PROJECT SUMMARY/ABSTRACT X-COR Therapeutics is creating the first extracorporeal CO2 removal (ECCO2R) device that uses dialysis-like approaches to accessibly treat hypercapnic respiratory failure (HRF) patients. HRF is a devastating consequence of critical lung disease caused by chronic obstructive pulmonary disease (COPD) and other respiratory disorders including acute respiratory distress syndrome (ARDS), a common complication of COVID-19. The current standard of care for severe disease is invasive mechanical ventilation, which results in a ~30% mortality rate and increased susceptibility to ARDS. While use of protective ventilatory strategies reduces mortality, resultant hypercapnia from protective ventilation resembles diseases like COPD. In both cases, impaired ventilation causes increased carbon dioxide (CO2) levels that lead to acidosis, coma, and death. For patients with hypercapnia, extracorporeal technologies that deliver oxygen and remove gaseous CO2 (e.g. ECMO) present possible alternatives but are highly invasive and costly. They require high blood flow rates (>1 L/min) and large-bore cannula only deployable in specialized facilities. Here, we propose investigating a hybrid device that resembles a hemodialysis-like blood filtration cartridge that contains a novel configuration of two filtration fibers for bicarbonate dialysis and gaseous CO2 capture. High efficiency CO2 removal allows a low blood rate of <250 ml/min, thus allowing small catheters (<13.5 Fr) to replace the 28-30 Fr cannula used today in most extracorporeal therapies. Less invasive and standard vascular access makes this therapy accessible and enables its use in parallel with invasive mechanical ventilation. With parallel therapy, the proposed device can prevent hypercapnia that results from protective ventilation and enable safer use of invasive mechanical ventilation with earlier extubation. Because it can use existing hemodialysis systems, the device can be deployed with existing workflows and capital equipment. The objective of this Phase I SBIR project is to optimize and then investigate ventilatory benefits from using a hybrid membrane filtration device that removes CO2 from ultra-low extracorporeal blood flow. Aim 1 is to determine optimal device geometries and operating parameters (e.g. size, fiber pack density, and fiber ratio) that meet desired CO2 capture requirements through iterative modification of a novel design using scalable production methods. Each iteration will be evaluated using bench-top ex-vivo perfusion testing. Aim 2 is to investigate the impact that extracorporeal CO2 capture has on patient spontaneous and assisted ventilatory requirements using a series of physiologic computational models using patient-specific boundary conditions. Successful completion of this project will result in a manufacture-ready device with candidate geometries and operating parameters for pre-clinical testing. This device will be able to: 1) remove >30% of CO2 produc...