DESCRIPTION (provided by applicant): This application is a competitive revision of the parent grant R01GM064619 and is being submitted in response to notice # NOT-OD-09-058. The competitive revision seeks to develop a point-of-care platform for measuring serum zinc concentrations in children with septic shock, the "zinc chip." The rationale for development of the zinc chip stems directly from data generated through the translational research program supported by the above parent grant. We have been conducting gene expression profiling studies (microarray) in children with septic shock. An unexpected finding is that pediatric septic shock is characterized by widespread and persistent repression of genes having functional annotations related to zinc biology. Functional validation of these data demonstrated that non-survivors of pediatric septic shock have abnormally low serum zinc concentrations compared to survivors. These data suggest that altered zinc homeostasis plays a role in the pathobiology of pediatric septic shock, and this assertion is well supported by a series of follow-up clinical and laboratory studies. Thus, we hypothesize that zinc supplementation may be an effective therapeutic strategy in pediatric septic shock, and are preparing to directly test this hypothesis by conducting zinc supplementation studies in critically ill children with septic shock. An important component for carrying out these studies in a safe and rigorous manner will be the capability to reliably and efficiently measure serum zinc concentrations in these patients. Current methods for measuring zinc are accurate, but costly and time consuming. Accordingly, we are proposing to develop a point-of-care platform to efficiently and accurately measure serum zinc concentrations. The zinc chip will be developed in collaboration with the University of Cincinnati Department of Engineering, which has a rich history of developing point-of-care platforms for clinical application, including the ability to measure heavy metals in biological fluids. The zinc chip will first be tested using donor serum samples spiked with known concentrations of zinc (Specific Aim 1). In Specific Aim 2 we will test the precision and accuracy of the zinc chip at the bedside of critically ill children by comparing zinc chip-derived measurements with reference laboratory data. We expect that successful development of the zinc chip will be an important advance in the safe and efficient conduct of the aforementioned zinc supplementation trials. This competitive revision meets the goals of the Recovery Act to stimulate the economy in two ways. In the short term, it will allow us to contract for additional needed skills by collaborating with the University of Cincinnati Department of Engineering to develop the zinc chip. In the long-term, development of the zinc chip will require larger scale production and could therefore lead to commercialization. Public health Relevance: The deliverable of this program will be the development of point-of-care platform for accurate and rapid measurement of serum zinc concentrations in critically ill children, the zinc chip. Child health will be positively impacted by developing the capability of conducting zinc supplementation trials in a safe and rigorous manner.

PROJECT NARRATIVE The deliverable of this program will be the development of point-of-care platform for accurate and rapid measurement of serum zinc concentrations in critically ill children, the zinc chip. Child health will be positively impacted by developing the capability of conducting zinc supplementation trials in a safe and rigorous manner.