Electrochemical biosensing across microsampled blood and interstitial fluid for metabolic, hormonal, and therapeutic monitoring

Electrochemical biosensing is advancing beyond traditional single-analyte glucose monitoring toward platforms capable of quantifying metabolites, hormones, and therapeutic agents across microsampled blood and continuously accessed interstitial fluid (ISF). Progress in biorecognition chemistry, signal transduction, and skin-integrated interfaces has enabled minimally invasive access to capillary blood and ISF using microneedle-based and implantable devices. ISF-based sensing introduces depth-dependent analyte gradients, ISF-blood transport kinetics, and characteristic signal lag, necessitating sampling-aware sensor design and quantitative models for systemic correlation. We review device architectures that support stable, multi-day operation and outline calibration strategies for predicting blood-equivalent concentrations. Emerging directions include hybrid systems that merge electrochemical detection with complementary modalities, multi-analyte platforms that capture metabolic interdependence, and closed-loop approaches coupling biochemical readout with automated intervention. Together, these advances establish electrochemical biosensing as a core technology for continuous and clinically interpretable biochemical monitoring across blood and ISF.