Cell Factories: A Matter of Life or Death

本学科跳跃项目是基于三位提议者的共同兴趣而提出的，目的是将受控的流体动力学条件应用于生物发酵，以精确控制细胞环境。传统上，细菌在研究实验室内的培养批次摇瓶中生长。随着细菌细胞的生长，生长培养基中的营养物质被消耗，有毒废物积累：细胞死亡。使用发酵罐和摇瓶，可以用新鲜的营养物质补充培养基，但是不可能去除废物。我们建议开发一种新型的串联毛细管生物反应器，它提供了将新鲜营养物质输送到固定化细胞的可能性，同时去除对生长有害的废物。我们建议研究微生物介导的生物转化在毛细管反应器内，检查大肠杆菌和荧光假单胞菌的生长在一个受控的微流体环境中，并调查基因启动子开关。知识转移是成功的关键：RJMG将获得单相和多相流体力学的基础知识，以及可视化和建模的最新发展，用于控制流环境的设计和优化。MJS和SPD将获得细胞生长和增殖方面的经验，以及在生物转化中使用细胞的经验。本介绍微生物学和生物化学，包括培养基和仪器灭菌方法，培养基制备和细胞处理，将提供一个背景知识，从该方法的反应器设计。我们的目标是建立一个实质性的长期合作，桥梁化学-化学工程接口，并将有泵启动学术和工业相关的新研究领域的增值效应。

SummaryThis discipline hopping project is proposed on the basis of mutual interest of the three proposers with the aim of applying controlled hydrodynamic conditions to biological fermentations for precise control of the cell environment. Traditionally, bacteria are grown in incubated batch shake flasks within the research laboratory. As the bacterial cells grow, the nutrients within the growth media are consumed and toxic waste products accumulate: cell death ensues. With both fermenters and shake flasks it is possible to supplement the media with fresh nutrients, however it is not possible to remove the waste products. We propose to develop a novel serial capillary bioreactor which affords the possibility of delivering fresh nutrients to immobilised cells whilst removing waste products, detrimental to growth. We propose to study biotransformations mediated by microbes within a capillary reactor, examine the growth of Escherichia coli and Pseudomonas fluorescens within a controlled microfluidic environment, and investigate gene promoter switching. Knowledge transfer is essential to the success of the hop: RJMG will gain experience of the fundamentals of both single and multiphase fluid mechanics, as well as the latest developments in visualisation and modelling for the design and optimisation of controlled flow environments. MJS and SPD will gain experience in cell growth and maintainance, and in the use of cells in biotransformations. This introduction to microbiology and biological chemistry including methods of media and instrument sterilisation, media preparation, and cell handling will provide a background understanding from which to approach the reactor design. Our aim is to establish a substantial long term collaboration that bridges the chemistry-chemical engineering interface and that will have the value-added effect of pump-priming new areas of research of both academic and industrial relevance.