Evaluation of the ambr 15 fermentation system for high cell density XSTM E.coli and XSTM P.pastoris: strain screening and scalability

Microbial strain screening in batch mode achieves only limited growth and in many cases results are not predictive of larger scale fed-batch fermentations. This study investigates the new ‘ambr 15 fermentation’ automated micro-bioreactor to improve predictability of microbial strain screening compared to batch microplate cultures.

XS^TM E.coli and XS^TM P.pastoris strains expressing a range of therapeutic proteins were evaluated under high density fed-batch conditions in ambr 15 and results compared to batch microplate screens and fed-batch ambr 250 and 1L Dasgip fermentations.

ambr 15 delivered the target feed addition profiles well and key process events were automated by calculated and time-based triggers. Replicate cultures showed high consistency for biomass and titre, within and between runs. High cell densities were achieved (E.coli > 35g/L, P.pastoris > 100g/L), as expected for benchtop fermentations. A comparison of normalised XS^TM E.coli titres between microplates, ambr 15 and ambr 250, indicated significantly improved resolution between strains and improved rank order prediction when moving from microplates to ambr 15. An XS^TM P.pastoris scalability study showed a very close match between ambr 15, ambr 250 and 1L scale for dry cell weight culture profiles and similar results for protein titre.

Overall the ambr 15 fermentation system shows high experimental consistency and good predictions for fed-batch XS^TM E.coli and XS^TM P.pastoris fermentations at benchtop scale, offering the potential to significantly improve early strain selection decisions compared to batch microplate cultures.