This paper presents a mixed integer linear programming (MILP) model for the optimal synthesis of chromatographic protein purification processes including the time line in which our target protein product is collected. The model is linearised using piecewise linear approximation strategies and tested on three example protein mixtures, containing up to 13 contaminants and selecting from a set of up to 21 candidate steps. The results are also compared with previous literature models attempting to solve the same problem and show that the proposed approach offers significant gains in computational efficiency without compromising the quality of the solution. (C) 2011 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.