Effect of viscosities of dispersed and continuous phases in microchannel oil-in-water emulsification

Although many aspects of microchannel emulsification have been covered in literature, one major uncharted area is the effect of viscosity of both phases on droplet size in the stable droplet generation regime. It is expected that for droplet formation to take place, the inflow of the continuous phase should be sufficiently fast compared to the outflow of the liquid that is forming the droplet. The ratio of the viscosities was therefore varied by using a range of continuous and dispersed phases, both experimentally and computationally. At high viscosity ratio (η _d/η _c), the droplet size is constant; the inflow of the continuous phase is fast compared to the outflow of the dispersed phase. At lower ratios, the droplet diameter increases, until a viscosity ratio is reached at which droplet formation is no longer possible (the minimal ratio). This was confirmed and elucidated through CFD simulations. The limiting value is shown to be a function of the microchannel design, and this should be adapted to the viscosity of the two fluids that need to be emulsified.     

Microchannel emulsification for mass production of uniform fine droplets: integration of microchannel arrays on a chip

We present a novel microchannel emulsification (MCE) system for mass-producing uniform fine droplets. A 60 × 60-mm MCE chip made of single-crystal silicon has 14 microchannel (MC) arrays and 1.2 × 10⁴ MCs, and each MC array consists of many parallel MCs and a terrace. A holder with two inlet through-holes and one outlet through-hole was also developed for simply infusing each liquid and collecting emulsion products. The MCE chip was sealed well by physically attaching it to a flat glass plate in the holder during emulsification. Uniform fine droplets of soybean oil with an average diameter of 10 μm were reliably generated from all the MC arrays. The size of the resultant fine droplets was almost independent of the dispersed-phase flow rate below a critical value. The continuous-phase flow rate was unimportant for both the droplet generation and the droplet size. The MCE chip enabled mass-producing uniform fine droplets at 1.5 ml h⁻¹ and 1.9 × 10⁹ h⁻¹, which could be further increased using a dispersed phase of low viscosity.     

Straight-through microchannel devices for generating monodisperse emulsion droplets several microns in size

The authors recently proposed a promising technique for producing monodisperse emulsions using a straight-through microchannel (MC) device composed of an array of microfabricated oblong holes. This research developed new straight-through MC devices with tens of thousands of oblong channels of several microns in size on a silicon-on-insulator plate, and investigated the emulsification characteristics using the microfabricated straight-through MC devices. Monodisperse oil-in-water (O/W) and W/O emulsions with average droplet diameters of 4.4–9.8 μm and coefficients of variation of less than 6% were stably produced using surface-treated straight-through MC devices that included uniformly sized oblong channels with equivalent diameters of 1.7–5.4 μm. The droplet size of the resultant emulsions depended greatly on the size of the preceding oblong channels. The emulsification process using the straight-through MC devices developed in this research had very high apparent energy efficiencies of 47–60%, defined as (actual energy input applied to droplet generation/theoretical minimum energy input necessary for making droplets) × 100. Straight-through MC devices with numerous oblong microfluidic channels also have great potential for increasing the productivity of monodisperse fine emulsions.     

Scalable attoliter monodisperse droplet formation using multiphase nano-microfluidics

We demonstrate a robust method to produce monodisperse femtoliter to attoliter droplets by using a nano-microfluidic device. Two immiscible liquids are forced through a nanochannel where a steady nanoscopic liquid filament forms, thinning close to the nanochannel exit to a microchannel due to the capillary focusing. When the nanoscopic filament enters the microchannel, monodisperse droplets are formed by capillary instability. In a certain range of physical parameters and geometrical configurations, the droplet size is only determined by the nanochannel height and independent of liquid flow rates and ratios, surfactants, and continuous phase viscosity. By using nanochannels with a height of 100–900 nm, 0.4–3.5 μm diameter droplets (volume down to 30 aL) have been produced. The generated droplets are stable for at least weeks.     

Controlled preparation of giant vesicles from uniform water droplets obtained by microchannel emulsification with bilayer-forming lipids as emulsifiers

We investigated a preparation method of giant vesicles using monodisperse water-in-oil (W/O) emulsions stabilized by bilayer-forming emulsifiers. A mixture of phosphatidylcholine, cholesterol and stearylamine was used both to stabilize the water droplets formed in the emulsion and to form the vesicles. Using this lipid mixture, we obtained monodisperse W/O emulsions with mean droplet diameters of 10–40 μm and coefficients of variation as small as ca 5% by means of the microchannel (MC) emulsification technique. Utilization of an asymmetric straight-through MC array device enabled a monodisperse droplet productivity of up to 80 ml/h. The obtained water droplets were converted to giant vesicles via evaporative removal of the continuous-phase solvent followed by addition of an aqueous buffer solution. The resulting vesicles were similar in size to their starting water droplets, and a hydrophilic fluorescent marker was entrapped inside the vesicles.     

Microchannel miter bend effects on pressure equalization and vortex formation

Simulations have been carried out for water flow in a square microchannel with a miter bend. The simulation considered a pressure-driven flow in a channel-hydraulic diameter of 5 μm for series of Reynolds number (Re) range from 0.056 to 560, in order to investigate water flow at bends. The result shows formation of two vortices after the miter bend, which are more discernible above Re 5.6. The critical inlet velocity for the generation of vortex in this particular geometry occurs at 1 m/s. A simple energy mechanism is postulated to explain the vortex formation as well as core skew direction. The high pressure region at the outer wall before and after the bend is a major factor for vortex formation since the liquid needs to reduce the additional energy effected by the high pressure region. Navier–Stokes equation is utilized with a no slip boundary condition for a total microchannel centerline length of 795 μm which is sufficient to produce a laminar flow pattern at the outlet.     

Liquid–liquid micro-dispersion in a double-pore T-shaped microfluidic device

For further understanding the dispersion process in the T-shaped microfluidic device, a double-pore T-shaped microchannel was designed and tested with octane/water system to form monodispersed plugs and droplets in this work. The liquid–liquid two-phase flow patterns were investigated and it was found that only short plugs, relative length L/w < 1.4, were produced. Additionally, the droplets flow was realized at phase ratios (F _C /F _D) just higher than 0.5, which is much smaller than that in the single-pore T-shaped microchannels. A repulsed effect between the initial droplets was observed in the droplet formation process and the periodic fluctuation flow of the dispersed phase was discussed by analyzing the resistances. Besides, the effect of the two-phase flow rates on the plug length and the droplet diameter was investigated. Considering the mutual effect of the initial droplets and the equilibrium between the shearing force with the interfacial tension, phase ratio and Ca number were introduced into the semi-empirical models to present the plug and droplet sizes at different operating conditions.     

Effect of dispersed phase viscosity on maximum droplet generation frequency in microchannel emulsification using asymmetric straight-through channels

Uniformly sized droplets of soybean oil, MCT (medium-chain fatty acid triglyceride) oil and n-tetradecane with a Sauter mean diameter of d _3,2 = 26–35 μm and a distribution span of 0.21–0.25 have been produced at high throughputs using a 24 × 24 mm silicon microchannel plate consisting of 23,348 asymmetric channels fabricated by photolithography and deep reactive ion etching. Each channel consisted of a 10-μm diameter straight-through micro-hole with a length of 70 μm and a 50 × 10 μm micro-slot with a depth of 30 μm at the outlet of each channel. The maximum dispersed phase flux for monodisperse emulsion generation increased with decreasing dispersed phase viscosity and ranged from over 120 L m⁻² h⁻¹ for soybean oil to 2,700 L m⁻² h⁻¹ for n-tetradecane. The droplet generation frequency showed significant channel to channel variations and increased with decreasing viscosity of the dispersed phase. For n-tetradecane, the maximum mean droplet generation frequency was 250 Hz per single active channel, corresponding to the overall throughput in the device of 3.2 million droplets per second. The proportion of active channels at high throughputs approached 100% for soybean oil and MCT oil, and 50% for n-tetradecane. The agreement between the experimental and CFD (Computational Fluid Dynamics) results was excellent for soybean oil and the poorest for n-tetradecane.     

Correlations of droplet formation in T-junction microfluidic devices: from squeezing to dripping

In this work, we have systematically analyzed the scaling law of droplet formation by cross-flow shear method in T-junction microfluidic devices. The droplet formation mechanisms can be distinguished by the capillary number for the continuous phase (Ca_c), which are the squeezing regime (Ca_c < 0.002), dripping regime (0.01 < Ca_c < 0.3), and the transient regime (0.002 < Ca_c< 0.01). Three corresponding correlations have been suggested in the different range of Ca_c. In the dripping regime, we developed a modified capillary number for the continuous phase (Ca_c′) by considering the influence of growing droplet size on the continuous phase flow rate. And the modified model could predict droplet diameter more accurately. In the squeezing regime, the final plug length was contributed by the growth and ‘squeeze’ stages based on the observation of dynamic break-up process. In the transient regime, we firstly suggested a mathematical model by considering the influences of the above two mechanisms. The correlations should be very useful for the application of controlling droplet size in T-junction microfluidic devices.     

Microfluidic phase change valve with a two-level cooling/heating system

A phase change (PC) microvalve with an integrated two-level cooling/heating system is developed for microfluidic applications in this article. This PC microvalve utilizes the liquid–solid PC of a small portion of the working medium in a microchannel to switch on/off the flow in the microchannel. The size of the working medium for the PC microvalve is 5-mm long, 50-μm high, and 80-μm wide (50 μm × 80 μm is the cross-sectional area of the channel) in this study. The switch is actuated by using a two-level cooling/heating system integrated on the chip. The first-level cooling/heating unit keeps the working medium in the valve area in the temperature range of supercooling state. Based on the supercooling state, the second-level cooling/heating unit either heats up or cools down the medium in the valve area to trigger its PC between liquid and solid for valving purposes. The proposed microfluidic PC microvalve is characterized experimentally in microfluidic chips. The thermal impact of one PC microvalve in one particular microchannel on its adjacent channels is discussed by establishing a preliminary analytical model and a numerical model. In addition to no leakage and no moving element, this PC microvalve with a two-level cooling/heating system can achieve a very short cooling time (i.e., 2.72 s).     

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.     

Development of microfluidic alginate microbead generator tunable by pulsed airflow injection for the microencapsulation of cells

Recently, microbead generation and microencapsulation of cells using microfluidic technology have been actively pursued for various applications. However, most of the proposed systems are not only technically demanding, but might also be harmful to the encapsulated cells. To tackle these issues, this study reports a microfluidic alginate microbead generator consisting of a polydimethylsiloxane (PDMS) microfluidic chip and an integrated quartz microcapillary tube. The working principle is based on the use of a pulsed airflow to segment a continuous alginate suspension flow to form suspension fragments in a microchannel and then alginate microbeads when they were delivered out the microfluidic system to a sterile calcium chloride solution through a microcapillary tube. In this study, the alginate suspension fragments with varied sizes in the microchannel can be generated either by modulating the alginate suspension flow rate or the pulsation frequency of airflow injection. By fine tuning the size of them, the alginate microbeads can be generated in a size-controllable manner. Results showed that alginate microbeads with the size ranging from 150 to 370 μm in diameter can be generated at the suspension flow rate and airflow injection frequency ranges of 2–4 μl/min and 0.6–35 Hz, respectively. Besides, the alginate microbeads generated by the system were tested with excellent size uniformity (CV: 3.1–5.1%). Moreover, its application for the microencapsulation of chondrocytes in alginate microbeads was also demonstrated with high cell viability (96 ± 2%). As a whole, the proposed device has paved an alternative route to perform alginate microbead generation or microencapsulation of cells in a simple, continuous, controllable, uniform, cell friendly, and less contaminated manner.     

Temperature effect on microchannel oil-in-water emulsification

Microchannel (MC) emulsification is a promising technique to produce monodisperse emulsions by spontaneous interfacial-tension-driven droplet generation. The purpose of this study was to systematically characterize the effect of temperature on droplet generation by MC emulsification, which is a major uncharted area. The temperature of an MC emulsification module was controlled between 10 and 70°C. Refined soybean oil was used as the dispersed phase and a Milli-Q water solution containing sodium dodecyl sulfate (1 wt%) as the continuous phase. Monodisperse oil-in-water (O/W) emulsions with a coefficient of variation below 4% were produced, and at all the operating temperatures, their average droplet diameter ranged from 32 to 38 μm. We also investigated the effect of flow velocity of the dispersed phase on droplet generation characteristics. The maximum droplet generation rate (frequency) from a channel at 70°C exceeded that at 10°C by 8.1 times, due to the remarkable decrease in viscosity of the two phases. Analysis using dimensionless numbers indicated that the flow of the dispersed phase during droplet generation could be explained using an adapted capillary number that includes the effect of the contact angle of the dispersed phase to the chip surface.     

Production of monodisperse water-in-oil emulsions consisting of highly uniform droplets using asymmetric straight-through microchannel arrays

This paper reports the production of monodisperse water-in-oil (W/O) emulsions using new microchannel emulsification (MCE) devices, asymmetric straight-through MC arrays that were hydrophobically modified. The silicon asymmetric straight-through MC arrays consisted of numerous pairs of microslots and circular microholes whose cross-sectional sizes were 10 μm. This paper primarily focused on investigating the effect of the osmotic pressure of a dispersed phase (Π_d) on MCE. This paper also investigated the effects of the type of continuous-phase oils and the dispersed-phase flux (J _d) on MCE. The dispersed phases were Milli-Q water and Milli-Q water solutions containing sodium chloride. The continuous phases were decane (as control), hexane, medium chain triacylglyceride (MCT), and refined soybean oil (RSO) solutions containing tetraglycerin monolaurate condensed ricinoleic acid ester (TGCR) as a surfactant. At Π_d of exceeding threshold, highly uniform aqueous droplets with coefficients of variation of less than 3% were stably generated via hydrophobic asymmetric straight-through MCs. Monodisperse W/O emulsions with average droplet diameters between 32 and 45 μm were produced using the alkane–oil and triglyceride–oil solutions as the continuous phase. This work also demonstrated that the hydrophobic asymmetric straight-through MC array had remarkable ability to produce highly uniform aqueous droplets at very high J _d of up to 1,200 L m⁻² h⁻¹.     

Numerical simulation of emergence of a water droplet from a pore into a microchannel gas stream

A numerical investigation on the dynamic behavior of liquid water entering a microchannel through a lateral opening (pore) in the wall is reported in this paper. The channel dimensions, flow conditions and transport properties are chosen to simulate those in the gas channel of a typical proton exchange membrane fuel cell (PEMFC). Two-dimensional transient simulations employing the volume of fluid method are used to explicitly track the liquid–gas interface, and to gain understanding into the dynamics of a water droplet subjected to airflow in the bulk of the microchannel. A series of parametric studies, including the effects of static contact angle, dimensions of the pore, air-inlet velocity, and water-inlet velocity are performed with a particular focus on the effect of hydrophobicity. The simulations show that the wettability of the microchannel surface has a major impact on the dynamics of the water droplet. Flow patterns are presented and analyzed showing the splitting of a droplet for a hydrophobic surface, and the tendency for spreading and film flow formation for a hydrophilic surface. The time evolution of the advancing and receding contact angles of the droplet are found to be sensitive to the wettability when the gas diffusion layer surface is hydrophilic, but independent of wettability when the surface is hydrophobic. The critical air velocity at which a droplet detaches is found to decrease with increasing hydrophobicity and with increasing initial dimension of the droplet. The critical air velocity found in the present study by taking into account the water transport and evolution of the droplet from a pore are found to differ significantly from previous works which consider a stagnant droplet sitting on the surface.     

Micro cell encapsulation and its hydrogel-beads production using microfluidic device

In this paper, we propose a cell encapsulation and hydrogel-beads production method using droplet formation in a microchannel. The hydrogel-beads produced by the microfluidic device developed here have smaller diameter and narrower distribution in their diameter compared to the conventional method, such as the droplet extrusion and the emulsification. The effects of the flow velocity and microchannel wall were analyzed based on fluid dynamical analysis. The results revealed that the wall effect of the microchannel strongly affected to the diameter of the droplet and the shape of the hydrogel-beads.     

Generation of droplets with different concentrations using gradient-microfluidic droplet generator

This study successfully uses the micro-mixers and flow-focusing devices, which are integrated into a gradient-microfluidic droplet generator, to generate the different sizes of the droplets with different concentrations simultaneously and applies these microcapsules for drug release. The sizes of these four types of droplet with different concentrations are uniformity with a coefficient of variation less than 5% and can be precisely controlled by adjusting the water phase flow rate and oil phase flow rate. Moreover, Ca-alginate microcapsules with different concentrations of the bovine serum albumin are used for uniform size drug release, and the Ca-alginate microcapsule size is from 60 to 105 μm in diameter. This developed microfluidic chip has the advantages of actively controlling the droplet diameter, simultaneously generating uniform-sized droplets with different concentrations, and having a simple process and a high throughput. This preparation approach for Ca-alginate microcapsules of four different concentrations will provide many potential applications for drug delivery and pharmaceutical area.     

Chitosan microfiber fabrication using a microfluidic chip and its application to cell cultures

In this study, a poly-methyl-methacrylate (PMMA) microfluidic chip with a 45° cross-junction microchannel is fabricated using a CO₂ laser machine to generate chitosan microfibers. Chitosan solution and sodium tripolyphosphate (STPP) solution were injected into the cross-junction microchannel of the microfluidic chip. The laminar flow of the chitosan solution was generated by hydrodynamic focusing. The diameter of laminar flow, which ranged from 30 to 50 μm, was controlled by changing the ratio between chitosan solution and STPP solution flow rates in the PMMA microfluidic chip. The laminar flow of the chitosan solution was converted into chitosan microfibers with STPP solution via the cross-linking reaction; the diameter of chitosan microfibers was in the range of 50–200 μm. The chitosan microfibers were then coated with collagen for cell cultivation. The results show that the chitosan microfibers provide good growth conditions for cells. They could be used as a scaffold for cell cultures in tissue engineering applications. This novel method has advantages of ease of fabrication, simple and low-cost process.     

Pressure field evaluation in microchannel junction flows through μPIV measurement

An experimental method for evaluating pressure fields in a microchannel flow was studied using μPIV measurement in conjunction with the pressure Poisson equation. The pressure error due to the influence of numbers of measurement planes, computational grids for solving pressure Poisson equation, and an experimental error in μPIV measurement was evaluated with respect to the exact solution of Navier–Stokes equation for straight microchannel flow. The mean velocity field in microchannel junction flows with bifurcation and confluence was measured by a μPIV system, which consists of a CCD camera and a microscope with an in-line illumination of white light from stroboscopes. The planar velocity fields at various cross-sections of the microchannel flow were measured by traversing the focal plane within a depth of focus of the microscope. The pressure contour in the microchannel flow was evaluated by solving the pressure Poisson equation with the experimental velocity data. The results indicate that the pressure field in the microchannel junction flow agrees closely with the numerical simulation of laminar channel flow, which suggests the validity of the present method.     

A two-port model for wave propagation along a long circular microchannel

A compact model for oscillatory flow in a long microchannel with a circular cross-section is derived from the linearised Navier–Stokes equations. The resulting two-port model includes the effects of viscosity due to rarefied gas in the slip flow regime, inertia, compressibility and losses due to heat exchange. Both an acoustic impedance T network and an acoustic admittance Π network are presented for implementation in system level and circuit simulation tools. Also, reduced T and Π networks with constant component values are given to be used in the low frequency region. They are useful in time domain simulations, too. To verify the analytical model, simulations with a harmonic finite element solver for acoustic viscous flow are performed for microchannels exploiting the axisymmetry. The simulation results with both open and closed outlet conditions are compared with the two-port model with excellent agreement. Contribution of the slip conditions and the accuracy of the simple model are demonstrated.