| There is an imperative need to design high resolution and cost effective downstream processing schemes for the large scale purification of biomolecules. Displacement chromatography can potentially offer a solution to these problems, as it can simultaneously concentrate and purify target proteins from very closely related impurities.; Despite its inherently high resolving power, displacement chromatography is yet to make a niche in the biotechnology industry. The major impediment towards the implementation of this technology has been the rather limited choice of non-toxic and inexpensive displacer compounds. This research addresses this issue as it endeavors to identify low molecular weight compounds with different functionalities and geometries as potential displacers for proteins. Some of the low molecular weight displacers that have been identified are protected amino acid esters, aminoglycosidic antibiotics, aromatic sulfonic acids and sulfated sugars. Experiments have been carried out on a model system of proteins in both cation and anion exchange systems to test the efficacy of these displacers under different operating conditions. The ability of these low molecular weight compounds to act as displacers is fundamentally very exciting as it runs counter to the conventional wisdom that large polyelectrolytes are almost always required to displace proteins in ion-exchange systems.; In addition to obtaining traditional displacement profiles, these low molecular weight displacers can also be employed to carry out selective displacement chromatography. Selective displacement chromatography is an attractive process as it has several operational advantages. Selective displacement can easily be carried out using low molecular weight displacers by changing the operating conditions of the displacement process. Theoretical and experimental results are presented to elucidate this concept.; While it is important to know the final order in an isotachic displacement train, it is also equally important to know the order in which the feed solutes arrange themselves in the loading stage. A unit selectivity plot based on the Steric Mass Action formalism is developed to predict a priori the order in the loading stage. The impact of the feed conditions on the performance of the displacement is shown through simulations. |
