Project Summary/Abstract Extremely preterm (EPT) infants have a high rate of mortality and morbidity, primarily due to the underdevelopment of the lungs. When born before 23 weeks of gestation, infants are generally considered non- viable, and have no options to keep them alive. Between 23-27 weeks, these infants still have high morbidity and mortality, with survival to discharge without major morbidity varying between 43% at 27 weeks to 2% at 23 weeks. An artificial placenta is an adaptation of extracorporeal membrane oxygenation (ECMO) designed for a premature infant and performs extracorporeal gas exchange. An artificial placenta simulates intrauterine physiology and may enable continued normal development outside of the uterus. However, current artificial placenta oxygenators in development use hollow-fiber membrane (HFM) technology, which is limited by high- dose anticoagulation requirements and large priming volumes. Anticoagulation is especially dangerous in EPT infants, who already have high rates of intracranial hemorrhage due to their underdeveloped cerebral vasculature. The SiMOx-AP is a novel microfluidic artificial placenta oxygenator designed to operate without anticoagulation, thus overcoming a key barrier to clinical translation of an artificial placenta device. It is based on breakthrough semiconductor silicon-based semi-permeable membranes made using microfabrication techniques. The rigid and flat-plate nature of the silicon membranes overcome limitations of HFM and flexible microfluidic oxygenators. In this R21, we will investigate the feasibility of a clinical-scale and anticoagulation-free SiMOx-AP device using a combination of computational, benchtop, and preclinical in-vivo studies.