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State estimation of biological process variables directly influences the performance of on-line monitoring and optimal control for fermentation process. A novel nonlinear state estimation method for fermentation process is proposed using cubature Kalman filter (CKF) to incorporate delayed measurements. The square-root version of CKF (SCKF) algorithm is given and the system with delayed measurements is described. On this basis, the sample-state augmentation method for the SCKF algorithm is provided and the implementation of the proposed algorithm is constructed. Then a nonlinear state space model for fermentation process is established and the SCKF algorithm incorporating delayed measurements based on fermentation process model is presented to implement the nonlinear state estimation. Finally, the proposed nonlinear state estimation methodology is applied to the state estimation for penicillin and industrial yeast fermentation processes. The simulation results show that the on-line state estimation for fermentation process can be achieved by the proposed method with higher estimation accuracy and better stability.

The approaches to discrete approximation of Pareto front using multi-objective evolutionary algorithms have the problems of heavy computation burden, long running time and missing Pareto optimal points. In order to overcome these problems, an approach to continuous approximation of Pareto front using geometric support vector regression is presented. The regression model of the small size approximate discrete Pareto front is constructed by geometric support vector regression modeling and is described as the approximate continuous Pareto front. In the process of geometric support vector regression modeling, considering the distribution characteristic of Pareto optimal points, the separable augmented training sample sets are constructed by shifting original training sample points along multiple coordinated axes. Besides, an interactive decision-making (DM) procedure, in which the continuous approximation of Pareto front and decision-making is performed interactively, is designed for improving the accuracy of the preferred Pareto optimal point. The correctness of the continuous approximation of Pareto front is demonstrated with a typical multi-objective optimization problem. In addition, combined with the interactive decision-making procedure, the continuous approximation of Pareto front is applied in the multi-objective optimization for an industrial fed-batch yeast fermentation process. The experimental results show that the generated approximate continuous Pareto front has good accuracy and completeness. Compared with the multi-objective evolutionary algorithm with large size population, a more accurate preferred Pareto optimal point can be obtained from the approximate continuous Pareto front with less computation and shorter running time. The operation strategy corresponding to the final preferred Pareto optimal point generated by the interactive DM procedure can improve the production indexes of the fermentation process effectively.

In this study, Saccharomyces cerevisiae (baker's yeast) was produced in a fed-batch bioreactor at the optimal dissolved oxygen concentration (DOC) and growth medium temperature. However, it is very difficult to control the DOC using conventional controllers because of the poorly understood and constantly changing dynamics of the bioprocess. A generalized predictive controller (GPC) based on a nonlinear autoregressive integrated moving average exogenous (NARIMAX) model is presented to stabilize the DOC by manipulation of air flow rate. The NARIMAX model is built by an improved recursive least-squares support vector machine, which is trained by an in-place computation scheme and avoids the computation of the inverse of a large matrix and memory reallocation. The proposed nonlinear GPC algorithm requires little preliminary knowledge of the fermentation process, and directly obtains the nonlinear model in matrix form by using iterative multiple modeling instead of linearization at each sampling period. By application of an on-line bioreactor control, experimental results demonstrate the robustness, effectiveness and advantages of the new controller.

Support vector machine (SVM) has shown great potential in pattern recognition and regressive estimation. Due to the industrial development demands, such as the fermentation process modeling, improving the training performance on increasingly large sample sets is an important problem. However, solving a large optimization problem is computationally intensive and memory intensive. In this paper, a geometric interpretation of SVM regression (SVR) is derived, and μ-SVM is extended for both L 1 -norm and L 2 -norm penalty SVR. Further, Gilbert algorithm, a well-known geometric algorithm, is modified to solve SVR problems. Theoretical analysis indicates that the presented SVR training geometric algorithms have the same convergence and almost identical cost of computation as their corresponding algorithms for SVM classification. Experimental results show that the geometric methods are more efficient than conventional methods using quadratic programming and require much less memory.

An iterative optimization strategy for fed-batch fermentation process is presented by combining a run-to-run optimization with swarm energy conservation particle swarm optimization (SEC-PSO). SEC-PSO, which is designed with the concept of energy conservation, can solve the problem of premature convergence frequently appeared in standard PSO algorithm by partitioning its population into several sub-swarms according to the energy of the swarm and is used in the optimization strategy for parameter identification and operation condition optimization. The run-to-run optimization exploits the repetitive nature of fed-batch processes in order to deal with the optimal problems of fed-batch fermentation process with inaccurate process model and unsteady process state. The kinetic model parameters, used in the operation condition optimization of the next run, are adjusted by calculating time-series data obtained from real fed-batch process in the run-to-run optimization. The simulation results show that the strategy can adjust its kinetic model dynamically and overcome the instability of fed-batch process effectively. Run-to-run strategy with SEC-PSO provides an effective method for optimization of fed-batch fermentation process.

On-line estimation of unmeasurable biological variables is important in fermentation processes, directly influencing the optimal control performance of the fermentation system as well as the quality and yield of the targeted product. In this study, a novel strategy for state estimation of fed-batch fermentation process is proposed. By combining a simple and reliable mechanistic dynamic model with the sample-based regressive measurement model, a state space model is developed. An improved algorithm, swarm energy conservation particle swarm optimization (SECPSO), is presented for the parameter identification in the mechanistic model, and the support vector machines (SVM) method is adopted to establish the nonlinear measurement model. The unscented Kalman filter (UKF) is designed for the state space model to reduce the disturbances of the noises in the fermentation process. The proposed on-line estimation method is demonstrated by the simulation experiments of a penicillin fed-batch fermentation process.

State estimation is the precondition and foundation of a bioprocess monitoring and optimal control. However, there are many difficulties in dealing with a non-linear system, such as the instability of process, un-modeled dynamics, parameter sensitivity, etc. This paper discusses the principles and characteristics of three different approaches, extended Kalman filters, strong tracking filters and unscented transformation based Kalman filters. By introducing the unscented transformation method and a sub-optimal fading factor to correct the prediction error covariance, an improved Kalman filter, unscented transformation based robust Kalman filter, is proposed. The performance of the algorithm is compared with the strong tracking filter and unscented transformation based Kalman filter and illustrated in a typical case study for glutathione fermentation process. The results show that the proposed algorithm presents better accuracy and stability on the state estimation in numerical calculations.

Biomass is a key factor in fermentation process, directly influencing the performance of the fermentation system as well as the quality and yield of the targeted product. Therefore, the on-line estimation of biomass is indispensable. The soft-sensor based on support vector machine (SVM) for an on-line biomass estimation was analyzed in detail, and the improved SVM called the weighted least squares support vector machine was presented to follow the dynamic feature of fermentation process. The model based on the modified SVM was developed and demonstrated using simulation experiments.