气液双升式反应器动物细胞培养及批式生长动力学模型

初步研究了气液双升式动物细胞反应器微载体培养 Bowes细胞和悬浮培养 M4G3杂交瘤细胞的生长条件 ,在不加入消泡剂和保护剂的情况下 ,批式培养 Bowes细胞的最大密度为 2 .6×1 0 6/ml,批式培养 M4G3细胞的最大密度为 1 .5× 1 0 6/ml。基于细胞生长的密度效应 ,建立了动物细胞生长动力学模型 :　　 μ=0　　 t相似文献   

新型气液双升式动物细胞反应器

为克服目前动物细胞反应器存在的不足 ,设计了一种新型气液双升式动物细胞反应器( ALLR)。该反应器结合了气升式反应器和流化床反应器的优点 ,同时在结构上使气泡与流体自然流动与分离 ,消除了气泡凝聚破裂给细胞造成的机械损伤。测定了 2 L反应器的液体循环流速及氧传质系数 KLa值 ,表明 ALLR具有较好的传质性能和极小的流体剪切力 ,适合动物细胞的大规模培养     

10升气升环流式生物反应器培养紫草细胞

本文采用自行设计研制的10升气升环流式生物反应器培养紫草细胞,培养周期34d．前14d为细胞生长培养,细胞生长呈正常的S型曲线,细胞增长到原细胞接人量的4倍．后20d为紫草色素生产培养,细胞增长到32倍。整个周期每升培养液可生产紫草色素0．6g,在反应器中,培养液pH值的变化与细胞生长呈正相关,与紫草色素的形成呈负相关,pH值变化规律可用于监测紫草细胞在生物反应器的生长和色素形成．     

内循环气升式生物反应器培养甘草细胞

自行设计研制了７Ｌ,９Ｌ及２５Ｌ内循环气升式生物反应器,并应用于甘草细胞的放大培养研究。在接种量为８％（Ｗ／Ｖ）通气率为０．２—０．２５ｖｖｍ的条件下,甘草细胞在反应器中生长迅速。其中在９Ｌ反应器中生长最好,最高生物量达１６．２５ｇ／Ｌ,生长速率达０．９ｇ／Ｌ．ｄ,均高于摇瓶培养。培养过程中ｐＨ值、溶氧状况通过电极自动显示记录,说明设计的气升式生物反应器适合于甘草细胞的大规模培养。     

外循环气升式反应器培养新疆紫草细胞

采用两步培养法进行新疆紫草细胞悬浮培养及5L外循环气升式反应器扩大培养,探讨了培养过程中细胞生长、紫草色素合成与培养液的电导率、可溶性糖含量变化之间的关系。第一步培养时细胞生长迅速,但也有一部分色素合成,电导率及可溶性糖含量迅速下降;第二步培养初期电导率也开始下降,但当色素合成达到高峰并有一部分外泌到培养基后,电导率又开始回升。可溶性糖捎耗很快,到后期巳测不出其存在。因此通过监测培养液中电导率及可溶性糖的变化情况,可以为新疆紫草细胞大规模培养与色素合成提供有用的参数指标。     

新型气升式反应器在发酵培养中的应用研究

本文以Ｌ－苹果酸生产为例,采用新型的分段内循环气升式反应器分批培养产延胡索酸酶的产氨短杆菌ＭＡ－２,并与同等规模机械搅拌反应器中接着的结果相比较。数据表明,采用气升式发酵设备进行培养,该菌体的收率能提高近３％,且发酵周期能缩短一半左右,显著降低培养成本,该类型的反应器具有广阔的应用前景。     

三七细胞在气升式反应器中的扩大培养研究

三七细胞在5升外循环、内循环气升式反应器中能正常生长并累积三七皂甙及多糖。外循环反应器中三七总皂甙含量最高可达9.48%;内循环反应器中三七多糖含量则可高达24%。但三七细胞生长比较缓慢的问题有待进一步研究。     

VerO细胞在气升式反应器中的微载体培养

哺乳动物细胞的大规模培养是生产许多医学上重要生物制品的一种主要方法之－⑴。很多有工业价值的动物细胞都是贴壁细胞,必须附着在一定的表面上才能生长,微载体培养是一种有效的体系⑵。用于微载体培养的反应器多为搅拌式反应器,近年来,流化床式反应器越来越引起生化工程学家的重视。有希望用于大规模动物细胞培养的主要是液升和气升式。液升式反应器的优点是培养液可以间接氧饱和,气泡和细胞不直接接触。在气升式流态反应器中,气泡与细胞直接接触,其优点是操作方便,设备筒单。本文报道通过气升流态化反应器实现高密度贴壁细胞培养工艺条件的研究。     

改进型气升式反应器能耗的研究

首次研究了操作条件和反应器结构（导流筒直径和静态混合元件数）对改进型气升式反应器功耗的影响。结果表明,优化导流筒结构可以实现节能降耗。曝气量相同时,在导流筒直径为4.0cm,静态混合元件数为39的条件下,改进型反应器的功耗最小,比普通反应器平均降低23.6%。达到相同供氧能力时,在导流筒直径为5.5cm,静态混合元件数为13的条件下,改进型反应器的功耗最小,比普通反应器平均降低43.9%。在改进型反应器中,升流区功耗最大,占70%～80%;底隙区次之,占20%左右;气液分离区最小,小于10%;降流区功耗可以忽略不计。最大体积功耗出现在底隙区。升流区是解决反应器能耗问题的重点。     

Itaconic acid production using an air-lift bioreactor in repeated batch culture of Aspergillus terreus

Repeated itaconic acid production using an air-lift bioreactor was carried out by three methods—two with cell recycling by means of centrifugation and filtration by a stainless steel filter set inside the bioreactor and one by repeated batch culture without cell recycling. In a flask culture, repeated itaconic acid production was stable for 9 cycles (45 d) and the production rate was 0.47 g/l/h. However, in the air-lift bioreactor, it was difficult to produce itaconic acid in the repeated batch culture with cell recycling for a long period due to a decrease in fluidity resulting from an increase in mycelium concentration. In the method without cell recycling, however, repeated itaconic acid production was stable for 4 cycles (21 d) and the production rate was 0.37 g/l/h.     

Continuous suspended cell culture of Mentha piperita in cell-recycled air-lift bioreactor

Summary A cell-recycled air-lift bioreactor was studied for its performance in cultivation of Mentha piperita cells producing essential oils. The reactor system sustained a stable operation over 30 days with the aid of a cell settler. The maximum cell concentration reached 50% packed cell volume and it occurred at the dilution rate of 0.27 day^-1. Volumetric productivity of essential oils in this system was substantially higher than that obtainable from batch culture.     

Exopolysaccharide production and mycelial growth in an air-lift bioreactor using Fomitopsis pinicola

For effective exopolysaccharide production and mycelial growth by a liquid culture of Fomitopsis pinicola in an air-lift bioreactor, the culture temperature, pH, carbon source, nitrogen source, and mineral source were initially investigated in a flask. The optimal temperature and pH for mycelial growth and exopolysaccharide production were 25degrees C and 6.0, respectively. Among the various carbon sources tested, glucose was found to be the most suitable carbon source. In particular, the maximum mycelial growth and exopolysaccharide production were achieved in 4% glucose. The best nitrogen sources were yeast extract and malt extract. The optimal concentrations of yeast extract and malt extract were 0.5 and 0.1%, respectively. K2HPO4 and MgSO4 x 7H2O were found to be the best mineral sources for mycelial growth and exopolysaccharide production. In order to investigate the effect of aeration on mycelial growth and exopolysaccharide production in an air-lift bioreactor, various aerations were tested for 8 days. The maximum mycelial growth and exopolysaccharide production were 7.9 g/l and 2.6 g/l, respectively, at 1.5 vvm of aeration. In addition, a batch culture in an air-lift bioreactor was carried out for 11 days under the optimal conditions. The maximum mycelial growth was 10.4 g/l, which was approximately 1.7-fold higher than that of basal medium. The exopolysaccharide production was increased with increased culture time. The maximum concentration of exopolysaccharide was 4.4 g/l, which was about 3.3-fold higher than that of basal medium. These results indicate that exopolysaccharide production increased in parallel with the growth of mycelium, and also show that product formation is associated with mycelial growth. The developed model in an air-lift bioreactor showed good agreement with experimental data and simulated results on mycelial growth and exopolysaccharide production in the culture of F pinicola.     

Analytical solution for a hybrid Logistic-Monod cell growth model in batch and continuous stirred tank reactor culture

Monod and Logistic growth models have been widely used as basic equations to describe cell growth in bioprocess engineering. In the case of the Monod equation, the specific growth rate is governed by a limiting nutrient, with the mathematical form similar to the Michaelis–Menten equation. In the case of the Logistic equation, the specific growth rate is determined by the carrying capacity of the system, which could be growth-inhibiting factors (i.e., toxic chemical accumulation) other than the nutrient level. Both equations have been found valuable to guide us build unstructured kinetic models to analyze the fermentation process and understand cell physiology. In this work, we present a hybrid Logistic-Monod growth model, which accounts for multiple growth-dependent factors including both the limiting nutrient and the carrying capacity of the system. Coupled with substrate consumption and yield coefficient, we present the analytical solutions for this hybrid Logistic-Monod model in both batch and continuous stirred tank reactor (CSTR) culture. Under high biomass yield (Y_x/s) conditions, the analytical solution for this hybrid model is approaching to the Logistic equation; under low biomass yield condition, the analytical solution for this hybrid model converges to the Monod equation. This hybrid Logistic-Monod equation represents the cell growth transition from substrate-limiting condition to growth-inhibiting condition, which could be adopted to accurately describe the multi-phases of cell growth and may facilitate kinetic model construction, bioprocess optimization, and scale-up in industrial biotechnology.