Timely monitoring and control of critical process parameters and product attributes are still the basic tasks in bioprocess development. The current trend of automation and digitization in bioprocess technology targets an improvement of these tasks by reducing human error and increasing through-put. The gaps in such automation procedures are still the sampling procedure, sample preparation, sample transfer to analyzers, and the alignment of process and sample data. In this study, an automated sampling system and the respective data management software were evaluated for system performance; applicability with HPLC for measurement of vitamins, product and amino acids; and applicability with a biochemical analyzer. The focus was especially directed towards the adaptation and assessment of an appropriate amino acid method, as these substances are critical in cell culture processes. Application of automated sampling in a CHO fed-batch revealed its potential with regard to data evaluation. The higher sampling frequency compared to manual sampling increases the generated information content, which allows easier interpretation of the metabolism, extraction of e.g., k_s values, application of smoothing algorithms, and more accurate detection of process events. A comparison with sensor technology shows the advantages and disadvantages in terms of measurement errors and measurement frequency.

中文翻译：

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用于CHO文化在线和实时监控的可靠自动化采样系统

关键过程参数和产品属性的及时监视和控制仍然是生物过程开发中的基本任务。生物工艺技术中当前的自动化和数字化趋势旨在通过减少人为错误和增加生产量来改善这些任务。这种自动化程序中的差距仍然是采样程序，样品制备，样品向分析仪的转移以及过程和样品数据的对齐。在这项研究中，评估了自动采样系统和相应的数据管理软件的系统性能；适用于HPLC测定维生素，产物和氨基酸; 以及与生化分析仪的适用性。重点尤其是针对适当氨基酸方法的适应和评估，因为这些物质在细胞培养过程中至关重要。在CHO补料批次中应用自动采样显示了其在数据评估方面的潜力。与手动采样相比，更高的采样频率会增加生成的信息内容，从而使新陈代谢的解释更容易，例如提取k_的值，平滑算法的应用以及对过程事件的更准确检测。与传感器技术的比较显示了在测量误差和测量频率方面的优缺点。