Cell Factories: A Matter of Life or Death

这一学科跳跃项目是基于三位提出者的共同利益而提出的，目的是将受控水动力条件应用于生物发酵，以精确控制细胞环境。传统上，细菌是在研究实验室的培养批摇瓶中培养出来的。随着细菌细胞的生长，生长介质中的营养物质被消耗，有毒废物积累：细胞死亡随之而来。用发酵罐和摇瓶都可以用新鲜的营养物质补充培养基，但不可能去除废品。我们建议开发一种新型的串联毛细管生物反应器，它提供了向固定化细胞输送新鲜营养物质的可能性，同时去除了不利于生长的废物。我们建议在毛细管反应器中研究微生物介导的生物转化，在受控微流控环境中检测大肠杆菌和荧光假单胞菌的生长，并研究基因启动子的切换。知识传授对HOP的成功至关重要：RJMG将获得单相和多相流体力学基础知识的经验，以及用于设计和优化受控流动环境的可视化和建模方面的最新发展。MJS和SPD将在细胞生长和维护以及在生物转化中使用细胞方面获得经验。本课程介绍微生物学和生物化学，包括介质和仪器灭菌、介质制备和细胞处理的方法，将提供对反应器设计的背景了解。我们的目标是建立一种实质性的长期合作，架起化学-化学工程接口的桥梁，并将产生推动学术和工业相关的新研究领域的增值效果。

This 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.