AI-enhanced surface functionalization in biosensors: From fundamentals to future prospects

Biosensors have become indispensable tools in healthcare, environmental monitoring, and biotechnology, with their performance critically dependent on interfacial chemistry and surface functionalization strategies. This review looks closely at recent advances in surface modification methods to enhance biosensor sensitivity and selectivity. The significant functionalization strategies addressed in this work include covalent and non-covalent immobilization procedures, along with novel nanomaterial-based enhancements that increase signal transmission and biorecognition precision. The fundamentals of surface interactions, biomolecule stability, and the shortcomings of conventional functionalization techniques are critically discussed. The primary focus is on the revolutionary effects of artificial intelligence (AI) in interfacial chemistry, where computational modelling and machine learning are transforming material design, property prediction, and biosensor optimization. The recent advancements at the convergence of AI, nanotechnology, and synthetic biology, which facilitate the development of intelligent biosensing platforms, are highlighted. A paradigm shift in biosensor development is represented by the use of AI models for functional material analysis, which provide data-driven answers to surface characterization challenges. Furthermore, the ethical issues and technical challenges related to AI-driven biosensor development are also covered, including data bias, repeatability, and sustainable production. This review systematically covers research activities during 2018–2025, providing a comprehensive overview of surface functionalization strategies, nanomaterial enhancements, and AI-driven approaches for biosensor development. Also, the review paper offers a roadmap for overcoming present constraints and opening up new possibilities in high-performance sensing technologies by combining interdisciplinary advancements in surface chemistry, nanotechnology, and AI.