We further demonstrate here that fouling-induced loss of sensor response is preventable via robust membrane protection or via a monolayer with a terminal moiety that has stronger antifouling properties than the simple hydroxyl group at the end of MCH or MCO. First, the impact of hydrogel membrane protection was assessed on multi-day sensor response in serum at 37 °C. We quickly note that for these results a roughened gold surface was used (see Methods) to promote adhesion of a zwitterionic polybetaine hydrogel to the electrode surface. While application of the hydrogel to our sensors reduced initial sensor response for MCH sensors (Figure ), for MCO sensors the initial sensor response was virtually unchanged (Figure ) compared to sensors without hydrogel (Figure ). More importantly, both hydrogel-protected MCH and MCO sensors were able to largely maintain their initial sensor responses from day 0 to day 3 (Figure ). These results indicate that the protection was largely successful in reducing fouling that leads to reduced sensor response, as large proteins such as albumin would have difficulty diffusing through the size-selective and well-hydrated hydrogel matrix.