Micro-bioreactors for fed-batch fermentations with integrated online monitoring and microfluidic devices
Micro-bioreactors for fed-batch fermentations with integrated online monitoring and microfluidic devices
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DOI：
10.1016/j.bios.2008.08.043
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发表时间：
2009-01-01
影响因子：
12.6
通讯作者：
Schnakenberg, U.
中科院分区：
文献类型：
--
作者：
Buchenauer, A.;Hofmann, M. C.;Schnakenberg, U.
在这项研究中，提出了一种基于48孔微量滴定板（MTP）格式的微生物反应器阵列。通过不同传感器、biolector（TM）测量技术和电导测量的组合，在线监测pH值和生物量。微流控装置将两种流体分别分配到每个孔中以控制发酵的pH值。微生物反应器由四个威尔斯孔和两个储液器组成。在每个孔中，集成了具有用于电导测量的铂电极的聚酰亚胺箔。微流控器件是使用软光刻技术制造的，并利用微阀驱动。该设备能够分配低于5 nl的体积。最后，在微型生物反应器系统中进行了大肠杆菌的发酵。在发酵过程中，pH值是光学测量的，生物量的发展是由散射光信号监测。同时，通过添加氢氧化钠和磷酸来控制发酵液的pH值，从而实现了微生物发酵过程在线监测和pH值控制的可能性。非对照培养物中的pH值在6.46-8.83范围内变化，而对照培养物中的pH值可保持在6.85-7.07范围内。这导致与几乎完全抑制的pH不受控培养物相比，pH受控培养物中的生物量增加。(C)2008 Elsevier B. V.保留所有权利。
In this study an array of micro-bioreactors based on the format of 48-well microtiter plates (MTP) is presented. The process parameters pH-value and biomass are monitored online by a combination of different sensors, the biolector(TM) measurement technology and conductance measurements. A microfluidic device dispenses two fluids individually into each well for controlling the pH-value of fermentations.The micro-bioreactor consists of four wells and two reservoirs. In each well a polyimide foil with platinum electrodes for conductance measurements is integrated. The microfluidic device is fabricated using softlithographic techniques and utilizes pneumatically actuated microvalves. The device is able to dispense volumes below 5 nl. Finally, fermentations of Escherichia coli are carried Out in the micro-bioreactor system. During the fermentation, the pH-value is measured optically and the biomass development is monitored by the scattered light signal. Meanwhile, the pH-value is controlled by dispensing sodium hydroxide and phosphoric acid.This micro-bioreactor demonstrates the possibility of online monitored and pH-controlled fermentations in micro-scale. The pH-value in the uncontrolled culture varies within the range of 6.46-8.83 whereas the pH-value in the controlled cultures can be kept within 6.85-7.07. This results in an increase in biomass in the pH-controlled culture compared to the nearly completely inhibited pH-uncontrolled culture. (C) 2008 Elsevier B.V. All rights reserved.