近日，來(lái)自中科院蘇州納米技術(shù)與納米仿生研究所國(guó)際實(shí)驗(yàn)室的研究人員設(shè)計(jì)并開發(fā)出了高通量微生物培養(yǎng)芯片,，該芯片目前設(shè)計(jì)已申請(qǐng)專利,，相關(guān)研究結(jié)果已在國(guó)際雜志Small和Lab on a Chip上發(fā)表。
微生物已經(jīng)在工業(yè),、農(nóng)業(yè),、能源、環(huán)境,、醫(yī)藥等諸多領(lǐng)域發(fā)揮著無(wú)可替代的作用,。篩選獲得優(yōu)良的菌種是提升相關(guān)產(chǎn)業(yè)技術(shù)水平的重要途徑。通常,，微生物的液體培養(yǎng)篩選需要同時(shí)在數(shù)十上百個(gè)培養(yǎng)瓶或試管中進(jìn)行,。這使得整個(gè)篩選過(guò)程勞動(dòng)強(qiáng)度大，效率較低,。
中科院蘇州納米技術(shù)與納米仿生研究所國(guó)際實(shí)驗(yàn)室的甘明哲博士設(shè)計(jì)開發(fā)了一種用于細(xì)菌平行懸浮培養(yǎng)的多通道微流控芯片（圖1）,，可以一次進(jìn)行多個(gè)細(xì)菌培養(yǎng)實(shí)驗(yàn)。該芯片在7.5×5 cm2面積上集成32個(gè)獨(dú)立平行的細(xì)菌培養(yǎng)單元,，每個(gè)單元的培養(yǎng)液需求量極少,，僅為50nL,。在集成的氣動(dòng)微泵驅(qū)動(dòng)下，培養(yǎng)單元內(nèi)的液體能夠循環(huán)流動(dòng),，帶動(dòng)細(xì)菌在培養(yǎng)液中懸浮生長(zhǎng),，且液體流速基本一致，適合進(jìn)行平行實(shí)驗(yàn),。由于整個(gè)芯片材料透明,，可以隨時(shí)觀察芯片內(nèi)細(xì)菌的生長(zhǎng)情況。在此芯片上,，分別進(jìn)行了大腸桿菌,、枯草芽孢桿菌、施氏假單胞菌,、運(yùn)動(dòng)發(fā)酵單胞菌等重要工業(yè)細(xì)菌的懸浮培養(yǎng)測(cè)試,，證實(shí)了該芯片對(duì)于不同細(xì)菌培養(yǎng)的通用性。該芯片制作工藝簡(jiǎn)單,、制作成本低,，是一種高效的細(xì)菌懸浮培養(yǎng)解決方案。
在此基礎(chǔ)上,，研究人員進(jìn)一步開發(fā)了第二代微生物懸浮培養(yǎng)芯片（圖2）,。與前代芯片相比，該芯片的集成度更高,，在相同的面積上培養(yǎng)單元數(shù)量提高到120個(gè),，且單元內(nèi)的液體循環(huán)流速更高，這拓展了該芯片的微生物適用范圍,。該芯片不僅可用于培養(yǎng)細(xì)菌,，也可用于培養(yǎng)體積更大的酵母菌。同時(shí),，芯片的制作工藝更加簡(jiǎn)化,，這為以后芯片的低成本批量化生產(chǎn)提供了可能。
此項(xiàng)工作是“高效菌篩選檢測(cè)系統(tǒng)”項(xiàng)目的一部分,，該項(xiàng)目旨在運(yùn)用微流控技術(shù),，開發(fā)用于微生物菌種高通量篩選和條件優(yōu)化的芯片化系統(tǒng)，加速微生物高效,、高產(chǎn)菌株選育及配套工藝的開發(fā),。后續(xù)工作將進(jìn)行微生物代謝物微量快速檢測(cè)模塊的設(shè)計(jì)構(gòu)建。
該項(xiàng)目工作得到了中科院百人計(jì)劃項(xiàng)目,、中科院知識(shí)創(chuàng)新工程重要方向項(xiàng)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.
