Defining mass transfer in a capillary wave micro-bioreactor for dose-response and other cell-based assays

Frey, Lasse Jannis; Vorländer, David; Rasch, Detlev; Meinen, Sven; Müller, Bernhard; Mayr, Torsten; Dietzel, Andreas; Grosch, Jan-Hendrik; Krull, Rainer

doi:10.1016/j.bej.2020.107667

Cited by 8 publications

(20 citation statements)

References 86 publications

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“…This glass chip was placed in a 3D-printed mounting, which ensures the fixation of the chip, sensor read-out via optical fibers and the minimization of evaporation ( Figure 2 e). For the mixing of the cultivation medium by capillary waves induced by vertical oscillation, as described by Frey et al [ 20 ], the cwMBR mounting was screwed onto an exciter platform. The platform was placed in an incubation chamber to provide optimal cultivation conditions in the cwMBR.…”

Section: Methodsmentioning

confidence: 99%

“…The cultivation medium is mixed by capillary waves induced by the vertical oscillation of the cwMBR, as described by Frey et al [ 20 , 44 ] and Meinen et al [ 21 ]. Therefore, the cwMBR mounting was placed on a quadratic polyvinyl chloride platform with an electromagnetic exciter (Ex 45 S, Visaton, Haan, Germany) under each corner.…”

Section: Methodsmentioning

confidence: 99%

“…Since the oxygen and the pH sensors have previously been characterized in different applications [ 8 , 11 , 20 , 32 , 37 , 41 , 44 , 45 ], the sensor characterization focuses on the glucose sensor, which has not been previously described.…”

Section: Methodsmentioning

confidence: 99%

“…This makes them less suitable for high parallelization and automatization and increases media and test substance consumption. Therefore, a 7 µL MBR was developed, which was previously presented by Frey et al [ 20 ] and Meinen et al [ 21 ] and is further optimized in this paper. This MBR is a promising tool combining minimal cultivation volume with integrated optical sensors for process characterization.…”

Section: Introductionmentioning

confidence: 99%

“…The cultivation droplet is mixed by capillary waves induced by the vertical oscillation of the MBR platform, giving the reactor its name: the capillary-wave microbioreactor (cwMBR). At the resonance frequencies of the droplet, capillary waves with specific wave patterns are formed on droplet surfaces, leading to the mixing of the cwMBR volume, as described by Frey et al [ 20 ]. Optimal mixing conditions with volumetric liquid-phase mass transfer coefficients ( k L a ) of more than 340 h − 1 and mixing times of 2 s can be achieved at the resonance frequencies of the droplet.…”

Section: Introductionmentioning

confidence: 99%

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Microsensor in Microbioreactors: Full Bioprocess Characterization in a Novel Capillary-Wave Microbioreactor

et al. 2022

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Microbioreactors (MBRs) with a volume below 1 mL are promising alternatives to established cultivation platforms such as shake flasks, lab-scale bioreactors and microtiter plates. Their main advantages are simple automatization and parallelization and the saving of expensive media components and test substances. These advantages are particularly pronounced in small-scale MBRs with a volume below 10 µL. However, most described small-scale MBRs are lacking in process information from integrated sensors due to limited space and sensor technology. Therefore, a novel capillary-wave microbioreactor (cwMBR) with a volume of only 7 µL has the potential to close this gap, as it combines a small volume with integrated sensors for biomass, pH, dissolved oxygen (DO) and glucose concentration. In the cwMBR, pH and DO are measured by established luminescent optical sensors on the bottom of the cwMBR. The novel glucose sensor is based on a modified oxygen sensor, which measures the oxygen uptake of glucose oxidase (GOx) in the presence of glucose up to a concentration of 15 mM. Furthermore, absorbance measurement allows biomass determination. The optical sensors enabled the characterization of an Escherichia coli batch cultivation over 8 h in the cwMBR as proof of concept for further bioprocesses. Hence, the cwMBR with integrated optical sensors has the potential for a wide range of microscale bioprocesses, including cell-based assays, screening applications and process development.

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Section: Methodsmentioning

confidence: 99%