title: Implementation of a thermal biosensor in a process environment: on-line monitoring of penicillin V in production-scale fermentations.
abstract: The production of penicillin V was monitored in 0.5 m3 and 160 m3 bioreactors. The thermal biosensor was an enzyme thermistor modified for split-flow analysis. The heat signal generated in the enzyme column was corrected for any nonspecific heat with the use of an identical but inactive reference column. The on-line monitoring was performed in the fermentation pilot plant and in a fermentation plant of Novo Nordisk A/S. Immobilized beta-lactamase was used to monitor three consecutive 0.5 m3 penicillin fermentations. Broth samples were continuously filtered through a tangential flow filtration unit in a sterile external loop. The on-line penicillin V values were 10% higher than those obtained by off-line HPLC analysis. Alternatively a polypropylene filtration probe was inserted into a 160 m3 bioreactor and samples were withdrawn at 0.5 ml/min. The same experiments were repeated with purified and immobilized penicillin V acylase. The on-line penicillin V values obtained with this enzyme correlated very well with those from HPLC analysis. The on-line monitoring was controlled and analysed by a software program written in Labtech Notebook.
authors.affiliation: Chemical Center, University of Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Rank
authors.forename: B
authors.initials: B
authors.lastname: Danielsson
authors.forename: J
authors.initials: J
authors.lastname: Gram
mesh_terms: D015374:Biosensing Techniques; D004345:Drug Industry; D005285:Fermentation; D006358:Hot Temperature; D006813:Humidity; D009862:Online Systems; D010404:Penicillin V / Q000032:analysis*; D013696:Temperature; D014732:Vibration
chemical_list: D010404:Penicillin V