A tiny device that can test extremely small blood samples was used to help save the life of a young girl just before Christmas. Although the device, developed by a U-M team including two University of Mott pediatric intensivists, Timothy Cornell, MD, and Thomas Shanley, MD and two engineers, Jianping Fu, PhD, and Katsuo Kurabayashi, PhD, is still in the research phase, its use was allowed under the FDA’s “Expanded Access” program to help treat a young cancer patient whose organs were shutting down.
How the device came into use for this patient
Just before Christmas in 2014, the device was put into action after a chance encounter in a hospital hallway. John Levine, MD, Professor of Pediatrics, had been treating a pediatric cancer patient who was experiencing a catastrophic immune system reaction called a cytokine storm and her organs were beginning to shut down. She had been receiving experimental cancer treatment as part of a study led by Children’s Hospital of Philadelphia (CHOP). CHOP is a member of the Clinical & Translational Science Awards consortium, as is the Michigan Institute for Clinical & Health Research (MICHR). While the results of that study have been promising, one of the side effects of the treatment can be a “cytokine storm.” Dr. Levine’s patient was in serious trouble and needed treatment that would best be guided by the blood level of the cytokines – but time was running out. Dr. Levine had worked with Dr. Cornell over the past 10 years, and was aware of the device that Dr. Cornell and his team were developing. In fact, they had previously talked about how Dr. Levine’s young patient might benefit from the information that the test could provide.
On the evening of December 22, the two doctors bumped into each other in a hospital hallway as Dr. Cornell was leaving for the evening. Dr. Levine asked if he could use Dr. Cornell’s device to get results for the patient. “It happened because we were walking down the hall and John said ‘Hey, I need you! Can you really measure cytokines with that device like you said you can?’”
Dr. Cornell contacted MICHR’s IND/IDE Investigator Assistance Program (MIAP) team. MIAP facilitated rapid FDA approval through the Expanded Access program, allowing Dr. Levine to focus on his patient and Dr. Cornell to focus on the test. As a result, Dr. Levine was able to use the information provided by the test to support adjustments to the patient’s course of treatment and immune therapy. Her condition rapidly improved because of the therapy and she was eventually discharged home. She is back in school and is doing well at home.
More about the device
Previous tests have required quantities of blood too large for use in pediatric patients. This test requires only a miniscule amount – one microliter of blood (a drop of blood is equal to 50 microliters).
Although the immune system cannot be monitored directly, this device provides a way to understand what the immune system is doing by measuring cytokines in the blood. Results from the new device are available in about 20 minutes, compared to several days through traditional blood analysis for cytokines. Once the cytokine levels are known, doctors can adjust treatment and increase the likelihood of a better outcome for the patient.
The idea for the device surfaced after a MICHR lecture several years ago. The lecturer was a mechanical engineer, Dr. Jianping Fu, who talked about his work with microfluidic devices. Drs. Cornell, Fu, and Kurabayashi, who is also a mechanical engineer, spoke after the presentation. Along with Dr. Shanley, they began a project for which they later received funding through a MICHR pilot grant and subsequent funding from the National Institutes of Health.
After attending a Fast Forward Medical Innovation (FFMI) course in 2014, Dr. Cornell realized that the device had potential to guide therapy without further revisions. The team decided to break it off from the main project and focus on the development of the cytokine measurement device over the next 4-6 months.
Moving from research use to clinical application
Because the device is still in the research stage and had not been approved for use in making clinical decisions, the patient’s blood could be tested, but the results could not be shared with her medical team without FDA approval. Once Dr. Cornell agreed that the device could be used for this patient, the medical team contacted MIAP for assistance in navigating the complex FDA Emergency Access approval process. It was two days before Christmas and many U-M staff members had already left for the upcoming holiday break, so Dr. Cornell was skeptical about getting the device’s use approved in time to help the patient.
However, the MIAP team, led by Kevin Weatherwax, was available and acted quickly. Mona Moore and Jeanne Wright worked with the FDA to get the necessary approval, a process that also included working closely with Moni Weber, Pediatric Intensive Care Unit Clinical Research Program Manager, to complete an emergency use Institutional Review Board (IRB) application for review and approval along with a parental consent document. Pediatric Intensive Care research technicians Walker McHugh and Kelli McDonough and Mechanical Engineering post-doc Pengyu Chen worked to ensure the device and device reader were ready and that the blood from the patient was collected and processed as quickly as possible.
“We were all anticipating the day we could use the device to help a patient, but we weren’t planning on it happening before FDA approval,” Dr. Cornell says, “so the results took a few hours compared to the usual 20 minutes because time was needed to activate the device and calibrate the device reader.”
“We pulled it off because of a true team effort. Everybody knew his or her individual responsibility, and everyone just did what they needed to do,” Dr. Cornell said. “They’re trained at it, they do it well, they know the regulations, and every step along the way people worked together to do what was best for the patient.”
Dr. Cornell says that while he is encouraged by this first clinical application of the device, there are some development factors to work through, such as making the detection system a little more user-friendly, ensuring that enough devices can be manufactured, and finding funding for completing the regulatory and commercialization process for the device. He has filed for patent protection and is working with FFMI and the Coulter Foundation to navigate the next steps in the commercial development of the device. U-M Tech Transfer is seeking commercialization partners to help bring the technology to market so that others can benefit.
Device Achieves Results in 20 Minutes
“One of the biggest issues we see in pediatrics and all of medicine is sepsis, an overwhelming infection that causes a dysregulation of the immune system,” said Timothy Cornell, MD, Assistant Professor of Pediatrics at U-M. “But we really have no way of rapidly monitoring the immune system itself.”
This device, developed by a multidisciplinary team led by Drs. Cornell, Shanley, Fu and Kurabayashi, is a microfluidic device that uses a miniscule amount of blood – a mere microliter – to achieve test results in 20 minutes. It is a laboratory-developed assay that measures a panel of cytokines, including TNF, IL4, IL6, IL10, and Gamma IFN. These test results can then be used to influence therapy for patients who are experiencing dysregulation of the immune system.
“The reason we want to be able to develop our assay device is to guide therapy in our patients,” Dr. Cornell said.
“Targeting therapies can really change outcomes for critically ill kids.”