Multiplex platform for point-of-care newborn screening of hyperbilirubinemia

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ABSTRACT Multiplex Platform for Point-of-Care Newborn Screening of Hyperbilirubinemia (PAR-13-090) Neonatal jaundice is a frequent condition which, when unmonitored or untreated, can lead to severe neonatal hyperbilirubinemia (HBR) and associated morbidities. Following guidelines set by the American Academy of Pediatrics, most babies in the U.S. are screened for hyperbilirubinemia by testing bilirubin levels as part of routine newborn screening, which identifies those neonates most at-risk for progressive HBR. Testing is performed near the patient due to bilirubin photolability and the need for urgent treatment prior to hospital discharge. There is currently not a single uniform test for HBR; some hospitals test total serum bilirubin (TSB) levels (laboratory-based) and others test transcutaneous bilirubin (TcB; point-of-care). Significant shortcomings for both these tests are large blood sample (~15 drops of blood) required for TSB, and the inaccuracy and qualitative nature of TcB. In addition, other markers for hyperbilirubinemia, including testing for glucose-6- phosphate dehydrogenase (G6PD) deficiency and bilirubin binding capacity, are not part of routine newborn screening. The few states that do offer newborn G6PD screening utilize molecular screening, the results of which are reported too late to impact the clinical course of any neonate with hyperbilirubinemia. To minimize testing blood volume and provide a rapid test that is both sensitive and thorough, we propose to develop a comprehensive hyperbilirubinemia testing panel using digital microfluidics. Our device would revolutionize near-patient newborn screening for hyperbilirubinemia by 1) bringing the accuracy of the TSB test to the newborn nursery and 2) combining with the point-of-care convenience of TcB using just a single drop of blood. In addition, our panel will provide the G6PD status and bilirubin binding capacity as secondary markers for a more complete picture of hyperbilirubinemia status, which if known earlier, will change the clinical course and more importantly, avoid re-hospitalizations. Jaundiced newborns are not discharged from the hospital until TSB results are known; our rapid and comprehensive test will enable quicker time to result. In Phase I, we used a disposable digital microfluidic cartridge to demonstrate technical feasibility for an expanded bilirubin testing panel from whole blood that included TSB, G6PD, albumin, carboxyhemoglobin, and bilirubin binding capacity. We challenged our assays through key method comparisons using discarded whole blood samples. The proposed Phase II project will refine assay development by multiplexing the key three assays (TSB, G6PD deficiency and bilirubin binding capacity) on a single cartridge, developing an on-board reagent storage method, and fully implementing a device to be used near the patient. Analytical validation along with a clinical evaluation at Duke University and Stanford University will demonstrate optimal system performance. The final product will be a single platform for comprehensive hyperbilirubinemia testing using low blood volumes; the target market will initially be hospitals and smaller clinics or pediatrician offices.