Improved Precision in Surface-Enhanced Raman Scattering Quantification of Analyte through Dual-Modality Multisite Sensing

Accurate quantification of analyte using surface-enhanced Raman spectroscopy (SERS) is a desired, yet unfulfilled, ability that could enable a plethora of diagnostic- and defense-related applications. The major hurdles to overcome to achieve this goal are expensive manufacturing for highly ordered and reproducible substrates and low reproducibility of substrates produced through low cost methods. A technology that can set industry standards for manufacturing/processing of SERS substrates is still yet to be achieved. A dual-modality multisite sensing approach was developed, that overcomes the limitations experienced when fabricating bottom-up, reproducible, sensitive, and low-cost SERS substrates. Electrochemistry was combined with SERS for dual-modality sensing to improve precision by adding redundancy and encoding features, thus increasing measurement robustness and predictability. This technique works by calibrating SERS response with respect to active surface area, a parameter known to be proportional to charge, which can be estimated via electrochemical measurements. The dual-modality multisite measurement demonstrates at least 2.8× improvement in assay precision compared to the traditional single-site Raman measurements. The technique yields overall improved precision of measurement and is not limited to any particular SERS substrate or geometry, and thus it can be adapted and incorporated readily in any SERS sensing assay.