Micromixing of miscible liquids in segmented gas-liquid flow

We present an integrated microfluidic system that achieves efficient mixing between two miscible liquid streams by introducing a gas phase, forming a segmented gas-liquid (slug) flow, and completely separating the mixed liquid and gas streams in a planar capillary separator. The recirculation motion associated with segmented flow enhances advection in straight microchannels without requiring additional fabrication steps. Instantaneous velocity fields are quantified by microscopic particle image velocimetry (muPIV). Velocities in the direction normal to the channel amount to approximately 30% of the bulk liquid velocity inside a liquid segment. This value depends only weakly on the length of a liquid segment. Spatial concentration fields and the extent of mixing (EOM) are obtained from pulsed-laser fluorescence microscopy and confocal scanning microscopy measurements. The mixing length is reduced 2-3-fold in comparison with previously reported chaotic micromixers that use three-dimensional microchannel networks or patterned walls. Segmented gas-liquid microflows allow mixing times to be varied over several orders of magnitude between milliseconds and second time scales.     

Transpiration-inspired Capillary for Synchronous Synthesis and Patterning of Silver Nanoparticles

Traditional synthesis strategy of nanomaterials with complicated process and high cost limits their applications. Here, we propose a facile process for the synchronous synthesis and patterning of silver nanoparticles(Ag NPs) through the self-driven microchannel reactor with the capillary effect inspired by transpiration. The evaporation contributes to capillary and accumulation effects in the microchannels. The silver reactant-containing droplets can be spontaneously divided and distributed in multiple microchannels during the whole fabrication process by the capillary effect. The newly formed Ag NPs at the gas-liquid interface can be assembled on both sides of the microchannels by the accumulation effect. The capillary effect decreases the disturbances, which ensures the uniformity of the patterning. By the combination of microchannels with different widths, various Ag NPs-assembled patterns with stable electrical properties are achieved. This efficient strategy with a simple fabrication procedure is towards the technological engineering of nanoscale architected materials.     

Sustained superhydrophobic friction reduction at high liquid pressures and large flows

This Article introduces and experimentally explores a novel self-regulating method for reducing the friction losses in large microchannels at high liquid pressures and large liquid flows, overcoming previous limitations with regard to sustainable liquid pressure on a superhydrophobic surface. Our design of the superhydrophobic channel automatically adjusts the gas pressure in the lubricating air layer to the local liquid pressure in the channel. This is achieved by pneumatically connecting the liquid in the microchannel to the gas-pockets trapped at the channel wall through a pressure feedback channel. When liquid enters the feedback channel, it compresses the air and increases the pressure in the gas-pocket. This reduces the pressure drop over the gas-liquid interface and increases the maximum sustainable liquid pressure. We define a dimensionless figure of merit for superhydropbic flows, W(F) = P(L)D/γ cos(θ(c)), which expresses the fluidic energy carrying capacity of a superhydrophobic microchannel. We experimentally verify that our geometry can sustain three times higher liquid pressure before collapsing, and we measured better friction-reducing properties at higher W(F) values than in previous works. The design is ultimately limited in time by the gas-exchange over the gas-liquid interface at pressures exceeding the Laplace pressure. This method could be applicable for reducing near-wall laminar friction in both micro and macro scale flows.     

Enzymatic degradation of p-chlorophenol in a two-phase flow microchannel system

Enzymatic degradation of p-chlorophenol was carried out in a two-phase flow in a microchannel (100 microm width, 25 microm depth) fabricated on a glass plate (70 mm x 38 mm). This is the first report on the enzymatic reaction in a two-phase flow on a microfluidic device. The surface of the microchannel was partially modified with octadecylsilane groups to be hydrophobic, thus allowing clear phase separation at the end-junction of the microchannel. The enzyme (laccase), which is surface active, was solubilized in a succinic aqueous buffer and the substrate (p-chlorophenol) was in isooctane. The degradation of p-chlorophenol occurred mainly at the aqueous-organic interface in the microchannel. We investigated the effects of flow velocity and microchannel shape on the enzymatic degradation of p-chlorophenol. Assuming that diffusion of the substrate (p-chlorophenol) is the rate-limiting step in the enzymatic degradation of p-chlorophenol in the microchannel, we proposed a simple theoretical model for the degradation in the microchannel. The calculated degradation values agreed well with the experimental data.     

Microchannel wall coatings for protein separations by capillary and chip electrophoresis

The necessity for microchannel wall coatings in capillary and chip-based electrophoretic analysis of biomolecules is well understood. The regulation or elimination of EOF and the prevention of analyte adsorption is essential for the rapid, efficient separation of proteins and DNA within microchannels. Microchannel wall coatings and other wall modifications are especially critical for protein separations, both in fused-silica capillaries, and in glass or polymeric microfluidic devices. In this review, we present a discussion of recent advances in microchannel wall coatings of three major classes--covalently linked polymeric coatings, physically adsorbed polymeric coatings, and small molecule additives. We also briefly review modifications useful for polymeric microfluidic devices. Within each category of wall coatings, we discuss those used to eliminate EOF, to tune EOF, to prevent analyte adsorption, or to perform multiple functions. The knowledgeable application of the most promising recent developments in this area will allow for the separation of complex protein mixtures and for the development of novel microchannel wall modifications.     

Patterning of a random copolymer of poly[lactide-co-glycotide-co-(epsilon-caprolactone)] by UV embossing for tissue engineering

The random copolymer, poly[lactide-co-glycotide-co-(epsilon-caprolactone)] (PLGACL) diacrylate was prepared by ring-opening polymerization of L-lactide, glycolide, and epsilon-caprolactone initiated with tetra(ethylene glycol). The diacrylated polymers were extensively characterized. With a UV embossing method, these copolymers were successfully fabricated into microchannels separated by microwalls with a high aspect (height/width) ratio. The PLGACL network films showed good cytocompatibility. Varieties of microstructures were fabricated, such as 10 x 40 x 60, 10 x 80 x 60, 25 x 40 x 60, or 25 x 80 x 60 microm(3) structures (microwall width x microchannel width x microwall height). The results demonstrated that smooth muscle cells (SMCs) can grow not only on the microchannel surfaces but also on the surfaces of the microwall and sidewall. The SMCs aligned along the 25 microm wide microwall with an elongated morphology and proliferated very slowly in comparison to those on the smooth surface with a longer cell-culture term. Few cells could attach and spread on the surface of the 40 microm wide microchannel, while the cells flourished on the 80 microm, or more than 80 microm, wide microchannel with a spindle morphology. The biophysical mechanism mediated by the micropattern geometry is discussed. Overall, the present micropattern, consisting of biodegradable and cytocompatible PLGACL, provides a promising scaffold for tissue engineering.     

Continuous particle separation in spiral microchannels using Dean flows and differential migration

Microparticle separation and concentration based on size has become indispensable in many biomedical and environmental applications. In this paper we describe a passive microfluidic device with spiral microchannel geometry for complete separation of particles. The design takes advantage of the inertial lift and viscous drag forces acting on particles of various sizes to achieve differential migration, and hence separation, of microparticles. The dominant inertial forces and the Dean rotation force due to the spiral microchannel geometry cause the larger particles to occupy a single equilibrium position near the inner microchannel wall. The smaller particles migrate to the outer half of the channel under the influence of Dean forces resulting in the formation of two distinct particle streams which are collected in two separate outputs. This is the first demonstration that takes advantage of the dual role of Dean forces for focusing larger particles in a single equilibrium position and transposing the smaller particles from the inner half to the outer half of the microchannel cross-section. The 5-loop spiral microchannel 100 microm wide and 50 microm high was used to successfully demonstrate a complete separation of 7.32 microm and 1.9 microm particles at Dean number De = 0.47. Analytical analysis supporting the experiments and models is also presented. The simple planar structure of the separator offers simple fabrication and makes it ideal for integration with on-chip microfluidic systems, such as micro total analysis systems (muTAS) or lab-on-a-chip (LOC) for continuous filtration and separation applications.     

Pressure drop of slug flow in microchannels with increasing void fraction: experiment and modeling

Pressure drop in a gas-liquid slug flow through a long microchannel of rectangular cross-section was investigated. Pressure measurements in a lengthy (～0.8 m) microchannel determined the pressure gradient to be constant in a flow where gas bubbles progressively expanded and the flow velocity increased due to a significant pressure drop. Most of the earlier studies of slug flow in microchannels considered systems where the expansion of the gas bubbles was negligible in the channel. In contrast, we investigated systems where the volume of the gas phase increased significantly due to a large pressure drop (up to 1811 kPa) along the channel. This expansion of the gas phase led to a significant increase in the void fraction, causing considerable flow acceleration. The pressure drop in the microchannel was studied for three gas-liquid systems; water-nitrogen, dodecane-nitrogen, and pentadecane-nitrogen. Inside the microchannel, local pressure was measured using a series of embedded membranes acting as pressure sensors. Our investigation of the pressure drop showed a linear trend over a wide range of void fractions and flow conditions in the two-phase flow. The lengths and the velocities of the liquid slugs and the gas bubbles were also studied along the microchannel by employing a video imaging technique. Furthermore, a model describing the gas-liquid slug flow in a long microchannel was developed to calculate the pressure drop under conditions similar to the experiments. An excellent agreement between the developed model and the experimental data was obtained.     

Micro-magnetic particles frit for capillary electrochromatography

This paper presents a new method for making frit using soft-ferrite-based micro-magnetic particles (MMPs) in a micro-space, such as in a capillary tube. The MMPs-frit was made by injecting an aliquot of 10 microm (outer diameter; o.d.)-MMPs-suspension in methanol (ca. 1mg/ml) into a capillary tube (75 microm inner diameter (i.d.) x 375 microm o.d. x ca. 35 cm length) that was already sandwiched between a pair of cylindrical Neodium (Nd-Fe-B) magnets (1.5 mm o.d. x 1.5 mm height, 280 mT) at a position where the frit was made. The MMPs were trapped in the capillary tube as a frit due to the attraction of the magnets placed at surface on the capillary tube. With regard to durability, the frit was stable for methanol flow with a flow rate of 400 microl/min at room temperature. Using such a frit, a capillary column (20 cm long) was prepared by injecting a 5 microm (o.d.)-ODS-particle suspension in methanol (ca. 0.4 mg/microl) into the capillary tube. The MMPs-frits-ODS-packed column was stable for methanol for a flow pressure less than 20MPa. When comparing the present column with a conventional sintered-frits-ODS-packed column for the purposes of separating five kinds of biogenic amines by means of an on-column derivatization capillary electrochromatography (CEC), the performance of the MMPs-frits capillary column was almost equivalent to that of the sintered-frits-ODS-packed column.     

A simple microfluidic chlorine gas sensor based on gas-liquid chemiluminescence of luminol-chlorine system

In this work, a microfluidic chlorine gas sensor based on gas-liquid interface absorption and chemiluminescence detection was described. The liquid chemiluminescence reagent-alkaline luminol solution can be stably sandwiched between two convex halves of a microchannel by surface tension. When chlorine gas was introduced into the micro device, it was dissolved into the interfacial luminol solution and transferred to ClO(-), and simultaneously luminol was excited and chemiluminescence emitted. The emitted chemiluminescence light was perpendicularly detected by a photomultiplier tube on a certain detection region. The remarkable advantage of the detection system is that both adsorption and detection were carried out at the gas-liquid interface, which avoids the appearance of bubbles. The whole analytical cycle including filling CL reagent, sample injection, CL detection and emptying the device was as short as 30 s. The linear concentration range of chlorine gas detection with direct introduction of sample method is from 0.5 to 478 ppm. The detection limit of this method is 0.2 ppm for standard chlorine gas and the relative standard deviation of five determinations of 3.19 ppm spiked chlorine sample was 5.2%.     

A method for simultaneously determining the zeta potentials of the channel surface and the tracer particles using microparticle image velocimetry technique

The zeta potentials of channel surfaces and tracer particles are of importance to the design of electrokinetic microfluidic devices, the characterization of channel materials, and the quantification of the microparticle image velocimetry (microPIV) measurement of EOFs. A method is proposed to simultaneously measure the zeta potentials of the channel surface and the tracer particles in aqueous solutions using the microPIV technique. Through the measurement of the steady velocity distributions of the tracer particles in both open- and closed-end rectangular microchannels under the same water chemistry condition, the electrophoretic velocity of the tracer particles and the EOF field of the microchannel are determined using the expressions derived in this study for the velocity distributions of charged tracer particles in the open- and closed-end rectangular microchannels. Thus, the zeta potentials of the tracer particles and the channel surfaces are simultaneously obtained using the least-square method to fit the microPIV measured velocity distribution of the tracer particles. Measurements were carried out with a microPIV system to determine the zeta potentials of the channel wall and the fluorescent tracer particles in deionized water and sodium chloride and boric acid solutions of various concentrations.     

Faster and improved microchip electrophoresis using a capillary bundle

Joule heating generated in CE microchips is known to affect temperature gradient, electrophoretic mobility, diffusion of analytes, and ultimately the efficiency and reproducibility of the separation. One way of reducing the effect of Joule heating is to decrease the cross-section area of microchannels. Currently, due to the limit of fabrication technique and detection apparatus, the typical dimensions of CE microchannels are in the range of 50-200 microm. In this paper, we propose a novel approach of performing microchip CE in a bundle of extremely narrow channels by using photonic crystal fiber (PCF) as separation column. The PCF was simply encapsulated in a poly(methyl methacrylate) (PMMA) microchannel right after a T-shaped injector. CE was simultaneously but independently carried out in 54 narrow capillaries, each capillary with diameter of 3.7 microm. The capillary bundle could sustain high electric field strength up to 1000 V/cm due to efficient heat dissipation, thus faster and enhanced separation was attained.     

Supercooled micro flows and application for asymmetric synthesis

Supercooled micro flow in microchannels was demonstrated. In order to clarify fundamental properties of the supercooling state in microchannels, freezing temperature was measured in the microchannels having widths ranging from 70 microm to 300 microm. The freezing temperature decreased with decreasing width of the microchannel when the microchannel wall was chemically modified with octadecylsilane group. The lowest freezing temperature was observed as -28 degrees C for water in the 70 microm wide microchannel. By contrast, the freezing temperature was -15 degrees C and did not depend on width when a microchannel with a bare glass surface was used. Next, the freezing point was measured with flow rates ranging from 0.1 to 2.0 microl min(-1) and no dependence on flow rate was observed. Then, the supercooled micro flow was applied to an asymmetric reaction in micro two-phase flow of aqueous and CH2Cl2 phases. As expected from thermodynamic prediction, enantiomeric selectivity increased in the supercooled state of water.     

Surface modification of polymer microfluidic devices using in-channel atom transfer radical polymerization

In-channel atom transfer radical polymerization (ATRP) was used to graft a PEG layer on the surface of microchannels formed in poly(glycidyl methacrylate)-co-(methyl methacrylate) (PGMAMMA) microfluidic devices. The patterned and cover plates were first anchored with ATRP initiator and then thermally bonded together, followed by pumping a solution containing monomer, catalyst, and ligand into the channel to perform ATRP. A PEG-functionalized layer was grafted on the microchannel wall, which resists protein adsorption. X-ray photoelectron spectroscopy (XPS) was used to investigate the initiator-bound surface, and EOF was measured to evaluate the PEG-grafted PGMAMMA microchannel. Fast, efficient, and reproducible separations of amino acids, peptides, and proteins were obtained using the resultant microdevices. Separation efficiencies were higher than 1.0x10(4) plates for a 3.5 cm separation microchannel. Compared with microdevices modified using a previously reported ATRP technique, these in-channel modified microdevices demonstrated better long-term stability.     

Confinement effects on the morphology of photopatterned porous polymer monoliths for capillary and microchip electrophoresis of proteins

We find that the morphology of porous polymer monoliths photopatterned within capillaries and microchannels is substantially influenced by the dimensions of confinement. Porous polymer monoliths were prepared by UV-initiated free-radical polymerization using either the hydrophilic or hydrophobic monomers 2-hydroxyethyl methacrylate or butyl methacrylate, cross-linker ethylene dimethacrylate and different porogenic solvents to produce bulk pore diameters between 3.2 and 0.4 microm. The extent of deformation from the bulk porous structure under confinement strongly depends on the ratio of characteristic length of the confined space to the monolith pore size. The effects are similar in cylindrical capillaries and D-shaped microfluidic channels. Bulk-like porosity is observed for a confinement dimension to pore size ratio >10, and significant deviation is observed for a ratio <5. At the extreme limit of deformation a smooth polymer layer 300 nm thick is formed on the surface of the capillary or microchannel. Surface tension or wetting also plays a role, with greater wetting enhancing deformation of the bulk structure. The films created by extreme deformation provide a rapid and effective strategy to create robust wall coatings, with the ability to photograft various surface chemistries onto the coating. This approach is demonstrated through cationic films used for electroosmotic flow control and neutral hydrophilic coatings for electrophoresis of proteins.     

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.     

A novel microfluidic concept for bioanalysis using freely moving beads trapped in recirculating flows

There are only a few examples in which beads are employed for heterogeneous assays on microfluidic devices, because of the difficulties associated with packing and handling these in etched microstructures. This contribution describes a microfluidic device that allows the capture, preconcentration, and controlled manipulation of small beads (<6 microm) in etched microchannels using fluid flows only. The chips feature planar diverging and converging channel elements connected by a narrow microchannel. Creation of bi-directional liquid movement by opposing electro-osmotic and pressure-driven flows can lead to the generation of controlled recirculating flow at these elements. Small polymer beads can actually be captured in the controlled rotating flow patterns. The clusters of freely moving beads that result can be perfused sequentially with different solutions. A preliminary binding curve was determined for the reaction of streptavidin-coated beads and fluorescein-labelled biotin, demonstrating the potential of this bead-handling approach for bioanalysis.     

A parametric study of human fibroblasts culture in a microchannel bioreactor

The culture of cells in a microbioreactor can be highly beneficial for cell biology studies and tissue engineering applications. The present work provides new insights into the relationship between cell growth, cell morphology, perfusion rate, and design parameters in microchannel bioreactors. We demonstrate the long-term culture of mammalian (human foreskin fibroblasts, HFF) cells in a microbioreactor under constant perfusion in a straightforward simple manner. A perfusion system was used to culture human cells for more than two weeks in a plain microchannel (130 microm x 1 mm x 2 cm). At static conditions and at high flow rates (>0.3 ml h(-1)), the cells did not grow in the microchannel for more than a few days. For low flow rates (<0.2 ml h(-1)), the cells grew well and a confluent layer was obtained. We show that the culture of cells in microchannels under perfusion, even at low rates, affects cell growth kinetics as well as cell morphology. The oxygen level in the microchannel was evaluated using a mass transport model and the maximum cell density measured in the microchannel at steady state. The maximum shear stress, which corresponds to the maximum flow rate used for long term culture, was 20 mPa, which is significantly lower than the shear stress cells may endure under physiological conditions. The effect of channel size and cell type on long term cell culture were also examined and were found to be significant. The presented results demonstrate the importance of understanding the relationship between design parameters and cell behavior in microscale culture system, which vary from physiological and traditional culture conditions.     

Microfluidic flow control on charged phospholipid polymer interface

A type of charged phospholipid polymer biointerface was constructed on a quartz microfluidic chip to control the electroosmotic flow (EOF) and to suppress non-specific protein adsorption through one-step modification. A negatively charged phospholipid copolymer containing 2-methacryloyloxyethyl phosphorylcholine (MPC), n-butyl methacrylate (BMA), potassium 3-methacryloyloxypropyl sulfonate (PMPS) and 3-methacryloxypropyl trimethoxysilane (MPTMSi) moieties (referred to as PMBSSi) was synthesized to introduce such phosphorylcholine segments as well as surface charges onto the silica-based microchannels via chemical bonding. At neutral pH, the homogenous microchannel surface modified with 0.3 wt% PMBSSi in alcoholic solution, retained a significant cathodic EOF ((1.0 +/- 0.1) x 10(-4) cm(2) V(-1) s(-1)) with approximately one-half of the EOF of the unmodified microchannel ((1.9 +/- 0.1) x 10(-4) cm(2) V(-1) s(-1)). Along with another non-charged copolymer (poly(MPC-co-MPTMSi), PMSi), the regulation of the surface charge density can be realized by adjusting the concentration of PMBSSi or PMSi initial solutions for modification. Coincidently, the zeta-potential and the EOF mobility at neutral pH showed a monotonically descending trend with the decrease in the charge densities on the surfaces. This provides a simple but feasible approach to controlling the EOF, especially with regard to satisfying the requisites of miniaturized systems for biological applications requiring neutral buffer conditions. In addition, the EOF in microchannels modified with PMBSSi and PMSi could maintain stability for a long time at neutral pH. In contrast to the EOF in the unmodified microchannel, the EOF in the modified microchannel was only slightly affected by the change in pH (from 1 to 10). Most importantly, although PMBSSi possesses negative charges, the non-specific adsorptions of both anionic and cationic proteins (considering albumin and cytochrome c, respectively, as examples) were effectively suppressed to a level of 0.15 microg cm(-2) and lesser in the case of the 0.3 wt% PMBSSi modification. Consequently, the variation in the EOF mobility resulting from the protein adsorption was also suppressed simultaneously. To facilitate easy EOF control with compatibility to biomolecules delivered in the microfluidic devices, the charged interface described could provide a promising option.