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首页> 外文期刊>Biotechnology Progress >Optimal Synthesis of Chromatographic Trains for Downstream Protein Processing
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Optimal Synthesis of Chromatographic Trains for Downstream Protein Processing

机译：用于下游蛋白质加工的色谱图的最佳合成

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摘要

Downstream bioprocessing and especially chromatographic steps, commonly used for the purification of multicomponent systems, are significant cost drivers in the production of therapeutic proteins. There has been an increased interest in the development of systematic methods for the design of such processes, and the appropriate selection of a series of chromatographic steps is still a major challenge to be addressed. Several models have been developed previously but have assumed that 100% recovery of the desired product is obtained at each chromatographic step. In this work, a mathematical framework is proposed, based on mixed integer optimisation techniques, that removes this assumption and allows full flexibility on the position of retention time cut-points, between which the desired product fraction is collected. The proposed model is demonstrated on three example protein mixtures, each containing up to 13 contaminants and selecting from a set of up to 21 candidate steps. The proposed model results in a reduction of one to three chromatographic steps over solutions that no losses are allowed.
机译：通常用于纯化多组分系统的下游生物处理，尤其是色谱步骤，是生产治疗性蛋白质的重要​​成本驱动因素。人们对开发用于设计此类方法的系统方法的兴趣日益增加，并且适当选择一系列色谱步骤仍然是要解决的主要挑战。先前已经开发了几种模型，但是已经假定在每个色谱步骤中都能100％回收所需产物。在这项工作中，提出了一种基于混合整数优化技术的数学框架，该数学框架消除了这一假设，并允许在保留时间切割点的位置上完全灵活，在此之间可以收集所需的产品馏分。在三个示例蛋白质混合物上证明了所提出的模型，每种蛋白质混合物包含多达13种污染物，并从多达21种候选步骤中进行选择。与不允许损失的解决方案相比，建议的模型可将色谱步骤减少一到三个。

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