Neutrophil Decision Making in Confined Environments in Health and Disease

脓毒症诊断提出了重大的临床和科学挑战。美国败血症的发病率是 充血性心力衰竭的发病率是结肠癌的6倍，艾滋病的发病率是20倍， 败血症是医疗保险预算中最重要的一项费用。早期和更准确地诊断脓毒症 可以挽救生命，降低成本，改善治疗。然而，当今早期脓毒症诊断的精确性 约为70%（每三名患者中就有一名被误诊）。血培养是金标准但他们的结果 在作出临床决定后3-4天内可用。朝着早期和准确脓毒症的目标迈进 诊断，我们将专注于测量中性粒细胞炎症和抗微生物功能的微流体工具。 我们将寻求三种使能技术，以更好地了解中性粒细胞在以下背景下的功能： 败血症我们将增加灵敏度，并减少持续时间的一个新的测定脓毒症的基础上， 中性粒细胞自发迁移，我们将精确测量中性粒细胞与肝脏的合作， 微生物使用新的群集阵列，我们将设计设备来捕获嗜中性粒细胞衍生的染色质， 血液（cNET），并确定败血症期间血液中的细菌。

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.