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Updated: May 1, 2026

Process Optimization using High Throughput Automated Micro-Bioreactors in Chinese Hamster Ovary Cell Cultivation
Published on: May 18, 2020
Model-based design and integration of a two-step biopharmaceutical production process
Bruno Otero1, Marcus Degerman, Thomas Budde Hansen
1Department of Chemical Engineering, Lund University, Box 124, 221 00, Lund, Sweden.
Simultaneous optimization of protein PEGylation and purification boosts productivity by 100% without sacrificing yield. Recycling unreacted protein increases yield by 30%, but batch mode is best for maximum productivity.
Area of Science:
- Biochemical Engineering
- Protein Modification
- Chromatographic Separation
Background:
- PEGylation is a crucial protein modification technique.
- Chromatographic purification is essential for isolating target PEGylated proteins.
- Separating mono-PEGylated proteins from unreacted and di-PEGylated forms presents challenges.
Purpose of the Study:
- To design and optimize a two-step process for protein PEGylation and purification.
- To compare the effects of separate versus simultaneous optimization of the PEGylation and purification steps.
- To investigate the impact of recycling unreacted protein on yield and productivity.
Main Methods:
- A two-step process involving protein PEGylation followed by chromatographic purification.
- Comparative analysis of separate and simultaneous optimization strategies.
- Evaluation of protein recycling strategies.
- Assessment of process productivity and yield.
Main Results:
- Simultaneous optimization increased productivity by up to 100% without reducing yield.
- Simultaneous optimization leverages the easier separation of di-PEGylated protein for improved yield and productivity.
- Recycling unreacted protein enhanced yield by 30%.
- Batch mode operation is preferred for maximizing productivity.
Conclusions:
- Simultaneous optimization of PEGylation and purification offers significant advantages over separate optimization.
- The process design effectively manages impurities like di-PEGylated proteins.
- Recycling strategies can improve overall yield, while batch mode maximizes productivity.
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