Digital twin in high throughput chromatographic process development for monoclonal antibodies

Tiago Castanheira Silva, Michel Eppink, Marcel Ottens*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

20 Downloads (Pure)


The monoclonal antibody (mAb) industry is becoming increasingly digitalized. Digital twins are becoming increasingly important to test or validate processes before manufacturing. High-Throughput Process Development (HTPD) has been progressively used as a tool for process development and innovation. The combination of High-Throughput Screening with fast computational methods allows to study processes in-silico in a fast and efficient manner. This paper presents a hybrid approach for HTPD where equal importance is given to experimental, computational and decision-making stages. Equilibrium adsorption isotherms of 13 protein A and 16 Cation-Exchange resins were determined with pure mAb. The influence of other components in the clarified cell culture supernatant (harvest) has been under-investigated. This work contributes with a methodology for the study of equilibrium adsorption of mAb in harvest to different protein A resins and compares the adsorption behavior with the pure sample experiments. Column chromatography was modelled using a Lumped Kinetic Model, with an overall mass transfer coefficient parameter (kov). The screening results showed that the harvest solution had virtually no influence on the adsorption behavior of mAb to the different protein A resins tested. kov was found to have a linear correlation with the sample feed concentration, which is in line with mass transfer theory. The hybrid approach for HTPD presented highlights the roles of the computational, experimental, and decision-making stages in process development, and how it can be implemented to develop a chromatographic process. The proposed white-box digital twin helps to accelerate chromatographic process development.

Original languageEnglish
Article number464672
Number of pages13
JournalJournal of Chromatography A
Publication statusPublished - 2024


  • Harvest High-throughput screening
  • High-throughput process development
  • Lumped kinetic model
  • Overall mass transfer coefficient


Dive into the research topics of 'Digital twin in high throughput chromatographic process development for monoclonal antibodies'. Together they form a unique fingerprint.

Cite this