Production of uniform droplets using membrane, microchannel and microfluidic emulsification devices

This review provides an overview of major microengineering emulsification techniques for production of monodispersed droplets. The main emphasis has been put on membrane emulsification using Shirasu Porous Glass and microsieve membrane, microchannel emulsification using grooved-type and straight-through microchannel plates, microfluidic junctions and flow focusing microfluidic devices. Microfabrication methods for production of planar and 3D poly(dimethylsiloxane) devices, glass capillary microfluidic devices and single-crystal silicon microchannel array devices have been described including soft lithography, glass capillary pulling and microforging, hot embossing, anisotropic wet etching and deep reactive ion etching. In addition, fabrication methods for SPG and microseive membranes have been outlined, such as spinodal decomposition, reactive ion etching and ultraviolet LIGA (Lithography, Electroplating, and Moulding) process. The most widespread application of micromachined emulsification devices is in the synthesis of monodispersed particles and vesicles, such as polymeric particles, microgels, solid lipid particles, Janus particles, and functional vesicles (liposomes, polymersomes and colloidosomes). Glass capillary microfluidic devices are very suitable for production of core/shell drops of controllable shell thickness and multiple emulsions containing a controlled number of inner droplets and/or inner droplets of two or more distinct phases. Microchannel emulsification is a very promising technique for production of monodispersed droplets with droplet throughputs of up to 100?l?h^?1.     

Microchannel geometry design for rapid and uniform reagent distribution

Rapid and uniform reagent distribution is critical to the performance of a high-throughput microfluidic system, and its geometric design of the microchannels dominates the accuracy and distribution uniformity of the daughter droplets. This research’s purpose is to optimize the geometry of the T-junction to achieve a uniform distribution of two daughter droplets from a single liquid droplet. Models of gas–liquid flow were realized in the transient numerical simulations to investigate the geometry-dependent pressure distributions and the flowing velocities inside the droplet during the splitting process that leads to an improved design of the T-junction that can increase the stability of the droplet splitting process. To validate that increasing the stability of the splitting process can help improve the distribution uniformity of the daughter droplets, microfluidic devices were manufactured on poly(methyl methacrylate) substrates with micromilling and thermal bonding for experiments. In the multiple experiments, 2 μl of reagent was loaded into the microfluidic device and a uniform pneumatic pressure was applied to push the droplet into the T-junction for splitting. The experimental results, after statistical analysis, show that the improved T-junction can achieve better distribution uniformity of the daughter droplets with a higher reliability and a less reagent loss during the splitting process.     

Exploitation of a microfluidic device capable of generating size-tunable droplets for gene delivery

This study presents a new microfluidic chip that generates micro-scale emulsion droplets for gene delivery applications. Compared with conventional methods of droplet formation, the proposed chip can create uniform droplets (size variation <7.1%) and hence enhance the efficiency of the subsequent gene delivery. A new microfluidic chip was developed in this study, which used a new design with a pneumatic membrane chamber integrated into a T-junction microchannel. Traditionally, the size of droplets was controlled by the flow rate ratio of the continuous and disperse phase flows, which can be controlled by syringe pumps. In this study, a pneumatic chamber near the intersection of the T-junction channel was designed to locally change the flow velocity and the shear force. When the upper air chamber was filled with compressed air, the membrane was deflected and then the droplet size could be fine-tuned accordingly. Experimental data showed that using the new design, the higher the air pressure applied to the active tunable membrane, the smaller the droplet size. Finally, droplets were used as carriers for DNA to be transfected into the Cos-7 cells. It was also experimentally found that the size of the emulsion droplets plays an important role on the efficiency of the gene delivery. The preliminary results of this paper have been presented at the 2007 IEEE International Conference of Nano/Molecular Medicine and Engineering (IEEE NANOMED 2007), Macau, China, 6–9 August, 2007.     

Droplet arrangement and coalescence in diverging/converging microchannels

We experimentally examine the dynamics of droplet assembly and recombination processes in a two-dimensional pore-model system. Monodisperse trains of droplets are formed by focusing streams of immiscible fluids into a square microchannel that is connected to a diverging/converging slit microfluidic chamber. We focus on the limit of dilute emulsions and investigate the formation and stability of crystal-like structures when droplets are hydrodynamically coupled in the chamber. The minimal distance between droplets and the spread of droplet lattices are measured as a function of initial control parameters and the relationship between droplet velocity and trajectory is discussed. We demonstrate that the onset of coalescence depends on both the capillary number based on the viscosity of the external phase and the droplet concentration. The draining time of the thin film between droplets in apparent contact is found to depend on fluid characteristics. Such property allows us to examine the crossover between non-coalescing and coalescing droplet microflows by varying the residence time of the dispersion in the microfluidic chamber. This work characterizes droplet interaction and coalescence phenomena during multiphase transport in a simple extensional microgeometry.     

Fission and fusion of droplets in a 3-D crossing microstructure

We demonstrate a 3-D crossing microstructure that has simple and versatile features for the fission and fusion of droplets. For their fission, the size of daughter droplets is readily controllable solely on modulating the ratio of flow rates at the inlets. We observed two distinct scenarios of droplet fission and propose dripping-like and squeezing-like mechanisms to explain such anomalous phenomena. Depending on the width of the outlet channel, the microstructure exhibits chronologically differentiated dynamics of droplet fusion and fission, leading to diverse droplet mixing. With this microstructure, droplets of diverse size and concentration can be accordingly produced from two individual droplets of distinct constituents. As the 3-D structure allows for both droplet dispersion and mixing, it is beneficially applicable for biochemical and biomedical applications such as drug dosing and drug delivery. Diverse droplet manipulations are realized with this 3-D crossing microstructure, shedding new light on droplet-based microfluidic systems.     

Droplet generation in a microchannel with a controllable deformable wall

We report the droplet generation behavior of a microfluidic droplet generator with a controllable deformable membrane wall using experiments and analytical model. The confinement at the droplet generation junction is controlled by using external pressure, which acts on the membrane, to generate droplets smaller than junction size (with other parameters fixed) and stable and monodispersed droplets even at higher capillary numbers. A non-dimensional parameter, i.e., controlling parameter K _p, is used to represent the membrane deformation characteristics due to the external pressure. We investigate the effect of the controlled membrane deformation (in terms of K _p), viscosity ratio λ and flow rate ratio r on the droplet size and mobility. A correlation is developed to predict droplet size in the controllable deformable microchannel in terms of the controlling parameter K _p, viscosity ratio λ and flow rate ratio r. Due to the deflection of the membrane wall, we demonstrate that the transition from the stable dripping regime to the unstable jetting regime is delayed to a higher capillary number Ca (as compared to rigid droplet generators), thus pushing the high throughput limit. The droplet generator also enables generation of droplets of sizes smaller than the junction size by adjusting the controlling parameter.     

Y- and T-junction microfluidic devices: effect of fluids and interface properties and operating conditions

Water-in-oil emulsions were produced in microchannels with Y- and T-junction geometries by individual droplet generation. For each microchannel configuration, the effect of the fluids and interface properties as well as of the process conditions was evaluated. The size of the droplets depended mainly on the relative velocity between continuous and dispersed phases and the relative fluid viscosity between phases. Those variables were related to the shear stress between the phases, which caused the droplet detachment. In addition, the interfacial forces played a minor role in Y-junction, and they had no effect in the droplets formation in T-junction microchannels. In Y-junction, a large variation in the droplet size was observed, depending on the system composition and the operating conditions. At low relative velocity and fluid viscosity, no droplets were generated. In contrast, the process in T-junction resulted in a lower variation of droplets size and the droplets were formed even at less favorable conditions. Such results indicate that the knowledge of the mechanism of droplets generation in each microchannel geometry makes it possible to choose the appropriate configuration according to the type of fluid, and the operating conditions can be adjusted to obtain the desired final emulsion.     

Fiber Bragg grating sensor for two-phase flow in microchannels

A new non-intrusive measurement technique for two-phase flow in microchannels is presented. The development of an evanescent field-based optical fiber Bragg grating (FBG) sensor is described, and experiments coupled with flow visualization demonstrating the performance of this sensor are presented. Two adjacent 1-mm FBGs in etched D-shaped fiber are embedded into the surface of a PDMS microchannel. Experiments are conducted in both droplet and slug flow regimes and high-speed digital video is captured synchronously with the sensor data. The FBGs exhibit an on?Coff type response to the passage droplets which is shown to correlate precisely with the passage of the liquid phase. This correlation enables the measurement of droplet average velocity and size using only the sensor data. In addition to the use of both FBG signals for the purpose of measuring droplet speed and size, it is shown that for droplets larger than the FBG length, a single FBG can be used to estimate the convection velocity and size of fast moving droplets. This sensing method is potentially useful for monitoring two-phase flow in fuel cells and microfluidic applications such as micro-heat exchangers and lab-on-a-chip systems.     

Generation of droplets in the T-junction with a constriction microchannel

Droplet microfluidics plays an essential role in science and technology with various applications such as chemical engineering, environment, energy and other fields. T-junction with a constriction microchannel is designed for the controlled production of monodisperse microdroplets, which could produce droplets with the same size under a lower flow resistance. The influence of the microchannel structure, operating conditions, and physical properties on the dispersion rules is systematically investigated by combinations of micro-particle image velocimetry (Micro-PIV), high-speed camera and numerical simulation. Compared to the traditional T-junction channel, the T-junction with a constriction microchannel can generate smaller droplets whose size conforms to the size prediction formula of the traditional T-junction channel. It is found that the velocity vector of the T-junction with a constriction microchannel is faster than that in the T-junction channel at each stage of droplet generation. The droplet size is mainly based on the Ca number, the flow rate ratio and viscosity ratio of the continuous phases in our channel, and the range of the index of Ca with the droplet size is found. The constriction width has a significant influence on the dispersion rule, as there is a decreasing tendency for the droplet size with reducing constriction width.     

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.     

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.     

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.     

Droplet group production in an AC electro-flow-focusing microdevice

We report the production of droplet groups with a controlled number of drops in a microfluidic electro-flow-focusing device under the action of an AC electric field. This regime appears for moderate voltages (500–700 V peak-to-peak) and signal frequencies between 25 and 100 Hz, much smaller than the droplet production rate (\({\sim }\,{500}\) Hz). For this experimental condition the production frequency of a droplet package is twice the signal frequency. Since the continuous phase flow in the microchannel is a Hagen–Poiseuille flow, the smaller droplets of a group move faster than the bigger ones leading to droplet clustering downstream.     

Using a cross-flow microfluidic chip for monodisperse UV-photopolymerized microparticles

In this paper, we report a microfluidic chip containing a cross-junction channel for the manipulation of UV-photopolymerized microparticles. Hydrodynamic-focusing is used to form a series of using 365 nm UV light to solidify the hydrogel droplets. We were able to control the size of the hydrogel droplets from 75 to 300 μm in diameter by altering the sample and by changing the flow rate ratio of the mineral oil in the center inlet channel to that of the side inlet channels. We found that the size of the emulsions increases with an increase in average velocity of the dispersed phase flow (polymer solution flow). The size of the emulsions decreases with an average velocity increase of the continuous phase flow (mineral oil flow). Experimental data show that the emulsions are very uniform. The developed microfluidic chip has the advantages of ease of fabrication, low cost, and high throughput. The emulsions generated are very uniform and have good regularity.     

Precise droplet volume measurement and electrode-based volume metering in digital microfluidics

In this work, for the first time, we demonstrate nanoscale droplet generation from a continuous electrowetting microchannel using a simple and precise image-based droplet volume metering technique. One of the most popular ways of droplet generation in electrowetting devices is to split a droplet from a preloaded volume as a fluid reservoir. This method is effective, but lowers volume consistency after multiple droplets are generated. Impedance- and capacitance-based methods of volume metering have been successfully used in digital microfluidics, but require complex circuitry and feedback signal processing. In this work, we demonstrate nanoliter droplet generation from a continuous electrowetting channel used as a replenishable fluid reservoir which compensates for the loss of reservoir volume as droplets are sequentially split. This improves volume consistency especially for applications requiring multi-droplet generation. Based on the area of the electrode, the volume of each droplet split from the electrowetting channel can be obtained by a simple and precise image processing technique with no need for additional hardware and measurement errors of ±0.05 %. This simple technique can be used in a wide range of applications that require precise volume metering, such as immunoassay.     

A facile on-demand droplet microfluidic system for lab-on-a-chip applications

We present a facile microfluidic droplet-on-demand (DOD) system in which a pulsed pressure generated by a high-speed solenoid valve is used to control the formation and movement of water-in-oil emulsion droplets in a T-junction microchannel. We investigated the working principle of the DOD system and established a scaling model for the droplet volume in terms of the amplitude and duration of the pulse and the hydraulic resistance of the injection channel. The droplet formation was characterized in three designs at various pressure pulses. The experimental results support our scaling model very well. In the DOD system we developed, nanoliter-volume droplets with a throughput of a few droplets per second were on-demand generated. Moreover, we examined the applicable scope of the DOD system. As examples of practical applications of the DOD system, we demonstrated a digital display module to show droplets formed at a prescribed time and a droplet array with a concentration gradient to show droplets formed with a precise volume. We expect our work can provide design guidelines for a robust DOD system and improve the capabilities of droplet-based microfluidics in ‘lab-on-a-chip’ systems.     

A simple method for the formation of water-in-oil-in-water (W/O/W) double emulsions

A simple, low-cost and reliable method for the formation of double emulsions is proposed and demonstrated experimentally. The formation process consists of two steps: (1) the formation of water-in-oil droplets at a co-flowing structure formed by a syringe needle and a flexible microtubing, and (2) the formation of water-in-oil-in-water compound droplets at the tip of the microtubing by buoyancy. Since the droplets flow directly from the first step to the second step in the tubing without any disturbance, problems such as droplet coalescence, breakup, leakage and contamination can be avoided automatically. The breakup processes of the core droplets and the compound droplets are analyzed. The sizes of the core and the shell droplets and the volume fraction in the compound droplets are controlled by adjusting the corresponding flow rates. Scaling relationships for the number of cores and the size of the compound droplets are proposed. Due to the simplicity of this method and the flexibility in controlling the properties of the double emulsions, this method shows great potential in the relevant applications .     

Microfluidic sorting of droplets by size

Droplet sorting by size was achieved in microfluidic channels through controlling the bifurcating junction geometry and the flow rates of the daughter channels. The sorting designs separated droplets with a radius difference of as little as 4 μm. The developed droplet channel design can be potentially used in combination with other particle sorting system to improve the sorting efficiency without the control of electrodes or fluidic valves.     

Design of a flow-controlled asymmetric droplet splitter using computational fluid dynamics

In this work the design of a segmented flow microfluidic device is presented that allows droplet splitting ratios from 1:1 up to 20:1. This ratio can be dynamically changed on chip by altering an additional oil flow. The design was fabricated in PDMS chips using the standard SU-8 mold technique and does not require any valves, membranes, optics or electronics. To avoid a trial and error approach, fabricating and testing several designs, a computational fluid dynamics model was developed and validated for droplet formation and splitting. The model was used to choose between several variations of the splitting T-junction with the extra oil inlet, as well to predict the additional flow rate needed to split the droplets in various ratios. Experimental and simulated results were in line, suggesting the model’s suitability to optimize future designs and concepts. The resulting asymmetric droplet splitter design opens possibilities for controlled sampling and improved magnetic separation in bio-assay applications.     

Optical measurement of flow field and concentration field inside a moving nanoliter droplet

Droplets-based method has been employed to enhance mixing in microfluidic systems. This paper presents experimental studies of the recirculating flow field inside a moving droplet and the characterization of the mixing of two aqueous droplets. In the first part, the velocity field inside the moving water droplet was measured using the micro-particle image velocimetry (micro-PIV) technique. The PIV measurements showed that recirculation flow exists inside the droplet. However, the findings suggested that the outer layer of droplets move at a faster velocity than the central part. The result is different from what is reported by other researchers. In the second part, two water droplets, a de-ionized (DI) water droplet and another DI water droplet with fluorescent dye, were brought together by the carrier fluid to form a bigger droplet. The mixing between the two aqueous droplets was characterized by the fluorescent dye concentration distribution.