arXiv:2512.03460q-bio.QMcs.AI2025-12被引 2

针对生物工艺数据少、反馈稀疏的问题,比较多种机器学习方法在细胞培养监测中的表现。

Learning From Limited Data and Feedback for Cell Culture Process Monitoring: A Comparative Study

  • 采用降维、在线学习和即时学习等策略应对数据有限挑战
  • 即时学习在冷启动场景下表现优于批量学习,提升适应性
  • 融合拉曼光谱与滞后离线数据可显著提高监测精度

在细胞培养生物制造中,实时批次过程监控(BPM)涉及对活细胞密度、营养物质水平、代谢物浓度和产物滴度等关键变量的全程跟踪分析,有助于早期发现异常并及时干预,保障细胞生长和产品质量。然而,开发高精度软传感器面临历史数据有限、反馈稀疏、过程条件异质及高维传感输入等挑战。本研究系统评估了多种机器学习方法在处理少量且相关性低的历史数据时的表现,涵盖特征降维、在线学习和即时学习,基于一个仿真数据集和两个真实实验数据集进行验证。结果表明,训练策略对模型性能至关重要:在同质环境下批量学习有效,而在冷启动场景中,即时学习与在线学习展现出更强的适应能力。同时识别出喂料介质组成和过程控制策略等元特征显著影响模型迁移性。此外,将拉曼光谱预测与滞后的离线测量结合,可显著提升监控精度,为未来生物工艺软传感器开发提供可行方向。

原文摘要 · Abstract (English)

In cell culture bioprocessing, real-time batch process monitoring (BPM) refers to the continuous tracking and analysis of key process variables such as viable cell density, nutrient levels, metabolite concentrations, and product titer throughout the duration of a batch run. This enables early detection of deviations and supports timely control actions to ensure optimal cell growth and product quality. BPM plays a critical role in ensuring the quality and regulatory compliance of biopharmaceutical manufacturing processes. However, the development of accurate soft sensors for BPM is hindered by key challenges, including limited historical data, infrequent feedback, heterogeneous process conditions, and high-dimensional sensory inputs. This study presents a comprehensive benchmarking analysis of machine learning (ML) methods designed to address these challenges, with a focus on learning from historical data with limited volume and relevance in the context of bioprocess monitoring. We evaluate multiple ML approaches including feature dimensionality reduction, online learning, and just-in-time learning across three datasets, one in silico dataset and two real-world experimental datasets. Our findings highlight the importance of training strategies in handling limited data and feedback, with batch learning proving effective in homogeneous settings, while just-in-time learning and online learning demonstrate superior adaptability in cold-start scenarios. Additionally, we identify key meta-features, such as feed media composition and process control strategies, that significantly impact model transferability. The results also suggest that integrating Raman-based predictions with lagged offline measurements enhances monitoring accuracy, offering a promising direction for future bioprocess soft sensor development.

生物工艺软传感器小样本学习

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