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Open AccessArticle

Reproduction of Large-Scale Bioreactor Conditions on Microfluidic Chips

1
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425 Jülich, Germany
2
Multiscale Bioengineering, Bielefeld University, 33615 Bielefeld, Germany
3
Bioprocess Engineering, Department of Biotechnology, Technische Universität Berlin, 13355 Berlin, Germany
4
Microscale Bioengineering, Aachener Verfahrenstechnik (AVT.MSB), RWTH Aachen University, 52074 Aachen, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Microorganisms 2019, 7(4), 105; https://doi.org/10.3390/microorganisms7040105
Received: 18 March 2019 / Revised: 3 April 2019 / Accepted: 15 April 2019 / Published: 19 April 2019
(This article belongs to the Special Issue Microbial Cultivation and Analysis in Microsystems)
Microbial cells in industrial large-scale bioreactors are exposed to fluctuating conditions, e.g., nutrient concentration, dissolved oxygen, temperature, and pH. These inhomogeneities can influence the cell physiology and metabolism, e.g., decelerate cell growth and product formation. Microfluidic systems offer new opportunities to study such effects in great detail by examining responses to varying environmental conditions at single-cell level. However, the possibility to reproduce large-scale bioreactor conditions in microscale cultivation systems has not yet been systematically investigated. Hence, we apply computational fluid dynamics (CFD) simulations to analyze and compare three commonly used microfluidic single-cell trapping and cultivation devices that are based on (i) mother machines (MM), (ii) monolayer growth chambers (MGC), and (iii) negative dielectrophoresis (nDEP). Several representative time-variant nutrient concentration profiles are applied at the chip entry. Responses to these input signals within the studied microfluidic devices are comparatively evaluated at the positions of the cultivated cells. The results are comprehensively presented in a Bode diagram that illustrates the degree of signal damping depending on the frequency of change in the inlet concentration. As a key finding, the MM can accurately reproduce signal changes that occur within 1 s or slower, which are typical for the environmental conditions observed by single cells in large-scale bioreactors, while faster changes are levelled out. In contrast, the nDEP and MGC are found to level out signal changes occurring within 10 s or faster, which can be critical for the proposed application. View Full-Text
Keywords: microfluidics; single-cell analysis; modelling; simulation; computational fluid dynamics; frequency response; life line; monolayer growth chamber; mother machine; negative dielectrophoresis microfluidics; single-cell analysis; modelling; simulation; computational fluid dynamics; frequency response; life line; monolayer growth chamber; mother machine; negative dielectrophoresis
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MDPI and ACS Style

Ho, P.; Westerwalbesloh, C.; Kaganovitch, E.; Grünberger, A.; Neubauer, P.; Kohlheyer, D.; Lieres, E. Reproduction of Large-Scale Bioreactor Conditions on Microfluidic Chips. Microorganisms 2019, 7, 105.

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