Background:

Bioseparations, such as chromatography, rely on bioinstructive adsorbents, which enable highly specific interactions with target molecules through nanoscale material structures and tailored surface functionalizations. Here, the 3D interactions of the active sites distributed in the pores of the adsorbent influence the affinity and selectivity to specific target molecules. However, information about the detailed 3D structure of commercially available adsorbents is often unknown. Therefore, a model of a digital twin of a commercial chromatography resin was developed using molecular dynamics simulations. This resin has a polymer backbone and has both electrostatic and hydrophobic interactions.

Task:

The aim of the work is to validate the previously developed model of a digital twin for a polymer-based mixed-mode resin. The work is divided into an experimental and a simulative part. In the experimental part, the adsorption of initially small molecules on the resin under different binding conditions is to be determined. High-throughput chromatography experiments will be performed to cover a wide range of parameters. Fully automated, flow-based systems will be compared with fully automated, batch-based incubation systems. In the simulative part of the work, the experiments will be simulated using molecular dynamics simulations. Different workflows will be used to calculate the binding energy of the target molecules to the adsorber under the conditions investigated. In a final step, the experimental and simulated results will be correlated to validate the model.