Sepsis represents a systemic inflammatory response caused by microbial infection in blood. Herein, we present a novel comprehensive approach to mitigate inflammatory responses through broad spectrum removal of pathogens, leukocytes and cytokines based on biomimetic cell margination. Using a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), we performed extracorporeal blood filtration with the developed microfluidic blood margination (ampersand-flag-changemu;BM) device. Circulating bacteremia, leukocytes and cytokines in blood decreased post-filtration and significant attenuation of immune cell and cytokine responses were observed 3-5 days after intervention, indicating successful long-term immunomodulation. A dose-dependent effect on long-term immune cell count was also achieved by varying filtration time. As proof of concept for human therapy, the ampersand-flag-changemu;BM device was scaled up to achieve ampersand-flag-changesim;100-fold higher throughput (ampersand-flag-changesim;150 mL h-1). With further multiplexing, the ampersand-flag-changemu;BM technique could be applied in clinical settings as an adjunctive treatment for sepsis and other inflammatory diseases.
