Theoretical and experimental investigation of band-broadening effects in innovative chromatography system

With the advent of demanding novel research fields in the pharmacological and biotechnological industry involving very complex samples, there is an ongoing quest for separation techniques that are able to reveal a detailed and complete picture of the sample constituents. In combination with highly sensitive detectors, chromatography is the ultimate separation technique to fulfill these stringent requirements. Although strong performance improvements have already been made for the traditional packed-bed columns, the number of possible optimization strategies is greatly enlarged with the recent introduction of innovative chromatographic systems like monolithic columns, ordered microstructured columns and shear-driven flow techniques. Knowledge of the mechanisms determining column performance and insight in their relative contributions is however indispensible to direct the optimization of these novel systems. In this PhD, several band broadening effects that limit the performance of chromatographic systems have therefore been studied in detail. The work comprised a theoretical analysis of adsorption/desorption effects in shear-driven chromatographic systems and a numerical study of mass-transfer resistance effects in complex monolithic structures. In addition, a novel support structure was developed that combines the versatility and mass loadability of silica monolithic columns with the high degree of order of microstructured columns. The promising chromatographic properties of this hybrid column structure could be demonstrated experimentally.