Generation Of Monodisperse Droplets Research Articles

Generating nano/microliter droplets with on-demand repetition rates by femtosecond filament-fabricated superhydrophobic bevel needle nozzles

Nano- and micro-droplets provide a platform for microanalysis of a variety of biochemical reactions with less consumption of reagents and large-extent elimination of cross-contamination, but stable generation of such monodisperse droplets with an on-demand size and repetition rate should be first established. Here, we present a simple and robust approach to generate nano/microliter (nL/μL) droplets with predetermined size and repetition rate by using femtosecond laser filament-fabricated stainless bevel needle nozzles (BNNs). We demonstrate that hierarchically heterogeneous micro/nanostructures can be directly formed on both the inner and outer surfaces of BNNs by femtosecond laser filament processing, and that after a heat treatment the fabricated BNNs show an excellent superhydrophobic property with the water contact angle of ∼160° and the rolling-off angle of ∼0.4°. With the superhydrophobic BNNs (19–27 gauge), we produce monodisperse water droplets (2.5 μL–87 nL) with nearly the same sizes as the needle diameters, and dispense them repeatedly with on-demand repetition rates from sub-1 Hz to more than 100 Hz over several orders of the flow rate. The results provide a new way for generating microdroplets on demand for various droplet-based applications.

Experimental and numerical study of droplet generation in the normal and modified cross-junction

In this work, a visualization experimental combined with numerical approach was used to analyze the process intensification achieved by incorporating a rectangular obstacle into the downstream section of a cross-junction channel for droplet generation. A comparative experimental study was conducted to evaluate the performance of the droplet generation in the modified and normal cross-junction channel. Five typical flow regimes were observed, including squeezing, dripping, jetting, tubing and a first described tip-multi-breaking which differs from those previously reported in capillary devices. among these regimes, squeezing and dripping were found to be the preferred flow regime to generate monodisperse droplets with a variation coefficient of the droplet size less than 3 %. The presence of the rectangular obstacle in the modified channel increases the fluid resistance within the main channel, leading to a higher pressure drop before and on the obstacle, which induces the earlier appearance of necking stage and more prompt pinching-off of the thread in the modified channel. As a result, smaller monodisperse droplets with higher generation frequency were observed within a much wider distribution of squeezing and dripping regimes in the modified channel.

Automated dynamic inlet microfluidics system: 3D printer adaptation for cost-effective, low volume, on-demand multi-analyte droplet generator.

The paper demonstrates an adaptation of a 3D printer (Prusa Mini+) with novel modules to develop a droplet generation system that generates combinatorial droplets from a standard 96 well plate. The calibration methodology developed would allow any fused deposition modeling (FDM) printer to generate monodisperse droplets (coefficient of variance (CV%) < 5%) from well plates or vials of any geometry. The system maintains precision across various volumes while maintaining a C.V. range of 0.81% to 3.61%, with an increased precision for larger volumes. The cost of the system developed is 70% less than commercially available droplet generation packages. Successful droplet library storage is accomplished via 3D printed cartridge connectors. The implemented system has been calibrated for Tygon® and PTFE at different velocities and volumetric configurations.

Plane-symmetric co-flow capillary for the generation of monodisperse droplets

Plane-symmetric co-flow capillary for the generation of monodisperse droplets

Generator of Monodisperse Droplets and Some Applications

A device for generation of monodisperse droplets with adjustable size and generation frequency is presented. The solid particles are formed by usage of drying techniques of droplets of different solutions in the glass tube. Experimental investigation are performed in order to create periodical structures (particularly photonic crystals) using these solid particles. For focusing and “trapping” of particles thermo-phoretic force is applied. For fabrication of opal photonic crystals self-assembly techniques is used.

Droplets size characterization for cold water clouds by means of Generalised Scattering Imaging

This paper describes an experimental investigation carried out at the Italian Aerospace Research Centre (CIRA) laboratory for the application of the Generalized Scattering Imaging (GSI) technique. The droplets were generated by a monodisperse droplet generator and a multi-disperse conical nozzle. This latter is currently used for making the artificial cloud in the CIRA Icing Wind Tunnel (IWT). The measurements are devoted to assessing the application of GSI for the characterization of the cold cloud of CIRA-IWT. The experiments were conducted considering two camera models and demanding technical solutions for the illumination and layout constraints faced for the future implementation of GSI in IWT. To reduce into a linear pattern the enlarged defocused interference fringes, it is found that the optimal aperture of the slit is 5 mm. For the monodisperse droplet distribution, the results show discrepancies between the predicted and the measured diameters regardless of the sharp distribution of the occurrences of the droplet diameters. However, the dispersion found for the droplets generated by the conical nozzle exhibits the expected large variability. This effect is more emphasized when the imaged region is discretized in sub-windows, the number of droplets in each dramatically decreases, however compromising the results of the statistics. Different camera models and imaging configurations led to a variety of measurements at different spatial resolutions.

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.

Mapping flow-focusing microfluidic droplet formation to determine high-throughput droplet generation configurations

Droplet microfluidics enables the generation of monodisperse droplets of desired size using immiscible multiphase flows. These droplets serve as individual reactors in bio (chemical) analysis. In addition to monodispersity, high throughput is also necessary for many applications, especially in synthesizing nano- and microscale materials. Therefore, high-frequency droplet formation in the stable regimes (dripping and squeezing) is of great importance. In this work, the flow-focusing geometry is numerically investigated to determine the geometrical dimensions and flow rate ratio by which high-frequency, high mass flow rate, and monodispersed droplet formation are achievable. 3D numerical simulation has been performed with the commercial software ANSYS Fluent using the VOF method. The lowest and highest error values were 1.5% and 7% in the validation results, respectively, confirming the solver's reliability. The numerical model determined droplets' diameter and mass flow rate, and their generation frequency for a simple geometry that had been experimentally studied. The geometry, then, was changed both in dimension and junction, seeking the best performing configuration. Our results demonstrated that the highest mass flow rate and generation frequency are obtained with the flow rate ratio of 5 between the continuous and dispersed phases. Furthermore, by introducing a modified geometry using a rib, it was revealed that reducing the channel width in the simple geometry leads to much more improvement in the generation frequency and droplet diameter than using the modified geometry. Subsequently, the aspect ratio study showed that the aspect ratio 1 creates the highest production frequency in the simple geometry. Finally, taking into account all the previous findings, a relation is introduced which determines the required channel dimensions when a specific droplet diameter is of interest.

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.

Microfluidic Generation of Therapeutically Relevant Polycaprolactone (PCL) Microparticles: Computational and Experimental Approaches

Drug releasing microparticles play an important role in drug delivery as they can be used for site specific delivery as well as control over the release time of therapeutics. The use of microfluidic technologies for the fabrication of these particles is of increasing interest since they provide enhanced control over microparticle size and size distribution compared to bulk production methods. However, the use of microfluidic platforms in the production of drug releasing microparticles with therapeutically relevant cargo still requires optimization depending on their application, and the effect of the addition of cargo on the production process is still unexplored. Here we show the formation of therapeutically relevant (in terms of size and dose of cargo) polycaprolactone (PCL) microparticles using a microfluidic platform and analyze the effect of the addition of cargo in the microparticle size and size distribution. This microfluidic platform was designed with the aid of computational fluid dynamic simulations, allowing us to construct a polydimethylsiloxane (PDMS) microfluidic device capable of making microparticles in the range of 15 to 35 μm with low coefficient of variation (CV) both with and without cargo by varying the flow rate ratios of the phases used during droplet generation. Our data show the effect of the addition of cargo on the droplet and microparticle sizes and monodispersity. Our fabrication method allows the formation of spherical microparticles, optimal for biomedical applications. In addition, our microfluidic platform can maintain the generation of monodisperse droplets (with an average size of 52.5 μm) over extended periods of time, suggesting it has the capacity to be used for scaled-up production of PCL microparticles. This microfluidic device is a robust and reliable method for the fabrication of PCL microparticles with cargo, which can potentially be loaded with other relevant therapeutic molecules for biomedical applications.

Two-Color Laser-Induced Fluorescence Thermometry In Micrometric Ethanol Droplets Using A Fluorescein And Sulforhodamine 101 Dye Mixture

In this work, two-color laser-induced fluorescence (2c-LIF) is applied to measure the temperature in micrometric ethanol droplets, containing a novel dye mixture of fluorescein (FL) and sulforhodamine 101 (SRh). A monodisperse droplet generator is used to generate 100 µm sized droplets with temperatures from 293 K to 343 K. The addition and excitation of the dye mixture allow the simultaneous detection of the fluorescence signal with two detection systems. A fiber coupled spectrometer and an imaging system with two sCMOS cameras provide both, spectral and spatial information. Measuring both signals at the same time, lasing effects (or morphology-dependent resonances) in the droplet can be clearly recognized in the spectra and circumvented in further measurements. &amp;nbsp;Additionally, absorption measurements are conducted, which demonstrate the difference in temperature sensitivity between the two dyes and show potential re-absorption effects. At high temperatures, the photon absorption of FL increases strongly while SRh shows a steady absorption at all temperatures. By measuring the emission spectra, the implied temperature dependence can be observed for FL. On the contrary, the emission signal of SRh is constant at any temperature measured. The wavelength regions with highest sensitivity are elaborated and respective filters are chosen for the color channels in the imaging system. No lasing effects were observed in these filter regions in planar and spectral measurements. Temperature-dependent signal ratios of the two channels are obtained for the detected spectra and images. The resulting calibration curves are compared and discussed. A much steeper slope and thus larger sensitivity is achieved by measuring with the spectrometer. Both calibration curves show only very little standard deviations, which proves the applicability and reliability of the setup, the method and the utilized dyes, for application in technical spray systems.

A Lab-in-a-Fiber optofluidic device using droplet microfluidics and laser-induced fluorescence for virus detection

Microfluidics has emerged rapidly over the past 20 years and has been investigated for a variety of applications from life sciences to environmental monitoring. Although continuous-flow microfluidics is ubiquitous, segmented-flow or droplet microfluidics offers several attractive features. Droplets can be independently manipulated and analyzed with very high throughput. Typically, microfluidics is carried out within planar networks of microchannels, namely, microfluidic chips. We propose that fibers offer an interesting alternative format with key advantages for enhanced optical coupling. Herein, we demonstrate the generation of monodisperse droplets within a uniaxial optofluidic Lab-in-a-Fiber scheme. We combine droplet microfluidics with laser-induced fluorescence (LIF) detection achieved through the development of an optical side-coupling fiber, which we term a periscope fiber. This arrangement provides stable and compact alignment. Laser-induced fluorescence offers high sensitivity and low detection limits with a rapid response time making it an attractive detection method for in situ real-time measurements. We use the well-established fluorophore, fluorescein, to characterize the Lab-in-a-Fiber device and determine the generation of sim 0.9 nL droplets. We present characterization data of a range of fluorescein concentrations, establishing a limit of detection (LOD) of 10 nM fluorescein. Finally, we show that the device operates within a realistic and relevant fluorescence regime by detecting reverse-transcription loop-mediated isothermal amplification (RT-LAMP) products in the context of COVID-19 diagnostics. The device represents a step towards the development of a point-of-care droplet digital RT-LAMP platform.

OsciDrop: A Versatile Deterministic Droplet Generator.

This paper describes OsciDrop, a versatile chip-free droplet generator used to produce size-tunable droplets on demand. Droplet generation is fundamental to miniaturized analysis. We designed OsciDrop to segment the fluid flowing out of the orifice of a disposable pipette tip into droplets by oscillating its distal end underneath an immiscible continuous phase. We described the theoretical model and investigated the effect of flow rate, oscillating amplitude, frequency, and waveform on droplet generation. Our study revealed a previously underexplored Weber number-dominated regime that leverages inertial force instead of viscous force to generate droplets. The same pipette tip allowed robust and deterministic generation of monodisperse droplets with programmable sizes ranging from 200 pL to 2 μL by asymmetrical oscillation. We validated this platform with two droplet-based nucleic acid amplification tests: a digital loop-mediated isothermal amplification assay for absolute quantification of African swine fever virus and a multi-volume digital polymerase chain reaction assay for the high dynamic range measurement of human genomic DNA. The OsciDrop method opens a facile avenue to miniaturization, integration, and automation, exhibiting full accessibility for digital molecular diagnostics.

Effect of parameters on ME process by near-field electrospun PTFE membrane

BackgroundMembrane emulsification (ME) is an attractive membrane process to produce various kind of simple or multiple emulsions. The membrane utilized in ME process should have high dispersed phase flux, narrow pore size distribution and excellent antifouling property. MethodsThis work proposed a novel near-field electrospun (NFES) poly(tetrafluoroethylene) (PTFE) membranes with ordered rectangular pore geometry. Compared with other membranes, the order pore geometry of NFES PTFE membrane was helpful to obtain a more homogeneous and more stable water-in-oil (W/O) emulsion. Significant findingsThe droplet size was simply controlled by the NFES PTFE membrane pore size. And NFES PTFE membrane was more conducive to the formation of droplets with narrow droplet size distribution because of its unique straight rectangular membrane pore geometry. In addition, W/O emulsion droplet size be regulated in coordination with operating parameters and phase parameters. Results indicated that a smaller rectangular pore area of PTFE membrane would lead to a smaller droplet size. Introducing of shear stress in the continuous phase was contributed to the generation of monodisperse droplets. When the emulsifier (Span 80) content was 1wt%, the smallest droplet size (∼103.6 nm) was obtained.

A 3D printed size-tunable flow-focusing droplet microdevice to produce cell-laden hydrogel microspheres

Flow-focusing droplet generators have been extensively employed for the generation of monodisperse droplets. However, the droplet device is usually designed with an application-specific performance that includes prescribed droplet size and generation frequency. To achieve an ideal device, cost- and time-inefficient iterations for the chip design and fabrication are usually needed. In this study, we take an advantage of 3D printing technology to rapidly prototype the droplet device that enables the facile control of the droplet size as well as the droplet generation frequency. Our device was designed with a screw-and-nut combination and the gap height (hg) between the dispersed phase outlet and the orifice could be easily and finely controlled by rotating the head of the threaded screw. The hg values can be precisely adjusted from 0 to 2000 μm supported by 20 designated control teeth on the screw head, which enable us to produce droplets in different sizes or in the same size with different generation frequencies. The proposed 3D printed device was employed to synthesize a variety of Ca-alginate microspheres containing A549 cells. The facile assembly of the screw-and-nut components allows us to prepare the droplet generator in a simple yet effective manner, and the size controllability of the droplets resulted in the production of various sizes of A549 cell-encapsulated microspheres, which can be used for drug screening.

Precise monodisperse droplet generation by pressure-driven microfluidic flows

In a T-junction microdroplet generator, as monodisperse droplets are formed for the droplet digital polymerase chain reaction (PCR), a mathematical model which can describe the nonlinear relation of droplet generation under pressure-driven microfluidic flows is established. For various viscosity of the fluids, the relation between the droplet length and the driving-pressure ratio is measured at a low capillary number (Ca < 0.01) of droplet generation. It can be observed that the droplet length varies nonlinearly with the driving-pressure ratio for a specific geometry of the T-junction. In particular, the relation between the droplet length and the driving-pressure ratio is tested experimentally for different geometries of the T-junctions. At low capillary numbers, the nonlinear relation between the droplet length and the driving-pressure ratio is basically determined by the geometrical parameters of the T-junction. Most importantly, a closed-loop control droplet microfluidic system is demonstrated, and the size of the droplets can be controlled more accurately by pressure-driven flows. The control precision of the droplet size is quantitatively studied for a wide range of typical conditions of droplet generation. In particular, the relative standard deviation of the droplet size for various flow conditions is less than 2%, which is of great importance for improving the detection accuracy of nucleic acid based on the droplet digital PCR.

Improved Size Uniformity of Microcapillaries in Microcapillary Films by Separate Gas Injection

AbstractMicrocapillary films (MCFs) are microextrusion‐processed plastic films containing an array of parallel microcapillaries, and have been widely utilized as microfluidic platforms. However, the nonuniform size distribution within a single MCF strip limits the application of MCFs in monodisperse droplet generation. In this paper, the mechanisms that lead to uneven microcapillary dimensions in conventional MCFs whose gas pressures in all channels are the same is first clarified. The effect of gas pressure in a single channel on the microcapillary dimensions in the film is then studied. Finally, the size uniformity of the microcapillaries is improved by separate gas injection in different channels, providing new possibilities for the generation of highly monodisperse microdroplets.

Secondary breakup of water and surrogate fuels: Breakup modes and resultant droplet sizes

Secondary breakup of water and single-component surrogates of diesel such as n-dodecane and n-hexadecane, has been experimentally investigated in the present study. The experimental arrangement involves injection of mono-disperse droplets of the test liquid into an air jet issuing from a contoured nozzle. The mono-disperse droplet generator (MDG) is used to produce liquid droplets of diameter around 200 ± 4-µm, which is close to those found in practical sprays. The aerodynamic Weber number (We) is varied by changing the air-jet velocity. In the present study, apart from the most-reported regimes namely bag breakup, bag and stamen breakup, shear breakup and catastrophic breakup - two more regimes, viz. dual-bag breakup and multi-bag breakup regimes, have also been observed. The dual bag regime occurs in the Weber number range of 30 to 46 followed by the multi-bag regime in the Weber number of 46 to 80. These two regimes have been very rarely reported in the technical literature. The temporal droplet deformation observed in the present study during bag regime and bag and stamen regime is observed to match well with data reported in the literature. The size of core droplet in the bag and stamen mode is observed to increase with Weber number and after a Weber number of 30 it is of sufficient size for its Weber number to be above the critical Weber number. This core droplet undergoes a subsequent breakup resulting in dual-bag breakup mode. Variation of SMD of resultant droplets is measured and reported for all the breakup modes ranging from We = 10 up to 500 and data at some salient points is observed to match well with data from literature. Detailed droplet probability distributions for bag, bag and stamen, dual bag and multi-bag regimes has been reported. A tri-modal droplet size distribution is observed in bag and bag and stamen breakup regimes, where the first peak corresponding to film, second peak corresponding to rim and the third corresponding to nodes on the rim and stamen. The rim, nodes and stamen of the bag is observed to contribute up to around 90% of mass from the parent droplet. With increase in Weber number, the droplet distribution transforms in to a bi-modal distribution. The droplet size distribution resulting from water breakup is different from those of the other two liquids in the larger droplet size range due to the higher surface tension of water. The experimental data presented is useful to validate computational models in terms of their capability to predict the droplet deformation dynamics, resultant droplet sizes and distribution with water and diesel fuel surrogates such as n-dodecane and n-hexadecane.

Formation and Elimination of Satellite Droplets during Monodisperse Droplet Generation by Using Piezoelectric Method.

One of the key questions in the generation of monodisperse droplets is how to eliminate satellite droplets. This paper investigates the formation and elimination of satellite droplets during the generation of monodisperse deionized water droplets based on a piezoelectric method. We estimated the effects of two crucial parameters—the pulse frequency for driving the piezoelectric transducer (PZT) tube and the volume flow rate of the pumping liquid—on the generation of monodisperse droplets of the expected size. It was found that by adjusting the pulse frequency to harmonize with the volume flow rate, the satellite droplets can be eliminated through their coalescence with the subsequent mother droplets. An increase in the tuning pulse frequency led to a decrease in the size of the monodisperse droplets generated. Among three optimum conditions (OCs) (OC1: 20 mL/h, 20 kHz; OC2: 30 mL/h, 30 kHz; and OC3: 40 mL/h, 40 kHz), the sizes of the generated monodisperse deionized water droplets followed a bimodal distribution in OC1 and OC2, whereas they followed a Gaussian distribution in OC3. The average diameters were 87.8 μm (OC1), 85.9 μm (OC2), and 84.8 μm (OC3), which were 8.46%, 6.14%, and 4.69% greater than the theoretical one (81.0 μm), respectively. This monodisperse droplet generation technology is a promising step in the production of monodisperse aerosols for engineering applications.

Simultaneous measurement of surface tension and viscosity of oscillating droplet using time-resolved rainbow refractometry

Oscillation of micron-sized liquid droplet is an interesting and common phenomenon, and is used to measure surface tension and viscosity with the recently developed time-resolved rainbow refractometry. Droplets produced by a monodisperse droplet generator are excited to oscillate at a small amplitude (less than 1%) and high frequency (of the order of 10 kHz) by applying a periodic tiny disturbance. The aspect ratio of a spheroidal droplet is quantified by time-resolved angular shift of rainbow signal. Thus the droplet shape oscillation is quantified by its unsphericity, instead of calculated from the polar radius or the variation of surface area. Experiments on several liquids were conducted to evaluate the validation of the experimental system. The results present that the relative errors of measured values of the surface tension and viscosity are less than 5% and 10%, respectively, promising the great potential of rainbow refractometry for liquid surface properties measurement.