Pulse-Operated First-Generation Biosensors with Extended Linear Range for Continuous Glycemia Monitoring in Oxygen-Deficient Environments

We report on the Prussian Blue (PB) and glucose oxidase (GOx) based first-generation biosensor with a linear calibration range remarkably extended to high concentrations, which is suitable for continuous monitoring in oxygen-deficient media. The increase of the apparent Michaelis constant by several orders of magnitude, resulting in a record linear range, was achieved by reduction of the GOx amount immobilized in the sensor membrane. The latter allowed one to diminish the O2 deficiency and keep its transport in pace with glucose oxidation. To compensate a predictable decrease in sensitivity, we suggested pulse power generation readout providing 100-fold response amplification. As a result, for the pulse-operated first-generation biosensors, the optimal linear range from 0.5 to 30 mM, high sensitivity (over 10 mA M-1 cm-2), extinguished dependence of the response on O2 content, and improved operational stability were achieved. Such characteristics allowed the adaptation of the PB based biosensors for glycemia control upon continuous in vivo monitoring of the interstitial fluid glucose.