Mechanistic modeling of the elution behavior and convective entrapment of vesicular stomatitis virus on an ion exchange chromatography monolith

• Flow rate-dependent tailing effect identified as convective entrapment • Separation of virus populations due to convective entrapment • Mechanistic modeling of an enveloped virus particle ion exchange chromatography • Convective entrapment in a monolith is modelled using a Langmuir retention term Developing a downstream purification process for replication-competent enveloped virus particles presents a significant challenge. This is largely due to the highly complex particle structures, as well as complexities of emerging purification modalities for such virus particles. In this study, an unexpected fluid-dynamic effect was observed during the elution of enveloped virus particles from an ion exchange chromatography monolith. This effect led to peak tailing and the separation of virus particle subpopulations. Upon considering possible causes, convective entrapment was identified as a plausible explanation. To investigate this effect, a mechanistic modeling approach representing the electrostatic resin interactions and the convective entrapment effect was implemented. The introduced Langmuir approximation of the convective entrapment showed good alignment with reference data from experiments. The model reproduced the retention effect, and furthermore suggested two virus particle populations due to the stronger retention effect on the tailing subpopulation caused by convective entrapment.