Capillary Reactor Research Articles

The interplay of irradiated- and shaded zones in photoreactor scale-up

Photochemical processes enable highly-selective synthesis routes under mild reaction conditions. Yet, photoreactions are seldom implemented on industrial scale. One of the main challenges is the exponential light attenuation with increasing optical depth. As a result, few photons are available at positions far from the light source, leading to shaded zones of low reactivity. To study the effect of shaded zones, a compartment photoreactor model is presented and used for optimization of the reaction conditions, in particular during scale-up. Using photooxidation in a Taylor-flow capillary reactor as a benchmark case, the photosensitizer concentration, the light intensity and liquid mixing are identified as the key parameters for the formation and impact of shaded zones on reactor performance. It is shown that shading reduces the conversion already on lab-scale by up to 13% for operating conditions with high photosensitizer concentration and light intensity. In an upscaled reactor, intensified liquid mixing leads to an up to 4.3-fold increase in conversion

Visible‐Light‐Induced Diastereoselective Cascade Cyclization to Construct Polycyclic Spiroindolines

AbstractWe herein reported, a visible‐light‐induced K2S2O8 mediated cascade reaction of 3‐(2‐isocyanoethyl)indoles with α‐oxocarboxylic acids leading to diastereoselective synthesis of polycyclic spiroindolines bearing an N‐formyl unit derivative utilising the alkali metal salt K2S2O8 as a mediator under mild reaction conditions. This study offers an illustration of α‐oxocarboxylic acids and 3‐(2‐isocyanoethyl)indoles‐based reactions as it shows the involvement of glyoxolate ions without decarboxylation to access polycyclic spiroindolines bearing an N‐formyl unit analogue. The batch process can be extended to a continuous flow system using a glass tube loaded with K2S2O8 placed between the PFA capillary reactor, which can greatly advance the reaction efficiency and can even be promoted to gram‐scale synthesis.

Kinetic verification and Comsol modeling of the Diels-Alder reaction of conjugated pentadiene with maleic anhydride in a continuous flow capillary reactor

Synthesis of 3/4-methyltetrahydrophthalic anhydride was carried out by the Diels-Alder reaction in a continuous flow capillary reactor. The efficient liquid–liquid reaction of pentadiene with molten maleic anhydride provided a theoretical basis for replacing the conventional batch reaction process. Different inner diameter sizes of the channel tubes were adjusted in the range of 0.50 ∼ 2.00 mm to find the optimal size to match the strong exothermic reaction. Under the capillary channel size of 0.8 mm, the conversion rate of C5 and MA reached 100 % when nC5: nMA = 1.08:1 at 65 °C for 8 min. The D-A reaction process is accompanied by the autopolymerization of diolefin in the batch reactor. Our results showed that choosing a continuous flow capillary reactor of appropriate size can directly improve the selectivity of the reaction and the quality of the product. The accurate reaction rate constant and activation energy were obtained by establishing a kinetic model, and the effects of temperature, reaction time and pipe diameter were designed using Comsol software.

In‐situ experimental study on the hydrolysis and pyrolysis processes of polylactic acid

AbstractIn order to better understand the hydrolysis and pyrolysis process of polylactic acid (PLA), we carried out in‐situ experiments by observing the decomposition process of PLA at high temperature (up to 285°C) in both aqueous and anhydrous environments through fused silica capillary reactor (FSCR) combined with Raman spectroscopy analysis. By analyzing the strength change of characteristic peaks of PLA with increasing temperature, it was found that the initial melting temperature of PLA, in both the hydrolysis and pyrolysis processes, is around 170°C. Based on infrared spectroscopy analysis, it was found that the products of PLA pyrolysis are CO2, CH3CHCO, and CH3CHO, indicating that the pyrolysis process of PLA results from a free radical reaction. By comparing the Raman peak area ratios at different peak positions at different temperatures, it was found that the hydrolysis process of PLA mainly involves breaking the COC and CCO bonds of PLA, producing lactic acid, ethanol, CO2, and H2O. The hydrolysis reaction rate of PLA increases with the increase of temperature and exhibits a slow‐fast‐slow S‐shaped trend. The kinetic process of hydrolysis of PLA was well described using the Logistic model. The activation energy for the hydrolysis (Q) of PLA is 18.1 kcal∙mol−1 in the temperature range of 250–285°C. The results of this study provide important insights and crucial parameters for the production and application of PLA.

Enhancement of liquid–liquid micromixing performance in curved capillary microreactor by generation of Dean vortices

Micromixing efficiency is an important parameter for evaluating the multiphase mass transfer performance and reaction efficiency of microreactor. In this work, the novel curved capillary reactor with different shapes were designed to generate Dean flow, which was used to enhance the liquid–liquid micromixing performance. The Villermaux–Dushman probe reaction was employed to characterize the micromixing performance in different curved cpillary microreactor. The effects of experiment parameters such as liquid flow rate, inner diameter, tube length, and curve diameter on micromixing performance were systematically investigated. Under the optimal condition, the minimum value of the segmentation factor XS was 0.008. It was worth noting that at the low Reynolds number (Re < 30), the change of curved shape on capillary microreactor can significantly improve the micromixing performance with XS reduced by 37.5%. Further, the correlations of segment index XS with dimensionless factor as Reynolds number or Dean number were developed, which can be used to predict the liquid–liquid micromixing performance in capillary microreactor.

Cu/TiO2 Photo-catalyzed CO2 Chemical Reduction in a Multiphase Capillary Reactor

Cu/TiO2 Photo-catalyzed CO2 Chemical Reduction in a Multiphase Capillary Reactor

Evaluating scaling of capillary photo-biofilm reactors for high cell density cultivation of mixed trophies artificial microbial consortia.

Capillary biofilm reactors (CBRs) are attractive for growing photoautotrophic bacteria as they allow high cell-density cultivation. Here, we evaluated the CBR system's suitability to grow an artificial consortium composed of Synechocystis sp. PCC 6803 and Pseudomonas sp. VBL120. The impact of reactor material, flow rate, pH, O2, and medium composition on biomass development and long-term biofilm stability at different reactor scales was studied. Silicone was superior over other materials like glass or PVC due to its excellent O2 permeability. High flow rates of 520μLmin-1 prevented biofilm sloughing in 1m capillary reactors, leading to a 54% higher biomass dry weight combined with the lowest O2 concentration inside the reactor compared to standard operating conditions. Further increase in reactor length to 5m revealed a limitation in trace elements. Increasing trace elements by a factor of five allowed for complete surface coverage with a biomass dry weight of 36.8gm-2 and, thus, a successful CBR scale-up by a factor of 25. Practical application: Cyanobacteria use light energy to upgrade CO2, thereby holding the potential for carbon-neutral production processes. One of the persisting challenges is low cell density due to light limitations and O2 accumulation often occurring in established flat panel or tubular photobioreactors. Compared to planktonic cultures, much higher cell densities (factor 10 to 100) can be obtained in cyanobacterial biofilms. The capillary biofilm reactor (CBR) offers good growth conditions for cyanobacterial biofilms, but its applicability has been shown only on the laboratory scale. Here, a first scale-up study based on sizing up was performed, testing the feasibility of this system for large-scale applications. We demonstrate that by optimizing nutrient supply and flow conditions, the system could be enlarged by factor 25 by enhancing the length of the reactor. This reactor concept, combined with cyanobacterial biofilms and numbering up, holds the potential to be applied as a flexible, carbon-neutral production platform for value-added compounds.

Spatial organization and proteome of a dual-species cyanobacterial biofilm alter among N2-fixing and non-fixing conditions.

Many disciplines have become increasingly interested in cyanobacteria, due to their ability to fix CO2 while using water and sunlight as electron and energy sources. Further, several species of cyanobacteria are also capable of fixing molecular nitrogen, making them independent of the addition of nitrate or ammonia. Thereby they hold huge potential as sustainable biocatalysts. Here, we look into a dual-species biofilm consisting of filamentous diazotrophic cyanobacteria Tolypothrix sp. PCC 7712 and heterotrophic bacteria Pseudomonas taiwanensis VLB 120 growing in a capillary biofilm reactor. Such systems have been reported to enable high cell densities continuous process operation. By combining confocal laser scanning and helium-ion microscopy with a proteomics approach, we examined these organisms' interactions under two nitrogen-feeding strategies: N2-fixing and nitrate assimilation. Not only did Pseudomonas facilitate the biofilm formation by forming a carpet layer on the surface area but also did N2-fixing biofilms show greater attachment to the surface. Pseudomonas proteins related to surface and cell attachments were observed in N2-fixing biofilms in particular. Furthermore, co-localized biofilm cells displayed a resilient response to extra shear forces induced by segmented media/air flows. This study highlights the role of Pseudomonas in the initial attachment process, as well as the effects of different nitrogen-feeding strategies and operation regimes on biofilm composition and growth. IMPORTANCE Cyanobacteria are highly interesting microorganisms due to their ability to synthesize sugars from CO2 while using water and sunlight as electron and energy sources. Further, many species are also capable of utilizing molecular nitrogen, making them independent of artificial fertilizers. In this study, such organisms are cultivated in a technical system, which enables them to attach to the reactor surface, and form three-dimensional structures termed biofilms. Biofilms achieve extraordinarily high cell densities. Furthermore, this growth format allows for continuous processing, both being essential features in biotechnological process development. Understanding biofilm growth and the influence technical settings and media composition have on biofilm maturation and stability are crucial for reaction and reactor design. These findings will help to open up these fascinating organisms for applications as sustainable, resource-efficient industrial workhorses.

Wall Layer Formation in Continuously Operated Tubular Reactors for Free‐Radical Polymerizations

AbstractPolymer fouling is a major problem for the operation of continuous reactors. Therefore, it is important to understand and quantitatively describe the mechanisms leading to formation of fouling deposits. In this work, a CFD model for the radical polymerization of N‐vinylpyrrolidone is presented, where the reaction kinetics, a viscosity model, and a transport model for polymer moments are determined from independent experiments. The model is compared to experimental obtained residence time distributions in capillary reactors over a wide range of concentrations. Model predictions are in good agreement with experimental findings.

Kinetic aspects of iron(III)-chelation therapy with deferasirox (DFX) revealed by the solvolytic dissociation rate of the Fe(III)–DFX complex estimated with capillary electrophoretic reactor

Capillary electrophoresis was used to estimate the solvolytic dissociation rate (kd) of metal complexes of deferasirox (DFX, H3L), a drug used to treat iron overload. Inert CoIIIL23− did not dissociate. The estimated kd value for FeIIIL23− was (2.7 ± 0.3) × 10−4 s−1 (298 K, pH 7.4). The kd values of other complexes (AlIIIL23−, NiIIL24−, and MnIIL−) were in the range 10−3–10−4 s−1. In contrast, ZnIIL− and CuIIL− were too labile to allow kd estimation. The fact that the half-life of FeIIIL23− (43.3 min) is shorter than the blood half-life of DFX (8–16 h) implies that the blood concentration of DFX should be high enough to prevent dissociation of FeIIIL23−. The possibility of a safer iron-chelation therapy that avoids excretion of other essential metal ions such as ZnII is discussed, highlighting the importance of selectivity in terms of kinetic stability.

Optimization of a novel liquid phase capillary discharge plasma reactor for continuous methyl ester synthesis

Conventional transesterification processes not only require large amounts of methanol and catalysts but are also time-consuming and operate at high temperatures. Advanced methods such as non-thermal plasma have been studied for biodiesel production because they mainly reduce the temperature as well as the reaction time. In this study, a liquid-phase capillary discharge plasma reactor was developed for the continuous production of biodiesel from sunflower oil at ambient temperature and pressure. The four main operational parameters were examined each with three levels, including molar ratio (4, 6, 8), catalyst concentration (0.5, 1, 1.5 wt%), applied voltage (10, 15, 20 kV), and reactant flowrate (2, 4, 6 ml/s). The response surface method (RSM) was used to optimize FAME content. The results show that the capillary discharge reactor is possible to continuously produce 95.9 % methyl ester content (FAME- content) in a MeOH/oil molar ratio of 6.2:1, catalyst concentration of 1.2 wt%, applied voltage of 18 kV and flow rate of 4.6 ml/s. The power consumed in this process was 46.16 kJ/lit. These results indicate that the studied technology is able to continuously produce methyl ester with high conversion efficiency at low temperatures and with minimum amounts of inputs compared to common methods.

Spontaneous Phase Segregation Enabling Clogging Aversion in Continuous Flow Microfluidic Synthesis of Nanocrystals Supported on Reduced Graphene Oxide

Eliminating clogging in capillary tube reactors is critical but challenging for enabling continuous-flow microfluidic synthesis of nanoparticles. Creating immiscible segments in a microfluidic flow is a promising approach to maintaining a continuous flow in the microfluidic channel because the segments with low surface energy do not adsorb onto the internal wall of the microchannel. Herein we report the spontaneous self-agglomeration of reduced graphene oxide (rGO) nanosheets in polyol flow, which arises because the reduction of graphene oxide (GO) nanosheets by hot polyol changes the nanosheets from hydrophilic to hydrophobic. The agglomerated rGO nanosheets form immiscible solid segments in the polyol flow, realizing the liquid-solid segmented flow to enable clogging aversion in continuous-flow microfluidic synthesis. Simultaneous reduction of precursor species in hot polyol deposits nanocrystals uniformly dispersed on the rGO nanosheets even without surfactant. Cuprous oxide (Cu2O) nanocubes of varying edge lengths and ultrafine metal nanoparticles of platinum (Pt) and palladium (Pd) dispersed on rGO nanosheets have been continuously synthesized using the liquid-solid segmented flow microfluidic method, shedding light on the promise of microfluidic reactors in synthesizing functional nanomaterials.

Whole-genome sequence of the filamentous diazotrophic cyanobacterium Tolypothrix sp. PCC 7712 and its comparison with non-diazotrophic Tolypothrix sp. PCC 7601.

Cyanobacteria are highly promising microorganisms in forthcoming biotechnologies. Besides the systematic development of molecular tools for genetic engineering, the design of chassis strains and novel reactor concepts are in focus. The latter includes capillary biofilm reactors (CBR), which offer a high surface area-to-volume ratio and very high cell densities. In this context, Tolypothrix sp. PCC 7712 was found to be highly suited for this reactor system due to maximal surface coverage, extraordinarily strong biofilm attachment, and high biomass formation. Here, we provide the genome sequence of Tolypothrix sp. PCC 7712 to potentially allow targeted strain engineering. Surprisingly, it was almost identical to an available incomplete genome draft of Tolypothrix sp. PCC 7601. Thus, we completely sequenced this strain as well and compared it in detail to strain PCC 7712. Comparative genome analysis revealed 257 and 80 unique protein-coding sequences for strains PCC 7601 and PCC 7712, respectively. Clustering genomes based on average nucleotide identity (ANI) and 16S rRNA homology showed 99.98% similarity and only minor distance, respectively, between the two strains in contrast to 21 other cyanobacterial genomes. Despite these high similarities, both strains differ in the ability to fix atmospheric nitrogen and show specific sequence variations, which are discussed in the paper.

Continuous-flow synthesis of amphiphilic rhodamine B-polymethylsilsesquioxane fluorescent microspheres for micro-PIV analysis

• Rhodamine B- polymethylsilsesquioxane fluorescent microspheres were prepared. • Synthetic process was performed in a one-step continuous-flow microreaction system. • The hydrophilic and hydrophobic RhB-PMSQ microspheres were synthesized. • Amphiphilic RhB-PMSQ particles were used as tracer particles for micro-PIV analysis. Tracer particle is a key element in the micro-PIV flow field measurements. The oil-dispersible tracer particles are mainly obtained by post modification, resulting in relatively poor uniformity and dispersibility. In this work, we developed a molecular-level amphiphilic tracer particle, i.e., rhodamine B-polymethylsilsesquioxane (RhB-PMSQ) fluorescent microspheres. The RhB-PMSQ microspheres were synthesized in a continuous-flow microreaction system with the aqueous solution of NH 4 OH and RhB as the continuous phase and methyltrimethoxysilane (MTMS) as the dispersed phase. The microreaction system consisted of a T -junction micromixer, a capillary reactor for MTMS hydrolysis, and a millimeter-scale tubular reactor for condensation reaction. By controlling the condensation degree of surface Si-OH groups, the hydrophilic and hydrophobic RhB-PMSQ microspheres could be synthesized with the same reaction system, and they could be uniformly dispersed in the aqueous phase and oil phase, respectively. The density, pore structure, and fluorescence property of the RhB-PMSQ microspheres were investigated in detail. The RhB-PMSQ microspheres were employed as the tracer particles of water and liquid paraffin, and the two-phase velocity profiles were measured via micro-PIV technique in a step T -junction microchannel. The micro-PIV results indicated that amphiphilic RhB-PMSQ microspheres could serve as the tracer particles for the flow field measurement both of aqueous phase and oil phase.

Silver Ions Promoted Palladium-Catalyzed Inactive β-C(sp3)-H Bond Arylation in Batch and Continuous-Flow Conditions.

A palladium(II)-catalyzed protocol for inactive β-C(sp3)-H bond functionalization has been first accomplished. The reaction proceeds through five-membered carbocycles for the formation of C-C bonds via the Pd(II)/Pd(IV) cycle. This reaction was carried out with various aryl iodides and benzothiazoles/benzoxazoles/benzimidazoles, which were well-tolerated in this reaction and successfully generated β-C(sp3)-H arylated products. Further implementation of this batch protocol to continuous flow by utilizing a PTFE (polytetrafluoroethylene) capillary reactor enhanced the reaction efficiency and decreased the reaction time (18.4 min) as compared to batch conditions (8 h). Even on the gram scale, the process produced excellent yield with negligible diarylations. Functional group tolerance, a continuous-flow approach, and easy-to-handle reaction conditions make this inactive β-C(sp3)-H bond functionalization protocol very attractive.

Boosting Efficiency in Light‐Driven Water Splitting by Dynamic Irradiation through Synchronizing Reaction and Transport Processes**

This work elaborates the effect of dynamic irradiation on light‐driven molecular water oxidation to counteract deactivation. It highlights the importance of overall reaction engineering to overcome limiting factors in artificial photosynthesis reactions. Systematic investigation of a homogeneous three‐component ruthenium‐based water oxidation system revealed significant potential to enhance the overall catalytic efficiency by synchronizing the timescales of photoreaction and mass transport in a capillary flow reactor. The overall activity could be improved by a factor of more than 10 with respect to the turnover number and a factor of 31 referring to the external energy efficiency by controlling the local availability of photons. Detailed insights into the mechanism of light driven water oxidation could be obtained using complementary methods of investigation like Raman, IR, and UV/Vis/emission spectroscopy, unraveling the importance of avoiding high concentrations of excited photosensitizers.

Evaluation of self-sustaining cyanobacterial biofilms for technical applications

Cyanobacteria are potent microorganisms for sustainable photo-biotechnological production processes, as they are depending mainly on water, light, and carbon dioxide. Persisting challenges preventing their application include low biomass, as well as insufficient process stability and productivity. Here, we evaluate different cyanobacteria to be applied in a novel capillary biofilm reactor. Cultivated as biofilms, the organisms self-immobilize to the reactor walls, reach high biomass and enable long and robust production processes. As ‘best performer’ Tolypothrix sp. PCC 7712 emerged from this study. It reached the highest biomass in the reactors with 62.6 ± 6.34 gBDWL−1, produced 0.14 μmole H2 mgChl a−1h−1 under N2-fixing conditions, showed optimal surface coverage of the available growth surface, and only minor detachment in contrast to other tested species, highlighting its potential for photobiotechnology in the near future.

A Comprehensive 2D-LC/MS Online Platform for Screening of Acetylcholinesterase Inhibitors

The continuous interest in discovering new bioactive molecules derived from natural products (NP) has stimulated the development of improved screening assays to help overcome challenges in NP-based drug discovery. Here, we describe a unique platform for the online screening of acetylcholinesterase inhibitors without the need for pre-treating the sample. In the current study, we have demonstrated the ability to combine reversed-phase separation with a capillary immobilized enzyme reactor (cIMER) in two-dimensional liquid chromatography system coupled with mass spectrometry detection. We systematically investigated the effects of method parameters that are of practical significance and are known to affect the enzyme assay and interfere in the analysis such as: bioreactor dimensions, loop sizes, amount of immobilized enzyme, second dimension flow rates, reaction time, substrate concentration, presence of organic modifier, limit of detection and signal suppression. The performance of this new platform was evaluated using a mixture containing three known AChE inhibitors (tacrine, galanthamine and donepezil) and an ethanolic extract obtained from the dry bulbs of Hippeastrum calyptratum (Amaryllidaceae) was investigated to provide a proof of concept of the applicability of the platform for the analysis of complex mixtures such as those derived from NPs.

3D-printed capillary force trap reactors (CFTRs) for multiphase catalytic flow chemistry

Figure of 3D illustration of a capillary trap force reactor (CFTR) with transiently trapped liquid nanoparticle catalysts in dimple-shaped capillary traps in the presence of a gas–liquid segmented flow, for the hydrogenation of 1-hexene to n-hexane.

Chloride-Mediated Peroxide-Free Photochemical Oxidation of Proteins (PPOP) in Mass Spectrometry-Based Structural Analysis.

Ultraviolet (UV) laser photolysis of hydrogen peroxide (H2O2) for the in situ generation of hydroxyl radicals (•OH) is a widely utilized strategy in the oxidation footprinting of native proteins and mass spectrometry (MS)-based structural analysis. However, it remains challenging to realize peroxide-free photochemical oxidation footprinting. Herein, we describe the footprinting of native proteins by chloride-mediated peroxide-free photochemical oxidation of proteins (PPOP). The protein samples are prepared within biocompatible phosphate-buffered saline (PBS) containing 10 mM Gln as radical scavengers and oxidized in a capillary flow reactor directly under a single-pulse (10 ns) irradiation of a 193 nm ArF UV laser. The main oxidized protein residues are CMYWFHLI. We demonstrate that the PPOP-MS strategy is highly sensitive to the protein high-order structures and can be applied to monitor the protein-drug interfaces, which provides a promising footprinting alternative for protein structure-function explorations.