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ASME GFP Whole Cell Microbial Biosensors: Scale-up and scale-down effects on biopharmaceutical processes
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By Frank Delvigne, Alison Brognaux, Shanshan Han, SørenJ. Sørensen & Philippe Thonart

Biomedical & Nanomedical Technologies (B&NT): Concise Monographs Series

Up to 40 volumes are planned for this concisemonograph series, which focuses on the implementation of variousengineering principles in the conception, design, development,analysis and operation of biomedical, biotechnological andnanotechnology systems and applications.

Abstract: Two strategies are usually consideredfor the optimization of microbial bioprocesses. The first oneinvolves genetic or metabolic engineering of the target microbialstrains in order to improve its production efficiency or itstolerance to adverse conditions. The second one is based on thechemical engineering improvement of the bioreactors and scaling-uprules. This work is more particularly dedicated to this secondclass of parameters. Recent developments in bioreactor technologiesfollow the scaling-out principle, i.e. carrying out severalcultures in parallel with controlled conditions for screeningpurposes. Several mini-bioreactor concepts, i.e. bioreactor withworking volume of 1 to 100 mL with controlling devices, have beendeveloped following this principle. In general, chemicalengineering similarities between conventional stirred bioreactorsand their miniature equivalent are well characterized. However, theactual scaling-up rules are not able to cope with the complexity ofthe microbial stress response. Indeed, microbial stress responsestill remains not completely understood considering the processperturbations and the environmental fluctuations accompanying thescaling-up to industrial bioreactors.

At this time, this kind of response can only be experimentallypredicted by using scale-down bioreactors, i.e. lab-scalebioreactors designed in order to reproduce mixing imperfectionsthat have to be expected at large-scale. However, the use of suchan approach is time consuming and requires an experimented staff toelaborate the scaling-down protocols. Indeed, bioprocessdevelopment involves several steps which cannot be necessarilylinked with each other considering the different cultivationequipment used.

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Hardcover

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