Neutrophil Decision Making in Confined Environments in Health and Disease

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Sepsis diagnosis poses significant clinical and scientific challenges. The incidence of sepsis in the US is twice the rate of congestive heart failure, six times the rate of colon cancer, and 20 times the incidence of AIDS, and sepsis is the single most significant expense in Medicare budget. Early and more accurate diagnostic of sepsis could save lives, reduce costs, and improve treatment. However, the precision of early sepsis diagnosis today is ~70% (one in every three patients is misdiagnosed). Blood cultures are the gold standard, but their results are available 3-4 days after clinical decisions have been made. Towards the goal of early and accurate sepsis diagnosis, we will focus on microfluidic tools that measure neutrophil inflammatory and anti-microbial functions. We will pursue three enabling technologies to better understand the functionality of neutrophils in the context of sepsis. We will increase the sensitivity and reduce the duration of a new assay for sepsis based on the spontaneous neutrophil migration, we will make precision measurements of neutrophil cooperation against live microbes using new swarming arrays, and we will design devices to trap neutrophil-derived chromatin from blood (cNETs) and identify bacteria in blood during sepsis.