Processes, Volume 6, Issue 10 (October 2018) – 32 articles

In the context of an increasing participation of renewable energy in the electricity market, demand response is a strategy promoted by electricity companies to balance the non-programmable supply of electricity with its usage. Through the use of differential electricity prices, a switch in energy consumption patterns is stimulated. In recent years, energy self-storage in batteries has been proposed as a way to take advantage of differential prices without a major disruption in daily routines. Although a promising solution, charge and discharge cycles also degrade batteries, thus expected savings in the energy bill may actually be non-existent if these savings are counterbalanced by the capacity lost by the battery. In this work a convex optimization problem that finds the operating schedule for a battery and includes the effects of current-induced degradation is presented. The goal is to have a tool that facilitates for a consumer the evaluation of the convenience of installing a battery-based energy storage system under different but given assumptions of electricity and battery prices. The problem is solved assuming operation of a commercial Li-ion under two very different yet representative electricity pricing policies. Full article

The unchecked and unnoticed disposal of industrial leachates is a common malpractice in developing countries. Untreated effluents from industries drastically deteriorate the soil, altering nearly all of its characteristics. An increase in urbanization has led to construction on these deteriorated lands. In this study, the chemical impact of two industrial effluents, dyeing (acidic) and tannery (basic), is studied on two cohesive soils, i.e., high plastic clay (CH) and low plastic clay (CL). Properties such as liquid limit, plasticity index, specific gravity, maximum dry density, unconfined compressive strength, swell potential, swell pressure, and compression indices decrease with effluent contamination, with the exception of the basic effluent, for which the trend changes after a certain percentage. This study also examines the time variation of properties at different effluent percentages, finding that unconfined compressive strength of both soils increases with time upon dyeing (acidic) contamination and decreases with tannery (basic). The stabilizing effect of two industrial by-products, i.e., marble dust and ground granulated blast furnace slag (GGBFS) have been evaluated. Unlike their proven positive effect on uncontaminated soils, these industrial by-products did not show any significant stabilization effect on leachate-contaminated cohesive soils, thereby emphasizing the need to utilize special remediation measures for effluent treated soils. Full article

With the rapid growth of energy consumption, how to utilize energy in an efficient and cheap way becomes an intensive problem. This paper proposes an optimal operation strategy to reduce system fuel costs and increase system stability by independently considering cooling loads and adjusting CHP heat to power ratio seasonally. In this paper, a mathematical model of CHP operation is introduced to reveal the relationship between the supplementary volume of diesel oil and CHP heat to power ratio. Meanwhile, by analyzing the influence of seasonal factor on energy consumption, CHP heat to power ratio is optimized seasonally. Then, by independently considering the impacts of the cooling loads on system operation, the particle swarm optimization (PSO) algorithm is used to optimize the operation strategy of each device. Finally, this paper validates the positive effects of storage devices on improving system economy and stability under the premise of the time-of-use gas price. Results show that system fuel costs can be reduced by 5.2% if the seasonal factor is considered. Additionally, by optimizing the operation strategy, the peak valley gap of electrical loads in summer reduces by 40.7%. Moreover, the proposed strategy successfully utilizes storage capacity to shift loads and respond to gas price. Full article

The distribution of reclaimed soil particle size under seepage conditions after the management period will directly determine the success or failure of reclamation work. The geotechnical experimental method was used in this paper to study the changes in the granulometric composition of soil. The results show that the granulometric composition of the reclaimed soil varied obviously at different depths. The granulometric composition of the soil at a depth of 10 cm was not much different from undisturbed reclaimed soil (URS). At a depth of 30 cm, as the sharp decrease of the content of fine particles resulted in coarser reclaimed soil, the soil became more uniform, with an increase in porosity and water content. At a depth of 50 cm, the fine particle content was generally slightly lower than that of URS. At a depth of 70 cm, the fine particle content of the soil greatly exceeded that of the URS, with the finest soil particles and lowest porosity. The main reason for the above-mentioned changes of granulometric composition in the reclaimed soil was the seepage in soil caused by irrigation during the management period. The research results can provide a reference for management after land reclamation at non-metallic mines in Xinjiang, China. Full article

For the requirements of performance assessment of the thermal power plant control process, the combustion control system of a 330 MW generator unit in a power plant is studied. Firstly, the five variables that affect the process control performance are determined by the mechanism analysis method. Then, a data-driven performance assessment method based on the operational data collection from the supervisory information system was proposed. Using principal component analysis technique, we found that five different variables have different degrees of effect on the performance of the combustion process. By means of qualitative and quantitative analysis, five contribution rates of different variables affecting the performance index of the system were obtained. After that, the data is normalized to the non-dimensional variable, the performance assessment index of the boiler combustion process is defined, and the classification and assessment criterion of it are given. Through using the proposed method on the operation data of the 1# boiler and 2# boiler within 1 day, the performance indexes are calculated and achieved during different time periods. Analysis of the results shows that this method will not generate additional disturbance to the normal operation of the system, and it can achieve a simple, reliable, accurate and rapid qualitative and quantitative analysis of the performance of the boiler combustion control system, and also it can be extended and applied to other multivariable control systems. Full article

Taking Nanfen open-pit iron mine in Liaoning Province as the engineering background, this study analyzes the effect of water-rock circulation on the mechanical properties of rock through a combination of macro-mechanical experiments and microstructure tests in the laboratory. Uniaxial compression experiments and acoustic wave tests are used to determine the degradation law of the mechanical properties of chlorite under the periodic action of water. The experimental results show that dry-wet cycles have a continuous and gradual effect on the rock sampled: Its uniaxial compressive strength, elastic modulus, and acoustic velocity all decrease gradually with an increase in the number of cycles. After 15 wet-dry cycles, the uniaxial compressive strength and elastic modulus of the rock decreased by 34.21% and 44.63%, respectively. Electron microscope scans of the rock indicate that the particle size, characteristics, and pore distribution at the rock surface had changed significantly after water-rock interaction. Finally, a drainage system and sliding force monitoring devices have been arranged at the mine site that can effectively reduce the impact of water-rock interaction on the stability of the mine. This combination of macro-experiments and micro-analysis allowed the weakening effect of dry-wet cycles on slope rock to be studied quantitatively, providing a theoretical reference for stability evaluation in geotechnical engineering. Full article

The compressor fuel cost minimization problem (FCMP) for natural gas pipelines is a relevant problem because of the substantial energy consumption of compressor stations transporting the large global demand for natural gas. The common method for modeling the FCMP is to assume key modeling parameters such as the friction factor, compressibility factor, isentropic exponent, and compressor efficiency to be constants, and their nonlinear relationships to the system operating conditions are ignored. Previous work has avoided the complexity associated with the nonlinear relationships inherent in the FCMP to avoid unreasonably long solution times for practical transportation systems. In this paper, a mixed-integer linear programming (MILP) based method is introduced to generate piecewise-linear functions that approximate the previously ignored nonlinear relationships. The MILP determines the optimal break-points and orientation of the linear segments so that approximation error is minimized. A novel FCMP model that includes the piecewise-linear approximations is applied in a case study on three simple gas networks. The case study shows that the novel FCMP model captures the nonlinear relationships with a high degree of accuracy and only marginally increases solution time compared to the common simplified FCMP model. The common simplified model is found to produce solutions with high error and infeasibility when applied on a rigorous simulation. Full article

This paper presents an interactive tool focused on the study of proportional-integral-derivative (PID) controllers. Nowadays, PID control loops are extensively used in industrial applications. However, it is reported that many of them are badly tuned. From an educational point of view, it is essential for undergraduate students in control engineering to understand the importance of tuning a control loop correctly. For this reason, the tool provides different PID tuning methods in the frequency domain for stable open-loop time-delay-free processes. The different designs can be compared interactively by the user, allowing them to understand concepts about stability, robustness, and performance in PID control loops. A survey and a comparative study were performed to evaluate the effectiveness of the proposed tool. Full article

In situ gasification chemical looping combustion (iG-CLC) is a novel and promising coal combustion technology with inherent separation of CO₂. Our previous studies demonstrated the feasibility of performing iG-CLC with a high-flux circulating fluidized bed (HFCFB) riser as the fuel reactor (FR) and a counter-flow moving bed (CFMB) as the air reactor (AR). As an extension of that work, this study aims to further investigate the fundamental effects of the AR coupling on the oxygen carrier (OC) circulation and gas leakages with a cold-state experimental device of the proposed iG-CLC system. The system exhibited favorable pressure distribution characteristics and good adaptability of solid circulation flux, demonstrating the positive role of the direct coupling method of the AR in the stabilization and controllability of the whole system. The OC circulation and the gas leakages were mainly determined by the upper and lower pressure gradients of the AR. With the increase in the upper pressure gradient, the OC circulation flux increased initially and later decreased until the circulation collapsed. Besides, the upper pressure gradient exhibited a positive effect on the restraint of gas leakage from the FR to the AR, but a negative effect on the suppression of gas leakage from the AR to the FR. Moreover, the gas leakage of the J-valve to the AR, which is directly related to the solid circulation stability, was exacerbated with the increase of the lower pressure gradient of the AR. In real iG-CLC applications, the pressure gradients should be adjusted flexibly and optimally to guarantee a balanced OC circulation together with an ideal balance of all the gas leakages. Full article

In this present work, a study of the modelling and simulation for a top-sprayed fluidized bed granulator (SFBG) is presented, which is substantially used by the pharmaceutical industry to prepare granules. The idea is to build a number-based mathematical model using the notion of population balances by dividing a top SFBG into two different zones, namely the wet zone and dry zone. To solve a two-compartment model, an existing accurate and efficient finite volume scheme is implemented. In order to validate the compartmental model, a new class of analytical moments is derived corresponding to various combinations of aggregation and breakage kernels. To verify the accuracy of a modified finite volume scheme, the zeroth and first order moments computed using the finite volume scheme are compared with the newly-derived analytical results. Moreover, the stability of the compartmental model and the numerical scheme is tested by varying the size of the wet zone. It is also shown that the relative errors in both order moments increase with the increase in the size of the wet zone. Full article

This study investigates the effect of carbon nanotube (CNT) dispersion on the mechanical properties and microstructures of ultra-light foamed concrete. A type of uniform and stable CNT dispersion solution is obtained by adding nano-Ce(SO₄)₂. Results show that CNT dispersion increases the compressive and breaking strengths of foamed concrete. CNTs play a nuclear role in the crystallization of C–S–H, and CNT dispersion effectively promotes the grain growth of C–S–H. The effect of CNT dispersion on the compressive and breaking strengths of foamed concrete is predicted through simulation. Full article

Natural gas liquefaction is an energy intensive process where the feed is cooled from ambient temperature down to cryogenic temperatures. Different liquefaction cycles exist depending on the application, with dual mixed refrigerant processes normally considered for the large-scale production of Liquefied Natural Gas (LNG). Large temperature spans and small temperature differences in the heat exchangers make the liquefaction processes difficult to analyze. Exergetic losses from irreversible heat transfer increase exponentially with a decreasing temperature at subambient conditions. Consequently, an accurate and robust simulation tool is paramount to allow designers to make correct design decisions. However, conventional process simulators, such as Aspen Plus, suffer from significant drawbacks when modeling multistream heat exchangers. In particular, no rigorous checks exist to prevent temperature crossovers. Limited degrees of freedom and the inability to solve for stream variables other than outlet temperatures also makes such tools inflexible to use, often requiring the user to resort to a manual iterative procedure to obtain a feasible solution. In this article, a nonsmooth, multistream heat exchanger model is used to develop a simulation tool for two different dual mixed refrigerant processes. Case studies are presented for which Aspen Plus fails to obtain thermodynamically feasible solutions. Full article

A mixture of sandstone and mudstone particles is often used as the main filling material for many agriculture-related and civil engineering projects, including rock-fill dams and foundations. The long-term rheological deformation experienced by rock-fill dams and foundations filled with this mixture is much bigger than that of coarse-grained and cohesive soils, due to the deterioration and softening of the mudstone particles. This study focuses on the rheological deformation of a sandstone-mudstone particle mixture, prepared by mixing sandstone and mudstone particles, based on the content by weight of four mudstone particle types. Confined uniaxial compression tests were performed to test the rheological deformation of 24 samples of the mixture, and a stress-strain curve was obtained for each test. On the basis of compression curves, the rheological process of the mixture was divided into four phases: linear, attenuation rheological, secondary attenuation rheological and stable phases. The three defining features of the curve, namely the rheological attenuation factors, attenuation rheology critical strain and limited rheological strain, were then determined and modeled. A segmented rheological model was then proposed, based on a modified attenuation rheological constitutive model for coarse-grained soil. The modelled results compared well with the experimental data, and the modelled compression-curve prediction was able to describe the two-stage attenuation rheology features (attenuation rheological and secondary attenuation rheological phases) of the sandstone-mudstone particle mixture. Full article

Because of the limitation of mining techniques and economic conditions, large amounts of residual coal resources have been left in underground coal mines around the world. Currently, with mining technology gradually developing, residual coal can possibly be remined. However, when residual coal is remined, caving areas might form, which can seriously affect the safety of coal mining. Hence, grouting technology is put forward as one of the most effective technologies to solve this problem. To study the grouting diffusion in fractured rock mass, this paper developed a visualization platform of grouting diffusion and a three-dimensional grouting experimental system that can monitor the grout diffusion range, diffusion time and grout pressure; then, a grouting experiment is conducted based on this system. After that, the pattern of the grouting pressure variation, grout flow and grout diffusion surface are analyzed. The relationship among some factors, such as the grouting diffusion radius, compressive strength of the grouted gravel, porosity, water-cement ratio, grouting pressure, grouting time, permeability coefficient and level of grout, is quantitatively analyzed by using MATLAB. The study results show that the flow pattern of the grout in fractured porous rock mass has a parabolic shape from the grouting hole to the bottom. The lower the level is, the larger the diffusion range of the grout is. The grouting pressure has the greatest influence on the grouting diffusion radius, followed by the grouting horizon and water-cement ratio. The grouting permeability coefficient has the least influence on the grouting diffusion radius. The grout water-cement ratio has the greatest influence on the strength of the grouted gravel, followed by the grouting permeability. The grouting pressure coefficient has the least amount of influence on the grouting diffusion radius. According to the results, the grouting parameters are designed, and a layered progressive grouting method is proposed. Finally, borehole observation and a core mechanical property test are conducted to verify the application effect. This grouting technology can contribute to the redevelopment and efficient utilization of wasted underground coal resources. Full article

The mechanical properties and seepage characteristics of gas-bearing coal evolve with changes in the loading pattern, which could reveal the evolution of permeability in a protected coal seam and allow gas extraction engineering work to be designed by using the effect of mining multiple protective seams. Tests on gas seepage in raw coal under three paths (stepped-cyclic, stepped-increasing-cyclic, and crossed-cyclic loading and unloading) were carried out with a seepage tester under triaxial stress conditions. The permeability was subjected to the dual influence of stress and damage accumulation. After being subjected to stress unloading and loading, the permeability of coal samples gradually decreased and the permeability did not increase before the stress exceeded the yield stage of the coal samples. The mining-enhanced permeability of the coal samples in the loading stage showed a three-phase increase with the growth of stress and the number of cycles and exhibited an N-shaped increase under the stepped-cyclic loading while it linearly increased under the other two paths in the unloading stage. With the increase of peak stress and the accumulation of damage in coal samples, the sensitivity of the permeability of coal samples to stress gradually declined. The relationship between the damage variable and the number of cycles conformed to the Boltzmann function. Full article

The aim of this study was to microencapsulate an optimized extract of purple cactus pear fruit (Opuntia ficus indica), rich in phenolic compounds (PC), betacyanins (BC), and betaxanthins (BX), with antioxidant capacity (AC), by two methodologies: combined water-in-oil-in-water double emulsions-spray drying (W/O/W-SP) and conventional spray drying, studying the effect of spray drying (SP) on PC and AC. Optimal extraction conditions for bioactive compounds were: 52 °C, for 30 min, using aqueous ethanol (40%_w/w) as the solvent, with a 0.85 desirability function, obtaining 17.39 ± 0.11 mg GAE/g_dw (gallic acid equivalents per gram of dry weight) for PC, 0.35 mg BE/g_dw (betanin equivalents per gram of dry weight) for BC, and 0.26 mg IE/g_dw (indicaxanthin equivalents per gram of dry weight) for BX. The best combination of temperatures for conventional SP and W/O/W-SP was 160–80 °C obtaining the highest retention and encapsulation efficiencies for PC. For conventional SP, results were: 107% and 100% PC and AC retention efficiencies (RE-PC and RE-AC), respectively, with 97% of PC encapsulation efficiency (EE-PC), meanwhile for the W/O/W-SP results were: 78% and 103% RE-PC and RE-AC, respectively, with 70% of EE-PC. Microcapsules obtained with W/O/W-SP maintained their structure and integrity and showed a considerable reduction in globule size in the reconstituted W/O/W emulsions due to the spray drying stress. Despite having lower EE-PC than conventional SP, spray dried W/O/W emulsions seem as a promising controlled-delivery vehicle for antioxidant compounds. Full article

The genetic modification of human T lymphocytes with established non-viral methods is inefficient. Linear polyethylenimine (l-PEI), one of the most popular non-viral transfection agents for mammalian cells in general, only achieves transfection rates in the single digit percentage range for these cells. Here, a well-defined 24-armed poly(2-dimethylamino) ethyl methacrylate (PDMAEMA) nanostar (number average of the molecular weight: 755 kDa, polydispersity: <1.21) synthesized via atom transfer radical polymerization (ATRP) from a silsesquioxane initiator core is proposed as alternative. The agent is used to prepare polyplexes with plasmid DNA (pDNA). Under optimal conditions these polyplexes reproducibly transfect >80% of the cells from a human T-cell leukemia cell line (Jurkat cells) at viabilities close to 90%. The agent also promotes pDNA uptake when simply added to a mixture of cells and pDNA. This constitutes a particular promising approach for efficient transient transfection at large scale. Finally, preliminary experiments were carried out with primary T cells from two different donors. Results were again significantly better than for l-PEI, although further research into the response of individual T cells to the transfection agent will be necessary, before either method can be used to routinely transfect primary T lymphocytes. Full article

Multicellular systems play an important role in many biotechnological processes. Typically, these exhibit cell-to-cell variability, which has to be monitored closely for process control and optimization. However, some properties may not be measurable due to technical and financial restrictions. To improve the monitoring, model-based online estimators can be designed for their reconstruction. The multicellular dynamics is accounted for in the framework of population balance models (PBMs). These models are based on single cell kinetics, and each cellular state translates directly into an additional dimension of the obtained partial differential equations. As multicellular dynamics often require detailed single cell models and feature a high number of cellular components, the resulting population balance equations are often high-dimensional. Therefore, established state estimation concepts for PBMs based on discrete grids are not recommended due to the large computational effort. In this contribution a novel approach is proposed, which is based on the approximation of the underlying number density functions as the weighted sum of Gaussian distributions. Thus, the distribution is described by the characteristic properties of the individual Gaussians, like the mean and covariance. Thereby, the complex infinite dimensional estimation problem can be reduced to a finite dimension. The characteristic properties are estimated in a recursive approach. The method is evaluated for two academic benchmark examples, and the results indicate its potential for model-based online reconstruction for multicellular systems. Full article

The objective of the research was to compare the flotation performance of medical waste incinerator fly ash (MWIFA) by considering two methods: the cyclonic-static micro-bubble flotation column (FCSMC) method and conventional flotation cell (CFC) method. The results indicated that for FSCMC, the optimum parameters were kerosene = 3.5 g/kg·ash, methyl isobutyl carbinol (MIBC) = 0.2 g/kg·ash, Tween 80 = 7.5% of kerosene concentration, slurry concentration = 100 g/L, and pump speed = 380 r/min. The optimized conditions resulted in a higher dioxin removal efficiency (90.98%), carbon removal efficiency (91.88%) and lower loss on ignition (LOI) (4.96%). The data obtained from the CFC under different optimum operating conditions were 88.65%, 90.63% and 5.68%, respectively. FSCMC was proven to be more efficient for the flotation of MWIFA than CFC. Full article

Porous medium burners are characterized by high efficiency and good stability. In this study, a new burner was proposed based on the combustion mechanism of the methane-air mixture in the porous medium and the preheating effect. The new burner is a two-section and double-deck porous medium with gas inlets at both ends. A mathematical model for the gas mixture combustion in the porous medium was established. The combustion performance of the burner was simulated under different equivalence ratios and inlet velocities of premixed gas. The methane combustion degree, as well as the temperature and pressure distribution, was estimated. In addition, the concentrations of emissions of NO_x for different equivalence ratios were investigated. The results show that the new burner can not only realize sufficient combustion but also save energy. Furthermore, the emission concentration of NO_x is very low. This study provides new insights into the industrial development and application of porous medium combustion devices. Full article

Bioprocesses for the production of renewable energies and materials lack efficient separation processes for the utilized microorganisms such as algae and yeasts. Dissolved air flotation (DAF) and microflotation are promising approaches to overcome this problem. The efficiency of these processes depends on the ability of microorganisms to aggregate with microbubbles in the flotation tank. In this study, different new or adapted aggregation models for microbubbles and microorganisms are compared and investigated for their range of suitability to predict the separation efficiency of microorganisms from fermentation broths. The complexity of the heteroaggregation models range from an algebraic model to a 2D population balance model (PBM) including the formation of clusters containing several bubbles and microorganisms. The effect of bubble and cell size distributions on the flotation efficiency is considered by applying PBMs, as well. To determine the sensitivity of the results on the model assumptions, the modeling approaches are compared, and suggestions for their range of applicability are given. Evaluating the computational fluid dynamics (CFD) of a dissolved air flotation (DAF) system shows the heterogeneity of the fluid dynamics in the flotation tank. Since analysis of the streamlines of the tank show negligible back mixing, the proposed aggregation models are coupled to the CFD data by applying a Lagrangian approach. Full article

Model-based design principles have received considerable attention in biotechnology and the chemical industry over the last two decades. However, parameter uncertainties of first-principle models are critical in model-based design and have led to the development of robustification concepts. Various strategies have been introduced to solve the robust optimization problem. Most approaches suffer from either unreasonable computational expense or low approximation accuracy. Moreover, they are not rigorous and do not consider robust optimization problems where parameter correlation and equality constraints exist. In this work, we propose a highly efficient framework for solving robust optimization problems with the so-called point estimation method (PEM). The PEM has a fair trade-off between computational expense and approximation accuracy and can be easily extended to problems of parameter correlations. From a statistical point of view, moment-based methods are used to approximate robust inequality and equality constraints for a robust process design. We also apply a global sensitivity analysis to further simplify robust optimization problems with a large number of uncertain parameters. We demonstrate the performance of the proposed framework with two case studies: (1) designing a heating/cooling profile for the essential part of a continuous production process; and (2) optimizing the feeding profile for a fed-batch reactor of the penicillin fermentation process. According to the derived results, the proposed framework of robust process design addresses uncertainties adequately and scales well with the number of uncertain parameters. Thus, the described robustification concept should be an ideal candidate for more complex (bio)chemical problems in model-based design. Full article

No unified electromagnetic anti-fouling mechanism is currently available. Most research has focused on the effects of structural parameters and water quality parameters on electromagnetic fields; variations in water quality parameters under the influence of electromagnetic fields have not been reported. A variable-frequency vertical electromagnetic field is proposed in this study. Relationships between conductivity, pH value, dissolved oxygen, turbidity, fouling resistance, and magnetic acting time were carefully analyzed using statistical analysis. Results show that the conductivity difference was the most explanatory predictive variable on magnetic acting time in the multiple stepwise regression model. Magnetic acting time has a greater impact on conductivity than pH value and dissolved oxygen. Conductivity is used as an adaptive feedback control parameter for the optimum anti-fouling state. Fouling resistance on the heat-exchanging surface of the magnetic experiment was smaller than that of the contrast experiment. The anti-fouling efficiency in 1 kHz and 5 kHz magnetic and contrast experiments was 91.23% and 46.97%, respectively. Better anti-fouling performance was realized under the influence of low-frequency electromagnetic fields, confirming that physical water treatment is an effective and environmentally friendly method to eliminate heat exchanger fouling. This research serves as a reference for the development of an electromagnetic-adaptive closed-loop water treatment device. Full article

In this study, process integration for crystallization of a priori purified Artemisia annua L. is investigated. For this total process, the integration operation boundaries and behavior of the crystals are studied. This is performed focusing on a conceptual process design study for artemisinin, aiming towards the development of a crystallization step under given parameters by process integration. At first, different crystallization systems consisting of ethanol-water or acetone-water mixtures are compared. In subsequent steps, the metastable zone width and the behavior of the crystals regarding agglomeration and breakage are checked. Furthermore, the sensitivities of process variables based on several process parameters are investigated. Additionally, the final process integration of crystallization as a combined purification and isolation step is studied. Full article

In this study, the purification of an extract from Artemisia annua L. using chromatographic methods is studied. In a first step, a screening of different phases and solvents using thin-layer chromatography (TLC) was performed. Then, a laboratory-scale high performance liquid chromatography (HPLC) method was developed and transferred to a pilot scale. A reproducibility study based on 120 injections was carried out. The batch process that was developed and the results from a designed continuous simulated moving bed (SMB) chromatography were compared based on characteristic process numbers and economy. Full article

Liquid-liquid extraction (LLE) is an established unit operation in the manufacturing process of many products. However, development and integration of multistage LLE for new products and separation routes is often hindered and is probably more cost intensive due to a lack of robust development strategies and reliable process models. Even today, extraction columns are designed based on pilot plant experiments. For dimensioning, knowledge of phase equilibrium, hydrodynamics and mass transport kinetics are necessary. Usually, those must be determined experimentally for scale-up, at least in scales of DN50-150 (nominal diameter). This experiment-based methodology is time consuming and it requires large amounts of feedstock, especially in the early phase of the project. In this study the development for the integration of LLE in a new manufacturing process for artemisinin as an anti-malaria drug is presented. For this, a combination of miniaturized laboratory and mini-plant experiments supported by mathematical modelling is used. System data on extraction and washing distributions were determined by means of shaking tests and implemented as a multi-stage extraction in a process model. After the determination of model parameters for mass transfer and plant hydrodynamics in a droplet measurement apparatus, a distributed plug-flow model is used for scale-up studies. Operating points are validated in a mini-plant system. The mini-plant runs are executed in a Kühni-column (DN26) for extraction and a packed extraction column (DN26) for the separation of side components with a throughput of up to 3.6 L/h, yield of up to 100%, and purity of 41% in the feed mixture to 91% after washing. Full article

The production of plant-based extracts is significantly influenced by traditional techniques and the natural variability of feedstock. For that reason, the discussion of innovative approaches to improve the manufacturing of established products and the development of new products within the regulatory framework is essential to adapt to shifting quality standards. This perspective of members of the DECHEMA/ProcessNet working group on plant-based extracts outlines extraction business models and the regulatory framework regarding the extraction of traditional herbal medicines as complex extracts. Consequently, modern approaches to innovative process design methods like QbD (Quality by Design) and quality control in the form of PAT (Process Analytical Technology) are necessary. Further, the benefit of standardized laboratory equipment combined with physico-chemical predictive process modelling and innovative modular, flexible batch or continuous manufacturing technologies which are fully automated by advanced process control methods are described. A significant reduction of the cost of goods, i.e., by a factor of 4–10, and decreased investments of about 1–5 mil. € show the potential for new products which are in line with market requirements. Full article

The terminal sugar molecules of the N-linked glycan attached to the fragment crystalizable (Fc) region is a critical quality attribute of therapeutic monoclonal antibodies (mAbs) such as immunoglobulin G (IgG). There exists naturally-occurring heterogeneity in the N-linked glycan structure of mAbs, and such heterogeneity has a significant influence on the clinical safety and efficacy of mAb drugs. We previously proposed a constraint-based modeling method called glycosylation flux analysis (GFA) to characterize the rates (fluxes) of intracellular glycosylation reactions. One contribution of this work is a significant improvement in the computational efficiency of the GFA, which is beneficial for analyzing large datasets. Another contribution of our study is the analysis of IgG glycosylation in continuous perfusion Chinese Hamster Ovary (CHO) cell cultures. The GFA of the perfusion cell culture data indicated that the dynamical changes of IgG glycan heterogeneity are mostly attributed to alterations in the galactosylation flux activity. By using a random forest regression analysis of the IgG galactosylation flux activity, we were further able to link the dynamics of galactosylation with two process parameters: cell-specific productivity of IgG and extracellular ammonia concentration. The characteristics of IgG galactosylation dynamics agree well with what we previously reported for fed-batch cultivations of the same CHO cell strain. Full article

Phragmites australis straw (PAS) is an abundant and renewable wetland lignocellulose. Bacillus coagulans IPE22 is a robust thermophilic strain with pentose-utilizing capability and excellent resistance to growth inhibitors. This work is focused on the process study of lactic acid (LA) production from P. australis lignocellulose which has not been attempted previously. By virtue of thermophilic feature of strain IPE22, two fermentation processes (i.e., separated process and integrated process), were developed and compared under non-sterilized conditions. The integrated process combined dilute-acid pretreatment, hemicellulosic hydrolysates fermentation, and cellulose utilization. Sugars derived from hemicellulosic hydrolysates and cellulose enzymatic hydrolysis were efficiently fermented to LA in a single vessel. Using the integrated process, 41.06 g LA was produced from 100 g dry PAS. The established integrated process results in great savings in terms of time and labor, and the fermentation process under non-sterilized conditions is easy to scale up for economical production of lactic acid from PAS. Full article