This paper discusses the challenges associated with the reliable and optimal operation of perfusion bioreactors and presents methods for modeling and identification of perfusion bioreactors as well as the vision for their integration. After presenting a generic model of perfusion bioreactors, the paper shows how to use the concept of basis flux modes to uniquely compute reaction rates. The advantage of this concept with respect to elementary flux nodes and similar concepts in metabolic flux analysis is the reduced number of flux modes that need to be modeled. In addition, a procedure to identify the model and estimate the parameters for each reaction using Monod-type kinetics is presented. It is shown that the rational structure of these kinetic models results in optimization problems that are amenable to tractable computation of globally optimal parameter estimates. The methods are illustrated via examples with simulated or experimental data.

本文讨论了与灌注生物反应器的可靠和最佳运行相关的挑战，并提出了用于建模和识别灌注生物反应器的方法，以及它们的集成前景。在介绍了灌注生物反应器的通用模型之后，本文展示了如何使用基本通量模式的概念来唯一地计算反应速率。该概念相对于基本通量节点和代谢通量分析中类似概念的优点是减少了需要建模的通量模式的数量。此外，还介绍了使用Monod型动力学方法识别模型并估算每个反应的参数的过程。结果表明，这些动力学模型的合理结构会导致优化问题，这些问题适合于对全局最优参数估计进行可计算的计算。通过带有模拟或实验数据的示例说明了这些方法。