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Issue 11, 2012
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A disposable picolitre bioreactor for cultivation and investigation of industrially relevant bacteria on the single cell level

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Abstract

In the continuously growing field of industrial biotechnology the scale-up from lab to industrial scale is still a major hurdle to develop competitive bioprocesses. During scale-up the productivity of single cells might be affected by bioreactor inhomogeneity and population heterogeneity. Currently, these complex interactions are difficult to investigate. In this report, design, fabrication and operation of a disposable picolitre cultivation system is described, in which environmental conditions can be well controlled on a short time scale and bacterial microcolony growth experiments can be observed by time-lapse microscopy. Three exemplary investigations will be discussed emphasizing the applicability and versatility of the device. Growth and analysis of industrially relevant bacteria with single cell resolution (in particular Escherichia coli and Corynebacterium glutamicum) starting from one single mother cell to densely packed cultures is demonstrated. Applying the picolitre bioreactor, 1.5-fold increased growth rates of C. glutamicum wild type cells were observed compared to typical 1 litre lab-scale batch cultivation. Moreover, the device was used to analyse and quantify the morphological changes of an industrially relevant L-lysine producer C. glutamicum after artificially inducing starvation conditions. Instead of a one week lab-scale experiment, only 1 h was sufficient to reveal the same information. Furthermore, time lapse microscopy during 24 h picolitre cultivation of an arginine producing strain containing a genetically encoded fluorescence sensor disclosed time dependent single cell productivity and growth, which was not possible with conventional methods.

Graphical abstract: A disposable picolitre bioreactor for cultivation and investigation of industrially relevant bacteria on the single cell level

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Publication details

The article was received on 13 Feb 2012, accepted on 13 Mar 2012 and first published on 15 Mar 2012


Article type: Paper
DOI: 10.1039/C2LC40156H
Citation: Lab Chip, 2012,12, 2060-2068
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    A disposable picolitre bioreactor for cultivation and investigation of industrially relevant bacteria on the single cell level

    A. Grünberger, N. Paczia, C. Probst, G. Schendzielorz, L. Eggeling, S. Noack, W. Wiechert and D. Kohlheyer, Lab Chip, 2012, 12, 2060
    DOI: 10.1039/C2LC40156H

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