Protein concentration determination is a necessary in-process control for the downstream operations within biomanufacturing. As production transitions from batch mode to an integrated continuous bioprocess paradigm, there is a growing need to move protein concentration quantitation from off-line to in-line analysis. One solution to fulfill this process analytical technology need is an in-line index of refraction (IoR) sensor to measure protein concentration in real time. Here the performance of an IoR sensor is evaluated through a series of experiments to assess linear response, buffer matrix effects, dynamic range, sensor-to-sensor variability, and the limits of detection and quantitation. The performance of the sensor was also tested in two bioprocessing scenarios, ultrafiltration and capture chromatography. The implementation of this in-line IoR sensor for real-time protein concentration analysis and monitoring has the potential to improve continuous bioprocess manufacturing.

中文翻译：

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通过在线折射率测定下游生物制造过程中的蛋白质浓度

蛋白质浓度测定是生物制造中下游操作的必要过程控制。随着生产从批处理模式转变为集成的连续生物过程范例，越来越需要将蛋白质浓度定量从离线分析转移到在线分析。满足这一过程分析技术需求的一种解决方案是使用在线折射率 (IoR) 传感器实时测量蛋白质浓度。在这里，通过一系列实验评估 IoR 传感器的性能，以评估线性响应、缓冲基质效应、动态范围、传感器间的可变性以及检测和定量限制。传感器的性能也在两种生物处理场景中进行了测试，即超滤和捕获色谱。