Systematic consideration of inhomogeneity at the large scale: towards a stringent development of industrial bioprocesses
acronym: SCILS

RESULTS of SCILS: Presentation can be found here.

Project coordinator:
- Prof. Dr. Marco Oldiges - Institute of Bio- and Geosciences, IBG-1: Biotechnology / Forschungszentrum Jülich GmbH - Germany
Project leaders:
- Prof. Dr. rer. nat. Peter Neubauer - Technische Universität Berlin - Germany
- CTO Friedel-Herbert Schawartz - Sequip S & E GmbH, Düsseldorf - Germany
- Dr. Carlos Barreiro - Asociación de Investigación (INBIOTEC) Instituto de Biotecnología de León - Spain
- Chief Operating Officer, PhD Kjeld, Raunkjær Kjeldsen - Vitalys I/S, Esbjerg N - Denmark
- Prof. Chris D. Rielly - Department of Chemical Engineering, Loughborough University, Leicestershire - UK
- Research Manager Håvard Sletta - SINTEF Materials and Chemistry, Department of Biotechnology, Trondheim - Norway

The project aims to systematically elucidate the influence of increasing bioreactor inhomogeneity which occurs in industrial-scale bioreactor, with respect to microbial physiology and production performance of Corynebacterium glutamicum, a microorganism with broad industrial applications. Early consideration of inhomogeneity issues during lab scale process development will facilitate the selection of the most potent production strain, accelerate the upscaling process and improve the performance at production scale. Such inhomogeneous conditions can be mimicked at lab scale by a so called scale-down simulator bioreactor, consisting of a well-mixed stirred tank reactor (STR) and a plug-flow reactor (PFR) connected in series to it. During operation the cultivation volume is continuously pumped from the STR through the PFR simulating zones of inhomogeneity known to be present at the large scale.

This central challenge of inhomogeneity is addressed, for the first time, by an effort bridging both, the cellular and the process level, enabled by scale-down simulator bioreactor technology, innovative process analytical technology, multi-omics analysis and genetic engineering.

General objectives of the project

scale-down simulator bioreactor studies for lab scale analysis of bioreactor inhomogeneity using process and multi-omics data
development of novel tools for advanced bioprocess characterization and analytics
engineering of microbial systems with improved robustness to bioreactor inhomogeneity
evaluation of bioreactor inhomogeneity by computational fluid dynamics (CFD) and linkage with metabolic network models

Expected results

knowledge about influence of inhomogeneous conditions on metabolic regulation, stress patterns and omics data and methods for improved scale-up
integration of novel in-situ optical sensor technology to study morphology and physiology aspects
framework for application of flow-following mobile sensors (sensor pill) in bioreactors and concepts for the harvesting and data collection procedures
novel robust strains which are less sensitive to inhomogeneous conditions at larger scale for more effective processes and accelerated upscaling
prediction of large scale process performance by linking CFD with metabolic network modeling and process data


Results and inventions will be translated into innovation and will attract attention from industry and the scientific community. Knowledge will be patented/licensed and proper dissemination of results will be achieved by high-quality peer-reviewed publications, presentation at conferences and industrial meetings. The project has the potential to lead to highly innovative industrial applications and to improve the competitiveness of European companies in the bioprocessing sector.