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Microfluidics in Biotechnology pp 67–100Cite as

Microbioreactors for Process Development and Cell-Based Screening Studies

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Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 179))

Abstract

Microbioreactors (MBRs) have emerged as potent cultivation devices enabling automated small-scale experiments in parallel while enhancing their cost efficiency. The widespread use of MBRs has contributed to recent advances in industrial and pharmaceutical biotechnology, and they have proved to be indispensable tools in the development of many modern bioprocesses. Being predominantly applied in early stage process development, they open up new fields of research and enhance the efficacy of biotechnological product development. Their reduced reaction volume is associated with numerous inherent advantages – particularly the possibility for enabling parallel screening operations that facilitate high-throughput cultivations with reduced sample consumption (or the use of rare and expensive educts). As a result, multiple variables can be examined in a shorter time and with a lower expense. This leads to a simultaneous acceleration of research and process development along with decreased costs.

MBRs range from simple miniaturized cultivations vessels (i.e., in the milliliter scale with limited possibilities for process control) to highly complex and automated small-scale microreactors with integrated sensors that allow for comprehensive screenings in very short time or a precise reflection of large-scale cultivation conditions. Progressive developments and improvements in manufacturing and automation techniques are already helping researchers to make use of the advantages that MBRs offer. This overview of current MBR systems surveys the diverse application for microbial and mammalian cell cultivations that have been developed in recent years.

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Abbreviations

μBC:

Microbubble column-bioreactor

μ max :

Specific growth rate

CHO:

Chinese hamster ovary

cwMBR:

Capillary wave MBR

D:

Dilution rate

DMF:

Digital microfluidics

DO:

Dissolved oxygen

EWOD:

Electrowetting on dielectric

hMBR:

Horizontally arranged plug flow-based microbioreactor

k L a :

Volumetric liquid phase oxygen transfer coefficient

K S :

Monod constant

LHS:

Liquid handling system

MBR:

Microbioreactor

MTP:

Microtiter plate

n crit :

Critical shaking frequency

OD:

Optical density

OTR :

Oxygen transfer rate

OUR :

Oxygen uptake rate

P/V:

Mean volumetric power input

PCR:

Polymerase chain reaction

PDMS:

Poly(dimethylsiloxane)

PMMA:

Polymethylmethacrylate

q P :

Specific product formation rate

q S :

Specific substrate consumption rate

Re :

Reynolds number

SAW:

Surface acoustic waves

t M :

Mixing time

u G :

Superficial gas velocity

Y X/S , Y P/S, Y P/X :

Biomass- and product-related yield coefficients from substrate/biomass, respectively

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Acknowledgments

The authors gratefully acknowledge financial support from the German Research Foundation (DFG) within the project Development of micro-reactors for biopharmaceutical applications (KR 1897/5-1, 310619924).

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  1. Institute of Biochemical Engineering (ibvt), Technische Universität Braunschweig, Braunschweig, Germany

    Lasse Jannis Frey & Rainer Krull

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  1. Institute of Physics, University of Augsburg, Augsburg, Germany

    Janina Bahnemann

  2. Multiscale Bioengineering, Faculty of Technology, Bielefeld University, Bielefeld, Germany

    Alexander Grünberger

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Frey, L.J., Krull, R. (2020). Microbioreactors for Process Development and Cell-Based Screening Studies. In: Bahnemann, J., Grünberger, A. (eds) Microfluidics in Biotechnology. Advances in Biochemical Engineering/Biotechnology, vol 179. Springer, Cham. https://doi.org/10.1007/10_2020_130

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