Novel swirl flow-focusing microfluidic device for the production of monodisperse microbubbles

A novel swirl flow-focusing microfluidic axisymmetric device for the generation of monodisperse microbubbles at high production rates to be used as in-line contrast agents for medical applications is presented. The swirl effect is induced upstream of the discharge orifice by a circular array of microblades which form a given angle with the radial direction. The induced vortical component on the focusing liquid stabilizes the gas meniscus by the vorticity amplification due to vortex stretching as the liquid is forced through the discharge orifice. The stabilized meniscus tapers into a steady gas ligament that breaks into monodisperse microbubbles. A reduction up to \(57\%\) in the microbubble diameter is accomplished when compared to conventional axisymmetric flow-focusing microdevices. An exhaustive experimental study is performed for various blade angles and numerous gas to liquid flow rate ratios, validating previous VoF numerical simulations. The microbubbles issued from the stabilized menisci verify prior scaling law of flow-focusing.     

Scaling the formation of slug bubbles in microfluidic flow-focusing devices

The present study aims at scaling the formation of slug bubbles in flow-focusing microfluidic devices using a high-speed digital camera and a micro particle image velocimetry (μ-PIV) system. Experiments were conducted in two different polymethyl methacrylate square microchannels of respectively 600 × 600 and 400 × 400 μm. N₂ bubbles were generated in glycerol–water mixtures with several concentrations of surfactant sodium dodecyl sulfate. The influence of gas and liquid flow rates, the viscosity of the liquid phase and the width of the microchannel on the bubble size were explored. The bubble size was correlated as a function of the width of the microchannel W _c, the ratio of the gas/liquid flow rates Q _g/Q _l and the liquid Reynolds number. During the pinch-off stage, the variation of the minimum width of the gaseous thread W _m with the remaining time could be scaled as _boxclose_boxclose ()^ - 0.15 (T - t)^1/3 . W_{\text{m}} \propto ({\frac{{Q_{\text{g}} }}{{Q_{\text{l}} }}})^{ - 0.15} (T - t)^{1/3} . The velocity fields in the liquid phase around the thread, determined by μ-PIV measurements, were obtained around a forming bubble to reveal the role of the liquid phase.     

Liquid flooded flow-focusing microfluidic device for in situ generation of monodisperse microbubbles

Current microbubble-based ultrasound contrast agents are administered intravenously resulting in large losses of contrast agent, systemic distribution, and strict requirements for microbubble longevity and diameter size. Instead we propose in situ production of microbubbles directly within the vasculature to avoid these limitations. Flow-focusing microfluidic devices (FFMDs) are a promising technology for enabling in situ production as they can produce microbubbles with precisely controlled diameters in real-time. While the microfluidic chips are small, the addition of inlets and interconnects to supply the gas and liquid phase greatly increases the footprint of these devices preventing the miniaturization of FFMDs to sizes compatible with medium and small vessels. To overcome this challenge, we introduce a new method for supplying the liquid (shell) phase to a FFMD that eliminates bulky interconnects. A pressurized liquid-filled chamber is coupled to the liquid inlets of an FFMD, which we term a flooded FFMD. The microbubble diameter and production rate of flooded FFMDs were measured optically over a range of gas pressures and liquid flow rates. The smallest FFMD manufactured measured 14.5 × 2.8 × 2.3 mm. A minimum microbubble diameter of 8.1 ± 0.3 μm was achieved at a production rate of 450,000 microbubbles/s (MB/s). This represents a significant improvement with respect to any previously reported result. The flooded design also simplifies parallelization and production rates of up to 670,000 MB/s were achieved using a parallelized version of the flooded FFMD. In addition, an intravascular ultrasound (IVUS) catheter was coupled to the flooded FFMD to produce an integrated ultrasound contrast imaging device. B-mode and IVUS images of microbubbles produced from a flooded FFMD in a gelatin phantom vessel were acquired to demonstrate the potential of in situ microbubble production and real-time imaging. Microbubble production rates of 222,000 MB/s from a flooded FFMD within the vessel lumen provided a 23 dB increase in B-mode contrast. Overall, the flooded design is a critical contribution towards the long-term goal of utilizing in situ produced microbubbles for contrast enhanced ultrasound imaging of, and drug delivery to, the vasculature.     

Flow rate effect on droplet control in a co-flowing microfluidic device

Flow rate effect on droplet formation in a co-flowing microfluidic device is investigated numerically. Transition conditions are discovered that the droplet size is either approximately independent of or strongly dependent on the flow rate ratio. This phenomenon is explained by the relation between strain rate and droplet diameter. Regions of four drop patterns are demarcated and conditions that give polydisperse drops are described, which is helpful to assure the accuracy and efficiency in droplet production.     

Computational fluid dynamics analysis of microbubble formation in microfluidic flow-focusing devices

Bubble formation in a microfluidic flow-focusing device is simulated using the volume-of-fluid approach to achieve a complete solution of the Navier–Stokes equations for both the gas and liquid phases. The results of the simulation show good agreement with previous experimental results. A detailed examination of the predicted pressure and velocity profiles from the simulation also provide further validation for the conclusions drawn previously with experimental results. The simulation results show the existence of two distinct modes of bubble formation. Simulations of systems an order of magnitude smaller than those investigated experimentally indicate that such reduced systems sizes are a viable approach that would result in much smaller bubble sizes.     

Pinch-off mechanism for Taylor bubble formation in a microfluidic flow-focusing device

The present work aims at studying the nonlinear breakup mechanism for Taylor bubble formation in a microfluidic flow-focusing device by using a high-speed digital camera. Experiments were carried out in a square microchannel with cross section of 600 × 600 μm. During the nonlinear collapse process, the variation of the minimum radius of bubble neck (r ₀) with the remaining time until pinch-off (τ) can be scaled by a power–law relationship: \(r_{0} \propto \tau^{\alpha } .\) Due to the interface rearrangement around the neck, the nonlinear collapse process can be divided into two distinct stages: liquid squeezing collapse stage and free pinch-off stage. In the liquid squeezing collapse stage, the neck collapses under the constriction of the liquid flow and the exponent α approaches to 0.33 with the increase in the liquid flow rate Q _l. In the free pinch-off stage, the value of α is close to the theoretical value of 0.50 derived from the Rayleigh–Plesset equation and is independent of Q _l.     

Emulsification in a microfluidic flow-focusing device: effect of the viscosities of the liquids

We report the results of a comparative study of microfluidic emulsification of liquids with different viscosities. Depending on the properties of the fluids and their rates of flow, emulsification occurred in the dripping and jetting regimes. We studied the characteristic features and typical dependence of the size and of the size distribution of droplets in each regime. For each liquid, we identified a range of hydrodynamic conditions promoting generation of highly monodisperse droplets. Viscosity played an important role in emulsification: highly viscous liquids were emulsified into larger droplets with lower polydispersity. Although it was not possible to provide a unified scaling for the volumes of the droplets, our results suggest that the break-up dynamics of the lower viscosity fluids resembles the rate-of-flow-controlled break-up, as reported earlier for the formation of bubbles in flow-focusing geometries [Garstecki P, Stone HA, Whitesides GM (2005) Phys Rev Lett 94:164501]. The results of this study can be helpful for a rationalized selection of liquids for the controlled formation of droplets with a predetermined size and with a narrow distribution of sizes.     

New regime of droplet generation in a T-shape microfluidic junction

We present an experimental study of a new regime of monodisperse micro-droplet generation that we named the balloon regime. A dispersion of oil in water in a T-junction microfluidic system was studied. Several microfluidic devices having different cross-sections of the continuous and the dispersed phases micro-channels were tested. This new regime appears only for low- dispersed phase velocity. The micro-droplet size is mainly related to the geometry of the T-junction micro-channels especially its width and depth, and independent of the continuous and dispersed phases velocities. In our experiments, the velocities of the continuous and the dispersed phases $\overline v_{\rm c}$ and $\overline v_{\rm d}$ respectively, have been varied in a wide range: $\overline v_{\rm c}$ from 0.5 to 500 mm/s, and $\overline v_{\rm d}$ from 0.01 to 30 mm/s. We show that the continuous phase only controls the micro-droplet density, while the dispersed phase linearly changes the frequency of the micro-droplet generation. Another particularity of the present regime, which differentiates it from all other known regimes, is that the micro-droplet retains its circular shape throughout its formation at the T junction, and undergoes no deformation due to the drag forces. We propose a mechanism to explain the formation of micro-droplets in this new regime.     

A droplet-based microfluidic system capable of droplet formation and manipulation

Formation of emulsion droplets is crucial for a variety of industrial and scientific applications. This study presents a new droplet-based microfluidic system capable of generating tunable and uniform-sized droplets and subsequently deflecting these droplets at various inclination angles using a combination of flow-focusing and moving-wall structures. A pneumatic air chamber was used to activate the moving-wall structures, located nearby the outlet of the flow-focusing microchannels, such that the sheath flows can be locally accelerated. With this approach, the size of the droplets can be fine-tuned and sorted without adjusting the syringe pumps. Experimental data showed that droplets with diameters ranging from 31.4 to 146.2 μm with a variation of less than 5.39% can be generated. Besides, droplets can be sorted upwards or backwards with an inclination angle ranging from 0° to 53.5°. The development of this emulsion system may be promising for the formation and collection of emulsion products for applications in the pharmaceutical, cosmetics and food industries.     

Development of an injection molding tool for complex microfluidic geometries

This paper will track the design and results of an injection molding tool developed to manufacture microfluidic chips. The mold design and injection molding process was complicated by the presence of integrated capillary fluidic interconnects. We determined that design of the runner and gate system responsible for delivering molten plastic to the cavity had a significant impact on the quality of parts produced by the mold and the size of the process window. Numerical results confirm our findings that reducing gate lengths and increasing part thickness dramatically improved the filling profile and lowered injection pressures by 37%. Finally, the influence of gate location on part shrinkage is analyzed and discussed.     

Valve-based microfluidic droplet micromixer and mercury (II) ion detection

A valve-based microfluidic micromixer was developed for multiply component droplets generation, manipulation and active mixing. By integrating pneumatic valves in microfluidic device, droplets could be individually generated, merged and well mixed automatically. Moreover, droplet volume could be controlled precisely by tuning loading pressure or the flow rate of the oil phase, and certain droplets fusion conditions were also investigated by adjusting the droplet driving times and oil flow rates. In these optimized conditions, fluorescence enhancement of droplets was used to detect Hg (II) ions in droplet by mixing with probe droplets (Rhodamine B quenched by gold nanoparticle). This method would have powerful potential for tiny volume sample assay or real-time chemical reaction study.     

An investigation on the mechanism of droplet formation in a microfluidic T-junction

This paper reports the findings of a numerical investigation on the droplet break-up in a microfluidic T-junction. The numerical flow visualization of the droplet formation process is validated with the experimental flow visualization. From the computational results, we show that the pressure profile of the dispersed phase and the continuous phase in the squeezing regime changes as the droplet break-up process proceeds. The assumption taken by other researchers that the dispersed phase pressure profile, during the droplet formation process at a T-junction, remains constant and only the continuous phase pressure changes according to the blockage of the channel is proved to be invalid. We provide new insights on the pressure difference between the dispersed phase and the continuous phase during the droplet break-up process and show that the minimum pressure difference happens at the last moment of the droplet break-up and not during the second and third stage of the droplet formation mechanism in the squeezing regime as suggested by other researchers.     

Generation of uniform-size droplets by multistep hydrodynamic droplet division in microfluidic circuits

A microfluidic system is presented to generate multiple daughter droplets from a mother droplet, by the multistep hydrodynamic division of the mother droplet at multiple branch points in a microchannel. A microchannel network designed based on the resistive circuit model enables us to control the distribution ratio of the flow rate, which dominates the division ratios of the mother droplets. We successfully generated up to 15 daughter droplets from a mother droplet with a variation in diameter of less than 2%. In addition, we examined factors affecting the division ratio, including the average fluid velocity, interfacial tension, fluid viscosity, and the distribution ratio of volumetric flow rates at a branch point. Additionally, we actively controlled the volume of the mother droplets and examined its influence on the size of the daughter droplets, demonstrating that the size of the daughter droplets was not significantly influenced by the volume of the mother droplet when the distribution ratio was properly controlled. The presented system for controlling droplet division would be available as an innovative means for preparing monodisperse emulsions from polydisperse emulsions, as well as a technique for making a microfluidic dispenser for digital microfluidics to analyze the droplet compositions.     

Effects of topological changes in microchannel geometries on the asymmetric breakup of a droplet

Passive asymmetric breakups of a droplet could be done in many microchannels of various geometries. In order to study the effects of different geometries on the asymmetric breakup of a droplet, four types of asymmetric microchannels with the topological equivalence of geometry are designed, which are T-90, Y-120, Y-150, and I-180 microchannels. A three-dimensional volume of fluid multiphase model is employed to investigate the asymmetric rheological behaviors of a droplet numerically. Three regimes of rheological behaviors as a function of the capillary numbers Ca and the asymmetries As defined by As = (b1 ? b2)/(b1 + b2) (where b1 and b2 are the widths of two asymmetric sidearms) have been observed. A power law model based on three major factors (Ca, As and the initial volume ratio r ₀) is employed to describe the volume ratio of two daughter droplets. The analysis of pressure fields shows that the pressure gradient inside the droplet is one of the major factors causing the droplet translation during its asymmetric breakup. Besides the above similarities among various microchannels, the asymmetric breakup in them also have some slight differences as various geometries have different enhancement or constraint effects on the translation of the droplet and the cutting action of flows. It is disclosed that I-180 microchannel has the smallest critical capillary number, the shortest splitting time, and is hardest to generate satellite droplets.     

A droplet microfluidic approach to single-stream nucleic acid isolation and mutation detection

In this work, a droplet microfluidic platform for genetic mutation detection from crude biosample is described. Single-stream integration of nucleic acid isolation and amplification is realized on a simple fluidic cartridge. Subsequent DNA melting curve is employed with signal normalizing algorithm to differentiate heterozygous K-ras codon 12 c.25G>A mutant from the wild type. This technique showcases an alternative to modular bench-top approaches for genetic mutation screening, which is of interest to decentralized diagnostic platforms.