Fundamentals and applications of SERS-based bioanalytical sensing

<jats:title>Abstract</jats:title> <jats:p>Plasmonics is an emerging field that examines the interaction between light and metallic nanostructures at the metal-dielectric interface. Surface-enhanced Raman scattering (SERS) is a powerful analytical technique that uses plasmonics to obtain detailed chemical information of molecules or molecular assemblies adsorbed or attached to nanostructured metallic surfaces. For bioanalytical applications, these surfaces are engineered to optimize for high enhancement factors and molecular specificity. In this review we focus on the fabrication of SERS substrates and their use for bioanalytical applications. We review the fundamental mechanisms of SERS and parameters governing SERS enhancement. We also discuss developments in the field of novel SERS substrates. This includes the use of different materials, sizes, shapes, and architectures to achieve high sensitivity and specificity as well as tunability or flexibility. Different fundamental approaches are discussed, such as label-free and functional assays. In addition, we highlight recent relevant advances for bioanalytical SERS applied to small molecules, proteins, DNA, and biologically relevant nanoparticles. Subsequently, we discuss the importance of data analysis and signal detection schemes to achieve smaller instruments with low cost for SERS-based point-of-care technology developments. Finally, we review the main advantages and challenges of SERS-based biosensing and provide a brief outlook.</jats:p>