Research progress in microneedle-based electrochemical sensing for health monitoring

The shift in healthcare from hospital-based diagnosis to home-based management has created an urgent demand for monitoring technologies that are minimally invasive, continuous, and capable of real-time molecular readout. Blood, despite serving as the clinical gold standard for biochemical analysis, relies on venipuncture or finger-prick sampling that is incompatible with high-frequency, long-term use in daily life. Among available alternative peripheral biofluids, interstitial fluid (ISF) has emerged as the preferred medium for wearable molecular monitoring. ISF is continuously present in the dermis, closely mirrors plasma composition with a short lag time, and contains a comprehensive panel of clinically relevant biomarkers spanning metabolites, electrolytes, hormones, cytokines, nucleic acids, and therapeutic drugs. Microneedle arrays penetrate the stratum corneum with minimal tissue disruption to provide direct access to ISF, while electrochemical transduction delivers high sensitivity, rapid response, low power consumption, and inherent compatibility with miniaturization and wireless integration. The integration of microneedle-based ISF sampling with electrochemical transduction establishes a unified technological platform for in situ, dynamic molecular assessment. Representative studies now span chronic disease management, early disease detection, and therapeutic drug monitoring, charting a trajectory from single-analyte, short-term demonstrations toward multiplexed, multi-day integrated systems. However, the ultimate goal of a long-term wearable smart closed-loop skin interface has yet to be realized, constrained by three cross-cutting bottlenecks: insufficient long-term in vivo stability of advanced nanomaterial-based transducers, signal drift of miniaturized flexible reference electrodes, and progressive biofouling at the sensing interface. Resolving these challenges is the critical breakthrough needed to advance this technology from laboratory prototypes to robust clinical deployment, and from episodic snapshot measurements to truly continuous, intelligent molecular surveillance.