Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process
Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process
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DOI：
10.3390/ph11020031
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发表时间：
2018-06-01
期刊：
影响因子：
4.6
通讯作者：
Gras, Sally L.
中科院分区：
文献类型：
--
作者：
Krysiak-Baltyn, Konrad;Martin, Gregory J. O.;Gras, Sally L.
为了满足日益增长的对作为抗生素替代品的噬菌体的需求，需要具有成本效益和可扩展的噬菌体生产方法。计算模型可以帮助优化这样的生产过程。本文建立了一个模型，可以模拟噬菌体种群在两阶段自循环过程中的生长和生产动态。该模型结合了作为细菌生长速度函数的可变感染参数，并使用常微分方程式，允许应用于具有多个反应器的装置。该模型根据包括底物浓度、进料量和循环次数在内的关键操作参数提供了简单的成本估算。对于所研究的噬菌体和细菌配对，成本和生产率变化了三个数量级，最低的成本对进水底物浓度和第一个容器中的低液位设置最敏感。文中还给出了一个噬菌体生产的实例研究，展示了参数值如何影响生产成本和估计生产时间。提出的方法是灵活的，可用于通过最小化成本或最大化生产率来优化实验室或工厂规模的噬菌体生产。
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.