Advances in process chromatography gradient elution using binary linear gradients

A number of chromatography techniques utilize mobile phase gradients with changing buffer concentration to effect separation. At process scale the majority of gradients are stepwise or isocratic. There are a number of instances where process performance or economics indicate that linear gradients would deliver better theoretical performance. However, to date this process advantage has not been implemented due to concerns about the accuracy, reliability or reproducibility of equipment used to produce linear changes in gradient composition. In this manuscript, recent developments in simple feedforward control and data from the resultant process-scale performance are presented. Information is provided on the practical heuristics underlying the control strategy. The data presented in this paper illustrate how the feedforward control strategy has been implemented on a commercial system to achieve better than ±2% accuracy of process-scale linear gradients.