Droplet-based Microreactor Research Articles

Bioinspired Hierarchical T Structures for Tunable Wettability and Droplet Manipulation by Facile and Scalable Nanoimprinting.

Developing surfaces that effectively repel low-surface-tension liquids with tunable adhesive properties remains a pivotal challenge. Micronano hierarchical re-entrant structures emerge as a promising solution, offering a robust structural defense against liquid penetration, minimizing area fraction, and creating narrow gaps that generate substantial upward Laplace pressure. However, the absence of an efficient, scalable, and tunable construction method has impeded their widespread applications. Here, drawing inspiration from springtail epidermal structures, octopus suckers, and rose petals, we present a scalable manufacturing strategy for artificial micronano hierarchical T-shaped structures. This strategy employs double-transfer UV-curing nanoimprint lithography to form nanostructures on microstructured surfaces, offering high structural tunability. This approach enables precise control over topography, feature size, and arrangement of nano- and microscale sections, resulting in superamphiphobic surfaces that exhibit high contact angles (>150°) and tunable adhesive forces for low-surface-energy liquids. These surfaces can be applied to droplet-based microreactors, programmable droplet-transfer systems, and self-cleaning surfaces suitable for various liquids, particularly those with low surface tension. Remarkably, we have also succeeded in fabricating the hierarchical structures on flexible and transparent substrates. We demonstrate the advantages of this strategy in the fabrication of hierarchical micronanostructures, opening up a wide range of potential applications.

Single-particle dynamics in a low-Reynolds-number fluid under spherical confinement

Non-colloidal dynamics of a single particle suspended in a low-Reynolds-number fluid under spherical confinement was studied numerically. We calculated hydrodynamic mobilities of a sphere, a prolate spheroid and an oblate spheroid parallel and transverse to the particle-cavity line of centres. The mobilities show maximum in the cavity centre and decay as the particle moves towards the no-slip wall. For prolate and oblate spheroids, their mobilities are also affected by the angle between the particle's axis of revolution and the particle-cavity line of centres due to particle anisotropy. It was observed that the effect of particle anisotropy becomes stronger as the confinement level increases. When the external force on the particle is not parallel or transverse to the particle-cavity line of centres, a drift velocity perpendicular to the force occurs because of the confinement-induced anisotropy of the mobility in the cavity. The normalized drift velocity depends on the particle location, size, shape and orientation of the non-spherical particle. We also studied the motion of a non-neutrally buoyant particle under external forces in a rotating flow inside the cavity. Cooperation between the external force, rotation-induced centrifugal or centripetal force and the force from particle–wall interactions leads to multiple modes of particle motion. A fundamental understanding of single-particle dynamics in this work forms the basis for studying more complex particle dynamics in intracellular transport, and can guide particle manipulation in microfluidic applications ranging from droplet-based microreactors to microfluidic encapsulation.

Continuous Production of Monodisperse Silver Nanoparticles Suitable for Catalysis in a Droplet-Based Microreactor System

Silver nanoparticles (Ag NPs) with sizes below 50 nm have high value in catalysis, especially in electrocatalysis. However, due to the low efficiency of mass and heat transfer, conventional batch synthesis is unable to produce high-quality Ag NPs repeatedly at a large scale. To tackle this obstacle, a droplet-based microreactor system was designed in this work. Continuous and controllable synthesis of Ag NPs with sizes ranging from 7 to 30 nm, polydispersity indexes less than 10%, and high stability which could be stored at room temperature for 2.5 months were achieved by regulating residence time and introducing seed-mediated growth. Based on the Lifshitz–Slyozov–Wagner model and experimental data, growth kinetics were analyzed and revealed it as a diffusion-limited reaction, providing more powerful theoretical support for the synthesis of metal nanomaterials by the microreactor system.

Recent Advances in Microfluidic Devices for the Radiosynthesis of PET-imaging Probes.

In order to accommodate the growing demand for positron emission tomography (PET), it will be necessary to create innovative radiochemical and engineering technologies to optimize the manufacture and development of PET probes. Microfluidic devices allow radiosynthesis to be performed in microscale amounts, significantly impacting PET tracer production. Compared to traditional methods, microfluidic devices can produce PET tracers in a shorter time, higher yields, with lower reagent consumption, higher molar activity, and faster purification. This review examines microfluidic devices from an engineering perspective. Recently developed microfluidic radiosynthesis devices are classified into three categories according to their reaction volume: continuous-flow, batch-flow, and droplet-based microreactors. The principles of device architecture, radiosynthesis process, and the relative strengths and limitations of each category are emphasized by citing typical examples. Finally, the possible future applications of this technology are outlined. A flexible, miniature, fully automated radiochemical microfluidic platform will offer more straightforward and cheaper molecular imaging procedures and the potential for precision medicine that could allow operators to create customized tracers for individual patient doses.

Design of a simple nanoscale hydrophilic-hydrophobic heterojunction system with under-liquid dual superlyophobicity for application in controllable droplet-based microreactor system and oil/water emulsions separation

Recently, many superwetting materials have emerged to deal with environmental problems. Among them, the under-liquid dual superlyophobic superwetting surface has attracted widespread attention due to the possessing of underwater superoleophobicity and underoil superhydrophobicity at the same time, and without the requirement of any energy stimulation when compared to conventional or responsive superwetting surfaces. However, A rational design of this deliciated surface state still lacking. Herein, a novel dual superlyophobic surface was achieved by simply modulating the relative proportion of a nanoscale hydrophilic-hydrophobic heterojunction system - cellulose nanofibrils (CNFs) and graphited multiwalled carbon nanotubes (gMWCNTs), and without any additional chemical modification. Besides, the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory or extended-DLVO (EDLVO) theory was introduced first to help understand the wettability variation of such a heterogeneous surface, which is mainly attributed to the changing stability of oil or water film covering the membrane surface. Additionally, this novel nanoscale hydrophilic-hydrophobic heterojunction system with dual superlyophobicity and excellent flexibility can not only separate both oil-in-water emulsion and water-in-oil emulsion simultaneously, but also achieve the lossless transfer in the droplet-based microreactor system under both water and oil environments. This may bring novel applications to the field of dual superlyophobicity. Moreover, this nanoscale hydrophilic-hydrophobic heterojunction system offers new and universal theoretical guidance for facile preparation of dual superlyophobic surfaces, owing to the richness in the functionality of low dimensional nanomaterials, it is foreseeable that more potential applications in various fields can be coupled with such an adaptable platform.

A nano-liter droplet-based microfluidic reactor serves as continuous large-scale production of inorganic perovskite nanocrystals

Lead halide perovskite nanocrystals (NCs) exhibit high photoluminescence quantum yield (PLQY), high defect tolerance, narrow half peak width, and wide luminous gamut, making them the ideal optoelectronic materials in numerous fields. Nonetheless, their production still suffers from the limited productivity at the bench level. In this work, we fabricated CsPbX3 (X = Cl, Br, I) NCs within droplet-based micro-reactors, where both the nucleation and growth processes could be precisely controlled inside 130-nL microdroplets. This provides a new paradigm for the large-scale synthesis of perovskite NCs with high PLQY. Compared with other synthetic methods, this method can increase the concentration of reactant precursors by 3–116 times, while lowering the ligand to reactant ratio to 2%–50% of the commonly used hot-injection method. By modulating the reaction temperature and residence time, the structure-function relationship between the morphology of NCs and PL properties was extensively investigated. The microfluidic-based process allows the flexible adjustment in the proportion of PbX2 precursors to achieve the fabrication of perovskite NCs whose luminescence range covers the entire visible spectrum (406–677 nm) within one reaction. Finally, perovskite NCs with different halide ions were encapsulated in polymethyl methacrylate to prepare a colored light-emitting diode strip.

Continuous flow nitration of 3-[2-chloro-4-(trifluoromethyl) phenoxy] benzoic acid and its chemical kinetics within droplet-based microreactors

• The synthesis of Acifluorfen by continuous flow nitration was performed within droplet-based microreactor. • The effects of operating parameters were characterized by hydrodynamics and thermodynamics. • The apparent and intrinsic kinetic model was established. Aromatic nitration still faces unmet technical challenges in relation to being heterogeneous and highly exothermic. In this work, a continuous flow aromatic nitration was developed with mixed acid within droplet-based microreactors. The effects of key operating parameters were characterized on the nitration of 3-[2-chloro-4-(trifluoromethyl)phenoxy] benzoic acid. The optimized reaction temperature, M-ratio and N/S were found to be 308 K, 1.6 and 0.57, respectively. Under these conditions, a conversion of 83.03% and selectivity of 79.52% were achieved. The addition of acetic anhydride improved both the solubility of etherate in the organic phase and the absorbability of water produced from the reaction, leading to increase in conversion, however increased by-products accordingly with reduced selectivity. Pseudo-homogeneous kinetics models were developed of apparent and intrinsic reaction rate constant, supporting the second-order reaction assumption. The calculated results based on the kinetics model were found to be in good agreement with the experimental results.

Digital Microfluidic Mixing via Reciprocating Motions of Droplets Driven by Contact Charge Electrophoresis.

Contact charge electrophoresis (CCEP) is an electrically controllable manipulation technique of conductive droplets and particles by charging and discharging when in contact with the electrode. Given its straightforward operation mechanism, low cost, and ease of system construction, it has gained traction as a versatile and potential strategy for the realistic establishment of lab-on-a-chip (LOC) in various engineering applications. We present a CCEP-based digital microfluidics (DMF) platform with two parallel electrode modules comprising assembled conventional pin header sockets, allowing for efficient mixing through horizontal and vertical shaking via droplet reciprocating motions. The temporal chromic change caused by the chemical reaction between the pH indicator and base solutions within the shaking droplets is quantitatively analyzed under various CCEP actuation conditions to evaluate the mixing performance in shaking droplets by vertical and horizontal reciprocating motions on the DMF platform. Furthermore, mixing flow patterns within shaking droplets are successfully visualized by a high-speed camera system. The suggested techniques can mix samples and reagents rapidly and efficiently in droplet-based microreactors for DMF applications, such as biochemical analysis and medical diagnostics.

Large-Scale Production of Ligand-Engineered Robust Lead Halide Perovskite Nanocrystals by a Droplet-Based Microreactor System.

Cesium lead halide perovskite nanocrystals (CLHP NCs) have a wide range of potential applications benefited from the properties of high photoluminescence quantum yield (PLQY), wide luminous gamut, and narrow half peak width. However, due to the ionic nature and sensitivity to moisture, oxygen, or heat, perovskite nanocrystals are too fragile to maintain their crystal structure and optical properties. This work proposes solutions to two key issues in the development of CLHP NCs. First, a productive droplet-based microreactor system is designed to accomplish the scale-up production of CLHP NCs, obtaining sub-gram high-purity nanocrystal powders in a single production process. Second, CLHP NCs which are stable in polar solvents, air environment, and high temperature by using 3-aminopropyl triethoxysilane (APTES) as basic ligand are obtained. Wrapped with Si-O-Si generated by APTES, the CLHP NCs exhibit a longer fluorescence lifetime and higher quantum yield. Especially, the PLQY of CsPbBr3 @APTES can be stable at higher than 90% for more than 10 days. The Si-O-Si protective layer can also suppress the anion exchange between CsPbBr3 and CsPbI3 , maintaining the monochromaticity of nanocrystal luminescence. Eventually, full-spectrum quantum light-emitting diode (QLED) beads with robust nanocrystals are fabricated. The gamut of CsPbX3 @APTES encompasses 140% of the NTSC color gamutstandard.

Oscillation-Induced Mixing Advances the Functionality of Liquid Marble Microreactors.

Droplet-based microreactors often uncover fascinating phenomena and exhibit diverse functionality, which make them applicable in various fields. Liquid marbles (LMs) are non-wetting droplets coated with particles, and these features highlight their potential as microreactors. However, sophisticated experimental designs are typically hindered because it is difficult to obtain sufficient substance mixing in these miniature, damage-prone, self-supporting liquid containers. Here, we demonstrate that subjecting LMs to vertical oscillations by audio signals represents a controllable approach that allows sufficient mixing with variable dynamic modes. The characteristics and key issues in LM oscillation are systematically explored. The effects of oscillation on application potential are examined. Under oscillation conditions, homogeneous mixing can be achieved within a few seconds in LMs consisting of either water or viscous liquids. Importantly, the structures of materials synthesized in LMs can be regulated by modulating the oscillation modes. The variable modes, flexible adjustability, high efficiency, and wide applicability of this oscillation method make it a verified manipulation strategy for advancing the functionality of LM microreactors.

Microfluidic Synthesis, Control, and Sensing of Magnetic Nanoparticles: A Review.

Magnetic nanoparticles have attracted significant attention in various disciplines, including engineering and medicine. Microfluidic chips and lab-on-a-chip devices, with precise control over small volumes of fluids and tiny particles, are appropriate tools for the synthesis, manipulation, and evaluation of nanoparticles. Moreover, the controllability and automation offered by the microfluidic chips in combination with the unique capabilities of the magnetic nanoparticles and their ability to be remotely controlled and detected, have recently provided tremendous advances in biotechnology. In particular, microfluidic chips with magnetic nanoparticles serve as sensitive, high throughput, and portable devices for contactless detecting and manipulating DNAs, RNAs, living cells, and viruses. In this work, we review recent fundamental advances in the field with a focus on biomedical applications. First, we study novel microfluidic-based methods in synthesizing magnetic nanoparticles as well as microparticles encapsulating them. We review both continues-flow and droplet-based microreactors, including the ones based on the cross-flow, co-flow, and flow-focusing methods. Then, we investigate the microfluidic-based methods for manipulating tiny magnetic particles. These manipulation techniques include the ones based on external magnets, embedded micro-coils, and magnetic thin films. Finally, we review techniques invented for the detection and magnetic measurement of magnetic nanoparticles and magnetically labeled bioparticles. We include the advances in anisotropic magnetoresistive, giant magnetoresistive, tunneling magnetoresistive, and magnetorelaxometry sensors. Overall, this review covers a wide range of the field uniquely and provides essential information for designing “lab-on-a-chip” systems for synthesizing magnetic nanoparticles, labeling bioparticles with them, and sorting and detecting them on a single chip.

Secondary Flows, Mixing, and Chemical Reaction Analysis of Droplet-Based Flow inside Serpentine Microchannels with Different Cross Sections

Chemical bioreactions are an important aspect of many recent microfluidic devices, and their applications in biomedical science have been growing worldwide. Droplet-based microreactors are among the attractive types of unit operations, which utilize droplets for enhancement in both mixing and chemical reactions. In the present study, a finite-volume-method (FVM) numerical investigation is conducted based on the volume-of-fluid (VOF) applying for the droplet-based flows. This multiphase computational modeling is used for the study of the chemical reaction and mixing phenomenon inside a serpentine microchannel and explores the effects of the aspect ratio (i.e., AR = height/width) of rectangular cross-sectional geometries as well as three other cross-sectional geometries including trapezoidal, triangular, and circular, on consumption and production rates of chemical species. It is found that in these droplet bioreactors, the reaction begins from the forward section of the droplet. We investigate the secondary flows and chemical reactions inside the droplets in a serpentine microchannel with different cross-sectional geometries. Different transient Dean vortices and secondary flows in the presence and absence of the droplets are studied and explained based on the position of the droplets. It is found that as the droplets pass through the microchannel turns, the patterns and magnitude of the secondary flows change, depending on the cross-sectional geometry. Eventually, the results demonstrate that the AR = 2 rectangular cross-section is the most helpful geometry, whereas the trapezoidal cross-section takes into account the least efficient one between all geometries.

Remote, selective, and in situ manipulation of liquid droplets on a femtosecond laser-structured superhydrophobic shape-memory polymer by near-infrared light

Droplet manipulation plays a significant role in the fields of biomedical detection, microfluidics, and chemical engineering. However, it still remains a great challenge to simultaneously achieve remote, selective, and in situ droplet manipulation on the same surface. Here, Fe3O4 nanoparticles were doped in a shape-memory polymer (SMP) to prepare a photothermal-responsive Fe3O4-SMP composite which showed remarkable near-infrared (NIR) light-triggered shape-memory property. Superhydrophobic micropillar array was constructed on such Fe3O4-SMP composite through femtosecond laser microfabrication and fluoroalkylsilane modification. The surface wettability of the as-prepared surface can transform from a low-adhesive sliding state to a high-adhesive pinning state as the micropillars are deformed by pressing. Interestingly, the deformed micropillars can stand up and restore to their original morphology under remote NIR light irradiation, resulting in the reversible and repeatable recovery of the ultralow-adhesive superhydrophobicity. With such light-triggered wettability switching, the droplets pinning on the sample surface can be remotely, selectively, and in situ released. Furthermore, the superhydrophobic Fe3O4-SMP surface is successfully applied in lossless liquid transfer, selective droplet release, and droplet-based microreactor. The as-fabricated superhydrophobic surfaces with NIR light-controlled reversible wettability will hold great promise in the fields of liquid manipulation, lab-on-a-chip, and microfluidics.

3D-Printed Bioinspired Cassie-Baxter Wettability for Controllable Microdroplet Manipulation.

It is a great challenge to fabricate a surface with Cassie-Baxter wettability that can be continuously adjusted from hydrophilicity to superhydrophobicity by changing of geometric parameters. In this paper, we propose and demonstrate a bioinspired surface fabricated by using a projection micro-stereolithography (PμSL) based 3D printing technique to address the challenge. Independent of materials, the bioinspired textured surface has a maximum contact angle (CA) of 171°, which is even higher than that of the omniphobic springtail skin we try to imitate. Most significantly, we are able to control the CA of the bioinspired surface in the range of 55-171° and the adhesion force from 71 to 99 μN continuously by only changing the geometric parameters of the bioinspired microstructures. The underlying mechanisms of the CA control of our bioinspired surface are also revealed by using a multi-phase lattice Boltzmann model. Furthermore, we demonstrate potential applications in droplet-based microreactors, nonloss water transportation, and coalescence of water droplets by employing our 3D-printed bioinspired structures with their remarkable precise Cassie-Baxter wettability control and petal effects. The present results potentially pave a new way for designing next generation functional surfaces for microdroplet manipulation, droplet-based biodetection, antifouling surfaces, and cell culture.

Continuous and controllable synthesis of MnO2/PPy composites with core–shell structures for supercapacitors

A slug-based microreactor system was constructed to integrate the redox reaction between KMnO4 and MnSO4 with the chemical oxidative polymerization of pyrrole for the preparation of MnO2/PPy composite with a typical core–shell structure. MnO2 was formed as the core while PPy acted as the shell. The size distribution variation of MnO2 particles was elaborated by the crystallization theory and the comparison between the micromixing time and the nucleation induction time. It was found that the morphology of the MnO2/PPy composite was significantly affected by the molar ratio among KMnO4, MnSO4 and pyrrole and the residence time due to the competition between the pyrrole polymerization and the MnO2 crystallization. A probable mechanism for the formation of the PPy/MnO2 composite was proposed. The electrochemical performance of the MnO2/PPy composite with core–shell was better than that of MnO2. The enhanced performance demonstrated the synergistic effect between MnO2 and PPy for the fabrication of the core–shell structure. This work developed the design of particles with core–shell structures from the droplet-based microreactor to the slug-based microreactor with a relatively higher flux. The size of the prepared material decreased from microscale in the droplet-based microreactor to nanoscale in this slug-based microreactor. Such a novel strategy can be applied for efficiently preparing functional materials with controllable structures and properties.

Liquid Marbles as Miniature Reactors for Chemical and Biological Applications

The need for miniaturised reaction systems has led to the development of various microreactor platforms, such as droplet-based microreactors. However, these microreactors possess inherent drawbacks, such as rapid evaporation and difficult handling, that limit their use in practical applications. Liquid marbles are droplets covered with hydrophobic particles and are a potential platform that can overcome the weaknesses of bare droplets. The coating particles completely isolate the interior liquids from the surrounding environment, thus conveniently encapsulating the reactions. Great efforts have been made over the past decade to demonstrate the feasibility of liquid marble-based microreactors for chemical and biological applications. This review systemically summarises state-of-the-art implementations of liquid marbles as microreactors. This paper also discusses the various aspects of liquid marble-based microreactors, such as the formation, manipulation, and future perspectives.

Anisotropic, adhesion-switchable, and thermal-responsive superhydrophobicity on the femtosecond laser-structured shape-memory polymer for droplet manipulation

Smart superhydrophobic surfaces with reversible wettability are attracting increasing attention. However, most of the reported smart superhydrophobic surfaces switch their wettability through reversibly changing surface chemistry rather than surface microstructure. In this paper, femtosecond laser direct writing was exploited to create microgroove array structure on the shape-memory polymer (SMP) substrates. The groove-structured surface exhibited superhydrophobicity and anisotropic wettability after fluoroalkylsilane modification. Due to the excellent shape-memory property of the SMP substrate, the morphology of the microgroove array could be transformed between original stand shape and deformed shape in response to heat. Correspondingly, water droplet on the surface was reversibly changed between sliding and sticky states through alternant pressing and heating treatments, indicating switchable adhesion of the laser-induced microgroove array. Meanwhile, the anisotropic wettability could also recover with the restoration of the grooved microstructure. Such wettability conversion on the resultant surface could be cycled 10 times without decline of the superhydrophobicity and anisotropic wettability. The anisotropic superhydrophobic SMP surface with both ultralow and ultrahigh water adhesion was successfully applied in rewritable liquid pattern, droplet-based microreactor, and gas sensing. By taking advantage of femtosecond laser, reversible microstructures and surface wettability can be obtained on various SMP substrates. We believe that such surfaces with thermal-responsive superhydrophobicity, anisotropic wettability, and switchable adhesion will have enormous potential applications in non-loss droplet transfer, biological detection, and lab-on-chip devices.

Continuous preparation of itraconazole nanoparticles using droplet-based microreactor

Abstract The nano-sized drug is an alternative strategy for enhancing the dissolution rate of pharmaceutical ingredients with poor solubility. Microfluidic technology has been widely applied for the preparation of nanoparticles because of its controllability. Combining the above two concerns, this study proposed an anti-solvent precipitation method to obtain itraconazole (ITZ) nanoparticles using a continuous flow droplet-based microreactor. In addition to the experimental study of the generation of different shapes of droplets, the influencing factors of nanoparticle preparation such as the flow rate ratio of the dispersed phase to the continuous phase, the residence time, the drug initial concentration and the stabilizer were further analyzed. The advantages of the droplets system were fully demonstrated in comparison with the conventional laminar flow system in the form of the T microfluidic device. The results showed that smaller nanoparticles of itraconazole with narrower size distribution were prepared in droplets and addressed that the particle agglomeration and growth would be restrained in droplets under the increased residence time, higher initial concentration or amphiphilic stabilizers.

Droplet-based microreactor for the production of micro/nano-materials.

Droplet-based microreactors are of great interest to researchers due to their incredible ability in the synthesis of micro/nano-materials with multi-function and complex geometry. In recent years, a broad range of micro/nano-materials has been synthesized in droplet-based microreactors, which provide apparent advantages, such as better reproducibility, reliable automation, and accurate manipulation. In this review, we give a comprehensive and in-depth insight into droplet-based microreactors, covering fundamental research from droplet generation and manipulation to the applications of droplet-based microreactors in micro/nano-material generation. We also explore the outlook for droplet-based microreactors and challenges that lie ahead and give a possible effort direction. We hope this review will promote communications among researchers and entrepreneurs.

Suzuki-Miyura cross-coupling reaction in droplet-based microreactor

An ionic liquid (IL)-based Suzuki-Miyaura cross-coupling reaction was implemented successfully in a droplet-based microreactor. FC-40 fluorocarbon-based liquid was introduced as the continuous phase to disperse reactants into uniform droplets. The negligible effect of the existence of FC-40 on reaction and product analysis was clarified, and then the reaction performance within droplets was investigated under different operating conditions. The application of droplet-based microreactor not only solved the clogging problem in a microchannel due to high viscosity of ionic liquids, but also improved the reaction yield by intensifying mixing. Compared with a batch reactor, the yield in the droplet-based microreactor improved evidently, i.e., from 59.4% to 68.7% at 83 °C with the reaction time at 10 min.