Data Driven Modeling and Model Predictive Control of Bioreactor for Production of Monoclonal Antibodies

S. Sarna, Nikesh Patel, P. Mhaskar, Brandon Corbett, Christopher R Mccready
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Abstract

This manuscript focuses on data driven modeling and control of an industrial bioreactor used by Sartorius to grow cells to produce monoclonal antibodies, demonstrated using a high fidelity simulation test bed. The contribution of this paper is the development of a subspace model based model predictive controller (MPC) for the bioreactor with constraints in place to manage the delicate cell health and growth. Subspace identification is first utilized for developing a linear model, and utilized, along with a state observer, to formulate and implement the Model Predictive Controller. Three implementations are shown, the first which simply tracks a desired trajectory of the viable cell density while maximizing the total product, the second maximizing the total product, and finally a formulation to enable trajectory tracking of titer. In each case the MPC is able to successfully operate the bioreactor and show improvements compared to the existing proportional-integral controller. The success of the MPC implementation on the simulation test bed paves the way for implementation on the bioreactor, as well as the development much more ambitious MPC designs.
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单克隆抗体生产生物反应器的数据驱动建模与模型预测控制
这篇论文的重点是数据驱动的建模和工业生物反应器的控制,该反应器由赛多利斯用于培养细胞以产生单克隆抗体,并使用高保真度模拟试验台进行演示。本文的贡献是开发了一种基于子空间模型的模型预测控制器(MPC),用于具有适当约束的生物反应器,以管理微妙的细胞健康和生长。子空间识别首先用于开发线性模型,并与状态观测器一起用于制定和实现模型预测控制器。显示了三种实现,第一种是在最大化总产物的同时简单地跟踪活细胞密度的期望轨迹,第二种是最大化总产物,最后是一个公式来实现滴度的轨迹跟踪。在每种情况下,MPC都能够成功地操作生物反应器,并且与现有的比例积分控制器相比显示出改进。MPC在模拟试验台上的成功实现为生物反应器的实现以及更雄心勃勃的MPC设计的开发铺平了道路。
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