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The mixing and drying behavior in a continuous fluidized bed dryer were investigated experimentally by characterizing the residence time distribution (RTD) and incorporating a micromixing model together with the drying kinetics obtained from batch drying. The RTD of the dryer was modeled using a tank‐in‐series model. It was found that a high initial material loading and a low material flow rate resulted in a reduced peak height and broaded peak width of the RTD curve. To predict the continuous dryer effluent moisture content, we combined: (a) the drying kinetics as determined in a batch fluidized bed dryer, (b) the RTD model, and (c) micromixing models—segregation and maximum mixedness models. It was found that the segregation model overpredicted the effluent moisture content by up to 5% for the cases we have studied while the maximum mixedness model gave a good prediction of the effluent moisture content. [ABSTRACT FROM AUTHOR]

After designing and constructing an electrochemical reactor with concentric electrodes and tangential feed (RECT), it is necessary to characterize it and to study its performance. The experimental study of the residence time distribution (RTD) was conducted for flow rates of 2.78 × 10–6 m3 s–1, 8.33 × 10–6 m3 s–1 and 13.9 × 10–6 m3 s–1. According to the values obtained from the Pe number (0.67–1.52), the RECT fits as tubular with great dispersion. The determined empirical correlation (Sh = 18.16 Re0.50 Sc0.33) showed a laminar flow behavior in the range of Reynolds number (Re) between 23 and 117. In order to use RECT in effluent treatment, an electrochemical oxidation study of the Diuron model molecule (Nortox®) was performed to analyze reactor performance in a closed system with total reflux. A decay kinetics of pseudo-first order was associated with the decay of the concentration of diuron and 30% mineralization in 180 min of process were obtained, having a total volume of 4 × 10–3 m3 and an initial concentration of commercial Diuron in 215.83 mg dm–3. Eleven by-products were identified by HPLC–MS analysis and, from this, it was possible to propose a route of degradation of the diuron. From these observations, it can be inferred that the studied electrochemical reactor had applicability in the degradation of recalcitrant compounds, as is the case of commercial diuron. Make some changes in the electrochemical reactor studied and other advanced oxidative processes, such as electro-Fenton, can be associated with the studied system to achieve a better conversion efficiency. [ABSTRACT FROM AUTHOR]

Reactor performance, solids‐(gas)‐mixing, flow through porous media, distillation columns, or through granulators improve as the fluid dynamics approach ideal plug flow. The residence time distribution (RTD) is a diagnostic measure of how close fluid flow approaches ideal conditions. The technique introduces a step change to the inlet concentration—a Dirac‐δ function, Heaviside step function, or a rectangular pulse (bolus)—while high frequency detectors monitor the concentration along the vessel and/or at the exit. The effluent concentration profile spreads due to the variance in the process lines leading to the vessel and at the exit, the detector response, and the system. We quantify how much each of these contributes to the overall variance in a fluidized bed with 9 g of fluid cracking catalyst in 8 mm diameter quartz tubes. The injection variance is lowest for a GC sample loop configuration, compared to a 3‐way valve or 4‐way valve geometry. RTD measurements detect bypassing due to dead zones in vessels and the axial‐dispersion model and continuous stirred‐tank model to characterize deviation from plug flow. However, when the contribution to variance from the ancillary lines and detector is large compared to the system, the uncertainty in the model parameters is high. Research on RTD fundamentals concentrate on boundary conditions while, here, we focus on experimental errors: mechanical, physicochemical mathematical, and instrumental. [ABSTRACT FROM AUTHOR]

• A column packed with non-porous beads was developed for continuous virus inactivation. • The reactor performed more efficiently than Jig in a Box and the Coiled Flow Inverter. • The model predicted worst-case virus clearance based on residence time distribution. • Nanoparticle tracers (20 nm and 300 nm) travelled through the column with the same dynamics. A narrow residence time distribution (RTD) is highly desirable for continuous processes where a strict incubation time must be ensured, such as continuous virus inactivation. A narrow RTD also results in faster startup and shut down phases and limits the broadening of potential disturbances in continuous processes. A packed bed reactor with non-porous inert beads was developed to achieve narrow RTDs. The performance was defined as the ratio between the onset of the cumulative RTD and the median residence time (t x % / t 50%). Laboratory-scale packed columns were used to study the influence of the column parameters on the RTD. A larger column with a void volume of 0.65 L and a length of 89 cm, packed with beads in a size range of 125 to 250 μm, achieved t 0.5% / t 50% >0.93 across flow rates from 0.1 to 9.8 mL/min. The RTD was significantly narrower than the RTDs of other reactor designs, such as the Coiled Flow Inverter and Jig in a Box. The pressure drop remained under 3 kPa for all tested flow rates. Fluorescent nanoparticles (30 and 200 nm) were used to mimic viruses. These two sizes showed less than 2% difference in terms of t 1% / t 50% and t 0.01% / t 50% scores. These results indicated that viruses travelled through the column at rates independent of size. This proposal of packed beds as incubation chambers for continuous virus inactivation is simple, scalable, and can be realized as single-use devices. Due to the low pressure drop, the system can be easily integrated into a fully continuous process. [ABSTRACT FROM AUTHOR]

The main drivers for application of small‐scale reactors in the pharmaceutical industry are the possibility of rapid synthesis and screening of novel drugs as well as the readiness of the scale‐up. The characterization of fluid flow pattern was performed through step‐up and step‐down residence time distribution experiments using a tracer at six different flow rates. Four single‐parameter models were considered for representing deviations from ideal plug flow and ideal laminar flow in tubes. The model that provided the best results was the axial dispersion model and the Peclet and Reynolds numbers could be well correlated. Obtained Peclet values from 44 to 244 were close to Pe > 100, in which axial dispersion can be neglected and the reactor can be considered as plug flow reactor. [ABSTRACT FROM AUTHOR]

Experiments on continuously operated spray fluidized bed agglomeration are presented in this work. The process is conducted with glass beads and water-based binder hydroxypropylmethylcellulose (HPMC). By varying the process parameters, the results show that by the decrease of air temperature or feed rate and by the increase of binder concentration, larger particles can be achieved. Larger particle size also results in higher bed mass and more fluctuations in the process. Besides parameters variations, different internal and outlet weir configurations are used. Tracers are used in the experiments to characterize the particle residence time distribution. The separation effect can be decreased and the particle residence time can be optimized by the installation of internal weirs and lower height of outlet weir. The results show that the jets from the spray nozzles are increasing the motion and mixing of particles significantly. Unlabelled Image • Experimental investigation of continuously operated spray agglomeration in a pilot horizontal fluidized bed. • Influences of fluidization air temperature, feed rate, binder concentration and weir configurations were investigated. • Evolution of particle size and process stability were illustrated and compared. • Particle residence time distributions were measured by tracer method. [ABSTRACT FROM AUTHOR]

This work aims to expand the typical raw material attributes that can successfully be processed on a continuous direct compression line with a particular focus on the continuous dry powder blender. Three grades of Acetaminophen were investigated as model active pharmaceutical ingredients and chosen to span a broad range of material attributes wider than what would normally be considered for a direct compression process. An experimental design was set-up for each grade of Acetaminophen to investigate the effect of throughput, impeller speed and impeller configuration on the critical process responses and attributes. The strain experienced by the in-process material was found critical to improve content uniformity. The impeller speed and design can be optimised at a given throughput to obtain a strain which would deliver the required content homogeneity. The content uniformity of the final tablets can be modelled as a function of the strain using an exponential decay model. Unlabelled Image • Wide range of parameters deliver acceptable tablet content uniformity. • Blender throughput, speed and configuration significantly affect residence mass. • Final tablet uniformity is a function of the mean residence time and impeller speed. • Prediction of final tablet content uniformity from process imparted strain. [ABSTRACT FROM AUTHOR]

• Residence time distribution modelling in industrial-scale screws is performed. • A novel experimental methodology suited to harsh thermodynamic conditions is used. • AD, PF-CSTR and a model based on the Zusatz function are adjusted and compared. • The non-ideal flow behavior observed is likely to be due to material backflow. The raise of environmental concerns in the past decades consequently increased the need of obtaining cleaner sources of energy. Among the studied alternatives, second generation biofuels (produced from non-food resources) are one of the most promising solutions and nearly reached industrialization. The production of cellulosic bioethanol is one of the possibilities of second generation biofuels, and the studies involving the use of cellulosic compounds to produce bioethanol recently increased. Its production involves four dependent steps: pretreatment, enzymatic hydrolysis, fermentation and distillation. This work considered the pretreatment stage, aiming at modifying the structure of the lignocellulosic biomass so that cellulose becomes more accessible to enzymatic hydrolysis step. This work particularly focused on the biomass flow characterization in the transport and compression screws involved in the pretreatment step of an industrial-scale process. The main challenge was firstly to perform measurements on an industrial-scale device working under harsh conditions. Residence time distribution (RTD) experiments were thus performed using a novel methodology adapted to these working conditions. Sodium carbonate was selected as a tracer. Due to the reaction with the acidified biomass, both electrical conductivity and pH were monitored at the exit of the screws. A chemical model was developed, allowing the determination of tracer concentrations from the measured data. The measurements obtained were compared with three optimized models: a combination of plug flow and continuous stirred tank reactor in series (PFR-CSTR), plug flow with axial dispersion (AD) and a model based on the Zusatz function. The results of this work pointed out the non-plug flow behavior of these screws in their standard working conditions. In accordance with the physical motion of the tracer inside the screws, the use of the PF-CSTR is recommended for representing RTD inside screws in conditions in which backflow is likely to occur. [ABSTRACT FROM AUTHOR]

Mechanical expression is widely applied for oil recovery from oilseeds using continuous screw presses. Despite significant recent advances in the field of press design and automation, it remains difficult to predict the press performances based on the theoretical approaches, and more experimental investigations are needed to clarify and characterize the seeds flow and expression behavior in the press. Residence Time Distribution (RTD) is a frequently used tool in chemical engineering to characterize the material flow by simple tracer tests. In this paper, we explore the feasibility of using RTD for the screw presses, in order to check the flow patterns homogeneity and identify the possible deviations depending on the press geometry and the operating conditions. Both theoretical modeling and experimental investigation are conducted for two different screw press designs (Reinartz and Olexa), and at the different rotation speeds. An original and reliable experimental methodology was developed by using erucic acid as tracer in the form of pulse injection and gas chromatography as detection method. Experimental results coupled with statistical calculations showed the influence of the screw geometry and the rotation speed on the seeds flow inside the press. The matter displacement was much faster and the experimental residence time was very close to the theoretical one indicating more homogeneity and less dispersion in the Olexa arrangement in comparison to the Reinartz arrangement. The higher variance observed at lower rotation speed (2.4 rpm) suggested the presence of flow defects like mixing and axial dispersion in the press. To complete the experimental work, axial dispersion model was applied, and allowed obtaining the valuable information, such as axial dispersion degree and distribution functions. Obtained results can be very useful to predict the performance of existing screw presses and design more efficient industrial equipments. [ABSTRACT FROM AUTHOR]

There are few studies concerning the process simulation of vertical roller mills (VRMs). In this research work, the application of population balance model for simulation of a VRM in a cement clinker grinding circuit was investigated. The residence time distribution (RTD) was measured, and the tank-in-series and Weller models were employed to describe the residence time distribution. Two sampling surveys were carried out on the VRM circuit. The data from the first survey were used for model calibration, and the specific breakage rates were back-calculated. The model parameters obtained were used for simulation of the second survey, and validation of the model. The results showed that the clinker particle spent a short time inside the VRM and the mean residence time is about 67s. The tanks-in series model compares to Weller model was more proper to describe the residence time distributions in the VRM. The simulation results showed that the specific breakage rates increased with increasing particle size. However, the particles larger than 25.4 mm particles sizes are too large to be properly nipped by master rollers. Finally, it can be concluded that the grinding process of the VRM is very well-predictable with the population balance model. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) computational fluid dynamics (CFD) simulations were performed to study solids flow dynamics and solids back-mixing behavior in a screw reactor (designed for thermal conversion of dry biomass particles) based on the Eulerian-Eulerian method. Simulation results were compared against experimental data with respect to filling degree and mean residence time of particles. The mean deviations for filling degree and for mean residence time between simulation and experiment were about 0.01 and 11.4 s, respectively, which shows that the model is reasonably accurate in predicting solids flow behavior in the screw reactor. The solids flow dynamics inside the reactor were discussed. The solids residence time distribution (RTD) was calculated and the degree of solids back-mixing in the forward transportation direction of the reactor was analyzed. It was found that solids being flung over the shaft and solids back-leakage, resulting from the low solids forward transportation velocity at the clearance between the flight and the bottom shell of the screw reactor, were responsible for solids back-mixing. The degree of solids back-mixing can be reduced at higher screw rotating speeds when keeping inlet mass flow rate of solids constant. Image 101347 • A 3D Eulerian-Eulerian model was developed for a rotating screw reactor. • Solids rotating flow and forward transportation flow were discussed. • Solids residence time distribution inside the screw reactor was predicted. • Possible mechanisms for solids back-mixing were proposed. [ABSTRACT FROM AUTHOR]

In this study, 9-anthracenemethyl methacrylate (AMMA) and styrene (St) as monomers and benzoyl peroxide as an initiator were used to synthesize P(St-co-AMMA), a macromolecule tracer with a fluorescence effect, via free radical copolymerization. A fluorescent online detection device was built on the basis of the principle of fluorescence online detection by using the single-screw extrusion platform of a torque rheometer to explore the effect of the amount of macromolecular tracer and screw speed on the residence time distribution of polystyrene in single-screw extrusion. Fourier transform infrared spectroscopy, 1H-NMR, thermal stability, fluorescence properties, and rheological properties show that the resulting product P(St-co-AMMA) has a degree of thermal stability, fluorescence, and rheological properties similar to polystyrene, so this product can be used to characterize the residence time distribution during single-screw extrusion. The amount of macromolecular tracer P(St-co-AMMA) does not affect the residence time distribution of polystyrene during single-screw extrusion processing, meanwhile, the minimum residence time decreases and the residence time distribution becomes narrow as the screw speed increases, that is, the axial mixing capacity of the single-screw extruder decreases as the screw speed increases. [ABSTRACT FROM AUTHOR]

Purpose: During continuous manufacturing, there may be some out of specification tablets that need to be diverted in real time, in order to ensure the quality of the final product. Specifically, the content uniformity of each tablet must be guaranteed before it can be released to market. However, currently, no methods or tools are available that can assure the content uniformity and divert the non-confirming products in real time. The aim of this work is to develop and evaluate a strategy to divert the non-confirming tablets in real time and thereby assure drug concentration of final tablets. Methods: This work has been conducted in silico using a combination of MATLAB and Simulink. A methodology to implement a residence time distribution (RTD)-based control system for drug concentration-based tablet diversion which uses the convolution integral was developed and implemented in MATLAB. Comparisons between the performance of "fixed window" and "RTD-based" approaches for diversion have also been presented and used to assess optimal usability. Results: In this work, two novel strategies namely, "fixed window approach" and "RTD-based approach" have been developed and evaluated for real-time diversion of non-confirming tablets. The RTD-based control system was designed, developed, and implemented in silico. A framework for its implementation in a real-time system has also been elaborated on. This methodology was compared to an alternative fixed window approach. The proposed control system is analyzed for various manufacturing scenarios, systems, and disturbances. Conclusions: A comparison of the two proposed strategies suggests that the "RTD-based control system" is more efficient in every simulated scenario. The relative performance is best when the disturbances in the system are characterized by short pulse-like changes. [ABSTRACT FROM AUTHOR]

In this short communication, the residence time distribution of molten polymer in a liquefier of a material extrusion process is numerically investigated. The Laplace transform is used to easily fit the residence time distribution. As a result, the liquefier can be decomposed into a plug flow and a continuous stirred tank reactor in series. The local mean residence time is also studied numerically to provide information about the flow structure. [ABSTRACT FROM AUTHOR]

The performance of particle coating is essentially determined by the morphology and uniformity of coating shells, which significantly depend on particle circulation. In this study, the geometry of a Wurster fluidized bed is changed by regulating particle circulation port size and nozzle position, and their effects on particle circulation and coating properties are investigated by combining coating experiments and CFD – Discrete Element Model (DEM). By increasing the circulation port size, the particle circulation rate first increases then decreases slightly, accordingly, the uniformity of particle circulation increases then decreases, while the shell porosity decreases. By increasing the nozzle height, the particle circulation rate decreases slightly, accordingly, the uniformity of particle circulation increases then decreases, while the shell porosity decreases. At extremes with a too small circulation port size or too high nozzle position, particle residence and cycle time distribution are broader, and an obvious nonuniformity of particle growth is observed. [Display omitted] • Effects of the geometry of a Wurster fluidized bed on coating are investigated. • Particle motion and coating are studied by combining experiments and CFD – DEM. • High nozzle height broadens particle circulation and increases coat shell porosity. • Small circulation port size worsens drying condition and increases shell porosity. [ABSTRACT FROM AUTHOR]

In order to explore the effect of operation pattern on performance, hydrodynamic behavior and start-up performance including molecular weight distribution (MWD) of soluble organic compounds in a periodic anaerobic baffled reactor (PABR) handling traditional Chinese medicine (TCM) wastewater. Residence time distribution test with tap water in the clean PABR was carried out at a certain hydraulic residence time of 48 h in experiments and in computational fluid dynamics (CFD) simulations, both of which were in good agreement for the 'every second' (switching period T = 48 h), the 'clockwise sequential' (T = 96 h), and the 'no switching' (T = ∞) operation pattern. The CFD model output visualized the hydrodynamic-mass transport, which heavily influenced by operation pattern, successfully inside a PABR. The PABRs run in those three operation patterns were subjected to three successive step changes in average organic loading rate at about 1, 2, 4 and 6 kg COD m−3 d−1 for 12, 24, 24 and 6 d, respectively. Pollutants in the TCM wastewater had the longest time to be digested and degraded within PABR run in the 'every second' operation pattern, resulting in a most stable performance among the three. Performance of PABR was consistent with the variation in MWD of soluble organic compounds no matter what the operation pattern was. High- MW species (93–130 kDa) broke down into simpler intermediate- MW solutes (7–56 kDa) by the metabolism of anaerobic flocs sludge mostly in the compartment which contributed most to the total COD removal of PABR. Then, intermediate- MW solutes were mineralized step by step into low- MW solutes (100 Da) and biogas in the follow-up compartments in the sequence of flow pattern. • 'Every second' operation pattern was most suitable to treat TCM wastewater in PABR. • RTD test with CFD simulation visualized hydrodynamic-mass transport in PABR. • Performance of PABR agreed with the variation in MWD of soluble organic compounds. [ABSTRACT FROM AUTHOR]

Continuous manufacturing (CM) is defined as a process in which the input material(s) are continuously fed into and transformed, and the processed output materials are continuously removed from the system. CM can be considered as matching the FDA’s so-called ‘Desired State’ of pharmaceutical manufacturing in the twenty-first century as discussed in their 2004 publication on ‘Innovation and Continuous Improvement in Pharmaceutical Manufacturing’. Yet, focused attention on CM did not really start until 2014, and the first product manufactured by CM was only approved in 2015. This review describes some of the benefits and challenges of introducing a CM process with a particular focus on small molecule solid oral dosage forms. The review is a useful introduction for individuals wishing to learn more about CM.

Twin-screw wet granulation is a crucial unit operation in shifting from pharmaceutical batch to continuous processes, but granulation kinetics as well as residence times are yet poorly understood. Experimental findings are highly dependent on screw configuration as well as formulation, and thus have limited universal validity. In this study, an experimental design with a repetitive screw setup was conducted to measure the effect of specific feed load (SFL), liquid-to-solid ratio (L/S), and inclusion of a distributive feed screw on particle size distribution (PSD) and shape as well as residence time distribution of a hydrophilic lactose/microcrystalline cellulose based formulation. An intermediate sampling point was obtained by changing inlet ports along the screw axis. Camera-based particle size analysis (QICPIC) indicated no significant change of PSD between the first and second kneading section, except for low L/S and low SFL where fines increase. Mean residence time was approximated as a bilinear fit of L/S and SFL. Moreover, large mass flow pulsations were observed by continuous camera measurements of residence time distribution and correlated to hold-up of the twin-screw granulator. These findings indicate fast granulation kinetics and process instabilities for high mean residence times, questioning current standards of two kneading compartments for wet granulation. The present study further underlines the necessity of developing a multiscale simulation approach including particle dynamics in the future.

• Pulse experiments with a fluorescein tracer were conducted in micro-reactors. • RTD of a coil, shape-8 coil and serpentine channel in laminar/transitional flow. • Effect of spacing arrangements between LL micro-mixers on the RTD evaluated. • Longer straight spacing lengths lead to unidirectional laminar flow and RTD tailing. • RTD of the LL micro-mixer plates are modeled, with near plug flow behaviour. Micro-reactors, enabling continuous processes at small scales, have been of growing interest due to their advantages over batch. These advantages include better scaling, as well as improved mass and heat transfer, though many new challenges arise due to the small scales involved such as non-negligible entrance effects and significant pressure losses. The flow in coils, rectangular channel serpentine plates, mix-and-reside plates, and liquid–liquid (LL) mixing plates was investigated and characterized using residence time distribution (RTD) tests. A pulse test was used to determine the RTD curve of these reactors at flowrates ranging from 15 to 100 g/min of water. A semi-empirical, multi-parameter model was used to describe the asymmetrical curves, while the axial dispersion model was used to describe the symmetrical ones. The Peclet number is given in function of the Reynolds number for the LL plates that were found to be near-plug flow (Pe > 100). In a plate with continuous LL micro-mixers, the Pe ranged from 193 to 467 with Pe increasing as Re increased. Importantly, the effect of straight channel segments interspaced between mixers is also evaluated as a method of volume gain for scale-up of micro-reactors. For a given average energy dissipation rate, the Pe number was maintained for the shorter channel segments between LL micro-mixers whereas longer spacing lengths likely lead to the development of unidirectional laminar flow and resulting in the observed increased axial dispersion and tailing in the RTD. [ABSTRACT FROM AUTHOR]

Continuous manufacturing is an emerging technology in secondary pharmaceutical manufacturing of oral solid dosage forms such as tablets. Continuous blending is a crucial process step in continuous manufacturing. Residence mass (i.e. fill level or hold-up mass) is a critical process parameter of continuous blending and it is defined as amount of material in the blender at controlled state conditions. Residence mass affects for example on the blending efficiency and the residence time distribution. Aim of the study was to elucidate the characteristics of residence mass and its implications. Results showed that residence mass can consist of proportions that are involved in blending process (i.e. effective residence mass) and proportions that are not involved in the blending process (i.e. dead mass). The dead mass has several implications related to the quality attributes of the finished product, detection and segregation of nonconforming material and raw material traceability. Unlabelled Image • Dead mass is defined as a proportion of residence mass not taking part to blending. • Dead mass was found to be adhered onto the low or no shear zones of the blender. • Amount of dead mass was quantified by residence time distribution experiments. • Dead mass has implications on finished product quality and material traceability. [ABSTRACT FROM AUTHOR]

• Characterisation of flow and conversion behaviour using numerical simulation. • Parameter study including variations of reactor geometry and fluid properties. • Applicability test of existing design criteria for conventional fixed-bed reactors. • Novel design criterion based on reactor geometry, fluid properties and flow velocity. The concept of single pellet string reactors (SPSR), where particles are packed in tubes of only slightly larger diameter has been subject of recent studies which demonstrate a renewed interest in this reactor concept, including its use for catalyst testing. However, there remains the need for a thorough characterisation of the reactor performance. In this study, an attempt is made to systematically investigate the flow and conversion behaviour of SPSRs consisting of spherical, non-porous particles in cylindrical confining walls using computational fluid dynamics (CFD). A parameter study with variations on reactor geometry is conducted considering laminar flow and an isothermal, irreversible hypothetical first order reaction taking place at the catalytic particle surface. In addition to reaction simulation, the residence time behaviour is investigated based on numerical tracer experiments. The results showed that conversion close to plug flow can be achieved with SPSRs using favourable parameter settings. Conversion was found to be enhanced in reactors at larger scale, with smaller cylinder-to-particle diameter ratio and with a larger number of catalytic particles. The applicability of existing design criteria for conventional fixed-bed reactors is evaluated. Based on the observations a design criterion for SPSRs is proposed which allows prediction of the deviation to plug flow conversion based on reactor geometry, fluid properties and flow velocity. [ABSTRACT FROM AUTHOR]

The design and fabrication of a continuous-flow μPCR device with very short amplification time and low power consumption are presented. Commercially available, 4-layer printed circuit board (PCB) substrates are employed, with in-house designed yet industrially manufactured embedded Cu micro-resistive heaters lying at very close distance from the microfluidic network, where DNA amplification takes place. The 1.9-m-long microchannel in combination with desirably high flow velocities (for fast amplification) challenged the robustness of the sealing that was overcome with the development of a novel bonding method rendering the microdevice robust even at extreme pressure drops (12 bars). The proposed fabrication methods are PCB compatible, allowing for mass and reliable production of the μPCR device in the established PCB industry. The μPCR chip was successfully validated during the amplification of two different DNA fragments (and with different target DNA copies) corresponding to the exon 20 of the BRCA1 gene, and to the plasmid pBR322, a commonly used cloning vector in E. coli. Successful DNA amplification was demonstrated at total reaction times down to 2 min, with a power consumption of 2.7 W, rendering the presented μPCR one of the fastest and lowest power-consuming devices, suitable for implementation in low-resource settings. Detailed numerical calculations of the DNA residence time distributions, within an acceptable temperature range for denaturation, annealing, and extension, performed for the first time in the literature, provide useful information regarding the actual on-chip PCR protocol and justify the maximum volumetric flow rate for successful DNA amplification. The calculations indicate that the shortest amplification time is achieved when the device is operated at its enzyme kinetic limit (i.e., extension rate). [ABSTRACT FROM AUTHOR]

Radiotracer investigations were carried out for measurement and analysis of residence time distribution (RTD) of coal particles in a pilot-scale gasifier fitted with a flat air/steam distributor. Measurements were made at different operating conditions using gold-198 (198Au) labeled coal particles as a radiotracer. The measured RTDs were treated and mean residence times (MRTs) were determined. Furthermore, the treated RTDs were simulated using a suitably conceptualized mathematical model and detailed information about hydrodynamics of coal particles within the gasifier was obtained. Results of model simulation indicated that the gasifier behaved as an ideal mixer of fine coal particles exiting from the top of the gasifier. A small fraction of the coarser particles was found to be bypassing at ambient temperature. • Radiotracer investigations were carried out in a coal gasifier. • Gold-198-labeled coal particles were used as a radiotracer. • RTDs of coal particle were measured and MRTs determined. • The gasifier behaved as an ideal mixer at all the operating conditions for fine particles. • A small fraction of coarser particles was found to be bypassing at ambient temperature. [ABSTRACT FROM AUTHOR]

The feed frame system is one of the key elements of a rotary tablet press. The powder in the funnel flows through the feed frame system, which ensures a uniform powder flow to the die disc. The objective of the present study was to investigate the effect of different feed frame designs of a production-scale rotary tablet press on the residence time distribution of two microcrystalline cellulose blends, one of them serving as a tracer blend and the other serving as a filling material. With these powder blends, the effect of a reduction of the filling volume of a three chamber feed frame on the powder residence time was investigated. It was shown, that the volume reduction of the three chamber feed frame equipped with three modified large hub wheels led to a decrease of the powder residence time as well as to low intermixing of the powder particles. Furthermore, the residence time distribution within the three chamber feed frame was compared to that within a single chamber cone-shaped feed frame. Both feed frame designs had a similar filling volume but different powder paths through the respective feed frame chambers. The results showed that the single chamber feed frame led to a narrower distribution of the powder residence time and a lower intermixing than the three chamber feed frame. An interesting output of the study was that the variation of the feed frame design had a more pronounced effect on the powder behavior than the variation of the filling volume. [ABSTRACT FROM AUTHOR]

• NIR as a PAT tool for in-line monitoring of blend potency in the feed frame of a rotary tablet press. • Residence time distribution determination inside a rotary tablet press by means of pulse-response experiments. • Existence of different layers inside the feed frame of a tablet press. • The use of in-line acquired NIR spectra to predict the final tablet content needs to be done carefully. • Probe location influences the representativity of the in-line measurements for tablet concentrations. In the current study, the ability to use in-line NIR inside the feed frame of a tablet press to monitor the residence time distribution inside the tablet press was investigated. Pulse-response experiments were performed. In-line measurements inside the feed frame were compared to measurements on the actual produced tablets and the influence of different tableting parameters on the concentration profiles were studied. Turret speed had a major influence on the concentration profiles and RTD parameters. The in-line and off-line concentration profiles did not align with each other as spiking material was still detected in the tablets when no spiking material was observed in the powder blend by the in-line measuring method. The cause of this mismatch between the in-line and off-line curves was the in-line measuring position. By adjusting the position of the NIR probe to the bottom of the feed frame instead of at the top of the feed frame, a perfect alignment between in-line and off-line concentration curves was acquired. In-line measurements at the bottom of the feed frame could, if optimisation to avoid probe fouling is possible, be ideal for real-time measurement and control of the blend concentration during tableting. When probe fouling cannot be avoided, the correlation between the in-line measured concentration at the top of the feed frame and the concentration of the produced tablets should be investigated and modelled to enable real-time measurement and control based on in-line measurements. [ABSTRACT FROM AUTHOR]

Highlights • The residence time distribution of the gas in the pyrolysis plant was studied. • The E curves have been determined for the pyrolysis plant. • Two models have been proposed to simulate the gas flow pattern. • The flow model has been coupled with the kinetic one to study pyrolysis kinetics. Abstract A novel strategy has been proposed for the rigorous kinetic modeling of tyre pyrolysis in a conical spouted bed reactor. A kinetic model coupled with a gas flow model was used in the fitting of experimental results obtained in a bench scale unit in the 425–610 °C range. A gas flow model should be incorporated to account for the delay and mixing phenomena observed in tracer experiments, as these phenomena cause remarkable deviations in the assessment of the kinetic parameters. The gas flow pattern from the reactor to the measuring device was modeled using two different approaches based on ideal flow reactors. Furthermore, two kinetic schemes considering lumped products have been proposed; the first one is based on four parallel independent reactions accounting for the volatile products (gas, liquid, aromatics and tar). The second one considers an additional secondary reaction of aromatic formation from the liquid. The strategy proposed for coupling the kinetics and the flow model led to a suitable fitting of the experimental results, with the performance of the model considering a secondary reaction being slightly better than the simple one. [ABSTRACT FROM AUTHOR]

A standardised hydrocyclone is examined as an alternative reactor for the electrochemical processing of two-phase systems. Experimental measurements and computational predictions of residence time distributions demonstrate an appropriate hydrodynamics of the equipment. A main peak near the mean residence time was detected revealing that a fluid by-pass or dead regions are absent and the Peclet number, obtained by correlation of the experimental data, was higher than 9. Mass-transfer measurements made by using a segmented, or a grooved or a smooth cathode corroborate the good performance of the cylindrical body of the hydrocyclone. The presence of the gas phase has little influence on the residence time distribution as well as on the mass-transfer behaviour of this device. Sulphur dioxide reduction to colloidal sulphur was used as a test reaction to check the performance of the reactor. The best results were obtained at a cathodic potential of −0.5 V, against a saturated calomel electrode, where hydrogen evolution is not possible as a cathodic side reaction. Thus, a 56% current efficiency with a specific energy consumption of 20.4 kWh kg−1 and a space time yield of 10.4 kg m−3 h−1 were attained under a two-phase flow of 5% SO 2 in nitrogen. The sulphur particles obtained from the spigot present an average size of 6.7 μm being those carried by the overflow stream smaller, both of them of high purity. • The hydrocyclone has high mass-transfer conditions under single- or two-phase flow. • The reaction performance of the cylindrical part is better than in the conical section. • A modified hydrocyclone is suitable for electrochemical processing of two-phase systems. [ABSTRACT FROM AUTHOR]

In the present study, residence time distribution measurements were carried out in an industrial-scale ethyl acetate reactors using Bromine-82 as radiotracer. The process fluid is re-circulated into the reactor at a high flow instead of mechanical agitation inside the reactor to facilitate the mixing. The objective of the study was to measure the effect of recirculation rate on the mean residence time and flow pattern process of material in the reactor. The results showed that recirculation significantly affects the flow characteristics and mean residence time of the reactors. A bypass stream and stagnant fluid zones present in the system and their fraction affected by recirculation in both the reactors. [ABSTRACT FROM AUTHOR]

Abstract The distribution and volume fraction of the dead zones in the shell side of the trefoil-baffle heat exchanger were studied, and a structure optimization was presented to improve flow condition. By applying the residence time distribution method, the dead zones were analyzed quantitatively, and it is found that the volume fraction of dead zone is about 28% in the shell side of the trefoil-baffle heat exchanger, which is larger by about 13% than that in the shell side of the segmental baffle heat exchanger. According to the velocity contours in the shell side, the magnitude of the fluid velocity in the main flow region is much larger than that near wall, and the fluid near the shell wall flows in much slower velocity. The dead zones mainly distribute near the walls of shell and baffles. Another study was carried out adopting the unit duct model without concerning the influence of the shell wall, and it is shown that the volume fraction of the dead zone is less than 0.5%. It is concluded that the main dead zone in the shell side is near the wall of the shell. To reduce the main dead zone, an optimized structure of tube layout was presented, and it is found that the volume fraction of dead zone reduced by about 13% at the different flow rates. The methods and conclusions provide a reference for analysis of dead zone and structure improvement of heat exchangers. Highlights • Flow dead zones in TBHE and SBHE were analyzed by adopting the RTD method. • Volume fraction of dead zone in TBHE is about 28% and larger than that in SBHE. • The dead zones in TBHE distribute mainly near the shell wall. • An optimized structure was presented to reduce dead zone by about 13%. • The numerical results were verified by a fluid velocity test using LDV. [ABSTRACT FROM AUTHOR]

Over the recent decade, benefits of continuous manufacturing (CM) of pharmaceutical products have been acknowledged widely. In contrast to batch processes, the product is not physically separated into batches in CM, which creates a few challenges. Product release is done for batches that should have a uniform quality over time, materials need to be tracked along the line, and locations to reject product must be established. To enable these, the residence time distributions (RTDs) of all unit operations must be known. In this paper, three CM tableting lines, each employing a different granulation technique, were investigated. The RTDs of their main unit operations were characterized, utilizing different measurement techniques successfully. All of these RTD measurement techniques could have been performed in any of the lines. The differences were related to the techniques themselves. Overall, external tracer with in-line Near-Infrared detection or color tracer with video recording proved most usable techniques, with few limitations. The RTDs for full lines were calculated by convoluting the unit operation RTDs, which enables material tracking through entire lines. The lines exhibited both truly continuous and quasi-continuous unit operations. Quasi-continuous unit operations divide the material stream into lots that can be utilized for tracking and rejection. [ABSTRACT FROM AUTHOR]

Constructed wetlands (CWs) are used for the treatment of wastewater by natural processes. Knowledge of the flow dynamics of wastewater through the CWs is required to evaluate their performance, operation and design. The residence time distribution (RTD) approach was used to evaluate the above-mentioned parameters in a CW. The RTD of wastewater flowing through a pilot-scale CW was measured using Technetium-99 m (99mTc) as a radiotracer. The measured data were analyzed, and mean residence time and stagnant volumes were quantified under different operating conditions. A plug flow component in series along with a tank-in-series model with an exchange between the active and dead zones was used to simulate the measured RTD curves and investigate the flow dynamics of the flowing wastewater. The results of the study showed that the optimum flow rate and wastewater level in the CW was 2.3 m3/s and 0.6 m, respectively. Moreover, the results of the study will help in the operation and design of the existing wetland and design of new wetlands. • RTD measurements were carried out in a CW using the radiotracer technique. • Technetium-99 m as sodium pertechnetate was used as the radiotracer. • Flow fractions across different transacts of the wetland were estimated. • Mean residence time, dead volume, and hydraulic efficiency were quantified. • A model was conceptualized and used to simulate the experimental data. [ABSTRACT FROM AUTHOR]

The ideal plug flow reactor is a common model with narrow residence time distribution in reaction engineering. This contribution explains a design strategy of a coiled flow inverter (CFI) with narrow residence time and flexible adjustable process conditions. The design space diagram illustrates the design limits of inner diameter and coil diameter on the base of dimensionless numbers. Standard coil tube diameters allow for rational design of a limited number of devices. The reactor performance diagram enables the facile scale‐up and adaption of new process conditions with the CFI with economic boundary conditions. [ABSTRACT FROM AUTHOR]

One of the biggest advantages of plug flow reactors lies in their narrow residence time distribution. The pulse experiment, as a common method on acquiring that distribution, relies on the tracer injection being a perfect pulse. A deviation from a perfect pulse leads to erroneous results if not taken into account. With a numerical analysis of experimental data, this effect is quantified in turbulent and laminar flow regime and the results are compared to an analytical method. Significant deviations occur mostly in the turbulent regime, which has the greatest technical relevance. [ABSTRACT FROM AUTHOR]

Extrusion is an inexpensive process in terms of production costs used to produce continuous shapes of plastic materials. The mixture design method and regression analysis have been applied to evaluate the performance of the single screw extruder. The performance values of the single-screw extruder system with a glass barrel are calculated by the residence time distribution results of the tracers. Then calculated particle distributions are compared with visual data. Ethylene vinyl acetate (EVA 210W) is used as the polymeric material. In the study, the EVA 210W is studied with various screw configurations and also process conditions. Optimization is fulfilled using the response optimizer to determine the optimum screw configuration. This method is aimed at feeding and metering zones in screw design and focuses on the search for a solution for optimum screw selection. In addition, the robustness of solutions in process conditions has been redefined. [ABSTRACT FROM AUTHOR]