Fed-batch microbioreactor platform for scale down and analysis of a plasmid DNA production process
The rising costs of bioprocess research and development emphasize the need for high-throughput, low-cost alternatives to bench-scale bioreactors for process development. In particular, there is a need for platforms that can go beyond simple batch growth of the organism of interest to include more ad...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019
|
| Online Access: | https://hdl.handle.net/1721.1/122647 |
| _version_ | 1826194897546248192 |
|---|---|
| author | Bower, Diana Morgan Lee, Kevin Shao-Kwan Ram, Rajeev J Prather, Kristala L |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Bower, Diana Morgan Lee, Kevin Shao-Kwan Ram, Rajeev J Prather, Kristala L |
| author_sort | Bower, Diana Morgan |
| collection | MIT |
| description | The rising costs of bioprocess research and development emphasize the need for high-throughput, low-cost alternatives to bench-scale bioreactors for process development. In particular, there is a need for platforms that can go beyond simple batch growth of the organism of interest to include more advanced monitoring, control, and operation schemes such as fed-batch or continuous. We have developed a 1-mL microbioreactor capable of monitoring and control of dissolved oxygen, pH, and temperature. Optical density can also be measured online for continuous monitoring of cell growth. To test our microbioreactor platform, we used production of a plasmid DNA vaccine vector (pVAX1-GFP) in Escherichia coli via a fed-batch temperature-inducible process as a model system. We demonstrated that our platform can accurately predict growth, glycerol and acetate concentrations, as well as plasmid copy number and quality obtained in a bench-scale bioreactor. The predictive abilities of the micro-scale system were robust over a range of feed rates as long as key process parameters, such as dissolved oxygen, were kept constant across scales. We have highlighted plasmid DNA production as a potential application for our microbioreactor, but the device has broad utility for microbial process development in other industries as well. Keywords: microbioreactors; Escherichia coli; plasmid biopharmaceuticals; bioprocess development |
| first_indexed | 2024-09-23T10:03:53Z |
| format | Article |
| id | mit-1721.1/122647 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:03:53Z |
| publishDate | 2019 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1226472022-09-26T15:29:08Z Fed-batch microbioreactor platform for scale down and analysis of a plasmid DNA production process Bower, Diana Morgan Lee, Kevin Shao-Kwan Ram, Rajeev J Prather, Kristala L Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Research Laboratory of Electronics The rising costs of bioprocess research and development emphasize the need for high-throughput, low-cost alternatives to bench-scale bioreactors for process development. In particular, there is a need for platforms that can go beyond simple batch growth of the organism of interest to include more advanced monitoring, control, and operation schemes such as fed-batch or continuous. We have developed a 1-mL microbioreactor capable of monitoring and control of dissolved oxygen, pH, and temperature. Optical density can also be measured online for continuous monitoring of cell growth. To test our microbioreactor platform, we used production of a plasmid DNA vaccine vector (pVAX1-GFP) in Escherichia coli via a fed-batch temperature-inducible process as a model system. We demonstrated that our platform can accurately predict growth, glycerol and acetate concentrations, as well as plasmid copy number and quality obtained in a bench-scale bioreactor. The predictive abilities of the micro-scale system were robust over a range of feed rates as long as key process parameters, such as dissolved oxygen, were kept constant across scales. We have highlighted plasmid DNA production as a potential application for our microbioreactor, but the device has broad utility for microbial process development in other industries as well. Keywords: microbioreactors; Escherichia coli; plasmid biopharmaceuticals; bioprocess development 2019-10-22T20:21:04Z 2019-10-22T20:21:04Z 2012-03 2012-03 2019-10-10T12:53:19Z Article http://purl.org/eprint/type/JournalArticle 0006-3592 https://hdl.handle.net/1721.1/122647 Bower, Diana M. et al. "Fed‐batch microbioreactor platform for scale down and analysis of a plasmid DNA production process." Biotechnology and Bioengineering 109, 8 (March 2012) © 2012 Wiley Periodicals, Inc en http://dx.doi.org/10.1002/bit.24498 Biotechnology and Bioengineering Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Prof. Prather |
| spellingShingle | Bower, Diana Morgan Lee, Kevin Shao-Kwan Ram, Rajeev J Prather, Kristala L Fed-batch microbioreactor platform for scale down and analysis of a plasmid DNA production process |
| title | Fed-batch microbioreactor platform for scale down and analysis of a plasmid DNA production process |
| title_full | Fed-batch microbioreactor platform for scale down and analysis of a plasmid DNA production process |
| title_fullStr | Fed-batch microbioreactor platform for scale down and analysis of a plasmid DNA production process |
| title_full_unstemmed | Fed-batch microbioreactor platform for scale down and analysis of a plasmid DNA production process |
| title_short | Fed-batch microbioreactor platform for scale down and analysis of a plasmid DNA production process |
| title_sort | fed batch microbioreactor platform for scale down and analysis of a plasmid dna production process |
| url | https://hdl.handle.net/1721.1/122647 |
| work_keys_str_mv | AT bowerdianamorgan fedbatchmicrobioreactorplatformforscaledownandanalysisofaplasmiddnaproductionprocess AT leekevinshaokwan fedbatchmicrobioreactorplatformforscaledownandanalysisofaplasmiddnaproductionprocess AT ramrajeevj fedbatchmicrobioreactorplatformforscaledownandanalysisofaplasmiddnaproductionprocess AT pratherkristalal fedbatchmicrobioreactorplatformforscaledownandanalysisofaplasmiddnaproductionprocess |