Glass Capillary Microfluidic Device Research Articles

Predicting microfluidic droplet diameters in glass capillary devices using machine learning

Using actual experimental data of single emulsion diameters generated from glass capillary microfluidic devices, we report predictions for droplet diameters in both dripping and jetting regimes using an artificial intelligence neural network. This is the first time that glass capillary microfluidic experimental data has been employed to train a neural network and predict droplet diameters for these particular devices. The neural network inputs are fluid properties and co-flow geometries of glass capillary devices. Specifically, the inputs are orifice width, capillary spacing, flow rate ratio, inner and outer capillary number, and the regime, dripping or jetting. The experimental data set consists of 800 points; 80% of the data is for training the model and 20% is for testing. Droplet sizes generated with single emulsion devices varied from 161 microns to 1085 microns in diameter, with most droplet sizes in the dripping regime. Three model algorithms – Neural Network, Linear Regression, and Support Vector Regression – were compared for droplet diameter prediction. A neural network performed best in the dripping regime with an accuracy of 91.1%. Linear regression performed the best of the three models in the jetting regime with a 92.6% accuracy. The support vector regression, with a 10-fold cross validation average score of 0.278, was outperformed by the neural network and linear regression models with 10-fold cross validation average scores of 0.623 and 0.604, respectively. Finally, we have also successfully generated a graphic user interface that predicts microfluidic droplet diameters for glass capillary devices using the neural network.

Effective colloidal emulsion droplet regulation in flow-focusing glass capillary microfluidic device via collection tube variation.

Colloidal emulsion droplets, created using glass capillary microfluidic devices, have been found in a myriad of applications, serving as subtle microcarriers, delicate templates, etc. To meet the objective requirements under varying circumstances, it is crucial to efficiently control the morphology and dimensions of the droplets on demand. The glass capillary collection tube is a crucial component of the flow-focusing microfluidic system due to its close association with the geometrical confinement of the multiphasic flow. However, there are currently no guidelines for the design of the morphology and dimensions of the glass capillary collection tube, which shall result in a delay in assessing serviceability until after the microfluidic device is prepared, thereby causing a loss of time and effort. Herein, an experimental study was conducted to investigate the effect of the geometrical characteristics of glass capillary collection tubes on the production of colloidal emulsion droplets. After characterizing the generated colloidal emulsion droplets, it was found that the geometrical variations of the glass capillary collection tube resulted in numerical disparities of droplets due to different degrees of flow-focusing effects. The stronger flow-focusing effect produced smaller droplets at a higher frequency, and the dimensional variation of colloidal emulsion droplets was more responsive to varying flow rates. Furthermore, the transformation from colloidal single-core double-emulsion droplets to multi-core double-emulsion droplets also changed with the flow rate due to the glass capillary collection tube morphology-determined varying flow-focusing effect. These experimental findings can offer qualitative guidance for the design of glass capillary microfluidic devices in the preliminary stage, thus facilitating the smooth production of desired colloidal emulsion droplets.

Microfluidic Fabrication of Monodisperse and Recyclable TiO2-Poly(ethylene glycol) Diacrylate Hybrid Microgels for Removal of Methylene Blue from Aqueous Medium.

Nearly monodisperse titanium oxide-polyethylene glycol diacrylate [TiO2-P(EGDA)] hybrid microbeads containing 0.5 wt % TiO2 nanoparticles entrapped within a P(EGDA) cross-linked polymeric network were synthesized using a modular Lego-inspired glass capillary microfluidic device. TiO2-P(EGDA) hybrid microgels were characterized by optical microscopy, scanning electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and thermogravimetric analysis. The fabricated TiO2-P(EGDA) hybrid microgel system showed 100% removal efficiency of methylene blue (MB) from its 1-3 ppm aqueous solutions after 4 h of UV light irradiation at 0.2 mW/cm2 at the loading of 25 g/L photocatalyst beads in the reaction mixture, corresponding to the loading of naked TiO2 of just 0.025 g/L. No decrease in photocatalytic efficiency was observed in 10 repeated runs with recycled photocatalyst using a fresh 1 ppm MB solution in each cycle. The rate of photocatalytic degradation was controlled by the UV light irradiance, catalyst loading, and the initial dye concentration. Physical adsorption of MB onto the surface of composite microgel was also observed. The adsorption data was best fitted with the Langmuir adsorption isotherm and the Elovich kinetic model. TiO2-P(EGDA) microgel beads are biocompatible, can be prepared with a tunable size in the microfluidic device, and can easily be separated from the reaction mixture by gravity settling. The TiO2-P(EGDA) system can be used for the removal of other toxic dyes and micropollutants from industrial wastewater.

Lego-Inspired Glass Capillary Microfluidic Device: A Technique for Bespoke Microencapsulation of Phase Change Materials.

We report a Lego-inspired glass capillary microfluidic device capable of encapsulating both organic and aqueous phase change materials (PCMs) with high reproducibility and 100% PCM yield. Oil-in-oil-in-water (O/O/W) and water-in-oil-in-water (W/O/W) core-shell double emulsion droplets were formed to encapsulate hexadecane (HD, an organic PCM) and salt hydrate SP21EK (an aqueous PCM) in a UV-curable polymeric shell, Norland Optical Adhesive (NOA). The double emulsions were consolidated through on-the-fly polymerization, which followed thiol-ene click chemistry for photoinitiation. The particle diameters and shell thicknesses of the microcapsules were controlled by manipulating the geometry of glass capillaries and fluid flow rates. The microcapsules were monodispersed and exhibited the highest encapsulation efficiencies of 65.4 and 44.3% for HD and SP21EK-based materials, respectively, as determined using differential scanning calorimetry (DSC). The thermogravimetric (TGA) analysis confirmed much higher thermal stability of both encapsulated PCMs compared to pure PCMs. Polarization microscopy revealed that microcapsules could sustain over 100 melting-crystallization cycles without any structural changes. Bifunctional microcapsules with remarkable photocatalytic activity along with thermal energy storage performance were produced after the addition of 1 wt % titanium dioxide (TiO2) nanoparticles (NPs) into the polymeric shell. The presence of TiO2 NPs in the shell was confirmed by higher opacity and whiteness of these microcapsules and was quantified by energy dispersive X-ray (EDX) spectroscopy. Young's modulus of HD-based microcapsules estimated using micromanipulation analysis increased from 58.5 to 224 MPa after TiO2 incorporation in the shell.

Novel glass capillary microfluidic devices for the flexible and simple production of multi-cored double emulsions

HypothesisDouble emulsions with many monodispersed internal droplets are required for the fabrication of multicompartment microcapsules and tissue-like synthetic materials. These double emulsions can also help to optically resolve different coalescence mechanisms contributing to double emulsion destabilization. Up to date microfluidic double emulsions are limited to either core–shell droplets or droplets with eight or less inner droplets. By applying a two-step jet break-up within one setup, double emulsion droplets filled with up to several hundred monodispersed inner droplets can be achieved. ExperimentsModular interconnected CNC-milled Lego®-inspired blocks were used to create two separated droplet break-up points within coaxial glass capillaries. Inner droplets were formed by countercurrent flow focusing within a small inner capillary, while outer droplets were formed by co-flow in an outer capillary. The size of inner and outer droplets was independently controlled since the two droplet break-up processes were decoupled. FindingsWith the developed setup W/O/W and O/W/O double emulsions were produced with different surfactants, oils, and viscosity modifiers to encapsulate 25–400 inner droplets in each outer drop with a volume percentage of inner phase between 7% and 50%. From these emulsions monodispersed multicompartment microcapsules were obtained. The report offers insights on the relationship between the coalescence of internal droplets and their release.

Generation of Monodisperse Microbubbles with a Controlled Size of Less Than 10 µm at a Generation Rate on the Order of 10<sup>5</sup> Bubbles/s in Glass Capillary Microfluidic Devices

Generation of Monodisperse Microbubbles with a Controlled Size of Less Than 10 µm at a Generation Rate on the Order of 10<sup>5</sup> Bubbles/s in Glass Capillary Microfluidic Devices

Experimental and Computational Analysis of Mixing Inside Droplets for Microfluidic Fabrication of Gold Nanoparticles

Emulsions formed by mixing reactant streams inside microdroplets are efficient microscale reactors for the synthesis of nano/microparticles/crystals due to small quantities of reagents confined within each droplet and the separation of droplet contents from the reactor walls. In this work, the synthesis of size-tunable gold nanoparticles (AuNPs) within emulsion droplets generated in a three-phase glass capillary microfluidic device was investigated experimentally and numerically using computational fluid dynamics (CFD). AuNPs were produced by micromixing two aqueous streams, 1.15 mM HAuCl4 containing the 1% poly(vinylpyrrolidone) capping agent and 20 mM ascorbic acid solutions, inside monodispersed droplets created by three-dimensional (3D) counter-current flow focusing in a medium-chain triglyceride. The mean particle size of AuNPs was tunable in the range between 26 and 56 nm and depended on the degree of premixing of the reactant streams shortly before droplet generation, and the mixing efficiency within droplets, which was controlled by hydrodynamic conditions within the microfluidic device. The CFD results were compared and validated against experimental observations and revealed the presence of a recirculation zone near the outer wall of the injection capillary tip. The mixing efficiency was higher at smaller droplet size causing a reduction in the particle size of the AuNPs.

Continuous-mode encapsulation of human stem cell spheroids using droplet-based glass-capillary microfluidic device for 3D bioprinting technology

Droplet-based microfluidics generates droplets with reproducibility, repeatability, and monodispersity, resulting in decreased reaction time with high yield production. Due to its advantages, its technology has been used to encapsulate biologics for cell therapy, biomaterials, and tissue engineering. However, the encapsulation of superior in vitro culture models, such as cellular spheroids is an ongoing challenge. In this work, we present a continuous process for the encapsulation of mesenchymal stem cell spheroids into alginate hydrogel droplets, using a glass-capillary-based microfluidic device. The device geometry comprises co-flow and hydrodynamic focusing techniques, in which two round glass capillaries are aligned inside a square glass capillary. The encapsulated spheroids were composed of human adipose-derived mesenchymal cells (ASCs) with a diameter of 400 µm. The encapsulation of ASC spheroids was performed into single droplets with approximately 600 µm in size, under a total volumetric flow rate of 14 mL h-1. The developed microdevice was able to generate 200 droplets/min. Moreover, they were able to promote the gelation simultaneously with spheroids encapsulation without compromising their morphology. The stability of the droplet was achieved using 10% of surfactant. In addition, encapsulated spheroids were able to be seeded into PLA scaffolds without compromising either the droplet and their morphology. The successful and homogeneous encapsulation of stem cell spheroids has high applicability in forefront regenerative medicine strategies, such as droplet-based bioprinting. Hence, biofabricating physiological relevant tissue-like constructs with cost and time efficiency.

On-demand modulation of 3D-printed elastomers using programmable droplet inclusions

One of the key thrusts in three-dimensional (3D) printing and direct writing is to seamlessly vary composition and functional properties in printed constructs. Most inks used for extrusion-based printing, however, are compositionally static and available approaches for dynamic tuning of ink composition remain few. Here, we present an approach to modulate extruded inks at the point of print, using droplet inclusions. Using a glass capillary microfluidic device as the printhead, we dispersed droplets in a polydimethylsiloxane (PDMS) continuous phase and subsequently 3D printed the resulting emulsion into a variety of structures. The mechanical characteristics of the 3D-printed constructs can be tuned in situ by varying the spatial distribution of droplets, including aqueous and liquid metal droplets. In particular, we report the use of poly(ethylene glycol) diacrylate (PEGDA) aqueous droplets for local PDMS chemistry alteration resulting in significant softening (85% reduced elastic modulus) of the 3D-printed constructs. Furthermore, we imparted magnetic functionality in PDMS by dispersing ferrofluid droplets and rationally designed and printed a rudimentary magnetically responsive soft robotic actuator as a functional demonstration of our droplet-based strategy. Our approach represents a continuing trend of adapting microfluidic technology and principles for developing the next generation of additive manufacturing technology.

Microfluidic fabrication and characterization of Sorafenib-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery.

Lipid polymer hybrid nanoparticles (LPHNPs) have been merged as potential nanocarriers for treatment of cancer. In the present study, LPHNPs loaded with Sorafenib (SFN) were prepared with PLGA, Lecithin and DSPE-PEG 2000 by using the bulk nanoprecipitation and microfluidic (MF) co-flow nanoprecipitation techniques. Herein, a glass capillary microfluidic device was primed to optimize the LPHNPs and compared to the bulk nanoprecipitation method. The morphological analysis of prepared LPHNPs revealed the well-defined spherical nano-sized particles in bulk nanoprecipitation method. Whereas, core shell morphology was observed in the MF method. The formulation prepared by the MF method (MF1-MF3) indicated relatively higher % EE (95.0%, 93.8% and 88.7%) and controlled release of the SFN from the particles as compared to the LPHNPs obtained by the bulk nanoprecipitation method. However, the release of SFN from all LPHNP formulation followed Higuchi model (R2=0.9901-0.9389) with Fickian diffusion mechanism. Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and powder X-rays diffraction (pXRD) studies depicted the compatibility of SFN with all the structural components. In addition, the colloidal stability, in vitro cytotoxicity and cell growth inhibition studies of LPHNPs also demonstrated stability in biological media, biocompatibility and safety with enhanced anti-proliferative effects than the free SFN in breast cancer and prostate cancer cells. In conclusion, LPHNPs provided a prospective platform for the cancer chemotherapy and substantially improved the knowledge of fabrication and optimization of the hybrid nanoparticles.

Numerical Simulation and Experimental Validation of Liquid Metal Droplet Formation in a Co-Flowing Capillary Microfluidic Device.

A two-phase flow axisymmetric numerical model was proposed to understand liquid metal droplet formation in a co-flowing capillary microfluidics device based on a phase field model. The droplet detachment processes were observed in the experiment and are in good agreement with the simulation method. The effects of the viscosities and flowrates of the continuous phase fluid, interfacial tension as well as the wetting property of the metallic needle against the bulk liquid metal on the droplet formation and production rate were numerically investigated. It was found that the droplet diameter decreased with the increment of the viscosities and flowrates of the outer phase carrier fluid. The dispersed phase fluid with high interfacial tension tended to prolong the time for equilibrium between the viscous drag force and interfacial tension on the liquid–liquid fluid surface, delaying the droplet to be pinched off from the capillary orifice and causing large droplet diameter. Finally, the wetting performance of the metallic needle against the liquid metal was explored. The result indicate that the droplet diameter became less dependent on the contact angle while the size distribution of the liquid metal droplet was affected by their wetting performance. A more hydrophilic wetting performance were expected to prepare liquid metal droplet with more monodispersity. The numerical model and simulation results provide the feasibility of predicting the droplet formation with a high surface tension in a glass capillary microfluidic device.

Microfluidic production of aqueous suspensions of gellan-based microcapsules containing hydrophobic compounds

We discuss the production of microcapsules with hydrogel-based shells by ionotropic gelation of gellan gum from monodispersed oil-in-water-in-oil (O/W/O) double emulsion templates obtained using glass-capillary microfluidic devices. An oil extraction step was added after the shell gelation process to enable the dispersion of the microcapsules in an aqueous medium. The proposed approach for producing biopolymer-based microcapsules for hydrophobic agents dispersed in a water phase has a broad range of applications in delivery of hydrophobic compounds dispersed in an aqueous medium. We report the operability window for the production of monodispersed microcapsules as a function of the flow rate of each fluid phase and the dimensions of the device. Microcapsules with mean diameters ranging from 95 to 260 µm and a maximum coefficient of variation of 5% were formed. The results show how to independently control the capsule diameter and shell thickness by varying the outer and middle phase flow rates.

Single-step microfluidic production of W/O/W double emulsions as templates for β-carotene-loaded giant liposomes formation

We demonstrated the microfluidic production of W/O/W double emulsion droplets aiming formation of β-carotene-incorporated giant liposomes for food and/or pharmaceutical applications. For this purpose, glass-capillary microfluidic devices were fabricated to create a truly three-dimensional flow aiming production of giant unilamellar liposomes by solvent evaporation process after W/O/W double emulsion droplet templates formation. A great challenge of microfluidic production of monodisperse and stable W/O/W double emulsion templates for this proposal is the replacement of organic solvents potentially toxic for phospholipids dissolution. Besides, the high cost of several semi-synthetic phospholipids commonly used for giant liposome formation remains as a major technological challenge to be overcome. Thus, β-carotene-incorporated giant liposomes were generated using biocompatible solvents with low toxic potential (ethyl acetate and pentane) and non-purified soybean lecithin - a food-grade phospholipid mixture with low cost - by dewetting and evaporation of the solvents forming the oily intermediate phase of W/O/W double emulsion droplet templates. Our results showed monodisperse β-carotene-loaded giant liposomes with diameter ranging between 100 μm and 180 μm and a stability of approximately 7 days. In this way, a single-step microfluidic process with highly accurate control of size distribution was developed. This microfluidic process proposed is potentially useful for a broad range of applications in protection and delivery of active compounds.

Versatile reconfigurable glass capillary microfluidic devices with Lego® inspired blocks for drop generation and micromixing

Novel cost effective, versatile, reconfigurable, reusable and easy to assemble glass capillary microfluidic devices were developed and used to generate micro/nano-materials with controlled size and morphology. The devices are composed of coaxial assemblies of glass capillaries held between two interchangeable plastic blocks fabricated from chemically inert polyoxymethylene copolymer using computer numerical control (CNC) machining. Three different blocks were combined and locked together using Lego® inspired stud-and-hole coupling system to achieve different flow configurations. The device allows a truly axisymmetric round capillary inside a round capillary geometry and self-alignment of capillaries. The synthesis of polyvinylpyrrolidone capped gold nanoparticles and liposomes of controlled size was demonstrated in the co-flow device by mixing the contents of two parallel laminar streams. The flow focusing device was used to generate piroxicam monohydrate crystals of controlled size (10–29 μm) by antisolvent crystallisation. Silver nanoparticles with tailored size (40–90 nm) were prepared in the three-phase device by merging silver nitrate and tannic acid/citrate streams inside droplets. The same device was used to prepare fluorescently labelled double emulsion droplets with controlled number of inner droplets. The droplet morphology was modified and tuned during operation by adjusting the distance between the inner capillaries. Water-in-oil emulsions consisted of Eudragit S100 solution at pH > 7 dispersed in Miglyol® 840 were prepared and gellified in situ over 6 h without fouling. The setup time of the novel devices was reduced from ∼30 min in manually made capillary devices to just several minutes.

Size-Controlled Preparation of Monodisperse Microbubbles using Co-Flow Glass Capillary Microfluidic Device

Size-Controlled Preparation of Monodisperse Microbubbles using Co-Flow Glass Capillary Microfluidic Device

A micro-needle induced strategy for preparation of monodisperse liquid metal droplets in glass capillary microfluidics

Monodisperse micro-sized liquid metal droplets have received considerable attention for developing flexible electronics, microfluidics actuators and reconfigurable devices. Herein we report an innovative and efficient strategy for large-scale preparation of Galinstan liquid metal microdroplets with controllable sizes using a micro-needle induced glass capillary microfluidic device. By inserting a stainless steel micro-needle into the inner liquid metal phase in the glass capillary, the hydrodynamic instability of the liquid metal stream is significantly suppressed to guarantee steady fluid flow before the liquid metal is pinched off by the outer phase flow, giving rise to a stable generation of monodisperse liquid metal microdroplets. The microdroplet size dependence on the flow ratio of the continuous and dispersed-phase is investigated experimentally. A theoretical framework based on the Plateau–Rayleigh instability is proposed to explain the advantage of the micro-needle induced strategy. This strategy has great potential for the generation of high interfacial tension liquid metal emulsions.

Integration of glass micropipettes with a 3D printed aligner for microfluidic flow cytometer

In this study, a facile strategy for fabricating a microfluidic flow cytometer using two glass micropipettes with different sizes and a 3D printed millifluidic aligner was presented. Particle confinement was achieved by hydrodynamic focusing using a single sample and sheath flow. Device performance was extracted using the forward and side-scattered optical signals obtained using fiber-coupled laser and photodetectors. The 3-D printing assisted glass capillary microfluidic device is ultra-low-cost, not labor-intensive and takes less than 10 min to fabricate. The present device offers a great alternative to conventional benchtop flow cytometers in terms of optofluidic configuration.

Controlled Generation of Double Emulsions for Laser Fusion Target Fabrication Using a Glass Capillary Microfluidic Device

We report the controllable generation of double emulsions for target fabrication using glass capillary microfluidic devices. Instead of a conventional triple-orifice droplet generator, user-friendly glass capillary devices are used to produce micrometer to millimeter-sized water-in-oil-in-water emulsions. The double emulsions have a relatively uniform size distribution with an average outer diameter of 1420 μm. The sizes of the emulsions can also be varied by changing the ratio of the inner, middle, and outer fluids. Increasing the flow rate ratio of the outer fluid to the other fluids [Qo/(Qm+Qi)] from 3 to 11, the outer radii of the emulsions decrease from 1120 to 950 μm. On the other hand, increasing the flow rate ratio of the middle fluid to the inner fluid (Qm/Qi) from 0.7 to 1.6, the aspect ratio of the emulsions increases from 4 to 8. Our experimental values are in good agreement with a simple theoretical model. These results suggest that our present method to control the generation of double emulsions can be used as an alternative approach to fabricate polystyrene targets for future laser fusion experiments.

Continuous synthesis of PVP stabilized biocompatible gold nanoparticles with a controlled size using a 3D glass capillary microfluidic device

A reliable glass capillary microfluidic method was developed for a continuous production of well-controlled gold nanoparticles (AuNPs) capped with polyvinylpyrrolidone (PVP) of different molecular weights (PVP K15, PVP K30 and PVP K90). A two-phase co-flow glass capillary microfluidic device with an injection orifice diameter ranging between 100 and 240µm was used to synthesise 100–240µm was used to synthesise AuNPs via the chemical reduction between tetrachloroaurate trihydrate (HAuCl4·3H2O) and ascorbic acid. AuNPs with an average diameter between 48 and 135nm were synthesised, as determined by DLS measurements. Decreasing the injection orifice diameter, increasing the flow rate of ascorbic acid stream and its pH resulted in smaller AuNPs. The polydispersity index (PDI) was found to be independent on the injection orifice diameter or the molecular weight of PVP, but increased with the increase of flow rate and the pH of ascorbic acid stream. The stability study over 6-week period confirmed that PVP K30 with an average Mw of 40000g/mol was the best capping agent to synthesize and stabilise smaller AuNPs. The reactor fouling due to deposition of AuNPs on reactor walls and orifices was mitigated by hydrophobization of reactor/capillary walls with octadecyltrimethoxisilane and the use of ascorbic acid solution of higher pH.

Osmotic Pressure Triggered Rapid Release of Encapsulated Enzymes with Enhanced Activity

In this study, a single‐step microfluidic approach is reported for encapsulation of enzymes within microcapsules with ultrathin polymeric shell for controlled release triggered by an osmotic shock. Using a glass capillary microfluidic device, monodisperse water‐in‐oil‐in‐water double emulsion droplets are fabricated with enzymes in the core and an ultrathin middle oil layer that solidifies to produce a consolidated inert polymeric shell with a thickness of a few tens to hundreds of nanometers. Through careful design of microcapsule membranes, a high percentage of cargo release, over 90%, is achieved, which is triggered by osmotic shock when using poly(methyl methacrylate) as the shell material. Moreover, it is demonstrated that compared to free enzymes, the encapsulated enzyme activity is maintained well for as long as 47 days at room temperature. This study not only extends industrial applications of enzymes, but also offers new opportunities for encapsulation of a wide range of sensitive molecules and biomolecules that can be controllably released upon applying osmotic shock.