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動(dòng)物細(xì)胞懸浮培養(yǎng)流場(chǎng)動(dòng)力與測(cè)控技術(shù)研究

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  本文關(guān)鍵詞:動(dòng)物細(xì)胞懸浮培養(yǎng)流場(chǎng)動(dòng)力與測(cè)控技術(shù)研究 出處:《江蘇大學(xué)》2016年碩士論文 論文類型:學(xué)位論文


  更多相關(guān)文章: 動(dòng)物細(xì)胞培養(yǎng) 軟測(cè)量技術(shù) 廣義回歸神經(jīng)網(wǎng)絡(luò) 生物反應(yīng)器 流場(chǎng)仿真 ARM9


【摘要】:隨著人們對(duì)健康醫(yī)療領(lǐng)域的日益關(guān)注,生物醫(yī)藥制品的需求逐漸增大,規(guī);瘎(dòng)物細(xì)胞培養(yǎng)作為生物產(chǎn)品制備的關(guān)鍵技術(shù),已成為工業(yè)生產(chǎn)的重要環(huán)節(jié)。生物反應(yīng)器是維持細(xì)胞體外生長(zhǎng)繁殖的核心設(shè)備,為了滿足規(guī);瘎(dòng)物細(xì)胞培養(yǎng)中混合度高且剪切力小的要求,相應(yīng)反應(yīng)器的研究是重要難點(diǎn)之一。計(jì)算流體力學(xué)軟件能全面模擬生物反應(yīng)器內(nèi)流場(chǎng)狀態(tài),通過(guò)關(guān)鍵工程因素的計(jì)算結(jié)果直觀反映流場(chǎng)特性,從而為反應(yīng)器參數(shù)結(jié)構(gòu)的設(shè)計(jì)提供依據(jù)。同時(shí)動(dòng)物細(xì)胞產(chǎn)業(yè)化培養(yǎng)也為過(guò)程參數(shù)的測(cè)控帶來(lái)挑戰(zhàn),關(guān)鍵參數(shù)的準(zhǔn)確測(cè)量是控制的必要前提,但由于傳統(tǒng)測(cè)量技術(shù)的局限性與動(dòng)物細(xì)胞培養(yǎng)過(guò)程的復(fù)雜性,關(guān)鍵參數(shù)的測(cè)量問(wèn)題一直是測(cè)控過(guò)程中的首要難題,這些技術(shù)問(wèn)題密切關(guān)系著動(dòng)物細(xì)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(wèn)題具有實(shí)際價(jià)值與意義。針對(duì)以上技術(shù)問(wèn)題,本文主要從以下幾個(gè)方面展開(kāi)研究:1.將流體仿真軟件運(yùn)用于反應(yīng)器內(nèi)流場(chǎng)的模擬,以4000L動(dòng)物細(xì)胞生物反應(yīng)器為研究對(duì)象,首先設(shè)計(jì)了流場(chǎng)計(jì)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(biāo)法在有限元分析軟件中對(duì)計(jì)算域進(jìn)行網(wǎng)格劃分,模擬了反應(yīng)器內(nèi)不同擋板組數(shù)產(chǎn)生的流場(chǎng)效果,依照仿真結(jié)果選取最佳擋板組數(shù),最后計(jì)算了不同攪拌速度下產(chǎn)生的流場(chǎng),對(duì)比分析速度矢量場(chǎng)與剪切矢量場(chǎng)的仿真結(jié)果,為實(shí)際培養(yǎng)過(guò)程攪拌速度的設(shè)定提供依據(jù)。2.運(yùn)用軟測(cè)量技術(shù)解決了動(dòng)物細(xì)胞培養(yǎng)中不可測(cè)關(guān)鍵參數(shù)預(yù)估的問(wèn)題,以口蹄疫疫苗懸浮培養(yǎng)為研究對(duì)象,采用一致關(guān)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(luò)的軟測(cè)量模型,實(shí)現(xiàn)對(duì)葡萄糖濃度、乳酸濃度、丙氨酸濃度和細(xì)胞密度的預(yù)測(cè),并在仿真實(shí)驗(yàn)中與徑向基神經(jīng)網(wǎng)絡(luò)模型的預(yù)估效果對(duì)比,仿真結(jié)果表明廣義回歸神經(jīng)網(wǎng)絡(luò)具有更優(yōu)異的預(yù)測(cè)精度與泛化能力,顯示出其在動(dòng)物細(xì)胞培養(yǎng)過(guò)程軟測(cè)量建模中的可行性。3.采用ARM9微處理器為主控CPU設(shè)計(jì)了動(dòng)物細(xì)胞培養(yǎng)的數(shù)字控制系統(tǒng),為軟測(cè)量研究成果運(yùn)用于實(shí)際生產(chǎn)中提供平臺(tái)。首先對(duì)基于ARM9的硬件控制系統(tǒng)進(jìn)行了設(shè)計(jì),并詳細(xì)描述數(shù)字系統(tǒng)中的數(shù)據(jù)存儲(chǔ)與通訊接口技術(shù),接著設(shè)計(jì)了溫度、溶氧、酸堿度的實(shí)際檢測(cè)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(dòng)物細(xì)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(xué)位授予單位】:江蘇大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2016
【分類號(hào)】:TP183;Q813

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