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Mastering bioprocess Integration and intensification across scales

Final Report Summary - BIOINTENSE (Mastering bioprocess Integration and intensification across scales)

BIOINTENSE was a single stage knowledge-based bio-economy (KBBE) collaborative project which ran from 2012-2016. The main objective of BIOINTENSE was to increase biocatalyst productivity and process intensity through the development and application of novel microfluidic and modelling tools. The original premise was that applying such tools would result in economically feasible processes with a shorter development time. Such objectives are of great importance to the industrial implementation of novel biotechnological processes.
The consortium of 6 academic partners (Danmarks Tekniske Universitet (DK), Technische Universität Graz (A), Univerza Ljubljana (SL), Universiteit Gent (B), University of Manchester (UK) and Lunds Universitet (SE)) and 8 industrial partners (DSM Innovative Systems BV (NL), Vlaamse Instelling voor Technologisch Onderzoek N.V. (B), iX-Factory GmbH (D), Microfluidic Chipshop GmbH (D), Luxcel Biosciences Ltd. (IE), LentiKat´s a.s. (CZ), C-Lecta GmbH (D) and Sigma Aldrich (CH)) agreed to focus on enzyme-catalyzed reactions for the production of chiral amine products (using aminotransferases (ATAs)). The production of chiral amines is of great importance in the fine chemical and pharmaceutical industry, making this synthesis a very attractive test system, of immediate commercial relevance.
This highly successful project resulted in the development of (1) new miniaturized devices for evaluating ISPR options, (2) intensified bioprocesses with in-situ product recovery and substrate supply, (3) new miniaturized sensors for monitoring and control, (4) methodologies for understanding and benchmarking the scale-up and numbering-up of biocatalytic processes, (5) a cost effective fermentation and DSP protocol for ATA preparations, (6) multi-objective screening protocols to identify new transaminases fit for process conditions, (7) understanding of inactivation and stability mechanisms for ATAs, (8) cost effective immobilization procedures for increased biocatalyst productivity, (9) economic and environmental evaluation methods to quantify process improvements, and (10) process modelling methods to optimize process performance and experimental protocols through optimal experimental design.
This project has brought together biotechnological scientists as well as microfluidic and modeling experts. This interdisciplinary interaction was at the beginning not straightforward but it resulted in a highly valuable rapid development and progress in the investigated field. This can be observed for instance by the development of new microfluidic products (i.e. the design of 17 new micro-reactors resulting in 24 different micro-reactor prototypes), 24 mass fabrication compatible micro-reactors for further commercial application, standardization of device formats, making the systems applicable with standard laboratory equipment, the development of 6 new chemical products, by using screening of ATA against a library of potential substrates, novel LentiKats® particles with immobilized ATA for the production of fine chemicals, as well as new enzyme products.
The partners of the project have been highly active in the dissemination of the results. The high amount of peer reviewed scientific publications (31) as well as an impressive number of oral and poster presentations at scientific conferences (163) are a good indicator for the scientific dissemination. Additionally, two international conferences on the Implementation of Microreactor Technology in Biotechnology – IMTB (2013 and 2015) were organized within the project. Finally an explanatory animated video about the project has been produced addressing a broader public audience.
This short list of some of the highlights shows the potential of a systematic collaboration across disciplines. Furthermore, it shows the potential for application of miniaturized systems to contribute to the accelerated development of biotechnological-based processes beyond ATA-based reactions.

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