Badri Parshad, Xingyu Hu, Isabelle Nagle, Shatruhan Singh Rajput, Fei Peng, Emmanouil Roussakis, Juan Pedro Cascales, Tyler McPartland, Anna Wiatrowski, Julia B. Slade, Trọng Hung Nguyen, Rachel S. Knipe, Mark W. Grinstaff, Conor L. Evans
Real-time, quantitative biosensing within extracorporeal perfusion (ECP) and extracorporeal membrane oxygenation (ECMO) systems is key to advancing this life-support technology beyond the hospital setting to emergency care. Measuring and monitoring $$\hbox {O}_2$$ concentration in blood is particularly important but is challenged by fouling of the sensor. Here we report a novel hydrogel nanocomposite coating, composed of polysulfobetaine, polyethylene glycol, and titanium dioxide nanoparticles, for a metalloporphyrin-based oxygen sensor. The hydrogel nanocomposite exhibits minimal cytotoxicity and hemolytic effects (< 5%), as well as non-adhesive and non-coagulant properties in contact with lung endothelial cells and human plasma, ensuring its compatibility with blood-contacting applications. The incorporation of titanium dioxide nanoparticles provides a white, light-scattering surface to improve sensor signal reflection, enhances the hydrogel’s mechanical strength (storage modulus > 1000 Pa), and maintains a pore area on the order of μm2 to facilitate efficient fluid and gas diffusion to the oxygen sensing film. Notably, the hydrogel nanocomposite enables rapid, accurate (within 2 mmHg of the analytical reference), and continuous monitoring of oxygen partial pressures ( $$\hbox {pO}_2$$ ) in PBS and blood for over 90 minutes within a miniaturized flow cell integrated in an extracorporeal perfusion-mimicking system. To our knowledge, this is the first report of a blood-compatible biomaterial that enables real-time $$\hbox {pO}_2$$ monitoring in a lightweight, compact sensor, suitable for integration into ECP and ECMO circuits.