Gradient elution chromatography (GEC) is not only commonly used in lab
oratory settings, but also increasingly used in separation and purific
ation of biochemical and pharmaceutical products. These processes ofte
n deal with very precious materials. Thus, it is extremely important t
o obtain operational conditions so that the process efficiency is opti
mum. However, this class of optimal control problems is highly nonstan
dard, and hence cannot be solved using conventional optimal control te
chniques. There are three specific characteristics associated with thi
s class of optimal control problems: (i) the process contains a set of
interrelated subprocesses with different time or space intervals; (ii
) the min-max objective function is not in the conventional form; and
(iii) state dependent time lag appears in the control variables. This
paper considers a related optimal control problem in which optimal con
trol strategies of gradient elution linear chromatography (GELC) are t
o be obtained for protein separations. The ionic strength, the gradien
t of which affects the linear equilibrium constants in affinity chroma
tography systems, is selected as the control variable. Using the contr
ol parametrization technique, the control variables are approximated b
y piecewise linear functions. Thus, a sequence of nonstandard optimal
parameter selection problems is obtained. Each of these approximate pr
oblems is then shown to be equivalent to a standard min-max optimizati
on problem, and hence is solvable by existing optimization software. F
or illustration, the proposed methodology is used in a case study.