Implantable microelectrode biosensors for monitoring neurometabolic markers

Implantable microelectrode biosensors enable the monitoring of neurometabolic markers with high spatial and temporal resolution. This review provides an overview of the designs, surface modifications, and electrochemical principles of enzyme-based biosensors that can continuously monitor glucose, lactate, and pyruvate in vivo. It includes the evolution of single-channel and multi-channel microelectrode architectures alongside with advances in surface functionalization strategies that enhance sensitivity, selectivity, and biocompatibility. Critical challenges including foreign body responses, enzymatic stability, and sensor drift are addressed through innovations in soft materials, antifouling chemistries, and enzyme immobilization approaches. Recent findings demonstrate that simultaneous monitoring of multiple neurometabolic markers reveals astrocyte-neuron metabolic coupling, metabolic-vascular coordination, and metabolic stress signatures under physiological and pathological conditions. Integrating wireless telemetry, on-chip signal processing, and machine learning-enabled calibration enables chronic implantation in freely moving animals, supporting fundamental neuroscience and translational neurometabolic research. Emerging developments in multimodal integration that combine chemical sensing, electrophysiology, and neuromodulation promises a new generation of implantable devices for personalized neurological monitoring and adaptive therapeutic interventions. This review highlights the interdisciplinary advances driving implantable biosensors toward clinical translation, as well as the opportunities and challenges remaining for enabling next-generation in vivo brain monitoring technologies.