Multiplexed biosensing: A review of surface plasmon resonance platforms for biomarker analysis

Surface plasmon resonance (SPR) has emerged as an important optical technology for the real-time, label-free analysis of biomolecular interactions. While its utility in detecting single analytes is well-established, the growing complexity of disease diagnostics demands tools capable of simultaneous multi-analyte detection. Many complex diseases, such as cancer, involve multiple biomarkers. Conversely, a single biomarker can be associated with several different diseases. This review article focuses specifically on recent advances in multiplex detection of biomarkers using SPR-based biosensors. We delve into the mechanisms and materials that enable multiplexing across various SPR platforms, including traditional prism-based SPR, localized surface plasmon resonance (LSPR), and SPR imaging (SPRi). The review highlights how these techniques overcome the limitations of single-analyte assays by providing a more comprehensive disease profile through the concurrent measurement of multiple biomarkers and their ratios. Key applications in medical diagnostics, employing immunosensor, aptasensor and protein-based assays, are examined to illustrate the performance of current multiplex SPR systems. This work concludes by discussing the implementation of machine learning in SPR-based detection, comparing various SPR biosensing techniques, and identifying future directions for enhancing sensor performance, analysis in complex matrices, and the expansion of multiplex SPR applications.