Application of Mini- and Micro-Bioreactors for Microbial Bioprocesses

Ladner, Tobias; Grünberger, Alexander; Probst, Christopher; Kohlheyer, Dietrich; Büchs, Jochen; Delvigne, Frank

doi:10.1016/b978-0-444-63663-8.00015-x

Cited by 18 publications

(14 citation statements)

References 115 publications

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“…A complementary way to evaluate the microbial phenotypic heterogeneity under realistic bioprocess conditions is by employing scale down single cell micro-cultivation devices in which large scale reactors conditions are mimicked. Single cells in lab-on-a-chip microfluidic devices allow parallelization and high throughput experiments ( Grünberger et al, 2014 ; Dusny and Schmid, 2015 ; Rosenthal et al, 2015 ; Oliveira et al, 2016 ), contributing to large-scale bioprocess improvement ( Grünberger et al, 2012 ; Ladner et al, 2017 ). Sorting of different subpopulations of cells in order to understand the physiological responses in fluctuating microenvironments was also performed by microarray analysis ( Hewitt et al, 2007 ).…”

Section: Experimental Methodsmentioning

confidence: 99%

Heterogeneity in Pure Microbial Systems: Experimental Measurements and Modeling

et al. 2017

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Cellular heterogeneity influences bioprocess performance in ways that until date are not completely elucidated. In order to account for this phenomenon in the design and operation of bioprocesses, reliable analytical and mathematical descriptions are required. We present an overview of the single cell analysis, and the mathematical modeling frameworks that have potential to be used in bioprocess control and optimization, in particular for microbial processes. In order to be suitable for bioprocess monitoring, experimental methods need to be high throughput and to require relatively short processing time. One such method used successfully under dynamic conditions is flow cytometry. Population balance and individual based models are suitable modeling options, the latter one having in particular a good potential to integrate the various data collected through experimentation. This will be highly beneficial for appropriate process design and scale up as a more rigorous approach may prevent a priori unwanted performance losses. It will also help progressing synthetic biology applications to industrial scale.

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Section: Experimental Methodsmentioning

confidence: 99%

Heterogeneity in Pure Microbial Systems: Experimental Measurements and Modeling

et al. 2017

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“…The high degree of control of cell culture conditions by microfluidic systems has been widely reported in literatures (Mehling & Tay, 2014;W, Huangb, & Lee, 2010). The subsequent development of microfluidic-based microbioreactors offer numerous advantages, including easy operation, automated, and low cost (Ladner et al, 2017). The first considerations when culturing cells on microfluidics are adherent culture conditions for adherent cells.…”

Section: Antibody Expression Technologymentioning

confidence: 99%

Application of Microfluidic Technology in Field of Antibody Preparation

Sun¹,

Hu²,

wang³

2021

Preprint

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Microfluidic technology is a science and technology that can accurately manipulate fluids in micro-sized channels. In recent years, microfluidic devices have attracted wide attention due to its easy manipulation, miniaturized size, high throughput and precise control, which provide a potential platform for antibody screening. This review paper provides an overview of recent advances in microfluidic methods application in the field of antibody preparation. While hybridoma technology and four antibody engineering techniques including phage display, single B cell antibody screening, antibody expression and cell-free protein synthesis are mainly introduced, important advances of experimental models and results are also discussed. Furthermore, the authors expound on the limitations of current microfluidic screening system and present future directions of antibody screening platform based on microfluidics. Antibody preparation on microfluidics combined with other technologies has huge application potential in the field of biomedicine, and it is anticipated to be further developed.

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Section: Mathematical Characterization Of Microbial Population Heteromentioning

confidence: 99%

“…Dynamics of microbial population heterogeneity can be followed either by using flow cytometry (FC) or dedicated microfluidic cultivation devices where cells can be tracked via time-lapse imaging [68]. Flow cytometry enables high-throughput characterization of cell suspensions, a feature being reinforced by the implementation of on-line platforms.…”

Section: Approaches For Quantifying Microbial Population Heterogeneitymentioning

confidence: 99%

“…In the case of flow cytometry data, measuring dynamics of the population suffers from the lack of knowledge at the level of the specific cell trajectories and physicochemical gradients within the cultivation volume. This is due to the fact that population heterogeneity is generally captured as a temporal physiological snapshot of the population . In the case of microscopy imaging, environmental factors can be controlled, but image analysis can be tedious and prone to error when generating high‐throughput physiological data .…”

Section: Controlling Microbial Phenotypic Heterogeneity: State‐of‐thementioning

confidence: 99%

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Taking control over microbial populations: Current approaches for exploiting biological noise in bioprocesses

Delvigne

Baert

Sassi

et al. 2017

Biotechnology Journal

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Phenotypic plasticity of microbial cells has attracted much attention and several research efforts have been dedicated to the description of methods aiming at characterizing phenotypic heterogeneity and its impact on microbial populations. However, different approaches have also been suggested in order to take benefit from noise in a bioprocess perspective, e.g. by increasing the robustness or productivity of a microbial population. This review is dedicated to outline these controlling methods. A common issue, that has still to be addressed, is the experimental identification and the mathematical expression of noise. Indeed, the effective interfacing of microbial physiology with external parameters that can be used for controlling physiology depends on the acquisition of reliable signals. Latest technologies, like single cell microfluidics and advanced flow cytometric approaches, enable linking physiology, noise, heterogeneity in productive microbes with environmental cues and hence allow correctly mapping and predicting biological behavior via mathematical representations. However, like in the field of electronics, signals are perpetually subjected to noise. If appropriately interpreted, this noise can give an additional insight into the behavior of the individual cells within a microbial population of interest. This review focuses on recent progress made at describing, treating and exploiting biological noise in the context of microbial populations used in various bioprocess applications.

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Application of Mini- and Micro-Bioreactors for Microbial Bioprocesses

Cited by 18 publications

References 115 publications

Heterogeneity in Pure Microbial Systems: Experimental Measurements and Modeling

Heterogeneity in Pure Microbial Systems: Experimental Measurements and Modeling

Application of Microfluidic Technology in Field of Antibody Preparation

Taking control over microbial populations: Current approaches for exploiting biological noise in bioprocesses

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