Surfactant-enhanced liquid-liquid extraction in microfluidic channels with inline electric-field enhanced coalescence

Continuous microfluidic liquid-liquid extraction is realized in a microfluidic device by generating emulsions with large interfacial areas for mass transfer, and subsequently breaking these emulsions using electric fields into easily separated segments of immiscible liquids (plugs). The microfluidic device employs insulated electrodes in a potassium hydroxide-etched channel to create large electric fields (100 kV m(-1)) that drive coalescence of the emulsion phase. The result is a transition from disperse to slug flow that can then readily be separated by gravity. Extractions of phenol and p-nitrophenol from an aqueous to hexane-surfactant solution serve as model systems. In addition to the increased surface area in the emulsion, extraction efficiency is enhanced by reverse micelles resulting from the presence of surfactants. The surfactant concentration is varied approximately 1-10 wt% and a general two-parameter model is developed to quantify the extraction behavior and demonstrate the effectiveness of reverse micelle enhanced extraction.     

Effects of viscosity on droplet formation and mixing in microfluidic channels

This paper characterizes the conditions required to form nanoliter-sized droplets (plugs) of viscous aqueous reagents in flows of immiscible carrier fluid within microfluidic channels. For both non-viscous (viscosity of 2.0 mPa s) and viscous (viscosity of 18 mPa s) aqueous solutions, plugs formed reliably in a flow of water-immiscible carrier fluid for Capillary number less than 0.01, although plugs were able to form at higher Capillary numbers at lower ratios of the aqueous phase flow rate to the flow rate of the carrier fluid (in all the experiments performed, the Reynolds number was less than 1). The paper also shows that combining viscous and non-viscous reagents can enhance mixing in droplets moving through straight microchannels by providing a nearly ideal initial distribution of reagents within each droplet. The study should facilitate the use of this droplet-based microfluidic platform for investigation of protein crystallization, kinetics, and assays.     

Control and applications of immiscible liquids in microchannels

Photolithography was used in combination with photocleavable self-assembled monolayers to pattern surface free energies inside microchannels enabling the control of the boundary between immiscible liquids. While aqueous solutions are confined to the hydrophilic pathways by surface forces alone, organic liquids are confined to the hydrophobic region only if the aqueous liquid first occupies the hydrophilic region. In this way, stable liquid boundaries between immiscible liquids are possible as long as the pressures are maintained below critical values. The maximum pressures are determined by the interfacial tension of the aqueous solution and organic liquid, channel depth, and advancing contact angle (theta;(a)). Experimental results on maximum pressures are in good agreement with the analytical values. The ability to confine and position the boundary between immiscible liquids inside microchannels leads to a broad range of applications in microfluidic systems, which is exemplified by fabrication of a semipermeable membrane in a surface-patterned channel via interfacial polymerization.     

Polyacrylamide gel plugs enabling 2-D microfluidic protein separations via isoelectric focusing and multiplexed sodium dodecyl sulfate gel electrophoresis

In situ photopolymerized polyacrylamide (PAAm) gel plugs are used as hydrodynamic flow control elements in a multidimensional microfluidic system combining IEF and parallel SDS gel electrophoresis for protein separations. The PAAm gel plugs offer a simple method to reduce undesirable bulk flow and limit reagent/sample crosstalk without placing unwanted constraints on the selection of separation media, and without hindering electrokinetic ion migration in the complex microchannel network. In addition to improving separation reproducibility, the discrete gel plugs integrated into critical regions of the chip enable the use of a simple pressure-driven sample injection method which avoids electrokinetic injection bias. The gel plugs also serve to greatly simplify operation of the spatially multiplexed system by eliminating the need for complex external fluidic interfaces. Using an FITC-labeled Escherichia coli cell lysate as a model system, the use of gel plugs is shown to significantly enhance separation reproducibility in a chip containing five parallel CGE channels, with an average variance in peak elution time of only 4.1%.     

Microfluidic approach for rapid interfacial tension measurement

A novel microfluidic approach to measure interfacial tension of immiscible fluids rapidly is reported. This method rests upon quantitative force balance analysis of drop formation dynamics in a coaxial microfluidic device. The values of interfacial tension for several two liquids without/with surfactants are measured. These measurements compare well with those measured by the commercial interfacial tensiometry. The viscosity of water phase fluid can also be accurately measured in the same microfluidic device. Several model systems with interfacial tension from 1.0 to 10.0 mN/m and water phase viscosity from 1.0 to 10.0 mPa.s are tested in this work.     

不相溶液体的性质和应用

文章综述了不相溶液体的性质和应用。一些关于不相溶液体在微尺度下的流动行为的研究表明,由于液体之间不同的黏度、密度和界面自由能,这种不相溶液体的流动行为不同于具有相似或相同性质的液体,因此在生物医学和化学工业中有着不可替代的作用。     

液滴在不互溶液体表面上的相对界面自由能曲面及Neumann三角形的导出

根据系统的界面Helmholtz自由能自发地趋于最低的热力学原理,以浮在不互溶液体(2)表面上透镜状液滴(3)在气(1)、液₂、液₃三相交界处,气-液₃、液₂-液₃界面各自和气-液₂界面通过液滴内部的夹角θ₁、θ₂为变量(0°≤θ₁≤180°,0°≤θ₂≤180°),证明出3个界面张力γ₁₂、γ₁₃、γ₂₃各种可能组合情况下液体₃稳定时的θ₁、θ₂值与它们之间的关系,导出Neumann三角形;并按照计算数据绘出几种类型相对于气相中圆球形液滴的界面自由能曲面图。     

Control of initiation, rate, and routing of spontaneous capillary-driven flow of liquid droplets through microfluidic channels on SlipChip

This Article describes the use of capillary pressure to initiate and control the rate of spontaneous liquid-liquid flow through microfluidic channels. In contrast to flow driven by external pressure, flow driven by capillary pressure is dominated by interfacial phenomena and is exquisitely sensitive to the chemical composition and geometry of the fluids and channels. A stepwise change in capillary force was initiated on a hydrophobic SlipChip by slipping a shallow channel containing an aqueous droplet into contact with a slightly deeper channel filled with immiscible oil. This action induced spontaneous flow of the droplet into the deeper channel. A model predicting the rate of spontaneous flow was developed on the basis of the balance of net capillary force with viscous flow resistance, using as inputs the liquid-liquid surface tension, the advancing and receding contact angles at the three-phase aqueous-oil-surface contact line, and the geometry of the devices. The impact of contact angle hysteresis, the presence or absence of a lubricating oil layer, and adsorption of surface-active compounds at liquid-liquid or liquid-solid interfaces were quantified. Two regimes of flow spanning a 10(4)-fold range of flow rates were obtained and modeled quantitatively, with faster (mm/s) flow obtained when oil could escape through connected channels as it was displaced by flowing aqueous solution, and slower (micrometer/s) flow obtained when oil escape was mostly restricted to a micrometer-scale gap between the plates of the SlipChip ("dead-end flow"). Rupture of the lubricating oil layer (reminiscent of a Cassie-Wenzel transition) was proposed as a cause of discrepancy between the model and the experiment. Both dilute salt solutions and complex biological solutions such as human blood plasma could be flowed using this approach. We anticipate that flow driven by capillary pressure will be useful for the design and operation of flow in microfluidic applications that do not require external power, valves, or pumps, including on SlipChip and other droplet- or plug-based microfluidic devices. In addition, this approach may be used as a sensitive method of evaluating interfacial tension, contact angles, and wetting phenomena on chip.     

Multi-step synthesis of nanoparticles performed on millisecond time scale in a microfluidic droplet-based system

This paper reports a plug-based, microfluidic method for performing multi-step chemical reactions with millisecond time-control. It builds upon a previously reported method where aqueous reagents were injected into a flow of immiscible fluid (fluorocarbons)(H. Song et al., Angew. Chem. Int. Ed., 2003, 42, 768). The aqueous reagents formed plugs--droplets surrounded and transported by the immiscible fluid. Winding channels rapidly mixed the reagents in droplets. This paper shows that further stages of the reaction could be initiated by flowing additional reagent streams directly into the droplets of initial reaction mixture. The conditions necessary for an aqueous stream to merge with aqueous droplets were characterized. The Capillary number could be used to predict the behavior of the two-phase flow at the merging junction. By transporting solid reaction products in droplets, the products were kept from aggregating on the walls of the microchannels. To demonstrate the utility of this microfluidic method it was used to synthesize colloidal CdS and CdS/CdSe core-shell nanoparticles.     

Microfluidic chip for electrochemically-modulated liquid∣liquid extraction of ions

A microfluidic device with integrated electrodes for the electrochemically-modulated extraction of ions across immiscible aqueous–organic liquid–liquid interfaces is presented. Using a Y-shaped microfluidic channel with in situ electrodes and co-flowing aqueous and organic immiscible electrolyte solutions, the manipulation of the applied interfacial potential enabled the extraction of ions from the aqueous phase into the organic phase. Data for the extraction of tetraethylammonium cations from aqueous electrolyte into 1,2-dichloroethane electrolyte are presented. The device demonstrates the benefits of combination of microfluidics and liquid–liquid electrochemistry.     

A microfluidic flow distributor generating stepwise concentrations for high-throughput biochemical processing

In this paper, we describe a microfluidic device in which solutions with stepwise concentrations can be accurately generated by continuously introducing two kinds of miscible liquids from each inlet, and biochemical processing can be conducted at the various conditions. Introduced liquid flows are geometrically divided into a number of downstream flows through multiple distribution channels, and each divided flow is then mixed with the divided flow of another liquid at a confluent point. The lengths of the precisely designed distribution channels determine the mixing ratio of the two liquids, without the influence of flow rate. In this study, a PDMS microfluidic device able to generate nine different concentrations was fabricated, and the performance of this device was estimated via colorimetric assay. As a biological application of this device, cell cultivation was performed under different concentration conditions. Due to its simplicity of operation, this microfluidic flow distributor will be applied to various kinds of biological analysis and screening systems.     

Spontaneous Liquid/Liquid Displacement in a Capillary

When a two-phase column consisting of paraffin oil and silicon oil is placed in an otherwise air-filled, horizontal glass capillary, the column starts moving spontaneously. Silicon oil displaces paraffin oil, which in its turn displaces air at atmospheric conditions; a stable film of silicon oil is left at the receding silicon oil/air meniscus. The driving force for the motion is the difference in capillary pressure at the free interfaces. However, the column moves considerably more slowly than predicted by the driving forces; it appears that the forces resisting the motion at the moving liquid/liquid/solid line are much larger than one would expect on the basis of the interfacial tension and the viscosities of the two phase system. Some considerations are made on the relationship of the theory of Fowkes to our system. Also, a method for measuring low interfacial tensions between immiscible liquids is proposed.     

Infrared controlled waxes for liquid handling and storage on a CD-microfluidic platform

A novel active valving technique, whereby paraffin wax plugs in microchannels on a centrifugal microfluidic platform are actuated using focused infrared (IR) radiation is demonstrated in this report. Microchannels were simultaneously or sequentially opened using a stationary IR source by forming wax plugs with similar or differing melting points. The presented wax plugs offer key advantages over current active valving techniques, including a less involved fabrication procedure, a simpler actuation process, and the ability to multiplex experiment with active valves. In addition, a new technique for automated liquid reagent storage and release on the microfluidic disc platform, based on the formation and removal of a wax layer, is demonstrated. Overall, the techniques presented in this report offer novel methods for liquid handling, separation, and storage on the centrifugal microfluidic disc platform.     

Simultaneous bioassays in a microfluidic channel on plugs of different magnetic particles

Magnetic particles coated with specific biomolecules are often used as solid supports for bioassays but conventional test tube based techniques are time consuming and labour intensive. An alternative is to work on magnetic particle plugs immobilised inside microfluidic channels. Most research so far has focussed on immobilising one type of particle to perform one type of assay. Here we demonstrate how several assays can be performed simultaneously by flushing a sample solution over several plugs of magnetic particles with different surface coatings. Within a microchannel, three plugs of magnetic particles were immobilised with external magnets. The particles featured surface coatings of glycine, streptavidin and protein A, respectively. Reagents were then flushed through the three plugs. Molecular binding occurred between matching antigens and antibodies in continuous flow and was detected by fluorescence. This first demonstration opens the door to a quicker and easier technique for simultaneous bioassays using magnetic particles.     

Shape relaxation of an elongated viscous drop

The shape relaxation of a distorted viscous drop suspended in a quiescent immiscible liquid is analyzed in the creeping flow limit. The shape of the drop is axisymmetric, but otherwise arbitrary. The relaxation process is assumed to be driven by a constant interfacial tension and rate-limited by the Newtonian viscosities of the dispersed and continuous phases. For analysis, a least squares technique is developed which, compared to the more common boundary integral methods, is simpler to implement and especially suited for systems where one liquid is much more viscous than the other (i.e., when the viscosity ratio lambda, defined as the ratio of the dispersed to continuous phase viscosities, approaches either zero or infinity). To demonstrate the validity of the proposed least squares technique, its results are shown to agree well with boundary integral calculations for moderate values of lambda, and with experimental data when lambda is much larger than unity (approximately 10(6)). Predictions at infinite viscosity ratio--the regime in which the least squares technique is most useful--are then used to evaluate interfacial tensions associated with a system of practical importance, namely, the dispersion of heavy crude oil in an aqueous environment. This amounts to a novel and accurate technique for determining interfacial tensions--especially those of low values (1 mN/m or less)--between density-matched liquids where at least one of the phases is highly viscous. The experimental part of this study involves the use of suction pipettes to manipulate the shapes of individual micrometer-sized droplets, thus avoiding the need for complex flow-generating devices to create drop deformations.     

Integrated ionic liquid-based electrofluidic circuits for pressure sensing within polydimethylsiloxane microfluidic systems

This paper reports a novel pressure sensor with an electrical readout based on electrofluidic circuits constructed by ionic liquid (IL)-filled microfluidic channels. The developed pressure sensor can be seamlessly fabricated into polydimethylsiloxane (PDMS) microfluidic systems using the well-developed multilayer soft lithography (MSL) technique without additional assembly or sophisticated cleanroom microfabrication processes. Therefore, the device can be easily scaled up and is fully disposable. The pressure sensing is achieved by measuring the pressure-induced electrical resistance variation of the constructed electrofluidic resistor. In addition, an electrofluidic Wheatstone bridge circuit is designed for accurate and stable resistance measurements. The pressure sensor is characterized using pressurized nitrogen gas and various liquids which flow into the microfluidic channels. The experimental results demonstrate the great long-term stability (more than a week), temperature stability (up to 100 °C), and linear characteristics of the developed pressure sensing scheme. Consequently, the integrated microfluidic pressure sensor developed in this paper is promising for better monitoring and for characterizing the flow conditions and liquid properties inside the PDMS microfluidic systems in an easier manner for various lab on a chip applications.     

Vortex fluidic induced mass transfer across immiscible phases

Mixing immiscible liquids typically requires the use of auxiliary substances including phase transfer catalysts, microgels, surfactants, complex polymers and nano-particles and/or micromixers. Centrifugally separated immiscible liquids of different densities in a 45° tilted rotating tube offer scope for avoiding their use. Micron to submicron size topological flow regimes in the thin films induce high inter-phase mass transfer depending on the nature of the two liquids. A hemispherical base tube creates a Coriolis force as a ‘spinning top’ (ST) topological fluid flow in the less dense liquid which penetrates the denser layer of liquid, delivering liquid from the upper layer through the lower layer to the surface of the tube with the thickness of the layers determined using neutron imaging. Similarly, double helical (DH) topological flow in the less dense liquid, arising from Faraday wave eddy currents twisted by Coriolis forces, impact through the less dense liquid onto the surface of the tube. The lateral dimensions of these topological flows have been determined using ‘molecular drilling’ impacting on a thin layer of polysulfone on the surface of the tube and self-assembly of nanoparticles at the interface of the two liquids. At high rotation speeds, DH flow also occurs in the denser layer, with a critical rotational speed reached resulting in rapid phase demixing of preformed emulsions of two immiscible liquids. ST flow is perturbed relative to double helical flow by changing the shape of the base of the tube while maintaining high mass transfer between phases as demonstrated by circumventing the need for phase transfer catalysts. The findings presented here have implications for overcoming mass transfer limitations at interfaces of liquids, and provide new methods for extractions and separation science, and avoiding the formation of emulsions.

Micron to submicron size Coriolis and Faraday wave induced high shear topological flow regimes in 45° titled rapidly rotating tubes result in high inter-phase mass transfer of immiscible liquids and spontaneous demixing.     

Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing

The design and fabrication of a multilayered polymer micro-nanofluidic chip is described that consists of poly(methylmethacrylate) (PMMA) layers that contain microfluidic channels separated in the vertical direction by polycarbonate (PC) membranes that incorporate an array of nanometre diameter cylindrical pores. The materials are optically transparent to allow inspection of the fluids within the channels in the near UV and visible spectrum. The design architecture enables nanofluidic interconnections to be placed in the vertical direction between microfluidic channels. Such an architecture allows microchannel separations within the chip, as well as allowing unique operations that utilize nanocapillary interconnects: the separation of analytes based on molecular size, channel isolation, enhanced mixing, and sample concentration. Device fabrication is made possible by a transfer process of labile membranes and the development of a contact printing method for a thermally curable epoxy based adhesive. This adhesive is shown to have bond strengths that prevent leakage and delamination and channel rupture tests exceed 6 atm (0.6 MPa) under applied pressure. Channels 100 microm in width and 20 microm in depth are contact printed without the adhesive entering the microchannel. The chip is characterized in terms of resistivity measurements along the microfluidic channels, electroosmotic flow (EOF) measurements at different pH values and laser-induced-fluorescence (LIF) detection of green-fluorescent protein (GFP) plugs injected across the nanocapillary membrane and into a microfluidic channel. The results indicate that the mixed polymer micro-nanofluidic multilayer chip has electrical characteristics needed for use in microanalytical systems.     

Continuous fabrication of biocatalyst immobilized microparticles using photopolymerization and immiscible liquids in microfluidic systems

We report a novel technique for manufacturing polymeric microparticles containing biocatalysts by the behavior of immiscible liquids in microfluidic systems and in situ photopolymerization. The approach utilizes a UV-polymerizable hydrogel/enzyme solution and an immiscible oil solution. The oil and hydrogel solutions form emulsions in pressure-driven flow in microchannels at high values of the dimensionless capillary number (Ca). The resultant hydrogel droplets are then polymerized in situ via exposure to 365 nm UV light. This technique allows for the generation of monodisperse particles whose size can be controlled by the regulation of flow rates. In addition, both manufacturing microparticles and immobilizing biocatalysts can be performed simultaneously and continuously.