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Optimal design and operation of high performance liquid chromotographic processes

Teoh, Hooi Kim; (2002) Optimal design and operation of high performance liquid chromotographic processes. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Due to its high selectivity and ability to realise high levels of product(s) purity, chromatographic separation has become an integral technique in the purification of many fine chemicals, pharmaceuticals and biologics. In this work, different feasible column designs and operating policies of high performance liquid chromatographic processes are investi gated so as to minimise the major purification cost elements involved whilst at the same time enhancing the column performance. This overall objective has been demonstrated for mixtures with practical relevance. Dynamic mathematical models for general chromatographic units were employed as the basis for this study so as to take advantage of advances in computational capability currently available. Experimental and mathematical verification of these models has been performed to increase the accuracy and reliability of the simulations. Recognising the importance of the isotherm model in chromatography separation, a systematic procedure for isotherm determination which requires only minimal experimental effort and offers significant reduction in time, has been developed. The mathematical models coupled with a rigorous dynamic optimisation technique have been employed to determine the best column design configuration for a series of representative chromatographic processes. This approach exploits the full potential of the chromatographic separation process by taking into account key design parameters and operating variables such as column length, column diameter, particle size, flow rate, valve switching action etc. The optimal design leads to improvements in production rate as well as in separation power. Significant effort is allocated to the investigation of different operating policies for chro matographic separations including: conventional recycling, a peak shaving technique and multiple feed injection. Optimisation results show that by application of the described op erating policies, the column performance can be enhanced whilst keeping the volume of the matrix constant, hence leading to substantial cost savings. The optimal solution is shown to be highly dependent on the separation conditions. As a result, careful consideration is required to decide which policy and which separation conditions should be adopted for a given process. The thesis concludes with recommendations on how best to implement the results of the study in an industrial context and outlines areas for future study.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Optimal design and operation of high performance liquid chromotographic processes
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Applied sciences; Chromatographic separation
URI: https://discovery.ucl.ac.uk/id/eprint/10098828
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