Microfluidic Reactor Research Articles

Low cost fabrication of continuous flow optofluidic microreactor for efficient dye degradation using graphene QDs@MOF (Ti) photocatalyst

The optofluidic microreactor, a convergence of optics and microfluidics, offers advanced functionalities that can be pivotal in the rapid assessment of nanocatalysts for tackling environmental contamination issues. This article presents an efficient approach for degrading Methylene blue (MB) dye, commonly used in the textile industry, within a cost-effective polydimethylsiloxane (PDMS) based continuous flow optofluidic microreactor. This microreactor combines graphene quantum dots (QDs) and NH2-MIL-125 (MOF(Ti)) as a highly effective photocatalyst coating within its microchannels. By directly incorporating graphene QDs@MOF(Ti) into the microchannels, the photocatalytic medium is brought into close proximity with the flowing MB dye solutions, thereby reducing the necessary interaction time and enhancing purification efficiency. Furthermore, the findings demonstrate an impressive degradation efficiency of ∼99% for MB dye at a flow rate of 50 μL min−1 under visible light irradiation, achieved in a single pass. Additionally, the microfluidic reactor exhibits prolonged stability of the photocatalyst, enabling its reuse without significant efficiency loss. In addition, a comparative analysis highlights the advantages of microreactor-based photocatalysis over traditional methods. These advancements in the features of the graphene QDs@MOF(Ti) nanocomposite substantiate their demonstrated superiority in degradation efficiency.

A Critical View on the Use of DNA Hydrogels in Cell‐Free Protein Synthesis

Numerous studies have reported in the past that the use of protein‐encoding DNA hydrogels as templates for cell‐free protein synthesis (CFPS) leads to better yields than the use of conventional templates such as plasmids or PCR fragments. Systematic investigation of different types of bulk materials from pure DNA hydrogels and DNA hydrogel composites using a commercially available CFPS kit showed no evidence of improved expression efficiency. However, protein‐coding DNA hydrogels were advantageously used in microfluidic reactors as immobilized templates for repetitive protein production, suggesting that DNA‐based materials offer potential for future developments in high‐throughput profiling or rapid in situ characterization of proteins.

A Critical View on the Use of DNA Hydrogels in Cell-Free Protein Synthesis.

Numerous studies have reported in the past that the use of protein-encoding DNA hydrogels as templates for cell-free protein synthesis (CFPS) leads to better yields than the use of conventional templates such as plasmids or PCR fragments. Systematic investigation of different types of bulk materials from pure DNA hydrogels and DNA hydrogel composites using a commercially available CFPS kit showed no evidence of improved expression efficiency. However, protein-coding DNA hydrogels were advantageously used in microfluidic reactors as immobilized templates for repetitive protein production, suggesting that DNA-based materials offer potential for future developments in high-throughput profiling or rapid in situ characterization of proteins.

Sustainable and Advanced LED-Implanted Microfluidic Photoreactor with Coupled Optical Fiber Enabling Efficient Photocatalytic Synthesis Beside Online Reaction Progress Monitoring.

The conventional methods for the photoinduced synthesis of benzimidazoles may need further improvement regarding a safer and energy-efficient synthesis platform with in-process monitoring for maximum yield within a much reduced reaction time. This work describes the use of a novel optofluidic Lab-on-a-Chip technology for safer, energy-efficient, and expedited synthesis of benzimidazole derivatives in excellent yields along with real-time quantitative measurement during product formation. This innovative method involves synthesis within LED-embedded microfluidic reactors, allowing for rapid synthesis of benzimidazole derivatives via photoinduced condensation cyclization reactions of aryl aldehydes and o-phenylenediamines using a Rose Bengal/fluorescein photocatalyst. It results in good to excellent yields (85-94%) in a notably shorter period of time (10 min) as compared to that for the batch protocol reaction (2-3 h). The incorporation of a reaction-monitoring microfluidic device precisely connected to the microfluidic reactor (microreactor) unit successfully avoids interference from light sources, ensuring consistent UV-vis spectroscopic observations of the produced benzimidazole derivatives. This LED-embedded microfluidic device's capability of photoinduced synthesis, along with real-time spectroscopic analysis, represents a promising breakthrough in organic synthesis. The proposed approach minimizes the potential for accidents, prevents waste of chemicals, maximizes atom economy, and designs an energy-efficient synthesis route, along with real-time in-process monitoring.

Laminar Flow Infrared Spectroelectrochemistry.

In this work, we advance lab-on-chip electrochemistry and spectroscopy by combining these capabilities onto a single platform, thereby achieving mid-infrared spectroelectrochemistry (SEC) for the first time. The key feature of this technique is the use of deterministic laminar flow patterns to precisely transport a reacted solution from upstream electrodes to a downstream spectral detection region. Laminar flow spectroelectrochemistry (LF-SEC) is therefore a completely new approach, which derives its distinction and advantage over traditional SEC by physically separating electrode and attenuated total reflection (ATR) elements. As such, these functional elements retain optimal properties, such as inert, highly conductive electrodes and a bare ATR element for sensitive Fourier transform infrared (FTIR) spectroscopy. By combining ATR-FTIR with a scanning aperture system, LF-SEC provides the additional advantage of spectroscopically monitoring reactions at individual electrodes. The LF-SEC system design is first optimized through a series of targeted experiments using a ferricyanide/ferrocyanide redox pair to validate electrochemical functionality, undertake spectroscopic calibration, optimize experimental parameters, and finally validate the quantitative relationship between FTIR results and the reaction rate under galvanostatic control. After optimization, we demonstrate the technique by monitoring the oxidation of the therapeutic compound ascorbic acid (vitamin C) in the presence of biomolecular interference from a molecule with an overlapping oxidation potential. We find that molecular availability causes the reaction to switch between reaction pathways, which we could finely monitor using LF-SEC. This work opens the door to future developments that take advantage of the microfluidic reactor setup, with benefits ranging from portability to high-throughput studies under precise reaction conditions.

Salt scaling dynamics in microfluidic channels: Impact of channel geometry and process parameters

Salt scaling, a prevalent challenge in industrial processes, often leads to reduced efficiency, equipment failure, and environmental impact. Understanding and mitigating scaling in miniaturized systems for process intensification applications is crucial. In this study, we indigenously developed and utilized microfluidic reactors to investigate calcium carbonate (CaCO3) scaling dynamics in microfluidic channels, offering real-time visualization under continuous flow; a significant advancement over static methods. We explore the impact of channel geometry (curvature of 0°, 45°, 90°, and 135°) and process parameters (temperature, supersaturation index (SI), and flow velocity) on CaCO3 deposition behavior. Our findings reveal significant influences: higher temperature and SI promote deposition, while microchannel curvature and increased flow velocity enhance removal. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses confirmed the morphology and phase changes of the deposited CaCO3. Calcite and aragonite were the dominant polymorphs, with their occurrence influenced by temperature and SI. These insights can be translated to the design and operation of miniaturized equipment for process intensification, such as micro heat exchangers. By understanding and controlling scaling phenomena, this research might pave the way for improved performance, sustainability, and resource efficiency in various industrial settings.

Heat and mass transfer visualisation of an exothermic acid-base microfluidic reactor using infrared thermospectroscopy

ABSTRACT Here, a microfluidic reactor that is transparent in the mid-wave infrared spectrum with an effective path length of 38 µm is developed for characterisation via operando Fourier-transform Infrared (FTIR) thermospectroscopy. This imaging technique couples an infrared (IR) camera with an FTIR spectrometer to quantify heat and mass transfer in the exothermic acid-base reaction between hydrochloric acid (HCl) and sodium hydroxide (NaOH). The absorbance fields of the reaction are used to simultaneously derive the molar concentration fields of the reactants (HCl and NaOH) and products (sodium chloride [NaCl]) at the microscale through a linear inverse method. The heat generated at the reaction interface is visualised through a thermal field captured from the measured proper emission. Concentration and thermal fields are then compared to an advection-diffusion model for validation. The results proposed in this work present a refined contactless calorimetry process for characterising the heat and mass transport in an acid-base reaction. Further refinement of this work will enable accurate and non-invasive measurements for the enthalpy of reaction in chemical reactions.

Green synthesis of ZIF-67 nanoparticles via microfluidics: Towards sustainable nanomaterial production

This study explored the synthesis of zeolitic imidazolate framework-67 (ZIF-67) nanoparticles using a microfluidic reactor, focusing on the effects of reactant concentration, temperature, and flow rate on the material’s properties. Design Expert software was utilized to optimize these variables to enhance the synthesis process while preventing reactor clogging due to precipitate formation. The experiments varied concentrations of cobalt (II) nitrate hexahydrate and 2-methylimidazole, along with temperature and flow rates. After synthesis, the samples underwent extensive characterization, including FTIR, NMR, TEM, SAED, and XRD analyses. FTIR results confirmed the successful formation of ZIF-67, with varying conditions leading to shifts in peak positions and intensities, indicating changes in bonding and molecular structure. NMR spectra provided insights into the hydrogen environments within the nanoparticles. TEM and SAED analyses revealed that the nanoparticles predominantly exhibited a uniform rhombic dodecahedral morphology with diameters ranging from 5 to 10 nm. XRD patterns were consistent with simulated data, showing variations in peak positions and crystallinity with changes in synthesis conditions. The study highlighted that increasing reactant concentrations, temperature, and flow rate generally enhanced the production rate and crystallinity of ZIF-67, with 2-methylimidazole concentration having the most significant impact. The findings contributed to optimizing ZIF-67 synthesis, demonstrating the feasibility of using microfluidic reactors and green solvents for producing high-quality nanoparticles with controlled properties.

Photoresponsive microfluidic three-phase emulsions for tandem reactions

The long-term objective of tandem reaction is to investigate ‘intelligent’ tandem reaction systems akin to living cells. Here we’ve prepared an ‘intelligent’ droplet microreactor for the tandem reaction using droplet microfluidic technology constructing a photoresponsive microfluidic tandem reaction system. The method leverages a three-phase emulsion’s ‘two membranes and three phases’ structure to segregate incompatible reagents, and introduces a stimulating surfactant to control the structure of this emulsion structure for intelligent reaction sequence control, enablingefficient,orderlytandem reactionwithin the same system. Validating this concept, we applied the droplet microreactor to the condensation-reduction cascade reaction, as envisioned, incompatible condensation and reduction reactions, were coordinated by cycling the UV light on /off for a smooth cascade reaction. Compared to batch reaction, the droplet microreactor showed sixfold catalytic efficiency enhancement and > 99 % reaction selectivity. Our work offers novel insights into realizing intelligent cascade reactions.

Fuel transport mechanisms and power generation enhancement in air-breathing microfluidic fuel cells with discrete-hole anode

Current challenges in air-breathing microfluidic fuel cells (AMFCs) technology include insufficient fuel transfer and unsatisfactory power density. To address these issues, this study develops a three-dimensional computational model to optimize the performance of AMFC with a discrete-hole anode. This model reveals that the "petal-shaped" non-uniform fuel distribution is due to the shearing and dilution effects of the electrolyte. Additionally, discrete-hole structures such as size have a slight influence on fuel transport and current production, with performance deviations under 1.6%. Significant improvements are achieved by reducing the electrolyte flow rate and electrode length. Transitioning from a single cell with a long anode to a series/parallel stack of cells with short electrodes significantly boosts net power output and fuel utilization. Under optimal conditions, a maximum power density of 349.9 mW cm−3 and an output of 19.2 mW are obtained. This research provides valuable insights into fuel transport mechanisms and power enhancement strategies in the AMFCs, guiding the future design and optimization of microfluidic reactors for energy conversion.

Heterophase Pt/EG-catalyzed hydrosilylation in droplet microfluidics: Spectral monitoring and efficient 3D-printed reactors

Homogeneous Pt-catalyzed hydrosilylation is an industrially important process for the synthesis of organosilanes. Reusable heterophase (biphase) Pt-catalysts can solve economic and ecological issues arising from the high cost of Pt and its irretrievable “scattering”. Previously, we proposed a sustainable and convenient-to-handle heterophase Pt/EG-catalytic system (EG – ethylene glycol). In the current research heterophase Pt/EG-catalyzed hydrosilylation was transferred in a microfluidic regime that combined several advantages. A stable droplet or segmented Taylor flow with a well-defined contact area allow for the improvement of mass and heat transfer during the scaling of such a biphase and exothermic reaction, compared to batch mode. In situ Raman spectroscopy monitoring allows for fast and continuous data collection throughout the experiment and opens an opportunity for automation of conversion analysis. We demonstrate an efficient reaction of a range of reagents in the microfluidic reactor. In this work its universal components were constructed and modified using either commercially available units or via additive technologies (3D-printing). To the best of our knowledge, this is the first example of a semi-automatic recyclization device for a real heterophase catalytic process. These results open up new perspectives for scaling and automating industrially relevant heterophase hydrosilylation reactions.

De novo construction of amine-functionalized metal-organic cages as heterogenous catalysts for microflow catalysis

Microflow catalysis is a cutting-edge approach to advancing chemical synthesis and manufacturing, but the challenge lies in developing efficient and stable multiphase catalysts. Here we showcase incorporating amine-containing metal-organic cages into automated microfluidic reactors through covalent bonds, enabling highly continuous flow catalysis. Two Fe4L4 tetrahedral cages bearing four uncoordinated amines were designed and synthesized. Post-synthetic modifications of the amine groups with 3-isocyanatopropyltriethoxysilane, introducing silane chains immobilized on the inner walls of the microfluidic reactor. The immobilized cages prove highly efficient for the reaction of anthranilamide with aldehydes, showing superior reactivity and recyclability relative to free cages. This superiority arises from the large cavity, facilitating substrate accommodation and conversion, a high mass transfer rate and stable covalent bonds between cage and microreactor. This study exemplifies the synergy of cages with microreactor technology, highlighting the benefits of heterogenous cages and the potential for future automated synthesis processes

Development of a Microbioreactor for Bacillus subtilis Biofilm Cultivation.

To improve our understanding of Bacillus subtilis growth and biofilm formation under different environmental conditions, two versions of a microfluidic reactor with two channels separated by a polydimethylsiloxane (PDMS) membrane were developed. The gas phase was introduced into the channel above the membrane, and oxygen transfer from the gas phase through the membrane was assessed by measuring the dissolved oxygen concentration in the liquid phase using a miniaturized optical sensor and oxygen-sensitive nanoparticles. B. subtilis biofilm formation was monitored in the growth channels of the microbioreactors, which were designed in two shapes: one with circular extensions and one without. The volumes of these microbioreactors were (17 ± 4) μL for the reactors without extensions and (28 ± 4) μL for those with extensions. The effect of microbioreactor geometry and aeration on B. subtilis biofilm growth was evaluated by digital image analysis. In both microbioreactor geometries, stable B. subtilis biofilm formation was achieved after 72 h of incubation at a growth medium flow rate of 1 μL/min. The amount of oxygen significantly influenced biofilm formation. When the culture was cultivated with a continuous air supply, biofilm surface coverage and biomass concentration were higher than in cultivations without aeration or with a 100% oxygen supply. The channel geometry with circular extensions did not lead to a higher total biomass in the microbioreactor compared to the geometry without extensions.

Boosting Microfluidic Enzymatic Cascade Reactions with pH-Responsive Polymersomes by Spatio-Chemical Activity Control.

Microfluidic flow reactors permit the implementation of sensitive biocatalysts in polymeric environments (e.g., hydrogel dots), mimicking nature through the use of diverse microstructures within defined confinements. However, establishing complex hybrid structures to mimic biological processes and functions under continuous flow with optimal utilization of all components involved in the reaction process represents a significant scientific challenge. To achieve spatial, chemical, and temporal control for any microfluidic application, compartmentalization is required, as well as the unification of different sensitive compartments in the reaction chamber for the microfluidic flow design. This study presents a self-regulating microfluidic system fabricated by a sequential photostructuring process with an intermediate chemical process step to realize pH-sensitive hybrid structures for the fabrication of a microfluidic double chamber reactor for controlled enzymatic cascade reaction (ECR). The key point is the adaptation and retention of the function of pH-responsive horseradish peroxidase-loaded polymersomes in a microfluidic chip under continuous flow. ECR is successfully triggered and controlled by an interplay between glucose oxidase-converted glucose, the membrane state of pH-responsive polymersomes, and other parameters (e.g., flow rate and fluid composition). This study establishes a promising noninvasive regulatory platform for extended spatio-chemical control of current and future ECR and other cascade reaction systems.

Sample-in-answer-out centrifugal microfluidic chip reaction biosensor powered by Thermus thermophilus Argonaute (TtAgo) for rapid, highly sensitive and multiplexed molecular diagnostics of foodborne bacterial pathogens

Foodborne pathogens endanger public health and rapid, sensitive and accurate detection of them is vital. Argonaute stands in the frontline as the next generation nucleic acid detection tool, bearing a few comparable advantages. Centrifugal microfluidic chips (CMCs) use centrifugal force to achieve liquid flowing, mixing and reaction, eliminating complicated designs of valves and pumps. In this study, for the first time, we devised a Thermus thermophilusArgonaute (TtAgo)-powered centrifugal microfluidic chip reaction biosensor for Sample-in-Answer-out detection of Pathogen S. aureus (termed as ASAP) with ultrahigh rapidity and sensitivity in a one-pot fashion. The samples subjected to testing were mixed with a home-made nucleic acid fast extraction reagent and then the mixture was injected into the sample cell of CMC, which was centrifuged down into the reaction cell. The reaction cell was preloaded with both LAMP (Loop-mediated isothermal amplification) and TtAgo systems. As such, the species-specific nuc genes were amplified by LAMP, while the TtAgo performed site-specific cleavage to output fluorescent (FL) signals. The sample-to-answer time was 17 min, and the limit of detection (LOD) reached 1 CFU/mL. ASAP was able to perform simultaneous multiplexed detection and up to 16 samples can be detected at the same time. ASAP reduced reagent consumption and minimized the influence of carry-over and cross-contamination. ASAP was capable of detecting S. aureus in foods, but also detecting physiological samples from infect, holding great promise for practical applications. Overall, our work has enriched the Argonaute-powered biosensing and CMC biosensor technology by providing a conceptually novel bacterial detection platform.

Carbon dioxide hydrate crystallization thickening & morphology in a micro-confined environment for carbon capture & sequestration processes

Carbon dioxide capture and sequestration (CCS) are critical processes that are necessary to mitigate the impacts of climate change. In pipelines used for CCS and for ocean sequestration, the formation of CO2 hydrates can occur and be detrimental to the safety and integrity of the CCS equipment and process. Understanding the crystallization thickening behavior of CO2 hydrates is vital for understanding hydrate formation in CO2 pipelines and in other CCS applications, such as sequestration and CO2 capture or storage. In this study, a microfluidic chip reactor was used to crystalize and thicken CO2 hydrates at the channel walls. The morphology of the CO2 hydrates was visually analyzed and quantified using in situ Raman spectroscopy. Two hydrate layers were consistently observed. An annealed, dense layer of hydrate shared an interface with liquid water, while a porous hydrate layer shared an interface with CO2 gas. Capillary-like pore spaces could be observed in the porous layer, which confirms one proposed mechanism for hydrate film thickening. Subcooling (0.5–1.5 K), pressure (2.51, 3.10 MPa), and flow rate of CO2 (0.167, 1.67 mm3/s) were studied for their impact on the overall CO2 hydrate film thickness over time. Over the ranges of these chosen parameters, only CO2 flow rate was found to have a significant impact on the thickening of CO2 hydrates, and a higher flow rate led to thicker crystalline hydrate films. A first principles mass transfer model for hydrate film thickness was developed and applied to the measurement data collected for overall hydrate film thickness.

CFD assisted engineering of spiral microfluidic reactors for room temperature synthesis of ZnO nanoparticles

In microfluidic reactors designed for the synthesis of nanomaterials, hydrodynamics and mixing performance play a crucial role in the characteristics of the synthesized nanoparticles. In the current study, CFD simulation is utilized to shed light on flow characteristics inside a spiral microfluidic device and the way it affects the mixing during ZnO synthesis. Before microfabrication, the optimal number of spiral loops and flow rate in the microfluidic reactor was determined through mixing index calculation according to the CFD results in terms of the concentration distribution. Furthermore, this synthesis method is compared with batch nanoparticle fabrication techniques. In the microfluidic system, the concentrations of precursors were 50 times more diluted rather than batch methods. The droplet-based microfluidic ZnO synthesis was eight-fold faster than batch synthesis. The ZnO nanoparticles were characterized by XRD, SEM, and FTIR techniques. The outcomes of the FTIR analysis demonstrated that both the batch and microfluidic samples exhibit identical vibrational peaks. The experiments showed that the microfluidic system is reliable for controlling size. Besides, the CFD results indicated that a spiral micromixer with five loops provides sufficient mixing. The acquired findings from the characterization analyses can lead us toward a clue that once the ZnCl2/NaOH concentration ratio is greater than unity, a narrower size distribution of ZnO particles is probable. Consequently, the microfluidic reactor can be an efficient method for nanomaterial construction owing to the minimization of energy consumption and independence of the operational synthesis temperature.

Detection of α-Galactosidase A Reaction in Samples Extracted from Dried Blood Spots Using Ion-Sensitive Field Effect Transistors.

Fabry disease is a lysosomal storage disorder caused by a significant decrease in the activity or absence of the enzyme α-galactosidase A. The diagnostics of Fabry disease during newborn screening are reasonable, due to the availability of enzyme replacement therapy. This paper presents an electrochemical method using complementary metal-oxide semiconductor (CMOS)-compatible ion-sensitive field effect transistors (ISFETs) with hafnium oxide-sensitive surfaces for the detection of α-galactosidase A activity in dried blood spot extracts. The capability of ISFETs to detect the reaction catalyzed by α-galactosidase A was demonstrated. The buffer composition was optimized to provide suitable conditions for both enzyme and ISFET performance. The use of ISFET structures as sensor elements allowed for the label-free detection of enzymatic reactions with melibiose, a natural substrate of α-galactosidase A, instead of a synthetic fluorogenic one. ISFET chips were packaged with printed circuit boards and microfluidic reaction chambers to enable long-term signal measurement using a custom device. The packaged sensors were demonstrated to discriminate between normal and inhibited GLA activity in dried blood spots extracts. The described method offers a promising solution for increasing the widespread distribution of newborn screening of Fabry disease.

Rapid and portable microfluidic chip-based qPCR for quality assurance of commercial seaweeds (lavers) in the supply chain

Lavers, an important type of seaweed rich in health-promoting substances, have seen a surge in global demand. However, their similar morphological characteristics among different species make them vulnerable to food fraud. To address this issue and ensure quality assurance, we developed a portable microfluidic quantitative polymerase chain reaction (qPCR) method to monitor six laver species, comparing its effectiveness with conventional qPCR. Our portable microfluidic qPCR system used a plate-shaped heat block for rapid heat transfer, combined with a microfluidic-based biochip for quick detection. The primers were specifically designed to target the chloroplast genes rbcL and rbcS. Specificity using 17 seaweed species showed no cross-reactivity, and the sensitivity of the assay was 1 × 10−4 ng. Furthermore, we enhanced the portable microfluidic qPCR for field applications by integrating it with a simple DNA extraction method. To validate the on-site rapid identification of laver species, we evaluated 79 laver samples collected from fish farms in Korea and commercially available laver products. We discovered instances where products were adulterated with cheaper species or replaced with others that resemble them. This method proves to be rapid, sensitive, reliable, and applicable for effectively managing and monitoring lavers in the supply chain.

A Real-Time LSPR-Based Study of Metal-Organic Framework (MOF) Growth.

MOFs are known for their absorption properties and widely used for accumulation, filtering, sensorics, photothermal, catalytical and other applications. Their combination with plasmonic metal nanoparticles leads to hybrid structures that profit from the stabilizing effect and high porosity of the MOF as well as the optical and electronic properties of the nanoparticles. The growth of MOFs on plasmonic nanoparticles can be monitored in-situ using LSPR spectroscopy, simultaneously applying microfluidic reaction conditions for the fabrication of NP@MOF structures. Here, a systematic study is conducted using LSPR spectroscopy for the monitoring of the Layer-by-Layer deposition of twelve different MOFs, determining the suitability of LSPR spectroscopy for this purpose. In addition to some well-investigated materials like HKUST-1, other MOFs such as MIL-53, MIL-88 A and Cu-BDC are deposited successfully. For some MOFs such as Zn-Fum, the LSPR experiment indicates that no deposition had taken place. The results are confirmed with AFM, SEM and XPS measurements. This work shows that LSPR spectroscopy is suitable for the in-situ monitoring of LbL MOF growth and the microfluidic setup is a very promising method for the controlled manufacturing of NP@MOF hybrid structures. Further studies may include the optimization of the synthesis process or the transfer to other materials.