SCILS - Systematic consideration of inhomogeneity at the large scale: towards a stringent development of industrial bioprocesses

SCILS - 大规模不均匀性的系统考虑：迈向工业生物过程的严格发展

• 批准号: BB/L001284/1
• 负责人: Chris Rielly
• 金额: $ 35.9万
• 依托单位: Loughborough University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL001284%2F1
• 关键词: SCILS; Systematic; consideration; inhomogeneity; large

The proposal relates to the UK contribution to an approved ERA-IB 3rd Transnational project (within ERA-NET Scheme of the 7th EU Framework Programme) led by Professor Marco Oldiges, Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, FRG.Biotechnological production in large scale bioreactors is a state-of-the-art technology. Nevertheless, full scale production is often accompanied by loss of performance compared to lab scale conditions, due to the effects of increasing bioreactor inhomogeneity. For example, cells experience a varying dissolved oxygen (DO) concentration as they are convected in the flow around a large scale bioreactor; in contrast, in small scale bioreactors it is much easier to ensure uniform DO concentrations and hence cells respire and grow in the same way throughout the fermenter. The inhomogeneities in the large scale environment, can lead to heterogeneous populations of cells, which is undesirable. Application of conventional scale-up criteria to match hydrodynamic conditions between different scales is rather difficult; the presence of inhomogeneities cannot simply be overcome at production scales by mixing more intensely, since the required energy inputs are not economically feasible. These inhomogeneity issues are not usually considered at the early stages of engineering and selecting suitable strains of organism for bioproduction, nor during lab-scale bioprocess development. Not surprisingly, this leads to critical points and failures during scale-up, necessitating additional iterations of strain or process engineering to achieve successful and economic production performance. Despite the great advances in strain engineering and understanding of cellular regulatory processes, the consideration of scale up effects such as an oscillatory environment for the biological system is mostly missing. Closing this gap can make the difference between economic efficiency and inefficiency and can provide more efficient processes at large scale.

该提案涉及英国对批准的ERA-IB第三跨国项目(在第七个欧盟框架计划的ERA-NET计划内)的贡献，该项目由IBG-1生物和地球科学研究所Marco Oldiges教授领导：生物技术，Forschungszentrum Jülich，FRG。在大型生物反应器中进行生物技术生产是一项最先进的技术。然而，由于生物反应器不均质性增加的影响，与实验室规模的条件相比，大规模生产往往伴随着性能的损失。例如，当细胞在大型生物反应器周围的流动中流动时，细胞经历不同的溶解氧(DO)浓度；相比之下，在小型生物反应器中，更容易确保均匀的DO浓度，因此细胞在整个发酵罐中以相同的方式呼吸和生长。大规模环境中的不均一性会导致细胞种群的异质性，这是不可取的。应用传统的放大标准来匹配不同尺度之间的水动力条件是相当困难的；不均匀的存在不能简单地通过更密集地混合来克服，因为所需的能量投入在经济上是不可行的。这些不均质性问题通常不会在工程设计和选择适合生物生产的微生物菌株的早期阶段考虑，也不会在实验室规模的生物过程开发中考虑。毫不奇怪，这会导致在扩大规模的过程中出现临界点和故障，从而需要进行额外的应变或工艺工程迭代，以实现成功和经济的生产性能。尽管菌株工程和对细胞调控过程的了解有了很大的进步，但对生物系统的放大效应(如振荡环境)的考虑大多是缺失的。缩小这一差距可以造成经济效率和效率低下之间的差异，并可以在大规模提供更高效的流程。