Microneedle-Based Optical Biosensors for Point-of-Care Glucose Monitoring in Interstitial Fluid: Recent Advances, Current Challenges, and Future Perspectives

Microneedle (MN)-based optical biosensors are emerging as minimally invasive platforms for point-of-care testing (POCT) and wearable glucose monitoring by enabling direct access to interstitial fluid (ISF), which closely reflects plasma glucose dynamics. This review summarizes recent advances in MN-based glucose sensing with particular emphasis on optical biosensors. Blood-to-ISF glucose transport, physiological time lag, MN architectures, fabrication strategies, and ISF sampling mechanisms are discussed. Glucose recognition mechanisms are outlined together with optical transduction approaches, including colorimetric, fluorescence, surface-enhanced Raman scattering (SERS), photonic, and plasmonic sensing. Many colorimetric MN platforms currently function as single-use or endpoint POCT systems, whereas reversible fluorescence- and photonic-based sensors provide greater potential for repeated measurements and continuous glucose monitoring. Advanced functional materials, smartphone-assisted readout, and emerging artificial intelligence/machine-learning approaches for signal processing, calibration, and glucose prediction are also examined. Key analytical, mechanical, biocompatibility, and ex vivo/in vivo performance parameters are critically evaluated, together with patents, clinical investigations, and commercialization status. Compared with previous reviews that mainly address ISF sampling, general MN biosensing, glucose monitoring across multiple sensing modalities, or wearable optical sensors separately. This review provides an integrated glucose-specific framework linking ISF physiology, MN-mediated sampling, point-of-care and emerging continuous optical sensing, advanced materials, digital/AI analysis, performance validation, and clinical translation. Finally, current limitations involving biofouling, signal drift, long-term stability, manufacturing scalability, and clinical validation are discussed to highlight future directions toward advanced point-of-care platforms and emerging intelligent, wearable, and continuous glucose-monitoring systems.