New non-invasive respiration monitor for newborns wins “People’s Choice” at Pediatric Surgical Innovation Symposium | By Sarah Hansen | December 08, 2014
“Gentler than a kiss.” That’s how Govind Rao described the non-invasive respiration monitor his lab designed for premature newborns at the Pediatric Surgical Innovation Symposium sponsored by the Sheikh Zayed Institute. Rao is Director of the Center for Advanced Sensor Technology (CAST) at the University of Maryland, Baltimore County (UMBC) and Professor of Chemical, Biochemical, and Environmental Engineering.
The new device for monitoring oxygen and carbon dioxide levels in preemies’ blood is safe, fast, and painless—and it already has a market. “I already have a line of doctors waiting to see me,” Rao said. He envisions the invention going global, as he has relationships with doctors in Ethiopia, the Philippines, India, Mexico, and Nepal who are potential partners.
The device Rao and his team created is much safer than current techniques because it is completely non-invasive, removing risks associated with conventional methods that either cause burns or require so many pinpricks the tiny babies need blood transfusions. In clinical trials under David Woo, Assistant Professor of Pediatrics at the University of Maryland School of Medicine, tests on nine newborns showed that the new technique is also accurate: it measured carbon dioxide and oxygen levels with 90 percent accuracy compared to traditional tests.
“I’ve never had something work this well right out of the gate,” Rao said. But he expects it to get even better. “This is something that we haven’t even attempted to model or refine, so once we do more optimization I expect to push the number higher.” The new method is faster, too. Invasive methods take at least 15 minutes, while the new technique takes only about one.
So how does this invention work? A doctor holds a hollow sampling chamber about the size of a penny against the baby’s skin. Two small tubes connect the sampler to a box containing two valves, pumps, and sensors for oxygen and carbon dioxide and then to a nitrogen tank. The doctor initiates the measurement cycle by opening a valve that pumps nitrogen through the sampling chamber to remove residual carbon dioxide and oxygen. When she closes the valve, there’s more carbon dioxide and oxygen inside the baby than in the chamber, so the gases diffuse across the skin into the chamber. The device pumps the chamber contents past the sensors continuously so they can measure the CO2 and O2 diffusion rate into the chamber, which correlates with the amount in the baby’s blood. “Our core innovation was to come up with a little chamber that you put against the skin like a hollow stethoscope, and to evacuate that with nitrogen,” Rao said.
CAST has other projects that target newborns up its sleeve, including a disposable incubator and non-invasive glucose and temperature monitors. All these efforts got started when Steven Falk, the Chief Engineer from General Electric’s maternal health care division visited CAST for a lab tour. He saw a poster on the wall that got him thinking about applications for neonatal health. “He gave me a crash course in the whole field of neonatal needs,” Rao said, and since then, CAST has been developing products to support at-risk newborns around the world. “These technologies allow anyone in the world to get quality care.” That’s the passion of the engineers, scientists, and doctors collaborating with CAST. “We’re using our technical talents to make the world a better place.”
Rao’s pitch at the symposium was strong enough to earn the “People’s Choice” award. Audience members chose Rao’s project as number one among eight finalists for “relevance and clinical significance” and second choice for marketability. It’s true that he brought groupies—about 25 students taking his Survey of Sensors and Instrumentation course at UMBC—but even without their votes the respiration monitor would have been squarely in the top two in both categories.
The project was competing for one of two $50,000 grants from the Sheikh Zayed Institute. CAST wanted the funding to work on improvements for the device, such as a standard band to hold the chamber on the baby’s skin and insure a proper seal or new technology to allow use of a smaller nitrogen tank, which would make the device more portable. However, the judges awarded the funding to two other promising projects.
Rao is glad his students were there to experience the symposium and the competition. It teaches them that you have to keep going, even if you don’t win every time. “Just don’t quit. That’s the main thing,” he said. And they won’t. No one ever said the world of entrepreneurship was “gentler than a kiss.”
About the Author: Sarah Hansen
Sarah Hansen Sarah Hansen earned her bachelor’s degree in Biological Engineering from Cornell University, which she immediately followed with a Master of Arts in Teaching degree also from Cornell. After teaching middle school science at the Holton-Arms School in Bethesda, Md for four years, she entered the master’s program in Biological Sciences at the University of Maryland, Baltimore County. She will graduate in May, 2015 and pursue a science writing career. In summer 2014 she served as the Science Communication Intern at the Smithsonian Environmental Research Center. When her coursework allows, she blogs about research, teaching and events in STEM departments at UMBC at http://my.umbc.edu/groups/helix. She also serves on UMBC’s Graduate Student Association Executive Board and the D.C. Science Writer’s Association Board. In her sparse free time, Sarah plays viola in the UMBC Symphony Orchestra, trains for marathons, and spends time with her family.
What’s New at NCC-PDI ?
The University of Maryland’s A. James Clark School of Engineering hosted the ceremonial groundbreaking of the new A. James Clark Hall at the University of Maryland, College Park, on Friday, Nov. 21. The new building will cultivate transformative new engineering and biomedical technologies to accelerate advancements in human health.
Located at the site of the future building in the Paint Branch Parking Lot, adjacent to the Jeong H. Kim Engineering Building, the event brought together honored guests, dignitaries, and representatives of the University of Maryland and University System of Maryland to celebrate the impact Clark Hall will have on the advancement of biomedical research.
“Our researchers are hard at work on biomedical projects that are staggering in their potential impact—a cure for multiple sclerosis, a cancer vaccine, a magnetic pain reduction system and many others,” said University of Maryland President Wallace Loh. “When complete, this new building will give them the space and facilities to finish the job.”
The 184,000-square-foot building will accommodate the Clark School’s rapidly growing programs and foster collaboration among the many disciplines involved with human health innovation, from bioengineering and mechanical engineering to biology and information technology.
“I’m proud that Maryland continues to be a leader in the biotech industry, and A. James Clark Hall will help us continue to build the skilled workforce we need to remain competitive, support groundbreaking advances in the biomedical and engineering fields, and attract additional economic opportunities,” stated Congressman Steny Hoyer (D-Md.). “This world-class facility will not only attract faculty and students, but it will also ensure that the University of Maryland remains at the forefront of engineering and biomedical technologies to advance human health innovation. I look forward to the new opportunities for federal research partnerships and will continue to support significant research advancements at the University of Maryland and throughout our great state.”
Clark Hall will facilitate world-class research and educational programs, offering state-of-the-art laboratories, student project space, and a new home for the Fischell Department of Bioengineering and the Robert E. Fischell Institute for Biomedical Devices. Located within an hour’s drive from many of the nation’s top bioscience research forces, including the National Institutes of Health (NIH), Walter Reed National Military Medical Center, and the University of Maryland School of Medicine in Baltimore, Clark Hall will serve as a central hub for new partnerships for organizations throughout the Maryland and Washington, D.C. region.
“This new start-of-the-art facility for bioengineering research and education will attract exceptional faculty and students to Maryland, support leading edge research and education, and benefit the state of Maryland’s innovation ecosystem through the creation of new companies and new jobs,” said University System of Maryland Chancellor William E. Kirwan.
While the vision, design, and development of Clark Hall brought together the minds of University of Maryland and Clark School administrators, faculty, and staff, as well as a team of talented architects and builders, the plans could not be executed without the generosity of two benefactors – A. James Clark (B.S. ’50) and Dr. Robert E. Fischell (M.S. ’53, Honorary Sc.D. ’95).
Clark’s steadfast commitment to undergraduate education moved him to endow a fund for undergraduate scholarships in 1994, and in 2005, a new A. James Clark Scholarship Fund to provide financial support to undergraduate engineering students based on merit, need, and diversity. In recognition of Clark’s philanthropic leadership, the University of Maryland School of Engineering was named the A. James Clark School of Engineering. Inspired by his strong interest in the promise of biosciences and biotechnology, Clark made a generous gift to support the design and construction of A. James Clark Hall, which will be the 27th structure built by Clark Construction on the University of Maryland campus.
“Mr. Clark’s contribution to this new building and the University of Maryland is not only a symbol of commitment to his alma mater, but a symbol of his vision for the future of human health,” said Darryll Pines, Clark School Dean and Farvardin Professor.
Fischell is the inventor behind major medical breakthroughs, including highly flexible, drug-eluding coronary stents, the first implantable insulin pump, and a magnetic pulse device for treating human pain ranging from migraine headaches to backaches. His latest inventions include the first rechargeable pacemaker for cardiac patients, an implantable device that warns a patient and medical personnel of a heart attack at the very first sign of its start, and a neurostimulator implanted in the skull that can detect abnormal electrical activity in the brain and correct it before a seizure occurs.
In 2005, Fischell and his family helped to establish the Fischell Department of Bioengineering and the future Robert E. Fischell Institute for Biomedical Devices at the University of Maryland, and, most recently, Fischell committed a generous gift toward the establishment of A. James Clark Hall.
“Dr. Fischell’s commitment to the commercialization of health innovations has made an enormous impact on society, and the Fischell Institute for Biomedical Devices will help our students and faculty to take part in the improvement of human health worldwide,” said William Bentley, the Robert E. Fischell Distinguished Professor of Engineering and Chair of the Fischell Department of Bioengineering.
Slated to open in 2017, Clark Hall was designed by a team of architects at Ballinger and will be developed by Clark Construction Group.
More information about A. James Clark Hall is available online.
Keynote_Childrens_3144With the second annual symposium, held on October 24, 2014, the Sheikh Zayed Institute for Pediatric Surgical Innovation brought together key leaders from the National Institutes of Health, the Food and Drug Administration, medical device industry, law firms, pediatric societies and advocacy groups, along with scientists, engineers, clinicians and policy makers.
The symposium’s keynote address was delivered by Margaret A. Hamburg, MD, commissioner of the FDA. The event drew more than 220 attendees and was held at The Newseum in Washington, D.C. The program included panel discussions on the clinical and regulatory pathways for pediatric devices, lessons to be learned from pediatric drug development, growth capital for pediatric innovation and coverage reimbursement from the payor perspective.
Prize-Winners_Childrens_3354As part of the Symposium, in a competition, two pediatric medical device innovators, Velano Vascular and REBIScan, were selected from eight finalists to each receive a $50,000 Sheikh Zayed Award in Pediatric Device Innovation. A total of 56 submissions from five countries were received for the competition. The finalists each made five-minute presentations to the symposium audience and then responded to judges’ questions.
Sharing their device for the first time in a public forum, the team from Velano Vascular, of Philadelphia and San Francisco, presented a novel innovation that enables safe, effective needle-free blood draws for hospitalized children. Award-winner REBIScan, of Cambridge, Mass., presented a handheld vision scanner for the eradication of amblyopia (“lazy eye”).
In its first year of operation, the NCC-PDI funded five device companies/teams as part of the first Annual Pediatric Device Innovation competition held on April 3, 2014. These winning companies/teams and their projects are:
- Vittamed Corporation | Non-Invasive Intracranial Pressure (ICP) Meter Head Frame Modification for Children | PI: Remis Bistras, PhD, MBA | Award: $50,000
- Vasoptic Medical, Inc. and University of Maryland Baltimore | Development of Laser Speckle Contrast Imaging as a Non-Invasive Diagnostic for Retinopathy of Prematurity | PIs: Janet Alexander, MD and Jason Brooke, MSE, JD | Award: $50,000
- Procyrion, Inc. | Development of a Novel Catheter-Deployed Cavopulmonary Support Device for Management of Single Ventricle Physiologies Associated with the Fontan Procedure | PIs: Omar Benavides, PhD and Jason Heuring, PhD | Award: $50,000
- Otomagnetics LLC and Children’s National Health System | Magnetic System to Direct Therapy to Middle Ear Infections in Children | Benjamin Shapiro, PhD and Diego Preciado, MD, PhD | Award: $50,000
- University of Maryland Baltimore, Center for Advanced Sensor Technology | Engineering Optimization of a Low-Cost Multifunctional Incubator | PI: Govind Rao, PhD | Award: $25,000
In addition to seed funding, in its first year, the NCC-PDI provided consultation to 36 projects at different stages of device development lifecycle. These consultations included expert advice in the following.
- Patent Applications Filed: 20
- Initial Prototypes Generated: 18
- Advanced Prototypes Generated: 18
- Licenses or Option Agreements Executed: 3
- Animal Studies Advised: 15
- Other Preclinical Studies: 16
- Human Studies Advised: 15
- HDE/HUD: 5
- IDEs Advised: 5
- 510(k) Applications Advised: 7
Building on top of the infrastructure provided by this FDA Pediatric Device Consortium Grant, The NCC-PDI team, its affiliate members, and external institution was able to leverage up and obtained competitive funds from various sources totaling $1.6 million.
Lysosomal storage diseases (LSDs) are rare inherited metabolic disorders that result from defects in lysosomal function, triggered when a particular enzyme exists in too small an amount or is missing altogether. When this happens, excess products destined for breakdown and recycling instead accumulate in the cell. As a result, these genetic defects impair lysosomal degradation, and this impairment often results in fatal cellular and tissue dysfunctions, such as those illustrated in LSDs.
Although the incidence of LSDs is still relatively low – about 1:2000 live births – the financial burden to families and the health system is overwhelming. The cost of current therapies averages $150,000+/per patient-year and yet, such therapies are mostly suboptimal in alleviating these chronic conditions.
While LSDs account for approximately 50 fatal conditions, they are one of the best examples of genetic diseases for which treatment has become clinically available, according to Silvia Muro, Associate Professor with the Fischell Department of Bioengineering and the Institute for Bioscience and Biotechnology Research at the University of Maryland.
One such example of available treatment is that of enzyme replacement therapies (ERTs) by infusion of recombinant enzymes.
Recombinant enzymes are administered via frequent systemic infusions – approximately every two weeks – and require patients to travel to reference centers and endure repeat hospitalizations. This treatment therefore increases cost, risk, and burden to patients.
Additionally, after one decade of its clinical implementation, the success of ERTs by infusion of recombinant enzymes is restricted to few diseases that affect only visceral organs – liver, spleen and kidneys – since injected ERTs access these organs via natural mechanisms of blood clearance.
“This strategy is not practical for most other diseases due to suboptimal enzyme accumulation in other organs, poor transport into tissues across blood-to-tissue barriers, and generation of antibodies against the injected enzymes,” Muro said.
As such, Muro and members of her research team are working toward achieving encapsulatation of recombinant enzymes in protective nanocarriers that are targeted to cell surface markers involved in transport, such as the intercellular adhesion molecule involved in natural blood-to-tissue passage of white blood cells. Their published results using animal models show that enzyme delivery is markedly enhanced throughout the body using this strategy, which they hope will help lessen the burdens patients face and improve the effectiveness of treatment for LSDs. Muro’s patent application on this technology was issued this past November.
In addition to causing cellular and tissue dysfunctions, lysosomal storage appears to alter endocytosis, a cellular process where cells engulf in membranous compartments and subsequently internalize extracellular materials and membrane components.
Many basic functions in the body depend on endocytosis, including uptake of nutrients and signaling molecules by cells, defense against pathogens and toxic substances, and recycling of components located at the interface between the cell and extracellular environment. Endocytosis is also commonly used to achieve intercellular transport of therapeutics, Muro said.
“Endocytosed drug carriers usually traffic to lysosomes, where drugs are released and carriers are expected to be degraded in order to avoid side effects,” she said. “Therefore, lysosomes are key to drug delivery. Lysosomes are also key to cell function including catabolism of macromolecules, recycling of membrane components, and autophagy.”
Whether accumulation of drug carriers – or their component – within lysosomes in cells causes similar disruptions to those observed in lysosomal diseases is yet unknown, Muro said. But, emphasized by Muro’s studies on lysosomal diseases, the field of drug delivery recognizes that this is an important question in understanding – and minimizing – potential side effects of drug delivery systems.
“If we understand for how long carriers or carrier-derived components accumulate in lysosomal compartments in cells and what their effects are regarding lysosomal functioning, we could optimize the design of materials used for fabrication of drug carriers, their clearance within cells, and their dosage and administration regime, while reducing their size effects,” Muro said.
- Onsite Tools and Technologies for Heart, Lung, and Blood Clinical Research Point-of-Care STTR (R41/R42) • RFA-HL-14-017
- Onsite Tools and Technologies for Heart, Lung, and Blood Clinical Research Point-of-Care SBIR (R43/R44) • RFA-HL-14-011
- HHS Changes Standard Due Dates for SBIR/STTR Grant Applications • NOT-OD-15-038
- Use of 3-D Printers for the Production of Medical Devices (R41/R42) – Phase I and Fast-Track http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-15-023.html
- Use of 3-D Printers for the Production of Medical Devices (R43/R44) – Phase I and Fast-Track