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Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process

Cost effective and scalable methods for phage production are required to meet an increasing demand for phage, as an alternative to antibiotics. Computational models can assist the optimization of such production processes. A model is developed here that can simulate the dynamics of phage population...

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Detalles Bibliográficos
Autores principales: Krysiak-Baltyn, Konrad, Martin, Gregory J. O., Gras, Sally L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026895/
https://www.ncbi.nlm.nih.gov/pubmed/29642497
http://dx.doi.org/10.3390/ph11020031
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author Krysiak-Baltyn, Konrad
Martin, Gregory J. O.
Gras, Sally L.
author_facet Krysiak-Baltyn, Konrad
Martin, Gregory J. O.
Gras, Sally L.
author_sort Krysiak-Baltyn, Konrad
collection PubMed
description Cost effective and scalable methods for phage production are required to meet an increasing demand for phage, as an alternative to antibiotics. Computational models can assist the optimization of such production processes. A model is developed here that can simulate the dynamics of phage population growth and production in a two-stage, self-cycling process. The model incorporates variable infection parameters as a function of bacterial growth rate and employs ordinary differential equations, allowing application to a setup with multiple reactors. The model provides simple cost estimates as a function of key operational parameters including substrate concentration, feed volume and cycling times. For the phage and bacteria pairing examined, costs and productivity varied by three orders of magnitude, with the lowest cost found to be most sensitive to the influent substrate concentration and low level setting in the first vessel. An example case study of phage production is also presented, showing how parameter values affect the production costs and estimating production times. The approach presented is flexible and can be used to optimize phage production at laboratory or factory scale by minimizing costs or maximizing productivity.
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spelling pubmed-60268952018-07-13 Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process Krysiak-Baltyn, Konrad Martin, Gregory J. O. Gras, Sally L. Pharmaceuticals (Basel) Communication Cost effective and scalable methods for phage production are required to meet an increasing demand for phage, as an alternative to antibiotics. Computational models can assist the optimization of such production processes. A model is developed here that can simulate the dynamics of phage population growth and production in a two-stage, self-cycling process. The model incorporates variable infection parameters as a function of bacterial growth rate and employs ordinary differential equations, allowing application to a setup with multiple reactors. The model provides simple cost estimates as a function of key operational parameters including substrate concentration, feed volume and cycling times. For the phage and bacteria pairing examined, costs and productivity varied by three orders of magnitude, with the lowest cost found to be most sensitive to the influent substrate concentration and low level setting in the first vessel. An example case study of phage production is also presented, showing how parameter values affect the production costs and estimating production times. The approach presented is flexible and can be used to optimize phage production at laboratory or factory scale by minimizing costs or maximizing productivity. MDPI 2018-04-08 /pmc/articles/PMC6026895/ /pubmed/29642497 http://dx.doi.org/10.3390/ph11020031 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Krysiak-Baltyn, Konrad
Martin, Gregory J. O.
Gras, Sally L.
Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process
title Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process
title_full Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process
title_fullStr Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process
title_full_unstemmed Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process
title_short Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process
title_sort computational modelling of large scale phage production using a two-stage batch process
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026895/
https://www.ncbi.nlm.nih.gov/pubmed/29642497
http://dx.doi.org/10.3390/ph11020031
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