Macroscopic investigation of the transient hydrodynamic memory behavior of preparative packed chromatography beds

The goal of the present work was to examine the hydrodynamic behavior of preparative scale packed chromatography beds during long-term cyclical operation at high loads using an experimental set-up with a high resolution measuring device of bed height. One agarose-based resin and one methacrylic-based resin were examined in a 140 mm column. Both resins exhibited hysteresis behavior during compression/relaxation cycles. The hystereses were less pronounced with decreasing hydrodynamic stress rate. The occurrence of hystereses was an indication for hydrodynamic memory behavior of the chromatography packing. During long-term cyclical operation at high loads of the column filled with methacrylic resin, oscillations of the steadily with time decreasing flow rate were observed for the first time. These oscillations were attributed to the viscoelasticity of the polymer particles network representing a system with materials with fading memory. Such nonlinear systems with feed-back are known to exhibit inherent self-oscillations. A decoupling of the two processes of bed compression and decrease of bed permeability was observed. The presented results explain why preparative packed-bed chromatography often yields unsatisfactory reproducible data and why unwanted phenomena like medium wall detachment or other symptoms of deteriorated chromatography beds are frequently observed.