Abstract The overall goal of this project is to optimize performance and hemocompatibility of prototype blood oxygenators enabled by silicon nanomembranes. To achieve this, the project brings together expertise in blood-contacting medical device hemodynamics (Co-PI Steven Day; Chair and Prof. Biomedical Engi- neering, Rochester Institute of Technology) with silicon nanomembrane production at SiMPore Inc. (Co-PI James Roussie). Together, SiMPore and RIT offer a high impact and innovative approach for pro- ducing device geometries and material systems. SiMPore?s nanomembranes offer orders-of-magnitude higher permeability than polymer membranes used in current ECMO oxygenators and compelling pre- liminary data are demonstrative of these advantages. Since the overall volume of an oxygenator is de- pendent on the surface area and permeability of its membranes, incorporating SiMPore?s highly perme- able silicon nanomembranes into an efficient blood delivery and gas exchange system will lead to scaled down circuit blood volumes and dramatically lower surface areas of blood exposure. Leveraging Co-PI Day?s expertise in modeling and testing of hemolytic and thrombogenic potential of blood-con- tacting medical devices, a blood delivery network will be iteratively designed in silico and tested with installed nanomembranes in vitro so that the full permeability of nanomembrane-based oxygenation is realized within a safe and efficient device geometry. Aim 1 will focus on iterative in silico prototype oxy- genator design and initial empirical performance characterization, while Aim 2 will focus on a perfected design?s hemocompatibility and comparative performance versus currently in-use polypropylene mem- brane oxygenators. Success out of this R21 project will lay the basis for testing of the nanomembrane- based oxygenator in animal models.