An Innovative Unbound Bilirubin Assay to Identify Bilirubin-Induced Neurological Dysfunction (BIND) Risk as Part of a Comprehensive and Novel Point-of-Care Newborn Screening Panel

ABSTRACTAn Innovative Unbound Bilirubin Assay to Identify Bilirubin Induced Neurological DysfunctionBINDRisk asPart of a Comprehensive and Novel Point of Care Newborn Screening PanelFast Track SBIRNeonatal hyperbilirubinemiaor elevated bilirubinoccurs in overof newborns and results in jaundiceWhen treated promptlyhyperbilirubinemia is usually benign but if left untreated elevated bilirubin levels can result in bilirubin toxicity and severe neurological dysfunctionDespite routine newborn screening for elevated total serum bilirubinTSBlevels as an indicator of hyperbilirubinemiaunderlying causes such as glucosephosphate dehydrogenaseG PDdeficiency and the risk for bilirubin induced neurological dysfunctionBINDremain an unaddressed public health concernWhile many enzyme dysfunction disorders are screened in U Sstate public health laboratories as part of the normal dried blood spot newborn screening processG PDandapos s relatively high incidence and its association with neonatal jaundice make it uniquely suited to be both screened and severity assessed at the point of birthWith existing fundingwe are developing FINDERa small footprint digital microfluidic device for near patientmedium risk assessment testing in a hospitalthe launch panel will assess for hyperbilirubinemia risk by measuring TSBalbumindirect bilirubin and G PD deficiencyWe expect to submit the FINDER device and launch panel of assays for FDA review within the next yearThis Fast Track project will focus on two key factors that are missing from FINDER for comprehensive G PD screening and BIND risk assessmentthe presence of the challengingbut vitally importantunbound bilirubinUBassayanda digital architecture to support the simplicity requirements of CLIA waived screening and the necessity to integrate screening results to an eventual large scale databaseThe ability to measure unbound bilirubin will allow clinicians to have a more complete understanding of bilirubin binding and thus the risk for bilirubin toxicityneurotoxicityincluding BIND and kernicterusresult from poor bilirubin binding in plasmaPhase I aims will focus on assay development and preliminary digital architecture implementation while Phase II aims will center on a method comparison of the unbound bilirubin assay to a predicate deviceThe resulting assay panel and platform will be field tested atclinical sites with a high percentage of G PD deficient patientsThis product has the potential to be a paradigm shift in the U Sfor near patientuniversal biochemical screeningnormally delegated to state public health laboratoriesand can be used in the hospital or physicianandapos s office to identify newborns who might need to be admitted to the hospital for prompt treatmentDespite its prevalence and critical role in neonatal hyperbilirubinemiaG PD enzyme deficiency is rarely screened in the U Shemolysiscrisistriggersinadequate treatment with phototherapyand challenges related to follow up all put neonates at risk of BINDThe association of G PD deficiency with BIND risk is indisputableand a comprehensive screening panel that includes a G PD assay and a combination of UBalbumin and TSB measurements can assess bilirubin binding capacity in the newborn to determine BIND risk PROJECT NARRATIVE Neonatal hyperbilirubinemia occurs in overof newborns and results in jaundiceWhen treated promptly with phototherapy or exchange transfusionhyperbilirubinemia is usually benign but if left untreatedelevated bilirubin levels can result in bilirubin toxicity and severe neurological dysfunctionOne common factor towards hyperbilirubinemia is glucosephosphate dehydrogenaseG PDdeficiencyG PD deficiency is quite prevalent but remarkably is not routine screenedHigh levels of unconjugatedunbound bilirubincombined with the presence of G PDcan lead to bilirubin induced neurologic dysfunctionBINDand irreversible kernicterusIt is imperative that a comprehensive assessment program is in place for evaluation at the point ofcare to identify G PD deficient neonates at risk for BIND so that informedprompt clinical decisions can be made