UC San Diego

The greatest risk of childhood deaths occurs in the first few weeks of life. Two of the major concerns, birth asphyxia, and sepsis are responsible for the loss of over 2.5 million infants in this vulnerable period. Worse, the survivors are at a high risk for long-term morbidity. This doctoral research work focuses on developing screening tools to influence timely clinical decision-making for targeted treatment for such high risk-infants. First, we developed a web-based decision support tool to encourage timely initiation of therapeutic hypothermia, the only available therapy for infants at risk for brain injury due to birth asphyxia. This tool provides access to widely accepted clinical guidelines and strategies in a simplified way which can be easy to follow and access in clinical settings. Such a clinical decision support tool can obviate some of the time and effort needed for rigorous training and refresher sessions for providers at low acuity, low volume birthing centers. Second, we developed a platform for rapid, reliable and automated identification of bloodborne pathogens responsible for neonatal sepsis using DNA melting analysis directly after digital PCR amplification. Specifically, we designed a high resolution digital melt platform with precise thermal control to accomplish reliable, high-throughput heat ramping of microfluidic chip digital PCR reactions. We characterized the sources of variability to minimize run to run variations with the system using synthetic DNA oligos. We also demonstrate the use of novel rate-dependent melt signatures for enhancing automated melt genotyping. Further, we developed software for analysis to classify melt curves and identify novel pathogens. Our hope is that in future, this platform can translate into a near-point of care, cost-effective technology for screening for sepsis.