Biosensors of the Well-being of Cell Cultures
Genetically-encoded biosensors offer advantages over traditional analytical technologies in biological manufacturing. Various biosensor architectures can be employed based on activation of transcription, translation, or folding of a reporter. Such biosensors can be used in small volume, high throughput culture devices to provide a more complete picture of cellular physiology. In addition, because of their simple read out, genetically encoded biosensors can be employed for monitoring during production and offer the opportunity for increased measurement density. This chapter reviews current applications of biosensors to measure cellular health and well-being including designs for detecting the activation of cell stress responses as well as sensing of critical metabolites. Many of these designs have been demonstrated to be relevant to bioprocess engineering or cell line selection, but to date very few have been adopted by industry. In future, ensuring that biosensors function robustly under industrial conditions is a priority, as is designing systems that are compatible with industrial workflows. In the long term, engineering systems that move beyond sensing, to include the ability to adjust the environment of the culture based on signals, will allow biotechnology to fully capitalize on the advantages that genetically encoded biosensors can bring.
KeywordsBioprocess engineering Bioreactor Biosynthesis Metabolism Cell stress response Recombinant protein production Metabolic engineering
- Brognaux A, Han SS, Sorensen SJ, Lebeau F, Thonart P, Delvigne F (2013a) A low-cost, multiplexable, automated flow cytometry procedure for the characterization of microbial stress dynamics in bioreactors. Microb Cell Factories 12. https://doi.org/10.1186/1475-2859-12-100PubMedPubMedCentralCrossRefGoogle Scholar
- Goers L, Kylilis N, Tomazou M, Wen KY, Freemont P, Polizzi K (2013) Engineering microbial biosensors. In: Harwood C, Wipat A (eds) Microbial synthetic biology. Methods in microbiology, vol 40. Academic, Oxford, pp 119–156Google Scholar
- Lim B, Gross CA (2011) Cellular response to heat shock and cold shock. In: Bacterial stress responses, 2nd edn. American Society of Microbiology, Washington, DCGoogle Scholar
- Millipore M (2018) 21CFR Part 11 Compliance Guidelines for Guava® ViaCount® Reagent Assay. https://www.merckmillipore.com/GB/en/life-science-research/cell-analysis-flow-cytometry/guava-easycyte-flow-cytometers/Flow-Cytometry-Applications/bioprocess/Yo.b.qB.dwoAAAFE5k1zAv6g,nav?ReferrerURL=https%3A%2F%2Fwww.google.co.uk%2F&bd=1