Chromatographic framework for coffee ring effect-driven separation of small molecules in surface enhanced Raman spectroscopy analysis.

The applications of coffee ring effect (CRE) in analytical chemistry have been increasingly expanded from particles and macromolecules to small molecules, in particular coupled to surface-enhanced Raman spectroscopy (SERS). Despite the theory behind the formation of CRE itself from a single drop evaporation onto the dry surface is well established, the theoretical aspects of CRE-driven separation, especially the analyte-surface interactions involving small molecules, have not been conceived. Herein, we have developed a theoretical framework to describe the CRE-driven separation process of small molecules, using SERS analysis of dimethylarsinic acid (DMA), dimethylmonothioarsinic acid (DMMTA), and dimethyldithioarsinic acid (DMDTA) on gold nanofilm (AuNF) as an example. By combining the CRE theory for the radial flow and the Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory for mass transfer between solution and AuNF surface, we adapted the conventional chromatographic theory to derive a modified van Deemter equation for the CRE-driven separation. By using this model, we predicted the travel distances of arsenicals based on the different affinity of analytes to the AuNF and evaluated the possibility of separation of unknown analytes by CRE-based SERS, demonstrating the successful adaptation of classic chromatographic theory to CRE-driven nanochromatography.