近日,来自中科院苏州纳米技术与纳米仿生研究所国际实验室的研究人员设计并开发出了高通量微生物培养芯片,该芯片目前设计已申请专利,相关研究结果已在国际杂志Small和Lab on a Chip上发表。
微生物已经在工业、农业、能源、环境、医药等诸多领域发挥着无可替代的作用。筛选获得优良的菌种是提升相关产业技术水平的重要途径。通常,微生物的液体培养筛选需要同时在数十上百个培养瓶或试管中进行。这使得整个筛选过程劳动强度大,效率较低。
中科院苏州纳米技术与纳米仿生研究所国际实验室的甘明哲博士设计开发了一种用于细菌平行悬浮培养的多通道微流控芯片(图1),可以一次进行多个细菌培养实验。该芯片在7.5×5 cm2面积上集成32个独立平行的细菌培养单元,每个单元的培养液需求量极少,仅为50nL。在集成的气动微泵驱动下,培养单元内的液体能够循环流动,带动细菌在培养液中悬浮生长,且液体流速基本一致,适合进行平行实验。由于整个芯片材料透明,可以随时观察芯片内细菌的生长情况。在此芯片上,分别进行了大肠杆菌、枯草芽孢杆菌、施氏假单胞菌、运动发酵单胞菌等重要工业细菌的悬浮培养测试,证实了该芯片对于不同细菌培养的通用性。该芯片制作工艺简单、制作成本低,是一种高效的细菌悬浮培养解决方案。
在此基础上,研究人员进一步开发了第二代微生物悬浮培养芯片(图2)。与前代芯片相比,该芯片的集成度更高,在相同的面积上培养单元数量提高到120个,且单元内的液体循环流速更高,这拓展了该芯片的微生物适用范围。该芯片不仅可用于培养细菌,也可用于培养体积更大的酵母菌。同时,芯片的制作工艺更加简化,这为以后芯片的低成本批量化生产提供了可能。
此项工作是“高效菌筛选检测系统”项目的一部分,该项目旨在运用微流控技术,开发用于微生物菌种高通量筛选和条件优化的芯片化系统,加速微生物高效、高产菌株选育及配套工艺的开发。后续工作将进行微生物代谢物微量快速检测模块的设计构建。
该项目工作得到了中科院百人计划项目、中科院知识创新工程重要方向项目的大力支持。(生物谷Bioon.com)
doi:10.1039/C1LC20670B
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A scalable microfluidic chip for bacterial suspension culture
Mingzhe Gan , Jing Su , Jing Wang , Hongkai Wu and Liwei Chen
Microfluidic systems could, in principle, enable high-throughput breeding and screening of microbial strains for industrial applications, but parallel and scalable culture and detection chips are needed before complete microbial selection systems can be integrated and tested. Here we demonstrate a scalable multi-channel chip that is capable of bacterial suspension culture. The key invention is a multi-layered chip design, which enables a single set of control channels to function as serial peristaltic pumps to drive parallel culture chamber loops. Such design leads to scalability of the culture chip. We demonstrate that E. coli growth in the chip is equivalent or superior to conventional suspension culture on shaking beds. The chip could also be used for suspension culture of other microbes such as Bacillus subtilis, Pseudomonas stutzeri, and Zymomonas mobilis, indicating its general applicability for bacterial suspension culture.
doi:10.1002/smll.201102322
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Massively Parallel Bacterial and Yeast Suspension Culture on a Chip
Mingzhe Gan1, Yunfang Tang1, Yiwei Shu2, Hongkai Wu2, Liwei Chen1,*
A new microfluidic chip integrated with 120 parallelmicrobial suspension culture units is demonstrated. Various bacterial strains and even yeast can be cultivated on the chip. With a high degree of integration and simple fabrication process, this chip could be a central component for future high-throughput microbial screening and selection systems.