Biosensor Detects Brain-Damaging Proteins in Heart Surgery

Glial fibrillary acidic protein sensor (Johns Hopkins University)

Engineers and medical researchers at Johns Hopkins University in Baltimore developed a tiny sensor for technology to detect potential brain damage among patients undergoing heart surgery, particularly children. The team led by Howard Katz, chair of Johns Hopkins’s engineering and materials science department, published its findings in today’s issue of the journal Chemical Science (paid subscription required). The university’s technology transfer office also filed a patent for the invention.

The sensor addresses a problem seen by cardiac surgeons among patients, particularly young children with heart defects, who undergo surgery to correct those defects, only to develop neurological problems later on, as a result of the procedures. Allen Everett, a pediatric cardiologist at Johns Hopkins and co-author of the paper, contacted Katz two years ago about the problem and the need to find a solution for it.

“These are very sick children” says Everett in a university statement, “and we have done a brilliant job of improving overall survival from congenital heart surgery, but we have far to go to improve the long-term outcomes of our patients.” He cites recent studies that some 40 percent of infant cardiac patients will show evidence of brain abnormalities in MRI scans.

That damage, says Everett, is most often caused by strokes triggered when the brain is susceptible to injury, leading to impairment of the child’s mental development and motor skills, delay in learning speech, and hyperactivity. In addition, the problems can take years to appear.

Katz, Everett, and colleagues devised a sensor to detect glial fibrillary acidic proteins believed to control the functioning of astroglial cells in the brain and spinal cord that support the neurons or nerve cells, where fluctuations in glial fibrillary acidic protein levels could serve as an indicator of potential brain damage. The researchers built the sensor on an organic thin film transistor architecture that in other applications (e.g., explosive detection) been found to detect a variety of gases, chemicals, and biological molecules in real time.

Organic thin film transistors have other desirable properties. They are low in cost and require little power. Organic thin film transistors can likewise be made with less complex fabrication techniques, and built into lightweight and foldable products.

The sensor developed by the Johns Hopkins team has a sensing area some 7 mm (about a quarter of an inch) square on each side, with a layer of antibodies on the sensing area to attract glial fibrillary acidic proteins. Reactions of the antibodies affect an electrical current going through the sensor, allowing the current to be measured, thus detecting changes in the presence of glial fibrillary acidic proteins (GFAPs).

In lab tests, Katz and colleagues found the sensor to be quite sensitive. “As far as we’ve been able to determine,” says Katz,,” this is the most sensitive protein detector based on organic thin film transistors.” Katz adds, “It recognized GFAP even when there were many other protein molecules nearby.”

Everett says the sensor, when built into medical  monitors, can provide data allowing surgical teams to adjust their practices to prevent damaging strokes. “We could improve our control of blood pressure or redesign our cardiopulmonary bypass machines, notes Everett. “We could learn how to optimize cooling and rewarming procedures and have a benchmark for developing and testing new protective medications.”

Johns Hopkins says its technology transfer office filed a patent application for the invention. Katz and colleagues are looking for collaborators in industry for further research and development to build the sensor into a working medical device that can be tested with human patients.

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