Fluorescent Microneedle Sensor Array for Continuously Monitoring Sodium and Hydrogen Ion Concentrations in Interstitial Fluid and Its Application in Diabetes Complication Management

The homeostasis and regulation of sodium and hydrogen ions are crucial in the pathophysiology of diabetes, as metabolic dysregulation often leads to electrolyte disturbances and acid-base imbalance. Current diagnostic tools, such as blood gas analysis in a hospital, are invasive, time-consuming, and strictly demanding professional skills. To cope with this problem, we have worked out a minimally invasive, dual-ion-sensitive microneedle sensor array to simultaneously monitor interstitial sodium and hydrogen ion concentrations. By integrating two ion-sensitive fluorescent materials and a long-lifetime phosphorescent reference material into hydrogel-based microneedles, we fabricated a fluorescence microneedle sensor (FMNS) array that possesses sufficient mechanical strength and flexibility to penetrate the stratum corneum and to contact the interstitial fluid. The array demonstrates fully reversible responses to variations of hydrogen and sodium ions and is capable of measuring the concentration of both ions with high sensitivity, good selectivity, high accuracy, and quick response. In vivo experiments on diabetic and diabetic ketoacidosis mouse models showed that the measured values correlate well with that from the blood gas analysis, confirming the high accuracy of the FMNS array. Moreover, the full reversibility and the quick response of the FMNS array suggest a minimally invasive alternative to blood gas analysis, enabling real-time and home-based measurement of multiple critical parameters for the comprehensive management of diabetes complications.