Design and development of scale-down approaches, such as microbioreactor (µBR) technologies with integrated sensors, are an adequate solution for rapid, high-throughput and cost-effective screening of valuable reactions and/or production strains, with considerably reduced use of reagents and generation of waste. A significant challenge in the successful and widespread application of µBRs in biotechnology remains the lack of appropriate software and automated data interpretation of µBR experiments. Here, it is demonstrated how mathematical models can be usedas helpful tools, not only to exploit the capabilities of microfluidic platforms, but also to reveal the critical experimental conditions when monitoring cascade enzymatic reactions. A simplified mechanistic model was developed to describe the enzymatic reaction of glucose oxidase and glucose in the presence of catalase inside a commercial microfluidic platform with integrated oxygen sensor spots. The proposed model allowed an easy and rapid identification of the reaction mechanism, kinetics and limiting factors. The effect of fluid flow and enzyme adsorption inside the microfluidic chip on the optical sensor response and overall monitoring capabilities of the presented platform was evaluated via computational fluid dynamics (CFD) simulations. Remarkably, the model predictions were independently confirmed for µL- and mL- scale experiments. It is expected that the mechanistic models will significantly contribute to the further promotion of µBRs in biocatalysis research and that the overall study will create a framework for screening and evaluation of critical system parameters, including sensor response, operating conditions, experimental and microbioreactor designs.

中文翻译：

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具有集成光学传感器的微生物反应器的生物催化过程和性能的基于模型的分析

设计和开发按比例缩小的方法，例如带有集成传感器的微生物反应器 (μBR) 技术，是快速、高通量和经济高效地筛选有价值的反应和/或生产菌株的适当解决方案，同时大大减少了试剂的使用和废物的产生。µBR 在生物技术中的成功和广泛应用的一个重大挑战仍然是缺乏适当的软件和 µBR 实验的自动数据解释。在这里，展示了如何将数学模型用作有用的工具，不仅可以利用微流体平台的功能，还可以在监测级联酶促反应时揭示关键的实验条件。开发了一个简化的机械模型来描述在具有集成氧传感器点的商业微流体平台内在过氧化氢酶存在下葡萄糖氧化酶和葡萄糖的酶促反应。所提出的模型可以轻松快速地识别反应机理、动力学和限制因素。通过计算流体动力学 (CFD) 模拟评估了微流控芯片内的流体流动和酶吸附对所提出平台的光学传感器响应和整体监测能力的影响。值得注意的是，模型预测得到了 µL 和 mL 规模实验的独立确认。