The standard palliative surgery for a single ventricle defect is a total cavopulmonary connection (TCPC), which separates the pulmonary and systemic circulations. This Fontan circulation eventually fails with high long-term mortality. A failing Fontan includes cavopulmonary failure (CPF) and/or ventricular failure. No cavopulmonary assist (CPA) device is available for CPF. Our ultimate goal is to develop a percutaneous CPA system for total ambulatory support of CPF patients. Our enabling technology is a CPA dual lumen cannula (DLC) with paired membrane umbrellas. Via ony 1 venous cannulation, this DLC connects the TCPC to an external pump without major surgery. This system provided total CPA and reversed CPF hemodynamics/renal dysfunction in our lethal CPF sheep model, enabling 96 hr survival. To move our CPA DLC toward clinical application, the following specific aims were developed: Specific Aim 1: To design, optimize, and fabricate a new CPA DLC for least thrombogenic/ hemolytic potential and smooth installation/deployment. Two membrane umbrellas ensure efficient/reliable performance. Slipknots ensure easy DLC installation/umbrella deployment. Validated computational fluid dynamics will be used for design optimization. The CPA DLC body will be made of ultrathin reinforced polyurethane (PU) with a PU membrane sleeve infusion lumen. The two membrane umbrellas will be molded onto DLC. Specific Aim 2: [To assess the anatomic fittingness of the CPA DLC in patient specific TCPC silicone models and evaluate the potential of reversing pathophysiology in CPF patients using our established mathematical model validated with CPF patients’ comprehensive hemodynamic data]. Patient specific silicone TCPC models will be made from MRIs in our Fontan database. A mock loop with these models will assess the CPA DLC for: 1) ability to fit/function well; 2) flow stasis/high shear stress areas. Our patient specific Fontan simulation platform will quantify CPA flow rates that mitigate liver congestion. Specific Aim 3: To evaluate final CPA DLC prototype in a [patient specific TCPC mock loop] for performance, reliability, and 30 day durability. This mock loop with 37% glycerin will test CPA DLC for: 1) flow efficiency/reliability at 360° [axial] rotation/8 cm dislocation, and 2) 30 day durability at 4 L/min flow. Specific Aim 4: To evaluate the CPA DLC prototype for in vivo performance, reliability, and ease of installation/deployment in a CPF sheep model. Ease of installation/deployment and performance/reliability will be assessed in 6 hr studies (n=15). A 2-week preclinical study (n=15) will confirm full reversal of CPF hemodynamics/end-organ dysfunction and will assess biocompatibility.