The most ubiquitous interference is molecular oxygen, which is difficult to avoid in point-ofuse sensing due to measurements being conducted in ambient air or oxygen-rich media such as blood . Oxygen can interfere with all types of oxidoreductase-based electrochemical biosensors through various mechanisms. For reductase-based sensors , enzymatic analyte reduction typically requires applied electrode potentials that are more negative than the potential for the O2 reduction reaction. As a result, O2 is reduced directly at the electrode, leading to an overestimation of the analyte concentration . In contrast, in oxidase-based sensors, the oxidase intrinsically utilize O2 as a natural electron acceptor . This property of oxidases was exploited in first-generation electrochemical biosensors, which were poised to detect the product of O2 reduction by the oxidase, hydrogen peroxide . However, this O2 dependency inherently limits the sensor's performance, especially at high substrate concentrations . In second-generation biosensors, artificial electron mediators are employed to accept the electrons from the oxidase and shuttle them to the electrode, theoretically making the sensing independent of O2 . Nevertheless, O2 still competes with the artificial mediators for the electrons generated by the oxidase , diverting them away from the electrode (Figure ). The result is a decrease in the current signal, which leads to an underestimation of the analyte concentration (21) (Figure ).