In this paper, we determined the optimal flow rate trajectory during the loading phase of a mAb capture column. For this purpose, a multi-objective function was used, consisting of productivity and resin utilization. Several general types of trajectories were considered, and the optimal Pareto points were obtained for all of them. In particular, the presented trajectories include a constant-flow loading process as a nominal approach, a stepwise trajectory, and a linear trajectory. Selected trajectories were then applied in experiments with the state-of-the-art protein A resin mAb Select PrismA^TM, running in batch mode on a standard single-column chromatography setup, and using both a purified mAb solution as well as a clarified supernatant. The results show that this simple approach, programming the volumetric flow rate according to either of the explored strategies, can improve the process economics by increasing productivity by up to 12% and resin utilization by up to 9% compared to a constant-flow process, while obtaining a yield higher than 99%. The productivity values were similar to the ones obtained in a multi-column continuous process, and ranged from 0.23 to 0.35 mg/min/mL resin. Additionally, it is shown that a model calibration carried out at constant flow can be applied in the simulation and optimization of flow trajectories. The selected processes were scaled up to pilot scale and simulated to prove that even higher productivity and resin utilization can be achieved at larger scales, and therefore confirm that the trajectories are generalizable across process scales for this resin.

在本文中，我们确定了mAb捕获柱加载阶段的最佳流速轨迹。为此，使用了一个多目标函数，包括生产率和树脂利用率。考虑了几种一般类型的轨迹，并为所有轨迹获得了最佳帕累托点。特别地，所呈现的轨迹包括作为标称方法的恒流加载过程，逐步轨迹和线性轨迹。然后将选定的轨迹应用于最新的蛋白A树脂mAb Select PrismA ^{TM的实验中}，以分批模式在标准单柱色谱设置上运行，并同时使用纯化的mAb溶液和澄清的上清液。结果表明，与恒定流工艺相比，这种简单的方法（根据两种探索的策略之一对体积流量进行编程）可通过将生产率提高多达12％和将树脂利用率提高多达9％来提高工艺经济性，同时获得高于99％的产率。生产率值类似于在多柱连续法中获得的值，范围为0.23至0.35 mg / min / mL树脂。此外，还显示了在恒定流量下执行的模型校准可以应用于流动轨迹的仿真和优化。