Preparative gradient chromatography

During a chromatographic separation, it is convenient to keep the essential operating parameters like temperature, pressure, mobile phase flow-rate, and mobile phase composition constant. Though, it is well known that in contrast to this isocratic operation the intelligent modulation of certain operating parameters can improve the separation performance significantly. Such gradient approaches are widely applied in analytical (linear) chromatography to reduce the time of analysis and to enhance the selectivity. In contrast, the extent of application of these gradients is still rather limited in the field of preparative (nonlinear) chromatography. The first part of this paper is devoted to the discussion of the principal differences between lineat- and nonlinear and isocratic and gradient chromatography. The second part focuses on introducing a countercurrent process that allows separation in a continuous manner, efficiently exploiting a two-step solvent composition gradient.