As an important primary producer in aquatic ecosystems, the various parameters within the mathematical models are used to describe the growth of microalgae and need to be estimated by carefully designed experiments. Non-uniform sampling has proved to generate a deliberately optimized sampling temporal schedule that can benefit parameter estimation. However, the current non-uniform sampling method depends on prior knowledge of the nominal values of the model parameters. It also largely ignores the uncertainty associated with the nominal values, thus inducing unacceptable parameter estimates. This study focuses on the uncertainty problem and describes a new sampling design that couples the traditional uniform and non-uniform sampling schedules to benefit from the merits of both methods. Based on D-optimal design, we first derive the non-uniform optimal sampling points by maximizing the determinant of the Fisher information matrix. Then the confidence interval around the non-uniform sampling points is determined by Monte Carlo simulations based on the prior knowledge of parameter distribution. Finally, we wrap the non-uniform sampling points with the uniform sampling points within the confidence interval to obtain the ultimate optimal experimental design. Scenedesmus obliquus
, whose growth curve follows a four-parameter model, was used as a case study. Compared with the traditional sampling design, the simulation results show that our proposed coupled sampling schedule can partly eliminate the uncertainty in parameter estimates caused by fixed systematic errors in observations. Our coupled sampling can also retain some advantages belonging to non-uniform sampling, in exploiting information maximization and managing the cost of sampling.
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