LAUSR

The discovery of noble metal plasmonic nanoparticles (PNPs) has introduced surface-enhanced Raman scattering (SERS) as a highly sensitive and specific bioanalytical technique with greater potential in point-of-need disease diagnosis. This Tutorial provides an overview of the principles governing a gold PNP-based biosensor design for sensitive and reliable SERS-based detection of disease biomarkers. First, we will highlight the optical transducer properties of PNPs, the principles of SERS, the benefits of SERS detection, and the modes of SERS for biomarker detection. The analytical performance (sensitivity and specificity) and the reliability (accuracy and reproducibility) of a SERS biosensor are mainly dictated by (i) the chemical and optical transducer properties of PNPs, (ii) the functional nano interface, where the interaction(s) between PNPs and target biomolecules take place, and (iii) SERS data acquisition and evaluation metrics. Maintaining a balance between SERS signal enhancement and reproducibility is critical for advancing the field deployment of SERS technologies. However, the reproducibility of SERS biosensors is often overlooked in lieu of the assay sensitivity. Consequently, next, we will discuss the systematic optimization strategies for fabricating gold PNPs as SERS substrates and designing their functional interface to design SERS biosensors with sufficient sensitivity, specificity, and reproducibility. We will highlight the choice of PNPs and their integration into biosensing platforms depending on the mode of SERS detection. Last, we will discuss the SERS data acquisition and performance evaluation as an integral part of the SERS biosensors development workflow.