High throughput screening was employed in concert with several analytical techniques to identify and evaluate the behavior of chemically selective displacers for protein purification in ion exchange systems. A robotic liquid handling system was adapted to efficiently carry out this parallel batch screen of selective displacers on multiple protein pairs. The results identified potential selective displacers and important functional group chemistries and also indicated that this selectivity was due primarily to the selective binding between the displacer and targeted proteins. Nuclear Magnetic Resonance was then conducted on several protein/displacer mixtures verifying the binding of the selective displacers to targeted proteins and the location of the binding event. Surface plasmon resonance experiments and molecular dynamic simulations were also carried out to corroborate the NMR results. This proof of concept study shows that more specific selectivities may also be possible by utilizing affinity based selective displacers for explicit protein systems.