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首页> 外文期刊>Biotechnology Progress >A New Microfluidic Concept for Parallel Operated Milliliter-Scale Stirred Tank Bioreactors
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A New Microfluidic Concept for Parallel Operated Milliliter-Scale Stirred Tank Bioreactors

机译：并联操作的搅拌釜生物反应器的微流控新概念。

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Parallel miniaturized stirred tank bioreactors are an efficient tool for "high-throughput bioprocess design." As most industrial bioprocesses are pH-controlled and/or are operated in a fed-batch mode, an exact scale-down of these reactions with continuous dosing of fluids into the miniaturized bioreactors is highly desirable. Here, we present the development, characterization, and application of a novel concept for a highly integrated microfluidic device for a bioreaction block with 48 parallel milliliter-scale stirred tank reactors (V = 12 mL). The device consists of an autoclavable fluidic section to dispense up to three liquids individually per reactor. The fluidic section contains 144 membrane pumps, which are magnetically driven by a clamped-on actuator section. The micropumps are designed to dose 1.6 μL per pump lift. Each micropump enables a continuous addition of liquid with a flow rate of up to 3 mL h~(-1). Viscous liquids up to a viscosity of 8.2 mPa s (corresponds to a 60% v/v glycerine solution) can be pumped without changes in the flow rates. Thus, nearly all feeding solutions can be delivered, which are commonly used in bioprocesses. The functionality of the first prototype of this microfluidic device was demonstrated by double-sided pH-con-trolled cultivations of Saccharomyces cerevisiae based on signals of fluorimetric sensors embedded at the bottom of the bioreactors. Furthermore, fed-batch cultivations with constant and exponential feeding profiles were successfully performed. Thus, the presented novel microfluidic device will be a useful tool for parallel and, thus, efficient optimization of controlled fed-batch bioprocesses in small-scale stirred tank bioreactors. This can help to reduce bioprocess development times drastically.
机译：平行小型搅拌釜生物反应器是用于“高通量生物工艺设计”的有效工具。由于大多数工业生物过程是pH控制的和/或以分批补料的方式运行，因此非常需要在向微型化生物反应器中连续加液的过程中精确缩小反应规模。在这里，我们介绍了用于具有48个平行毫升级搅拌釜反应器（V = 12 mL）的生物反应块的高度集成微流控设备的新型概念的开发，表征和应用。该设备由可高压灭菌的流体部分组成，每个反应器最多可分别分配三种液体。流体部分包含144个隔膜泵，它们由一个夹紧的执行器部分磁力驱动。微型泵设计为每泵升程剂量为1.6μL。每个微型泵都能够以高达3 mL h〜（-1）的流速连续添加液体。可以泵送粘度高达8.2 mPa s的粘性液体（相当于60％v / v甘油溶液），而无需改变流速。因此，几乎所有的进料溶液都可以被输送，这在生物过程中是常用的。基于嵌入在生物反应器底部的荧光传感器的信号，通过双面pH值控制的酿酒酵母对这种微流体装置的第一个原型的功能进行了演示。此外，成功进行了具有恒定和指数进料曲线的分批进料培养。因此，提出的新颖的微流体装置将是用于小规模搅拌釜生物反应器中的平行且因此有效优化受控补料分批生物工艺的有用工具。这可以帮助大大减少生物工艺开发时间。

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