A number of chromatography techniques utilize mobile phase gradients with c
hanging buffer concentration to effect separation. At process scale the maj
ority of gradients are stepwise or isocratic. There are a number of instanc
es where process performance or economics indicate that linear gradients wo
uld deliver better theoretical performance. However, to date this process a
dvantage has not been implemented due to concerns about the accuracy, relia
bility or reproducibility of equipment used to produce linear changes in gr
adient composition. In this manuscript, recent developments in simple feedf
orward control and data from the resultant process-scale performance are pr
esented. Information is provided on the practical heuristics underlying the
control strategy. The data presented in this paper illustrate how the feed
forward control strategy has been implemented on a commercial system to ach
ieve better than +/-2% accuracy of process-scale linear gradients. (C) 2001
Published by Elsevier Science B.V.