Operation Of Continuous Processes Research Articles

Process Optimization of an In-Situ Bioleaching Section with Associated Membrane Filtration in a Field Test Laboratory

The winning of critical raw materials from secondary resources, e.g., from abandoned mines, mining residues, electronic waste or low-grade ores, is a potential source with promising outcomes due to innovative and more efficient extraction methods. The research and education mine “Reiche Zeche” at the TU Bergakademie Freiberg, Germany offers a scientific lab in a real application environment for an in-situ bioleaching section from a low-grade sulfide ore vein with on-site associated membrane downstream processing. The evaluation and resumption of previous research activities showed both the feasibility and the potential for further up-scaling. But there was also potential evaluated for improving the effectiveness, especially in terms of individual process elements within the leaching and membrane cycle as well as regarding microbiology. Based on this, further optimization was carried out and effectiveness was evaluated and compared to the prior state. The results regarding the leaching outcome proved that process optimization leads to stable and continuous leaching process operations as well as to improved and more favorable conditions for the microorganisms due to the implementation of a bioreactor and changing the whole leaching operation from a direct into an indirect process. Furthermore, cleaning in place (CIP) resulted in the maintenance of selectivity despite discontinuous membrane process operation.

ПРИНЦИПЫ, ОБЩАЯ СХЕМА И ОБОСНОВАНИЕ ЭФФЕКТИВНОСТИ ТЕПЛОПЕРЕДАЧИ ПРИ ПРОИЗВОДСТВЕ МЯСНЫХ ПРОДУКТОВ ПИТАНИЯ

The article studies flow chart development for production line of liquid packaged broths in the form of a finished fast-food product. It reports on the results of analytical justification of technological operations and heat transfer process of meat cooking in liquid packaged broths production. The research was based on theoretical analysis of thermal conductivity patterns from hydrodynamic and capacitive properties of medium and processed product. Based on the results of the study, closed flow line was developed, being an integral structured system. It includes all technological process operations and their interaction in complex in liquid packaged broth production. Optimization of continuous process operations ensures high sterility, liquid broth quality and resource economy.

Recursive Estimation of Modifiers for Real-Time Optimization with Gradient Adaptation

Because of the uncertainties during the design phase of processes, the drift of process parameters during the plant lifetime and exogenous factors affecting the supply or demand of materials, the operation of continuous processes needs to be updated to track the economically optimal conditions that maximize the profit. For this reason, the practice of RealTime Optimization (RTO) has been established in the process industry to assist in selecting the setpoints to be used in the process. Real Time Optimization works by updating the setpoints of a plant using a model. To cope with the inevitable inaccuracy of the available models, various techniques have been developed, most notably parameter adaptation and Modifier Adaptation (MA). MA corrects the process model by bias and gradient correction terms for the variables of interest (typically the cost function and constraints), such that the RTO algorithm is guaranteed to reach a true (local) plant optimum upon convergence. The most crucial part in RTO-MA schemes is the estimation of the gradients, which requires the evaluation of the plant response at several points and determines the overall complexity of the RTO-MA problem. The goal of this contribution is to show how a recursive estimator that shares some similarities with the Kalman filter can be used to estimate the modifiers.

Transfer of continuous manufacturing process principles for mAb production in a GMP environment: A step in the transition from batch to continuous.

Implementation of continuous in lieu of batch upstream processing (USP) and downstream process (DSP) for the production of recombinant therapeutic protein is a significant paradigm change. The present report describes how the first kilograms of monoclonal antibody were produced with equipment originally designed for batch operations while using continuous manufacturing processes and principles. Project timelines for the delivery of clinical material have driven this ambition and helped the transition. Nevertheless, because of equipment availability, a tradeoff between the envisaged continuous downstream process (cDSP) operations and the ones described in this article had to be taken. A total of 2.1 kg of monoclonal antibody were produced in two GMP runs for clinical trials. For USP, a 200-L single-use pilot scale bioreactor was upgraded to enable perfusion operation. DSP steps were designed to be easily transferable to cDSP for later clinical or commercial productions. An in-line conditioning buffer preparation strategy was tested in a discontinuous way to prove its efficiency and the purification cascade was structured in parallel to the continuous collection of antibody-containing cell culture supernatant. This strategy will avoid any process change when later moving to the continuous equipment that is currently under qualification. Alignment between small-scale references runs and the GMP runs in terms of productivity and quality confirmed that the presented approach was valid. Thus, we demonstrate that existing fed-batch infrastructure can be adapted to continuous manufacturing without significant additional investments. Such approach is useful to evaluate next-generation manufacturing processes before making large investments.

Comparison of Protein A affinity resins for twin-column continuous capture processes: Process performance and resin characteristics

Continuous chromatography is a promising technology for downstream processing of biopharmaceuticals. The operation of continuous processes is significantly different to batch-mode chromatography and needs comprehensive evaluation. In this work, the performances of four Protein A affinity resins were studied systematically for twin-column continuous capture processes. A model-based approach was used to evaluate the process performance (productivity and capacity utilization) under varying operation conditions, and the objective was to reveal the crucial resin properties for continuous capture. The trade-off between productivity and capacity utilization was found, and it is necessary to select appropriate resins for different feedstock and operation conditions. The capacity utilization heavily depends on mass transfer, and steep breakthrough curves are favorable for high capacity utilization. The productivity is determined by both equilibrium binding capacity and mass transfer, and the balance of feed amount and feed time is critical. Moreover, the influence of binding capacity and mass transfer on process productivity and parameter sensitivity with two important resin properties (equilibrium binding capacity qmax and effective pore diffusion coefficient De) were assessed by the model, and suitable resin parameter ranges for twin-column continuous capture were determined. The model-based approach is an effective and useful tool to evaluate the complex performance of different resins and guide the design of next-generation resins for continuous processes.

Development and design of a mobile power plant in the form of a standalone power supply

The work is devoted to increasing the energy efficiency of uninterruptible power supplies in enterprises with a continuous technological cycle. During the operation of continuous technological processes, a power failure even for a short period of time leads to significant economic damage. The most modern technical solution to this problem is the creation of guaranteed power supply systems using diesel power plants (DES) and uninterruptible power supplies (UPS), based on rechargeable batteries and supercapacitor modules. It is proposed to use supercapacitors in parallel with the battery in order to ensure the stable operation of the diesel generators under starting conditions, as well as during load transfer. In this case, when using supercapacitors, it becomes possible to reduce the power capacity of the generators and uninterruptible power supplies along with the size of their batteries. Therefore, the cost of the solution decreases and its energy efficiency increases. To test the efficiency of the system, a computer model was created using MATLAB. The system showed a successful operation in supplying the load from all the power sources as well as maintaining Unity Power Factor at the Mains/Generator side.

Control induced instabilities in fluidized bed spray granulation

This contribution is concerned with the stability problems occurring during the operation of continuous fluidized bed spray granulation processes with external sieve mill cycle. These processes are in general operated by a mass controller, which guarantees that the overall mass of particles in the granulation chamber stays in well-defined bounds. It is well-known that, depending on the milling diameter, instabilities may occur, which result in a nonlinear limit cycle of the particle size distribution. To overcome this problem two approaches have been proposed in the literature, constrain the admissible parameter space to exclude regions of instability and design additional stabilizing control loops. In the present contribution, the cause of this instability phenomenon will be studied. It will be shown that the instability is not inherent to the process, which turns out to be open-loop stable over the studied parameter range, but due to the mass controller. More specifically, it will be demonstrated that the zero dynamics of the granulation process become unstable for certain parameter ranges resulting in closed-loop unstable process behavior. To point out, that this behavior does not depend on the specific mass controller design procedure, three prototypical mass controllers of practical relevance are designed and analyzed.

Continuous Cultivation as a Tool Toward the Rational Bioprocess Development With Pichia Pastoris Cell Factory.

The methylotrophic yeast Pichia pastoris (Komagataella phaffii) is currently considered one of the most promising hosts for recombinant protein production (RPP) and metabolites due to the availability of several tools to efficiently regulate the recombinant expression, its ability to perform eukaryotic post-translational modifications and to secrete the product in the extracellular media. The challenge of improving the bioprocess efficiency can be faced from two main approaches: the strain engineering, which includes enhancements in the recombinant expression regulation as well as overcoming potential cell capacity bottlenecks; and the bioprocess engineering, focused on the development of rational-based efficient operational strategies. Understanding the effect of strain and operational improvements in bioprocess efficiency requires to attain a robust knowledge about the metabolic and physiological changes triggered into the cells. For this purpose, a number of studies have revealed chemostat cultures to provide a robust tool for accurate, reliable, and reproducible bioprocess characterization. It should involve the determination of key specific rates, productivities, and yields for different C and N sources, as well as optimizing media formulation and operating conditions. Furthermore, studies along the different levels of systems biology are usually performed also in chemostat cultures. Transcriptomic, proteomic and metabolic flux analysis, using different techniques like differential target gene expression, protein description and 13C-based metabolic flux analysis, are widely described as valued examples in the literature. In this scenario, the main advantage of a continuous operation relies on the quality of the homogeneous samples obtained under steady-state conditions, where both the metabolic and physiological status of the cells remain unaltered in an all-encompassing picture of the cell environment. This contribution aims to provide the state of the art of the different approaches that allow the design of rational strain and bioprocess engineering improvements in Pichia pastoris toward optimizing bioprocesses based on the results obtained in chemostat cultures. Interestingly, continuous cultivation is also currently emerging as an alternative operational mode in industrial biotechnology for implementing continuous process operations.

The integration of scheduling and control: Top-down vs. bottom-up

The flexible operation of continuous processes often requires the integration of scheduling and control. This can be achieved by top-down or bottom-up approaches. We compare the two paradigms in-silico using an air separation unit as a benchmark process. To demonstrate the top-down paradigm, we identify data-driven models of the closed-loop process dynamics based on a mechanistic model and use them in scheduling calculations that are performed offline. The resulting target trajectories are passed to a linear model predictive control (LMPC) system and implemented in the process. To demonstrate the bottom-up paradigm, we define an economic nonlinear model predictive control (eNMPC) scheme, which performs dynamic optimization using the full model in closed-loop to directly obtain the control variable profiles to be implemented in the process. We provide implementations of the process model equations as both a gPROMS and a Modelica model to encourage future comparison of approaches for flexible operation, process control, and/or handling disturbances. The performance, advantages, and disadvantages of the two strategies are analyzed using demand-response scenarios with varying levels of fluctuations in electricity prices, as well as considering the cases of known, instantaneous, and completely unknown load changes. The similarities and differences of the two approaches as relevant to flexible operation of continuous processes are discussed. Integrated scheduling and control leverages existing infrastructure and can be immediately applied to real operation tasks. Both operation strategies achieve successful process operation with remarkable economic improvements (up to 8%) compared to constant operation. eNMPC requires more computational resources, and is – at the moment – not implementable in real-time due to maximum optimization times exceeding the controller sampling time. However, eNMPC achieves up to 2.5 times higher operating cost savings compared to the top-down approach, owing in part to the more accurate modeling of key process dynamics.

Multi-objective optimization of a biodiesel production process using process simulation

Economic and environmental aspects have been contributing to the gradual reduction of fossil fuels and to the growth of research on renewable energy, such as biodiesel, that has been gaining representation in the national and world market. In this scenario, the optimal operation of continuous biodiesel processes may be an attractive tool to optimize some economic/environmental indicators, e.g., biodiesel production and purity, residues, and energy consumption. To develop a multicriteria optimization, a multi-objective methodology must be performed in which two or more functions are used as performance measurements. In this sense, the present work aims to propose the multi-objective optimization (MOO) of a continuous biodiesel plant. The purpose of the optimization was to maximize the biodiesel flow rate and minimize the energy rate consumption subject to a minimum biodiesel purity. An additional study was performed to quantify a set of potential environmental impacts (PEIs) of the optimized scenarios. The results of MOO showed that there is a set of optimal solutions depending on the weights assigned to each individual objective function. It was verified that the reactor temperature has a significant influence on biodiesel production, but less influence on the energy rate consumption. The suggested methodology could serve as a basis for future work addressing multi-criteria optimization, where the optimal operating point solution depends on the decision-maker. These results suggest that the PEIs can serve as environmental constraints for the optimization problem, allowing the decision maker to evaluate these criteria for choosing the optimum operating point.

Aerobic denitrification by a novel Pseudomonas sp. JN5 in different bioreactor systems

The present study evaluated the nitrate removal efficiency of a potent aerobic denitrifying bacterium in different bioreactor systems. The isolated bacterial strain characterized as Pseudomonas sp. based on biochemical and 16S rDNA sequence analysis. The strain showed an unusual ability of nitrate removal in both aerobic and anaerobic conditions, with the highest efficiency in aerobic conditions. Denitrification efficiency assessed and at low nitrate concentrations (50 mg/L), complete removal has occurred within 24 h and in high concentration (216 mg/L) removal was on 48th h of cultivation. The bacterial growth pattern was similar in all tested nitrate concentrations, and the tolerant strain JN5 could perform the aerobic denitrification at higher concentrations. In a fermenter with an initial nitrate concentration of 100 mg/L, complete removal observed within 24 h of incubation. Around 50% of nitrate removal achieved during the logarithmic growth phase of the bacterium and the remaining portion in a stationary phase under high dissolved oxygen conditions. The aerobic denitrifying efficiency of the newly isolated bacterial strain JN5 improved in a combined fermenter-packed bed reactor system with circulating batch and continuous process operations. The isolate JN5 efficiently used as an aerobic denitrifier in a bio-augmentation based system and the combinations of reactor systems improved the performance of nitrate removal by the aerobic denitrifying microorganism.

Progress to Date in the Design and Operation of Continuous Crystallization Processes for Pharmaceutical Applications

Continuous crystallization has gained interest in the pharmaceutical sector as part of the drive toward the transition from exclusive batch manufacturing to integrated continuous manufacturing in this industry. As a result, the design and operation of continuous crystallization processes for the preparation of pharmaceutical materials has been featured strongly in recent scientific literature. This review is an effort to gather together all of the published understanding on continuous crystallization with a pharmaceutical focus and to benchmark progress to date in realizing the potential benefits of transitioning this stalwart pharmaceutical unit operation from batch to continuous configurations.

Aerobic Oxidation of 5-(Hydroxymethyl)furfural Cyclic Acetal Enables Selective Furan-2,5-dicarboxylic Acid Formation with CeO2 -Supported Gold Catalyst.

The utilization of 5-(hydroxymethyl)furfural (HMF) for the large-scale production of essential chemicals has been largely limited by the formation of solid humin as a byproduct, which prevents the operation of stepwise batch-type and continuous flow-type processes. The reaction of HMF with 1,3-propanediol produces an HMF acetal derivative that exhibits excellent thermal stability. Aerobic oxidation of the HMF acetal with a CeO2 -supported Au catalyst and Na2 CO3 in water gives a 90-95 % yield of furan 2,5-dicarboxylic acid, an increasingly important commodity chemical for the biorenewables industry, from concentrated solutions (10-20 wt %) without humin formation. The six-membered acetal ring suppresses thermal decomposition and self-polymerization of HMF in concentrated solutions. Kinetic studies supported by DFT calculations identify two crucial steps in the reaction mechanism, that is, the partial hydrolysis of the acetal into 5-formyl-2-furan carboxylic acid involving OH- and Lewis acid sites on CeO2 , and subsequent oxidative dehydrogenation of the in situ generated hemiacetal involving Au nanoparticles. These results represent a significant advance over the current state of the art, overcoming an inherent limitation of the oxidation of HMF to an important monomer for biopolymer production.

Fast Estimation of Plant Steady State for Imperfectly Known Dynamic Systems, with Application to Real-Time Optimization

Experimental assessment or prediction of plant steady state is important for many applications in the area of modeling and operation of continuous processes. For example, the iterative implementation of static real-time optimization requires reaching steady state for each successive operating point, which may be quite time-consuming. This paper presents an approach to speed up the estimation of plant steady state for imperfectly known dynamic systems that are characterized by (i) the presence of fast and slow states, with no effect of the slow states on the fast states, and (ii) the fact that the unknown part of the dynamics depends only on the fast states. The proposed approach takes advantage of measurement-based rate estimation, which consists in estimating rate signals without the knowledge or identification of rate models. Since one can use feedback control to speed up the convergence to steady state of the fast part of the plant, this rate estimation allows estimating the steady state of the slow pa...

Maintaining Constant DC-link Voltage of Adjustable Speed Drive using CUK Converter

Three phase Induction Motors (IM) are normally used in industries. The continuous process operations of the industries are controlled by Adjustable Speed Drive (ASD) fed IM. The power quality (PQ) problems which occur in the power system are mainly voltage sag and swell. They affect the performance of IM. This is due to the decrease in DC-link voltage of an ASD. It leads to the reliability problem and heavy financial losses happen to the industries. To maintain the constant DC-link voltage of an ASD, ride-through alternate has to be provided.

Torrefaction of pine in a bench-scale screw conveyor reactor

Numerous works are reported in the literature regarding the torrefaction of biomass in batch processes. However, in industrial applications, continuous reactors and processes may by more interesting as this allows for the integration of continuous mass and heat flows. To shed light on the operation of continuous torrefaction processes, this work presents the findings of continuous, bench-scale (2.5 kg h−1) torrefaction experiments using pine wood particles as a feed material in a screw conveyor reactor. The shifts in product mass yields were in line with theoretical expectations for changes in reactor temperature and reactor residence times whereas the degree of filling within the screw reactor and the flow of the nitrogen purge gas were found to be negligible. The process allowed for the measurement of the particle surface temperatures throughout the length of the reactor and significant temperature differences where measured between the wall of the reactor and the reactor screw. The proximate composition and the higher heating value of the torrefied biomass were found to be correlated to the ratio of the mass of dry biomass feed to the mass of the torrefied biomass produced. Important observations regarding the operability of such a process, also relevant to larger-scale processes, include the need to prevent the occurrence of torrefaction vapour condensation (which leaves the torrefaction reactor in the form of a saturated vapour) in the presence of fine, solid particles as this leads to rapid particle agglomeration and process blockage.

Rapid Determination of the Residence Time Distribution (RTD) Function in an Oscillatory Baffled Reactor (OBR) Using a Design of Experiments (DoE) Approach

Abstract Residence time distribution (RTD) profiles were investigated in a standard oscillatory baffled reactor (OBR) as a function of oscillatory and bulk flow components using a design of experiments (DoE) approach. A second-order, polynomial model (R2=92.1%) was fitted to N values estimated from concentration profiles and used to maximise plug flow conditions. The velocity ratio (Ψ) required to maximise plug flow was 1.9, agreeing well with the range previously identified by Stonestreet and van der Veeken (1.8 < Ψ < 2.0), suggesting that the approach used here is valid. This method could be used to rapidly quantify and maximise plug flow in various OBR designs in a simple and robust manner which could prove valuable for the operation and design of continuous processes using OBR technology.

Consistent hierarchical economic NMPC for a class of hybrid systems using neighboring-extremal updates

A hierarchical two-layer control algorithm is developed for a class of hybrid (discrete-continuous dynamic) systems to support economically optimal operation of batch or continuous processes with a predefined production schedule. For this class of hybrid systems, the optimal control moves as well as the controlled switching times between two adjacent modes are determined online. In contrast to closely related schemes for integrated scheduling and control, the sequence of modes is not optimized. On the upper layer, the economic optimal control problem is solved rigorously by a slow hybrid economic model predictive controller at a low sampling rate. On the lower layer, a fast hybrid neighboring-extremal controller is based on the same economic optimal control problem as the slow controller to ensure consistency between both layers. The fast neighboring-extremal controller updates rather than tracks the optimal trajectories from the upper layer to account for disturbances. Consequently, the fast controller steers the process to its operational bounds under disturbances and the economic potential of the process is exploited anytime. The suggested two-layer control algorithm provides fully consistent control action on the fast and slow time-scale and thus avoids performance degradation and even infeasibilities which are commonly encountered if inconsistent optimal control problems are formulated and solved.

Design-of-experiment strategy for the formulation of laccase biocatalysts and their application to degrade bisphenol A

Immobilizing enzymes can expand their applicability to continuous process operations and facilitates process intensification. An optimized formulation of immobilized biocatalysts is therefore of strategic interest in the field of industrial biotechnology. Nevertheless, biocatalyst formulation still largely relies on empirical approaches which lack effectiveness in the identification of optimum immobilization conditions. In the present study, design of experiments, multiple linear regressions and modeling were used to screen, interpret and finally optimize crucial immobilization parameters. A laccase preparation from Coriolopsis polyzona MUCL38443 was immobilized via a sequential adsorption-crosslinking process on mesoporous silica particles. As a target variable, biocatalyst activity was doubled (∼280 U g(-1)) while dramatically reducing processing time (two hours instead of 26 hours) and reagent inputs (80 mm instead of 1m glutaraldehyde (GLU)). Immobilization yield (∼50%) and thermostability (∼60% residual activity after 24 hours at 45°C) could be maintained under the optimized conditions. As an example of its application in environmental biotechnology, the optimized biocatalyst was implemented in a continuous stirred-tank membrane reactor (CSTMR) to continuously degrade the endocrine disruptor bisphenol A (BPA) in wastewater. A 90% removal of 50 μm BPA was achieved over 30 reactor volumes (hydraulic residence time (HRT) of 1.85 hours, 50 mL working volume).

Hierarchical Economic NMPC for a Class of Hybrid Systems Using Neighboring-Extremal Updates

A two-layer control algorithm is developed for a class of hybrid (discrete-continuous dynamic) systems comprising important applications such as the economically optimal operation of recipe-driven batch or continuous processes. On the upper layer, the economic optimal control problem is solved rigorously by a slow controller at a low sampling rate, whereas a fast neighboring-extremal controller updates rather than tracks the optimal trajectories to account for disturbances. Consequently, the process is steered to its operational bounds, while the optimal switching times under disturbances can be determined such that the economic potential of the process is fully exploited anytime.