Requirements for fast multianalyte detection and characterisation via electrochemical-assisted SERS in a reusable and easily manufactured flow cell

Surface-enhanced Raman spectroscopy (SERS) is a highly sensitive analytical technique that captures vibrational spectra of analytes adsorbed to rough coin metal surfaces with remarkable signal intensities. However, its wider application is limited by challenges in substrate range, quantification, and the disposable nature of SERS substrates partly due to irreversible analyte adsorption-commonly referred to as the 'memory effect'. Overcoming these limitations and achieving real-time analysis in flow-through systems remains a key challenge for the advancement of SERS. This study presents a SERS flow cell incorporating an Ag-based SERS substrate and a Pt counter-electrode, enabling the investigation of how electrochemical methods can address existing challenges. Our approach demonstrates that signal intensities can be both enhanced and spectroelectrochemically modified. Additionally, the combination of constant solvent flow and electrochemical potentials enhances the longevity of the SERS substrate, facilitating multianalyte measurements while mitigating the memory effect. Key parameters have been systematically studied, including SERS substrate materials (silver and copper), solvents, buffers, supporting electrolytes, and electrochemical protocols. We achieved consistent and reproducible electrochemical tuning of SERS signals by using halogen-free electrolytes in polar solvents commonly used in techniques like HPLC. The versatility of the system was validated through the analysis of several model compounds and the sequential detection of multiple analytes. We also successfully applied the system to detect and characterise contaminants and pharmaceuticals, highlighting its potential for a wide range of analytical applications.