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Microbioreactors for nutrient-controlled microbial cultures: Bridging the gap between early bioprocess development and industrial scale use
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  • Kartik Totlani,
  • Rinke van Tatenhove-Pel,
  • Michiel Kreutzer,
  • Walter M. van Gulik,
  • Volkert van Steijn
Kartik Totlani
Delft University of Technology Faculty of Applied Sciences

Corresponding Author:[email protected]

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Rinke van Tatenhove-Pel
Delft University of Technology Faculty of Applied Sciences
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Michiel Kreutzer
Delft University of Technology Faculty of Applied Sciences
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Walter M. van Gulik
Delft University of Technology Faculty of Applied Sciences
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Volkert van Steijn
Delft University of Technology Faculty of Applied Sciences
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Abstract

It is common practice in the development of bioprocesses to genetically modify a microorganism and study a large number of resulting mutants in order to select the ones that perform best for use at the industrial scale. At industrial scale, strict nutrient-controlled growth conditions are imposed to control the metabolic activity and growth rate of the microorganism, thereby enhancing the expression of the product of interest. Although it is known that microorganisms that perform best under these strictly controlled conditions are not the same as the ones that perform best under uncontrolled batch conditions, screening, and selection is predominantly performed under batch conditions. Tools that afford high throughput on the one hand and dynamic control over cultivation conditions on the other hand are not yet available. Microbioreactors offer the potential to address this problem, resolving the gap between bioprocess development and industrial scale use. In this review, we highlight the current state-of-the-art of microbioreactors that offer the potential to screen microorganisms under dynamically controlled conditions. We classify them into: (i) microtiter plate-based platforms, (ii) microfluidic chamber-based platforms, and (iii) microfluidic droplet-based platforms. We conclude this review by discussing the opportunities of nutrient-fed microbioreactors in the field of biotechnology.
27 Oct 2022Submitted to Biotechnology Journal
30 Oct 2022Submission Checks Completed
30 Oct 2022Assigned to Editor
03 Nov 2022Reviewer(s) Assigned
19 Nov 2022Review(s) Completed, Editorial Evaluation Pending
21 Nov 2022Editorial Decision: Revise Major
27 Feb 20231st Revision Received
28 Feb 2023Submission Checks Completed
28 Feb 2023Assigned to Editor
07 Mar 2023Reviewer(s) Assigned
08 Mar 2023Review(s) Completed, Editorial Evaluation Pending
10 Mar 2023Editorial Decision: Accept