T-junction Microfluidic Device Research Articles

Experimental and Computational Investigation of Microbubble Formation in a Single Capillary Embedded T-junction Microfluidic Device.

In recent years, there has been a notable increase in the interest toward microfluidic devices for microbubble synthesis. The upsurge can be primarily attributed to the exceptional control these devices offer in terms of both the size and the size distribution of microbubbles. Among various microfluidic devices available, capillary-embedded T-junction microfluidic (CETM) devices have been extensively used for the synthesis of microbubbles. One distinguishing feature of CETM devices from conventional T-junction devices is the existence of a wall at the right-most end, which causes a backflow of the continuous phase at the mixing zone during microbubble formation. The back flow at the mixing zone can have several implications during microbubble formation. It can possibly affect the local velocity and shearing force at the mixing zone, which in turn can affect the size and production rate of the microbubbles. Therefore, in this work, we experimentally and computationally understand the process of microbubble formation in CETM devices. The process is modeled using computational fluid dynamics (CFD) with the volume-of-fluid approach, which solves the Navier-Stokes equations for both the gas and liquid phases. Three scenarios with a constant liquid velocity of 0.053 m/s with varying gas velocity and three with a constant gas velocity of 0.049 m/s at different liquid velocities were explored. Increase in the liquid and gas velocity during microbubble formation was found to enhance production rates in both experiments and simulations. Additionally, the change in microbubble size with the change in liquid velocity was found to agree closely with the findings of the simulation with a coefficient of variation of 10%. When plotted against the time required for microbubble generation, the fluctuations in the pressure showed recurrent crests and troughs throughout the microbubble formation process. The understanding of microbubble formation in CETM devices in the presence of backflow will allow improvement in size reduction of microbubbles.

Projection Micro-Stereolithography to Manufacture a Biocompatible Micro-Optofluidic Device for Cell Concentration Monitoring.

In this work, a 3D printed biocompatible micro-optofluidic (MoF) device for two-phase flow monitoring is presented. Both an air-water bi-phase flow and a two-phase mixture composed of micrometric cells suspended on a liquid solution were successfully controlled and monitored through its use. To manufacture the MoF device, a highly innovative microprecision 3D printing technique was used named Projection Microstereolithography (PμSL) in combination with the use of a novel 3D printable photocurable resin suitable for biological and biomedical applications. The concentration monitoring of biological fluids relies on the absorption phenomenon. More precisely, the nature of the transmission of the light strictly depends on the cell concentration: the higher the cell concentration, the lower the optical acquired signal. To achieve this, the microfluidic T-junction device was designed with two micrometric slots for the optical fibers' insertion, needed to acquire the light signal. In fact, both the micro-optical and the microfluidic components were integrated within the developed device. To assess the suitability of the selected biocompatible transparent resin for optical detection relying on the selected working principle (absorption phenomenon), a comparison between a two-phase flow process detected inside a previously fully characterized micro-optofluidic device made of a nonbiocompatible high-performance resin (HTL resin) and the same made of the biocompatible one (BIO resin) was carried out. In this way, it was possible to highlight the main differences between the two different resin grades, which were further justified with proper chemical analysis of the used resins and their hydrophilic/hydrophobic nature via static water contact angle measurements. A wide experimental campaign was performed for the biocompatible device manufactured through the PμSL technique in different operative conditions, i.e., different concentrations of eukaryotic yeast cells of Saccharomyces cerevisiae (with a diameter of 5 μm) suspended on a PBS (phosphate-buffered saline) solution. The performed analyses revealed that the selected photocurable transparent biocompatible resin for the manufactured device can be used for cell concentration monitoring by using ad hoc 3D printed micro-optofluidic devices. In fact, by means of an optical detection system and using the optimized operating conditions, i.e., the optimal values of the flow rate FR=0.1 mL/min and laser input power P∈{1,3} mW, we were able to discriminate between biological fluids with different concentrations of suspended cells with a robust working ability R2=0.9874 and Radj2=0.9811.

Generation of Photopolymerized Microparticles Based on PEGDA Hydrogel Using T-Junction Microfluidic Devices: Effect of the Flow Rates.

The formation of microparticles (MPs) of biocompatible and biodegradable hydrogels such as polyethylene glycol diacrylate (PEGDA) utilizing microfluidic devices is an attractive option for entrapment and encapsulation of active principles and microorganisms. Our research group has presented in previous studies a formulation to produce these hydrogels with adequate physical and mechanical characteristics for their use in the formation of MPs. In this work, hydrogel MPs are formed based on PEGDA using a microfluidic device with a T-junction design, and the MPs become hydrogel through a system of photopolymerization. The diameters of the MPs are evaluated as a function of the hydrodynamic condition flow rates of the continuous (Qc) and disperse (Qd) phases, measured by optical microscopy, and characterized through scanning electron microscopy. As a result, the following behavior is found: the diameter is inversely proportional to the increase in flow in the continuous phase (Qc), and it has a significant statistical effect that is greater than that in the flow of the disperse phase (Qd). While the diameter of the MPs is proportional to Qd, it does not have a significant statistical effect on the intervals of flow studied. Additionally, the MPs' polydispersity index (PDI) was measured for each experimental hydrodynamic condition, and all values were smaller than 0.05, indicating high homogeneity in the MPs. The microparticles have the potential to entrap pharmaceuticals and microorganisms, with possible pharmacological and bioremediation applications.

Development of a predictive response surface model for size of silver nanoparticles synthesized in a T-junction microfluidic device

Optimisation of the parameters governing the synthesis of silver nanoparticles (AgNPs) is a critical step in controlling particle size, which facilitates their application in diverse range of industrial and consumer related products. AT-junctionmicrofluidicsystemwas used together with design of experiments, regression-analysis and response surface methodology to build a predictive numerical model for the size of silver nanoparticles (AgNPs). Aqueous solutions of silver-precursor and reducing/stabilizing agent were supplied by two separate channels meeting at the T-junction, withthereaction occurring downstream intheoutlet tube. To improve the mixingof the reagents,the output tube was coiled onto a 3D-printed helical shape device, exploiting the creation of Dean vortices. The effects of both reaction and hydrodynamic conditions including the solution pH, collection temperature, helical curvature, flow rates and concentration of stabilising agent were investigated using a D-optimal experimental design.The obtainedexperimental size distributions for the AgNPs were fittedtoa polynomial model with an average prediction error of around 13% and a 37 % maximum error.The modelpredictedthe optimal synthesis conditionsforthe global and local-minimum sizes of AgNPswith an errorof around 7.0% and 16.1% respectively. The average prediction error of the testing set was estimated to be 6.8% with 16.1% being the maximum error.

Viscoelastic Particle Encapsulation Using a Hyaluronic Acid Solution in a T-Junction Microfluidic Device

The encapsulation of particles and cells in droplets is highly relevant in biomedical engineering as well as in material science. So far, however, the majority of the studies in this area have focused on the encapsulation of particles or cells suspended in Newtonian liquids. We here studied the particle encapsulation phenomenon in a T-junction microfluidic device, using a non-Newtonian viscoelastic hyaluronic acid solution in phosphate buffer saline as suspending liquid for the particles. We first studied the non-Newtonian droplet formation mechanism, finding that the data for the normalised droplet length scaled as the Newtonian ones. We then performed viscoelastic encapsulation experiments, where we exploited the fact that particles self-assembled in equally-spaced structures before approaching the encapsulation area, to then identify some experimental conditions for which the single encapsulation efficiency was larger than the stochastic limit predicted by the Poisson statistics.

Microdroplet-based synthesis of polymethylsilsesquioxane microspheres with controllable size, surface morphology, and internal structure

Monodispersed polysilsesquioxane (PSQ) microspheres are generally synthesized by the classical sol–gel method. Using this method, the particle size is limited to the range of several hundred nanometers to several microns. The preparation of monodispersed large-sized PSQ microspheres remains technically challenging. Herein, with the polymethylsilsesquioxane (PMSQ) microspheres as the model product, a microdroplet-based strategy was developed for the synthesis of PSQ microspheres with larger particle sizes. According to the properties of the reactants, a W/O microdroplet reaction system was realized, i.e., with the mixture of methyltrimethoxysilane (MTMS) and liquid paraffin as the continuous phase and ammonia solution as the dispersed phase. The monodispersed W/O microdroplets were generated in a step T-junction microfluidic device, and solidified into PMSQ microspheres via in-situ interfacial polycondensation (∼2 min) in a microtube reactor. The size, surface morphology and internal structure of the PMSQ microspheres could be tuned by adjusting the synthesis conditions, mainly including the two-phase flow rates, MTMS concentration, NH4OH concentration, and the structural parameters of the microfluidic device. Various PMSQ microspheres with corrugated or smooth surface morphology, and loose or dense internal structure could be synthesized. The microsphere size could be tuned from tens of microns (∼20 μm) to hundreds of microns.

Generating Lifetime-Enhanced Microbubbles by Decorating Shells with Silicon Quantum Nano-Dots Using a 3-Series T-Junction Microfluidic Device

Long-term stability of microbubbles is crucial to their effectiveness. Using a new microfluidic device connecting three T-junction channels of 100 μm in series, stable monodisperse SiQD-loaded bovine serum albumin (BSA) protein microbubbles down to 22.8 ± 1.4 μm in diameter were generated. Fluorescence microscopy confirmed the integration of SiQD on the microbubble surface, which retained the same morphology as those without SiQD. The microbubble diameter and stability in air were manipulated through appropriate selection of T-junction numbers, capillary diameter, liquid flow rate, and BSA and SiQD concentrations. A predictive computational model was developed from the experimental data, and the number of T-junctions was incorporated into this model as one of the variables. It was illustrated that the diameter of the monodisperse microbubbles generated can be tailored by combining up to three T-junctions in series, while the operating parameters were kept constant. Computational modeling of microbubble diameter and stability agreed with experimental data. The lifetime of microbubbles increased with increasing T-junction number and higher concentrations of BSA and SiQD. The present research sheds light on a potential new route employing SiQD and triple T-junctions to form stable, monodisperse, multi-layered, and well-characterized protein and quantum dot-loaded protein microbubbles with enhanced stability for the first time.

Combining Ultrasound and Capillary-Embedded T-Junction Microfluidic Devices to Scale Up the Production of Narrow-Sized Microbubbles through Acoustic Fragmentation.

Microbubbles are tiny gas-filled bubbles that have a variety of applications in ultrasound imaging and therapeutic drug delivery. Microbubbles can be synthesized using a number of techniques including sonication, amalgamation, and saline shaking. These approaches can produce highly concentrated microbubble suspensions but offer minimal control over the size and polydispersity of the microbubbles. One of the simplest and effective methods for producing monodisperse microbubbles is capillary-embedded T-junction microfluidic devices, which offer great control over the microbubble size. However, lower production rates (∼200 bubbles/s) and large microbubble sizes (∼300 μm) limit the applicability of such devices for biomedical applications. To overcome the limitations of these technologies, we demonstrate in this work an alternative approach to combine a capillary-embedded T-junction device with ultrasound to enhance the generation of narrow-sized microbubbles in aqueous suspensions. Two T-junction microfluidic devices were connected in parallel and combined with an ultrasonic horn to produce lipid-coated SF6 core microbubbles in the size range of 1-8 μm. The rate of microbubble production was found to increase from 180 microbubbles/s in the absence of ultrasound to (6.5 ± 1.2) × 106 bubble/s in the presence of ultrasound (100% ultrasound amplitude). When stored in a closed environment, the microbubbles were observed to be stable for up to 30 days, with the concentration of the microbubble suspension decreasing from ∼2.81 × 109/mL to ∼2.3 × 106/mL and the size changing from 1.73 ± 0.2 to 1.45 ± 0.3 μm at the end of 30 days. The acoustic response of these microbubbles was examined using broadband attenuation spectroscopy, and flow phantom imaging was performed to determine the ability of these microbubble suspensions to enhance the contrast relative to the surrounding tissue. Overall, this approach of coupling ultrasound with microfluidic parallelization enabled the continuous production of stable microbubbles at high production rates and low polydispersity using simple T-junction devices.

Numerical Investigations on Alternate Droplet Formation in Microfluidic Devices

We present numerical investigations on generating droplets in both single and double T-junction microfluidic devices using the Volume of Fluid (VOF) method. We validate our 2D simulation results with an experimental data reported in the past. The average pressure in the channel increases by 6% and capillary number by 16% for an increase in the width of side-channel from 50 μm to 100 μm in a single T-junction device. Similar increase in average pressure and capillary number is seen, for the increase in the width of one of the side channel in double T-junction device. The temporal variation of pressure in both the side channels shows that the pressure is lesser in the wider side channel. The average pressure in the channel decreases by 75% and capillary number by 15% for an increase in width of the main channel from 50 μm to 100 μm in a single T-junction device. Similar decrease in average pressure and capillary number is seen for the increase in the width of the main channel in double T-junction device. A gradual increase in the width of the main channel shows that, droplets generated in alternate regime when the width of the main channel is 1.4 times the width of side channel. In this regime, the temporal variation in pressure show a periodic change in both the side channel. Finally, in double T-junction device, the addition of surfactant has no significant effect on droplet generation in merging regime but it is seen in alternate regime.

Metformin-Loaded Polymer-Based Microbubbles/Nanoparticles Generated for the Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is increasingly common all over the world with a high risk of progressive hyperglycemia and high microvascular and macrovascular complications. The currently used drugs in the treatment of T2DM have insufficient glucose control and can carry detrimental side effects. Several drug delivery systems have been investigated to decrease the side effects and frequency of dosage, and also to increase the effect of oral antidiabetic drugs. In recent years, the use of microbubbles in biomedical applications has greatly increased, and research into microactive carrier bubbles continues to generate more and more clinical interest. In this study, various monodisperse polymer nanoparticles at different concentrations were produced by bursting microbubbles generated using a T-junction microfluidic device. Morphological analysis by scanning electron microscopy, molecular interactions between the components by FTIR, drug release by UV spectroscopy, and physical analysis such as surface tension and viscosity measurement were carried out for the particles generated and solutions used. The microbubbles and nanoparticles had a smooth outer surface. When the microbubbles/nanoparticles were compared, it was observed that they were optimized with 0.3 wt % poly(vinyl alcohol) (PVA) solution, 40 kPa pressure, and a 110 μL/min flow rate, thus the diameters of the bubbles and particles were 100 ± 10 μm and 70 ± 5 nm, respectively. Metformin was successfully loaded into the nanoparticles in these optimized concentrations and characteristics, and no drug crystals and clusters were seen on the surface. Metformin was released in a controlled manner at pH 1.2 for 60 min and at pH 7.4 for 240 min. The process and structures generated offer great potential for the treatment of T2DM.

Negative Pressure Provides Simple and Stable Droplet Generation in a Flow-Focusing Microfluidic Device.

Droplet microfluidics is an extremely useful and powerful tool for industrial, environmental, and biotechnological applications, due to advantages such as the small volume of reagents required, ultrahigh-throughput, precise control, and independent manipulations of each droplet. For the generation of monodisperse water-in-oil droplets, usually T-junction and flow-focusing microfluidic devices connected to syringe pumps or pressure controllers are used. Here, we investigated droplet-generation regimes in a flow-focusing microfluidic device induced by the negative pressure in the outlet reservoir, generated by a low-cost mini diaphragm vacuum pump. During the study, we compared two ways of adjusting the negative pressure using a compact electro-pneumatic regulator and a manual airflow control valve. The results showed that both types of regulators are suitable for the stable generation of monodisperse droplets for at least 4 h, with variations in diameter less than 1 µm. Droplet diameters at high levels of negative pressure were mainly determined by the hydrodynamic resistances of the inlet microchannels, although the absolute pressure value defined the generation frequency; however, the electro-pneumatic regulator is preferable and convenient for the accurate control of the pressure by an external electric signal, providing more stable pressure, and a wide range of droplet diameters and generation frequencies. The method of droplet generation suggested here is a simple, stable, reliable, and portable way of high-throughput production of relatively large volumes of monodisperse emulsions for biomedical applications.

Study on the Technology of Monodisperse Droplets by a High-Throughput and Instant-Mixing Droplet Microfluidic System.

In this study, we report a novel high-throughput and instant-mixing droplet microfluidic system that can prepare uniformly mixed monodisperse droplets at a flow rate of mL/min designed for rapid mixing between multiple solutions and the preparation of micro-/nanoparticles. The system is composed of a magneton micromixer and a T-junction microfluidic device. The magneton micromixer rapidly mixes multiple solutions uniformly through the rotation of the magneton, and the mixed solution is sheared into monodisperse droplets by the silicone oil in the T-junction microfluidic device. The optimal conditions of the preparation of monodisperse droplets for the system have been found and factors affecting droplet size are analyzed for correlation; for example, the structure of the T-junction microfluidic device, the rotation speed of the magneton, etc. At the same time, through the uniformity of the color of the mixed solution, the mixing performance of the system is quantitatively evaluated. Compared with mainstream micromixers on the market, the system has the best mixing performance. Finally, we used the system to simulate the internal gelation broth preparation of zirconium broth and uranium broth. The results show that the system is expected to realize the preparation of ceramic microspheres at room temperature without cooling by the internal gelation process.

Prediction of droplet sizes in a T-junction microchannel: Effect of dispersed phase inertial forces

The generation of monodispersed droplets in T-junction microchannels has wide range applications in biochemical analysis and material synthesis. While the generation of these monodispersed droplets was previously considered to be a balance between forces acting from continuous phase and interfacial force, it is shown here that the inertial force from the dispersed phase also plays an important role in determining the size of the generated droplets. A theoretical analysis for the size of monodisperse droplets generated in a microfluidic T-junction device is developed, and it is validated with a large set of experimental observations. The theoretical analysis accounts for the inertial forces from the dispersed phase along with the forces from the continuous phase and the interfacial forces to define the non-dimensional numbers that govern the droplet breakup in the T-junction microchannel.

Electrohydrodynamic droplet formation in a T-junction microfluidic device

Abstract

Study of the theory of microbubble bursting to obtain bio-inspired alginate nanoparticles

Through the bursting of microbubbles prepared by a T-junction microfluidic device with uniform particle size, bio-inspired alginate nanoparticles were obtained via shell disintegration process. The high-speed microscopy and digital image technology were used to observe the evolution of the microbubble raft before bubble bursting. To investigate the mechanism of nanoparticle formation, a theoretical approach combining the shell disintegration theory and the rule of the ligament breakup was developed through which the size of nanoparticles could be predicted. Such analysis showed that the bubble size and the viscosity of the alginate solution to generate bubbles were both key factors for determining the average particle size and size distribution and such results were proved experimentally. Also, the size distribution of the nanoparticles were found to be very well represented by gamma distributions, underlying the crucial role played by the ligament dynamics in building up the broad statistics of sprays.

Endothelialized microrods for minimally invasive in situ neovascularization

Despite the significant advancements in fabricating various scaffolding systems over the past decades, generation of functional tissues towards vascularization remains challenging for the currently available biofabrication approaches. On the other hand, the applicability of traditional surgical transplantation of vascularized tissue constructs is sometimes limited due to the sophisticated surgical procedures, which are invasive, leading to increased risks of scar formation and infection. Considering these facts, we present an innovative platform, the angiogenic microrods composed of sodium alginate/gelatin harboring proliferating endothelial cells using a specially designed double T-junction microfluidic device with an expansion chamber, for achieving minimally invasive neovascularization in situ. Such vessel-like microarchitectures could be derived through controlled penetration of the crosslinker genepin for the gelatin phase, ensuing differential degrees in crosslinking of peripheral and central portions of the microstructures, thus resulting in the formation of vascular lumen-like hollow cavities via endothelial cell migration and proliferation during culture in vitro. Furthermore, in vivo performance of the microrods was explored. We believe that the development of these modular microrods for minimally invasive delivery is of great interest and offers a convenient approach for vascularization in situ.

Self-assembled micro-stripe patterning of sessile polymeric nanofluid droplets

When sessile nanofluid droplets evaporate, solid nanoparticles can be organized in a wide variety of patterns on the substrate. The composition of the nanofluid, internal flow type of droplet and the rate of drying affect drop geometry, and the final pattern. Using poly(lactic-co-glycolic acid)-block-poly(ethylene glycol)(PLGA-b-PEG) as the example, we produced micro-stripe patterning from nanoparticles by drying of sessile fluid droplets. We investigated the nanoparticle properties and flow dynamics to clarify their effects on the patterning. Nanoparticles were prepared by hydrodynamic flow focusing using a T-junction microfluidic device with high production efficiency and the ability to generate an extremely narrow size distribution. PLGA-b-PEG was prepared as oil phase in acetonitrile and water/oil flow rate was changed from 1 to 3 at constant oil phase flow rate (50 μL/min). Then, nanofluid was collected on the surface as sessile droplets within acetonitrile/water binary dispersed phase. Depending on size, charge and size-distribution, the nanoparticles deposited on the surface exhibited various patterns. Dynamic Light and X-ray Scattering measurements showed that, approximately 100 nm particles with relatively low PDI (0.04) were produced for the first time in surfactant free conditions in a microfluidic device and they generated self-assembled ordered patterns, which are regulated by the type of internal flow in the sessile nanofluid droplet during sequential evaporation of acetonitrile and water.

Numerical study of droplet formation in the T-junction microchannel with wall velocity slip

Effect of hydrophobicity on droplet formation in the T-junction microfluidic devices is numerically studied. A Navier slip model is adopted. Results reveal that, as increasing of slip length, the velocity profile across the channel becomes flattened. With the increase of slip length, the shear stress on dispersed phase exerted by the continuous phase decreases, thus, the deformation of the dispersed phase weakens while the final droplet size increases. The pressure distributions along the central axis of main channel show a smaller pressure drop when the wall velocity slip length increases.

Formation of PEG-DA polymerized microparticles by different microfluidics devices: A T-junction device and a flow focusing device

Abstract Hydrogels have become a key class of materials that could be used in several fields such as biotechnology and nanotechnology. They can be classified as natural and synthetic according to their base material. Poly (ethylene glycol) diacrylate (PEG-DA) is a synthetic hydrogel, which can be considered for a wide variety of applications in the fields of biomedical research, drug delivery, tissue engineering and scaffolds among others. For these reasons, the design and the use of droplet-based microfluidics devices are important for the production of these microparticles of PEG-DA, which have gained popularity. In this research, two microfluidics devices are analyzed; a microfluidic T-junction device and a microfluidic flow focusing device. These devices are fabricated by using poly (dimethyl siloxane). The research is based on the flow rate variation of the dispersed phase (PEG-DA solution) and the continuous phase (Mineral oil) to establish the best conditions to the formation of the microparticles. Results show that the variation of the continuous phase flow rates and the geometry have an influence in the droplet formation mechanism. In addition, it is interesting to observe the flow rates in which the droplet formation occurs and which it does not.

Formation of Microdroplet in T-junction Microfluidic System: Experiment and Simulation

The purpose of this study is to investigate the formation of the water droplet in oil using T-junction microfluidic device. Both numerical and experimental methods have been developed to explore the dependence of droplet size on the flow rate of two immiscible liquids as well as the system geometry. The velocity of droplet in channel is also considered. The microfluidic system was fabricated with lithography technique. The 3D simulation was performed based on COMSOL software using level set method. The size of droplet is inversely proportional to the flow rate of continuous phase according to exponential function, increases linearly with the flow rate of dispersed phase, and decreases as the width of lateral channel decreases. While the decreasing of the width of the lateral channel gives rise to the increasing of droplet velocity, the velocity of droplet depends linearly on the flow rate of disperse phase. A good consistence was observed between the theory and the experiment.