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Development of a Novel Membrane Aerated Hollow-Fiber Microbioreactor

机译:新型膜曝气中空纤维生物反应器的研制

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A new challenge in biotechnological processes is the development of flexible bioprocessing platforms, allowing strain selection, facilitating scale-up and integrating separation steps. Miniaturization of such a cultivation system allows parallel use and the saving of resources but makes the supply of oxygen to the cells difficult. In this work we present a membrane aerated hollow-fiber microbioreactor (HFMBR) which consists of an acrylic glass module equipped with two different types of membrane fibers. Fibers of polyethersulfone and polyvinyldifluoride were used for substrate and oxygen supply, respectively. Cultivation of E. coli as model organism and production of His-tagged GFP were carried out in the extracapillary space of the membrane aerated HFMBR and compared with cultivations in shaking flask which are commonly used for screening experiments. The measurement of the oxygen transfer capacity and the online monitoring of the dissolved oxygen during the cultivation were performed using a fiber optic oxygen sensor. Online measurement of the optical density was also integrated to the bioreactor. Due to efficient oxygen transfer, a better cell growth than in the shaking flask experiments was achieved, while no negative influence on the GFP productivity was observed in the membrane aerated bioreactor. Thus the feasibility of a future integrated downstreaming could also be demonstrated.
机译:生物技术过程中的新挑战是开发灵活的生物加工平台,从而可以选择菌株,促进规模放大并整合分离步骤。这种培养系统的小型化允许并行使用和节省资源,但是使向细胞的氧气供应困难。在这项工作中,我们提出了一种带膜的中空纤维微生物反应器(HFMBR),该反应器由配有两种不同类型的膜纤维的丙烯酸玻璃组件组成。聚醚砜和聚二氟乙烯纤维分别用于基材和氧气供应。在膜通气的HFMBR的毛细血管外空间中进行了大肠杆菌作为模型生物的培养和His标记的GFP的生产,并与通常用于筛选实验的摇瓶中的培养进行了比较。使用光纤氧气传感器进行培养过程中氧气传输能力的测量和溶解氧的在线监测。在线测量光密度也被整合到生物反应器中。由于有效的氧气转移,比摇瓶实验获得了更好的细胞生长,而在膜曝气生物反应器中未观察到对GFP生产率的负面影响。因此,也可以证明未来整合下游技术的可行性。

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