Sub-second response algorithm for wearable glucose sensors: normalized slope-based calibration and microvolumes differential compensation measurements

Publication date: 5 Nov 2025

JournalSource: OPENALEXOpenAlex type: articleOpen Access
Authors: Vanessa Esposito, Elisa Sciurti, A. Calogiuri, Daniele Bellisario, Luciano Velardi, Flavio Casino, Laura Blasi, Luca Francioso

Traditional methods of blood glucose monitoring are invasive and can cause anxiety, pain and infection, resulting in poor patient compliance. Sweat-based glucose sensing has emerged as a promising non-invasive alternative, but the significantly lower glucose concentrations (10 to 100 times lower than in blood) pose a challenge for sensor sensitivity and operation. Here, we present different measurement protocols for enzymatic electrochemical glucose sensors with enhanced sensitivity and sub-second response calibration algorithm. The resulting amperometric response accurately reflects glucose concentration, demonstrating the sensor's potential for non-invasive monitoring of glucose in sweat. To enhance the reliability of the measurements and mitigate the variability among sensors arising from differences in sweat composition and secretion, a post-measurement protocol was developed. This protocol exploits a Response Correction Factor (RCF) calculated from the specific sensitivity of each sensor. This approach compensates for variability among different sensors reducing the standard deviation, thereby improving calibration accuracy (R 2 =0.995 vs. R 2 =0.822 without correction) allowing the prevention of phenomena related to enzyme inactivation or allogeneic reactions that may affect individual sensors in Continuous Glucose Monitoring (CGM) systems. An in-depth analysis was also conducted using sample microvolumes (20 μL), the typical amount of sweat available in wearable devices, to study thin-layer chronoamperometry response. To enhance the linearity of the sensor response, a differential compensation algorithm based on the slope of the response curve was adopted, employing a sensor without enzyme as a reference. This measurement method enhanced the dynamic range of slope values from 0.0085 μA/s to 0.0125 μA/s. The experimental results identified in a reliable way three operational regions: physiological (60-110 μM), warning values (110-160 μM) and alert/risk (>160 μM). The proposed strategies increase the robustness and applicability of sweat-based glucose monitoring for real-world applications.

Origin
Measurement Sensors
Volume
42
Pages
101977
Cited by
0