Microplate approach to resin screening and parameter estimation applied to chromatography column modeling of gradient...

The use of phenomenological models in preparative chromatography is often limited by the difficulty in accessing accurate model parameters. Although screening protocols are commonly used to select materials, the resulting data are not consistently used to estimate model parameters. A joint estimation procedure that integrates data from microplate screening with a single column experiment was proposed to estimate equilibrium and dispersion parameters for modeling gradient elution. Initial estimates of equilibrium isotherm parameters were derived from the screening data, which were then refined by incorporating column chromatogram data to estimate mass transport parameters and enhance isotherm predictions. The proposed method was validated using reverse-phase chromatography with a non-ionic surfactant and functionalized silica. The equilibrium parameters estimated with microplate data predicted a retention volume 8.9 % away from the experimental results, while the joint estimation prediction was 0.8 % in the best-case scenario. In this case, results show that the use of screening data combined with the l-curve method can effectively mitigate model overfitting, even when relying on a single gradient elution column assay. This approach has the potential to accelerate process development and reduce resource consumption.