Affinity separation can be achieved by batch and fixed bed modes. Mathematical models including film mass transfer, intraparticle diffusion, and reversible reaction are formulated for both fixed bed and batch adsorption processes. Orthogonal collocation method is used to numerically evaluate the performance of batch and fixed bed adsorption. The efficiencies are evaluated in terms of both the solute recovery and adsorbent utilization. The effect of the following parameters is simulated for the comparison purpose: solute concentration, reaction kinetics, ligand content, and particle size. Fixed bed mode is found to be efficient.