In Vitro Continuous 3 Months Operation of Direct Electron Transfer Type Open Circuit Potential Based Glucose Sensor: Heralding the Next CGM Sensor

Abstract

Background: While continuous glucose monitoring (CGM) systems allow precise and real-time blood glucose control, current electrochemicalbased CGM technologies inherently harbor enzyme instability issues. The direct electron transfer (DET) type open circuit potential (OCP) based enzyme sensing principle can minimize the catalytic turnover of the enzyme reaction, thereby providing longer-term operational stability in future CGM glucose sensors. Method: DET-type OCP based glucose sensors were constructed using gold disk electrodes with glucose dehydrogenase capable of DET which was immobilized using a self-assembled monolayer (SAM). The single enzyme layer prepared on the gold electrode was operated in the presence of glucose, using in vitro buffer solution, continuously for over 3 months with the OCP sensor signal monitored every 10 seconds at 25°C. Results: The DET-type OCP glucose sensor was continuously operated for more than 3 months without a significant decrease of the sensor signal and sensitivity (slope). These results suggest that the DET-type OCP glucose sensor is far more stable than the sensor constructed based on the amperometric principle. The long-term stability of DET-type OCP glucose sensor is attributed to the enzyme’s minimized catalytic reaction during the operation, thereby extending the lifetime of enzyme. Conclusion: The DET-type OCP glucose sensor can be continuously operated for more than 3 months at 25 °C, in vitro without significant decreases in sensor signal and sensitivity. While the further investigation will be required for in vivo validation, the DET-type OCP glucose sensor is ideal for next generation CGM’s, especially in long duration implantable use cases.