Abstract

Inflammation on a Chip

Daniel Irimia, Associate Professor/Associate Director, Massachusetts General Hospital & Harvard Medical School

Sepsis is an abnormal response of the immune system that injures one’s own body and leaves it vulnerable to infections. Sepsis affects ~1 million citizens each year in the US, has 30% mortality rate, and consumes the largest share of Medicare budget than any other condition (~7% of all expenses). Empirical evidence shows that early diagnosis is critical for reducing mortality from sepsis. However, our current abilities to diagnose sepsis early are very limited. To uncover the key pathological events leading to sepsis after injury and trauma, we focused on neutrophils, the white blood cells that are the earliest responders to tissue injury and microbial invasion. We designed and validated microfluidic technologies that helped measure the motility phenotype of neutrophils with higher precision than ever before. To circumvent the challenging logistics of neutrophil isolation in the clinic, we designed these devices to work directly with one droplet of blood. We validated the devices in the clinic and showed that using the devices we can identify patients with sepsis and monitor the course of the condition over time with high accuracy. Further studies of neutrophil phenotype in patients will enhance our understanding of the roles that neutrophils play before and during sepsis and will facilitate the design of new strategies for the diagnosis, monitoring, and prevention of sepsis.