Effect of Electrode Structure on Glucose Monitoring by Reverse Iontophoresis

Continuous glucose monitoring (CGM) based on reverse iontophoresis (RI) offers a promising noninvasive solution for diabetes management. However, in the application of this technology, there are two key issues that affect the glucose detection results: the sensor sensitivity is gradually reduced due to the influence of the extraction current; the insufficient glucose extraction flux affects the accuracy of glucose prediction. We found that the electrode structure has a regulatory effect on these two types of influences. However, to date, there was no comprehensive or systematic investigation into the role of electrode structure in influencing the efficiency and accuracy of reverse iontophoresis-based glucose monitoring. This study investigated the impact of electrode structure on RI through multiphysics simulation, in vitro experiments, and human trials. By optimizing the spatial arrangement, spacing, shape, and position of the electrodes, the sensor sensitivity decline was minimized and the glucose extraction flux was maximized. Human trials verified the optimized design, achieving 74% of data points within the clinically accurate Clarke error grid A zone, with a mean absolute relative difference (MARD) of 13.17%, compared to 62 and 21.06% for the previous structure. These findings highlight the crucial role of electrode geometry in enhancing the accuracy of RI-based CGM.