动物细胞悬浮培养流场动力与测控技术研究

发布时间：2018-01-15 00:04

本文关键词：动物细胞悬浮培养流场动力与测控技术研究　出处：《江苏大学》2016年硕士论文　论文类型：学位论文

【摘要】：随着人们对健康医疗领域的日益关注,生物医药制品的需求逐渐增大,规模化动物细胞培养作为生物产品制备的关键技术,已成为工业生产的重要环节。生物反应器是维持细胞体外生长繁殖的核心设备,为了满足规模化动物细胞培养中混合度高且剪切力小的要求,相应反应器的研究是重要难点之一。计算流体力学软件能全面模拟生物反应器内流场状态,通过关键工程因素的计算结果直观反映流场特性,从而为反应器参数结构的设计提供依据。同时动物细胞产业化培养也为过程参数的测控带来挑战,关键参数的准确测量是控制的必要前提,但由于传统测量技术的局限性与动物细胞培养过程的复杂性,关键参数的测量问题一直是测控过程中的首要难题,这些技术问题密切关系着动物细胞培养最终产物的产量与品质,因此深入研究这些技术问题具有实际价值与意义。针对以上技术问题,本文主要从以下几个方面展开研究:1.将流体仿真软件运用于反应器内流场的模拟,以4000L动物细胞生物反应器为研究对象,首先设计了流场计算域的几何结构与搅拌器结构,接着选用稳态的多参考系坐标法在有限元分析软件中对计算域进行网格划分,模拟了反应器内不同挡板组数产生的流场效果,依照仿真结果选取最佳挡板组数,最后计算了不同搅拌速度下产生的流场,对比分析速度矢量场与剪切矢量场的仿真结果,为实际培养过程搅拌速度的设定提供依据。2.运用软测量技术解决了动物细胞培养中不可测关键参数预估的问题,以口蹄疫疫苗悬浮培养为研究对象,采用一致关联度算法选择辅助变量,建立基于广义回归神经网络的软测量模型,实现对葡萄糖浓度、乳酸浓度、丙氨酸浓度和细胞密度的预测,并在仿真实验中与径向基神经网络模型的预估效果对比,仿真结果表明广义回归神经网络具有更优异的预测精度与泛化能力,显示出其在动物细胞培养过程软测量建模中的可行性。3.采用ARM9微处理器为主控CPU设计了动物细胞培养的数字控制系统,为软测量研究成果运用于实际生产中提供平台。首先对基于ARM9的硬件控制系统进行了设计,并详细描述数字系统中的数据存储与通讯接口技术,接着设计了温度、溶氧、酸碱度的实际检测方法与通讯接口技术,最后将软件操作系统Linux移植到控制器中,构建了较为完整的动物细胞培养数字控制系统。
[Abstract]:With the increasing attention to the field of health care, the demand for biomedical products is gradually increasing, and large-scale animal cell culture as a key technology for the preparation of biological products. Bioreactor is the core equipment to maintain cell growth and reproduction in vitro. In order to meet the requirements of high mixing degree and low shear force in large-scale animal cell culture. Computational fluid dynamics (CFD) software can simulate the state of flow field in bioreactor completely and reflect the characteristics of flow field directly through the calculation results of key engineering factors. Therefore, it provides the basis for the design of the reactor parameter structure. At the same time, the industrialized culture of animal cells also brings challenges to the measurement and control of the process parameters. The accurate measurement of the key parameters is the necessary prerequisite of the control. However, due to the limitations of traditional measurement techniques and the complexity of animal cell culture, the measurement of key parameters has always been the primary problem in the process of measurement and control. These technical problems are closely related to the yield and quality of the final product of animal cell culture, so it is of practical value and significance to further study these technical problems. The fluid simulation software was applied to simulate the flow field in the reactor. The 4000L animal cell bioreactor was used as the research object. Firstly, the geometric structure and agitator structure of the flow field are designed, and then the steady-state multi-reference coordinate method is used to mesh the computational domain in the finite element analysis software. The flow field effect of different baffle groups in the reactor was simulated. According to the simulation results, the optimal baffle group number was selected. Finally, the flow field under different stirring speed was calculated. The simulation results of velocity vector field and shear vector field are compared and analyzed. To provide the basis for the setting of stirring speed in the actual culture process. Using soft sensing technology to solve the problem of estimating the key parameters in animal cell culture, the suspension culture of foot-and-mouth disease vaccine was taken as the research object. A soft sensor model based on generalized regression neural network was established to predict glucose concentration, lactic acid concentration, alanine concentration and cell density. The simulation results show that the generalized regression neural network has better prediction accuracy and generalization ability than the radial basis function neural network model. It shows its feasibility in the soft sensor modeling of animal cell culture. (3) A digital control system for animal cell culture is designed using ARM9 microprocessor as the main control CPU. To provide a platform for the application of soft sensing research results in practical production. Firstly, the hardware control system based on ARM9 is designed, and the data storage and communication interface technology in digital system is described in detail. Then, the actual detection method of temperature, dissolved oxygen, pH and communication interface technology is designed. Finally, the software operating system Linux is transplanted into the controller. A complete digital control system of animal cell culture was constructed.
【学位授予单位】：江苏大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：TP183;Q813

【相似文献】