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Abstract

Preparative chromatographic techniques are widely employed today in pharmaceutical and biochemical industries. Optimal isolation of a target component with high purity is of significant importance in a sector with continuously increasing quality standards. The components of interest are often part of complex mixtures. Over the years, preparative batch chromatography has been successfully used to isolate target components from multi-component mixtures. It has been demonstrated frequently that by exploiting certain additional operational aspects, the separation performance of classical methods could be further enhanced. In this thesis, novel operating modes derived from classical schemes are evaluated focusing on the optimal separation of specific target components from multi-component mixtures. Initially, a general framework has been provided for finding the critical fractionation or cut-times required to evaluate performance. New strategies were developed to find the cut-times based on a discrete and a continuous approach. The efficiency of these methods was compared with that of a widely implemented algorithm based on the evaluation of local purities. The robustness of the methods was analyzed using two theoretical case studies. In the next part, the separation potential of a new scheme involving an initial solvent gradient and closed-loop recycling has been evaluated. Using specific objective functions, the separation performance of this new concept was compared with those of conventional operational modes. The new scheme showed an enhanced separation performance when the selectivities of the target component with respect to the neighboring components decreased with increase in elution strength. In the final part, a concept of coupling chromatographic segments with different stationary phases has been extended to preparative applications using a theoretical study. The relative lengths and order of the segments were found to have a significant influence on the performance of separating an intermediately eluting component. Extending this concept to a mixed mode configuration resulted in an improved separation performance. The trends seen in the theoretical study were demonstrated experimentally using a test system. Adsorption isotherm data was measured and later used to quantify the sensitivity of optimal relative segment lengths on isotherm nonlinearities. Rather than the factors inducing non-linearities themselves, their differences were found to have a larger influence on optimal separation.