Solving an Unmet Pediatric Clinical Need May Bring Big Dividends for ECMO

Insights from an MD / PhD and Prolific Innovator – Georgia Tech’s Dr. David Ku

According to the NIH, more than 60,000 pediatric patients including newborns, infants and children under 18 years of age have been reported to be supported by extracorporeal membrane oxygenation (ECMO) globally every year. “Modern tertiary and quaternary medical-surgical and cardiac Pediatric Intensive Care Units (PICU) rely on the ability to provide ECMO support to children with life-threatening conditions leading to cardiopulmonary failure or cardiac arrest.”

Dr. David Ku

While thrombosis, or clotting of blood, keeps us from “bleeding out” during acute, often traumatic events, and is one of the fastest, strongest bonds in biology, it can also cause heart attacks and strokes.

“ECMO technology, and the machines themselves, were initially designed for supporting adults in acute care settings,” said Dr. David Ku, Regents Professor in Mechanical Engineering and Lawrence P. Huang Chair for Engineering  Entrepreneurship in the Scheller College of Business at Georgia Tech. “Early ECMO technology suffered from poor outcomes in adults. The machine and system had significant clotting in its circuitry. ECMO can save a life, but the risk of creating a stroke from these clots is poor.”

Dr. Ku’s interest in the intersection of physics and health took a career turn in the early 1990s as the field of biomedical engineering was just beginning.

“Biomedical and biomechanical engineering perfectly fit my proficiency in mathematics and physics with the strong urge to improve the human condition in some tangible way,” Dr. Ku said.

His early work on unmet clinical needs in his area of expertise involved myopia and the human eye at Harvard. In graduate school, he switched to the mechanics of blood flow and how abnormal flow can cause heart attacks and strokes. How can we use physics to solve unmet clinical needs? How does blood flow? Why do certain arteries get clogged and not others? These questions have been integral to Dr. Ku’s work for decades.

As ECMO found greater clinical success in the pediatric domain thanks to leaders like Dr. Kevin Maher, the need to solve persistent ECMO clotting problem began to rise to the fore.

ECMO (extracorporeal membrane oxygenation) machine, hooked up to a pediatric patient at MUSC Shawn Jenkins Children’s Hospital. Image credit: Medical University of South Carolina

“No one had studied the thrombosis circuitry issue in ECMO machines as of 2016,” Dr. Ku said. “I told Kevin, give us your circuits after a clot and we’ll find the problem. The dominant hypothesis at that time was that the tubing was the culprit, given what we knew about clotting tendencies on artificial surfaces and the large amount of that surface area in the ECMO system’s tubing.

In contrast, our work with three pediatric centers discovered 80% of all clots in the ECMO circuit existed at the connectors, not on the tubing. We determined that biochemistry was not the cause of the clotting at the connectors; it was physics. It then became a relatively simple fluid mechanics exercise to eliminate the clots at the connectors. The old connectors created a dead-zone of stagnant blood flow. A certain amount of clotting at these connectors was always a near certainty.”

Drs. Susan Shea and Ku’s new connector design and geometry eliminates that stagnant flow completely. These connectors eliminate most of the clots in validation tests in a number of in-vivo models with the team at GCMI’s T3 Labs.

“The ECMO connector technology proves that effective solutions can be simple, not complex and elaborate in their design,” Dr. Ku said. “We have more evidence available than most FDA 510k submissions. We just need a partner or investor to help carry it over the manufacturing finish line, including ‘Good Manufacturing Practice’ regulatory requirements for a submission that should have large market potential for companies with ECMO devices in their portfolio.”

Learning from a true industry leader

When asked what other engineers or researchers should know about challenges specific to the commercialization process, especially for pediatric technologies, Dr. Ku said “One can have a commercial focus, but the need to create quality data and evidence is paramount. In my opinion it is better to focus on the unmet need and generate quality evidence prior to incorporating. Once you have a good market opportunity, good efficacy data, and regulatory pathway confidence, then forming a company and enlisting investors makes more sense.

“Secondly, watch out for what some describe as ‘vanity patents.’ Earning a patent does not mean freedom to operate, nor does it mean your technology has sufficient competitive advantage to displace existing products. Thus, the new patent may have little to zero value.

When asked what advice would Dr. Ku give aspiring engineers, physicists or those studying in fields with high potential applications to unmet clinical needs, he said, “First, work on clinically relevant projects with large numbers of patients. Focus on improving the lives of patients, and the clinicians that care for them, by working on common clinical problems. Second, strive for simple solutions that can be scaled. Just because one likes solving complex problems, that does not mean devices need to be elaborate to solve unmet clinical needs efficiently, effectively.”

We thank Dr. Ku for sharing his story and insights with the Georgia Tech Pediatric Technology community.