Efficiency of preparative and process column distribution systems.

An analytical method for computing the residence time distribution of the liquid distribution system in chromatography columns is described. The impact of the distributor design on the separation efficiency is predicted as a function of media properties and packed bed dimensions. The efficiency loss due to the distributor when increasing column diameter during scale-up is quantified. It is shown that this loss can be compensated by modulating the local bed height via a moderate inclination of the bed support. It is concluded that the selection of an appropriate distributor design concept with optimised dimensions enables a scale-up of chromatographic separations without any significant loss of chromatographic efficiency due to the distribution system.

Plasma protein fractionation with advanced membrane adsorbents.

High capacity membrane adsorbents have been used as a stationary phase for the preparative chromatographic purification of human serum albumin. A two-step ion exchange fractionation scheme yields albumin with 98% purity from clarified, microfiltrated, and desalted human plasma. Experiments with laboratory and pilot scale membrane modules are compared to literature data obtained with conventional Fast Flow Sepharose in a similar purification protocol. Increased productivity in combination with excellent reproducibility and stability was found using the membrane adsorbents. Scale-up of the process based on standard microfiltration equipment was successful but resulted in reduced capacity and productivity due to deteriorated flow characteristics of the module. This was attributed to the effects of substantial axial dispersion in the pilot scale module. Methods to reduce this limitation were identified. The concept of membrane adsorption chromatography for the fast purification of proteins is illustrated and engineering aspects important for the process design are discussed.