Enhancing the longevity of microparticle-based glucose sensors towards 1 month continuous operation

Luminescent microspheres encapsulating glucose oxidase have recently been reported as potential implantable sensors, but the operational lifetime of these systems has been limited by enzyme degradation. We report here that the longevity of these enzymatic microparticle-based sensors has been extended by the coimmobilization of glucose oxidase (GOx) and catalase (CAT) into the sensor matrix. A mathematical model was used to compare the response and longevity of the sensors with and without catalase. To experimentally test the longevity, sensors were continuously operated under normoglycemic dermal substrate concentrations and physiological conditions (5.5 mM glucose and 140 μM O2, 37 °C and pH 7.4). The sensors incorporating CAT were experimentally shown to be ∼5 times more stable than those without CAT; nevertheless, the response of sensors with CAT still changed by approximately 20%, when operated continuously for 7 days. The experimentally determined trends obtained for the variation in sensor response due to enzyme deactivation were in close agreement with modeling predictions, which also revealed a significant apparent loss in enzyme activity upon immobilization. It was further predicted via modeling that by incorporating 0.1 mM each of active GOx and CAT, the sensors will exhibit less than 2% variation in response over 1 month of continuous operation.