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Resonant Mixing in Glass Bowl Microbioreactor Investigated by Microparticle Image Velocimetry

1
Institute of Microtechnology, Technische Universität Braunschweig, 38124 Braunschweig, Germany
2
Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, 38106 Braunschweig, Germany
3
Institute of Biochemical Engineering, Technische Universität Braunschweig, 38106 Braunschweig, Germany
*
Author to whom correspondence should be addressed.
Micromachines 2019, 10(5), 284; https://doi.org/10.3390/mi10050284
Received: 8 April 2019 / Revised: 24 April 2019 / Accepted: 25 April 2019 / Published: 27 April 2019
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PDF [4075 KB, uploaded 27 April 2019]
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Abstract

Microbioreactors are gaining increased interest in biopharmaceutical research. Due to their decreasing size, the parallelization of multiple reactors allows for simultaneous experiments. This enables the generation of high amounts of valuable data with minimal consumption of precious pharmaceutical substances. However, in bioreactors of all scales, fast mixing represents a crucial condition. Efficient transportation of nutrients to the cells ensures good growing conditions, homogeneous environmental conditions for all cultivated cells, and therefore reproducible and valid data. For these reasons, a new type of batch microbioreactor was developed in which any moving mixer component is rendered obsolete through the utilization of capillary surface waves for homogenization. The bioreactor was fabricated in photosensitive glass and its fluid volume of up to 8 µL was provided within a bowl-shaped volume. External mechanical actuators excited capillary surface waves and stereo microparticle image velocimetry (µPIV) was used to analyze resulting convection at different excitation conditions in varied reactor geometries. Typical vortex patterns were observed at certain resonance frequencies where best mixing conditions occurred. Based on the results, a simplified 1D model which predicts resonance frequencies was evaluated. Cultivation of Escherichia coli BL21 under various mixing conditions showed that mixing in resonance increased the biomass growth rate, led to high biomass concentrations, and provided favorable growth conditions. Since glass slides containing multiple bowl reactors can be excited as a whole, massive parallelization is foreseen. View Full-Text
Keywords: microbioreactor; femtosecond laser structuring; photosensitive glass; microparticle image velocimetry; capillary waves microbioreactor; femtosecond laser structuring; photosensitive glass; microparticle image velocimetry; capillary waves
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Meinen, S.; Frey, L.J.; Krull, R.; Dietzel, A. Resonant Mixing in Glass Bowl Microbioreactor Investigated by Microparticle Image Velocimetry. Micromachines 2019, 10, 284.

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