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.     

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.     

An Integrated 2-D Active Optical Fiber Manipulator With Microfluidic Channel for Optical Trapping and Manipulation

We report a new two-axis active optical fiber manipulator for on-chip optical manipulation and detection in microfluidic environment. The system comprising of air chambers, fiber channels, controllable moving walls, and membrane structures were fabricated by using microelectromechanical systems technology. By adjusting air pressures to control the deflection of the pneumatic chambers placed orthogonal to and underneath the fiber channels, accurate alignment of a pair of approximately coaxial optical fibers, which was indicated by maximizing fiber-to-fiber optical-coupling measured in real time, has been achieved. A maximum displacement of a buried fiber as large as 13 mum at an applied pressure of 40 lb/in² for one air chamber has been demonstrated. It was sufficient to accurately align two approximately coaxial optical fibers to maximize the optical coupling efficiency. The maximum coupling efficiency for two single-mode optical fibers facing each other at a distance of 200 mum was measured to be 4.1%. The following features have been successfully demonstrated with this system: 1) stable optical trapping and stretching of a single red blood cell; 2) stable optical trapping of multiple microparticles; 3) optically driven controlled motion of single and multiple microparticles; and 4) integration of a counterpropagating dual-beam trap with single-beam optical tweezers. In addition to optical trapping and manipulation, the proposed device is promising for applications requiring coaxial input/output fibers for in-line optical analysis. Furthermore, it can be easily integrated with other microfluidic devices such as microcapillary electrophoresis channels or microflow cytometers for DNA, protein, and cell analysis.     

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.     

Electro-adaptive microfluidics for active tuning of channel geometry using polymer actuators

With the expanding role of microfluidics in biology and medicine, methodologies for on-chip fluid sample manipulation become increasingly important. While conventional methods of microfluidic actuation, such as pneumatic and piezoelectric valves, are well characterized and commonly used, they require bulky external setups and complex fabrication. To address the need for a simple microfluidic actuator, we introduce a hybrid device consisting of an electroactive polymer that controls the shape of a microfluidic channel with an applied bias voltage. The electro-adaptive microfluidic (EAM) device allowed tuning of fluidic resistances by up to 18.1 %. In addition, we have shown that the EAM device is able to clear microchannel blockages by actively expanding the channel cross section. Biocompatibility tests show the EAM device has little effect on cell viability within a voltage range and thus has the potential to be utilized in bio-microfluidic systems. All of these results indicate that this EAM device design may find use in applications from cell sorting and trapping and self-clearing channels, to the reduction of lab-on-a-chip complexity via tunable channel geometries.     

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.     

A micropump using amplified deformation of resilient membranes through oil hydraulics

Toward the development of micropumps that operate under low external air pressures, a new polydimethylsiloxane (PDMS), pneumatic micropump using amplified deformation of resilient PDMS membranes through oil hydraulics was presented in this study. The new micropump employed oil-hydraulic chambers with pre-filled mineral oil to amplify the deformation of flexible PDMS membranes; it therefore delivered a higher pumping rate and withstood a greater back pressure while requiring a significantly lower external air pressure for actuation. The optimized pumping rate and back pressure of the oil-hydraulic micropump compared favorably to previous pneumatic micropumps. Characterization of the micropump revealed that the oil hydraulics amplified the deformation of PDMS membranes by approximately threefold and improved the pumping rate and the back pressure by 77 and 21 %, respectively. With high pumping performances and the capability to be driven with only a low air pressure, this new micropump may therefore become a key component in future microfluidic devices and lab-on-a-chip systems.     

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 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.     

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     

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.     

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.     

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.     

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.     

Engineered hydrophobicity of discrete microfluidic elements for double emulsion generation

Microfluidic device fabrication has classically utilized methods that have limited devices to specific applications. More recently, discrete microfluidic elements have reimagined the design process of microfluidic device fabrication to that of building blocks that can be constructed in various forms to produce devices of many applications. Here, surface modification of discrete microfluidic elements via initiated chemical vapor deposition is demonstrated. Coated modular elements can quickly assemble to form complex 2-D or 3-D structures with step-like surface energy gradients for applications requiring discrete control of channel surface wettability. This platform is applied toward the generation of double emulsions to show the ease of design and manufacturing over existing methods developed to manage two-phase flows.     

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.

     

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.     

On-demand double emulsification utilizing pneumatically actuated,selectively surface-modified PDMS micro-devices

This article presents an active, two-step emulsification scheme that is capable of producing double emulsions with desired geometries and compositions on demand. Three-layer PDMS micro-devices with pneumatically actuated membrane-valves constructed on top of specially designed fluidic-channels are utilized to meter and shape immiscible fluids into double emulsions. By intermittently squeezing a fluid into another one, controlled emulsification is realized, and successive emulsification steps result in the formation of multiple emulsions. In the prototype demonstration, a three-layer PDMS molding and bonding process was employed to fabricate the proposed microfluidic devices, whose channel surfaces were selectively modified into hydrophilic by a photo-grafting process. A governing computer program cooperating with a set of control hardware was employed to coordinate the actuation of the prototype system. It has been demonstrated that: (1) both water-in-oil-in-oil and water-in-oil-in-water double emulsions can be produced; (2) the sizes of inner aqueous droplets and outer oil drops can be controlled independently; and (3) adjacent oil drops with varying overall sizes, and both diameters and numbers of inner aqueous droplets can be produced on demand. As such, the demonstrated emulsification scheme could potentially fulfill the real-time controllability on emulsion formation, which is desired for a variety of chemical and biological applications.     

Formation of fully closed microcapsules as microsensors by microfluidic double emulsion

Microcapsules templated from microfluidic double emulsions attract a great attention due to their broad new potential applications. We present a method to form transparent polymer microcapsules in small sizes of ~30 μm with aqueous cores and fully closed shells. We controlled the size ratio of the aqueous core to the polymer shell not only by flow rates of the double emulsions, but also by synergetic interaction between surfactants at the interface of immiscible fluids. We also found that fully closed shells can be formed by generating the double emulsion droplets in a jetting regime, in which the aqueous cores are confined centrally in the double emulsion droplets. We demonstrated the formation of barcodes in these microcapsules for multiplexed bioassays. These transparent microcapsules also have wide and high potentials for the development of various microsensors by functionalizing the liquid-state cores with compounds sensitive and responsive to temperature, light or electromagnetic field.