High-throughput parallel fermentation technology
With the rapid development of microbial metabolic engineering and synthetic biology, the demand for high-throughput screening of high-performance strain bank has been put forward, which further expands the application of parallel fermentation devices with different culture volumes in the field of industrial biotechnology.
Parallel fermentation culture technology refers to a parallel fermentation culture technology of multiple strains in multiple bioreactors with on-line multi-parameter collection, or to carry out parallel culture under multiple fermentation conditions for one strain.
The process needs to meet three basic elements: the consistency of strain and seed culture medium, the consistency of the performance of multiple reactors in parallel culture, and the consistency of detection and analysis of culture process parameters.
Application of parallel fermentation culture technology
1. Efficient process engineering development with DoE
DoE is a scientific experimental method to study the relationship between process input parameters and process output target parameters. By establishing a quantitative mathematical relationship between them to achieve a deep understanding of the process, it can significantly improve the development of fermentation process.
The core of DoE is to systematically study the relationship between critical process parameters (CPPs) and critical quality attributes (CQAs). Compared with the OFAT method, DoE can provide more accurate conclusions. Use the DoE strategy during the evaluation screening and process screening phases to identify key process parameters.
2. Multivariate batch model
Multivariate data analysis（MVDA）can transform a large number of online and offline parameter detection results of fermentation time nodes generated by Process analytical technology（PAT） into classified key process information.
and PLS-MVD batch model can determine whether the differences between the culture conditions of high-throughput parallel fermentation and the culture conditions of pilot and production scale will affect the performance of high-performance strains.
The PLS-MVD batch model established based on the data of parallel fermentation culture can identify the limit range of process parameter changes and the causes of accidents in future culture processes. This is key process information for further development of accurately controlled large-scale culture processes.
3. Process reduction model
Parallel fermentation equipment of micro bioreactors and process reduction models, the former refers to instrument equipment, and the latter refers to technical methods, are both key elements in implementing high-throughput process engineering development strategies under similar industrial conditions.
The establishment of a reduced model must first be based on the cultivation of the same bacteria, collect process parameters through high-throughput culture DoE experiments, establish a process DoE optimization model, and establish a process design space and a multi-variable process model.
Comparing process models and design space data for micro- and scale-cultures. If the results are consistent, a successful process reduction model is established on the micro parallel fermentation device used for this strain.
