Bioreactor system for Industrial Biotechnology process development

A multi-bioreactor system is requested which contains 16 reactor vessels each with accompanying ports, pumps, individual Peltier heating, condensation reduction, sensors for pH, dissolved oxygen, temperature, foaming and gas monitoring. This is controlled and monitored by a computer based control system. A 16 vessels system is required for an L16 Taguchi Design of Experiment orthogonal array. This allows for the simultaneous assessment of key process variables across the system. It also allows for replication after initial process development. We assessed other technologies including Biolector, but rejected this on the basis of vessel geometry and lack of scale up potential as well as non-standardised probes and sensors when compared to industrial units. The Applikon 250 ml MiniBio range of bioreactors is a true scale-down of the laboratory scale bioreactors in the 1 to 20 litre range. The MiniBio systems have the same flexibility as the laboratory scale and reflect pilot to industrial scale bioreactors. This means that the MiniBio systems can be customised to fit the demands of any process. The small volume reduces: 1) the production and costs of cultivation medium (e.g lignocellulosic hydrolysates); 2) the use of expensive bench space (approx. 1.8 m2) and 3) the time taken to generate large, continuous sets of scientific data. The Lucullus software communicates with the my-Control graphical interface and is compatible with Linux and Windows based operating systems with data export including both standard and processed formats. The fermentation data will complement bioinformatics data generated on the response and stability of microbial cell physiology undergoing bio-processes development. The integration of these data with RNA seq data for both wild-type and improved strains designed through rational genome editing will provide detailed information on biocatalyst performance and provide essential key molecular performance indicators during scale-up.

Industrial biotechnology is a core research platform at the Institute of Biological Environmental and Rural Sciences (IBERS) at Aberystwyth University (AU). This platform will benefit greatly from an automated bioreactor system that will enable 16 simultaneous fermentations to be performed on a multi-millilitre scale (50-250ml) enabling rapid development of industrially scalable fermentation processes. Data from this system will enable identification and testing of multi-factorial parameters critical to fermentation processes in order to optimise productivity and yield, prior to scale-up to an industrially relevant bioprocess. It will assess inhibitors produced as a result of pre-processing technologies and allow studies on microbe-microbe interactions and microbe communities. This equipment would result in a major reduction in time and expense in process optimisation and provide a step change increase in data acquisition and analysis. Additionally this system will enable identification of pathways and metabolic networks by complementing the metabolomics and next generations sequencing data sets produced at IBERS and elsewhere. The advent of the omics era has bought about an improved understanding and modelling of microbial metabolism in traditional, academically characterised bacterial and yeast fermentation systems such as Escherichia coli and Saccharomyces cerevisiae. However, this level of understanding rarely exceeds the scale of shake flask experimentation and pertinently may not reflect IB conditions or industrial production strains. Although tightly controlled, environmental heterogeneity for pH, temperature, rheology product titre and substrate availability is experienced in fermentation vessels during scale-up to industrially relevant volumes (multiple hundreds of litres). There is a paucity of academic and industrial knowledge on the impact of this heterogeneity on cellular physiology, metabolic pools and alterations in global gene expression of both academic model and industrial biocatalysts during scale-up. This equipment will complement existing fermentation systems at IBERS which includes 6x1L, 4x10L, 1x30L, 2x70L and 1x250L automated, precision controlled reaction vessels, allowing for similar control on a smaller scale. Au will provide technical support and make this equipment available to both the academic and industrial community and will highlight it on web sites, equipment databases and brochures.