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Implementation of a thermal biosensor in a process environment: on-line monitoring of penicillin V in production-scale fermentations

Authors
Journal
Biosensors and Bioelectronics
0956-5663
Publisher
Elsevier
Publication Date
Volume
7
Issue
9
Identifiers
DOI: 10.1016/0956-5663(92)85020-b
Keywords
  • Online Monitoring
  • Penicillin V
  • Biosensor
  • Fermentation
Disciplines
  • Biology

Abstract

Abstract The production of penicillin V was monitored in 0.5 m 3 and 160 m 3 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 β-lactamase was used to monitor three consecutive 0.5 m 3 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 Alternatively a polypropylene filtration probe was inserted into a 160 m 3 bioreactor and samples were withdrawn at 0.5 ml/min.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.

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