Microfluidic particle sorter employing flow splitting and recombining

This paper describes an improved microfluidic device that enables hydrodynamic particle concentration and size-dependent separation to be carried out in a continuous manner. In our previous study, a method for hydrodynamic filtration and sorting of particles was proposed using a microchannel having multiple branch points and side channels, and it was applied for continuous concentration and separation of polymer particles and cells. In the current study, the efficiency of particle sorting was dramatically improved by geometrically splitting fluid flow from a main stream and recombining. With these operations, particles with diameters larger than a specific value move toward one sidewall in the mainstream. This control of particle positions is followed by the perfect particle alignment onto the sidewall, which increases the selectivity and recovery rates without using a liquid that does not contain particles. In this study, a microchannel having one inlet and five outlets was designed and fabricated. By simply introducing particle suspension into the device, concentrations of 2.1-3.0-microm particles were increased 60-80-fold, and they were collected independently from each outlet. In addition, it was demonstrated that the measured flow rates distributed into each side channel corresponded well to the theoretical values when regarding the microchannel network as a resistive circuit.     

On-chip integration of sequential ion-sensing system based on intermittent reagent pumping and formation of two-layer flow

A sequential ion-sensing system using a single microchip was successfully realized. The system developed here involves intermittent pumping of plural organic phases into a microchannel, followed by contact with a single aqueous phase to form a stable organic-aqueous two-layer flow inside the microchannel. Because the plural organic phases created by intermittent flow contain the same lipophilic pH indicator dye but different ion-selective neutral ionophores, different ions can be sequentially and selectively extracted into the different organic phases, where they can be determined by thermal lens microscopy (TLM). We used KD-A3 as the lipophilic pH indicator dye and valinomycin and DD16C5 as neutral ionophores to demonstrate sequential ion sensing of potassium and sodium ions by measuring the deprotonated dye caused by the ion extraction. The integrated microfluidic system proposed here allows multi-ion sensing, which is not easily demonstrated by conventional ion sensor technology using a solvent polymeric membrane. The minimum volume of single organic phase needed to obtain an equilibrium response without dilution by cross dispersion of two organic phases was ca. 500 nL in our system, indicating that the required amounts of expensive reagents in one measurement could be reduced to 1.7 ng and 2.8 ng for the dye and ionophore molecules, respectively.     

Separation and recovery of critical metal ions using ionic liquids

Separation and purification of critical metal ions such as rare-earth elements (REEs), scandium and niobium from their minerals is difficult and often determines if extraction is economically and environmentally feasible. Solvent extraction is a commonly used metal-ion separation process, usually favored because of its simplicity, speed and wide scope, which is why it is often employed for separating trace metals from their minerals. However, the types of solvents widely used for the recovery of metal ions have adverse environmental impact. Alternatives to solvent extraction have been explored and advances in separation technologies have shown commercial establishment of liquid membranes as an alternative to conventional solvent extraction for the recovery of metals and other valuable materials. Liquid membrane transport incorporates solvent extraction and membrane separation in one continuously operating system. Both methods conventionally use solvents that are harmful to the environment, however, the introduction of ionic liquids (ILs) over the last decade is set to minimize the environmental impact of both solvent extraction and liquid membrane separation processes. ILs are a family of organic molten salts with low or negligible vapour pressure which may be formed below 100 ℃. Such liquids are also highly thermally stable and less toxic. Their ionic structure makes them thermodynamically favorable solvents for the extraction of metallic ions. The main aim of this article is to review the current achievements in the separation of REE, scandium, niobium and vanadium from their minerals, using ILs in either solvent extraction or liquid membrane processes. The mechanism of separation using ILs is discussed and the engineering constraints to their application are identified.     

溶液中镓的提取与分离研究进展

从钢铁、有色金属、煤化工及磷化工等行业中的含镓物料中回收镓,需面临从含有多种金属离子的溶液中分离镓的问题。综述了含镓溶液中提取和分离镓的研究现状,分析和讨论了溶剂萃取、液膜萃取、萃淋树脂萃取等工艺的关键影响因素,并展望了研究趋势。溶剂萃取、液膜萃取及萃淋树脂萃取工艺皆能有效提取和分离溶液中的镓,其中协同萃取、液膜萃取及萃淋树脂萃取的选择性和萃取效率高,而且流程短、环境友好,应用前景好,是今后研究的发展方向。     

Porocritical fluid extraction from liquids using near-critical fluids

In this article, Californian-based scientist Marc Sims describes a process of liquid/liquid extraction using supercritical or near critical CO₂ as the extractant solvent in a membrane separation process. Using hollow fibre or spiral wound membranes, Sims found that the transport of solutes through a membrane in a near critical fluid resulted in highly efficient separations.     

An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications

This paper describes a prototype of an integrated fluorescence detection system that uses a microavalanche photodiode (microAPD) as the photodetector for microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The prototype device consisted of a reusable detection system and a disposable microfluidic system that was fabricated using rapid prototyping. The first step of the procedure was the fabrication of microfluidic channels in PDMS and the encapsulation of a multimode optical fiber (100-microm core diameter) in the PDMS; the tip of the fiber was placed next to the side wall of one of the channels. The optical fiber was used to couple light into the microchannel for the excitation of fluorescent analytes. The photodetector, a prototype solid-state microAPD array, was embedded in a thick slab (1 cm) of PDMS. A thin (80 microm) colored polycarbonate filter was placed on the top of the embedded microAPD to absorb scattered excitation light before it reached the detector. The microAPD was placed below the microchannel and orthogonal to the axis of the optical fiber. The close proximity (approximately 200 microm) of the microAPD to the microchannel made it unnecessary to incorporate transfer optics; the pixel size of the microAPD (30 microm) matched the dimensions of the channels (50 microm). A blue light-emitting diode was used for fluorescence excitation. The microAPD was operated in Geiger mode to detect the fluorescence. The detection limit of the prototype (approximately 25 nM) was determined by finding the minimum detectable concentration of a solution of fluorescein. The device was used to detect the separation of a mixture of proteins and small molecules by capillary electrophoresis; the separation illustrated the suitability of this integrated fluorescence detection system for bioanalytical applications.     

Sensitive gas analysis system on a microchip and application for on-site monitoring of NH3 in a clean room

A portable, highly sensitive, and continuous ammonia gas monitoring system was developed with a microfluidic chip. The system consists of a main unit, a gas pumping unit, and a computer which serves as an operation console. The size of the system is 45 cm width × 30 cm depth × 30 cm height, and the portable system was realized. A highly efficient and stable extraction method was developed by utilizing an annular gas/liquid laminar flow. In addition, a stable gas/liquid separation method with a PTFE membrane was developed by arranging a fluidic network in three dimensions to achieve almost zero dead volume at the gas/liquid extraction part. The extraction rate was almost 100% with a liquid flow rate of 3.5 μL/min and a gas flow rate of 100 mL/min (contact time of ~15 ms), and the concentration factor was 200 times by calculating the NH(3) concentration (w/w unit) in the gas and liquid phases. Stable phase separation and detection was sustained for more than 3 weeks in an automated operation, which was sufficient for the monitoring application. The lower limit of detection calculated based on a signal-to-noise ratio of 3 was 84 ppt, which showed good detectability for NH(3) analysis. We believe that our system is a very powerful tool for gas analysis due to the advantages of portable size, high sensitivity, and continuous monitoring, and it is particularly useful in the semiconductor field.     

Generation of local concentration gradients by gas-liquid contacting

We present a generic concept to create local concentration gradients, based on the absorption of gases or vapors in a liquid. A multilayer microfluidic device with crossing gas and liquid channels is fabricated by micromilling and used to generate multiple gas-liquid contacting regions, separated by a hydrophobic membrane. Each crossing can acts as both a microdosing and microstripping region. Furthermore, the liquid and gas flow rate can be controlled independently of each other. The focus of this conceptual article is on the generation of pH gradients, by locally supplying acidic or basic gases/vapors, such as carbon dioxide, hydrochloric acid, and ammonia, visualized by pH-sensitive dyes. Stationary and moving gradients are presented in devices with 500-microm channel width, depths of 200-400 microm, and lengths of multiple centimeters. It is shown that the method allows for multiple consecutive switching gradients in a single microchannel. Absorption measurements in a microcontactor with the model system CO2/water are presented to indicate the dependence of gas absorption rate on channel depth and residence time. Achievable concentration ranges are ultimately limited by the solubility of used components. The reported devices are easy to fabricate, and their application is not limited to pH gradients. Two proof of principles are demonstrated to indicate new opportunities: (i) local crystallization of NaCl using HCl vapor and (ii) consecutive reactions of ammonia with copper(II) ions in solution.     

A polymeric microfluidic chip for CE/MS determination of small molecules

A polymeric microfluidic chip made of Zeonor 1020 was fabricated using conventional embossing techniques to perform capillary electrophoresis for selected ion monitoring and selected reaction monitoring mass spectrometric detection of small molecules. A silicon master was microfabricated using photolithographic and dry etching processes. The microfluidic channel was embossed in the plastic from a silicon master. The embossed chip was thermally bonded with a Zeonor 1020 cover to form an enclosed channel. This channel (60-microm width, 20-microm depth, 2.0- and 3.5-cm length) provided capillary electrophoresis (CE) separation of polar small molecules without surface treatment of the polymer. A microsprayer coupled via a microliquid junction provided direct electrospray mass spectrometric detection of CE-separated components. An electric field of 0.5-2 kV/cm applied between the microsprayer and a separation buffer reservoir produced a separation of carnitine, acylcarnitine, and butylcarnitine with separation efficiencies ranging from 1,650 to 18,000 plates. Injection quantities of 0.2 nmol of these compounds produced a separation of the targeted polar small molecules without surface treatment of the polymer-abundant ion current signals and baseline separation of these compounds in less than 10 s. These results suggest the feasibility of polymeric chip-based devices for ion spray CE/MS applications.     

聚丙烯中空纤维膜/二(2-乙基已基)膦酸体系萃取水溶液中铜离子的研究

研究了聚丙烯中空纤维膜接触萃取器中二(2-乙基已基)磷酸萃取金属铜离子的工艺条件以及溶剂夹带,分析了原料的pH值、两相流速、有机相初始铜离子浓度以及萃取膜面积对萃取效率的影响,结果表明,两相流速、萃取膜面积对萃取率基本无影响,而水溶液的pH值和有机相初始铜离子浓度的改变使萃取率在40%～99%之间变化.这主要是由于整个萃取过程的传质阻力主要来源于D2EHPA和Cu2 的界面配位络合反应阻力,当铜浓度比较高时,传质阻力或传质系数与铜浓度无关,其值基本不变;而当铜浓度降低时,传质阻力随着铜浓度的降低而增大,传质系数则随着铜浓度的降低而减小.     

Three-layer flow membrane system on a microchip for investigation of molecular transport

A stable three-layer flow system, water/organic solvent/water, has been successfully applied for the first time in a microchannel to get rapid transport through an organic liquid membrane. In the continuous laminar flow region, the analyte (methyl red) was rapidly extracted across the microchannel from the donor to the acceptor phase through the organic solvent phase (cyclohexane). Thermal lens microscopy was used to monitor the process. The thickness of the organic phase, sandwiched by the two aqueous phases, was approximately 64 microm, and it was considered as a thin liquid organic membrane. Permeability studies showed the effects of molecular diffusion, layer thickness, and organic solvent-water partition coefficient on the molecular transport. In the microchip, complete equilibration was achieved in several seconds, in contrast to a conventionally used apparatus, where it takes tens of minutes. The thickness of the organic and aqueous boundary layers was defined as equal to the microchannel dimensions, and the organic solvent-water partition coefficient was determined on a microchip using the liquid/liquid extraction system. Experimental data on molecular transport across the organic membrane were in agreement with the calculated permeability based on the three-compartment water/organic solvent/water model. This kind of experiment can be performed only in a microspace, and the system can be considered as a potential biological membrane for future in vitro study of drug transport.     

Acoustic particle filter with adjustable effective pore size for automated sample preparation

This article presents analysis and optimization of a microfluidic particle filter that uses acoustic radiation forces to remove particles larger than a selected size by adjusting the driving conditions of the piezoelectric transducer (PZT). Operationally, the acoustic filter concentrates microparticles to the center of the microchannel, minimizing undesirable particle adsorption to the microchannel walls. Finite element models predict the complex two-dimensional acoustic radiation force field perpendicular to the flow direction in microfluidic devices. We compare these results with experimental parametric studies including variations of the PZT driving frequencies and voltages as well as various particle sizes (0.5-5.0 microm in diameter). These results provide insight into the optimal operating conditions and show the efficacy of our device as a filter with an adjustable effective pore size. We demonstrate the separation of Saccharomyces cerevisiae from MS2 bacteriophage using our acoustic device. With optimized design of our microfluidic flow system, we achieved yields of greater than 90% for the MS2 with greater than 80% removal of the S. cerevisiae in this continuous-flow sample preparation device.     

Solvent extraction applied to the recovery of heavy metals from galvanic sludge

In this study, a hydrometallurgical treatment involving the solvent extraction and recovery of some heavy metals from a sulphuric acid leach solution of galvanic sludge, using di-(2-ethylhexyl)-phosphoric acid (D2EHPA) and bis-(2,4,4-trimethylpentyl)-phosphinic acid (Cyanex 272), both diluted in kerosene, has been investigated.

The preliminary tests revealed the necessity to remove other metal species than zinc and nickel, contained in the leach solution, and therefore, processes to cement copper and precipitate chromium were then applied to finally obtain a Zn and Ni pregnant solution prior to solvent extraction. For the experimental conditions studied, Cyanex 272 showed a good recovery of Zn after the stripping stage using H₂SO₄, but D2EHPA effectively promoted a higher Zn extraction than Cyanex 272 did. The dependence of the solvent extraction method on variables such as pH, contact time and concentration of extractant, as well as the effect of different concentrations of sulphuric acid on stripping, are discussed.

The discussion also includes the previous conditions developed to separate the main interfering metallic species from the leach solution in order to improve the extraction and recovery of zinc by solvent extraction. The final objective has been to achieve a solution as pure as possible to recover nickel sulphate.     

Selective ion extraction: a separation method for microfluidic devices

A separation concept, selective ion extraction (SIE), is proposed on the basis of the combination of hydrodynamic and electrokinetic flow controls in microfluidic devices. Using a control system with multiple pressure and voltage sources, the hydrodynamic flow and electric field in any section of the microfluidic network can be set to desired values. Mixtures of compounds sent into a T-junction on a chip can be completely separated into different channels on the basis of their electrophoretic mobilities. A simple velocity balance model proved useful for predicting the voltage and pressure settings needed for separation. SIE provides a highly efficient separation with minimal additional dispersion. It is an ideal technique for high-throughput screening systems and demonstrates the power of lab-on-a-chip systems.     

Microfluidic protein preconcentrator using a microchannel-integrated nafion strip: experiment and modeling

We propose a simple microfluidic device for protein preconcentration based on the electrokinetic trapping principle. It comprises a narrow Nafion strip that is simply cut from a commercial membrane and is integrated into a molded poly(dimethylsiloxane) (PDMS) microfluidic structure using a guiding channel. Mechanically clamping the PDMS/Nafion assembly with a glass substrate results in a rapid prototypable, leak-tight, and easily disposable device. Our device preconcentrates negatively charged fluorescent proteins located at the anodic microfluidic compartment side of the Nafion strip within a few minutes and up to a concentration factor of 10(4). Moreover, we present a numerical study of the preconcentration effect by solving the coupled Poisson, Nernst-Planck, and Navier-Stokes equations for our type of device, which provides microscopic insight into the mechanism of preconcentration. The electrical field across the ion-permselective Nafion generates concentration polarization, i.e., ion depletion at the anodic side and ion enrichment at the cathodic side for both types of ions, with a local excess of mobile positive ions in the depleted concentration polarization zone, inducing a nonequilibrium electrical double layer in close proximity to the Nafion membrane. A voltage difference applied over the anodic compartment is used to generate the electrophoretic flow velocity of the negatively charged tracer biomolecules. This, in combination with the electroosmotic flow in the opposite direction, which originates from the fixed charges on the channel walls and the induced space charge near the membrane, provides the basis for the local preconcentration of the negative tracer biomolecules.     

Design and analysis of single-cell capture microfluidic device

The aim of our study was to develop microfluidic devices using microchannel technology with the capability of capturing single cells. We analyzed and compared the cell-capturing efficiencies of series-loop microchannel and parallel-loop microchannel devices that were produced using polydimethylsiloxane (PDMS). Each set of microchannels was composed of a main flow channel and several branch channels with capturing zones. The microfluidic devices were designed to use the differences in flow rates between the main flow channel and the branch channels as a means of capturing single cells based on size and sequestering them within the microstructure of multiple capture zones. The data indicated that the flow medium encountered significant resistance in the series-loop microchannel device, which resulted in an inability to hold the captured cells within any of the capture zones. Flow resistance was, however, greatly reduced in the parallel-loop microchannel device compared to the series-loop device, and single cells were captured in all the capturing zones of the device. Our data suggest that the parallel-loop microchannel technology has significant potential for development toward high-throughput platforms capable of capturing single cells for physiological analyses at the single-cell level.     

粗糙度对微流道内流体连续自搬运的影响

微流控芯片中各功能单元间样品的运输依赖于流体在微通道中的流动,尺度效应加剧表面作用效果,使得微流道内流体无需外部动力即可实现连续铺展搬运。为了深入研究微流道内流体的流动机制和动力学特性,分析影响微流道内流体自搬运效率的因素,基于近似Derjaguin法的同时充分考虑表面能和Casimir效应,利用数值计算和实验相结合的方法分析了微流道内壁粗糙度对流体流动特性和自搬运效率的影响,明确了微流道内流体的本构方程和流动控制方程,并设计搭建实验台验证所得结果的有效性和可靠性。结果表明：内壁粗糙度是影响微流道内流体流动特性和连续自搬运效率的重要因素;当粗糙度等效齿数、等效齿高和等效齿倾角变化时,微流道内近壁面齿隙间的主漩涡和伴生涡都相应改变,导致流体自搬运效率发生相应变化。研究结果对解决微流控润滑和微流控芯片减阻防粘等设计和使用问题具有重要理论指导意义,对微电子机械系统的小型化和集成化设计具有一定的参考价值。     

Thermoswitchable electrokinetic ion-enrichment/elution based on a poly(N-isopropylacrylamide) hydrogel plug in a microchannel

This paper reports a novel protocol consisting of the thermomodulated electrokinetic enrichment, elution, and separation of charged species based upon a thermoswitchable swelling-shrinking property of a poly(N-isopropylacrylamide), PNIPAAm, hydrogel. A 0.2-1 mm long PNIPAAm hydrogel plug was photopolymerized inside a glass microfluidic channel to produce a composite device consisting of the PNIPAAm hydrogel plug and the glass microchannel (abbreviated as plug-in-channel). After voltage was applied to the composite device, anions, such as FITC, could be enriched at the cathodic end of the PNIPAAm plug when the temperature of the plug was kept below its lower critical solution temperature (LCST, ～32 °C). The concentrated analytes could then be eluted by electroosmotic flow when the temperature of the plug was heated above the LCST. The mechanism of the thermoswitchable ion enrichment/elution process was studied with the results presented. The analytical potential of the composite device was demonstrated for the temperature-modulated preconcentration, elution, and separation of FITC-labeled amino acids.     

Continuous dielectrophoretic size-based particle sorting

Continuous-flow dielectrophoretic (DEP) particle separation based on size is demonstrated in a microfluidic device. Polystyrene microspheres suspended in a neutrally buoyant aqueous solution are used as model particles to study DEP induced by an array of slanted, planar, interdigitated electrodes inside of a soft-lithography microchannel. The E-field gradients from the slanted electrodes impart a net transverse force component on the particles that causes them to "ratchet" across the channel. Over the length of the device, larger particles are deflected more than smaller particles according to the balance of hydrodynamic drag and DEP forces. Consequently, a flow-focused particle suspension containing different-sized particles is fractionated as the beads flow and separate down the length of the device. The flow behavior of spherical particles is modeled, and the total transverse particle displacement in the microfluidic device predicts fourth-order size and voltage and second-order inverse flow rate dependences. The model is verified experimentally for a range of flow rates, particle sizes, and E-field strengths.     

Facilitated transport of uranium(VI) across supported liquid membranes containing T2EHDGA as the carrier extractant

Facilitated transport of uranyl ion from nitric acid feed solutions was investigated across PTFE supported liquid membranes using N,N,N',N'-tetra-2-ethylhexyl-3-pentane-diamide (T2EHDGA) in n-dodecane as the carrier extractant containing 30% iso-decanol as the phase modifier. Solvent extraction studies indicated extraction of species of the type, UO(2)(NO(3))(2)·T2EHDGA. The distribution coefficients increased in the presence of NaNO(3) as compared to equivalent concentration of HNO(3) which was exactly the opposite of what was reported for Am(III)-TODGA extraction system. Supported liquid membrane studies indicated about 11h were required for quantitative transport of U(VI) from a feed of 3M HNO(3) using 0.2M T2EHDGA in n-dodecane containing 30% iso-decanol as the carrier extractant. Effect of various parameters such as feed acidity, T2EHDGA concentration, and nature of the strippant on the transport rate was investigated. The transport was found to be diffusion controlled in the membrane phase and the permeability coefficient was calculated to be (3.20 ± 0.13)× 10(-4)cm/s for the feed composition of 3M HNO(3), receiver phase composition of 0.01 M HNO(3) and membrane carrier phase of 0.2M T2EHDGA in n-dodecane containing 30% iso-decanol. The present results may be useful for the separation of U from lean solutions or radioactive wastes considered hazardous due to the presence of alpha-particle emitting radionuclides.