Rounded multi-level microchannels with orifices made in one exposure enable aqueous two-phase system droplet microfluidics

Exposure of a negative photoresist-coated glass slide with diffused light from the backside through a mask with disconnected features provides multi-level rounded channels with narrow orifices in one exposure. Using these structures, we construct microfluidic systems capable of creating aqueous two-phase system droplets where one aqueous phase forms droplets and the other aqueous phase forms the surrounding matrix. Unlike water-in-oil droplet systems, aqueous two-phase systems can have very low interfacial tensions that prevent spontaneous droplet formation. The multi-level channels fabricated by backside lithography satisfy two conflicting needs: (i) the requirement to have narrowed channels for efficient valve closure by channel deformation and (ii) the need to have wide channels to reduce the flow velocity, thus reducing the capillary number and enhancing droplet formation.     

Delayed coalescence behavior of droplets with completely miscible liquids

Because of capillary forces, sessile droplets usually fuse instantaneously after contact. We find however a delay of the droplet fusion by many seconds if the droplets consist of different but completely miscible liquids. After the initial contact, the main bodies of the droplets remain separated, connected only through a shallow conduit with a flow from the low to the high surface tension liquid. Sporadically, this connecting film can thicken with turbulent or pulsating flows. The droplets will finally fuse when the flow has sufficiently reduced the difference in composition and surface tension. We present calculations which explain this delayed droplet fusion with the compensation of the fusion-promoting capillary pressure by a droplet-separating dynamic pressure caused by the flow between the droplets. Droplets with high contact angles fuse instantaneously. In this case, no separation-stabilizing dynamic pressure can build up because the interdroplet flow becomes turbulent.     

Parallel synchronization of two trains of droplets using a railroad-like channel network

We present a simple method of water-in-oil droplet synchronization in a railroad-like channel network. The network consisted of a top channel, a bottom channel, and ladder-like channels interconnected between the two main channels. The presence of the pressure difference between the top and bottom channels resulted in the crossflow of carrier oil through the ladder network until the pressure in each channel was balanced automatically. The proposed model and method proved the feasibility of the parallel synchronization of two trains of droplets with up to 95% synchronization efficiency. Physical parameters that could improve the efficiency were investigated with the systematic variation of the droplet length and droplet generation frequency by controlling the flow rate in each channel. Under a subtle difference in the generation frequency, an unmatched droplet sandwiched between two matched droplets in the ladder network was switched and synchronized in turn. For perfect one-to-one droplet synchronization, the droplet length and the droplet generation frequency needed to be the same for both the top and bottom channels. In addition, one-to-multiple droplet synchronization was demonstrated by matching the product of the droplet length and the droplet generation frequency for both the top and bottom channels. The proposed method provides a simple unit operation for parallel synchronization of the trains of droplets that can be easily integrated with the conventional continuous-flow droplet-based microfluidic platform.     

Localized electric field induced transition and miniaturization of two‐phase flow patterns inside microchannels

Strategic application of external electrostatic field on a pressure‐driven two‐phase flow inside a microchannel can transform the stratified or slug flow patterns into droplets. The localized electrohydrodynamic stress at the interface of the immiscible liquids can engender a liquid‐dielectrophoretic deformation, which disrupts the balance of the viscous, capillary, and inertial forces of a pressure‐driven flow to engender such flow morphologies. Interestingly, the size, shape, and frequency of the droplets can be tuned by varying the field intensity, location of the electric field, surface properties of the channel or fluids, viscosity ratio of the fluids, and the flow ratio of the phases. Higher field intensity with lower interfacial tension is found to facilitate the oil droplet formation with a higher throughput inside the hydrophilic microchannels. The method is successful in breaking down the regular pressure‐driven flow patterns even when the fluid inlets are exchanged in the microchannel. The simulations identify the conditions to develop interesting flow morphologies, such as (i) an array of miniaturized spherical or hemispherical or elongated oil drops in continuous water phase, (ii) “oil‐in‐water” microemulsion with varying size and shape of oil droplets. The results reported can be of significance in improving the efficiency of multiphase microreactors where the flow patterns composed of droplets are preferred because of the availability of higher interfacial area for reactions or heat and mass exchange.     

Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up

This article describes the process of formation of droplets and bubbles in microfluidic T-junction geometries. At low capillary numbers break-up is not dominated by shear stresses: experimental results support the assertion that the dominant contribution to the dynamics of break-up arises from the pressure drop across the emerging droplet or bubble. This pressure drop results from the high resistance to flow of the continuous (carrier) fluid in the thin films that separate the droplet from the walls of the microchannel when the droplet fills almost the entire cross-section of the channel. A simple scaling relation, based on this assertion, predicts the size of droplets and bubbles produced in the T-junctions over a range of rates of flow of the two immiscible phases, the viscosity of the continuous phase, the interfacial tension, and the geometrical dimensions of the device.     

流动聚焦型微流控体系中的液滴的图案化排列和转变模式

流体在微流通道中形成剪切流场（低雷诺数）．不同于宏观体系,由于剪切力和表面张力的竞争作用,产生的液滴在微尺度下的微流通道中形成特殊的排列现象---周期性类似“晶格”排列现象．设计了新型流动聚焦型微流控芯片,分析研究在微流体系中液滴周期性图案化排列和转变机理性,液滴排列模式受两方面因素影响：水油两相的流速比值和微通道尺寸．当微通道宽度为250或300 μm时,液滴形成单层分散,双层和单层挤压排列．当微通道宽度为350 μm 时,液滴会形成单层分散到三层排列到双层挤压最后到单层挤压排列．当出口通道宽度增加到400 μm时,甚至出现了液滴四层排列的现象．同时研究了各个液滴排列模式的“转变点”.     

Microfluidic platforms for lab-on-a-chip applications

We review microfluidic platforms that enable the miniaturization, integration and automation of biochemical assays. Nowadays nearly an unmanageable variety of alternative approaches exists that can do this in principle. Here we focus on those kinds of platforms only that allow performance of a set of microfluidic functions--defined as microfluidic unit operations-which can be easily combined within a well defined and consistent fabrication technology to implement application specific biochemical assays in an easy, flexible and ideally monolithically way. The microfluidic platforms discussed in the following are capillary test strips, also known as lateral flow assays, the "microfluidic large scale integration" approach, centrifugal microfluidics, the electrokinetic platform, pressure driven droplet based microfluidics, electrowetting based microfluidics, SAW driven microfluidics and, last but not least, "free scalable non-contact dispensing". The microfluidic unit operations discussed within those platforms are fluid transport, metering, mixing, switching, incubation, separation, droplet formation, droplet splitting, nL and pL dispensing, and detection.     

Interface motion of capillary-driven flow in rectangular microchannel

In microchannel flow, gas-liquid interface behavior is important for developing a wide range of microfluidic applications, especially in passive microfluidic systems. This paper presents a discussion of interface motion driven by capillary action in a microchannel. We have extended the theory beyond the previous theory of capillary rise problem for a circular tube, to a rectangular microchannel. The same formula for the relation between nondimensional time and interface position is obtained as for a circular tube. We examined rectangular microchannels with several sizes (about 50 to 100 microm square) of glass capillaries and 85 x 68 microm and 75 x 45 microm polydimethylsiloxane (PDMS) microchannels fabricated by photolithography technique, respectively. We observed movement of the gas-liquid interface position and compared it to the dimensionless relation. We obtained the value of a dimensionless variable of driving force that is related to dynamic contact angles for glass-water, glass-ethanol, and PDMS-ethanol. Using this variable, interface motion can be predicted for any size of rectangular channels.     

Effect of Intersection Angle of Input Channels in Droplet Generators

In this paper, we studied the effects of the intersection angle between the inlet channels on the droplet diameter using a COMSOL Multiphysics^® simulation. We employed the level-set method to study the droplet generation process inside a microfluidic flow device. A flow-focusing geometry was integrated into a microfluidics device and used to study droplet formation in liquid–liquid systems. Droplets formed by this flow-focusing technique are typically smaller than the upstream capillary tube and vary in size with the flow rates. Different intersection angles were modeled with a fixed width of continuous and dispersed channels, orifices, and expansion channels. Numerical simulations were performed using the incompressible Navier–Stokes equations for single-phase flow in various flow-focusing geometries. As a result of modeling, when the dispersed flow rate and the continuous flow rate were increased, the flow of the continuous flow fluid interfered with the flow of the dispersed flow fluid, which resulted in a decrease in the droplet diameter. Variations in the droplet diameter can be used to change the intersection angle and fluid flow rate. In addition, it was predicted that the smallest diameter droplet would be generated when the intersection angle was 90°.     

Reconfigurable virtual electrowetting channels

Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.     

Comparison of monodisperse droplet generation in flow-focusing devices with hydrophilic and hydrophobic surfaces

A thin flow-focusing microfluidic channel is evaluated for generating monodisperse liquid droplets. The microfluidic device is used in its native state, which is hydrophilic, or treated with OTS to make it hydrophobic. Having both hydrophilic and hydrophobic surfaces allows for creation of both oil-in-water and water-in-oil emulsions, facilitating a large parameter study of viscosity ratios (droplet fluid/continuous fluid) ranging from 0.05 to 96 and flow rate ratios (droplet fluid/continuous fluid) ranging from 0.01 to 2 in one geometry. The hydrophilic chip provides a partially-wetting surface (contact angle less than 90°) for the inner fluid. This surface, combined with the unusually thin channel height, promotes a flow regime where the inner fluid wets the top and bottom of the channel in the orifice and a stable jet is formed. Through confocal microscopy, this fluid stabilization is shown to be highly influenced by the contact angle of the liquids in the channel. Non-wetting jets undergo breakup and produce drops when the jet is comparable to or smaller than the channel thickness. In contrast, partially-wetting jets undergo breakup only when they are much smaller than the channel thickness. Drop sizes are found to scale with a modified capillary number based on the total flow rate regardless of wetting behavior.     

CFD Simulation of Droplet Formation in a Wide-Type Microfluidic T-Junction

Droplet formation in a wide-type microfluidic T-junction was studied using the computational fluid dynamics (CFD) method. Two distinct regimes of droplet formation were confirmed: dripping and jetting; and, at both regimes, droplet size decreases with an increase in capillary number. CFD simulation demonstrated that droplet formation in the T-junction can be divided into three steps: droplet emergence and growing up; separation with the disperse phase; and detachment from the channel wall. The wettability of the channel wall significantly affects the process of droplet detachment from the channel wall; also, the simulation clearly showed that droplets can be formed only when the continuous phase fluid preferentially wets the channel wall, that is, its contact angle on the wall is smaller than 90°. Finally, the CFD study verified that the disperse phase flow rate can significantly affect the droplet size as well as the mechanism of droplet formation.     

Pillar-induced droplet merging in microfluidic circuits

A novel method is presented for controllably merging aqueous microdroplets within segmented flow microfluidic devices. Our approach involves exploiting the difference in hydrodynamic resistance of the continuous phase and the surface tension of the discrete phase through the use of passive structures contained within a microfluidic channel. Rows of pillars separated by distances smaller than the representative droplet dimension are installed within the fluidic network and define passive merging elements or chambers. Initial experiments demonstrate that such a merging element can controllably adjust the distance between adjacent droplets. In a typical scenario, a droplet will enter the chamber, slow down and stop. It will wait and then merge with the succeeding droplets until the surface tension is overwhelmed by the hydraulic pressure. We show that such a merging process is independent of the inter-droplet separation but rather dependent on the droplet size. Moreover, the number of droplets that can be merged at any time is also dependent on the mass flow rate and volume ratio between the droplets and the merging chamber. Finally, we note that the merging of droplet interfaces occurs within both compressing and the decompressing regimes.     

Integrated continuous microfluidic liquid-liquid extraction

We describe continuous flow liquid-liquid phase separation in microfluidic devices based on capillary forces and selective wetting surfaces. Effective liquid-liquid phase separation is achieved by using a thin porous fluoropolymer membrane that selectively wets non-aqueous solvents, has average pore sizes in the 0.1-1 microm range, and has a high pore density for high separation throughput. Pressure drops throughout the microfluidic network are modelled and operating regimes for the membrane phase separator are determined based on hydrodynamic pressure drops and capillary forces. A microfluidic extraction device integrating mixing and phase separation is realized by using silicon micromachining. Modeling of the phase separator establishes the operating limits. The device is capable of completely separating several organic-aqueous and fluorous-aqueous liquid-liquid systems, even with high fractions of partially miscible compounds. In each case, extraction is equivalent to one equilibrium extraction stage.     

Experimental investigation of droplet acceleration and collision in the gas phase in a microchannel

We developed a novel microfluidic system, termed a micro-droplet collider, by utilizing the spatial-temporal localized liquid energy to realize chemical processes, which achieved rapid mixing between droplets having a large volume ratio by collision. In this paper, in order to clarify the characteristics of the micro-droplet collider, dynamics of droplet acceleration, stationary motion and collision in the gas phase in a microchannel were experimentally investigated with visualized images using a microscope equipped with a high-speed camera. The maximum velocity of 450 mm s(-1) and acceleration of 1500 m s(-2) of a 1.6 nL water droplet were achieved at an air pressure of 100 kPa. Measurement results of dynamic contact angles of droplets indicated that wettability of the surface played an important role in the stability of droplet acceleration and collision. We found that the bullet droplet penetrated into the target droplet at collision, which differed from bulk scale. The deformation of the droplet was strongly suppressed by the channel structure, thus stable collision and efficient utilization of the droplet energy were possible. These results are useful for estimating the localized energy, for improving the system in order to realize extreme performance, and for extending the applications of microfluidic devices.     

Deformation and breakup of micro- and nanoparticle stabilized droplets in microfluidic extensional flows

Using a microfluidic flow-focusing device, monodisperse water droplets in oil were generated and their interface populated by either 1 μm or 500 nm amine modified silica particles suspended in the water phase. The deformation and breakup of these Pickering droplets were studied in both pure extensional flow and combined extensional and shear flow at various capillary numbers using a microfluidic hyperbolic contraction. The shear resulted from droplet confinement and increased with droplet size and position along the hyperbolic contraction. Droplet deformation was found to increase with increasing confinement and capillary number. At low confinements and low capillary numbers, the droplet deformation followed the predictions of theory. For fully confined droplets, where the interface was populated by 1 μm silica particles, the droplet deformation increased precipitously and two tails were observed to form at the rear of the droplet. These tails were similar to those seen for surfactant covered droplets. At a critical capillary number, daughter droplets were observed to stream from these tails. Due to the elasticity of the particle-laden interface, these drops did not return to a spherical shape, but were observed to buckle. Although increases in droplet deformation were observed, no tail streaming occurred for the 500 nm silica particle covered droplets over the range of capillary numbers studied.     

A dynamic liquid-liquid interfacial pressure detector for the rapid analysis of surfactants in a flowing organic liquid

Design and development of a dynamic interfacial pressure detector (DIPD) is reported. The DIPD measures the differential pressure as a function of time across the liquid-liquid interface of organic liquid drops (i.e., n-hexane) that repeatedly grow in water at the end of a capillary tip. Using a calibration technique based on the Young-Laplace equation, the differential pressure signal is converted, in real-time, to a relative interfacial pressure. This allows the DIPD to monitor the interfacial tension of surface active species at liquid-liquid interfaces in flow-based analytical techniques, such as flow injection analysis (FIA), sequential injection analysis (SIA) and high performance liquid chromatography (HPLC). The DIPD is similar in principle to the dynamic surface tension detector (DSTD), which monitors the surface tension at the air-liquid interface. In this report, the interfacial pressure at the hexane-water interface was monitored as analytes in the hexane phase diffused to and arranged at the hexane-water interface. The DIPD was combined with FIA to analytically measure the interfacial properties of cholesterol and Brij^®30 at the hexane-water interface. Results show that both cholesterol and Brij^®30 exhibit a dynamic interfacial pressure signal during hexane drop growth. A calibration curve demonstrates that the relative interfacial pressure of cholesterol in hexane increases as the cholesterol concentration increases from 100 to 10,000 μg ml⁻¹. An example of the utility of the DIPD as a selective detector for a chromatographic separation of interface-active species is also presented in the analysis of cholesterol in egg yolk by normal-phase HPLC-DIPD.     

An inkjet-printed microfluidic device for liquid-liquid extraction

A microfluidic device for liquid-liquid extraction was quickly produced using an office inkjet printer. An advantage of this method is that normal end users, who are not familiar with microfabrication, can produce their original microfluidic devices by themselves. In this method, the printer draws a line on a hydrophobic and oil repellent surface using hydrophilic ink. This line directs a fluid, such as water or xylene, to form a microchannel along the printed line. Using such channels, liquid-liquid extraction was successfully performed under concurrent and countercurrent flow conditions.     

Design of microfluidic channel geometries for the control of droplet volume, chemical concentration, and sorting

Passive microfluidic channel geometries for control of droplet fission, fusion and sorting are designed, fabricated, and tested. In droplet fission, the inlet width of the bifurcating junction is used to control the range of breakable droplet sizes and the relative resistances of the daughter channels were used to control the volume of the daughter droplets. Droplet fission is shown to produce concentration differences in the daughter droplets generated from a primary drop with an incompletely mixed chemical gradient, and for droplets in each of the bifurcated channels, droplets were found to be monodispersed with a less than 2% variation in size. Droplet fusion is demonstrated using a flow rectifying design that can fuse multiple droplets of same or different sizes generated at various frequencies. Droplet sorting is achieved using a bifurcating flow design that allows droplets to be separated base on their sizes by controlling the widths of the daughter channels. Using this sorting design, submicron satellite droplets are separated from the larger droplets.