Droplet Microreactors Research Articles

Efficient epoxidation of styrene within pickering emulsion-based compartmentalized microreactors

The epoxidation of styrene is an important route to synthesize organic intermediate, but how to effectively promote the formation of target superoxide radicals and then regulate the production of styrene oxide in two-phase reaction system remains an urgent challenge. In this study, MnOx nanocatalysts with abundant oxygen vacancies were fabricated using reverse-micelle as template, and then were endowed with an amphiphilic surface through post-modification. With such MnOx catalysts, Pickering emulsion could be formulated, in which numerous compartmentalized droplet microreactors were created for the epoxidation of styrene. The rich oxygen defects on MnOx were found to be useful to improve the chemisorption of t-butylhydroperoxide, and the active complexes formed by coordination of Mn3+ with N, N-dimethylformamide favored the generation of preferable superoxide radicals for the synthesis of styrene oxide. Moreover, it was also found that compartmentalization effects arising from Pickering emulsion droplets modifies the radicals reaction path, significantly improving the catalytic efficiency and selectivity. As a result, in the Pickering emulsion system, 90.0% selectivity towards styrene oxide and a turnover frequency of 581 h−1 could be obtained, which were higher than ever reported results. The Pickering emulsion-based compartmentalized microreactors can provide versatile platforms to efficiently control the epoxidation of styrene involving free radicals.

Efficient multi-gene expression in cell-free droplet microreactors

Cell-free transcription and translation systems promise to accelerate and simplify the engineering of proteins, biological circuits and metabolic pathways. Their encapsulation on microfluidic platforms can generate millions of cell-free reactions in picoliter volume droplets. However, current methods struggle to create DNA diversity between droplets while also reaching sufficient protein expression levels. In particular, efficient multi-gene expression has remained elusive. We here demonstrate that co-encapsulation of DNA-coated beads with a defined cell-free system allows high protein expression while also supporting genetic diversity between individual droplets. We optimize DNA loading on commercially available microbeads through direct binding as well as through the sequential coupling of up to three genes via a solid-phase Golden Gate assembly or BxB1 integrase-based recombineering. Encapsulation with an off-the-shelf microfluidics device allows for single or multiple protein expression from a single DNA-coated bead per 14 pL droplet. We envision that this approach will help to scale up and parallelize the rapid prototyping of more complex biological systems.

Ultrasound enhancing the mass transfer of droplet microreactor for the synthesis of AgInS2 nanocrystals

Droplet microreactors are powerful tools for synthesizing chemicals, nano materials and biomolecules, but traditional methods, such as mechanical stirring, are hard to enhance the internal mass transfer of droplet microreactor due to its small reaction space. In this study, we propose a novel ultrasonic-enhancing method for droplet microreactor, and report the effect of bubbles inside micro-droplets for the first time. On this basis, the synthesis of AgInS2 nanocrystals is selected as model reaction to study the enhancement mechanism. It is discovered that the flow field in micro-droplet is significantly improved owing to acoustic streaming and cavitation microstreaming. Benefiting from them, the mass transfer coefficient is enhanced by 72.5 %, and AgInS2 nanocrystals are successfully synthesized with smaller, more uniform particle size, as well as more adjustable performance compared with no ultrasonic radiation condition. This work provides a new method and a deep insight of ultrasound enhancing droplet microreactor, enabling the continuous production of fine chemical synthesis.

High-throughput activity screening and sorting of single catalyst particles with a droplet microreactor using dielectrophoresis

High-throughput activity screening and sorting of single catalyst particles with a droplet microreactor using dielectrophoresis

Integrated synthesis and ripening of AgInS2 QDs in droplet microreactors: An update fluorescence regulating via suitable temperature combination

Aqueous phase synthesized ternary I–III–VI2 Quantum dots (QDs) are getting more and more attention in biology researches, for their good biocompatibility and easy-to-adjust fluorescence properties. However, the quantum yield (QY) of these aqueous phase synthesized QDs are often pretty low, which seriously hindered their further applications in this field. In general, the ripening of the QDs helps to enhance their QY, closely related to the ripening temperature. But it is still hard to precisely control the fluorescence performance of the QDs products, due to the difficulties in precise temperature control and cumbersome temperature adjusting operations in batch reactors. Here we proposed an integrated droplet microfluidic chip for the automated and successive AgInS2 QDs synthesis and ripening, with both temperatures controlled independently, precisely but easily. Taking advantage of the space-time transformation of the droplet microfluidic chips, the suitable temperature combination for AgInS2 QDs synthesis and ripening was studied, and the high-performance AgInS2 QDs were obtained. In addition, the reason for the decrease of QY of AgInS2 QDs at higher ripening temperature was also explored.

Janus Emulsion Solar Concentrators as Photocatalytic Droplet Microreactors

AbstractEfficiently harvesting and conveying photons to photocatalytic reaction centers is one of the great obstacles in photocatalysis. To address this challenge, a new approach is reported that is based on employing biphasic complex emulsions as droplet‐based solar concentrators. Specifically, substrates and photocatalysts are compartmentalized into the confined space of Janus emulsion droplets comprised of a hydrocarbon partially encapsulated inside fluorocarbon oil with a large refractive index contrast. Optical confinement of the incident light due to total internal reflection at the concave internal interface of the biphasic emulsion droplets leads to a strong increase of the light intensity inside the reaction medium. In addition, the high gas solubility within the outer fluorocarbon phase promotes oxygen delivery in photocatalytic oxidation reactions. Both effects mutually contribute to a strong performance increase of a series of homogeneous and heterogeneous photocatalytic reactions even under diffuse sunlight conditions.

Instrumentation-Compact Digital Microfluidic Reaction Interface-Extended Loop-Mediated Isothermal Amplification for Sample-to-Answer Testing of Vibrio parahaemolyticus.

Vibrio parahaemolyticus is usually spread via consumption of contaminated seafood and causes vibriosis. By combination of digital microfluidic (DMF) and loop-mediated isothermal amplification (LAMP), we provided an automated instrumentation-compact DMF-LAMP device for sample-to-answer detection of V. parahaemolyticus. For the first time, how much the proper mixing might facilitate the DMF-LAMP process is explored. The results illustrated that increasing the number of flow configurations and decreasing the fluid-reversibility will extend the interfacial surface available for diffusion-based mass transfer within a droplet microreactor, thus contributing to the overall amplification reaction rate. Noticeably, the DMF-LAMP amplification plateau time is shortened by proper mixing, from 60 min in static mixing and traditional bulk LAMP to 30 min in 2-electrode mixing and 15 min in 3-electrode mixing. The device achieved much higher detection sensitivity (two copies per reaction) than previously reported devices. V. parahaemolyticus from spiked shrimps is detected by Q-tip sampling associated with 3-electrode mixing DMF-LAMPs. The detectable signal occurs within only 3 min at a higher concentration and, at most, is delayed to 18 min, with a detection limit of <0.23 × 103 CFU/g. Thus, the developed DMF-LAMP device demonstrates potential for being used as a sample-to-answer system with a quick analysis time, high sensitivity, and sample-to-answer format.

Tension gradient-driven oil/water interface rapid particle self-assembly and its application in microdroplet motion control

HypothesisA binary mixture was used during injection with one water-miscible component and the other water-immiscible, which can help particles to migrate toward and then self-assemble at the interface. ExperimentsThe ethanol-tetrachloromethane binary mixture was used to verify the self-assembly method, with the diameter of droplets being about 1 mm. As the ethanol diffused into the colloidal solution, the colloidal particles efficiently moved towards and self-assembled on the oil/water interface, while a colloidal particle film with high-coverage was able to rapidly form on the droplet surface even in an ultra-low concentration colloidal solution. The effects of ethanol concentration and particle concentration on self-assembly were investigated. FindingsThe driving force for self-assembly originated from the tension gradient generated by ethanol's concentration gradient at the particle/liquid interfaces, where the concentrations of ethanol and the colloidal solution had significant effects on self-assembly. The simulation and calculations results aligned well with experiments, providing the theoretical basis for this self-assembly method. Further, as-prepared magnetic particle-coated droplets transformed into a non-wetting soft solid, which had long lifetimes and could be precisely moved, coalesced, and transferred in various two-dimensional and three-dimensional liquid environments. Thus, wider applications are facilitated, such as droplet transfer, microreactor and other potential fields.

Directed self-propulsion of droplets on surfaces absent of gradients for cargo transport

HypothesisManipulating droplet transportation without inputting work is desired and important in microfluidic systems. Although the creation of wettability gradient on surfaces has been employed to achieve this goal, the transport distance is very limited, hindering its applications in long-term operations. ExperimentsHere, we show that programming long-ranged transport of droplets on surfaces can be achieved by the addition of trisiloxane surfactants and the creation of deep grooves. The former provides Marangoni stress to actuate the droplet motion and also reduces the inherent contact line pinning. The latter acts as a railing to guide the motion of surfactant-laden droplets to follow various layouts with geometric features of roads. FindingsIt is found that the droplets with microliters can move over 20 cm. This work-free method is applicable to a variety of substrate materials and liquids. By using self-running shuttles, a convenient platform for liquid cargos transport is developed and demonstrated. Moreover, the coalescence of cargos carried by different shuttles is accomplished in a three-branch layout, revealing new droplet microreactors.

Fe3O4/Porphyrin Covalent Organic Framework Core–Shell Nanospheres as Interfacial Catalysts for Enzymatic Esterification

A nanoscale core-shell-structured magnetic microsphere (abbreviated as Fe3O4@DhaTph-lipase), which consists of an Fe3O4 core, a porphyrin covalent organic framework DhaTph shell with loaded lipase, is reported. The obtained Fe3O4@DhaTph-lipase microsphere can be a powerful emulsifier to stabilize the water-in-n-hexane Pickering emulsion for at least one month without any demulsification under ambient conditions. Furthermore, Fe3O4@DhaTph-lipase with lipase enzyme and a large specific surface area is a droplet microreactor and displays excellent interfacial catalytic activity to promote enzymatic esterification reaction via visible light-induced photothermal conversion. On the other hand, the magnetically triggered Pickering emulsion interfacial catalyst can be recycled at least 10 times with robust performance. The potential utility of this strategy is highlighted by the fabrication of many more multifunctional covalent organic framework-based Pickering emulsion catalytic systems to promote various organic transformations in a green, smart, and facile way.

Controllable Droplet Generators by Light-Heat Energy Conversion for Selective Particle Encapsulation

Water-in-oil droplet generation for object encapsulation is of increasing importance in biochemical reaction, drug diagnostics, and environmental science. Optofluidic technique is a powerful tool for manipulating mesoscopic particles and droplets within a continuous liquid phase. Here, we report a flexible and miniaturized droplet generator based on a microvortex chip by light-heat energy conversion to fuse, trap, and release picoliter aqueous droplets in the immiscible carrier oil. The droplet sizes in the generators can be tuned by the flow rate of the vortices. Further, it is demonstrated that the generated droplet can realize size-selective encapsulation of micro-matters with tunable rotating trajectories. The results showed that the microvortex-based droplet generator propose a method for the stable fusion and encapsulation of droplet with controllable positions and volumes. This system will provide a controllable microfluidic environment for droplet tweezers, micro-reactors, micro-mixers, and object encapsulation in practical applications.

Interfacial Synthesis of Ag2S/ZnS Core/Shell Quantum Dots in a Droplet Microreactor

AbstractCoating a shell outside the silver chalcogenide quantum dots (QDs) is still difficult due to the large lattice mismatch between the core and the shell. In this work, benefited from the huge specific surface area of the droplets and the adsorption of nanoparticles (NPs) at the interface in a droplet microreactor, the problem was successfully solved. The Ag2S/ZnS core/shell QDs were rapidly synthesized by interfacial reaction for the first time in a droplet microreactor. By adjusting the concentration of precursors, the control of the shell thickness became workable. In addition, the quantum yield (QY) was improved approximately 20 times after growing a ZnS shell outside the Ag2S core. Besides, the effect of shell thickness on fluorescence was further studied, and it was found that only appropriate shell thickness could effectively improve fluorescence. The proposed method is novel, non‐toxic and controllable, providing a new way for the synthesis of core/shell QDs.

Multi-GBq production of the radiotracer [18F]fallypride in a droplet microreactor.

Microfluidics offers numerous advantages for the synthesis of short-lived radiolabeled imaging tracers: performing 18F-radiosyntheses in microliter-scale droplets has exhibited high efficiency, speed, and molar activity as well as low reagent consumption. However, most reports have been at the preclinical scale. In this study we integrate a [18F]fluoride concentrator and a microdroplet synthesizer to explore the possibility of synthesizing patient doses and multi-patient batches of clinically-acceptable tracers. In the integrated system, [18F]fluoride (up to 41 GBq [1.1 Ci]) in [18O]H2O (1 mL) was first concentrated ∼80-fold and then efficiently transferred to the 8 μL reaction chip as a series of small (∼0.5 μL) droplets. Each droplet rapidly dried at the reaction site of the pre-heated chip, resulting in localized accumulation of large amounts of radioactivity in the form of dried [18F]TBAF complex. The PET tracer [18F]fallypride was synthesized from this concentrated activity in an overall synthesis time of ∼50 min (including radioisotope concentration and transfer, droplet radiosynthesis, purification, and formulation), in amounts up to 7.2 GBq [0.19 Ci], sufficient for multiple clinical PET scans. The resulting batches of [18F]fallypride passed all QC tests needed to ensure safety for clinical injection. This integrated technology enabled for the first time the impact of a wide range of activity levels on droplet radiosynthesis to be studied. Furthermore, this substantial increase in scale expands the applications of droplet radiosynthesis to the production of clinically-relevant amounts of radiopharmaceuticals, and potentially even centralized production of clinical tracers in radiopharmacies. The overall system could be applied to fundamental studies of droplet-based radiochemical reactions, or to the production of radiopharmaceuticals labeled with a variety of isotopes used for imaging and/or targeted radiotherapeutics.

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

BackgroundConventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), we demonstrate that simple microvolume radiosynthesis techniques can improve the efficiency of production by consuming tiny amounts of precursor, and maintaining high molar activity of the tracers even with low starting activity.ProceduresThe synthesis was carried out in microvolume droplets manipulated on a disposable patterned silicon “chip” affixed to a heater. A droplet of [18F]fluoride containing TBAHCO3 was first deposited onto a chip and dried at 100 °C. Subsequently, a droplet containing 60 nmol of precursor was added to the chip and the fluorination reaction was performed at 90 °C for 5 min. Removal of protecting groups was accomplished with a droplet of HCl heated at 90 °C for 3 min. Finally, the crude product was collected in a methanol-water mixture, purified via analytical-scale radio-HPLC and formulated in saline. As a demonstration, using [18F]FET produced on the chip, we prepared aliquots with different molar activities to explore the impact on preclinical PET imaging of tumor-bearing mice.ResultsThe microdroplet synthesis exhibited an overall decay-corrected radiochemical yield of 55 ± 7% (n = 4) after purification and formulation. When automated, the synthesis could be completed in 35 min. Starting with < 370 MBq of activity, ~ 150 MBq of [18F]FET could be produced, sufficient for multiple in vivo experiments, with high molar activities (48–119 GBq/μmol). The demonstration imaging study revealed the uptake of [18F]FET in subcutaneous tumors, but no significant differences in tumor uptake as a result of molar activity differences (ranging 0.37–48 GBq/μmol) were observed.ConclusionsA microdroplet synthesis of [18F]FET was developed demonstrating low reagent consumption, high yield, and high molar activity. The approach can be expanded to tracers other than [18F]FET, and adapted to produce higher quantities of the tracer sufficient for clinical PET imaging.

Continuous Flow Routes toward Designer Metal Nanocatalysts

AbstractMono‐ and multimetallic nanoparticles (NPs) have diverse and tunable physicochemical properties that arise from their compositions as well as crystallite size and shape. The ability to control precisely the composition and structure of NPs through synthesis is central to achieving state‐of‐the‐art designer metal NPs for use as catalysts and electrocatalysts. However, a major limitation to the use of designer metal NPs as catalysts is the ability to scale their syntheses while maintaining structural precision. To address this challenge, continuous flow routes to metal NPs involving the use of droplet microreactors are being developed, providing the synthetic versatility necessary to achieve known and completely new nanostructures. This progress report outlines how the chemistry and process parameters of droplet microreactors can be used to achieve high performing nanocatalysts through control of NP composition, size, shape, and architecture and outlines directions toward previously unimaginable nanostructures.

Condensing-enriched magnetic photonic barcodes on superhydrophobic surface for ultrasensitive multiple detection.

The ultrasensitive detection of multiple nucleic acids has great significance in a broad range of medical fields since nucleic acid samples are usually of small volumes and highly diluted. Herein, we present a novel magnetic photonic crystal (PhC) barcode-integrated condensing-enriched superhydrophobic platform for the ultrasensitive multiple miRNA detection. Droplets containing targets could suck the hydrogel PhC barcodes without losing their targets due to the difference in wettability between the hydrophilic PhC barcodes and hydrophobic substrate. During the evaporation of water from the droplet microreactors, these targets could be effectively enriched in the barcodes for achieving higher sensitivities. As the encoding signals of the PhC barcodes are the characteristic reflection peaks generated by their ordered physical nanostructures, the barcodes are stable and free from any fluorescent background and photobleaching; thus, they are accurate for distinguishing different targets. In addition, with the integration of magnetic nanoparticles into the hydrogel PhC barcodes, they could be imparted with the features of immobilization during change of medium and flexible movement for controlling the reaction, both of which could facilitate the detection processes. Based on this platform, we have demonstrated that the detection limit of multiple miRNAs is improved by about three orders. Thus, our platform is an ideal alternative for the ultrasensitive simultaneous multiplex analysis in medical fields.

Controlled Actuation of Liquid Marbles on a Dielectric.

Motivated by the great potential of droplet microreactors for chemical and biological applications, a general and robust method utilizing an electric field is developed for sustained, directional and two-dimensional manipulation of nonwetting droplets (termed "liquid marbles"). With the understanding of the mechanism of actuation, this method allows individual liquid marbles to be actuated and coalesced on demand by fine-tuning the driving voltage. Moreover, in our system, cross-contamination between marbles during manipulation is avoided as confirmed by the absence of any trace DNA after amplification using a loop-mediated isothermal amplification reaction.

Synthesis of zeolitic imidazolate frameworks in droplet microfluidic system

The zeolitic imidazolate frameworks (ZIFs) have been extensively investigated in adsorption, separation and catalysis for their unique properties, e.g . , high surface area, ordered pore structures, tailorable frameworks and high chemical and thermal stability. Zn 2+ and Co 2+ are mostly used metal cations in ZIFs synthesis, because they prefer to form tetrahedron structures with imidazolates and their derived organic ligands. However the conventional preparation methods, which are generally performed at solvothermal condition in the sealed vessel, are time consuming and inhomogeneous process at micro-scale. As a result, the products are always different from batch to batch, which limits the scale-up of ZIFs by conventional synthesis methods. Therefore, facile ways to avoid these problems occurred in ZIFs synthesis are still needed to develop. The microfluidic system is of great advantages such as high surface to volume ratio, high mass and heat transfer efficiency and continuous flow processing. The continuous droplet microfluidic system is effective in mixing for the dynamic micro-environment inside droplets, and it is also effective in reducing the clogging problems for the confined synthesis of nanoparticles inside the microdroplets. Hence the droplet microfluidic system has been widely applied in nanomaterials synthesis. In this work, we design and fabricate a dual T type droplet microreactor to overcome the disadvantages of batch synthesis. The PDMS microchip was fabricated by a scaffold template assisting thermal curing process. Various ZIFs, including monoclinic C2 / c ZIF-7, ZIF-8 and Co doped ZIF-8, were first synthesized in this microfluidic system to demonstrate a universal applicable synthesis method. The concentration of starting material and reaction time were studied in the synthesis of all ZIFs in this work. The results indicated that the increasing of concentration and retention time led to the increasing particles size in all ZIFs, as well as the increasing of product yield. However, the space-time yield was dramatically decreased while the retention time increased from 1 to 5 min, while the yield was just slightly increased. It was because that the micro-synthesis process had been significantly intensified in 1 min for the high mixing and diffusion efficiency in the microfluidic system. Moreover, the mixture solvent of methanol and ammonia water strongly facilitated the formation of ZIFs as well. The high throughput microfluidic system showed an estimated space-time yield of monoclinic C2 / c ZIF-7 (461 kg/(cm 3 d)), ZIF-8 (267 kg/(cm 3 d)) and Co-ZIF-8 (160 kg/(cm 3 d)) in a single microreactor, respectively. It paves the way to massively produce ZIFs without scale-up effect. All the ZIFs obtained from microreactions had high crystallinity except ZIF-67. ZIF-7 synthesized in these conditions showed a typical monoclinic C2 / c ZIF-7 phase respect to the existence of water in the mixture solvents, which drove the structure from porous phase into the dense phase of monoclinic C2 / c ZIF-7. ZIF-8 and Co-ZIF-8 both exhibited sodalite structure respect to the tetra coordination properties of Zn 2+ and Co 2+ . The small polyhedron ZIF-8 particles had grown into large cubic particles with reaction time increased to 5 min. The Co doping exhibited strong effect on the particles morphology. The Co-ZIF-8 prepared from low concentration reactants showed spherical octadecahedron morphology, where {110} surfaces were the main surface. On the contrary, the high concentrated reactants resulted in cubic octadecahedron, where the {100} were mainly occupied the surface. The reason could be that the pure Co was difficult to form ZIF-67 in this condition; therefore the Co changes the formation of ZIF-8. Accordingly, this work provides a facile approach to massively produce diverse ZIFs with controllable morphology in microfluidic system.

Synthesis of AgInS2 QDs in droplet microreactors: Online fluorescence regulating through temperature control

For the synthesis of AgInS2 quantum dots (QDs), a suitable temperature is extremely important for control of the size, shape and fluorescence properties of QDs. Most of synthesis methods for AgInS2 QDs are based on batch reactors, which bring uneven distribution of temperature, affecting their fluorescence properties and size uniformity. Here we designed a droplet microreactor with a temperature-controllable region, and successfully synthesized water-soluble AgInS2 QDs. By accurately controlling temperature, we also studied how the reaction temperature affected the fluorescence properties of AgInS2 QDs. The results showed that with the increasing of reaction temperature, the QDs size increased and the fluorescence peak constantly red-shifted along with enhanced fluorescence intensity. Based on the droplet microreactor, we could achieve more appropriate reaction condition to synthesize AgInS2 QDs with higher fluorescence quantum yield (QY) and intensity.

An integrated gas-liquid droplet microfluidic platform for digital sampling and detection of airborne targets

The use of microfluidic droplets has become ubiquitous in many Lab-on-a-Chip (LOC) applications ranging from material synthesis to novel biochemical sensing. In this paper, we introduce a new droplet-based approach that incorporates a gas phase for generating liquid droplet microreactors in a microfluidic flow-focusing format. We demonstrate the subsequent on-chip transition, collection and handling of the droplets in a secondary liquid carrier inside a multilayer PDMS structure. The presented technique has potential applications in capturing and probing airborne particles and gaseous vapors using high surface-to-volume picoliter droplets. The discrete microfluidic gas-liquid interfaces created in this approach, greatly facilitate absorption and up-concentration of a gaseous target analyte into the droplet volume. The chip-based format of the units also allows for different microfluidic modules and analytical techniques to be integrated in this platform for droplet probing, providing highly-sensitive LOC detection systems. Here, we demonstrate the basic principles of sample partitioning with gas-liquid droplets by capturing and detection of vaporized ammonia at different gaseous concentrations using Nessler’s reaction inside the droplets. The results of this work provide a simple and robust quantification approach for determining gaseous ammonia which can be further expanded to other gas-phase analytes in next generation of airborne target detectors for human breath analysis and environmental monitoring.