Beyond Detection Limits: Integrated Biosensors for Molecular Diagnostics, Longitudinal Monitoring, and Clinical...

Biosensors are evolving from isolated analytical detectors into integrated systems for molecular diagnosis, longitudinal monitoring, dynamic tissue assessment, and clinical or preclinical decision support. This critical narrative review synthesizes literature from 2018 through July 2026 on biorecognition, biointerface engineering, transduction, wearable and microneedle architectures, CRISPR diagnostics, and sensor-integrated microphysiological systems. Unlike previous work that primarily classifies biosensors by analyte, recognition chemistry, or transduction modality, this review provides a unified translational framework that shifts evaluation from analytical sensitivity alone to the ability of systems to generate reliable, longitudinal, and clinically actionable information. A central distinction is made among snapshot assays, repeated discrete measurements, and genuine molecular trajectories, which require reversible recognition, controlled sampling, calibration, drift management, and temporal fidelity. Across applications, translational maturity depends on the measurement pathway. Continuous glucose monitoring remains the clearest benchmark because it combines durable chemistry, reproducible manufacture, workflow integration, and demonstrated clinical benefit. Other platforms have reached authentic-matrix testing, feasibility, prospective validation, or regulatory clearance but remain limited by fouling, matrix effects, calibration transfer, incomplete sample-to-answer operation, device variability, and insufficient manufacturing evidence. Future progress requires durable interfaces, claim-matched validation, reproducible scale-up, interoperable data systems, and measurements that remain trustworthy across time, users, devices, and settings.