Noaman Khan, Maurício A. Melo
Biosensor technology has witnessed a metamorphosis-from the groundbreaking enzyme-based electrodes introduced in the 1960s to today's smart multifunctional diagnostic platforms and AI based biosensors. The development from basic molecular recognition to highly-integrated systems described in this review indicates the driving forces behind recent advances in biorecognition elements and transduction mechanisms coupled with nanotechnology-enabled unprecedented sensitivity, selectivity, and real-time monitoring. Early designs like glucose oxidase electrodes demonstrated the basic concept of coupling biochemical events with electronic signals while limited by stability, oxygen dependence, and interference. Subsequent advances: the invention of aptamer, nanobody, and molecularly-imprinted polymers; emergence of electrochemical, optic, and piezoelectric transduction pathways; and incorporation of nanomaterials like graphene, carbon nanotubes, and MXenes have addressed such limitations by driving biosensing capabilities toward strong and miniaturized ways. The digital revolution redefined all, including lab-in-a-chip devices, wearable sensors, smartphone interfaces, and AI-influenced data integration.