generation of study will take less than two months. The same generation in dogs or pigs would take more than a year."

Once Nagle and Fiering have created the mouse-sized sensor array, Johnson and Cascio will use this new technology to study the electrical behavior of the mouse heart. The goal of these early studies will be to characterize the electrical behavior of the mouse heart and place it in the context of the information available on the electrical behavior of dog and pig hearts.

"The possibility of using mouse and rat hearts in cardiac research gives us many new opportunities," says Nagle. "The development of transgenic mice adds important capabilities and enables us to conduct more specific research."

If the research is successful, the goal of the NC State/UNC-CH team is to eventually become one of the National Institutes of Health's Research Resources--a nationwide series of laboratories that supply specific technology to researchers--and supply the tiny flexible heart sensor arrays to cardiac researchers across the nation. The NIH, through its research resource program, provides funding to support the development and fabrication of the technology of wide appeal to the medical research community. The sensor array research conducted by Nagle, Fiering, Johnson and Cascio is currently supported by a two-year NIH grant.

At the end of their first year of research, the team is close to having a workable prototype for testing. A few final design modifications are underway.

Technical contacts: Dr. Troy Nagle, (919) 515-3578, t.nagle@eos.ncsu.edu

Dr. Timothy Johnson, (919) 966-5201, tjohnson@card.unc.edu

Dr. Wayne Cascio, (919) 966-5201, wcascio@ischemia.card.unc.edu

Media contact: Jennifer Weston, (919) 515-3848, weston@ncsu.edu

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