Strategies for Multiplexing Plasmonic Biosensing

Plasmonic biosensing technologies have emerged as powerful analytical tools for sensitive and label-free characterisation of biomolecular interactions and complex samples. The increasing demand for comprehensive molecular profiling has accelerated the development of multiplexing strategies that enable simultaneous analysis of multiple analytes and molecular interactions. This Feature Paper examines multiplexing through the complementary spatial, spectral, and temporal dimensions of multiplexing, together with their hybrid combinations and associated analytical trade-offs. Compared with other optical biosensing approaches, including interferometric, photonic, and fluorescence-based sensing platforms, plasmonic biosensors remain attractive owing to their combination of label-free detection, real-time interaction monitoring, sensitive interfacial analysis, and compatibility with multiplexed assay formats. This Feature Paper critically discusses current multiplexing strategies, focusing primarily on surface plasmon resonance (SPR), imaging SPR (SPRi), localised SPR (LSPR), surface-enhanced Raman scattering (SERS), and related nanoplasmonic biosensing approaches, together with recent advances in surface biofunctionalisation, antifouling interfaces, and molecular recognition strategies. Representative applications in biomedical diagnostics and non-clinical settings are highlighted, with examples such as liquid biopsy, glycoprofiling, extracellular vesicle profiling, and food and environmental analysis, alongside key challenges in reproducibility, standardisation, data interpretation, and clinical translation. In addition, selected non-plasmonic optical biosensing technologies are briefly discussed to position plasmonic biosensing within the broader landscape of multiplexed optical biosensing. This Feature Paper argues that the future of multiplexed plasmonic biosensing will depend less on further improvements in sensor performance than on robust, standardised analytical systems.