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.     

Oscillations in light-triggered logic microfluidic circuit

Control of droplets in microfluidic environments has numerous applications ranging from analysis and sample preparation for biomaterials synthesis (Mann and Ozin Nature 382:313–318, 1996) and medical diagnostics (Pipper et al. Nat Med 13:1259–1263, 2007) to photonics (Schmidt and Hawkins Nat Photonics 5:598–604, 2011). Here we study the oscillations present in a microfluidic circuit capable of sorting curable droplets on demand by triggering the circuit with UV-light. Prior to this paper we showed that a simple circuit can self-sort particles and produce a binary output, sorted or rejected stream of particles, based on the hydrodynamic resistance induced by the particles as they flow through the microfluidic channels. We showed that the cross-linking of droplets can modulate the resistance, and demonstrated particle switching by sorting of otherwise identical droplets of uncured and cured photocurable solution immersed in mineral oil solution. Before arriving at the sorting circuit, droplets made of a photocurable solution were illuminated by a UV-light from a mercury lamp, curing them. By tuning the outlet pressures, the switching threshold could be tuned so that uncured droplets were rejected while cured droplets were switched (Raafat et al. μTAS Proc 1826–1828, 2010; Cartas-Ayala et al. Small 9:375–381, 2013). Here we use this system to study the oscillations in this circuit due to particle–particle interactions in the circuit. The circuit oscillation can be used as a counter with a light ON/OFF switch. The circuit behavior agrees well with theoretical predictions of droplet oscillations. Furthermore, the circuit oscillations can be switched on or off by UV-light illumination. This experiment demonstrates switching of particles based on deformability, illustrates the switching of particles by using light, and the possibility of creating new managing schemes for droplets by combining light control with droplet generation-rate control.     

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.     

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.     

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.     

Bistability in the hydrodynamic resistance of a drop trapped at a microcavity junction

We investigate the flow resistance of a droplet trapped at a constriction in a microcavity located at a microchannel bifurcation as a function of system parameters including capillary number, drop confinement, and viscosity ratio. Using a combination of experiments and volume-of-fluid numerical simulations, we measure the hydrodynamic resistance of the trapped drop and connect it to drop deformation in the microcavity. For drop sizes smaller than the microcavity, we observe a bistable behavior in terms of the resistance of the trapped drop as a function of capillary number. For these underfilled drops, we find that the resistance is low at small capillary number (Ca < 10^?3) and jumps to high resistance at a threshold capillary number. For drops equal to the microcavity size, we observe that the bistability vanishes and the drop resistance is of similar magnitude as that of underfilled drops at large capillary number. To explain these findings, we use confocal microscopy and simulations to obtain three-dimensional views of the drop deformation and continuous phase fluid in the microcavity. We observe that the low resistance is due to negligible drop deformation and unobstructed flow of continuous phase through the constriction. The high resistance is due to the drop interface protruding into the constriction restricting the flow of continuous phase through the gutters. Taken together, our results indicate that a trapped drop at a bifurcation can act as a nonlinear resistor and could be potentially used as a soft switch to control droplet trajectories in microfluidic devices.     

Moving shot,an affordable and high-throughput setup for direct imaging of fast-moving microdroplets

Droplet microfluidics have a great potential in chemical and biomedical applications, due to their high throughput, versatility, and massive parallelism. To enhance their throughput, many devices based on the droplet microfluidics are using a flow-through configuration, in which the droplets are generated, transported, and analyzed in a continuous stream with a high velocity. Direct imaging of moving droplets is often necessary to characterize the spatiotemporal dynamics of the chemical reaction and physical process in the droplets. However, due to the motion blur caused by the movement of the droplets during exposure, an expensive high-speed camera is required for clear imaging, which is cost prohibitive in many applications. In this paper, we are presenting ‘Moving shot’ to demonstrate direct imaging of fast-moving droplets in microfluidic channels at an affordable cost. A microfluidic device is translated at the same velocity but in the opposite direction of moving droplets in it, so that the droplets are stationary with respect to the objective lens. With this approach, we can image fluorescent droplets moving at 0.34 cm s⁻¹ with an exposure time up to 2 s without motion blur. We strongly believe that the proposed technique can enable cost-effective and high-throughput imaging of fast-moving droplets in a microfluidic channel.

     

Thin-film electrode based droplet detection for microfluidic systems

We report on a droplet-producing microfluidic system with electrical impedance-based detection. The microfluidic devices are made of polydimethylsiloxane (PDMS) and glass with thin film electrodes connected to an impedance-monitoring circuit. Immiscible fluids containing the hydrophobic and hydrophilic phases are injected with syringe pumps and spontaneously break into water-in-oil droplet trains. When a droplet passes between a pair of electrodes in a medium having different electrical conductivity, the resulting impedance change signals the presence of the particle for closed-loop feedback during processing. The circuit produces a digital pulse for input into a computer control system. The droplet detector allows estimation of a droplet's arrival time at the microfluidic chip outlet for dispensing applications. Droplet detection is required in applications that count, sort, and direct microfluidic droplets. Because of their low cost and simplicity, microelectrode-based droplet detection techniques should find applications in digital microfluidics and in three-dimensional printing technology for rapid prototyping and biotechnology.     

Surfactant-induced retardation in lateral migration of droplets in a microfluidic confinement

The present study deals with the effect of surfactants on the cross-stream migration of droplets in a confined fluidic environment, both experimentally and theoretically. Presence of an imposed flow induces droplet deformation and disturbs the equilibrium that results in subsequent surfactant redistribution along the interface. This further creates a gradient in surface tension, thus generating a Marangoni stress that significantly alters the droplet dynamics. On subsequent experimental investigation, it is found that presence of surfactants reduces the cross-stream migration velocity of the droplet. High-speed photography is utilized to visualize the transport of droplets in a microfluidic channel. It is shown that the channel confinement significantly enhances the surfactant-induced retardation of the droplet. In addition, a larger surfactant concentration is found to induce a greater reduction in cross-stream migration velocity of the droplet, the effect of which is reduced when the initial transverse position of the droplet is shifted closer to the channel centerline. To support our experimental results, an asymptotic approach is adopted to solve the flow field in the presence of bulk-insoluble surfactants and under the assumption of small shape deformation. A good match between our theoretical prediction and the experimental results is obtained. The present analysis provides us with a wide scope of application towards various droplet-based microfluidic as well as medical diagnostic devices where manipulation of droplet trajectory is a major issue.     

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.     

Dynamics of droplet formation at T-shaped nozzles with elastic feed lines

We describe the formation of water in oil droplets, which are commonly used in lab-on-a-chip systems for sample generation and dosing, at microfluidic T-shaped nozzles from elastic feed lines. A narrow nozzle forms a barrier for a liquid–liquid interface, such that pressure can build up behind the nozzle up to a critical pressure. Above this critical pressure, the liquid bursts into the main channel. Build-up of pressure is possible when the fluid before the nozzle is compressible or when the channel that leads to the nozzle is elastic. We explore the value of the critical pressure and the time required to achieve it. We describe the fluid flow of the sudden burst, globally in terms of flow rate into the channel and spatially resolved in terms of flow fields measured using micro-PIV. A total of three different stages—the lag phase, a spill out phase, and a linear growth phase—can be clearly discriminated during droplet formation. The lag time linearly scales with the curvature of the interface inside the nozzle and is inversly proportional to the flow rate of the dispersed phase. A complete overview of the evolution of the growth of droplets and the internal flow structure is provided in the digital supplement.     

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.     

Controlled dispensing and mixing of pico- to nanoliter volumes using on-demand droplet-based microfluidics

We present an integrated droplet-on-demand microfluidic platform for dispensing, mixing, incubating, extracting and analyzing by mass spectrometry pico- to nanoliter-sized droplets. All of the functional components are successfully integrated for the first time into a monolithic microdevice. Droplet generation is accomplished using computer-controlled pneumatic valves. Controlled actuation of valves for different aqueous streams enables accurate dosing and rapid mixing of reagents within droplets in either the droplet generation area or in a region of widening channel cross-section. Following incubation, which takes place as droplets travel in the oil stream, the droplet contents are extracted to an aqueous channel for subsequent ionization at an integrated nanoelectrospray emitter. Using the integrated platform, rapid enzymatic digestions of a model protein were carried out in droplets and detected online by nanoelectrospray ionization mass spectrometry.     

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.     

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.     

A mesoscopic simulation study of distributions of droplets in a bifurcating channel

A transport of a suspension of slightly deformed immiscible droplets in a bifurcating channel is studied by using a mesoscale simulation technique. The distribution of the droplets is represented by the fractional droplet flux into two daughters as a function of the volumetric flow ratio between the daughters. The data obtained in our simulations is compared with theoretical predictions obtained by assuming an exponential function for the distribution for positions of the droplets in the mother channel. The theoretical predictions show good agreement with the simulation results. Further, we compare our results with an experimental study of transports of spherical and disk-shaped particles in a bifurcating channel, and we confirm that our results show the same tendency towards non-linearity as the experimental result do. A non-uniform distribution of the droplets in the mother channel affects the non-linear separation of the droplet flux at the bifurcation.     

Electrostatically actuated metal-droplet microswitches integrated on CMOS chip

The dominance of surface tension over inertia in microscale and favorable scale effect for electrostatic actuation allow electrostatically driven metal-droplet systems practical. Because of such potential advantages as low contact resistance, naturally bistable operation, and high switch density, the liquid-metal droplet switch is an excellent candidate for reconfigurable circuit interconnections. Following earlier droplet microswitch examples and related studies of metal-droplet behavior, we report the first functioning droplet switch directly integrated on top of a functional CMOS circuit. While the surface tension dominance makes the droplet switches practical as a mechanical system and also brings bistability, it also requires a high electric field to move the droplet. We implement the concept of physical surface modification to lower the driving voltage to a value that a commercial CMOS process can provide. Unlike previous droplet switches, the reported device is planar-processed to allow the integration with the underlying CMOS circuits. The integrated switch is made functional by such provisions as self-limiting actuation and by optimizing the electrostatic force in the planar configuration and avoiding liquid-metal "flooding" into surface patterns. A fabrication process for low driving voltage and high compatibility is developed to integrate the droplet switch on the custom-developed CMOS chip. A packaging method adapted from well-established microelectronic packaging isolates the active switch space from the surrounding environment. Low driving voltage (as low as 15 V) and millisecond switching speed are achieved by the current on-chip device. While the current device uses /spl sim/150 /spl mu/m droplets for demonstration, additional theoretical and experimental results indicate that further miniaturization would lead to smaller devices and lower operation voltage.     

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.     

Control of serial microfluidic droplet size gradient by step-wise ramping of flow rates

This paper describes a method to control and detect droplet size gradient by step-wise flow rate ramping of water-in-oil droplets in a microfluidic device. The droplets are generated in a cross channel device with two oil inlets and a water inlet. The droplet images are captured and analyzed in a time sequence in order to quantify the droplet generation frequency. It is demonstrated that by controlling the ramping of the oil flow rates it is possible to manipulate the ramping of droplet sizes. Increasing or decreasing of droplet sizes is achieved for a step-wise triangular ramping profile of the oil flow rate. The dynamic behavior of droplets due to the step-wise flow pulses is investigated. Uniform linear size ramping of water-in-oil droplets from 73 to 83 μm in diameter is generated with an oil flow ramping range from 1 to 11 μL/min in a minimum of five steps while water flow rate is held constant at 2 μL/min.     

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.