Scale-up and control of droplet production in coupled microfluidic flow-focusing geometries

A single microfluidic chip consisting of six microfluidic flow-focusing devices operating in parallel was developed to investigate the feasibility of scaling microfluidic droplet generation up to production rates of hundreds of milliliters per hour. The design utilizes a single inlet channel for both the dispersed aqueous phase and the continuous oil phase from which the fluids were distributed to all six flow-focusing devices. The exit tubing for each of the six flow-focusing devices is separate and individually plumbed to each device. Within each flow-focusing device, the droplet size was monodisperse, but some droplet size variations were observed across devices. We show that by modifying the flow resistance in the outlet channel of an individual flow-focusing device it is possible to control both the droplet size and frequency of droplet production. This can be achieved through the use of valves or, as is done in this study, by changing the length of the exit tubing plumbed to the outlet of the each device. Longer exit tubing and larger flow resistance is found to lead to larger droplets and higher production frequencies. The devices can thus be individually tuned to create a monodisperse emulsion or an emulsion with a specific drop size distribution.     

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.     

Simulations of extensional flow in microrheometric devices

We present a detailed numerical study of the flow of a Newtonian fluid through microrheometric devices featuring a sudden contraction–expansion. This flow configuration is typically used to generate extensional deformations and high strain rates. The excess pressure drop resulting from the converging and diverging flow is an important dynamic measure to quantify if the device is intended to be used as a microfluidic extensional rheometer. To explore this idea, we examine the effect of the contraction length, aspect ratio and Reynolds number on the flow kinematics and resulting pressure field. Analysis of the computed velocity and pressure fields show that, for typical experimental conditions used in microfluidic devices, the steady flow is highly three-dimensional with open spiraling vortical structures in the stagnant corner regions. The numerical simulations of the local kinematics and global pressure drop are in good agreement with experimental results. The device aspect ratio is shown to have a strong impact on the flow and consequently on the excess pressure drop, which is quantified in terms of the dimensionless Couette and Bagley correction factors. We suggest an approach for calculating the Bagley correction which may be especially appropriate for planar microchannels. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Using an electro-spraying microfluidic chip to produce uniform emulsions under a direct-current electric field

An electro-spraying microfluidic chip was integrated with a parallel electrode and flow-focusing device to successfully generate uniform emulsions with an electric field. This approach utilizes a high electric field driven by a direct-current voltage to form a stable Taylor cone in the flow-focusing position. The Taylor cone can then generate stable and uniform emulsions that are less than 5?μm in diameter. The emulsion size is controlled by the surfactant concentration, the ratio of the water and oil phase flow rates and the strength of the electric field. When the strength of the electric field increases at a high surfactant concentration and low ratio of flow rates, the Taylor angle decreases, which causes the emulsion size to decrease. In this study, the water emulsion diameter ranged from 1 to 98?μm, and the poly(lactic-co-glycolic acid) (PLGA) emulsion size ranged from 7 to 70?μm. The microfluidic chip developed in this work has the advantages of actively controlling the emulsion size and generating uniform emulsions (the relative standard deviation was less than 10%) and represents a new emulsion generation process.     

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.     

Enhanced-throughput production of polymersomes using a parallelized capillary microfluidic device

We report a parallelized capillary microfluidic device for enhanced production rate of monodisperse polymersomes. This device consists of four independent capillary microfluidic devices, operated in parallel; each device produces monodisperse water-in-oil-in-water (W/O/W) double-emulsion drops through a single-step emulsification. During generation of the double-emulsion drops, the innermost water drop is formed first and it triggers a breakup of the middle oil phase over wide range of flow rates; this enables robust and stable formation of the double-emulsion drops in all drop makers of the parallelized device. Double-emulsion drops are transformed to polymersomes through a dewetting of the amphiphile-laden middle oil phase on the surface of the innermost water drop, followed by the subsequent separation of the oil drop. Therefore, we can make polymersomes with a production rate enhanced by a factor given by the number of drop makers in the parallelized device.     

Fabrication and in situ characterization of microcapsules in a microfluidic system

We have designed a microfluidic system that enables both the fabrication of calibrated capsules and the in situ characterization of their mechanical properties. The fabrication setup consists of a double flow-focusing system. A human serum albumin aqueous solution is introduced in the central channel of a first Y-junction. Intercepted by the lateral flows of a hydrophobic phase, it is dispersed into microdroplets. A cross-linking agent is then introduced at a second Y-junction allowing a membrane to form around the droplets. The time of cross-linking is controlled by the length of a wavy channel located downstream of the second junction. A cylindrical microchannel finally enables to deform and characterize the capsules thus formed. The mechanical properties of the capsule membrane are obtained by inverse analysis. The results show that the drop size increases with the flow rate ratio between the central and lateral channels. The mean shear modulus of the capsules fabricated after 23 s of cross-linking is of the order of the surface tension between the two phases indicating that a reaction time of 23 s is too short for an elastic membrane to form around the droplet. When the cross-linking time is increased to 60 s, the microcapsules surface is wrinkled, thus confirming that a solid membrane is formed around the drop. The mean shear modulus of the capsule membrane increases with the cross-linking time, which is in agreement with our previous chemical results and proves that a fine control of the mechanical properties is possible by choosing adequately the control parameters of the system.     

Combined circuit/device modeling and simulation of integrated microfluidic systems

A combined circuit/device model for the analysis of integrated microfluidic systems is presented. The complete model of an integrated microfluidic device incorporates modeling of fluidic transport, chemical reaction, reagent mixing, and separation. The fluidic flow is generated by an applied electrical field or by a combined electrical field and pressure gradient. In the proposed circuit/device model, the fluidic network has been represented by a circuit model and the functional units of the /spl mu/-TAS (micro Total Analysis System) have been represented by appropriate device models. We demonstrate the integration of the circuit and the device models by using an example, where the output from the fluidic transport module serves as the input for the other modules such as mixing, chemical reaction and separation. The combined circuit/device model can be used for analysis and design of entire microfluidic systems with very little computational expense, while maintaining the desired level of accuracy.     

Potentiometric characterisation of a dual-stream electrochemical microfluidic device

A microfluidic device is presented with off-chip electrodes residing in a reservoir and connected via micro-capillaries to the Y-shaped microfluidic channel. The device is tested by potentiometric measurements involving dual-stream laminar flow of two aqueous solutions carrying different electrolytes at various concentrations. Open circuit potentials are measured for a series of solutions of alkali metal chlorides and tetraalkylammonium chlorides as well as for dilute hydrochloric acid. The open circuit potential for the microfluidic chip was calculated by taking into account the diffusion potential at finite ionic strength as well as the potential difference introduced by the reference electrode system. The liquid junction potential developed at the boundary of the co-flowing aqueous solutions may be manipulated to have greater or lesser relative contributions to the measured open circuit potential based on use of electrolyte salts having cation and anion pairs of similar or dissimilar mobilities in solution. A reasonable agreement between theoretical and experimental values of the open circuit potential is observed for these situations. The results show that simple microfluidic structures possess a rich environment for exploration and application of the solution chemistry of ions.     

微沟道内两相流速比对液滴形成的影响

研究了流聚焦微沟道内不同两相流速比对单分散性液滴形成的影响.不相混容的两相系统能够快速、周期性地形成液滴,液滴的形态和生成率随着油相速度的变化而改变.研究采用模拟软件COMSOL Mutiphysics,模拟了不同流速下液滴的形成过程,并通过实验进行了验证,从流体动力学的角度解释了其物理机制.所得结论为在流聚焦微沟道内获得分散性良好且大小可控的液滴提供了理论和数据支持.     

Gas�Cliquid flow stability and bubble formation in non-Newtonian fluids in microfluidic flow-focusing devices

This communication describes the gas–liquid two-phase flow patterns and the formation of bubbles in non-Newtonian fluids in microfluidic flow-focusing devices. Experiments were conducted in two different polymethyl methacrylate (PMMA) square microchannels of, respectively, 600 × 600 and 400 × 400 μm. N₂ bubbles were generated in non-Newtonian polyacrylamide (PAAm) solutions of different concentrations. Slug bubble, missile bubble, annular and intermittent flow patterns were observed at the cross-junction by varying gas and liquid flow rates. Gas and liquid flow rates, concentration of PAAm solutions, and channel size were varied to investigate their effect on the mechanism of bubble formation. The bubble size was proportional to the ratio of gas/liquid flow rate for slug bubbles and could be scaled with the ratio of gas/liquid flow rate as a power–law relationship for missile bubbles under wide experimental conditions.     

Effect of operating conditions and liquid physical properties on the size of monodisperse microbubbles produced in a capillary embedded T-junction device

The aim of this study was to investigate the effect of operating parameters such as liquid flow rate, gas inlet pressure, and capillary diameter as well as the influence of the physical properties of the liquid, in particular viscosity, on the generation of monodisperse microbubbles in a circular cross section T-junction device. Aqueous glycerol solutions with viscosities ranging from 1- to 100 mPa s were used in the experiments. The bubble diameter generated was studied for systematically varied combinations of gas inlet pressure, liquid flow rate, and liquid viscosity with a fixed capillary inner diameter of 150 μm for the liquid and gas inlet channels as well as the outlet channel. In addition, the effect of channel geometry on bubble size was studied using capillaries with inner diameters of first 100 and then 200 μm. In all the experiments the distance between the coaxial capillaries at the junction was set to be 200 μm. All the microbubbles produced in this study were highly monodisperse (polydispersity index <1 %) and it was found, as expected, that bubble formation and size were influenced by the ratio of liquid to gas flow rate, capillary size, and liquid viscosity. The experimental data were then compared with empirical scaling laws derived for rectangular cross-section junctions. In contrast with these previous studies, which have found bubble size to be dependent on either the flow rate ratio (the squeezing regime) or capillary number (the dripping regime), in this experimental study bubble size was found to depend on both capillary number and flow ratio.     

Study of the geometry in a 3D flow-focusing device

We present a numerical and experimental study on a non-planar three-dimensional design of a microfluidic flow-focusing device for the well-controlled generation of monodisperse micron-sized droplets. Three relevant geometric parameters were identified: the distance between the inner inlet channel and the outlet channel, the width of the outlet channel, and its length. Simulation data extracted from a full parameter study and finite element simulations yielded four optimum designs that were then fabricated using soft lithography techniques. Under the predicted operating conditions, micro-droplets of a size of \({\sim}1\,\upmu \text {m}\) in diameter are obtained from a channel \(50\,\upmu \text {m}\) in width. This work represents an important breakthrough in the practical use of flow-focusing devices delivering a ratio of constriction to droplet size of 50 times, with the advantage of reduced clogging of the micro-channel, greatly improving the control and reliability of the device.     

Developing heatable microfluidic chip to generate gelatin emulsions and microcapsules

The heatable microfluidic chip developed herein successfully integrates a microheater and flow-focusing device to generate uniform-sized gelatin emulsions under various flow rate ratios (sample phase/oil phase, Q _s/Q _o) and driven voltages. The gelatin emulsions can be applied to encapsulate vitamin C for drug release. Our goal is to create the thermal conditions for thermo-sensitive hydrogel materials in the microfluidic chip and generate continuous and uniform emulsions under any external environment. The gelatin emulsion sizes have a coefficient of variation of <5 % and can be precisely controlled by altering the flow rate ratio (Q _s/Q _o) and driven voltage. The gelatin emulsion diameters range from 45 to 120 μm. Moreover, various sizes of these gelatin microcapsules containing vitamin C were used for drug release. The developed microfluidic chip has the advantages of a heatable platform in the fluid device, active control over the emulsion diameter, the generation of uniform-sized emulsions, and simplicity. This new approach for gelatin microcapsules will provide many potential applications in drug delivery and pharmaceuticals.     

Monodisperse droplets by impinging flow-focusing

We proposed a new flow-focusing technique for generation of monodisperse femtoliter droplets, based on the capillary micro-cross. A funnel-shaped interface of two phase system is observed in a capillary cross for mass production of uniform drops, where a tapered exit orifice is extruded into the dispersed feeding capillary. The droplets, down to 2 μm in size at frequency of 20 kHz, are controllable in size when choosing orifice and capillary sizes, as well as flow rates of inner and outer fluids. For a specific diameter of exit orifice, there is a maximal flow rate of outer fluid, beyond which the interface will be penetrated. Until then, the interface is in steady state and all droplets are highly uniform (<3%), implicating an absolute instability in the whole process.     

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.     

Suction-enhanced siphon valves for centrifugal microfluidic platforms

In traditional centrifugal microfluidic platforms pumping is restricted to outward fluid flow, resulting in potential real estate issues for embedding complex microsystems. To overcome the limitation, researchers utilize hydrophilic channels to force liquids short distances back toward the disk center. However, most polymers used for CD fabrication are natively hydrophobic, and creating hydrophilic conditions requires surface treatments/specialized materials that pose unique challenges to manufacturing and use. This work describes a novel technology that enjoys the advantages of hydrophilic fluidics on a hydrophobic disk device constructed from untreated polycarbonate plastic. The method, termed suction-enhanced siphoning, is based on exploiting the non-linear hydrostatic pressure profile and related pressure drop created along the length of a rotating microchannel. Theoretical analysis as well as experimental validation of the system is provided. In addition, we demonstrate the use of the hydrostatic pressure pump as a new method for priming hydrophobic-based siphon structures. The development of such techniques for hydrophobic fluidics advances the capabilities of the centrifugal microfluidic platform while remaining true to the goal of creating disposable polymer devices using feasible manufacturing schemes.     

On the thin-film-dominated passing pressure of cancer cell squeezing through a microfluidic CTC chip

Detection of circulating tumor cells (CTCs) shows strong promise for early cancer diagnosis, and cell-deformation-based microfluidic CTC chips have been playing an important role. For the design and optimization of high-throughput CTC chips, the dynamic pressure drop in the microfluidic chip during the CTC passing process is a key parameter related to the device sensitivity and filtering performance and has to be given very serious consideration. Although insights have been provided by previous researches, there is still a lack of understanding of the fundamental physics and complex interplay between viscous tumor cell and the flow inside the microfluidic filtering channel. In this paper, the process of the viscous cell squeezing through a microchannel is modeled by solving the governing equations of microscopic multiphase flows, with the tumor cell modeled by a droplet model and the immiscible cell–blood interface tracked by the volume-of-fluid method. Detailed dynamics regarding the filtering process is discussed, including the cell deformation, flow characteristics, passing pressure characteristics as well as the relationship between the pressure drop across the device and the thin film formed in the filtration channel. Current simulation shows a good agreement with analytic results, and an analytical formula is proposed to predict the passing pressure in the microchannel. Our study provides insights into the fluid physics of a viscous cell passing through a constricted microchannel, and the proposed formula can be readily applied to the design and optimization of cell-deformation-based microchannels for CTC detection.     

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.     

Generating gas/liquid/liquid three-phase microdispersed systems in double T-junctions microfluidic device

This article describes the generation of microdispersed bubbles and droplets in a double T-junctions microfluidic device to form immiscible gas/liquid/liquid three-phase flowing systems. Segmented gas plugs are controllably prepared in water at the first T-junction to form gas/liquid two-phase fluid with the perpendicular flow cutting method. Then using this two-phase fluid as the cross-shearing fluid for the oil phase at the second T-junction, the gas/liquid/liquid three-phase flowing systems are prepared. Interestingly, it is found that the break-up of the oil droplets is mainly dominated by the cutting effect of the gas/liquid interface or the pressure drop across the emerging droplet, but independent with the viscous shearing effect of the continuous phase, even at the capillary number (Ca = u _wμ_w/γ_ow) higher than 0.01. The size laws and the distributions of the bubbles and droplets are investigated carefully, and a mathematical model has been developed to relating the operating conditions with the dispersed sizes.