Optimal experimental design for linear time invariant state–space models

The linear time invariant state–space model representation is common to systems from several areas ranging from engineering to biochemistry. We address the problem of systematic optimal experimental design for this class of model. We consider two distinct scenarios: (i) steady-state model representations and (ii) dynamic models described by discrete-time representations. We use our approach to construct locally D–optimal designs by incorporating the calculation of the determinant of the Fisher Information Matrix and the parametric sensitivity computation in a Nonlinear Programming formulation. A global optimization solver handles the resulting numerical problem. The Fisher Information Matrix at convergence is used to determine model identifiability. We apply the methodology proposed to find approximate and exact optimal experimental designs for static and dynamic experiments for models representing a biochemical reaction network where the experimental purpose is to estimate kinetic constants.