Institute of Biotechnology, Martin-Luther-University, Halle, Germany.
Appl Microbiol Biotechnol. 2010 Jan;85(4):955-64. doi: 10.1007/s00253-009-2114-5. Epub 2009 Aug 13.
A simple well-performing adaptive control technique for pH control in fermentations of recombinant protein production processes is described and its design procedure is explained. First, the entire control algorithm was simulated and parameterized. Afterwards it was tested in real cultivation processes. The results show that this simple technique leads to significant reductions in the fluctuations of the pH values in microbial cultures at a minimum of expenditures. The signal-to-noise ratio and thus the information captured by the pH signal were increased by about an order of magnitude. This leads to a substantial improvement in the noise of many other process signals that are used to monitor and control the process. For instance, respiratory off-gas data of CO(2) and its derived carbon dioxide production rate signals from the cultures carry much less noise as compared to those values obtained with conventional pH control. Detailed process analysis revealed that even very small pH jumps of 0.03 values during the fermentation were shown to result in pronounced deflections in CO(2)-volume fraction of 8% (peak to peak). The proposed controller, maintaining the pH within the interval of 0.01 around the setpoint, reduces the noise considerably.
本文描述了一种用于重组蛋白生产过程发酵中 pH 控制的简单而有效的自适应控制技术，并解释了其设计过程。首先，对整个控制算法进行了模拟和参数化。然后，在实际培养过程中进行了测试。结果表明，这种简单的技术可在最小的投入下，显著降低微生物培养物中 pH 值的波动。信噪比，即 pH 信号所捕获的信息，提高了约一个数量级。这导致许多用于监测和控制过程的其他过程信号的噪声大大降低。例如，与传统 pH 控制相比，培养物的呼吸废气数据（CO2）及其衍生的二氧化碳生产率信号的噪声要小得多。详细的过程分析表明，发酵过程中 pH 值仅发生 0.03 的微小波动，就会导致 CO2-体积分数明显偏离 8%（峰峰值）。所提出的控制器将 pH 值维持在设定值上下 0.01 的区间内，可大大降低噪声。
