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41 result(s) for "segmented-flow"
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Flow Biocatalysis: A Challenging Alternative for the Synthesis of APIs and Natural Compounds
Biocatalysts represent an efficient, highly selective and greener alternative to metal catalysts in both industry and academia. In the last two decades, the interest in biocatalytic transformations has increased due to an urgent need for more sustainable industrial processes that comply with the principles of green chemistry. Thanks to the recent advances in biotechnologies, protein engineering and the Nobel prize awarded concept of direct enzymatic evolution, the synthetic enzymatic toolbox has expanded significantly. In particular, the implementation of biocatalysts in continuous flow systems has attracted much attention, especially from industry. The advantages of flow chemistry enable biosynthesis to overcome well-known limitations of “classic” enzymatic catalysis, such as time-consuming work-ups and enzyme inhibition, as well as difficult scale-up and process intensifications. Moreover, continuous flow biocatalysis provides access to practical, economical and more sustainable synthetic pathways, an important aspect for the future of pharmaceutical companies if they want to compete in the market while complying with European Medicines Agency (EMA), Food and Drug Administration (FDA) and green chemistry requirements. This review focuses on the most recent advances in the use of flow biocatalysis for the synthesis of active pharmaceutical ingredients (APIs), pharmaceuticals and natural products, and the advantages and limitations are discussed.
A Compact Microwave Microfluidic Sensor Using a Re-Entrant Cavity
A miniaturized 2.4 GHz re-entrant cavity has been designed, manufactured and tested as a sensor for microfluidic compositional analysis. It has been fully evaluated experimentally with water and common solvents, namely methanol, ethanol, and chloroform, with excellent agreement with the expected behaviour predicted by the Debye model. The sensor’s performance has also been assessed for analysis of segmented flow using water and oil. The samples’ interaction with the electric field in the gap region has been maximized by aligning the sample tube parallel to the electric field in this region, and the small width of the gap (typically 1 mm) result in a highly localised complex permittivity measurement. The re-entrant cavity has simple mechanical geometry, small size, high quality factor, and due to the high concentration of electric field in the gap region, a very small mode volume. These factors combine to result in a highly sensitive, compact sensor for both pure liquids and liquid mixtures in capillary or microfluidic environments.
Oil-in-water segmented flow in the optimized microfluidic system for surfactant-free ultrasonic emulsification
Droplet-based microfluidics is a promising technique for generating stable emulsions in various applications, including pharmaceuticals, food, cosmetics, and biosensors. However, conventional methods rely on surfactants, which pose potential toxicity and environmental concerns. To address this issue, we developed a microfluidic device for surfactant-free oil droplet generation, serving as a pre-processing stage for ultrasonic emulsification. Three microfluidic channels were designed: a conventional T-junction, a needle-inserted channel, and a needle-inserted glass capillary channel. Oil-water flow segmentation characteristics of the fabricated devices were analyzed using high-speed camera and image processing techniques. Results demonstrated that the needle-inserted glass capillary exhibited superior stability, effectively generating oil droplets rather than slugs by utilizing a higher water affinity and minimizing oil contact with the channel walls. Furthermore, when integrated with ultrasonic emulsification, the pre-fragmented oil droplets exhibited improved processing efficiency. These findings highlight the potential of combining microfluidic pre-processing with ultrasound emulsification as a viable alternative to surfactant-based methods, offering enhanced precision and sustainability in droplet generation and emulsion formation.
Synthesis of Defective MOF-801 via Air–Liquid Segmented Flow for Catalytic Transfer Hydrogenation of Furfural
As one of the most important platform chemicals, furfural (FAL) can be converted into high-value-added products such as furfuryl alcohol (FOL) through multiple pathways. Zirconium-based MOF-801 demonstrates exceptional catalytic potential for FAL conversion via catalytic transfer hydrogenation (CTH), owing to its unique crystal defects generated during growth. In this study, a series of defective MOF-801 samples were efficiently synthesized using an air–liquid segmented microfluidic technique. The characterization results reveal that the air–liquid segmented flow method not only regulates the defect content of MOF-801 to expose more active sites but also adjusts the crystal size and pore structures by precisely controlling the reaction time. The enhanced defects in MOF-801 significantly improved its catalytic performance. A-MOF-801-64 exhibited the highest activity, achieving over 99% FAL conversion and 98% FOL selectivity under mild conditions (130 °C, 12 h) using isopropanol as the hydrogen donor; this performance surpassed that of other reported Zr-based catalysts. This study will facilitate the practical applications of defect-engineered MOF-801 in upgrading biomass-derived chemicals.
Process Intensification Approach Using Microreactors for Synthesizing Nanomaterials—A Critical Review
Nanomaterials have found many applications due to their unique properties such as high surface-to-volume ratio, density, strength, and many more. This review focuses on the recent developments on the synthesis of nanomaterials using process intensification. The review covers the designing of microreactors, design principles, and fundamental mechanisms involved in process intensification using microreactors for synthesizing nanomaterials. The microfluidics technology operates in continuous mode as well as the segmented flow of gas–liquid combinations. Various examples from the literature are discussed in detail highlighting the advantages and disadvantages of microfluidics technology for nanomaterial synthesis.
Continuous Synthesis of Precision Gold Nanoparticles Using a Flow Reactor
Nanoparticle synthesis using flow chemistry has the potential to enhance the large-scale accessibility of precision-engineered nanomaterials at lower prices. This goal has been difficult to achieve primarily due to reactor fouling and the lack of efficient reagent mixing encountered, especially in those scaled-up systems. The present study aimed to overcome the two challenges by integrating a liquid-liquid biphasic segmented flow system with static mixing. This strategy was applied to the synthesis of gold nanoparticles (AuNPs) using citrate reduction chemistry. It was demonstrated that reactor fouling was eliminated by implementing the biphasic flow strategy. As a result, the overall mean particle size of the as-synthesized AuNPs was measured to be 15.5nm with a polydispersity index (PDI) of 0.07, and with the reproducibility of ±6.4%. The biphasic flow system achieved a reaction yield of 88.7±1.1% reliably with a throughput of 60mL/hour up to 8 hours.
An integrated chip-mass spectrometry and epifluorescence approach for online monitoring of bioactive metabolites from incubated Actinobacteria in picoliter droplets
We present a lab-on-a-chip approach for the analysis of secondary metabolites produced in microfluidic droplets by simultaneous epifluorescence microscopy and electrospray ionization mass spectrometry (ESI-MS). The approach includes encapsulation and long-term off-chip incubation of microbes in surfactant-stabilized droplets followed by a transfer of droplets into a microfluidic chip for subsequent analysis. Before the reinjected droplets are spaced and electrosprayed from an integrated emitter into a mass spectrometer, the presence of fluorescent marker molecules is monitored nearly simultaneously with a custom-made portable epifluorescence microscope. This combined fluorescence and MS-detection setup allows the analysis of metabolites and fluorescent labels in a complex biological matrix at a single droplet level. Using hyphae of Streptomyces griseus, encapsulated in microfluidic droplets of ~ 200 picoliter as a model system, we show the detection of in situ produced streptomycin by ESI-MS and the feasibility of detecting fluorophores inside droplets shortly before they are electrosprayed. The presented method expands the analytical toolbox for the discovery of bioactive metabolites such as novel antibiotics, produced by microorganisms.
Selective DNA extraction with microparticles in segmented flow
Droplet-based segmented flow microfluidic systems have proven their potential for high throughput detection and quantification of analytes. However, the required sample preparations are often performed off-chip, as on-chip methods are lacking. Microparticles are especially suited for the extraction and purification of target molecules from a sample and are successfully used in other microfluidic systems and in laboratory-scale methods. The current magnetic separation methods in segmented flow microfluidics are limited in their function to purify, as only a limited part of the original droplet volume can be removed from the particles. In this paper, we report the implementation of a selective DNA extraction assay with microparticles in a segmented flow microfluidic system. The combination of magnetic separation with asymmetric droplet splitting allows the removal of 90 % or even 95 % of the original sample volume in a single separation step. It is shown that the hybridization and capture efficiency of the particles are identical for off-chip and on-chip methods. Next, the effect of the particle separation efficiency on the extraction efficiency is tested for different splitting regimes. When up to 90 % of the droplet volume is removed, nearly all particles are correctly separated and the non-separated particle fraction remains below 5 %. Only if 95 % of the original volume is removed, the unseparated fraction becomes significant (>10 %). Finally, the impact of separation at a higher splitting ratio for the repeated washing of the particles is discussed. With this novel system, more complex and relevant bioassays can be implemented completely in a droplet-based segmented flow context.
Multivariate curve resolution for kinetic modeling and scale-up prediction
An imine synthesis was investigated in a nearly isothermal oscillating segmented flow microreactor at different temperatures using non-invasive Raman spectroscopy. Multivariate curve resolution provided a calibration-free approach for obtaining kinetic parameters. The two different multivariate curve resolution approaches, soft and hard modeling, were applied and contrasted, leading to similar results. Taking heat and mass balance into account, the proposed kinetic model was applied for a model-based scale-up prediction. Finally, the reaction was performed in a 0.5 L semi-batch reactor, followed by in-line Raman spectroscopy and off-line gas chromatography analysis. The successful scale-up was demonstrated with a good agreement between measured and predicted concentration profiles. Highlights • Oscillation segmented flow reactor with inline Raman spectroscopy. • Multivariate Curve Resolution with hard and soft constraints. • High quality kinetic model for scale-up predictions. Graphical abstract
Determination of Albumin, Glucose, and Creatinine Employing a Single Sequential Injection Lab-at-Valve with Mono-Segmented Flow System Enabling In-Line Dilution, In-Line Single-Standard Calibration, and In-Line Standard Addition
A mono-segmented sequential injection lab-at-valve (SI-LAV) system for the determination of albumin, glucose, and creatinine, three key biomarkers in diabetes screening and diagnosis, was developed as a single system for multi-analyte analysis. The mono-segmentation technique was employed for in-line dilution, in-line single-standard calibration, and in-line standard addition. This made adjustments to the sample preparation step easy unlike the batch-wise method. The results showed that the system could be used for both fast reaction (albumin) and slow reaction (glucose with enzymatic reaction and creatinine). In the case of slow reaction, the analysis time could be shortened by using the reaction rate obtained with the SI-LAV system. This proposed system is for cost-effective and downscaling analysis, which would be applicable for small hospitals and clinics in remote places with a small number of samples but relatively fast screening would be needed.