3D-Printed Biocompatible Hollow Microneedle-Based Electrochemical Sensor for Wireless Glucose Monitoring

Wearable electrochemical sensors have aroused tremendous attention due to their potential for in situ and continuous glucose monitoring. Glucose is a critical risk indicator of diabetes, and continuous glucose monitoring has been proven remarkable to reduce the deterioration of diabetes and prevent secondary complications.
Conventional fingerstick test is the easiest and most common method for glucose evaluation, but invasive and painful. Interstitial fluid (ISF) processes a similar composition profile as the blood, making it a valuable alternative for glucose monitoring. Despite promising, obtaining ISF is still challenged by minuscule volumes available in the dermis and the filtration effect caused by the applied force, leading to slow extraction rates for continuous sampling. Hollow microneedles (HMNs) have been reported to sample ISF via epidermis piercing and capillary force for glucose monitoring. To date, the combination of micropores and suction approach has improved the collection rate over sole needle-based extraction and reduced tissue damage caused by suction blisters. Fe-N-C-based single-atom nanozymes (SANs) have emerged as promising candidates for sensor development due to their low cost, ultrahigh activity, high stability, and superior peroxidase-like characteristics. These nanozymes have been extensively utilized for developing sensitive and reliable biosensors.
Herein, we present a novel biocompatible wearable electrochemical sensor for glucose monitoring in ISF. The sensor employed 3D-printed HMNs fabricated by using biocompatible resin, allowing minimally invasive sampling for ISF and ensuring safe interaction with the skin without irritation and toxicity concerns.
SANs significantly boosted the sensitivity for electrochemical sensing, with a linear range of 0.1 μM to 40 mM for glucose. Transmission electron microscopy and high-angle annular dark-field scanning transmission electron microscopy images confirmed the shape and size of the SANs and the single-atom dispersion of Fe and Zn, validating their high peroxidase-like activity. Cyclic voltammetry tests demonstrated their excellent electrocatalytic performance, with a significant reduction potential shift for H₂O₂ and a linear response to concentration, enabling real-time and accurate detection. The SANs-functionalized screen-printed electrode exhibited high sensitivity, excellent reproducibility and long-term stability, with a detection range from 0.1 μM to 50 mM, a low detection limit of 0.059 μM, and robust anti-interference capability.
The combination of 3D-printed HMNs and a finger-activated pump enabled efficient ISF extraction in a biocompatible and minimally invasive approach. Finite element analysis visualized the stress distribution in the HMN. SEM images suggested no apparent deformation was observed after compression tests and parafilm penetration tests, affirming excellent mechanical stability and successful penetration of HMNs to the dermis layer for ISF sampling. The sensor demonstrated wireless and accurate glucose detection in artificial ISF using a skin-mimicking model with parafilm and agarose hydrogel. Experiments showed a strong linear correlation (R² = 0.99) between glucose concentration (1-40 mM) and response current, validated by continuous glucose measurements. The device demonstrated high recovery rates (97-105%) and achieved reliable wireless transmission within a 20-meter range.
In summary, this study showcased a biocompatible, SANs-functionalized, 3D-printed hollow microneedle-based electrochemical sensor for wireless, continuous and real-time glucose monitoring in ISF. Our integrated wearable sensor provides a feasible solution for continuous glucose monitoring. Additionally, we aim to expand our device’s capabilities to monitor multiple biomarkers for comprehensive health management.