Real-time dissolved carbon dioxide monitoring I: Application of a novel in situ sensor for CO2 monitoring and control.,Biotechnology and Bioengineering

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Real-time dissolved carbon dioxide monitoring I: Application of a novel in situ sensor for CO2 monitoring and control.
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2020-01-11 , DOI: 10.1002/bit.27253
Viki R Chopda ₁ , Timothy Holzberg ₁ , Xudong Ge ₁ , Brandon Folio ₁ , Michael Tolosa ₁ , Yordan Kostov ₁ , Leah Tolosa ₁ , Govind Rao ₁

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Dissolved carbon dioxide (dCO2 ) is a well-known critical parameter in bioprocesses due to its significant impact on cell metabolism and on product quality attributes. Processes run at small-scale faces many challenges due to limited options for modular sensors for online monitoring and control. Traditional sensors are bulky, costly, and invasive in nature and do not fit in small-scale systems. In this study, we present the implementation of a novel, rate-based technique for real-time monitoring of dCO2 in bioprocesses. A silicone sampling probe that allows the diffusion of CO2 through its wall was inserted inside a shake flask/bioreactor and then flushed with air to remove the CO2 that had diffused into the probe from the culture broth (sensor was calibrated using air as zero-point calibration). The gas inside the probe was then allowed to recirculate through gas-impermeable tubing to a CO2 monitor. We have shown that by measuring the initial diffusion rate of CO2 into the sampling probe we were able to determine the partial pressure of the dCO2 in the culture. This technique can be readily automated, and measurements can be made in minutes. Demonstration experiments conducted with baker's yeast and Yarrowia lipolytica yeast cells in both shake flasks and mini bioreactors showed that it can monitor dCO2 in real-time. Using the proposed sensor, we successfully implemented a dCO2 -based control scheme, which resulted in significant improvement in process performance.

中文翻译：

实时溶解二氧化碳监测一：新型原位传感器在二氧化碳监测和控制中的应用。

溶解二氧化碳 (dCO2) 是生物过程中众所周知的关键参数，因为它对细胞代谢和产品质量属性具有重大影响。由于用于在线监测和控制的模块化传感器的选择有限，小规模运行的流程面临许多挑战。传统传感器体积庞大、成本高昂且具有侵入性，不适合小型系统。在这项研究中，我们提出了一种基于速率的新型技术的实施，用于实时监测生物过程中的 dCO2。将允许 CO2 通过其壁扩散的硅胶采样探针插入摇瓶/生物反应器内，然后用空气冲洗，以除去从培养液中扩散到探针中的 CO2（使用空气作为零点校准传感器）校准）。然后让探头内的气体通过不透气的管道再循环到二氧化碳监测仪。我们已经证明，通过测量 CO2 进入采样探头的初始扩散速率，我们能够确定培养物中 dCO2 的分压。该技术可以轻松实现自动化，并且可以在几分钟内完成测量。在摇瓶和微型生物反应器中用面包酵母和解脂耶氏酵母细胞进行的示范实验表明，它可以实时监测 dCO2。使用所提出的传感器，我们成功实施了基于 dCO2 的控制方案，从而显着提高了过程性能。

更新日期：2020-03-09

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