Multiplex Platform for Point-of-Care Newborn Screening of Hyperbilirubinemia

ABSTRACT Multiplex Platform for Point-of-Care Newborn Screening of Hyperbilirubinemia (SBIR Phase IIB) Hyperbilirubinemia (jaundice) affects more than half of all newborns and is typically benign if identified and treated promptly. Without proper treatment, high bilirubin leads to serious neurological dysfunction including neuro-motor, auditory, speech, cognition, and language disturbances. Rapid identification of newborns at risk for severe hyperbilirubinemia (HBR) is therefore a crucial component of standard newborn care. HBR risk assessment typically involves qualitative evaluation of transcutaneous bilirubin (jaundice) or quantitative measurement of total serum bilirubin (TSB); however, these methods fail to identify other critical risk factors such as glucose-6-phosphate dehydrogenase (G6PD) deficiency and altered bilirubin-albumin binding. Together, HBR and other risk factors significantly increase the chance of neonatal readmission to the hospital for elevated bilirubin levels, which must often be addressed through phototherapy, or in rare cases, exchange transfusion. To address the shortcomings of current newborn HBR screening methods prior to initial hospital discharge, we successfully developed a point-of-care digital microfluidic platform (FINDERTM) that simultaneously measures TSB, G6PD enzyme activity, and albumin from a single drop (50 µL) of whole blood. The results of our panel provide a comprehensive profile of HBR risk with a total testing time of 15 minutes. Sample preparation (plasma separation or blood lysis) and all test steps are automated on disposable cartridges that are preloaded with assay reagents, calibrants, and buffers. Throughout Phase I and II of this project (HD072853), the FINDER digital microfluidic platform and HBR assays were fully developed in collaboration with leading neonatologists and bilirubin specialists at Stanford and Duke Universities. Our fully functioning instrument and cartridge will exit development stage in early 2019. The TSB, G6PD, and albumin FINDER tests have undergone rigorous preliminary analytical evaluation, including reagent stability and shipping studies, and beta testing in the field. The proposed Phase IIB project will support full CLSI analytical validation and a rigorous clinical validation necessary to obtain FDA clearance for the testing system. We are actively engaged in pre-submission communications with the FDA regarding our validation protocols and designed the validation studies to meet 510k requirements based on single test predicate devices for each analyte. We are working closely with clinician partners to optimize the platform for the initial intended users in hospital laboratories. Funding through this Phase IIB mechanism will complete the developmental path for our FINDER HBR platform, from concept to market through anticipated FDA authorization. There is currently no single point-of-care testing platform on the market that can support rapid testing of TSB, G6PD, and albumin. Our FINDER hyperbilirubinemia testing platform has been purposefully designed to meet the technical requirements for low complexity testing in newborns and addresses a critical unmet need in the field.PROJECT NARRATIVE Neonatal hyperbilirubinemia occurs in over 50% of newborns. When treated promptly with phototherapy or exchange transfusion, hyperbilirubinemia is usually benign, but if left untreated, elevated bilirubin levels can result in bilirubin toxicity and severe neurological dysfunction. Our Phase IIB SBIR project builds upon our success developing the only single point-of-care testing platform to support rapid, low-blood volume testing of total serum bilirubin, glucose-6-phosphase dehydrogenase (G6PD), and albumin. The validation and commercialization of this product will allow for critical and comprehensive assessment of risk for complications related to hyperbilirubinemia in newborns and will potentially lead to improved health outcomes.