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.     

A serpentine laminating micromixer combining splitting/recombination and advection

Mixing enhancement has drawn great attention from designers of micromixers, since the flow in a microchannel is usually characterized by a low Reynolds number (Re) which makes the mixing quite a difficult task to accomplish. In this paper, a novel integrated efficient micromixer named serpentine laminating micromixer (SLM) has been designed, simulated, fabricated and fully characterized. In the SLM, a high level of efficient mixing can be achieved by combining two general chaotic mixing mechanisms: splitting/recombination and chaotic advection. The splitting and recombination (in other terms, lamination) mechanism is obtained by the successive arrangement of "F"-shape mixing units in two layers. The advection is induced by the overall three-dimensional serpentine path of the microchannel. The SLM was realized by SU-8 photolithography, nickel electroplating, injection molding and thermal bonding. Mixing performance of the SLM was fully characterized numerically and experimentally. The numerical mixing simulations show that the advection acts favorably to realize the ideal vertical lamination of fluid flow. The mixing experiments based on an average mixing color intensity change of phenolphthalein show a high level of mixing performance was obtained with the SLM. Numerical and experimental results confirm that efficient mixing is successfully achieved from the SLM over the wide range of Re. Due to the simple and mass producible geometry of the efficient micromixer, SLM proposed in this study, the SLM can be easily applied to integrated microfluidic systems, such as micro-total-analysis-systems or lab-on-a-chip systems.     

Three-dimensional multihelical microfluidic mixers for rapid mixing of liquids

Rapid mixing of liquids is important for most microfluidic applications. However, mixing is slow in conventional micromixers, because, in the absence of turbulence, mixing here occurs by molecular diffusion. Recent experiments show that mixing can be enhanced by generating transient flow resulting in chaotic advection. While these are planar microchannels, here we show that three-dimensional orientations of fluidic vessels and channels can enhance significantly mixing of liquids. In particular, we present a novel, multihelical microchannel system built in soft gels, for which the helix angle, helix radius, axial length, and even the asymmetry of the channel cross section are easily tailored to achieve the desired mixing. Mixing efficiency increases with helix angle and asymmetry of channel cross section, which leads to orders of magnitude reduction in mixing length over conventional mixers. This new scheme of generating 3D microchannels will help in miniaturization of devices, process intensification, and generation of multifunctional process units for microfluidic applications.     

Rapid method for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process

We developed a facile and rapid one-step technique for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process. A laser printing mechanism was dexterously adopted to pattern the microchannels with different gray levels using vector graphic software. With the present method, periodically ordered specific bas-relief microstructures can be easily fabricated on transparencies by a simple printing process. The size and shape of the resultant microstructures are determined by the gray level of the graphic software and the resolution of the laser printer. Patterns of specific bas-relief microstructures on the floor of a channel act as obstacles in the flow path for advection mixing, which can be used as efficient mixing elements. The mixing effect of the resultant micromixer in microfluidic devices was evaluated using CCD fluorescence spectroscopy. We found that the mixing performance depends strongly on the gray level values. Under optimal conditions, fast passive mixing with our periodic ordered patterns in microfluidic devices has been achieved at the very early stages of the laminar flow. In addition, fabrication of micromixers using the present versatile technique requires less than an hour. The present method is promising for fabrication of micromixers in microfluidic devices at low cost and without complicated devices and environment, providing a simple solution to mixing problems in the micro-total-analysis-systems field.     

AC electroosmotic micromixer for chemical processing in a microchannel

A rapid micromixer of fluids in a microchannel is presented. The mixer uses AC electroosmotic flow, which is induced by applying an AC voltage to a pair of coplanar meandering electrodes configured in parallel to the channel. To demonstrate performance of the mixer, dilution experiments were conducted using a dye solution in a channel of 120 microm width. Rapid mixing was observed for flow velocity up to 12 mm s(-1). The mixing time was 0.18 s, which was 20-fold faster than that of diffusional mixing without an additional mixing mechanism. Compared with the performance of reported micromixers, the present mixer worked with a shorter mixing length, particularly at low Peclet numbers (Pe < 2 x 10(3)).     

Passive and Active Mixing in Microfluidic Devices

In microfluidics the Reynolds number is small, preventing turbulence as a tool for mixing, while diffusion is that slow that time does not yield an alternative. Mixing in microfluidics therefore must rely on chaotic advection, as well-known from polymer technology practice where on macroscale the high viscosity makes the Reynolds numbers low and diffusion slow. The mapping method is used to analyze and optimize mixing also in microfluidic devices. We investigate passive mixers like the staggered herringbone micromixer (SHM), the barrier embedded micromixer (BEM) and a three-dimensional serpentine channel (3D-SC). Active mixing is obtained via incorporating particles that introduce a hyperbolic flow in e.g. two dimensional serpentine channels. Magnetic beads chains-up in a flow after switching on a magnetic field. Rotating the field creates a physical rotor moving the flow field. The Mason number represents the ratio of viscous forces to the magnetic field strength and its value determines the fate of the rotor: a single, an alternating single and double, or a multiple part chain-rotor results. The type of rotor determines the mixing quality with best results in the alternating case where crossing streamlines introduce chaotic advection. Finally, an active mixing device is proposed that mimics the cilia in nature. The transverse flow induced by their motion indeed enhances mixing at the microscale.     

Chaotic micromixers using two-layer crossing channels to exhibit fast mixing at low Reynolds numbers

We report two chaotic micromixers that exhibit fast mixing at low Reynolds numbers in this paper. Passive mixers usually use the channel geometry to stir the fluids, and many previously reported designs rely on inertial effects which are only available at moderate Re. In this paper, we propose two chaotic micromixers using two-layer crossing channels. Both numerical and experimental studies show that the mixers are very efficient for fluid manipulation at low Reynolds numbers, such as stretching and splitting, folding and recombination, through which chaotic advection can be generated and the mixing is significantly promoted. More importantly, the generation of chaotic advection does not rely on the fluid inertial forces, so the mixers work well at very low Re. The mixers are benchmarked against a three-dimensional serpentine mixer. Results show that the latter is inefficient at Re = 0.2, while the new design exhibits rapid mixing at Re = 0.2 and at Re of O(10(-2)). The new mixer design will benefit various microfluidic systems.     

Development of a passive micromixer based on repeated fluid twisting and flattening,and its application to DNA purification

We have developed a three-dimensional passive micromixer based on new mixing principles, fluid twisting and flattening. This micromixer is constructed by repeating two microchannel segments, a “main channel” and a “flattened channel”, which are very different in size and are arranged perpendicularly. At the intersection of these segments the fluid inside the micromixer is twisted and then, in the flattened channel, the diffusion length is greatly reduced, achieving high mixing efficiency. Several types of micromixer were fabricated and the effect of microchannel geometry on mixing performance was evaluated. We also integrated this micromixer with a miniaturized DNA purification device, in which the concentration of the buffer solution could be rapidly changed, to perform DNA purification based on solid-phase extraction.     

Active mixing inside microchannels utilizing dynamic variation of gradient zeta potentials

This study presents a new active micromixer with high mixing efficiency achieved by means of a gradient distribution of the surface zeta potential controlled by changing the frequency of voltage applied on shielding electrodes. Gradient surface zeta potential is generated by applying a high voltage to inclined buried shielding electrodes. While alternating the frequency of driving voltage, the zeta potential could be changed accordingly, thus providing a significant mixing effect inside microchannels. A theoretical model is proposed to predict the distribution of zeta potential. The results from this model are critically compared with the well-developed three-capacitor model. Additionally, two time-factor scales, the charge time of capacitor and mixing length flow time, are used to predict the optimum frequency. The prediction of optimum frequency, 0.5 Hz, is consistent with experimental results. Moreover, a five-pair inclined shielding electrode with a frequency of 0.5 Hz leads to a significant improvement in the mixing performance of the active micromixer. Numerical results indicate that a localized flow circulation is generated when the control voltage is applied to the inclined shielding electrodes. Furthermore, the streamlines are experimentally observed by using fluorescent beads. The shape of this circulation is dependent on the distribution of gradient zeta potential, which is determined by the arrangement of electrodes. The effects of the number of electrode pairs and the layout of shielding electrodes on the mixing performance of micromixer are also explored both numerically and experimentally. It is revealed that five-pair inclined electrodes at 0.5 Hz provide the highest mixing efficiency. Finally, a reaction between N-benzoyl-L-arginine-p-nitroanilide and trypsin enzyme is performed to verify the capability of micromixers. The experimental results reveal that the reaction can achieve a higher performance indicating a higher mixing efficiency. The active micromixers could be used in microfluidic systems for improving the mixing efficiency and thus enhancing the bioreaction.     

Three-dimensionally crossing manifold micro-mixer for fast mixing in a short channel length

In this study, we report a neo-conceptive three-dimensionally (3D) crossing manifold micromixer (CMM) embedded in microchannel. Fabricated by sequential processes of photolithography and two photon absorption stereolithography, this leads to a microfluidic system with a built-in micromixer in a site controlled manner. The effectiveness of CMM is investigated numerically and experimentally. Through the numerical simulation, it is estimated that a high mixing ratio of 90% can be obtained even in a channel length shorter than five times the channel width. This compares well with the conventional passive type of micromixers that have a gradual increase in mixing efficiency with the length of the channel. Furthermore, the mixing performance of the realized CMM built-in microchannel is observed by confocal microscopy.     

Disposable integrated microfluidic biochip for blood typing by plastic microinjection moulding

Blood typing is the most important test for both transfusion recipients and blood donors. In this paper, a low cost disposable blood typing integrated microfluidic biochip has been designed, fabricated and characterized. In the biochip, flow splitting microchannels, chaotic micromixers, reaction microchambers and detection microfilters are fully integrated. The loaded sample blood can be divided by 2 or 4 equal volumes through the flow splitting microchannel so that one can perform 2 or 4 blood agglutination tests in parallel. For the purpose of obtaining efficient reaction of agglutinogens on red blood cells (RBCs) and agglutinins in serum, we incorporated a serpentine laminating micromixer into the biochip, which combines two chaotic mixing mechanisms of splitting/recombination and chaotic advection. Relatively large area reaction microchambers were also introduced for the sake of keeping the mixture of the sample blood and serum during the reaction time before filtering. The gradually decreasing multi-step detection microfilters were designed in order to effectively filter the reacted agglutinated RBCs, which show the corresponding blood group. To achieve the cost-effectiveness of the microfluidic biochip for disposability, the biochip was realized by the microinjection moulding of COC (cyclic olefin copolymer) and thermal bonding of two injection moulded COC substrates in mass production with a total fabrication time of less than 20 min. Mould inserts of the biochip for the microinjection moulding were fabricated by SU-8 photolithography and the subsequent nickel electroplating process. Human blood groups of A, B and AB have been successfully determined with the naked eye, with 3 microl of the whole sample bloods, by means of the fabricated biochip within 3 min.     

Passive micromixer for luminol-peroxide chemiluminescence detection

This paper reports a microchip with an integrated passive micromixer based on chaotic advection. The micromixer with staggered herringbone structures was used for luminol-peroxide chemiluminescence detection. The micromixer was examined to assess its suitability for chemiluminescence reaction. The relationship between the flow rate and the location of maximum chemiluminescence intensity was investigated. The light intensity was detected using an optical fiber attached along the mixing channel and a photon detector. A linear correlation between chemiluminescence intensity and the concentration of cobalt(ii) ions or hydrogen peroxide was observed. This microchip has a potential application in environmental monitoring for industries involved in heavy metals and in medical diagnostics.     

Toolbox for the design of optimized microfluidic components

A computational "toolbox" for the a priori design of optimized microfluidic components is presented. These components consist of a microchannel under low-Reynolds number, pressure-driven flow, with an arrangement of grooves cut into the top and bottom to generate a tailored cross-channel flow. An advection map for each feature (i.e., groove of a particular shape and orientation) predicts the lateral transport of fluid within the channel due to that feature. We show that applying these maps in sequence generates an excellent representation of the outflow distribution for complex designs that combine these basic features. The effect of the complex three-dimensional flow field can therefore be predicted without solving the governing flow equations through the composite geometry, and the resulting distribution of fluids in the channel is used to evaluate how well a component performs a specified task. The generation and use of advection maps is described, and the toolbox is applied to determine optimal combinations of features for specified mixer sizes and mixing metrics.     

Influence of micromixer characteristics on polydispersity index of block copolymers synthesized in continuous flow microreactors

The influence of interdigital multilamination micromixer characteristics on monomer conversions, molecular weights and especially on the polydispersity index of block copolymers synthesized continuously in two microtube reactors is investigated. The micromixers are used to mix, before copolymerization, a polymer solution with different viscosities and the second monomer. Different geometries of micromixer (number of microchannels, characteristic lengths) have been studied. It was found that polydispersity indices of the copolymers follow a linear relationship with the Reynolds number in the micromixer, represented by a form factor. Thus, beside the operating conditions (nature of the first block and comonomer flow rate), the choice of the micromixer geometry and dimension is essential to control the copolymerization in terms of molecular weights and polydispersity indices. This linear correlation allows the prediction of copolymer features. It can also be a new method to optimize existing micromixers or design other geometries so that mixing could be more efficient.     

Visualization and quantification of chaotic mixing for helical-type micromixers

The paper presents a micro mixer structures fabricated by an interesting technique of embedded twisted threads in polydimethylsiloxane (PDMS), which is polymerized and cured. After removing the threads carefully, the remaining channel structure is studied concerning the flows and mixing characteristics. Three-, four-, and six-strand-helical fluid microchannels (d _h ?=?100?μm, L?=?3?mm) with a specified helix angle (θ?=?22°) were used to conduct the experiments. The electroosmotic flow, inlet velocity, local velocity at specified positions, and sample concentration distribution along a downstream direction were measured via microparticle image velocimetry and laser-induced fluorescence techniques, respectively. Local mixing efficiency and mixing length were obtained at very low Reynolds numbers (≤0.0242) and low Peclet numbers (≤65.8). Results show that four-strand micromixer has the best mixing performance. Finally, a correlation of mixing length with Pe was developed, which might be applicable to a microbiomedical device design.     

Facile fabrication of a rigid and chemically resistant micromixer system from photocurable inorganic polymer by static liquid photolithography (SLP)

Highly effective mixing in microchannels is important for most chemical reactions conducted in microfluidic chips. To obtain a rigid and chemically resistant micromixer system at low cost, we fabricated a Y-shaped microchannel with built-in mixer structures by static liquid photolithography (SLP) from methacrylated polyvinylsilazane (MPVSZ) as an inorganic polymer photoresist which was then converted to a silicate phase by hydrolysis in vaporized ammonia atmosphere at 80 °C. The microchannel incorporating herringbone mixer structures was bonded with a matching polydimethylsiloxane (PDMS) open channel which was pre-coated by perhydropolysilazane (PHPS)-based mixture, and finally treated by additional hydrolysis at room temperature to convert the PHPS layer to a silica phase. Finally, the chemical resistance of the microfluidic system with embedded micromixer was confirmed with various solvents, and the excellent mixing performance in a short mixing length of 2.3 cm was demonstrated by injecting two different colored fluids into the microchannel.     

A novel 3D Tesla valve micromixer for efficient mixing and chitosan nanoparticle production

Current three-dimensional micromixers for continuous flow reactions and nanoparticle synthesis are complex in structure and difficult to fabricate. This paper investigates the design, fabrication, and characterization of a novel micromixer that uses a simple spatial Tesla valve design to achieve efficient mixing of multiple solutions. The flow characteristics and mixing efficiencies of our Tesla valve micromixer are investigated using a combination of numerical simulations and experiments. The results show that in a wide range of flow rates, viscoelastic solutions with different concentrations can be well mixed in our micromixer. Finally, experiments on the synthesis of chitosan nanoparticles are conducted to verify the practicability of our micromixer. Compared with nanoparticles prepared by conventional magnetic stirring, the size of nanoparticles prepared by micromixing is smaller and the distribution is more uniform. Therefore, our Tesla valve micromixer has significant advantages and implications for mixing chemical and biological reactions.     

An easily integrative and efficient micromixer and its application to the spectroscopic detection of glucose-catalyst reactions

The focus of this paper is on the fabrication of a PDMS-based passive efficient micromixer to be easily integrated into the other on-chip microfluidic system. The mixing is achieved by "strong stretching and folding," which employs a three-dimensional microchannel structure. By the simultaneously vertical and transversal dispersion of fluids, strong advection is developed. Owing to this powerful mixing performance (more than 70% of the mixing is accomplished within 2.3 mm over a wide range of Reynold number (Re)), the smaller integrative mixer can be realized. The feasibility and the potential usefulness of an integrative micromixer were evaluated by incorporating two mixers into the microchannel for the spectroscopic detection of a glucose-catalyst reaction. The results demonstrate a promising performance for diverse applications in the assay or synthesis of biological or chemical materials.     

Optical sectioning for microfluidics: secondary flow and mixing in a meandering microchannel

Secondary flow plays a critical function in a microchannel, such as a micromixer, because it can enhance heat and mass transfer. However, there is no experimental method to visualize the secondary flow and the associated mixing pattern in a microchannel because of difficulties in high-resolution, non-invasive, cross-sectional imaging. Here, we simultaneously imaged and quantified the secondary flow and pattern of two-liquid mixing inside a meandering square microchannel with spectral-domain Doppler optical coherence tomography. We observed an increase in the efficiency of two-liquid mixing when air was injected to produce a bubble-train flow and identified the three-dimensional enhancement mechanism behind the complex mixing phenomena. An alternating pair of counter-rotating and toroidal vortices cooperated to enhance two-liquid mixing.     

Effects of surface heterogeneity on flow circulation in electroosmotic flow in microchannels

The characteristics of electroosmotic flow in a cylindrical microchannel with non-uniform zeta potential distribution are investigated in this paper. Two-dimensional full Navier–Stokes equation is used to model the flow field and the pressure field. The numerical results show the distorted electroosmotic velocity profiles and various kinds of flow circulation resulting from the axial variation of the zeta potential. The influences of heterogeneous patterns of zeta potential on the velocity profile, the induced pressure distribution and the volumetric flow rate are discussed in this paper. This work shows that using either heterogeneous patterns of zeta potential or a combination of a heterogeneous zeta potential distribution and an applied pressure difference over the channel can generate local flow circulations and hence provide effective means to improve the mixing between different solutions in microchannels.