Predictive modelling and control of nutrients for the cost-effective production of cultivated meat

随着对细胞农业作为解决动物农业的公共卫生、环境和动物福利挑战的手段的兴趣日益增长，从细胞和组织培养物生产肉类的概念正在成为解决类似挑战的方法。如果被证明是商业上的成功，人造肉有可能彻底改变我们的饮食方式和与环境的互动方式。为了实现这一潜力，必须采用具有成本效益的生产工艺。数学建模的使用可以在这奋进发挥重要作用。使用生长因子激活细胞增殖信号通路对于实现肉类生产所需的细胞数量和生物量至关重要。然而，由于它们对温度、pH和几种变性剂的高敏感性，在生物反应器系统内通常需要频繁添加和高剂量浓度的生长因子，以在每次实验运行中达到目标细胞数。生物反应器的设计配置，如设计类型、尺寸、搅拌器类型和搅拌器速度，也会导致生物反应器内的变异性，从而影响生长因子的降解和结合动力学。这些生长因子的成本非常高，并且目前是实现使养殖肉类成为商业上可行且价格有竞争力的市场产品所需的有效生产成本的主要瓶颈。本项目的目标是开发一个过程控制系统，精确控制养殖肉类生物过程的生长因子添加策略。这是为了促进内部生物反应器的工艺强化，提高生产率，提高产品质量，最重要的是降低成本。该项目的两个主要目标包括：量化和开发生物反应器内生长因子降解和生物活性动力学的数学模型，以及开发过程控制算法，以最大限度地减少生长因子的使用并提高整个生物过程的成本效益。所涉及的策略可能包括控制生长饲喂时间表、浓度和添加速率。生长因子的类型也可以包括在基于给定输入（即细胞类型和数量）和期望输出（即所需生物质）的优化策略中。该控制系统将改进生长因子的利用，以产生更具成本效益的过程。这一进展将在使养殖肉类生产商业化方面发挥重要作用。该项目属于EPSRC数学生物学研究领域的福尔斯。Ivy Farm将成为该项目的工业合作伙伴。

With growing interest in cellular agriculture as a means to address public health, environmental and animal welfare challenges of animal agriculture, the concept of producing meat from cell- and tissue- cultures is emerging as an approach to address similar challenges. If proved to be commercially successful, cultivated meat has the potential to revolutionize the way in which we eat and interact with our environment. To achieve this potential, cost-effective production processes are necessary. The use of mathematical modelling can play an important role in this endeavor. Use of growth factors to activate cell proliferation signaling pathways is crucial to achieve required cell numbers and biomass for meat production. However, due to their high sensitivities to temperature, pH and several denaturants, frequent additions and high dosage concentrations of growth factors are often required within the bioreactor system to achieve target cell numbers in each experimental run. Bioreactor design configurations such as design type, size, stirrer type and stirrer speeds also contribute to the variabilities within the bioreactor which affect the growth factors' degradation and binding kinetics. Cost of these growth factors are very high and are currently the main bottlenecks in achieving efficient production costs required to make cultivated meat a commercially viable and competitively priced product to market. The goal of this project is to develop a process control system that accurately controls the growth factor addition strategy of a cultivated meat bioprocess. This is with the aims to facilitate process intensification of an in-house bioreactor, increase productivity, improve product quality and most importantly, lower cost. The two main objectives of this project include: quantifying and developing a mathematical model of growth factor degradation and bioactivity kinetics within a bioreactor, and developing process control algorithms that minimize the usage of growth factors and improve cost efficiency of the bioprocess as a whole. The strategies involved might include controlling the growth feeding schedule, concentrations and addition rates. The type of growth factors might also be included in the optimization strategy based on a given input, i.e. cell type and numbers and desired output, i.e. required biomass. The control system will refine growth factor utilization to engender a more cost-efficient process. Such an advance will play a significant role in making cultivated meat production commercially viable. This project falls within the EPSRC Mathematical Biology research area. Ivy Farm would be the industrial partner for this project.