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.     

微沟道内两相流速比对液滴形成的影响

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

Circuit model for microfluidic bubble generation under controlled pressure

We explore the microfluidic generation of bubbles in a flow-focusing junction using a pressure-controlled device rather than the more common flow rate-controlled devices. This device is a prototype for extending microfluidic drop generation methods to molten polymers. We show that the bubble generation process is highly sensitive to pressure: small changes in pressure induce large changes in bubble size and bubble formation frequency. A simple resistance circuit model can explain this pressure dependence. Briefly, we show that bubble generation is possible only within a finite pressure range. Near the ends of this pressure range, the ratio of the flow rates of the dispersed to continuous phase is highly sensitive to pressure, and therefore so also is the bubble generation process. The circuit model offers a way to use existing models of drop generation (which are based on flow rate-controlled operation) to predict pressure-controlled operation. We also examine drop formation using a highly viscous polymer as the dispersed phase. Drops are formed far downstream of the flow-focusing junction, and they are far smaller than the microfluidic channel dimensions. These results suggest that existing microfluidic drop generation methods may be exploited to make complex particles from thermoplastic polymers.     

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

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

Parallelised production of fine and calibrated emulsions by coupling flow-focusing technique and partial wetting phenomenon

The capacity of microfluidic technology to fabricate monodisperse emulsion droplets is well established. Parallelisation of droplet production is a prerequisite for using such an approach for making high-quality materials for either fundamental or industrial applications where product quantity matters. Here, we investigate the emulsification efficiency of parallelised drop generators based on a flow-focusing geometry when incorporating the role of partial wetting in order to make emulsion droplets with a diameter below 10 μm. Confinement intrinsically encountered in microsystems intensifies the role played by interfaces between liquids and solids. We thus take advantage of partial wetting to enhance the maximum confinement accessible due to liquid flow focusing. We compare the performances brought by partial wetting to more established routes such as step emulsification. We show that the step configuration and the partial wetting regime are both well suited for being parallelised and thus open the way to the production of fine and calibrated emulsions for further applications. Finally, this new route of emulsification that exploits partial wetting between the fluids and the channel walls opens possibilities to the formation of substantially smaller droplets, as required in many fields of application.     

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

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

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.     

Novel swirl flow-focusing microfluidic device for the production of monodisperse microbubbles

A novel swirl flow-focusing microfluidic axisymmetric device for the generation of monodisperse microbubbles at high production rates to be used as in-line contrast agents for medical applications is presented. The swirl effect is induced upstream of the discharge orifice by a circular array of microblades which form a given angle with the radial direction. The induced vortical component on the focusing liquid stabilizes the gas meniscus by the vorticity amplification due to vortex stretching as the liquid is forced through the discharge orifice. The stabilized meniscus tapers into a steady gas ligament that breaks into monodisperse microbubbles. A reduction up to \(57\%\) in the microbubble diameter is accomplished when compared to conventional axisymmetric flow-focusing microdevices. An exhaustive experimental study is performed for various blade angles and numerous gas to liquid flow rate ratios, validating previous VoF numerical simulations. The microbubbles issued from the stabilized menisci verify prior scaling law of flow-focusing.     

Droplet bistability and its application to droplet control

Novel methods for controlling droplets precisely in the microchannels are presented, which employ microfluidic bifurcation channels with outlet restrictions based on droplet bistability, utilizing the Laplace pressure caused by interfacial tension that arises when a droplet encounters a narrow restriction. The bistable geometry possesses two symmetric branches and restrictions that operate as capillary valves allowing a droplet to be trapped in front of a restriction and released through it when the next droplet arrives at the other restriction. This trap-and-release occurs repeatedly and regularly by the succeeding droplets. Furthermore, a critical flow rate is found to exist, which is necessary for achieving droplet bistability. This occurs only when the apparent Laplace pressure surpasses the pressure drop across the droplet. By adopting a simplified hydrodynamic resistance model, the droplet bistable mechanism is clearly explained, and droplet bistability is shown to enable the simple and precise control of droplets at a bifurcation channel. Thus, precise droplet traffic control is achieved at a bifurcation channel connected with a single inlet channel and two outlet channels using an appropriate channel design that induces droplet bistability. In particular, droplets are distributed at a junction in a manner of perfect alternation or perfect switching between the two outlet channels. This article proposes that bistable components can be used as elaborately embedded droplet traffic signals for red light (trap), green light (release), and turn light (switching) in complex microfluidic devices, where droplets provide both the chemical or biological materials and the processing signal.     

Monodisperse droplets by impinging flow-focusing

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

Highly integrated polymeric microliquid flow controller for droplet microfluidics

Microfluidic applications demand accurate control and measurement of small fluid flows and volumes, and the majority of approaches found in the literature involve materials and fabrication methods not suitable for a monolithic integration of different microcomponents needed to make a complex Lab-on-a-Chip (LoC) system. The present work leads to a design and manufacturing approach for problem-free monolithic integration of components on thermoplastics, allowing the production of excellent quality devices either as stand-alone components or combined in a complex structures. In particular, a polymeric liquid flow controlling system (LFCS) at microscale is presented, which is composed of a pneumatic microvalve and an on-chip microflow sensor. It enables flow regulation between 30 and 230 μl/min with excellent reproducibility and accuracy (error lower than 5%). The device is made of a single Cyclic Olefin Polymer (COP) piece, where the channels and cavities are hot-embossed, sealed with a single COP membrane by solvent bonding and metalized, after sealing, to render a fully functional microfluidic control system that features on-chip flow sensing. In contrast with commercially available flow control systems, the device can be used for high-quality flow modulation in disposable LoC devices, since the microfluidic chip is low cost and replaceable from the external electronic and pneumatic actuators box. Functionality of the LFCS is tested by connecting it to a microfluidic droplet generator, rendering highly stable flow rates and allowing generation of monodisperse droplets over a wide range of flow rates. The results indicate the successful performance of the LFCS with significant improvements over existing LFCS devices, facing the possibility of using the system for biological applications such as generating distinct perfusion modes in cell culture, novel digital microfluidics. Moreover, the integration capabilities and the reproducible fabrication method enable straightforward transition from prototype to product in a way that is lean, cost-effective and with reduced risk.     

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.     

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.     

Developing heatable microfluidic chip to generate gelatin emulsions and microcapsules

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

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.     

Emulsification in a microfluidic flow-focusing device: effect of the viscosities of the liquids

We report the results of a comparative study of microfluidic emulsification of liquids with different viscosities. Depending on the properties of the fluids and their rates of flow, emulsification occurred in the dripping and jetting regimes. We studied the characteristic features and typical dependence of the size and of the size distribution of droplets in each regime. For each liquid, we identified a range of hydrodynamic conditions promoting generation of highly monodisperse droplets. Viscosity played an important role in emulsification: highly viscous liquids were emulsified into larger droplets with lower polydispersity. Although it was not possible to provide a unified scaling for the volumes of the droplets, our results suggest that the break-up dynamics of the lower viscosity fluids resembles the rate-of-flow-controlled break-up, as reported earlier for the formation of bubbles in flow-focusing geometries [Garstecki P, Stone HA, Whitesides GM (2005) Phys Rev Lett 94:164501]. The results of this study can be helpful for a rationalized selection of liquids for the controlled formation of droplets with a predetermined size and with a narrow distribution of sizes.     

Synthesis of bio-functionalized copolymer particles bearing carboxyl groups via a microfluidic device

Monodisperse copolymer particles carrying surface carboxyl groups in the range of 50–200 μm were prepared by in situ UV polymerization of ethyleneglycol dimethacrylate (EGDMA) with acrylic acid (AA) via a microfluidic flow-focusing device (MFFD). The design of the coaxial orifices in the MFFD enables the confinement of the comonomer liquid thread to the central axis of the microchannel, which can avoid the wetting problem of comonomer liquid with the microchannel and can successfully produce monodisperse copolymer microspheres with coefficient of variance below 5%. The effects of concentration of EGDMA and AA on droplet diameters and the distribution of carboxyl group on particle surfaces were examined. It has been found that, increasing the concentration of AA would decrease particle sizes, but increase the distribution of carboxyl group on particle surfaces. Bioconjugation of the carboxylated copolymer particles with the anti-rabbit IgG–Cy3 conjugates was successfully demonstrated. By increasing the concentration of AA accompanied with decreasing the particle sizes, high efficiency of bioconjugation on carboxylated copolymer particles was achieved. The rapid continuous synthesis of carboxylated copolymer particles via a microfluidic device provides a reliable control of particle sizes and composition for massive production in biotechnological applications.     

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.     

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.     

Precise control of the pressure-driven flows considering the pressure fluctuations induced by the process of droplet formation

The pressure-driven device is designed to control the flow rates of the droplet microfluidic systems, which can significantly reduce the flow-rate fluctuations coming from the pump source. As monodisperse droplets are formed in the microchannel, periodic pressure fluctuations can be induced by the dynamic process of droplet formation, which can influence the stability and control precision of the pressure-driven flows. The effects of the pressure fluctuations induced by the droplet formation process on the dynamic characteristics of the open-loop and closed-loop control pressure-driven devices are comparatively studied. Particularly, a proportional–integral controller (PI controller) is integrated with the closed-loop control pressure-driven device and the effects of the PI controller parameters on the stability and control accuracy of the pressure-driven flows are tested experimentally. Particularly, by properly choosing the parameters of the PI controller, the magnitude of the periodic pressure fluctuations can be reduced drastically, which obviously increases the control precision of the pressure-driven flows.