Droplet Generation Process Research Articles

Guide to microfluidic systems and the preparation of emulsions

AbstractMicrofluidic technology, as an effective method for precise manipulation of microfluid volumes, has demonstrated significant potential in the preparation of emulsions. This guideline introduces key components of a microfluidic operating system, including the design of microfluidic chips (such as T‐junction, flow‐focusing, and co‐flowing structures), fluid driving systems, control systems, and observation and detection systems, explaining how they collaborate to accurately control the droplet generation process. In terms of specific steps for emulsion preparation, the guideline details the workflow utilizing microfluidic technology to fabricate both single‐layer O/W and W/O emulsions, as well as complex multi‐layer emulsions, emphasizing critical considerations during experimentation. Through in‐depth understanding and judicious application of microfluidic technology, there is a promise to advance emulsion preparation techniques across various domains, including drug delivery, food technology, biotechnology, and materials science.

Characteristic evolution and energy variation during the generation of water droplet

Understanding water droplet characteristic is an important prerequisite for improving wet dust removal efficiency. Using the high-speed camera system, the process of water droplet generation under the different Ca2+ concentrations and injecting velocities was studied. The width and length of water droplet increased, whereas the ratio of droplet width and length decreased with generation time. The water droplet generation time decreased with injecting velocity increasing, whereas kept almost unchanged with Ca2+ concentration. The equivalent diameter of droplet decreased with injecting velocity, whereas presented first a slight decrease and then a slight increase with Ca2+ concentration. This result suggested that the injecting velocity effect was stronger than the Ca2+ effect on the water droplet generation time and size. Furthermore, the effective injecting force and capillary force were mainly forces to influence the droplet generation in force analysis. RF (ratio of capillary force and effective pressure force) was first used to evaluate the synergistic effect of capillary force and effective injecting force. The greater RF, the water droplet generation time was longer and water droplet diameter was larger. Furthermore, the relationship between surface energy per unit (E/S) of water droplet and RF was a negative correlation. Those results can provide valuable suggestions to the development theory of dust removal.

Investigation of co-flow step emulsification (CFSE) microfluidic device and its applications in digital polymerase chain reaction (ddPCR)

HypothesisThe co-flow step emulsification (CFSE) is very sensitive to the two-phase fluid interfaces, we conjecture that the CFSE hydrodynamic model depends on several key factors and the droplet generation process can be precisely controlled, thus to obtain droplet emulsions with the “ultra-high volume fraction of inner-phase” and “flexible droplet size” characteristics. The resulting droplets are expected to be applied to droplet digital PCR (ddPCR) with “high information density” and “wide dynamic range” advances. ExperimentsBy combining numerical simulation and fluid dynamics experiments, we have investigated the crucial parameters affecting the CFSE two-phase interface and finally achieved the prediction and guidance for CFSE droplet production. FindingsWith the help of the CFSE device, multivolume droplet populations were produced on demand. Then, ddPCR tests were performed with DNA concentrations from 10 copies/μL to 20,000 copies/μL. The CFSE device owns an ultra-wide dynamic range (up to 5 orders of magnitude), showing excellent quantification ability of nucleic acid targets.

Double emulsion generation in shear-thinning fluids under electric field effects

Double emulsions are encapsulated microstructures with medical, food, and cosmetics applications. Precise control over their parameters, such as volume, thickness, and size distribution, is crucial. This study numerically investigates, for the first time, the generation of double emulsions in a shear-thinning outer fluid under the influence of an external DC electric field. A dual co-flowing microfluidic device is chosen as the flow domain, and the shear-thinning behavior of the outer fluid is approximated by the Carreau–Yasuda rheological model. The governing equations are discretized on structured numerical grids using the VOF-CSF model and the finite volume method. The combined effects of the shear-thinning behavior and electric forces on compound droplet formation parameters, including volume, eccentricity, maximum thickness, and jet length, are studied carefully. Results show that for highly shear-thinning fluids, the application of electric forces can ensure the generation of desired compound droplets, which is not feasible without electric field effects. However, excessive electric forces can disrupt the droplet generation process, especially for moderate to low shear-thinning fluids. These findings provide new insights into the role of external electric fields in double emulsion generation and highlight their potential to optimize the production process.

Study on jetting droplet formation regime in a low-speed annular shear flow field

This study aims to explore the mechanism of droplet generation and the change rule of liquid bridge in an annular shear flow field. With the help of a two-phase system of continuous phase (deionized water)-dispersed phase (fluorescent oil), the process of droplet generation under the jetting mechanism was captured using a camera. By studying the effect of the dispersed phase flow rate on the length of the liquid bridge, it was found that the volume flow rate of the dispersed phase is positively correlated with the frequency of droplet formation and the droplet size, and that the distance of the liquid bridge is also positively correlated with the droplet size under the jetting mechanism. Besides, a prediction mechanism for the maximum stable droplet under the jetting mechanism is proposed based on the droplet formation process.

Effect of inevitable ions on kerosene droplet formation and evolution

AbstractBACKGROUNDUnderstanding the effect of ions on collector generation characteristics is crucial for adjusting the oil/water interface and enhancing mineral flotation.METHODSWe conducted a study of the kerosene droplet generation process in the presence of NaCl, MgCl2, and AlCl3 using a high‐speed motion acquisition system.RESULTS AND CONCLUSIONSThe results showed that the generation process of kerosene droplets could be divided into two stages, droplet expansion and column contraction, according to variations of the droplet width. With the increasing capillary inner diameter, the generation time of the kerosene droplet increased, while the w/h value (column width/column height) of the kerosene column decreased. When the w/h value decreased to 0, the droplet column ruptured, and the droplet separated from the capillary. As the ion valence increased, the equivalent diameter (d) of the kerosene droplet increased due to the ionic hydration and followed the order dAl3+ > dMg2+ > dNa+. Furthermore, as the ion concentration increased, the equivalent diameter increased with the same capillary inner diameter, and the w/h value decreased. A model of the kerosene column height and capillary inner diameter (R) was established to predict the characteristics of the generated kerosene droplet. © 2023 Society of Chemical Industry (SCI).

Analytical validation of the DropXpert S6 system for diagnosis of chronic myelocytic leukemia.

Digital PCR is a powerful method for absolute nucleic acid quantification and is widely used in the absolute quantification of viral copy numbers, tumor marker detection, and prenatal diagnosis. However, for most of the existing droplet-based dPCR systems, the droplet generation, PCR reaction, and droplet detection are performed separately using different instruments. Making digital PCR both easy to use and practical by integrating the qPCR workflow into a superior all-in-one walkaway solution is one of the core ideas. A new innovative and integrated digital droplet PCR platform was developed that utilizes cutting-edge microfluidics to integrate dPCR workflows onto a single consumable chip. This makes previously complex workflows fast and simple; the whole process of droplet generation, PCR amplification, and droplet detection is completed on one chip, which meets the clinical requirement of "sample in, result out". It provides high multiplexing capabilities and strong sensitivity while all measurements were within the 95% confidence interval. This study is the first validation of the DropXpert S6 system and focuses primarily on verifying its reliability, repeatability, and consistency. In addition, the accuracy, detection limit, linearity, and precision of the system were evaluated after sample collection. Among them, the accuracy assessment by calculating the absolute bias of each target gene yielded a range from -0.1 to 0.08, all within ±0.5 logarithmic orders of magnitude; the LOB for the assay was set at 0, and the LoD value calculated using probit curves is MR4.7 (0.002%); the linearity evaluation showed that the R2 value of the BCR-ABL was 0.9996, and the R2 value of the ABL metrics calculated using the ERM standard was 0.9999; and the precision evaluation showed that all samples had a CV of less than 4% for intra-day, inter-day, and inter-instrument variation. The CV of inter-batch variation was less than 7%. The total CV was less than 5%. The results of the study demonstrate that dd-PCR can be applied to molecular detection and the clinical evaluation of CML patients and provide more precise personal treatment guidance, and its reproducibility predicts the future development of a wide range of clinical applications.

Advancing scalable and controllable multi-core droplet generation with double disturbance flow focusing.

At present, a variety of active and passive methods for generating microdroplets with different morphologies are available. Microcapsules with multi-core or compartment structures not only exhibit characteristics such as encapsulation, isolation, and leak prevention, but also possess specific functions, including enhanced buffering performance and superior heat transfer characteristics. Nevertheless, the high-throughput manufacturing of controllable multi-core droplets remains a significant challenge, constrained by the complexity of the equipment, the inconvenience of control, and the high cost. This study introduces a novel flow focusing method that integrates biphasic excitation to produce uniformly distributed double-emulsion droplets with a controlled number of cores at high throughput. The breakup of coaxial jets has been studied under different excitation frequencies, amplitudes, and flow rates of inner and outer liquids, with a particular focus on the change of the droplet morphology as the controllable parameter varies. By applying excitation to both the inner and outer jets in the weak coupling mode, our technique exhibits promising outcomes in achieving uniformity and controllability in the number of cores of the generated droplets. The scaling laws of the compound droplet size have been obtained, providing theoretical guidance for practical applications. The proposed biphasic excitation approach enhances the precision and efficiency of droplet generation processes in a range of applications, including pharmaceuticals, biotechnology, and materials science.

Experiments on the onset of boiling entrainment from a falling liquid film with gas sheared flow

The process of droplet entrainment caused by nucleate boiling within a falling liquid film was visualized using a high-speed camera to investigate the mechanism and the onset conditions of the boiling entrainment. In the experiments, air was flowed along the liquid film to explore the potential effects of vapor core flow on the droplet generation process in diabatic annular two-phase flow. The two types of boiling entrainment mechanisms called the jet-type and the filament-type were observed in the present work. The jet-type boiling entrainment commenced at relatively low wall heat flux and produced small droplets. The filament-type was observed at higher wall heat flux and it produced larger droplets. Hence, the filament-type was supposed to have a greater impact on the liquid film flow rate in diabatic annular two-phase flow. The experimental data accumulated in this work were used to develop correlations for the onset conditions of the jet-type and filament-type boiling entrainments.

CFD modeling of droplet generation process for medical applications using the electrostatic impulse method

CFD modeling of droplet generation process for medical applications using the electrostatic impulse method

Coupled Eulerian Wall Film–Discrete Phase model for predicting respiratory droplet generation during a coughing event

Infectious respiratory diseases have long been a serious public health issue, with airborne transmission via close person-to-person contact being the main infection route. Coughing episodes are an eruptive source of virus-laden droplets that increase the infection risk of susceptible individuals. In this study, the droplet generation process during a coughing event was reproduced using the Eulerian wall film (EWF) model, and the absorption/expulsion of droplets was tracked using the discrete phase model (DPM). A realistic numerical model that included the oral cavity with teeth features and the respiratory system from the throat to the first bifurcation was developed. A coughing flow profile simulated the flow patterns of a single coughing episode. The EWF and DPM models were coupled to predict the droplet formation, generation, absorption, and exhalation processes. The results showed that a large droplet number concentration was generated at the beginning of the coughing event, with the peak concentration coinciding with the peak cough rate. Analysis of the droplet site of origin showed that large amounts of droplets were generated in the oral cavity and teeth surface, followed by the caudal region of the respiratory system. The size of the expelled droplets was 0.25–24 μm, with the peak concentration at 4–8 μm. This study significantly contributes to the realm on the site of origin and localized number concentration of droplets after a coughing episode. It can facilitate studies on infection risk assessment, droplet dispersion, and droplet generation mechanisms from other sneezing or phonation activities.

Dynamics of droplet generation in a wedge-shaped step-emulsification microchannel

The droplet generation in a wedge-shaped step-emulsification microchannel is investigated experimentally and the generation dynamics of dripping flow as a main applicable flow regime is primarily studied. The sodium alginate aqueous solution and liquid paraffin are used as dispersed phase and continuous phase respectively. The droplet generation process is divided into four stages: two-dimensional retracting stage, two-dimensional spreading stage, three-dimensional necking stage, and three-dimensional pinch-off stage. The head of the dispersed phase retracts and spreads faster under higher dispersed phase flow rate or viscosity. The critical neck width between the necking and the pinch-off stages is independent of the dispersed phase flow rate and viscosity. With the increase of dispersed phase flow rate, the droplet size increases while its formation period decreases. The droplet size and formation period increase with the increase in the dispersed phase viscosity. The flow regime of droplet generation relies primarily on the flow rate ratio and viscosities. A correlation is proposed for predicting the droplet size.

Droplet-Based Microfluidics as a Platform to Design Food-Grade Delivery Systems Based on the Entrapped Compound Type.

Microfluidic technology has emerged as a powerful tool for several applications, including chemistry, physics, biology, and engineering. Due to the laminar regime, droplet-based microfluidics enable the development of diverse delivery systems based on food-grade emulsions, such as multiple emulsions, microgels, microcapsules, solid lipid microparticles, and giant liposomes. Additionally, by precisely manipulating fluids on the low-energy-demand micrometer scale, it becomes possible to control the size, shape, and dispersity of generated droplets, which makes microfluidic emulsification an excellent approach for tailoring delivery system properties based on the nature of the entrapped compounds. Thus, this review points out the most current advances in droplet-based microfluidic processes, which successfully use food-grade emulsions to develop simple and complex delivery systems. In this context, we summarized the principles of droplet-based microfluidics, introducing the most common microdevice geometries, the materials used in the manufacture, and the forces involved in the different droplet-generation processes into the microchannels. Subsequently, the encapsulated compound type, classified as lipophilic or hydrophilic functional compounds, was used as a starting point to present current advances in delivery systems using food-grade emulsions and their assembly using microfluidic technologies. Finally, we discuss the limitations and perspectives of scale-up in droplet-based microfluidic approaches, including the challenges that have limited the transition of microfluidic processes from the lab-scale to the industrial-scale.

Robust generation of monodisperse droplets using a microfluidic step emulsification device with triangular nozzle

AbstractIn this work, the droplet generation process in the microfluidic step emulsification chip with a triangular nozzle (SE‐T) was investigated in the combination of visualization experiment and numerical simulation, through a comparison with a rectangular nozzle (SE‐R). The flow regimes, including dripping, dripping‐jetting transition, and jetting, were observed in the SE‐T, among which the dripping is the preferred flow regime to generate monodispersed droplet with corresponding C.V. (coefficient of variation) of the droplet size smaller than 1.9%. Compared with the SE‐R, the larger space and expanding structure of the triangular nozzle in the SE‐T enhance the wall wetting effects, which induces earlier appearance and accelerates shrinking of the neck. As a result, the SE‐T exhibits more robust droplet performance under the dripping regime, which produces the droplets with nearly unchanged size and higher monodispersity, especially little related to the variations of surfactant concentrations and dispersed phase flow rates.

Bent-Capillary-Centrifugal-Driven Monodisperse Droplet Generator with Its Application for Digital LAMP Assay.

We developed a bent-capillary-centrifugal-driven (BCCD) monodisperse droplet generator, which could achieve a perfect combination of driving and segmentation for the dispersed phase only using a rotating bent capillary immersed in the continuous phase (mineral oil). The sample could flow continuously to the bent-capillary outlet to form the droplet precursors, which were segmented into homogeneous droplets in the continuous phase. Through the investigation of influence factors on droplet size and stability, we found that the droplet size could be conveniently controlled by the rotational speed of the bent capillary. The droplet volumes could be adjusted with the range from 34 pL to 1 μL, and the coefficient variations (CVs) were less than 3%. Meanwhile, the BCCD droplet generator could realize the controllable droplet output with a high-efficiency sample utilization of 99.75 ± 1.15%, which offered a significant advantage in reducing the waste of precious samples in the droplet generation process. We validated this system with a digital loop-mediated isothermal amplification (dLAMP) assay for the absolute quantification of Mycobacterium tuberculosis complex nucleic acids. The results demonstrated that the BCCD droplet generator was easy to build, was of low cost, and was convenient to operate, as well as avoided sample loss and cross-contamination by coupling with a 96-well plate. Overall, the present platform, as a simple chip-free droplet generator, will provide an especially valuable droplet generation solution for biochemical applications based on droplets.

Interfacial tension driven open droplet microfluidics.

Droplet microfluidics enables compartmentalized reactions in small scales and has been utilized for a variety of applications across chemical analysis, material science, and biology. While droplet microfluidics is a successful technology, barriers include high "activation energy" to develop custom applications and complex peripheral equipment. These barriers limit the adoption of droplet microfluidics in labs or prototyping environments. We demonstrate for the first time an open channel droplet microfluidic system that autonomously generates droplets at low Capillary numbers. Hundreds of droplets are produced in a run using only an open channel, pipettes, and a commercially available carrier fluid. Conceptual applications that showcase the process of droplet generation, splitting, transport, incubation, mixing, and sorting are demonstrated. The open nature of the device enables the use of physical tools such as tweezers and styli to directly access the system; with this, a new method of droplet sorting and transfer unique to open systems is demonstrated. This platform offers enhanced usability, direct access to the droplet contents, easy manufacturability, compact footprint, and high customizability. This design is a first step in exploring the space of power-free open droplet microfluidic systems and provides design rules for similar channel designs.

Investigating Electrosprayed Droplets Using Particle-into-Liquid Sampling for Nanoliter Electrochemical Reactions

Electrospray ionization (ESI) is a powerful ionization technique that can generate charged solvent droplets and bare analyte ions from sample solutions. Despite seeing extensive use in mass spectrometry due in part to the low internal energy deposited into the ions formed during ionization, some unknowns persist regarding the exact dynamics of droplet breakup and molecule behavior during spray, and research is still underway regarding how various types of molecules acquire charge during the ESI process. Previously, the authors introduced a novel aerosol measurement technique, particle-into-liquid sampling for nanoliter electrochemical reactions (PILSNER). The current work introduces a new method utilizing PILSNER for the examination of the particles generated during ESI using simple analysis techniques with a commercially available potentiostat. This technique is applied in this work for the detection of charges on electrosprayed droplets, including the estimation of the number of charges on individual ESI droplets using a fluorescent proxy. This technique provides an additional tool for the exploration of the complex process of droplet generation and ion liberation during ESI.

Microfluidically-generated Encapsulated Spheroids (μ-GELS): An All-Aqueous Droplet Microfluidics Platform for Multicellular Spheroids Generation.

Spheroids are three-dimensional clusters of cells that serve as in vitro tumor models to recapitulate in vivo morphology. A limitation of many existing on-chip platforms for spheroid formation is the use of cytotoxic organic solvents as the continuous phase in droplet generation processes. All-aqueous methods do not contain cytotoxic organic solvents but have so far been unable to achieve complete hydrogel gelation on chip. Here, we describe an enhanced droplet microfluidic platform that achieves on-chip gelation of all-aqueous hydrogel multicellular spheroids (MCSs). Specifically, we generate dextran-alginate droplets containing MCF-7 breast cancer cells, surrounded by polyethylene glycol, at a flow-focusing junction. Droplets then travel to a second flow-focusing junction where they interact with calcium chloride and gel on chip to form hydrogel MCSs. On-chip gelation of the MCSs is possible here because of an embedded capillary at the second junction that delays the droplet gelation, which prevents channel clogging problems that would otherwise exist. In drug-free experiments, we demonstrate that MCSs remain viable for 6 days. We also confirm the applicability of this system for cancer drug testing by observing that dose-dependent cell death is achievable using doxorubicin.

Online Microfluidic Droplets Characterization Using Microscope Data Intelligent Analysis

Microfluidic devices have opened new opportunities for functional material chemical synthesis in a few applications. The screening of microfluidic synthesis processes is an urgent task of the experimental process in terms of automation and intellectualization. This study proposes a methodology and software for extracting the morphological and dynamic characteristics of generated monodisperse droplets from video data streams obtained from a digital microscope. For this purpose, the paper considers an approach to generating an extended feature space characterizing the process of droplet generation using a microfluidic device based on the creation of synthetic image datasets. YOLOv7 was used as an algorithm for detecting objects in the images. When training this algorithm, the values in the test dataset mAP@0.5 0.996 were obtained. The algorithms proposed for image processing and analysis implement the basic functionality to extract the morphological and dynamic characteristics of monodisperse droplets in the synthesis process. Laboratory validation and verification of the software demonstrated high results of the identification of key characteristics of the monodisperse droplets generated by the microfluidic device with the average deviation from the real values not exceeding 8%.

A novel droplet + arc additive manufacturing for aluminum alloy: Method, microstructure and mechanical properties

In this paper, a novel droplet + arc additive manufacturing (DAAM) has been proposed for building aluminum alloy components with high quality and high efficiency. A special droplet generation system (DGS) was designed to replace the traditional wire feeding system, making the material addition process and the arc heat input process two independent parts. During the DAAM process, the arc heat source with variable polarity is arranged tilted below the DGS, the droplets which generated from DGS drop vertically and sequentially into the molten pool, and the aluminum alloy component can be deposited layer-by-layer by moving substrate. The droplet generation process, droplet + arc deposition process, as well as the heat input strategy, microstructure and mechanical properties of the thin-wall component are discussed in detail. The experimental results show that the small and sequential droplet generation mode is beneficial to improve the continuity of deposition process and significantly reduce the harmful impact of droplets on the molten pool. Meanwhile, the DAAM process shows great inclusiveness of droplet falling deviation. A multi-layer thin-wall component and a ring-shaped structure were fabricated successfully by DAAM with the deposition rate of 140 mm3/s. The microstructure of the thin-wall component is dominated by columnar crystals and it has obvious periodic distribution along the deposition direction. The tilted growth of columnar crystals results in different grain morphology in the cross section and longitudinal section. After T6 heat treatment, the average ultimate tensile strength (UTS) and elongation in the horizontal direction are 435.0 MPa and 10.4%, while the average UTS and elongation in the vertical direction are 406.5 MPa and 16.4%, respectively. The fracture morphology is dominated by ductile fracture, but it exhibits some intergranular fracture characteristic in the horizontal direction. This novel DAAM provides a new choice for additive manufacturing of aluminum alloy, and shows great potential for the simultaneous improvement of the manufacturing quality and efficiency.