Glucose oxidase-based biosensors are a primary method for continuous glucose monitoring. b-glucose reacts with immobilized glucose oxidase to form gluconic acid and hydrogen peroxide. Hydrogen peroxide is oxidized on an adjacent electrode. The resulting anodic current is proportional to the concentration of glucose. The measured current may be influenced by oxidation of secondary species, such as ascorbic acid and acetaminophen, or fouling of the sensor via foreign body response.[1-3] A blocking layer, placed between the electrode and the immobilized enzyme layer, may act to prevent diffusion of secondary species to the electrode, and reduce the influence of the foreign body response.[3]

The influence of a blocking layer on the steady and transient operation of the sensor was evaluated numerically. A blocking layer was added to the steady and transient glucose sensor model outlined in previous work [4] to address the potential influence of acetaminophen. Sensor performance was evaluated for multiple blocking layer thicknesses, reacting species diffusion coefficients, and oxygen concentration. The polarization behavior of the sensor was modeled. Selectivity to glucose was improved by addition of a blocking layer, but sensitivity to oxygen was increased with increasing blocking layer thickness.

Numerical simulations of the transient response to a step change in glucose for a sensor with the blocking layer had a response time comparable to the response without the blocking layer, except when the hydrogen peroxide diffusion was greatly reduced in the blocking layer. A step change in acetaminophen yielded time constants comparable to that of the glucose step change in the absence of a blocking layer. The results are sensitive to the thickness of the blocking layer and to the diffusivity of the interfering species in the blocking layer.

References

1. Basu, A., & Veettil, S. (2016). Direct Evidence of Acetaminophen Interference with Subcutaneous Glucose Sensing in Humans: A Pilot Study. Diabetes Technology & Therapeutics, 18(S2), 43-47.
2. Surani, S., & Sharma, M. (2021). Interaction between vitamin C and point of care glucose monitoring. Are we overly wary of it or is it a valid concern? Current Medical Research and Opinion, 37(7), 1111-1113.
3. Yang, Y., Zhang, S., & Kingston, M. (2000). Glucose sensor with improved haemocompatibility. Biosensors and Bioelectronics, 15, 221-227.
4. Jacobs and M. E. Orazem, ``Transient Response of a Continuous Glucose Monitor," presented at the 240th Meeting of the Electrochemical Society, Orlando, Florida, October 10-14, 2021.

Acknowledgement

The support of Medtronic Diabetes (Northridge, CA) is gratefully acknowledged.