Comprehensive, Near Patient Assessment of Severe Hypoglycemia in Newborns Using Low Blood Volume

Hypoglycemia is the most common metabolic disorder in newborns and places the neonate at increased risk of seizures and permanent brain injuryThe etiology of severe neonatal hypoglycemiawhich affects aroundnewborns each year in the U Sis complexwith underlying causes including hyperinsulinismcortisol and or growth hormoneGHdeficienciesand defects in glycogen metabolismComprehensive evaluation of these physiological pathways is essential to guide appropriateeffective medical interventionsHoweverthe current panel of laboratory assays requires relatively large volumesmL or moreof whole bloodmaking newborn assessment challengingparticularly in preterm newbornsMore importantlyroutine turnaround times for these assays may behours or moreleading to critical delays in life saving treatmentThe overall goal of this Fast Track SBIR project is to develop a comprehensive near patient digital microfluidic systemFINDERfor the rapid assessment of severepersistent hypoglycemia disorders in newborns using microliter volumes of whole bloodFINDER will accept single use cartridges and will multiplexassays for the detection of insulincortisolgrowth hormoneglucosehydroxybutyrate and free fatty acids using andltL of whole blood for all assaysRun time will be approximatelyminutesThe team at Baebies will collaborate with leading clinical investigators in NeonatologyDrMichael Cottenand Pediatric EndocrinologyDrMichael Freemarkat Duke University on this projectThe system proposed herein addresses a critical unmet clinical need for rapid testing at the time of hypoglycemiathe final product will be substantially differentiated from current laboratory based assays in terms of lower blood volumelower cost and faster time to resultThe Phase I Specific Aims includeoptimize assay ready reagents for on cartridge drying and storagetranslate six laboratory based assays to the digital microfluidic cartridge and establish preliminary analytical performanceanddemonstrate preliminary feasibility of the assay panel on whole bloodThe key milestone for progression to Phase II will be the successful demonstration of all individual assays on cartridge using dry reagents and with high reliability and precisionA small feasibility study in Aimwill test our assay performance against clinical standard laboratory assaysThe Specific Aims for Phase II aremultiplex all assays to perform simultaneously on the same cartridgeperform analytical validations to determine device performanceandpreliminary clinical validation of the hypoglycemia panelresults obtained with FINDER will be compared to standard values obtained in the Duke Clinical LaboratoryAt the conclusion of Phase IIwe will have a commercializable product for rapidefficient and accurate assessment of severe hypoglycemia in newborns using microliter volumes of whole bloodWe will seek FDA approval of the final productwhich will initially be marketed for use in pediatric patients in U Shospitalswith a future market towards other patients who may benefit from the innovative features of the platform The overall goal of this project is to develop an ultra sensitive near patient system for the rapidcomprehensive assessment of severe hypoglycemiaand underlying causesin newborns using microliter volumes of whole bloodThe six laboratory assays necessary to evaluate severe hypoglycemia in newborns currently require up tomL of whole blood and time to result can be as long ashoursThere is a critical unmet needhighlighted by the recent clinical recommendations from the Pediatric Endocrine Societyfor faster blood tests that require smaller samples of blood in order to guide the expeditious diagnosis and effective treatment of this potentially disabling disorder in newborn patients