【加密3】【文章推荐】Parallel Reactor Systems for Bioprocess Develo

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Parallel Reactor Systems for Bioprocess Development
Dirk Weuster-Botz ( )
Lehrstuhl für Bioverfahrenstechnik, Technische Universität München,
Boltzmannstrasse 15, 85748 Garching,Germany
d.weuster-botz@lrz.tum.de
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
2 Parallel Bioreactors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
2.1 Shake Flask . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
2.2 Shaken Microtiter Plates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
2.3 Parallel Stirred-Tank Reactors . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
2.4 Parallel Bubble Columns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
3 Parallel Feeding Technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
3.1 Early Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
3.2 Intermittent Feeding and Parallel pH Control . . . . . . . . . . . . . . . . . . 132
4 Application Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
4.1 Parallel pH Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
4.2 Oxygen Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
4.3 Power Input . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
4.4 Scale-Up and Scale-Down . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
5 Discussion and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
Abstract Controlled parallel bioreactor systems allow fed-batch operation at early stages of process development. The characteristics of shaken bioreactors operated in parallel (shake flask, microtiter plate), sparged bioreactors (small-scale bubble column) and stirred bioreactors (stirred-tank, stirred column) are briefly summarized.Parallel fed-batch operation is achieved with an intermittent feeding and pH-control system for up to 16 bioreactors operated in parallel on a scale of 100 ml. Examples of the scale-up and scale-down of pH-controlled microbial fed-batch processes demonstrate that controlled parallel reactor systems can result in more effective bioprocess development. Future developments are also outlined, including units of 48 parallel stirred-tank reactors with individual pH- and pO2-controls and automation as well as liquid handling system, operated on a scale of ml. Keywords Bioprocess development · Parallel bioreactors · Intermittent feeding ·Parallel control · Scale-up/scale-down