Photoelectrochemical biosensors: critical review and foresight toward multiplexed and clinically relevant platforms

Photoelectrochemical (PEC) biosensors have attracted increasing attention as highly sensitive analytical platforms that integrate optical excitation, electrochemical transduction, and biomolecular recognition. Their unique signal generation mechanism enables ultra-low detection limits for a wide range of bioanalytes, including nucleic acids, proteins, metabolites, toxins, and pharmaceutical compounds. Despite substantial progress in photoactive materials and signal amplification strategies, the practical translation of PEC biosensors remains constrained by fundamental challenges such as signal instability, biofouling, calibration drift, limited reproducibility, and the predominance of monoanalyte sensing architectures. This review provides a critical and physics-oriented analysis of PEC biosensing systems, going beyond conventional material cataloging. We systematically examine charge generation and transfer mechanisms, energy-band alignment with bio-redox systems, and the interfacial origins of PEC signal modulation. Recent advances in antifouling strategies, split-type architectures, self-referencing and self-calibrating designs, and emerging multiplexed PEC platforms are critically assessed. In addition, a patent landscape analysis is integrated to evaluate the technological maturity of PEC biosensors and to identify underexplored directions with high translational potential. By linking materials physics, interface engineering, and system-level design, this foresight-oriented review identifies key technological bottlenecks and outlines realistic pathways toward multiplexed, stable, and clinically relevant PEC biosensing platforms. The insights provided aims to guide future research and accelerate the transition of PEC biosensors from laboratory demonstrations to practical analytical and diagnostic applications.