Mpofu, Kelvin TChauke, Sipho HThwala, Nomcebo LMthunzi-Kufa, Patience2025-07-222025-07-222025-023005-1193https://doi.org/10.1007/s44371-025-00094-2http://hdl.handle.net/10204/14317Optical biosensing has emerged as a vital tool for real-time, sensitive detection of biological analytes, with aptamers and antibodies leading as key molecular recognition elements. This review examines and compares their distinct roles, advantages, and limitations in optical biosensing. Antibodies, celebrated for their high specificity and mature production protocols, are often preferred in clinical diagnostics. However, challenges like cross-reactivity, environmental sensitivity, and production costs prompt exploration of alternative biorecognition molecules. Aptamers, nucleic acid–based recognition elements, offer several unique advantages, such as ease of synthesis, chemical stability, and amenability to modifications for improved target binding. While their relatively recent discovery means fewer standardized protocols and clinical applications compared to antibodies, aptamers show promise in complex sample matrices and emerging sensor platforms. This review also explores technological advances in both aptamer and antibody integration, surface modification strategies to enhance binding specificity and orientation, and regeneration methods to ensure biosensor reusability. Through a comprehensive comparison, the article aims to identify scenarios where one molecular recognition element holds distinct advantages over the other, paving the way for strategic applications in diagnostics, food safety, and environmental monitoring. In this review, we have explored the advancements and challenges associated with optical biosensing technologies, with a particular focus on LSPR-based sensors. Recent developments in nanoparticle fabrication, hybrid sensor platforms, and external stimulus-responsive systems have opened new avenues for biosensing applications in clinical diagnostics, environmental monitoring, and food safety. The review also discussed the integration of optical biosensors with Raman spectroscopy for enhanced analytical capabilities and highlighted innovations in metamaterial-based sensors for improved sensitivity and specificity. Despite these advances, several challenges remain, including surface stability, reproducibility, and limitations in detecting low-abundance analytes. Addressing these challenges will require further improvements in device design, bioreceptor immobilization strategies, and signal enhancement techniques. Future research efforts should also focus on the development of portable and cost-effective biosensing platforms that can be applied in resource-limited settings. Ultimately, this review provides valuable insights into future trends in aptamer and antibody-based biosensors, encouraging cross-disciplinary collaboration and innovation.FulltextenOptical biosensingAptamersAntibodiesPlasmonicsArticlen/a