Modelling and adaptive control of fed-batch penicillin fermentation

This paper describes a study to investigate the application of state estimation and parameter adaptive control in fed-batch fermentation for penicillin production. A model of the penicillin fermentation process is outlined and shown to be capable of matching industrial data. The penicillin mould biomass is controlled to a reference trajectory by applying self-tuning control to an estimate of biomass, obtained from measurements of carbon dioxide production rate and fermenter volume and by using the fermentation model with an extended Kalman filter. The manipulated variable, sugar feed to the fermenter, is calculated by an adaptive algorithm. Simulation results compare the performance of self-tuning control with that obtained using digital Proportional plus Integral control.     

微生物发酵过程优化控制技术进展

微生物发酵过程优化控制技术是发酵工程的重要技术。综述了近年来微生物发酵过程优化控制技术的研究现状,讨论了机理分析建模、黑箱建模、混合建模等发酵过程建模方法,对基于模型的优化控制策略进行了分析。指出了基于混合模型和多目标优化策略建立动态优化控制器,是微生物发酵过程优化控制的有效方法,并给出了实现优化控制需要解决的关键问题。     

Analysis of fed-batch fermentation processes by graphical methods

Graphical methods are used for many types of engineering calculations. Their appeal is often related to calculational simplicity, but probably the increased understanding that accompanies a graphical calculation method is chiefly responsible for their popularity. In the present work existing graphical concepts which have been used in chemical reaction engineering and fermentation technology have been extended to allow the calculation of biomass and product formation for a variety of fermentation processes. Comparisons in productivity are made among chemostat, batch, fed batch with variable and constant feed rate, and cyclic fed-batch operations.     

Mathematical modeling of fed-batch butanol fermentation with simultaneous pervaporation

A mathematical model was developed to describe a fed-batch acetone-butanol-ethanol (ABE) fermentation with simultaneous pervaporation. The model predicted satisfactorily batch or fed-batch fermentation with or without pervaporalion by introducing a parameter reflecting cell activity loss during fed-batch fermentation with pervaporation. The model also predicted the effect of membrane area, membrane thickness, and sweep air flow rate on glucose consumption rate and residual butanol concentration in the fermentation broth. Glucose consumption rate increased by 30% by either doubling the membrane area or decreasing membrane thickness by half.     

Robust and optimal control approach for exothermic reactor stabilization

In this paper, the possibility to stabilise open-loop unstable exothermic reactors with temperature measurements is studied. Moreover, the reactors are considered to be multi-input multi-output systems with parametric uncertainties. Robust static output feedback and optimal controllers are designed for stabilization of the exothermic reactors into their open-loop unstable steady states. Stabilization of reactors is simulated using designed controllers. The possibility of using both types of controllers for energy savings is studied and measured by coolant consumption. The approach is tested with a representative example. Obtained simulations results confirm that the robust static output feedback controllers outperform optimal controllers when systems with parametric uncertainties are controlled.     

Development of a computer algorithm based on a conjugate gradient approach for optimization of fed-batch fermentations

The problem of optimization of fed-batch fermentations using the substrate feed rate as the control variable is singular in nature. Previous approaches, including the boundary condition iteration method and transformation to a nonsingular problem using a different control variable, do not work well for solving optimization of systems governed by more than four differential equations. The applicability of a first-order conjugate gradient algorithm for optimizing fed-batch fermentations was tested for systems of varing complexity. This approach does not need any variable transformation ora priori knowledge of the control arc sequence. Constraints on the feed rate are handled in a simple and direct manner. The algorithm worked very well for three, four, and five-dimensional singular systems. The correctness of the optimal profile was judged by observing the variation in the sign of the gradient of the Hamiltonian. The gradient was found to be zero during the singular period and had the appropriate sign on the boundary arcs. The optimization method based on conjugated gradient approach can be complementary to the boundary condition iteration method for determination of the exact optimum profile.     

Nonequilibrium thermodynamics for multiphase reacting systems: an optimal control approach

This paper sets optimal control framework for balance and kinetic equations of multiphase reacting systems consistently with the second law of thermodynamics. Approaches effective in contemporary theory of nonequilibrium thermodynamics of single-phase systems are here extended to include interfacial discontinuities, surface reactions and interface transports which are phenomena typical of multiphase systems. We arrive at Lagrangian and Hamiltonian structures of transport equations and laws of chemical kinetics, which constitute efficient forms serving to generalize linear models to nonlinear regimes. Local disequilibria are predicted which are shown to be responsible for onset of interfacial and bulk instabilities.     

腈水合酶的发酵研究

Nocardh sp163#在含有脲和钴的培养基中发酵生产腈水合酶,可以催化丙烯腈水合为丙烯酰胺。调节培养条件使发酵液的酶活力达到815万u／ml。温度28—30℃,反应体系呈中性酶活性很高并且稳定。     

Robust adaptive control of yeast fed-batch cultures

Model-based control of bioprocesses is a difficult task due to the challenges associated with biological system modeling and the lack of on-line measurements. In this study, two robust controllers using minimal a priori process knowledge and minimal measurement information are designed to maximize biomass productivity in aerobic cultures of Saccharomyces cerevisiae. This latter objective can be achieved through the regulation of the ethanol concentration at a low constant value. The linearization of Sonnleitner’s model allows simple transfer function models to be derived, which describe the relation between the ethanol concentration, the substrate feed and an exponential disturbance – image of the substrate demand for cell growth – in the different operating (respirative and respiro-fermentative) regimes. The two controllers are based on these linear models and use a RST structure, but differ in the way the exponential growth disturbance is handled. In the first controller, the disturbance is represented by a linear model, whereas in the second controller, the disturbance is measured on-line via the oxygen transfer rate signal and a feedforward control action is used to cancel the disturbance effect on the ethanol concentration. Particular attention is paid to the robustification of the controllers to measurement noise, neglected high frequency dynamics and uncertain stoichiometry coefficients using the observer polynomial. Tests in simulation show the controller performance.     

Design of sliding mode controller for the optimal control of fed-batch cultivation of recombinant E. coli

Fed-batch fermentation processes are common methods for producing recombinant biological products from different microorganisms. Model-based control of bioprocess is a difficult task due to the challenges associated with bioprocess modeling and the lack of on-line measurements. In this paper a new hybrid adaptive feeding control strategy for fed-batch cultivation of high cell density Escherichia coli (E. coli) is designed which is capable of maintaining the growth of the cells in optimal critical value despite disturbances and modeling uncertainties. For this purpose first an optimal controller is suggested that fosters the growth rate to the optimal critical value and then a sliding mode controller is applied which powerfully strengthens the optimal controller against disturbances and uncertainties. The combined controller is capable of achieving the maximum amount of biomass and recombinant protein production despite a large number of uncertainties and disturbances. The process considered in this study is fed-batch cultivation of E. coli BL21 (DE3) [pET3a-ifnγ] under maximum attainable specific growth rate for producing γ-interferon protein.     

A fed-batch design approach of struvite system in controlled supersaturation

This paper focuses on struvite (MgNH₄PO₄·6H₂O) crystallization in controlled supersaturation. Struvite can be used as a slow-release fertilizer. Crystallization experiments were conducted using supersaturated solutions. The secondary focus of this paper is the design of a struvite recovery system in fed-batch-controlled supersaturation mode. The design and commissioning of fed-batch struvite crystallization included the determination of operating supersaturation of struvite crystallization, suitable seed materials and the composition of feed solution. Determination of operating supersaturation of struvite crystallization was conducted by two steps including thermodynamic simulation using gPROMS² (process simulation software) along with a set of batch experiments. Investigation of suitable seed materials was also conducted using set of batch experiments. Two types of seed materials including quartz sand and struvite seeds were used in the investigation of seed materials. Composition of feed solution included the investigation of struvite solution chemistry using PHREEQC³ thermodynamic modeling package. Based on the previously investigated design approach, struvite crystallization in fed-batch system was conducted using a 44-L of reactor with 15-L of initial reactant volume.     

Constraint handling optimal PI control of open-loop unstable process: Analytical approach

This paper proposes the closed-form analytical design of proportional-integral (PI) controller parameters for the optimal control of an open-loop unstable first order process subject to operational constraints. The main idea of the design process is not only to minimize the control performance index, but also to cope with the constraints in the process variable, controller output, and its rate of change. To derive an analytical design formula, the constrained optimal control problem in the time domain was transformed to an unconstrained optimization in a parameter space associated with closed-loop dynamics. By taking advantage of the proposed analytical approach, a convenient shortcut algorithm was also provided for finding the optimal PI parameters quickly, based on the graphical analysis for the optimal solution of the corresponding optimization problem in the parameter space. The resulting optimal PI controller guarantees the globally optimal closed-loop response and handles the operational constraints precisely.     

Trade-off optimal design of a biocompatible solvent for an extractive fermentation process

In this study, crisp and flexible optimization approaches are, respectively, introduced to design an optimal biocompatible solvent for an extractive fermentation process. The optimal design problem is formulated as a mixed-integer nonlinear programming model in which performance requirements of the compounds are reflected in the objective and the constraints. In general, the requirements for the objective and constraints are not rigid; consequently, the flexible or fuzzy optimization approach is applied to soften the rigid requirement for maximization of the extraction efficiency and to consider the mass flow rate and biocompatibility of solvent as the softened inequality constraints to the solvent design problem. Having elicited the membership function for the objective function and the constraint, the optimal solvent design problem can be formulated as a flexible goal attainment problem. Mixed-integer hybrid differential evolution is applied to solve the problem in order to find a satisfactory design.     

An input/output approach to the optimal transition control of a class of distributed chemical reactors

An input/output approach to the optimal concentration transition control problem of a certain type of distributed chemical reactors is proposed based on the concept of residence time distribution, which can be determined in practice by using data from experimental measurements or computer simulations. The main assumptions for the proposed control method to apply are that the thermal and fluid flow fields in the reactor are at pseudo-steady-state during transition and that the component whose concentration is to be controlled participates only in first-order reactions. Using the concept of cumulative residence time distribution, the output variable is expressed as the weighted sum of discretized inputs or input gradients in order to construct an input/output model, on the basis of which a constrained optimal control problem, penalizing a quadratic control energy functional in the presence of input constraints, is formulated and solved as a standard least squares problem with inequality constraints. The effectiveness of the proposed optimal control scheme is demonstrated through a continuous-stirred-tank-reactor (CSTR) network and a tubular reactor with axial dispersion and a first-order reaction. It is demonstrated through computer simulations that the proposed control method is advantageous over linear quadratic regulator (LQR) and proportional-integral (PI) control in terms of control cost minimization and input constraint satisfaction.     

Comparison of two methods of optimal control synthesis: Partial differential equation approach and integral equation approach

This study shows how the optimal control theory for distributed parameter systems can be implemented for a problem of tubular reactor with axial dispersion described by partial differential equations. Two methods are implemented. One is based on differential equation approach and the other is based on integral equation approach. It was found that the approach with partial differential equations is preferable to the one with integral equations for the type of problems treated in this study. Computation algorithms and programs for both cases are developed.     

优化控制在碳化工序中的应用

优化控制系统是建立在SUPCON JX-300X集散控制系统平台之上的软硬件网络系统,优化过程控制机理,以便实现生产过程平稳.     

Fuzzy control of ethanol concentration for emulsan production in a fed-batch cultivation ofAcinetobacter Calcoaceticus RAG-1

A fuzzy control system was organized and applied to the control of ethanol concentration in a fed-batch cultivation process for emulsan production byAcinetobacter calcoaceticus RAG-1. The membership functions and fuzzy rules were determined by sets of data and experiences obtained from the preliminary culture experiments. The input variables, error (the difference between the set point value and the process variable) and the change of the error, were fuzzified by using the membership functions and the output variable, change of the ethanol feed rate, was inferred based on the membership functions and the given fuzzy rules. To obtain the numerical value for the output variable, the center-of-gravity method was used in the defuzzification procedure. The results showed that the ethanol concentration was well regulated around optimal level and the emulsan yield was increased compared with that of the cultivation controlled by the conventional feedback control loop.     

Three mode control as an optimal control

Three mode control with Ziegler-Nichols or Cohen-Coon controller settings is shown to be the solution to an optimal control problem for a linear first order system with dead time and a quadratic cost functional. The implication of this result is that in the absence of an economically meaningful cost criterion there is no reason to prefer the results of optimal control theory to traditional design procedures for feedback control systems. The multivariable generalization of the optimal control problem solved here provides the means for extending classical control experience in design of single loop processes to multivariable control systems     

On-line optimal control of a seeded batch cooling crystallizer

In this paper, an on-line optimal control methodology is developed for the optimal quality control of a seeded batch cooling crystallizer process. An extended Kalman filter is successfully implemented to predict seven unmeasured state variables based on three measurements in the batch process. A PI controller is used in a feedback control system to implement the optimal path. It is found that the PI controller can ensure tracking of the optimal path. The simulation results show that on-line optimal control strategy leads to a substantial improvement of the end product quality expressed in terms of the mean size and the width of the distribution. The effects of the plant/model mismatch and disturbances are also tested and discussed.     

Problem of optimal control of monomethylaniline synthesis in a tubular reactor

A mathematical model of catalytic monomethylaniline synthesis in a tubular reactor is presented. A method for searching for the optimal control of monomethylaniline synthesis is proposed that reduces the variational problem to a static unconditional optimization problem. Problems of optimal control of the synthesis for various market conditions are solved.