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, ?-hydroxybutyrate and free fatty acids using < 50 L 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.
The overall goal of this project is to develop an ultra-sensitive near patient system for the rapid, comprehensive assessment of severe hypoglycemia, and underlying causes, in newborns using microliter volumes of whole blood. The six laboratory assays necessary to evaluate severe hypoglycemia in newborns currently require up to 3 mL of whole blood and time-to-result can be as long as 48 hours. There is a critical unmet need, highlighted by the recent clinical recommendations from the Pediatric Endocrine Society, for 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.
| Millington, David; Norton, Scott; Singh, Raj et al. (2018) Digital microfluidics comes of age: high-throughput screening to bedside diagnostic testing for genetic disorders in newborns. Expert Rev Mol Diagn 18:701-712 |
