Advancing non-faradaic impedance biosensors: sensitivity enhancement strategies using microfluidics, multiscale labeling, and CMOS technology

Impedance biosensors represent a critical technology for next-generation diagnostics, offering label-free detection with inherent compatibility for miniaturization. Among these, non-Faradaic impedance biosensors, which measure electrical property changes without electrochemical reactions, provide simplified operation but have historically suffered from limited sensitivity. This review examines three synergistic strategies that have transformed non-Faradaic sensor performance: micro/nanoparticle-assisted enhancement achieving 10- to 15-fold sensitivity improvements, microfluidic integration for enhanced mass transport, and complementary metal-oxide-semiconductor (CMOS) technology enabling high spatiotemporal resolution through on-chip integration. Recent innovations combining these approaches have achieved femtomolar detection limits for proteins and single bacterial sensitivity, representing a 10- to 100-fold improvement over conventional non-Faradaic methods. We analyze the strengths and limitations of each strategy, their synergistic potential, and emerging directions in material and system integration. This review provides a roadmap for developing advanced non-Faradaic biosensing platforms for healthcare diagnostics, environmental monitoring, and biomedical research.