ALow Blood Volume Platform for Global Newborn Screening of Common, Treatable Conditions

An estimated 80% of babies born worldwide (approximately 100 million each year) currently do not receive any newborn screening care. Newborn screening (NBS) is an immensely successful testing program that identifies those at increased risk for common, treatable congenital disorders; the pre-symptomatic identification of these disorders in newborns enables the rapid initiation of treatments and reduces or prevents serious health consequences such as mental disability, neurological dysfunction and premature death. While every child born in the U.S. is tested for at least 30 disorders, the overwhelming majority of children born in developing countries are not screened for even a single disorder. To help introduce newborn screening to regions lacking the infrastructure necessary to implement central laboratory based testing, we will develop a cost effective, low-to-medium throughput digital microfluidic testing platform. The platform will simultaneously measure total serum bilirubin (TSB), glucose-6-phosphate dehydrogenase (G6PD), galactose-1-phosphate uridyltransferase (GALT) and thyroid stimulating hormone (TSH) in whole blood in order to screen for hyperbilirubinemia risk, G6PD deficiency, classic galactosemia and congenital hypothyroidism, respectively. These represent four of the most common, treatable neonatal conditions in the developing world with a combined incidence of approximately 1 in 10. These tests will be performed on a modified cartridge and instrument that is based on our FDA-authorized digital microfluidic platform for measurement of enzyme activities that are indicative of lysosomal storage disorders. The tests for TSB, G6PD, GALT and TSH will be performed from less than 50 µl of whole blood using disposable cartridges with a total run time of less than 2 hours for all assays. In Phase I, we will translate 3 biochemical assays and a novel protein immunoassay (for TSH) to the digital microfluidic format and determine preliminary analytical and clinical feasibility. In Phase II, we will concentrate on technology modifications to the instrument (addition of absorbance detection) and cartridge (modified layout and addition of heaters). Once a modified instrument and cartridge is developed, the TSB, G6PD, GALT and TSH assays will be multiplexed to run on one cartridge and the analytical performance will be validated. A method comparison study will be performed to assess clinical utility against “gold standard” screening methods. The final product will be a flexible (low to medium) throughput newborn screening platform suitable for use in moderate complexity (hospital) settings in developing countries that currently lack a centralized newborn screening program. Once the technology is established for our initial 4-assay panel, we plan to expand our test offerings to cover additional time-sensitive neonatal conditions.PROJECT NARRATIVE Treatable conditions such as hyperbilirubinemia, G6PD deficiency and congenital hypothyroidism are common around the world and contribute to higher rates of newborn mortality and morbidity in developing countries. Earlier detection of these conditions through newborn screening has the potential to drastically improve the health outcomes of newborns in countries that currently lack widespread newborn screening. The goal of this Fast Track SBIR project is to develop and validate a distinctive, low blood volume automated platform that can perform a panel of clinical chemistry, enzymatic and immunoassays for newborn screening in emerging (medium resource) markets. The new platform will address the need for an inexpensive, scalable and distributable newborn screening platform to identify newborns at risk for hyperbilirubinemia, G6PD deficiency, congenital hypothyroidism and galactosemia.