Millifluidic Reactor Research Articles

Seeded-growth synthesis of 20–60 nm monodisperse citrate-capped gold nanoparticles in a millifluidic reactor

Seeded-growth synthesis of 20–60 nm monodisperse citrate-capped gold nanoparticles in a millifluidic reactor

Supercritical millifluidic reactor for the synthesis of efficient GaN nanophotocatalysts

Here, we demonstrate the continuous synthesis of gallium nitride (GaN) nanophotocatalysts exhibiting high quantum confinement using a preheated supercritical millireactor. The GaN quantum dots (QDs) are obtained from the direct thermolysis of a single source amido complex precursor (tris(dimethyl)amido gallium(III) dimer), in anhydrous supercritical cyclohexane. The quality of the synthesized QDs is highly dependent on the chemical pathways for the single source precursor thermolysis. Through the use of numerical modeling, we designed a millifluidic reactor allowing a sufficiently high heating rate for a direct precursor thermolysis towards efficient GaN nanoparticles. The as-designed preheated supercritical flow reactor yields highly reproducible GaN QDs (optical properties, crystallite phase and morphology) at high throughput, enabling gram scale production. Eventually, the photocatalytic properties of the GaN QDs were evaluated in a direct photochemical reaction through the degradation of a dye molecule (Methyl Orange). The obtained results demonstrate the higher photocatalytic activity of such photocatalysts compared to the commercially and reference available Degussa P25.

Continuous, green, and room-temperature synthesis of silver nanowires in a helically-coiled millifluidic reactor

Over the past decade, silver nanowires (AgNWs) have been considered as promising alternatives for manufacturing flexible and transparent conductive films used in the production of various electronic and wearable devices. Nevertheless, the continuous and large-scale synthesis of AgNWs without the use of high-energy methods and hazardous reagents can be challenging. In this study, we report the continuous, green and sustainable synthesis of AgNWs at room temperature in a helically-coiled plug flow millifluidic reactor, using tannic acid as an environmentally-friendly reducing and capping agent. The synthesized AgNWs were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and UV–visible spectroscopy (UV-Vis). We have showed that the presence of silicone oil and triton X-100 is necessary for the undisturbed synthesis of AgNWs. We further demonstrated that AgNWs synthesized in the millifluidic reactor had a higher yield (by 32%) compared to those synthesized in batch condition. We further showed how the synthesis of AgNWs can be affected by exposure to UV–visible light. Finally, we investigated the effect of coil diameter on the consumption of Ag+ ions, the morphology of silver nanostructures, and the yield of AgNWs. The proposed approach can serve as a promising technique for the continuous synthesis of AgNWs and further green and sustainable manufacturing in the field of nanomaterials synthesis.

(Invited) Slug-Flow Manufacturing of Nickel-Cobalt-Manganese-Oxide Cathode Particles for Lithium-Ion Batteries

With expanding demands of lithium-ion batteries in portable electronic devices (e.g., smartphones, tablet PCs) and environmental-friendly vehicles (e.g., electric and/or hybrid vehicles), it is important to further improve safety, extend battery life, increase charge capacity, and reduce cost. A key missing component is effective and efficient manufacturing of complex active cathode materials at needed scales, such as nickel-cobalt-manganese (NCM) oxide microparticles with layered structures. Specifically, the material microparticle quality and uniformity have been difficult to control within the current reactors, thus extra correction procedures are needed, which risk product quality and reduce process efficiency. This study examines the innovative slug-flow continuous manufacturing process to directly produce well-controlled microparticles with advanced battery performance and accelerated scale-up, while enhancing fundamental understandings. The process utilizes a slug-flow reactor in which a multiphase mixture of liquid and gas in a tube spontaneously separates into slugs of liquid or slurry separated by slugs of gas. We have devised the milli-fluidic reactor and flow conditions so that hydrodynamically stable slugs form spontaneously immediately upon contact of the liquid and gas. Typical liquid/slurry slugs are 2-mm in length and 2-mm in diameter. In addition, we are able to selectively inject additional reactants in individual slugs to carry out the follow-on reactions. The sequential addition of the desired NCM precursors have allowed us to control the NCM radial profile in each particle. Microscopically, in a slug-flow reactor, each particle experiences the same environment with spatially uniform reaction conditions (kinetics, hydrodynamics) throughout the nucleation-growth process, leading to uniform particles with controlled composition and properties. Macroscopically, the manufacturing setup and conditions can remain the same while allowing convenient tuning of the production rate (scaling up or down). The electrochemical performance of the produced cathode particles is further enhanced by innovating coating treatment. Nonetheless, the technology/process equipment is being so developed that new battery chemistry can be easily incorporated with new future developments. Battery performance using NCM811 are tested and the results will be reported. Figure 1

Batch-screening guided continuous flow synthesis of the metal-organic framework HKUST-1 in a millifluidic droplet reactor

Metal-organic frameworks (MOFs) are a class of crystalline and porous adsorbents, with wide-ranging applications in gas separations, membrane materials as well as sensors. Commonly used batch synthesis techniques for MOF production are limited by low productivity, high operating costs, and slow crystallization timescales, severely impeding the large-scale manufacturing of these materials. However, batch synthesis is a useful and easy technique to screen multiple reaction parameters to find an optimal chemistry. Therefore, in this study, we have used the batch process and screened a multidimensional reaction space consisting of 45 sample variations based on the crystallinity, yield, and instantaneous precipitation, which could lead to tube clogging under flow conditions. We have found one optimized reaction chemistry, that could be used in flow conditions, which in this study is a novel millifluidic droplet-based reactor for the continuous synthesis of HKUST-1 crystals. The biphasic flow in the millifluidic reactor consisted of droplets of the reactant solution, dispersed in a continuous phase of silicone oil. We investigate the differences in the quality and quantity of HKUST-1 synthesized via the continuous and batch techniques. Moreover, we have demonstrated that the HKUST-1 samples prepared via the continuous synthesis in a droplet based millifluidic reactor, at an ultra-low residence time exhibit excellent physical properties comparable to that obtained for the samples prepared by the traditional batch process. A clean, easy-to-install, and reusable millifluidic reactor presented in this work may pave the path for an economically viable, large-scale synthesis of HKUST-1.

Sustainable, Green, and Continuous Synthesis of Fivefold Palladium Nanorods Using l-Ascorbic Acid in a Segmented Millifluidic Flow Reactor.

Pd nanorods (PdNRs) have recently come to attention due to their wide array of applications. The green synthesis of PdNR with a relatively high yield and high aspect ratio is challenging. A continuous millifluidic flow reactor (CMFR) has been explored to precisely control mass and heat transfer as well as mixing in the PdNR synthesis processes. CMFRs demonstrate a few drawbacks, such as the presence of parabolic velocity profile in the laminar flow of the reaction solution, causing uneven axial residence time distribution. The CMFRs are likely to show irreversible fouling, which may cause the product quality to deteriorate or result in the channel being clogged. These shortcomings can be avoided or minimized using a segmented millifluidic flow reactor (SMFR) that consists of the solution forming a train of individual segments in another inert medium. This study explores the use of a sustainable reducing agent (l-ascorbic acid) in the presence of potassium bromide (KBr) as the capping agent and poly(vinyl pyrrolidone) (PVP) as the stabilizing agent for PdNR synthesis in an SMFR employing compartmentalized flow of a reaction solution, in which liquid segments consisting of a reaction solution will be immersed in the steam generated by boiling of the solvent water. The effect of reaction parameters such as reagent concentration has been studied on the size and morphology of synthesized Pd nanostructures. A kinetic study has been conducted to calculate the rate of reduction that can be used as a quantitative measure for manipulation of the type and relative concentration of initially formed seeds. It has been shown that the initial reduction rate during the first 45 min of residence time of the millifluidic reactor is about 66% faster compared to the rest of the reaction. A filtration procedure has been utilized to separate Pd nanostructures other than nanorods synthesized in the SMFR.

Supercritical Millifluidic Reactor for the Synthesis of Efficient Gan Nanophotocatalysts

Supercritical Millifluidic Reactor for the Synthesis of Efficient Gan Nanophotocatalysts

New concept of radiolytic synthesis of gold nanoparticles in continuous flow

Radiolytic synthesis has been used to produce a plethora of unsupported and supported metallic nanoparticles in batch. As proof of a new concept, we evaluated the formation of gold nanoparticles by radiolytic synthesis in continuous flow using a millifluidic reactor. A mixture of gold ions solution, branched polyethyleneimine, and ethylene glycol yielded gold nanoparticles with a mean size of 3.4 ± 1.0 nm after irradiation with an X-ray irradiator (127 Gy/min) at an absorbed dose of 5.1 kGy. The morphology and size distribution of gold nanoparticles was influenced by AgNO3, where its absence resulted in a mean size of 20.9 ± 15.8 nm. The radiolytic synthesis of gold nanoparticles in continuous flow was achieved in short reaction times (<60 min), at room temperature, and with low concentrations of both stabilizing and reducing agents. These results demonstrate the potential of radiolytic synthesis in continuous flow for high-throughput formation of metallic nanoparticles with controlled specifications in size and distribution.

Continuous-Flow Production of Liposomes with a Millireactor under Varying Fluidic Conditions.

Continuous-flow production of liposomes using microfluidic reactors has demonstrated advantages compared to batch methods, including greater control over liposome size and size distribution and reduced reliance on post-production processing steps. However, the use of microfluidic technology for the production of nanoscale vesicular systems (such as liposomes) has not been fully translated to industrial scale yet. This may be due to limitations of microfluidic-based reactors, such as low production rates, limited lifetimes, and high manufacturing costs. In this study, we investigated the potential of millimeter-scale flow reactors (or millireactors) with a serpentine-like architecture, as a scalable and cost-effective route to the production of nanoscale liposomes. The effects on liposome size of varying inlet flow rates, lipid type and concentration, storage conditions, and temperature were investigated. Liposome size (i.e., mean diameter) and size dispersity were characterised by dynamic light scattering (DLS); z-potential measurements and TEM imaging were also carried out on selected liposome batches. It was found that the lipid type and concentration, together with the inlet flow settings, had significant effects on the properties of the resultant liposome dispersion. Notably, the millifluidic reactor was able to generate liposomes with size and dispersity ranging from 54 to 272 nm, and from 0.04 to 0.52 respectively, at operating flow rates between 1 and 10 mL/min. Moreover, when compared to a batch ethanol-injection method, the millireactor generated liposomes with a more therapeutically relevant size and size dispersity.

Rapid Millifluidic Synthesis of Stable High Magnetic Moment FexCy Nanoparticles for Hyperthermia.

A millifluidic reactor with a 0.76 mm internal diameter was utilized for the synthesis of monodisperse, high magnetic moment, iron carbide (FexCy) nanoparticles by thermal decomposition of iron pentacarbonyl (Fe(CO)5) in 1-octadecene in the presence of oleylamine at 22 min nominal residence time. The effect of reaction conditions (temperature and pressure) on the size, morphology, crystal structure, and magnetic properties of the nanoparticles was investigated. The system developed facilitated the thermal decomposition of precursor at reaction conditions (up to 265 °C and 4 bar) that cannot be easily achieved in conventional batch reactors. The degree of carbidization was enhanced by operating at elevated temperature and pressure. The nanoparticles synthesized in the flow reactor had size 9–18 nm and demonstrated high saturation magnetization (up to 164 emu/gFe). They further showed good stability against oxidation after 2 months of exposure in air, retaining good saturation magnetization values with a change of no more than 10% of the initial value. The heating ability of the nanoparticles in an alternating magnetic field was comparable with other ferrites reported in the literature, having intrinsic loss power values up to 1.52 nHm2 kg–1.

An Exceptionally Mild and Scalable Solution-Phase Synthesis of Molybdenum Carbide Nanoparticles for Thermocatalytic CO2 Hydrogenation.

Transition metal carbides (TMCs) have demonstrated outstanding potential for utilization in a wide range of catalytic applications because of their inherent multifunctionality and tunable composition. However, the harsh conditions required to prepare these materials have limited the scope of synthetic control over their physical properties. The development of low-temperature, carburization-free routes to prepare TMCs would unlock the versatility of this class of materials, enhance our understanding of their physical properties, and enable their cost-effective production at industrial scales. Here, we report an exceptionally mild and scalable solution-phase synthesis route to phase-pure molybdenum carbide (α-MoC1-x) nanoparticles (NPs) in a continuous flow millifluidic reactor. We exploit the thermolytic decomposition of Mo(CO)6 in the presence of a surface-stabilizing ligand and a high boiling point solvent to yield MoC1-x NPs that are colloidally stable and resistant to bulk oxidation in air. To demonstrate the utility of this synthetic route to prepare catalytically active TMC NPs, we evaluated the thermochemical CO2 hydrogenation performance of α-MoC1-x NPs dispersed on an inert carbon support. The α-MoC1-x/C catalyst exhibited a 2-fold increase in both activity on a per-site basis and selectivity to C2+ products as compared to the bulk α-MoC1-x analogue.

Self-optimizing parallel millifluidic reactor for scaling nanoparticle synthesis.

We developed a 16-channel millifluidic reactor that uses a multiphase gas-liquid flow to continuously produce colloidal CsPbBr3 quantum dots with a throughtput of ∼1 L h-1. The optical properties of the product were monitored, and the reaction conditions were optimized in real time based on the in situ photoluminescence characteristics of the quantum dots.

A Millifluidic Reactor System for Multistep Continuous Synthesis of InP/ZnSeS Nanoparticles

AbstractDespite the growing interest in quantum dots for applications ranging from bioimaging to display technologies, the reproducible and high‐quality synthesis of Cd‐free quantum dots (QDs) on a large scale remains challenging. Conventional large‐scale batch synthesis techniques are limited by slow precursor heating/cooling/mixing, poor reproducibility and low productivity. In recent years, the continuous flow synthesis of QDs using microfluidic approaches has shown promise to overcome the shortcomings of batch synthesis. However, the application of microfluidic reactors for synthesis of Cd‐free QDs exhibiting high photoluminescence quantum yield (PL QY) at high production rate remains a challenge. Here, we report a modular millifluidic reactor for the fully continuous multi‐step synthesis of InP/ZnSeS core‐shell QDs, that integrates the precise control over reaction conditions with the potential for gram‐scale production rates. We use a design of experiment approach to understand and optimize the process parameters for the synthesis, resulting in PL QY up to 67% with good reproducibility in terms of both QY and peak position (less than 5% standard deviation). Additionally, by changing the process parameters for different reaction stages (core and shell reactors), the wavelength of the InP/ZnSeS particles can be tuned to cover nearly the entire visible spectrum (480–650 nm).

Silver Nanowire Synthesis in a Continuous Millifluidic Reactor

A millifluidic polyol process was used to produce high aspect ratio silver nanowires (AgNWs) with high selectivity. For comparison, AgNWs were synthesized in both a batch reactor and a continuous millifluidic reactor. The wires were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), Energy-dispersive X-ray (EDX) spectroscopy and UV-Visible (UV-Vis) spectroscopy. The effect of temperature was investigated to optimize morphology and selectivity. High selectivity of very long and thin AgNWs was obtained in the millifluidic reactor. In comparison with the batch reactor, superior selectivity and aspect ratios were obtained in the millifluidic reactor, and a lower operating temperature could be used. The effect of residence time (flow rate) on the diameter and length of the synthesized AgNWs was investigated. Finally, Reynolds and Peclet number were calculated to investigate the silver nanostructures flow behavior during the course of synthesis.

Hollow cross-linked enzyme aggregates (h-CLEA) of laccase with high uniformity and activity

Hollow cross-linked enzyme aggregates of laccase (h-CLEA laccase) can be prepared by employing a millifluidic reactor carrying two coaxial laminar flows. In a confluence zone where acetonitrile and an aqueous solution of laccase meet, diffusion of acetonitrile into the aqueous solution gives rise to rapid precipitation of laccase aggregates at the water/acetonitrile interface, as is evidenced by fluorescence images. By controlling the flow rates carefully in the laminar flow regions, h-CLEA laccase around 220±10nm can be obtained, and the size of the h-CLEA laccase increases with increasing flow rates of both solutions. The h-CLEA laccase particles are distinctly different from CLEA laccase prepared in batch processes. The former only consist a crust of cross-linked enzymes (with a hollow core) whereas the latter has a highly porous structure. When the h-CLEA laccase is used as biocatalysts, their activity (0.26U/mg) is comparable to that of free enzymes at neutral pH due to the hollow structure. Moreover, the activity of h-CLEA laccase is higher than that of free laccase at high pH. For example, trypan blue (a dye molecule) can be decolorized completely in the presence of h-CLEA laccase within 270min even at pH 10.0, at which the free enzyme completely loses its activity. Because of their uniform sizes, h-CLEA laccase can be trapped in a membrane for continuous degradation of trypan blue up to 96h without losing any activity. This study shows the superiority of h-CLEA laccase compared to other types of immobilized enzymes.

Millifluidic synthesis of amorphous drug-polysaccharide nanoparticle complex with tunable size intended for supersaturating drug delivery applications

The conventional bulk mixing method to prepare amorphous drug-polysaccharide nanoparticle complex (or drug nanoplex in short) has a major drawback in the lack of size control for the nanoplex produced, hence limiting its potential applications as a supersaturating drug delivery system for bioavailability enhancement of poorly soluble drugs. For this reason, we developed a continuous millifluidic synthesis platform of the drug nanoplex exhibiting high size tunability using curcumin (CUR) and chitosan (CHI) as the models for drug and polysaccharides, respectively. The nanoplex size tunability was achieved by controlling the residence time of the CUR and CHI solutions in the millifluidic reactor, where their slow diffusive mixing at the liquid-liquid interface resulted in a well-regulated nanoplex growth as a function of the residence time. The effects of the preparation pH, molecular weight of CHI, millifluidic tube diameter, and flowrate on the nanoplex size tunability were investigated from which the optimal preparation condition was determined. At the optimal condition, the CUR nanoplex was roughly ≈115nm in size with zeta potential of ≈15mV and ≈72% (w/w) CUR payload. The millifluidic synthesis also maintained the high CUR utilization rate (≈80%) exhibited by the bulk mixing method. Most importantly, the ability to produce significantly smaller nanoplex (sixfold smaller) via millifluidics led to the generation of higher (≈8.5× of CUR saturation solubility) and prolonged (≈8h) supersaturation level. These results bode well for the bioavailability enhancement potential of the drug nanoplex.

Entrapment of cross-linked cellulase colloids in alginate beads for hydrolysis of cellulose

Entrapment of enzymes in calcium alginate beads is a popular enzyme immobilization method. However, leaching of immobilized enzymes from the alginate beads is a common problem because enzyme molecules are much smaller than the pore size of alginate beads (∼200nm). To address this issue, we employ a millifluidic reactor to prepare cross-linked cellulase aggregate (XCA) colloids with a uniform size (∼300nm). Subsequently, these colloids are immobilized in calcium alginate beads as biocatalysts to hydrolyze cellulose substrates. By using fluorescent microscopy, we conclude that the immobilized XCA colloids distribute uniformly inside the beads and do not leach out from the beads after long-term incubation. Meanwhile, the pore size of the alginate beads is big enough for the cellulose substrates and fibers to diffuse into the beads for hydrolysis. For example, palm oil fiber and microcrystalline cellulose can be hydrolyzed within 48h and release reducing sugar concentrations up to 2.48±0.08g/l and 4.99±0.09g/l, respectively. Moreover, after 10 cycles of hydrolysis, 96.4% of the XCA colloids remain inside the alginate beads and retain 67% of the original activity. In contrast, free cellulase immobilized in the alginate beads loses its activity completely after 10 cycles. The strategy can also be used to prepare other types of cross-linked enzyme aggregates with high uniformity.

Continuous hydrolysis of carboxymethyl cellulose with cellulase aggregates trapped inside membranes

Enzymatic hydrolysis of cellulose is often conducted in batch processes in which hydrolytic products tend to inhibit enzyme activity. In this study, we report a method for continuous hydrolysis of carboxymethyl cellulose (CMC) by using cross-linked cellulase aggregate (XCA) trapped inside a membrane. XCA particles prepared by using a millifluidic reactor have a uniform size distribution around 350nm. Because of their large size, XCA particles in solutions can be filtered through a polyethersulfone membrane to collect 87.1±0.9% of XCA particles. The membrane with impregnated XCA can be used as a catalyst for hydrolysis of CMC in a continuous mode. When the CMC concentration is 1.0g/l and the flow rate is 2μl/min, 53.9% of CMC is hydrolyzed to reducing sugars. The membrane with XCA is very stable under continuously flowing solutions. After 72h of reaction, 97.5% of XCA remains inside the membrane.

Uniform cross-linked cellulase aggregates prepared in millifluidic reactors

HypothesisUniform cross-linked cellulase aggregate (XCA) can be prepared by using a millifluidic reactor which consists of two inlets and a Y-junction, because mixing pattern and spatial distribution of reactants can be controlled precisely. ExperimentsAqueous cellulase solution is mixed with acetonitrile (as a precipitant) and 20mM of glutaraldehyde (as a cross-linker) at the Y-junction. XCA is collected from the outlet of the reactor. FindingsUniform XCA, with an average size between 200nm and 400nm, can be formed inside the reactor. Unlike free cellulase, XCA is insoluble such that it can be filtered out from the solution. It can be used alone or absorb on silica gel (XCA-Si) as a catalyst for hydrolyzing carboxymethyl cellulose (CMC). Interestingly, XCA-Si shows highest activity at pH 4.8 and 50°C, which is similar to the optimal condition of free cellulase. Moreover, XCA-Si is more stable than free cellulase at high temperature (>60°C). It precipitates naturally and can be recycled at least 5 times after the hydrolysis of CMC.

A Simple Millifluidic Benchtop Reactor System for the High-Throughput Synthesis and Functionalization of Gold Nanoparticles with Different Sizes and Shapes

Despite the continuing interest in the applications of functionalized nanomaterials, the controlled and reproducible synthesis of many important functionalized nanoparticles (NPs) above the milligram scale continues to be a significant challenge. The synthesis of functionalized NPs in automated reactors provides a viable approach to circumvent some of the shortcomings of traditional nanomaterial batch syntheses, providing superior control over reagent addition, improved reproducibility, the opportunity to interface real-time product monitoring, and a viable high-throughput synthetic approach. Here, we demonstrate the construction and operation of a simple millifluidic reactor assembled entirely from commercially available components found in almost any chemical laboratory. This reactor facilitates the aqueous gram-scale synthesis of a variety of functionalized gold nanoparticles, including the synthesis of gold nanospheres with tightly controlled core diameters and gold nanorods with controlled aspect ratios between 1.5 and 4.0. The absolute dimensions (i.e., the transverse diameter) of gold nanorods synthesized within the reactor can also be tailored to produce different gold nanorod shapes, including "small" gold nanorods and gold nanocubes. In addition, we show that the reactor can interface with existing purification and monitoring techniques in order to enable the high-throughput functionalization/purification of gold nanorods and real-time monitoring of gold nanoparticle products for quality control. We anticipate that this millifluidic reactor will provide the blueprint for a versatile and portable approach to the gram-scale synthesis of monodisperse, hydrophilically functionalized metal NPs that can be realized in almost any chemistry research laboratory.