Generalized Modeling Framework of Metal Oxide-Based Non-Enzymatic Glucose Sensors: Concepts, Methods, and Challenges

Glucose sensors have transformed diabetes control. Most glucose sensors are enzymatic, but a non-enzymatic metal oxide-based glucose sensor on a nanostructured substrate is of considerable interest for future always-on wearable closed-loop sensing for hypoglycemia management. Recently, various research groups have demonstrated that different nanostructured substrates (fabricated by a variety of innovative techniques) boost the sensitivity of non-enzymatic glucose sensor. In this work, we develop a physics-based model to correlate the geometrical and chemical design parameters to the non-linear amperometric response of non-enzymatic glucose sensor on geometrically complex substrates. Using this model, we can interpret the scattered results in the literature within a common conceptual framework. Our results show that while non-enzymatic glucose sensor still does not have sufficient dynamic range to replace the classical blood glucose sensors, these sensors could be useful for low concentration glucose sensing applications involving sweat, saliva, and ocular fluid. Our model will predictably improve the design of non-enzymatic glucose sensors for the integration into a continuous glucose monitoring system embedded in wearable and implantable platforms.