Characterisation of cellular assemblies in microfluidic systems (synthetic biology to obtain novel antibiotics and optimized production systems)

微流体系统中细胞组装体的表征（合成生物学以获得新型抗生素和优化的生产系统）

• 批准号: BB/I00484X/1
• 负责人: Nicolas Szita
• 金额: $ 51.36万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI00484X%2F1
• 关键词: Characterisation; cellular; assemblies; microfluidic; systems

The proposed research project forms an integral part of the larger international proposal SYNMOD (Full name: Synthetic biology to obtain novel antibiotics and optimised production systems), which is a collaborative project with five partners in Europe and one in the UK. SYNMOD seeks to integrate the basic science of Synthetic Biology with the necessary bioprocess engineering in order to achieve new and improved antibiotics to overcome the growing problem of antimicrobial resistance. In order to realise this potential, it is necessary to undertake research to develop protocols and technologies that allow to quickly and easily characterise biological parts and cells, and to understand their behaviour in different growth conditions. Developing such technologies and protocols is the goal of this proposed research project. Currently, some tools, such as shaker flasks, are easy to set up for an experiment, but provide relatively little information per experiment. Other tools, such as bench-scale bioreactors with multiple probes, are costly and labour-intensive to set up for an experiment. It is therefore difficult to perform the large number of experiments required to fully understand the behaviour of biological parts and cells. The proposed research addresses this by using micro-fabrication methods to create chambers with gas permeable membranes to provide the oxygen cells need. Through such 'microfluidic' reactor systems for the cultivation of cells have been fabricated, they have mainly been designed to operate in 'batch' mode. This is a reactor operation mode where the culture conditions vary considerably during an experiment. Accordingly, the properties of the cells, such as size, composition, and functional characteristics vary considerably, too. In contrast, in a 'chemostat' operation mode, the cells are kept in the same growth condition, i.e. the cell biomass, the nutrient and the product concentrations in the culture remain constant. This is achieved by a controlled and continuous supply of nutrient combined with a controlled and continuous removal of product and of 'excess' cells. Therefore, in a 'chemostat' operation mode, it becomes possible to correlate a cellular behaviour with a particular growth condition. In this research, we propose to build 'microfluidic' reactor systems that operate in 'chemostat' mode. Once this is solved, it will then become possible to use the general advantages of 'microfluidic' systems, such as parallelisation and automation, to create a cost-effective tool with which cell behaviour can be rapidly investigated and characterised.

拟议的研究项目是更大的国际提案SYNMOD（全称：合成生物学获得新型抗生素和优化生产系统）的组成部分，SYNMOD是一个与欧洲五个合作伙伴和英国一个合作伙伴的合作项目。SYNMOD旨在将合成生物学的基础科学与必要的生物工艺工程相结合，以实现新的和改进的抗生素，以克服日益严重的抗菌素耐药性问题。为了实现这一潜力，有必要开展研究，开发能够快速、轻松地表征生物部件和细胞的方案和技术，并了解它们在不同生长条件下的行为。开发这样的技术和协议是这个拟议研究项目的目标。目前，一些工具，如摇瓶，很容易为实验设置，但每次实验提供相对较少的信息。其他工具，如带有多个探针的实验规模的生物反应器，在实验中是昂贵和劳动密集型的。因此，要进行大量的实验来充分了解生物部分和细胞的行为是很困难的。提出的研究解决了这个问题，通过使用微制造方法来制造带有气体渗透膜的腔室，以提供所需的氧气细胞。通过这种用于细胞培养的“微流控”反应器系统已经被制造出来，它们主要被设计成在“批量”模式下运行。这是一种反应器操作模式，在实验过程中，培养条件变化很大。因此，细胞的性质，如大小、组成和功能特征也有很大的不同。相反，在“恒化”操作模式下，细胞保持在相同的生长条件下，即细胞生物量、营养物和培养物中的产物浓度保持不变。这是通过控制和持续的营养供应，结合控制和持续去除产品和“多余”细胞来实现的。因此，在“恒化”操作模式下，可以将细胞行为与特定的生长条件联系起来。在这项研究中，我们建议建立在“恒化”模式下运行的“微流控”反应器系统。一旦这个问题得到解决，就有可能利用“微流体”系统的一般优势，如并行化和自动化，来创造一种经济有效的工具，用它可以快速研究和表征细胞行为。

项目成果

Electromagnetic stirring in a microbioreactor with non-conventional chamber morphology and implementation of multiplexed mixing.

• DOI: 10.1002/jctb.4762
• 发表时间: 2015-10
• 期刊: Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)
• 作者: Tan CK;Davies MJ;McCluskey DK;Munro IR;Nweke MC;Tracey MC;Szita N
• 通讯作者: Szita N

Oxygen transfer characteristics of miniaturized bioreactor systems.

微型生物反应器系统的氧转移特性。

• DOI: 10.1002/bit.24824
• 发表时间: 2013-04
• 期刊: BIOTECHNOLOGY AND BIOENGINEERING
• 影响因子: 3.8
• 作者: Kirk, Timothy V.;Szita, Nicolas
• 通讯作者: Szita, Nicolas

Development of a microbioreactor 'cassette' for the cultivation of microorganisms in batch and chemostat mode

开发用于以批量和恒化器模式培养微生物的微生物反应器“盒”

• 发表时间: 2013
• 期刊: Chimica Oggi - Chemistry Today
• 作者: Davies, MJ

Possible mechanisms of CO2 reduction by H2 via prebiotic vectorial electrochemistry.

H2 通过生命起源前矢量电化学还原 CO2 的可能机制。

• DOI: 10.1098/rsfs.2019.0073
• 发表时间: 2019
• 期刊: Interface focus
• 影响因子: 4.4
• 作者: Vasiliadou R

Quantification of the oxygen uptake rate in a dissolved oxygen controlled oscillating jet-driven microbioreactor.

• DOI: 10.1002/jctb.4833
• 发表时间: 2016-03
• 期刊: Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)
• 作者: Kirk TV;Marques MP;Radhakrishnan AN;Szita N
• 通讯作者: Szita N