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 injury. The etiology of severe neonatal hypoglycemia -- which affects around
25,000 newborns each year in the U.S. -- is complex, with underlying causes including hyperinsulinism,
cortisol and/or growth hormone (GH) deficiencies, and defects in glycogen metabolism. Comprehensive
evaluation of these physiological pathways is essential to guide appropriate, effective medical interventions.
However, the current panel of laboratory assays requires relatively large volumes (3 mL or more) of whole
blood, making newborn assessment challenging, particularly in preterm newborns. More importantly, routine
turnaround times for these assays may be 48 hours or more, leading to critical delays in life-saving treatment.
The overall goal of this Fast Track SBIR project is to develop a comprehensive near patient digital microfluidic
system, FINDER, for the rapid assessment of severe, persistent hypoglycemia disorders in newborns using
microliter volumes of whole blood. FINDER will accept single use cartridges and will multiplex 6 assays for the
detection of insulin, cortisol, growth hormone, glucose, β-hydroxybutyrate and free fatty acids using < 50 µL of
whole blood for all assays. Run time will be approximately 45 minutes. The team at Baebies will collaborate
with leading clinical investigators in Neonatology (Dr. Michael Cotten) and Pediatric Endocrinology (Dr. Michael
Freemark) at Duke University on this project. The system proposed herein addresses a critical unmet clinical
need for rapid testing at the time of hypoglycemia; the final product will be substantially differentiated from
current laboratory based assays in terms of lower blood volume, lower cost and faster time-to-result.
The Phase I Specific Aims include: 1) optimize assay-ready reagents for on-cartridge drying and storage; 2)
translate six laboratory based assays to the digital microfluidic cartridge and establish preliminary analytical
performance; and 3) demonstrate preliminary feasibility of the assay panel on whole blood. The 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 precision. A small feasibility study in Aim 3 will test our assay
performance against clinical standard laboratory assays. The Specific Aims for Phase II are: 1) multiplex all
assays to perform simultaneously on the same cartridge; 2) perform analytical validations to determine device
performance; and 3) preliminary clinical validation of the hypoglycemia panel: results obtained with FINDER
will be compared to standard values obtained in the Duke Clinical Laboratory.
At the conclusion of Phase II, we will have a commercializable product for rapid, efficient and accurate
assessment of severe hypoglycemia in newborns using microliter volumes of whole blood. We will seek FDA
approval of the final product, which will initially be marketed for use in pediatric patients in U.S. hospitals, with
a future market towards other patients who may benefit from the innovative features of the platform.
