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Review
. 2020 Oct 15:18:2908-2919.
doi: 10.1016/j.csbj.2020.10.004. eCollection 2020.

Flow-following sensor devices: A tool for bridging data and model predictions in large-scale fermentations

Jonas Bisgaard  1   2 , Monica Muldbak  2 , Sjef Cornelissen  3 , Tannaz Tajsoleiman  1   2 , Jakob K Huusom  2 , Tue Rasmussen  1 , Krist V Gernaey  2
Affiliations
Review

Flow-following sensor devices: A tool for bridging data and model predictions in large-scale fermentations

Jonas Bisgaard et al. Comput Struct Biotechnol J. .

Abstract

Production-scale fermentation processes in industrial biotechnology experience gradients in process variables, such as dissolved gases, pH and substrate concentrations, which can potentially affect the production organism and therefore the yield and profitability of the processes. However, the extent of the heterogeneity is unclear, as it is currently a challenge at large scale to obtain representative measurements from different zones of the reactor volume. Computational fluid dynamics (CFD) models have proven to be a valuable tool for better understanding the environment inside bioreactors. Without detailed measurements to support the CFD predictions, the validity of CFD models is debatable. A promising technology to obtain such measurements from different zones in the bioreactors are flow-following sensor devices, whose development has recently benefitted from advancements in microelectronics and sensor technology. This paper presents the state of the art within flow-following sensor device technology and addresses how the technology can be used in large-scale bioreactors to improve the understanding of the process itself and to test the validity of detailed computational models of the bioreactors in the future.

Keywords: Computational fluid dynamics; Flow-follower; Gradients; Industrial biotechnology; Large-scale bioreactor; Mixing; Model validation; Modelling; Sensor device.

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Conflict of interest statement

Tue Rasmussen, Tannaz Tajsoleiman (industrial Postdoc), and Jonas Bisgaard (industrial PhD student) are full-time employees at Freesense, a company that has a commercial interest in sensor devices. Monica Muldbak, Jakob K. Huusom, and Krist V. Gernaey are employed at the Technical University of Denmark, with no commercial interests in the sensor devices. Sjef Cornelissen is employed at Novozymes and has an interest in the sensor devices as an end user of the technology.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Illustration of the use of sensor devices in a large-scale stirred tank bioreactor. The sensor devices will be carried around with the liquid flow and measure relevant variables that potentially represent what microorganisms would experience when travelling throughout the volume. The measured values may deviate from the normal operating range in certain zones of the reactor volume.
Fig. 2
Fig. 2
Timeline highlighting important developments in Lagrangian technologies for bioreactors. (See above-mentioned reference for further information.)
Fig. 3
Fig. 3
Instrumented sensor devices: a) Sens-o-sphere . b) smartCAPS (pH version) . c) Bio-capsule . d) bPod .
Fig. 4
Fig. 4
Sensor devices with axial position tracking: a) Sensor particle . b) Fermsense 3D .
Fig. 5
Fig. 5
Stokes number as a function of the characteristic time for the reviewed sensor devices. The relationship is presented for water (0.001 Pa s) and for a low (0.01 Pa s) and a high viscosity (0.1 Pa s) fermentation. The figure serves as a comparison of how the diameter of the sensor devices and the fluid viscosity affects the flow following capabilities. The presented values are only rough estimates as the velocity of the sensor devices compared to the fluid is assumed to be constant, at 0.05 m/s. In addition, perfect buoyancy (ρp/ρf) = 1 is assumed.
See this image and copyright information in PMC

References

    1. Deloitte. Opportunities for the fermentation-based chemical industry. An analysis of the market potential and competitiveness of North-West Europe. 2014.
    1. Crater J., Lievense J.C. Scale-up of industrial microbial processes. FEMS Microbiol Lett. 2018;365:1–5. doi: 10.1093/femsle/fny138. - DOI - PMC - PubMed
    1. Lübbert A. Bubble columns and airlift loop bioreactors. In: Beroviĉ M., Nienow A.W., editors. Biochem. Eng. Princ., Ljubljana, Birmingham: Faculty of Chemistry and Chemical Technology. University of Ljubljana; Slovenia: 2005. pp. 110–125.
    1. Enfors SO. Continuous and fed-batch fermentation. In: Beroviĉ M, Nienow AW, editors. Biochem. Eng. Princ., 2005, p. 146–70.
    1. Stocks S.M. Industrial enzyme production for the food and beverage industries: process scale up and scale down. Microb Prod Food Ingredients, Enzym Nutraceuticals, Elsevier Ltd. 2013:144–172. doi: 10.1533/9780857093547.1.144. - DOI