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Abstract: The determination of proteins is increasingly becoming an important part of biomedical research. Here, we investigate a novel approach to separate and measure protein concentrations by HPLC. A metal chelating ligand is covalently bonded to a polystyrene/polydivinylbenzene substrate. The metal ion is bonded to the substrate in two ways: randomly, where the metal ion is bound to the ligand after the substrate polymerization, and, imprinted, where the metal ion is bound to the ligand before the substrate polymerization. It is hypothesized that the imprinted metal ion ligand will out-perform the randomized metal ion ligand in the recognition of proteins containing histidine residues. The mechanism of this recognition will be studied by measuring the separation parameters of the resulting chromatographs against certain variables of the polymerization process. These results will be presented.