Tuesday, August 14, 2012: 9:00 AM
Jefferson East, Concourse Level (Washington Hilton)
Substrate-limiting fed-batch processes are not easy to perform in µL-scale systems, since substrate delivery in this scale is challenging. In situ substrate release systems have been developed, which allow circumventing problems related to the µL-scale. One example is the enzyme-based delivery system EnBase®1. Automated approaches on liquid-handling systems allow for the integration of suitable experimental design approaches. A model-based design can accelerate the definition of optimal process operation points with respect to the media composition and the feeding strategy. Already in this scale, process development can include the consideration of typical scale-up issues like the appearance of substrate gradients in large-scale fed-batch processes. Models are further applied in the approach presented to design experiments in a two-compartment scale-down reactor, in which cells are continuously opposed to gradients2. Then concentration steps regarded as critical for the process based on model estimations are applied and their impacts are evaluated.
The presented concept enables a faster process development while final process modes and conditions are considered early, when engineering, biotechnology and modeling meet long before the industrial scale is reached.
1. Krause, M., K. Ukkonen, et al., A novel fed-batch based cultivation method provides high cell-density and improves yield of soluble recombinant proteins in shaken cultures. Microbial Cell Factories, 2010. 9.
2. Junne, S., A. Klingner, J. Kabisch, T. Schweder, and P. Neubauer, A two-compartment bioreactor system made of commercial parts for bioprocess scale-down studies: impact of oscillations on Bacillus subtilis fed-batch cultivations. Biotechnol J, 2011. 6(8): p. 1009-17.