Self-calibrating multiplexed microneedle electrode array for continuous mapping of subcutaneous multi-analytes in diabetes

Monitoring multiplexed biochemical markers is beneficial for the comprehensive evaluation of diabetes-associated complications. Techniques for multiplexed analyses in interstitial fluids have often been restricted by the difficulties of electrode materials in accurately detecting chemicals in complex subcutaneous spaces. In particular, the signal stability of enzyme-based sensing electrodes often inevitably decreases due to enzyme degradation or interference in vivo. In this study, we developed a self-calibrating multiplexed microneedle (MN) electrode array (SC-MMNEA) capable of continuous, real-time monitoring of multiple types of bioanalytes (glucose, cholesterol, uric acid, lactate, reactive oxygen species [ROSs], Na⁺, K⁺, Ca²⁺, and pH) in the subcutaneous space. Each type of analyte was detected by a discrete MN electrode assembled in an integrated array with single-MN resolution. Moreover, this device utilized an MN-delivery-mediated self-calibration technique to address the inherent problem of decreased accuracy of implantable electrodes caused by long-term tissue variation and enzyme degradation, and this technique might increase the reliability of the MN sensors. Our results indicated that SC-MMNEA could provide real-time monitoring of multiplexed analyte concentrations in a rat model with good accuracy, especially after self-calibration. SC-MMNEA has the advantages of in situ and minimally invasive monitoring of physiological states and the potential to promote wearable devices for long-term monitoring of chemical species in vivo.