本文關鍵詞：動物細胞懸浮培養(yǎng)流場動力與測控技術(shù)研究　出處：《江蘇大學》2016年碩士論文　論文類型：學位論文

  更多相關文章： 動物細胞培養(yǎng) 軟測量技術(shù) 廣義回歸神經(jīng)網(wǎng)絡 生物反應器 流場仿真 ARM9

【摘要】：隨著人們對健康醫(yī)療領域的日益關注,生物醫(yī)藥制品的需求逐漸增大,規(guī)�；瘎游锛毎囵B(yǎng)作為生物產(chǎn)品制備的關鍵技術(shù),已成為工業(yè)生產(chǎn)的重要環(huán)節(jié)。生物反應器是維持細胞體外生長繁殖的核心設備,為了滿足規(guī)�；瘎游锛毎囵B(yǎng)中混合度高且剪切力小的要求,相應反應器的研究是重要難點之一。計算流體力學軟件能全面模擬生物反應器內(nèi)流場狀態(tài),通過關鍵工程因素的計算結(jié)果直觀反映流場特性,從而為反應器參數(shù)結(jié)構(gòu)的設計提供依據(jù)。同時動物細胞產(chǎn)業(yè)化培養(yǎng)也為過程參數(shù)的測控帶來挑戰(zhàn),關鍵參數(shù)的準確測量是控制的必要前提,但由于傳統(tǒng)測量技術(shù)的局限性與動物細胞培養(yǎng)過程的復雜性,關鍵參數(shù)的測量問題一直是測控過程中的首要難題,這些技術(shù)問題密切關系著動物細胞培養(yǎng)最終產(chǎn)物的產(chǎn)量與品質(zhì),因此深入研究這些技術(shù)問題具有實際價值與意義。針對以上技術(shù)問題,本文主要從以下幾個方面展開研究:1.將流體仿真軟件運用于反應器內(nèi)流場的模擬,以4000L動物細胞生物反應器為研究對象,首先設計了流場計算域的幾何結(jié)構(gòu)與攪拌器結(jié)構(gòu),接著選用穩(wěn)態(tài)的多參考系坐標法在有限元分析軟件中對計算域進行網(wǎng)格劃分,模擬了反應器內(nèi)不同擋板組數(shù)產(chǎn)生的流場效果,依照仿真結(jié)果選取最佳擋板組數(shù),最后計算了不同攪拌速度下產(chǎn)生的流場,對比分析速度矢量場與剪切矢量場的仿真結(jié)果,為實際培養(yǎng)過程攪拌速度的設定提供依據(jù)。2.運用軟測量技術(shù)解決了動物細胞培養(yǎng)中不可測關鍵參數(shù)預估的問題,以口蹄疫疫苗懸浮培養(yǎng)為研究對象,采用一致關聯(lián)度算法選擇輔助變量,建立基于廣義回歸神經(jīng)網(wǎng)絡的軟測量模型,實現(xiàn)對葡萄糖濃度、乳酸濃度、丙氨酸濃度和細胞密度的預測,并在仿真實驗中與徑向基神經(jīng)網(wǎng)絡模型的預估效果對比,仿真結(jié)果表明廣義回歸神經(jīng)網(wǎng)絡具有更優(yōu)異的預測精度與泛化能力,顯示出其在動物細胞培養(yǎng)過程軟測量建模中的可行性。3.采用ARM9微處理器為主控CPU設計了動物細胞培養(yǎng)的數(shù)字控制系統(tǒng),為軟測量研究成果運用于實際生產(chǎn)中提供平臺。首先對基于ARM9的硬件控制系統(tǒng)進行了設計,并詳細描述數(shù)字系統(tǒng)中的數(shù)據(jù)存儲與通訊接口技術(shù),接著設計了溫度、溶氧、酸堿度的實際檢測方法與通訊接口技術(shù),最后將軟件操作系統(tǒng)Linux移植到控制器中,構(gòu)建了較為完整的動物細胞培養(yǎng)數(shù)字控制系統(tǒng)。
[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.
【學位授予單位】：江蘇大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：TP183;Q813

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