Understanding electrostatic interaction on strong cation-exchanger via co-ion valency effects

•Elucidation of transport phenomena in ion chromatography with continuum-based model.•Explanation of physicochemical interplay of solid surface and electrolyte in process.•Knowledge transfer solely via physical properties and a priori description of process.•Modified Poisson-Boltzmann theory captures valency, size, and concentration effects.•Revealed physics behind empirical stoichiometric displacement model for bioseparation. Empirical adsorption models have been extensively used to design and optimize ion exchange chromatography (IEC) processes for proteins. The equations go 40 years back to the qualitative findings about the electrical double layer (EDL) in ion exchangers and form the basis of the stoichiometric displacement (SD) model widely used in preparative chromatography. While the SD model reduces the experimental effort to find salt-eluting conditions for the separation, knowledge transfer is restricted from one system to another. However, this limitation can be overcome by understanding the physicochemical interaction mechanism between the solid adsorbent and the electrolyte. Via a theoretical and experimental approach, we investigated the physicochemical adsorption mechanism in IEC and developed a methodology to determine it quantitatively by measuring the effective EDL thickness. We performed negative adsorption experiments in high-performance liquid chromatography to measure the excluded volume of co-ions, citrate, or oxalate on strong cation exchange resin. Together with the physical specifications of the column and the deployment of a modified nonlinear Poisson-Boltzmann equation, we identified the effects of the electrolyte composition on the size of the EDL. While it depends on the concentration, valency, and size of the counterion, we derived that the expansion of the EDL is indicated by different valencies of the carboxylate co-ions in trace amounts. Our findings provide a self-consistent theory of the transport phenomena in a solid/fluid system with all parameters specified with the physical properties of the chromatographic process. Further, optimizing the resin design or improving the adsorption and desorption conditions for biomolecules may be facilitated. Altogether, our work may improve material designing and process development and, thereby, help to overcome the concurrent technological and economic bottlenecks of the well-deployed purification step of IEC.