A 3D-printed wearable biosensor for tracking interstitial fluid biomarkers in diabetic ketoacidosis

Continuous multi-biomarker monitoring is essential for the timely prevention and treatment of diabetic ketoacidosis (DKA), as it provides comprehensive insights into metabolic disorders and enhances the accuracy and safety of clinical decision-making. In this work, we develop a 3D-printed wearable biosensor, which combines microneedle-based interstitial fluid (ISF) extraction, electrochemical detection, and wireless signal transmission for the rapid detection of DKA-related biomarkers: glucose (Glu) and β-hydroxybutyrate (β-HB). The 3D-printed extraction system consists of a hollow microneedle array and a vacuum pump, which can deliver ISF to the detection area through the hollow microneedle array, enabling the continuous DKA-related multi-biomarkers monitoring. The electrochemical sensor is constructed by modifying a conductive MXene layer and a redox-active molecularly imprinted polymer (MIP) composite film on a screen-printed electrode (SPE), where the integrated MIP matrix provides both molecular recognition and electrochemical signal transduction. The integrated sensor also demonstrates good stability, regenerative capabilities, and high selectivity, as well as the excellent sensitivity in biological fluids for the DKA-related biomarkers, with detection limits as low as 42 μM for Glu and 41 μM for β-HB in PBS buffer, respectively. Moreover, the platform is capable of monitoring dynamic changes in ISF Glu and β-HB levels, assessing their correlation in healthy and DKA rats, and comparing ISF results with those obtained from a commercial blood glucose/ketone device. The platform's suitability for routine nutritional metabolic monitoring in normal rats and dynamic treatment monitoring in DKA model is further investigated. This fully integrated wearable electrochemical sensing platform presents a promising approach for ISF collection and DKA diagnosis.