Droplet Formation Utilizing Controllable Moving-Wall Structures for Double-Emulsion Applications

The formation of microscale single- and double-emulsion droplets with various sizes is crucial for a variety of industrial applications. In this paper, we report a new microfluidic device which can actively fine-tune the size of single- and double-emulsion droplets in liquids by utilizing controllable moving-wall structures. Moreover, various sizes of external and internal droplets for double emulsions are also successfully formed by using this device. Three pneumatic side chambers are placed at a T-junction and flow-focusing channels to construct the controllable moving-wall structures. When compressed air is applied to the pneumatic side chambers, the controllable moving-wall structures are activated, thus physically changing the width of the microchannels. The size of the internal droplets at the intersection of the T-junction channel is then fine-tuned due to the increase in the shear force. Then, the internal droplets are focused into a narrow stream hydrodynamically and finally chopped into double-emulsion droplets using another pair of moving-wall structures downstream. For single emulsions, oil-in-water droplets can be actively fine-tuned from 50.07 to 21.80 under applied air pressures from 10 to 25 psi with a variation of less than 3.53%. For a water-in-oil single emulsion, droplets range from 50.32 to 14.76 with a variation of less than 4.62% under the same applied air pressures. For double emulsions, the sizes of the external and internal droplets can be fine-tuned with external/internal droplet diameter ratios ranging from 1.69 to 2.75. The development of this microfluidic device is promising for a variety of applications in the pharmaceutical, cosmetics, and food industries.     

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.     

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.     

Detection of microdroplet size and speed using capacitive sensors

Detection of the presence, size and speed of microdroplets in microfluidic devices is presented using commercially available capacitive sensors which make the droplet based microfluidic systems scalable and inexpensive. Cross-contamination between the droplets is eliminated by introducing a passivation layer between the sensing electrodes and droplets. A simple T-junction generator is used to generate droplets in microchannels. Coplanar electrodes are used to form a capacitance through the microfluidic channel. The change in capacitance due to the presence of a droplet in the sensing area is detected and used to determine the size and speed of the droplet. The design of a single pair of electrodes is used to detect the presence of a droplet and the interdigital finger design is used to detect the size and speed of the droplet. An analytical model is developed to predict the detection signal and guide the experimental optimization of the sensor geometry. The measured droplet information is displayed through a Labview interface in real-time. The use of capacitance sensors to monitor droplet sorting at a T-junction is also presented. The discussions in this paper can be generalized to any droplet detection application and can serve as a guideline in sensor selection.     

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.     

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.     

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.     

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.     

A microfluidic platform for formation of double-emulsion droplets

A new method for actively controlling the number of internal droplets of water-in-oil-in-water (W/O/W) double-emulsion droplets was demonstrated. A new microfluidic platform for double-emulsion applications has been developed, which integrates T-junction channels, moving-wall structures, and a flow-focusing structure. Inner water-in-oil (W/O) single-emulsion droplets were first formed at a major T-junction. Then the droplets were sub-divided into smaller uniform droplets by passing through a series of secondary T-junctions (branches). The moving-wall structures beside the secondary T-junctions were used to control the number of the sub-divided droplets by selectively blocking the branches. Finally, double-emulsion droplets were formed by using a flow-focusing structure downstream. Experimental data demonstrate that the inner and outer droplets have narrow size distributions with coefficient of variation (CV) of less than 3.5% and 5.7%, respectively. Double-emulsion droplets with 1, 2, 3, and up to 10 inner droplets have been successfully formed using this approach. The size of the inner droplets and outer droplets could be also fine-tuned with this device. The development of this new platform was promising for drug delivery applications involving double emulsions.     

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.     

Formation of Microdroplets in Liquids Utilizing Active Pneumatic Choppers on a Microfluidic Chip

Monodispersed emulsions are of great significance for a variety of applications. The current study reports a new microfluidic system capable of formation of microdroplets in liquids for emulsification applications. This new emulsion chip can precisely generate uniform droplets using a novel combination of hydrodynamic-focusing and liquid-chopping techniques. Experimental data show that microdroplets with diameters ranging from 6 to 100 mum with a variation less than 3% can be precisely generated. The size of the droplets is tunable using three approaches including adjusting the relative sheath/sample flow velocity ratios, the applied air pressure and the applied chopping frequency. Moreover, focusing and chopping of multiple flows has been demonstrated to increase the emulsion process throughput     

A suction-type, pneumatic microfluidic device for liquid transport and mixing

This study presents a new suction-type, pneumatically driven microfluidic device for liquid delivery and mixing. The three major components, including two symmetrical, normally closed micro-valves and a sample transport/mixing unit, are integrated in this device. Liquid samples can be transported by the suction-type sample transport/mixing unit, which comprised a circular air chamber and a fluidic reservoir. Experimental results show that volume flow rates ranging from 50 to 300 μl/min can be precisely controlled during the sample transportation processes. Moreover, the transport/mixing unit can also be used as a micro-mixer to generate efficient mixing between two reaction chambers by regulating the time-phased deformation of the polydimethylsiloxane (PDMS) membranes. A mixing efficiency as high as 98.4% can be achieved within 5 s utilizing this prototype pneumatic microfluidic device. Consequently, the development of this new suction-type, pneumatic microfluidic device can be a promising tool for further biological applications and for chemical analysis when integrated into a micro-total analysis system (μ-TAS) device.     

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.     

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.     

3D-printed membrane microvalves and microdecoder

A microfluidic system for multichannel switching and multiphase flow control has potential uses in pneumatic soft robotics and biological sampling systems. At present, the membrane microvalves used in microfluidic systems are mostly constructed using a multilayer bonding process so that the device cannot withstand high pressures. In this paper, we demonstrate a design method and the properties of a bondless membrane microvalve fabricated using a commercial 3D printer. We used a multijet (MJP) 3D printer to print a 100-μm-thick and 6-mm-diameter membrane from a relatively hard material (1700 MPa). The membrane’s high toughness ensures that it does not need negative pressure to reopen. The measured operation frequency was less than 2.5 Hz under a pneumatic pressure of 14.5 kPa. We also 3D-printed an integrated Quake-style microfluidic decoder network by combining 8 valves in series to demonstrate the integrability of the microvalve. The decoder chip was demonstrated to control the ON/OFF state of the four coded fluidic channels, with the droplets being generated from selected channels according to the valve action. Therefore, such 3D-printed microvalves are highly integrable, have a high manufacturing efficiency, and can be applied in pneumatic controllers, sample switchers and integrated print heads.

     

Guiding of emulsion droplets in microfluidic chips along shallow tracks defined by laser ablation

We demonstrate controlled guiding of nanoliter emulsion droplets of polar liquids suspended in oil along shallow hydrophilic tracks fabricated at the base of microchannels located within microfluidic chips. The tracks for droplet guiding are generated by exposing the glass surface of polydimethylsiloxane (PDMS)-coated microscope slides via femtosecond laser ablation. The difference in wettability of glass and PDMS surfaces together with the shallow step-like transverse topographical profile of the ablated tracks allows polar droplets wetting preferentially the glass surface to follow the track. In this study, we investigate guiding of droplets of two different polar liquids (water/ethylene glycol) with and without surfactant suspended in an oil medium along surface tracks of different depths of 1, 1.5, and 2 \(\upmu\)m. The results of experiments are also verified with computational fluid dynamics simulations. Guiding of droplets along the tracks as a function of the droplet composition and size and the surface profile depth is evaluated by analyzing the trajectories of moving droplets with respect to the track central axis, and conditions for stable guiding are identified. The experiments and numerical simulations indicate that while the track topography plays a role in droplet guiding using 1.5- and 2-\(\upmu\)m deep tracks, for the case of the smallest track depth of 1 \(\upmu\)m, droplet guiding is mainly caused by surface energy modification along the track rather than the presence of a topographical step on the surface. Our results can be exploited to sort passively different microdroplets mixed in the same microfluidic chip, based on their inherent wetting properties, and they can also pave the way for guiding of droplets along reconfigurable tracks defined by surface energy modifications obtained using other external control mechanisms such as electric field or light.     

One-step fabrication of titania hollow spheres by controlled interfacial reaction in a droplet-based microfluidic system

We present a facile ethanol-in-oil droplet-based microfluidic approach for one-step fabrication of titania hollow spheres through controlled interfacial reaction. The method combines microfluidic generation of uniform ethanol-in-oil droplets and subsequent in situ controlled interfacial reaction within the microfluidic channel. Ethanol-based droplets are suspended in an oil continuous phase containing titanium tertabutoxide. The small amount of water in the droplet phase diffuses to the interface leading to hydrolysis and condensation, and titania solidifies around the droplet forming titania microcapsules. The vigorous reaction between titanium tetrabutoxide and water is controlled by analyzing a mass transfer model, and then by selecting suitable continuous and dispersed phases. Highly viscous paraffin oil in combination with a low-viscosity ethanol-based droplet phase facilitates the successful formation of titania at the interface rather than in the continuous phase. This research provides a new approach for the controlled fabrication of titania microcapsules having uniform particle size and unique folded and crumpled structure.     

Engineering droplet navigation through tertiary-junction microchannels

We present an experimental and in silico investigation of path selection by a single droplet inside a tertiary-junction microchannel using oil-in-water as a model system. The droplet was generated at a T-junction inside a microfluidic chip, and its flow behavior as a function of droplet size, streamline position, viscosity, and Reynolds number (Re) of the continuous phase was studied downstream at a tertiary junction having perpendicular channels of uniform square cross section and internal fluidic resistance proportional to their lengths. Numerical studies were performed using the multicomponent lattice Boltzmann method. Both the experimental and numerical results showed good agreement and suggested that at higher Re equal to 3, the flow was dominated by inertial forces resulting in the droplets choosing a path based on their center position in the flow streamline. At lower Re of 0.3, the streamline-assisted path selection became viscous force-assisted above a critical droplet size. As the Re was further reduced to 0.03, or when the viscosity of the dispersed phase was increased, the critical droplet size for transition also decreased. This multivariate approach can in future be used to engineer sorting of cells, e.g., circulating tumor cells (CTCs) allowing early-stage detection of life-threatening diseases.     

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.     

Electric field driven addressing of ATPS droplets in microfluidic chips

The possibility of controlled droplet motion (droplet addressing) mediated by DC electric field in aqueous two-phase systems (ATPS) is here reported for the first time. Three ATPS of polyethylene glycol (PEG)/salt type, namely PEG/phosphate, PEG/sulphate, and PEG/carbonate, were selected for this study. We observed fast motion of salty droplets dispersed in PEG continuous phase induced by electric field of relative low strength. Hence, three fluidic systems with separated electrode chambers for the evaluation of electrophoretic mobilities and for addressing experiments were fabricated. Electrophoretic mobilities of salty droplets always exceeded the value of \(1\times 10^{-7}\, \hbox {m}^2\hbox {V}^{-1}\hbox {s}^{-1}\), which is about by one magnitude higher value than those typically measured in water–oil droplet systems. The electrophoretic mobilities in systems with free surface are the same or even smaller than in closed microfluidic structures, which is accounted mainly to the fact that a significant part of salty droplets is exposed to air and does not contribute to droplet forcing. Series of addressing and merging experiments in a microfluidic chip shows that DC electric field can be used as a powerful tool for smart manipulation of droplets in microfluidic systems with PEG/salt ATPS.