Accelerated CO2 Removal for Artificial Lung Applications

Acute and chronic lung disease remains a major problem within the healthcare industry, accounts for one in seven deaths, and places lung disease as the third leading cause of death within the United States. Carbon dioxide removal (CO2R) devices are a viable alternative or adjuvant therapy to invasive mechanical ventilation, which can initiate and exacerbate lung injury, substantially contributing to patient mortality. The complexity and invasiveness of current respiratory assist devices used for extracorporeal CO2R has limited widespread use in ICUs. In this work we developed a bioactive hollow fiber membrane (HFM) which accelerates CO2 removal to facilitate the next generation of highly efficient CO2 respiratory assist devices. Since over 90% of blood CO2 is transported as bicarbonate (HCO3-), CO2R devices must overcome the small CO2 partial pressures (50mmHg) across HFMs limiting CO2 removal. Bioactive HFMs improve CO2 removal efficiency by converting bicarbonate to CO2 directly at the HFM surface. A 36% increase in the blood CO2 removal rate was achieved using CA-immobilized HFMs. Thromboresistance of CA-modified HFMs demonstrated 95% less platelet deposition compared to unmodified HFM. We characterized the CO2 mass transport processes within these biocatalytic devices to develop approaches towards improving bioactive HFM efficiency. The diffusional resistance from the liquid boundary layer was observed as the primary impediment to CO2 transport by both unmodified and bioactive HFMs under clinically relevant conditions. Strategies to increase CA loading on HFMs are not ideal avenues for improved efficiency of biocatalytic CO2R devices. Based on our findings, we proposed a bicarbonate/CO2 disequilibrium hypothesis to describe performance of CA-modified devices in blood. Improvement in CO2 removal rates using CA-modified devices in blood was realized by maximizing bicarbonate/CO2 disequilibrium at the fiber surface via blood acidification. Dilute acidic sulfur dioxide (SO2) sweep gas created an acidic microenvironment within the diffusional boundary layer adjacent to the HFM surface, and when used in combination with bioactive CA-HFMs had a synergistic effect to more than double CO2 removal efficiency while maintaining physiologic pH. Overall these findings revealed increased CO2 removal can be achieved through bioactive HFMs, enabling a next generation of more efficient CO2 removal intravascular and paracorporeal respiratory assist devices