Hearle, David Charles; (1997) An investigation into process related fouling of chromatographic supports. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This work focuses on the integration of chromatography, specifically ion exchange chromatography (lEC), within a process. Chromatography is commonly used after pretreatment of the crude process stream by at least one processing step designed to remove foulants and competitors which significantly alter the separation and may irreversibly damage the support. Since chromatography represents a considerable proportion of process costs, significant effort is made to reduce the amount of contaminants reaching the chromatographic stage by the use of pre-treatment, incurring a penalty in reduced product yield, increased process time and increased capital/operating costs. The selection of the appropriate pre-treatment is restricted by a lack of knowledge concerning the sensitivity of the chromatography to key contaminants. The development of methods for evaluating the susceptibility to specific foulants is the aim of this work. Initially a test separation of an intracellular enzyme, yeast alcohol dehydrogenase (ADH), was used to determine the changes in chromatographic separations with a variety of process stream compositions. By monitoring the yield and purity of the ADH , the performance was shown to be load and time dependant. This approach was unable to provide a general quantitative analysis: other techniques were used to elicit how the fouling occurred. Frontal analysis was used to relate changes in the chromatographic performance to a decrease in the effective diffusivity of the ion exchange support. The technique was rapid and could be used to define the limit of the feed stream loading. Moment analysis was used to determine a change in the effective diffusivity and the packed column axial dispersion for both functional ion exchange and the base matrices, but required rigorous experiments to obtain consistent results. Results indicated particulate fouling to be a major source of performance change, and that fouling species acted together to produce effects absent when the fouling species was present on it's own. The methods described are generic in application and could provide a basis for improving the integration of chromatography into processes.

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