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Heat transfer characteristics of a stirred single-use bioreactor

Müller, Matthias, Husemann, Ute, Greller, Gerhard, Meusel, Wolfram, Kraume, Matthias
Biochemical engineering journal 2018 v.140 pp. 168-177
biopharmaceuticals, bioreactors, engineering, films (materials), heat transfer, heat transfer coefficient, hosts, manufacturing, mixing, statistical analysis
Stirred single-use bioreactors are present throughout the biopharmaceutical manufacturing of high-value cell products. Lots of work has been done determining relevant process engineering parameters to enable reliable scale-up on a physical foundation. However, heat transfer capabilities of such systems are not well described, yet. As processes are further intensified and microbial hosts offer interesting opportunities, heat transfer becomes increasingly relevant. The present work gives a comprehensive overview on the specific implications of a stirred, 50 L, single-use bioreactor by means of heat transfer. This includes the dependency of overall heat transfer coefficients on process parameters, i.e. stirring frequency and jacket flow, with a corresponding statistical analysis. Experimental results are compared against a theoretical approach, based on Nu numbers. Although a systematic discrepancy on the description of the jacket-side heat transfer is present, there already is a good agreement between experimental and literature derived values. The jacket-side impact on the overall performance is then analyzed in detail by the Wilson plot method, underlining the major influence of this aspect. Since the polymer-film layer represents a significant feature of single-use bioreactors, this effect has been investigated for two film types as well. Finally, a first comparison of the 50 L against a 200 L bioreactor was carried out to identify scale-dependencies.