The interplay between nucleation and patterning during shear-induced crystallization from solution in a parallel plate geometry.

Cooling crystallization of small organic molecules from solution is an important operation for the separation and purification of drug products. In this research, shear-induced nucleation from a supersaturated solution is studied in a parallel plate geometry. Under conditions of shear and small gap sizes, narrow mesoscale circular bands of small crystals appeared spontaneously and reproducibly on the plate's surface. We have investigated the connection between nucleation and the emergence of these circular patterns. Our results show that nucleation occurs preferably in zones with high local shear rate (located at the outer edges of the plates), compared to zones with low local shear rate (at the center of the plates). The time before nucleation occurs decreases significantly for increasing mean shear rate and time. The circular crystalline patterns appear at the plate's surface, where heterogeneous nucleation first occurs. Multiple hypotheses are explored to understand the pattern formation in crystallization. Since no satisfactory explanation is found, a new mechanism is proposed. This hypothesis involves crystals initially forming on the surface of the plates and undergoing stick-slip motion, which influences the local nucleation kinetics. This results in an interplay between (secondary) nucleation and stick-slip motion at the start of the crystallization process. By modifying the surface of the plates, their ability to act as a heterogeneous nucleation site can be altered, allowing control over the formation of patterns.

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors.

Photochemical activation routes are gaining the attention of the scientific community since they can offer an alternative to the traditional chemical industry that mainly utilizes thermochemical activation of molecules. Photoreactions are fast and selective, which would potentially reduce the downstream costs significantly if the process is optimized properly. With the transition towards green chemistry, the traditional batch photoreactor operation is becoming abundant in this field. Process intensification efforts led to micro- and mesostructured flow photoreactors. In this work, we are reviewing structured photoreactors by elaborating on the bottleneck of this field: the development of an efficient scale-up strategy. In line with this, micro- and mesostructured bench-scale photoreactors were evaluated based on a new benchmark called photochemical space time yield (mol·day-1·kW-1), which takes into account the energy efficiency of the photoreactors. It was manifested that along with the selection of the photoreactor dimensions and an appropriate light source, optimization of the process conditions, such as the residence time and the concentration of the photoactive molecule is also crucial for an efficient photoreactor operation. In this paper, we are aiming to give a comprehensive understanding for scale-up strategies by benchmarking selected photoreactors and by discussing transport phenomena in several other photoreactors.

Microbubbles as Heterogeneous Nucleation Sites for Crystallization in Continuous Microfluidic Devices.

Injecting a stream of microbubbles and thereby introducing a heterogeneous interface is proposed for enhancing nucleation and controlling particle formation in continuous microfluidic devices. Different gas and liquid flow rates were investigated to establish the two-phase flow regime map and to identify the optimum characteristics for microbubble flow. Subsequently, the effect of microbubbles was studied for the cooling crystallization of paracetamol. An enhanced nucleation rate compared to that in the operation without bubbles was observed and the presence of microbubbles results in the formation of more crystals, which indicates that nucleation is faster than that in operation without bubbles, i.e., the metastable zone width is reduced. Determining the crystal yield confirmed that a larger mass of crystals is obtained in a two-phase flow with microbubbles. Furthermore, results showed that the presence of microbubbles allows crystallizing continuously without clogging of the microreactor.

3D printing in chemical engineering and catalytic technology: structured catalysts, mixers and reactors.

Computer-aided fabrication technologies combined with simulation and data processing approaches are changing our way of manufacturing and designing functional objects. Also in the field of catalytic technology and chemical engineering the impact of additive manufacturing, also referred to as 3D printing, is steadily increasing thanks to a rapidly decreasing equipment threshold. Although still in an early stage, the rapid and seamless transition between digital data and physical objects enabled by these fabrication tools will benefit both research and manufacture of reactors and structured catalysts. Additive manufacturing closes the gap between theory and experiment, by enabling accurate fabrication of geometries optimized through computational fluid dynamics and the experimental evaluation of their properties. This review highlights the research using 3D printing and computational modeling as digital tools for the design and fabrication of reactors and structured catalysts. The goal of this contribution is to stimulate interactions at the crossroads of chemistry and materials science on the one hand and digital fabrication and computational modeling on the other.

Development of a continuous reactor for emulsion-based microencapsulation of hexyl acetate with a polyuria shell.

Microencapsulation is almost exclusively performed in batch processes. With today's chemistry increasingly performed in flow reactors, this work aims to realise a continuous reactor setup for the encapsulation of an ester with a polyuria (PU) shell. The generation of an emulsion template is performed in a recirculation loop driven by a pump and equipped with static mixers, screen type and Kenics®. Calorimetric measurements are performed to characterise the energy dissipation rate inside the loop. The curing step is performed in a coiled tube reactor with two geometric configurations. Number based capsule size distributions are derived from micrograph analysis. Results indicate that the recycle pump is the main contributor to determine the capsule size distribution. A continuous setup is achieved for PU microcapsules containing hexyl acetate with a production rate of 198 g/h dry capsules, and a mean capsule diameter of 13.3 µm with a core content of 54 wt%.

Copper-Catalyzed Continuous-Flow Transfer Hydrogenation of Nitroarenes to Anilines: A Scalable and Reliable Protocol.

A robust supported catalyst that is made up of copper nanoparticles on Celite has been successfully prepared for the selective transfer hydrogenation of aromatic nitrobenzenes to anilines under continuous flow. The method is efficient and environmentally benign thanks to the absence of hydrogen gas and precious metals. Long-term stability studies show that the catalytic system is able to achieve very high nitrobenzene conversion (>99%) when working for up to 145 h. The versatility of the transfer hydrogenation system has been tested using representative examples of nitroarenes, with moderate-to-excellent yields being obtained. The packed bed reactor (PBR) permits the use of a setup that can provide products via simple isolation by SPE without the need for further purification. The recovery and reuse of either EG or the ion-exchange resin leads to consistent waste reduction; therefore, E-factor distribution analysis has highlighted the environmental efficiency of this synthetic protocol.

Homogeneous and isotropic cosmology in general teleparallel gravity.

We derive the most general homogeneous and isotropic teleparallel geometries, defined by a metric and a flat, affine connection. We find that there are five branches of connection solutions, which are connected via several limits, and can further be restricted to the torsion-free and metric-compatible cases. We apply our results to several classes of general teleparallel gravity theories and derive their cosmological dynamics for all five branches. Our results show that for large subclasses of these theories the dynamics reduce to that of closely related metric or symmetric teleparallel gravity theories, while for other subclasses up to two new scalar degrees of freedom participate in the cosmological dynamics.

Process intensification of continuous-flow seATRP by a sonicated multi-reactor setup.

Simplified electrochemically mediated atom transfer radical polymerization (seATRP) is a versatile technique for synthesizing polymers with precise control and complex architecture. Continuous-flow seATRP has recently been realized by using a sonicated microreactor but still faces limitations such as relatively low conversion and difficulties in synthesizing polymers with high molecular weight. Herein, a novel multi-reactor setup is demonstrated. By tuning the currents applied to different reaction stages in the setup, 90% conversion can be achieved while maintaining relatively low dispersity (<1.35). Meanwhile, the unique design enables a wider processing window for sonication due to greater viscous attenuation in the second reactor, thus largely addressing the problem associated with high viscosity during the synthesis of high molecular weight polymers. The developed setup also offers an alternative strategy for future scale-up of continuous-flow seATRP.

Emulsification mechanism in an ultrasonic microreactor: Influence of surface roughness and ultrasound frequency.

An ultrasonic microreactor with rough microchannels is presented in this study for oil-in-water (O/W) emulsion generation. Previous accounts have shown that surface pits or imperfections localize and enhance cavitation activity. In this study cavitation bubbles are localized on the rough microchannels of a borosilicate glass microreactor. The cavitation bubbles in the microchannel are primarily responsible for emulsification in the ultrasonic microreactor. We investigate the emulsification mechanism in the rough microchannels employing high-speed imaging to reveal the different emulsification modes influenced by the size and oscillation intensity of the cavitation bubbles. The effect of emulsification modes on the O/W emulsion droplet size distribution for different surface roughness and frequency is demonstrated. The positive effect of the frequency on minimizing the droplet size utilizing a reactor with large pits is presented. We also demonstrate microreactor systems for a successful generation of miniemulsions with high dispersed phase volume fractions up to 20%. The observed emulsification mechanism in the rough microchannel offers new insights into the utility and scale-up of ultrasonic microreactors for emulsification.

Continuous generation of cross-linked polymer nanoparticles employing an ultrasonic microreactor.

In this article, a new system employing an ultrasonic microreactor coupled with a tubular reactor is presented for the continuous generation of polymer nanoparticles. The continuous generation of cross-linked polymer nanoparticles utilizing the monomer butyl methacrylate and the cross-linker ethylene glycol dimethacrylate is demonstrated. Firstly, the miniemulsion polymerization of a monomer-in-water miniemulsion is studied in a batch system. Secondly, a coiled tubular reactor is employed for the continuous polymerization of the miniemulsion generated by an ultrasonic microreactor. Finally, the influence of monomer volume fraction and surfactant concentration on the synthesized polymer nanoparticles is studied. Polymer particles in a size range of 50-250 nm are synthesized and a high polymerization conversion is achieved utilizing the system demonstrated in this article.

Analysis of dynamic acoustic resonance effects in a sonicated gas-liquid flow microreactor.

In this work, we characterize acoustic resonance phenomena occurring between gas bubbles in a segmented gas-liquid flow in a microchannel irradiated with a frequency around 500 kHz. A large acoustic amplitude can be reached, leading to gas-liquid interface deformation, atomization of micrometer sized droplets, and cavitation. A numerical approach combining an acoustic frequency-domain solver and a Lagrangian Surface-Evolver solver is introduced to predict the acoustic deformation of gas-liquid interfaces and the dynamic acoustic magnitude. The numerical approach and its assumptions were validated with experiments, for which a good agreement was observed. Therefore, this numerical approach allows to provide a description and an understanding of the acoustic nature of these phenomena. The acoustic pressure magnitude can reach hundreds of kPa to tens of MPa, and these values are consistent with the observation of atomization and cavitation in the experiments. Furthermore, volume of fluid simulations were performed to predict the atomization threshold, which was then related to acoustic resonance. It is found that dynamic acoustic resonance gives rise to atomization bursts at the gas bubble surface. The presented approach can be applied to more complex acoustic fields involving more complex channel geometries, vibration patterns, or two-phase flow patterns.

Heterogeneous photochemical reaction enabled by an ultrasonic microreactor.

The presence of solids as starting reagents/reactants or products in flow photochemical reactions can lead to reactor clogging and yield reduction from side reactions. We address this limitation with a new ultrasonic microreactor for continuous solid-laden photochemical reactions. The ultrasonic photochemical microreactor is characterized by the liquid and solid residence time distribution (RTD) and the absorbed photon flux in the reactor via chemical actinometry. The solid-handling capability of the ultrasonic photochemical microreactor is demonstrated with a silyl radical-mediated metallaphotoredox cross-electrophile coupling with a solid base as a reagent.

Improved accuracy and precision of fat-suppressed isotropic 3D T2 mapping MRI of the knee with dictionary fitting and patch-based denoising.

PURPOSE: To develop an isotropic three-dimensional (3D) T2 mapping technique for the quantitative assessment of the composition of knee cartilage with high accuracy and precision. METHODS: A T2-prepared water-selective isotropic 3D gradient-echo pulse sequence was used to generate four images at 3 T. These were used for three T2 map reconstructions: standard images with an analytical T2 fit (AnT2Fit); standard images with a dictionary-based T2 fit (DictT2Fit); and patch-based-denoised images with a dictionary-based T2 fit (DenDictT2Fit). The accuracy of the three techniques was first optimized in a phantom study against spin-echo imaging, after which knee cartilage T2 values and coefficients of variation (CoV) were assessed in ten subjects in order to establish accuracy and precision in vivo. Data given as mean ± standard deviation. RESULTS: After optimization in the phantom, whole-knee cartilage T2 values of the healthy volunteers were 26.6 ± 1.6 ms (AnT2Fit), 42.8 ± 1.8 ms (DictT2Fit, p < 0.001 versus AnT2Fit), and 40.4 ± 1.7 ms (DenDictT2Fit, p = 0.009 versus DictT2Fit). The whole-knee T2 CoV reduced from 51.5% ± 5.6% to 30.5 ± 2.4 and finally to 13.1 ± 1.3%, respectively (p < 0.001 between all). The DictT2Fit improved the data reconstruction time: 48.7 ± 11.3 min (AnT2Fit) versus 7.3 ± 0.7 min (DictT2Fit, p < 0.001). Very small focal lesions were observed in maps generated with DenDictT2Fit. CONCLUSIONS: Improved accuracy and precision for isotropic 3D T2 mapping of knee cartilage were demonstrated by using patch-based image denoising and dictionary-based reconstruction. KEY POINTS: • Dictionary T2 fitting improves the accuracy of three-dimensional (3D) knee T2 mapping. • Patch-based denoising results in high precision in 3D knee T2 mapping. • Isotropic 3D knee T2 mapping enables the visualization of small anatomical details.

Encapsulation of Cadmium-Free InP/ZnSe/ZnS Quantum Dots in Poly(LMA-co-EGDMA) Microparticles via Co-flow Droplet Microfluidics.

Quantum dots (QDs) are semiconductor nanocrystals that are used in optoelectronic applications. Most modern QDs are based on toxic metals, for example Cd, and do not comply with the European Restriction of Hazardous Substances regulation of the European Union. Latest promising developments focus on safer QD alternatives based on elements from the III-V group. However, the InP-based QDs lack an overall photostability under environmental influences. One design path of achieving stability is through encapsulation in cross-linked polymer matrices with the possibility to covalently link the matrix to surface ligands of modified core-shell QDs. The work focuses on the formation of polymer microbeads suitable for InP-based QD encapsulation, allowing for an individual protection of QDs and an improved processibility via this particle-based approach. For this, a microfluidic based method in the co-flow regime is used that consists of an oil-in-water droplet system in a glass capillary environment. The generated monomer droplets are polymerized in-flow into poly(LMA-co-EGDMA) microparticles with embedded InP/ZnSe/ZnS QDs using a UV initiation. They demonstrate how a successful polymer microparticle formation via droplet microfluidics produces optimized matrix structures leading to a distinct photostability improvement of InP-based QDs compared to nonprotected QDs.

Size-controlled flow synthesis of gold nanoparticles using a segmented flow microfluidic platform.

Segmented flow is often used in the synthesis of nanomaterials to achieve narrow particle size distribution. The narrowness of the distribution is commonly attributed to the reduced dispersion associated with segmented flows. On the basis of the analysis of flow fields and the resulting particle size distribution, we demonstrate that it is the slip velocity between the two fluids and internal mixing in the continuous-phase slugs that govern the nature of the particle size distribution. The reduction in the axial dispersion has less impact on particle growth and hence on the particle size distribution. Synthesis of gold nanoparticles from HAuCl(4) with rapid reduction by NaBH(4) serves as a model system. Rapid reduction yields gold nuclei, which grow by agglomeration, and it is controlled by the interaction of the nuclei with local flow. Thus, the difference in the physical properties of the two phases and the inlet flow rates ultimately control the particle growth. Hence, a careful choice of continuous and dispersed phases is necessary to control the nanoparticle size and size distribution.

Continuous-flow self-supported seATRP using a sonicated microreactor.

Continuous-flow simplified electrochemically mediated atom transfer radical polymerization (seATRP) was achieved for the first time without supporting electrolytes (self-supported) using a novel sonicated tubular microreactor. Polymerizations of different acrylic monomers were carried out under different applied currents. The reaction was fast with 75% conversion achieved at ambient temperature in less than 27 minutes. Results also showed good evolution of molecular weight and maintained narrow molecular weight distribution. The reaction rate can be further manipulated by tuning the applied current. Sonication under proper conditions was found to be able to significantly improve both reaction rate and controllability. Self-supported reactions also enable more environmentally friendly and cost-effective operations.

Teflon-coated silicon microreactors: impact on segmented liquid-liquid multiphase flows.

We describe fluoropolymer modification of silicon microreactors for control of wetting properties in chemical synthesis applications and characterize the impact of the coating on liquid-liquid multiphase flows of solvents and water. Annular flow of nitrogen gas and a Teflon AF (DuPont) dispersion enable controlled evaporation of fluoropolymer solvent, which in turn brings about three-dimensional polymer deposition on microchannel walls. Consequently, the wetting behavior is switched from hydrophilic to hydrophobic. Analysis of microreactors reveals that the polymer layer thickness increases down the length of the reactor from ∼1 to ∼13 µm with an average thickness of ∼7 µm. Similarly, we show that microreactor surfaces can be modified with poly(tetrafluoroethylene) (PTFE). These PTFE-coated microreactors are further characterized by measuring residence time distributions in segmented liquid-liquid multiphase flows, which display reduced axial dispersion for the coated microreactors. Applying particle image velocimetry, changes in segment shape and velocity fluctuations are observed resulting in reduced axial dispersion. Furthermore, the segment size distribution is narrowed for the hydrophobic microreactors, enabling further control of residence distributions for synthesis and screening applications.

Acoustic resonance and atomization for gas-liquid systems in microreactors.

It is shown that a liquid slug in gas-liquid segmented flow in microchannels can act as an acoustic resonator to disperse large amounts of small liquid droplets, commonly referred to as atomization, into the gas phase. We investigate the principles of acoustic resonance within a liquid slug through experimental analysis and numerical simulation. A mechanism of atomization in the confined channels and a hypothesis based on high-speed image analysis that links acoustic resonance within a liquid slug with the observed atomization is proposed. The observed phenomenon provides a novel source of confined micro sprays and could be an avenue, amongst others, to overcome mass transfer limitations for gas-liquid processes in flow.

Micro-patterned membranes prepared via modified phase inversion: Effect of modified interface on water fluxes and organic fouling.

The introduction of patterns on a membrane-solute interface has been suggested as an effective method to tackle the reduced flux and fouling issues. Herein, the effectiveness of using spray-modified non-solvent induced phase separation (s-NIPS) to create a variety of micrometer-level structured interfaces is now studied. Circular, triangular and rectangular patterns with different dimensions were successfully created on polyacrylonitrile membranes. The rectangular pattern height was varied from 500 to 1500 µm, which resulted in a proportional increase in clean water permeance from 590 ± 47 L m-2 h-1 bar-1 to 1345 ± 108 L m-2 h-1 bar-1 respectively. This coincided with some BSA rejection loss for the highest patterns, indicating the fragile nature of these tall features. No significant rejection losses were found for the smaller pattern heights (145-250 µm) as compared to flat membranes, while fluxes more than doubled still. The critical pressure was also increased substantially for patterned membranes and showed a proportionality with the pattern height. These experimental findings were correlated with the reduced foulant adhesion due to a shear-induced slip boundary layer at the membrane-solution interface. Computational fluid dynamics simulations further showed higher shear stress values due to flow constriction within the membrane's valley regions. These findings indicate the high potential of s-NIPS patterned membranes in long-term industrial applications by requiring less membrane area for a given application and reducing cleaning interventions.

Synergistic effects of the alternating application of low and high frequency ultrasound for particle synthesis in microreactors.

Ultrasound (US) is a promising method to address clogging and mixing issues in microreactors (MR). So far, low frequency US (LFUS), pulsed LFUS and high frequency US (HFUS) have been used independently in MR for particle synthesis to achieve narrow particle size distributions (PSD). In this work, we critically assess the advantages and disadvantages of each US application method for the case study of calcium carbonate synthesis in an ultrasonic microreactor (USMR) setup operating at both LFUS (61.7 kHz, 8 W) and HFUS (1.24 MHz, 1.6 W). Furthermore, we have developed a novel approach to switch between LFUS and HFUS in an alternating manner, allowing us to quantify the synergistic effect of performing particle synthesis under two different US conditions. The reactor was fabricated by gluing a piezoelectric plate transducer to a silicon microfluidic chip. The results show that independently applying HFUS and LFUS produces a narrower PSD compared to silent conditions. However, at lower flow rates HFUS leads to agglomerate formation, while the reaction conversion is not enhanced due to weak mixing effects. LFUS on the other hand eliminates particle agglomerates and increases the conversion due to the strong cavitation effect. However, the required larger power input leads to a steep temperature rise in the reactor and the risk of reactor damage for long-term operation. While pulsed LFUS reduces the temperature rise, this application mode leads again to the formation of particle agglomerates, especially at low LFUS percentage. The proposed application mode of switching between LFUS and HFUS is proven to combine the advantages of both LFUS and HFUS, and results in particles with a unimodal narrow PSD (one order of magnitude reduction in the average size and span compared to silent conditions) and negligible rise of the reactor temperature.