Auto recalibration based on dual-mode sensing for robust optical continuous glucose monitoring

Boronic acid based optical continuous glucose monitoring systems (CGMs) hold promise for long-term glucose monitoring. However, these sensors suffer drifts induced inaccuracy and external calibration. One of the reasons is the denature of boronic acid structures and optical reporters. To solve this problem, a dual-mode glucose sensing method with auto-recalibration capabilities is developed using glucose-selective diboronic acid molecule (DBA) and optical reporter alizarin red S (ARS). DBA binds ARS at a 1:2 ratio and produces distinct changes in both the absorbance (Abs) and the fluorescence (FL) spectra of ARS. Through competitive binding with DBA, glucose induces a compensatory shift in both Abs and FL signals. The two signals were demonstrated to be strongly correlated and were combined to build Abs-FL-glucose 3D calibration curves for glucose determination. The mapping relationship of two signals drift closely with both changes of DBA and ARS concentration. By ascertain the right mapping relationship, the two strongly correlated signals can alert undesirable degradation of sensing components, identify the correct calibration curve, and accurately predict glucose concentration without external calibration. The introduction and adoption of the auto-recalibrating dual-mode sensing strategy could constitute a useful development in the pursuit of next generation long-term calibration-free CGM and wearable sensors technologies with superior precision.