From industrial fermentor to CFD-guided downscaling: what have we learned?

• Published in: Biochemical engineering journal 2018-12, Vol.140, p.57-71
• Main Authors: Haringa, Cees, Mudde, Robert F., Noorman, Henk J.
• Format: Article
• Language: English
• Subjects: CFD; Downscaling; Euler–Lagrange; Fermentation; Metabolic modeling
• ISSN: 1369-703X; 1873-295X
• DOI: 10.1016/j.bej.2018.09.001

[Display omitted] •A comprehensive overview of the Euler–Lagrange bioreactor simulation approach.•Application of Euler–Lagrange CFD to three different case studies.•Different strategies to design scale-down experiments using CFD data are discussed.•Approach selection chart based on hydrodynamic characteristics of modeled reactor.•The potential of combining Euler–Lagrange CFD with microfluidics is discussed. Euler–Lagrange computational fluid dynamics simulations offer great potential for the integration of transport dynamics and metabolic dynamics in fermentation systems. Since the seminal work of Lapin et al. [1,2], progress has been made, mainly in the analysis of CFD data and translation to laboratory setup designs. Different large-scale processes require different analysis methods; in this paper we discuss which analysis methods are best suited for given reactor types, by reviewing prior simulation cases as well as introducing new test cases. Furthermore, we address challenges in the translation from Euler–Lagrange simulations to laboratory scale systems, and propose methods to work around these shortcomings. Based on the current state of the art, we propose guidelines for the selection of data analysis methods, and we discuss the design of rational scale-down simulators. We conclude with a brief discussion regarding the requirements and possibilities of next-generation scale-down simulators, such as microfluidic single-cell analysis, and possible ways to approximate cellular lifelines from invasive intra-cellular measurements.