Severe hyperbilirubinemia (defined as serum bilirubin levels greater than 99th percentile) can cause a spectrum of neurologic dysfunction, of which kernicterus has the most devastating neurologic consequences. Kernicterus manifests as a life-long movement disorder with occulomotor and auditory dysfunction. In developing countries such as India, 5%-12% of all newborns are reported to develop severe hyperbilirubinemia in the newborn period. Among premature infants, incidence of hyperbilirubinemia warranting treatment has been reported to be as high as 78%. In China, 35% of full term newborns were noted to have significant hyperbilirubinemia. Even in light of incidence that is much higher than noted in the United States and the detrimental consequences associated, universal screening for hyperbilirubinemia is not currently available to the newborns in these developing nations. In cases of prolonged jaundice, measurement of total bilirubin alone does not suffice. Underlying causes such as glucose-6-phosphate dehydrogenase (G6PD) deficiency and congenital hypothyroidism (CH) should be strongly considered. Infants with jaundice secondary to these conditions may not respond to traditional modes of therapy (such as phototherapy) until the underlying illness is addressed. The challenges of implementing a successful population-based newborn screening program in developing countries such as India and China are very different from countries with established programs. The paradigm of centralized newborn screening that works well in developed countries is quite challenging to implement in highly populated developing countries such as India or China. This is due to larger number of births, lower percentage of hospital births, and lack of logistical infrastructure to transport samples. There is therefore a compelling need for an inexpensive, scalable, and distributable newborn screening platform for use in these countries. Building upon successful results from phase I, we propose to build a laboratory prototype of a highly distributable low cost newborn screening platform suitable for use in India and China (Aim 1). We will design a low cost digital microfluidic cartridge to perform assays for total bilirubin, G6PD and TSH and verify analytical performance (Aim 2) and clinical performance (Aim 3).
Advanced Liquid Logic, Inc. is developing a lab-on-a-chip on its proprietary digital microfluidic platform for newborn screening. The proposed project aims to demonstrate a near-patient platform for screening neonates for hyperbilirubinemia which, if not detected in time, could lead to kernicterus leaving the child developmentally challenged for entire life. This inexpensive device would be greatly useful in rapid identification and to enable early treatment.