Electrochemical self-powered biosensors for autonomous diagnostics and monitoring: energy sources, recognition interfaces, and translational design rules

Electrochemical self-powered biosensors are autonomous platforms that convert biochemical, microbial, photochemical, or mechanical energy into diagnostic signals, reducing dependence on batteries and conventional potentiostats. Their compact, low-power operation makes them attractive for wearable monitoring, point-of-care testing, implantable devices, and environmental analysis. This review primarily focuses on intrinsically self-powered electrochemical platforms, including enzymatic and microbial fuel cells, organelle-based systems, abiotic devices, and sample-powered sensors, while selected TENG/PENG-based systems are discussed to illustrate how mechanically harvested energy can support electrochemical sensing. Particular emphasis is placed on molecular recognition interfaces including enzymes, microbial biofilms, organelles, antibodies, aptamers, nucleic acids, molecularly imprinted polymers, nanozymes, ion-selective membranes, and nanostructured electrodes that link energy generation with analytical specificity. We discuss how these interfaces regulate current, voltage, power, photocurrent, electron transfer, and charge storage, and highlight strategies for improving recognition efficiency, electron transfer, mass transport, antifouling performance, and stability. Key challenges include low power density, unstable biointerfaces, mediator leaching, biofouling, matrix effects, motion artifacts, scalability, biocompatibility, and limited standardization. Finally, we propose design principles for developing robust, selective, manufacturable, and clinically relevant electrochemical self-powered biosensors for next-generation autonomous diagnostics.