Impact of aeration strategies on fed-batch cell culture kinetics in a single-use 24-well miniature bioreactor

Betts, John; Warr, Steve; Finka, Gary; Uden, Mark; Town, Margaret; Janda, Joachim; Baganz, Frank; Lye, Gary J.

doi:10.1016/j.bej.2013.11.010

Cited by 35 publications

(30 citation statements)

References 28 publications

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“…Moreover, growth phenotypes, likely induced by ventilation or temperature effects within the incubation chamber (Pacheco et al, ) or uneven CO 2 mass transfer into the wells (Han et al, ), were observed. With regard to extended cultivation times, evaporation control needs to be evaluated carefully, as high liquid loss may distort cultures’ performance (Betts et al, ; Silk et al, ). Many of the systems presented use top side illumination of the MTP potentially impeding the use of appropriate sterile barriers ensuring monoseptic conditions and restricting the accessibility with respect to integration into laboratory robotic platforms.…”

Section: Introductionmentioning

confidence: 99%

Design and validation of a parallelized micro‐photobioreactor enabling phototrophic bioprocess development at elevated throughput

Morschett

Schiprowski

Müller³

et al. 2016

Biotech & Bioengineering

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Microalgae offer great potential for the industrial production of numerous compounds, but most of the currently available processes fail on economic aspects. Due to the lack of appropriate microcultivation systems, especially screening and early stage laboratory process characterization limit throughput in process development. Consequently, a demand for high throughput photobioreactors has recently been identified upon which some prototype systems emerged. However, compared to microbial microbioreactors, the systems so far introduced suffer from at least one of several drawbacks, that is, inhomogeneous conditions, poor mixing or excessive evaporation. In this context, a microtiter plate based micro-photobioreactor was developed enabling 48-fold parallelized cultivation. Strict control of the process conditions enabled a high comparability between the distinct wells of one plate (±5% fluctuation in biomass formation). The small scale, resulting in a beneficial surface to volume ratio, as well as the fast mixing due to rigorous orbital shaking, ensured an excellent light supply of the cultures. Moreover, non-invasive online biomass quantification was implemented via a scattered light analyzer that is capable of biomass measurements during continuous illumination of the cultures. The system was shown to be especially qualified for parallelized laboratory screening applications like for instance media optimization. Easy automation via integration into a liquid handling platform is given by design. Thereby, the presented micro-photobioreactor system significantly contributes to improving the time efficiency during the development of phototrophic bioprocesses. Biotechnol. Bioeng. 2017;114: 122-131. © 2016 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

Design and validation of a parallelized micro‐photobioreactor enabling phototrophic bioprocess development at elevated throughput

Morschett

Schiprowski

Müller³

et al. 2016

Biotech & Bioengineering

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“…One of the key advantages of this system is that it offers the flexibility of culturing either mammalian or microbial cells, whereas the AMBR™ microbioreactor system is designed specifically for mammalian cell applications. This system has shown consistent results in terms of cell growth and process control and can serve as a scale-down model for initial clone evaluation workflows [31][32][33][34]. One potential drawback of the Micro-24™ microreactor system is the lack of onboard liquid handling.…”

Section: High-throughput Microbioreactor Screening and Process Developmentmentioning

confidence: 88%

High-throughput screening and automation approaches for the development of recombinant therapeutic proteins

Keil

2015

Pharmaceutical Bioprocessing

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Generation of recombinant therapeutic proteins involves the use of Chinese hamster ovary cells as one of the workhorses for complex protein production. This process requires screening large numbers of transfected cells to identify single clones that have high protein production and drug-specific quality attributes. Traditionally, this process was limited by manual operation; however, high-throughput screening methods and automation have made this process more efficient. Implementation of high-throughput screening and automation within bioprocess development have led to increased screening capacity, higher product yields, reductions in manual operation, reduction in human error and shorter development time lines. This review outlines the high-throughput methodologies and technologies currently used for clone screening, selection and evaluation in bioprocess development.

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“…Another commercial manufacturer Micro-24 (pall.com) [11] developed a microbioreactor for screening strains and cell lines besides optimization of growth and feed parameters. These microbioreactors support single-use cassettes with 24 columns with culture volume ranging from 3 to 7 ml and regulate pH using ammonia, carbon dioxide, and control over temperature.…”

Section: Types Of Microbioreactorsmentioning

confidence: 99%

Microbioreactors and Perfusion Bioreactors for Microbial and Mammalian Cell Culture

Ravindran¹,

Singh²,

Nene³

et al. 2019

Biotechnology and Bioengineering

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Screening for novel producer strains and enhanced therapeutic production at reduced cost has been the focus of most of the biopharmaceutical industries. The obligation to carry out prolonged intensive pilot scale experiments gave birth to micro-scale bioreactor systems. Screening large number of microorganisms using shake flasks and benchtop bioreactors is tedious and consumes resources. Microbioreactors that mimic benchtop bioreactors are capable not only of high throughput screening of producer strains, but also aid in optimizing the growth kinetics and expression of proteins. Modern technology has enabled the collection of precise online data for variables such as optical density (OD), pH, temperature, dissolved oxygen (DO), and adjusting in mixing inside microreactors. Microbioreactors have become an irreplaceable tool for biochemical engineers and biotechnologists to perform a large number of experiments simultaneously. Another aspect that is vital to any industry is the product yield and subsequent downstream processing. Perfusion bioreactors are one of the upcoming advances in bioreactor systems that have the potential to revolutionize biologics production. This chapter intends to take a review of different aspects of microbioreactors and perfusion bioreactors including their potential in high throughput pilot studies and microbial and mammalian cell cultivation technologies.

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Impact of aeration strategies on fed-batch cell culture kinetics in a single-use 24-well miniature bioreactor

Cited by 35 publications

References 28 publications

Design and validation of a parallelized micro‐photobioreactor enabling phototrophic bioprocess development at elevated throughput

Design and validation of a parallelized micro‐photobioreactor enabling phototrophic bioprocess development at elevated throughput

High-throughput screening and automation approaches for the development of recombinant therapeutic proteins

Microbioreactors and Perfusion Bioreactors for Microbial and Mammalian Cell Culture

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