High-throughput microbioreactor provides a capable tool for early stage bioprocess development
Abstract Tremendous advancements in cell and protein engineering methodologies and bioinformatics have led to a vast increase in bacterial production clones and recombinant protein variants to be screened and evaluated. Consequently, an urgent need exists for efficient high-throughput (HTP) screenin...
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Nature Portfolio
2021
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oai:doaj.org-article:2638648bdcb948bb8400c8e1cfce7a312021-12-02T15:23:38ZHigh-throughput microbioreactor provides a capable tool for early stage bioprocess development10.1038/s41598-021-81633-62045-2322https://doaj.org/article/2638648bdcb948bb8400c8e1cfce7a312021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81633-6https://doaj.org/toc/2045-2322Abstract Tremendous advancements in cell and protein engineering methodologies and bioinformatics have led to a vast increase in bacterial production clones and recombinant protein variants to be screened and evaluated. Consequently, an urgent need exists for efficient high-throughput (HTP) screening approaches to improve the efficiency in early process development as a basis to speed-up all subsequent steps in the course of process design and engineering. In this study, we selected the BioLector micro-bioreactor (µ-bioreactor) system as an HTP cultivation platform to screen E. coli expression clones producing representative protein candidates for biopharmaceutical applications. We evaluated the extent to which generated clones and condition screening results were transferable and comparable to results from fully controlled bioreactor systems operated in fed-batch mode at moderate or high cell densities. Direct comparison of 22 different production clones showed great transferability. We observed the same growth and expression characteristics, and identical clone rankings except one host-Fab-leader combination. This outcome demonstrates the explanatory power of HTP µ-bioreactor data and the suitability of this platform as a screening tool in upstream development of microbial systems. Fast, reliable, and transferable screening data significantly reduce experiments in fully controlled bioreactor systems and accelerate process development at lower cost.Mathias FinkMonika Cserjan-PuschmannDaniela ReinischGerald StriednerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Mathias Fink Monika Cserjan-Puschmann Daniela Reinisch Gerald Striedner High-throughput microbioreactor provides a capable tool for early stage bioprocess development |
| description |
Abstract Tremendous advancements in cell and protein engineering methodologies and bioinformatics have led to a vast increase in bacterial production clones and recombinant protein variants to be screened and evaluated. Consequently, an urgent need exists for efficient high-throughput (HTP) screening approaches to improve the efficiency in early process development as a basis to speed-up all subsequent steps in the course of process design and engineering. In this study, we selected the BioLector micro-bioreactor (µ-bioreactor) system as an HTP cultivation platform to screen E. coli expression clones producing representative protein candidates for biopharmaceutical applications. We evaluated the extent to which generated clones and condition screening results were transferable and comparable to results from fully controlled bioreactor systems operated in fed-batch mode at moderate or high cell densities. Direct comparison of 22 different production clones showed great transferability. We observed the same growth and expression characteristics, and identical clone rankings except one host-Fab-leader combination. This outcome demonstrates the explanatory power of HTP µ-bioreactor data and the suitability of this platform as a screening tool in upstream development of microbial systems. Fast, reliable, and transferable screening data significantly reduce experiments in fully controlled bioreactor systems and accelerate process development at lower cost. |
| format |
article |
| author |
Mathias Fink Monika Cserjan-Puschmann Daniela Reinisch Gerald Striedner |
| author_facet |
Mathias Fink Monika Cserjan-Puschmann Daniela Reinisch Gerald Striedner |
| author_sort |
Mathias Fink |
| title |
High-throughput microbioreactor provides a capable tool for early stage bioprocess development |
| title_short |
High-throughput microbioreactor provides a capable tool for early stage bioprocess development |
| title_full |
High-throughput microbioreactor provides a capable tool for early stage bioprocess development |
| title_fullStr |
High-throughput microbioreactor provides a capable tool for early stage bioprocess development |
| title_full_unstemmed |
High-throughput microbioreactor provides a capable tool for early stage bioprocess development |
| title_sort |
high-throughput microbioreactor provides a capable tool for early stage bioprocess development |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/2638648bdcb948bb8400c8e1cfce7a31 |
| work_keys_str_mv |
AT mathiasfink highthroughputmicrobioreactorprovidesacapabletoolforearlystagebioprocessdevelopment AT monikacserjanpuschmann highthroughputmicrobioreactorprovidesacapabletoolforearlystagebioprocessdevelopment AT danielareinisch highthroughputmicrobioreactorprovidesacapabletoolforearlystagebioprocessdevelopment AT geraldstriedner highthroughputmicrobioreactorprovidesacapabletoolforearlystagebioprocessdevelopment |
| _version_ |
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