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.     

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.     

Liquid–liquid micro-dispersion in a double-pore T-shaped microfluidic device

For further understanding the dispersion process in the T-shaped microfluidic device, a double-pore T-shaped microchannel was designed and tested with octane/water system to form monodispersed plugs and droplets in this work. The liquid–liquid two-phase flow patterns were investigated and it was found that only short plugs, relative length L/w < 1.4, were produced. Additionally, the droplets flow was realized at phase ratios (F _C /F _D) just higher than 0.5, which is much smaller than that in the single-pore T-shaped microchannels. A repulsed effect between the initial droplets was observed in the droplet formation process and the periodic fluctuation flow of the dispersed phase was discussed by analyzing the resistances. Besides, the effect of the two-phase flow rates on the plug length and the droplet diameter was investigated. Considering the mutual effect of the initial droplets and the equilibrium between the shearing force with the interfacial tension, phase ratio and Ca number were introduced into the semi-empirical models to present the plug and droplet sizes at different operating conditions.     

Micro-droplet formation in non-Newtonian fluid in a microchannel

Micro-droplet formation from an aperture with a diameter of micrometers is numerically investigated under the cross-flow conditions of an experimental microchannel emulsification process. The process involves dispersing an oil phase into continuous phase fluid through a microchannel wall made of apertured substrate. Cross-flow in the microchannel is of non-Newtonian nature, which is included in the simulations. Micro-droplets of diameter 0.76–30 μm are obtained from the simulations for the apertures of diameter 0.1–10.0 μm. The simulation results show that rheology of the bulk liquid flow greatly affects the formation and size of droplets and that dispersed micro-droplets are formed by two different breakup mechanisms: in dripping regime and in jetting regime characterized by capillary number Ca. Relations between droplet size, aperture opening size, interfacial tension, bulk flow rheology, and disperse phase flow rate are discussed based on the simulation and the experimental results. Data and models from literature on membrane emulsification and T-junction droplet formation processes are discussed and compared with the present results. Detailed force balance models are discussed. Scaling factor for predicting droplet size is suggested.     

Formation of satellite droplets in flow-focusing junctions: volume and neck rupture

This work focuses on the rupture of the neck of a main droplet, leading to the formation of satellite droplets in a flow-focusing junction. The size of these satellites is determined by image analysis. Emphasis is given to the influence of viscosity and rheological behaviour of the fluids, using both Newtonian and non-Newtonian fluids as continuous phases. The scaling of the size of the satellite droplet with the capillary number of the continuous phase shows two different areas separated by a critical capillary number of 10^?2. Below this critical capillary number, the size of satellites hardly changes. Above this critical value, the size of the droplet increases almost linearly with the capillary number. This critical value appears also as a difference in shape of the rupture of the neck of the droplet for Newtonian continuous fluids: symmetrical for low capillary numbers and asymmetrical rupture of the neck of the droplet for higher capillary numbers. The higher the viscosity ratio (viscosity of dispersed phase/viscosity of continuous phase), the bigger is the main satellite droplet. For more viscous dispersed phases, numerous satellite droplets can be formed. When the continuous phase is non-Newtonian (polyacrylamide solutions) the number of satellites droplets is even higher and their sizes are found interdependent according to a cascade scenario.     

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.     

A superposable double-gradient droplet array chip for preparation of PEGDA microspheres containing concentration-gradient drugs

This article describes a superposable double-concentration-gradient droplet array chip, which allows a variety of concentration combinations of two components to be formed simultaneously. The concentration gradients generated from two layers of the chip could be arbitrarily superimposed by adjusting the center angle between the two bonding layers. With the aqueous phase flow rate of 1.0 μL min^?1 and the oil phase flow rate of 30.0 μL min^?1, the droplets about 58 μm in diameter were produced, and the coefficients of variation were below 6.0% for single channel and 5.7% for all the channels. Using a dual-32-channel superposable gradient droplet array chip, poly(ethylene glycol) diacrylate (PEGDA) microspheres containing concentration-gradient combinations of rhodamine B and fluorescein were fabricated to demonstrate the capability of PEGDA for encapsulating hydrophilic and hydrophobic substances, as well as the proper concentration-gradient distribution. Furthermore, PEGDA microspheres loaded with two anticancer drugs, hydrophilic doxorubicin hydrochloride and hydrophobic paclitaxel, of 17 concentration combinations were simultaneously prepared. The drug-induced apoptosis of human uterine cervix cancer cells was investigated using the dual-drug-loaded PEGDA microspheres. The optimum synergistic concentration combination of the two drugs was 12.5 μg mL^?1 for doxorubicin hydrochloride and 43.75 μg mL^?1 for paclitaxel according to the preliminary screening. The superposable double-gradient droplet array generator was demonstrated to be a promising platform for screening multiple drug combination in microcarriers.     

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.     

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.     

Droplet generation in micro-sieve dispersion device

Microfluidic devices with micro-sieve plate as the dispersion medium have been widely used for the mass production of emulsions. While unfortunately, few studies have so far been made for the droplet generation rules in those devices. In this work, the droplet generation processes in micro-sieve dispersion devices are investigated with specially designed micro-sieve pore arrays. The effects of channel structure, pore arrangement, and feeding method of dispersed phase on the average size and distribution of droplets are studied carefully. It is found the dimensionless average droplet diameters (d _av/d _e) in micro-sieve dispersion devices can be represented by a linear relation with Ca^−1/4 of continuous phase, the same as the scaling law in T-junction microchannels. The flow distribution among pores and the steric hindrance between droplets affect the diameter distribution of generated droplet very much. Monodispersed droplets with polydispersity index less than 5% can be made at Ca number larger than 0.01 and phase ratio (Q _D/Q _C) less than 1/6 in the present investigation.     

Fiber Bragg grating sensor for two-phase flow in microchannels

A new non-intrusive measurement technique for two-phase flow in microchannels is presented. The development of an evanescent field-based optical fiber Bragg grating (FBG) sensor is described, and experiments coupled with flow visualization demonstrating the performance of this sensor are presented. Two adjacent 1-mm FBGs in etched D-shaped fiber are embedded into the surface of a PDMS microchannel. Experiments are conducted in both droplet and slug flow regimes and high-speed digital video is captured synchronously with the sensor data. The FBGs exhibit an on?Coff type response to the passage droplets which is shown to correlate precisely with the passage of the liquid phase. This correlation enables the measurement of droplet average velocity and size using only the sensor data. In addition to the use of both FBG signals for the purpose of measuring droplet speed and size, it is shown that for droplets larger than the FBG length, a single FBG can be used to estimate the convection velocity and size of fast moving droplets. This sensing method is potentially useful for monitoring two-phase flow in fuel cells and microfluidic applications such as micro-heat exchangers and lab-on-a-chip systems.     

Scalable attoliter monodisperse droplet formation using multiphase nano-microfluidics

We demonstrate a robust method to produce monodisperse femtoliter to attoliter droplets by using a nano-microfluidic device. Two immiscible liquids are forced through a nanochannel where a steady nanoscopic liquid filament forms, thinning close to the nanochannel exit to a microchannel due to the capillary focusing. When the nanoscopic filament enters the microchannel, monodisperse droplets are formed by capillary instability. In a certain range of physical parameters and geometrical configurations, the droplet size is only determined by the nanochannel height and independent of liquid flow rates and ratios, surfactants, and continuous phase viscosity. By using nanochannels with a height of 100–900 nm, 0.4–3.5 μm diameter droplets (volume down to 30 aL) have been produced. The generated droplets are stable for at least weeks.     

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.     

Optical separation of droplets on a microfluidic platform

This paper describes the optical separation of microdroplets according to their refractive indices. The behavior of the droplets was characterized in terms of the optical force and the hydrodynamic effects present upon illumination of the droplets in a direction normal to the flow direction in a rectangular microfluidic channel. The optical forces acting on the droplets and the resultant droplet trajectories were analyzed and compared with the numerically predicted values. The relationship between the drag force and optical force was examined to understand the system performance properties in the context of screening applications involving the removal of unwanted droplets. Two species of droplets were compared for their photophoretic displacements by varying the illumination intensity. Because the optical forces exerted on the droplets were functions of the refractive indices and sizes of the droplets, a variety of chemical species could be separated simultaneously.     

Flow of two immiscible liquids with low viscosity in Y shaped microfluidic systems: effect of geometry

This article investigates the formation of albumin droplets in fatty esters by means of a flow focussing geometry where the continuous oil phase is introduced in the two lateral branches of a Y junction. The effect of the geometry is investigated in order to clarify the scales controlling the droplet generation with this type of fluid couple. The transition from regular droplet flow to stratified flow is identified from the experiments. It is found that the droplet size varies linearly with the flow rate ratio between the disperse and continuous phases. This is similar to what is found in T junctions microfluidic systems for low capillary numbers.     

Integrated liquid and droplet dielectrophoresis for biochemical assays

Surface microfluidic systems have emerged as an attractive alternative to conventional closed-channel microfluidic devices. In many such systems, electric fields are leveraged for the manipulation and transport of discrete nanoliter droplets on open planar surfaces. The present research work discusses dielectrophoretic liquid and droplet actuations, which provide an attractive methodology for dispensing and manipulating nanoliter and picoliter droplets on planar surfaces. We demonstrate the integration of two independent sample actuation schemes, namely liquid dielectrophoresis (L-DEP) and droplet dielectrophoresis, and furthermore validate its applicability through model biochemical assays (DNA-PicoGreen^® assay and DNA FRET assay). We also describe and present ‘tapering L-DEP’ actuation scheme, whereby we demonstrate how to simultaneously create multiple droplets of different sizes and volumes in the range of nanoliter and picoliters, from a given larger parent sample droplet.     

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.     

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.     

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.     

Generating gas/liquid/liquid three-phase microdispersed systems in double T-junctions microfluidic device

This article describes the generation of microdispersed bubbles and droplets in a double T-junctions microfluidic device to form immiscible gas/liquid/liquid three-phase flowing systems. Segmented gas plugs are controllably prepared in water at the first T-junction to form gas/liquid two-phase fluid with the perpendicular flow cutting method. Then using this two-phase fluid as the cross-shearing fluid for the oil phase at the second T-junction, the gas/liquid/liquid three-phase flowing systems are prepared. Interestingly, it is found that the break-up of the oil droplets is mainly dominated by the cutting effect of the gas/liquid interface or the pressure drop across the emerging droplet, but independent with the viscous shearing effect of the continuous phase, even at the capillary number (Ca = u _wμ_w/γ_ow) higher than 0.01. The size laws and the distributions of the bubbles and droplets are investigated carefully, and a mathematical model has been developed to relating the operating conditions with the dispersed sizes.