P11: Evaluation of the BioLector Small-Scale Bioreactor for Identifying Recombinant Protein Production Differences in E. coli

Since Genentech’s founding in 1976, E. coli has been used to generate recombinant proteins for research and therapeutic applications.  Production of E. coli derived therapeutics at Genentech can require significant process development work, which is typically performed at the 10-L scale.  Fermentation development at the 10-L scale can be time consuming and costly due to limited staffing and available fermentors.

The BioLector system from DasGip/M2P Labs has the potential to reduce the resource requirements associated with fermentation process development by providing high-throughput screening at a smaller scale.  The BioLector was evaluated for its ability to reproduce comparative recombinant protein titer differences from historical 10-L fermentation data, as assessed by immunoblots.  In our hands, the system showed consistent microbial growth and accurate on-line measurements for dissolved oxygen, pH, and cell mass.  In most cases we were able to identify large differences in recombinant protein production from immunoblots of BioLector samples, which matched historical 10-L data.  However, we were unable to resolve subtle differences in titer seen at the 10-L scale.  Correctly identifying these titer differences is important for making process improvements, especially during initial development work. Consequently, the BioLector did not adequately match historical 10-L titer data, and did not meet our criteria for use as an initial screening method for recombinant proteins.