Factors that Affect Quantification in Surface-Enhanced Raman Scattering

Surface-enhanced Raman scattering (SERS) is an analytical technique capable of detecting trace amounts of specific species. The uniqueness of vibrational signatures is a major advantage of SERS. This combination of sensitivity and specificity has motivated researchers to develop diverse analytical methodologies leveraging SERS. However, even 50 years after its first observation, SERS is still perceived as an unreliable technique for quantification. This perception has precluded the application of SERS in laboratories that rely on consistent quantification (for regulatory purposes, for instance). In this review, we describe some of the aspects that lead to SERS intensity variations and how those challenges were addressed in the 50 years of the technique. The goal is to identify the sources of variations in SERS intensities and then demonstrate that, even with these pitfalls, the technique can be used for quantification when factors such as nature of the substrate, experimental conditions, sample preparation, surface chemistry, and data analysis are carefully considered and tailored for a particular application.