Towards the next generation of nanobiosensors

This review examines the evolution, current status, and future perspectives of nanobiosensors, highlighting key advances and persistent challenges. Since the introduction of the biosensor concept in 1962 with the enzyme electrode, biosensing technologies have evolved from simple electrical devices to optical, electrochemical, and hybrid transduction platforms, while consistently prioritizing miniaturization, integration, and ease of use.Over the past three decades, the integration of nanotechnology has driven rapid growth in the field. The emergence of the term “nanobiosensor” in the late 1990s reflects the convergence of biosensing with advances in nanomaterials and nanoscale engineering. By coupling biological or synthetic recognition elements, such as enzymes, antibodies, aptamers, nucleic acids, or molecularly imprinted systems, with nanoscale transducers, nanobiosensors have achieved improved sensitivity, lower detection limits, faster response times, and enhanced miniaturization. These developments have enabled applications across diagnostics, environmental monitoring, food safety, and biomedical research. The Figure shows some nanobiosensor designs taking advantage of nanomaterials and nanostructures.Despite extensive research activity, the translation of nanobiosensors into real-world applications remains limited. Many devices show excellent laboratory performance but struggle in complex environments due to issues of robustness, reproducibility, long-term stability, scalability, and cost. In some cases, excessive complexity or the unnecessary use of nanomaterials has failed to deliver meaningful performance gains.This review underscores the need for a stronger shift toward application-driven design. Future progress will depend on prioritizing performance in real samples, manufacturability, sustainability, affordability, and reliability beyond proof-of-concept demonstrations, enabling nanobiosensors to realize their full practical impact.