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.     

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.     

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.     

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.     

Design and simulation of the micromixer with chaotic advection in twisted microchannels

Chaotic mixers with twisted microchannels were designed and simulated numerically in the present study. The phenomenon whereby a simple Eulerian velocity field may generate a chaotic response in the distribution of a Lagrangian marker is termed chaotic advection. Dynamic system theory indicates that chaotic particle motion can occur when a velocity field is either two-dimensional and time-dependent, or three-dimensional. In the present study, micromixers with three-dimensional structures of the twisted microchannel were designed in order to induce chaotic mixing. In addition to the basic T-mixer, three types of micromixers with inclined, oblique and wavelike microchannels were investigated. In the design of each twisted microchannel, the angle of the channels' bottoms alternates in each subsection. When the fluids enter the twisted microchannels, the flow sways around the varying structures within the microchannels. The designs of the twisted microchannels provide a third degree of freedom to the flow field in the microchannel. Therefore, chaotic regimes that lead to chaotic mixing may arise. The numerical results indicate that mixing occurs in the main channel and progressively larger mixing lengths are required as the Peclet number increased. The swaying of the flow in the twisted microchannel causes chaotic advection. Among the four micromixer designs, the micromixer with the inclined channel most improved mixing. Furthermore, using the inclined mixer with six subsections yielded optimum performance, decreasing the mixing length by up to 31% from that of the basic T-mixer.     

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)).     

Ultrafast active mixer using polyelectrolytic ion extractor

We report on a low voltage, straight/smooth surface, and efficient active micromixer. The mixing principle is based on alternative ion depletion-enrichment using a pair of positively charged polyelectrolytic gel electrodes (pPGEs), which face each other joined by a microchannel. This system has an external AC signal source electrically connected to the pPGEs via the respective 1 M KCl solutions and Ag/AgCl electrodes. When an electric bias is applied between the two pPGEs, anions are extracted through one of the pPGEs to create a local ion-deficient region. Simultaneously, an ion-rich area appears near the other pPGE due to an inward anionic flux. As the direction of the charge flow is periodically reversed by the AC signal source, the ion depletion-enrichment regions are alternately swapped with each other on the 'push-pull' basis. The turmoil between the pPGEs quickly mixes the solutions in the microchannel without any mechanical moving part or specially machined structures. In the proposed system, both AC frequency and current density can be easily and finely controlled so that one can quickly find the optimal conditions for a given sample. The micromixer as made showed a mixing efficiency higher than 90% for sample solutions of 1 mM Rhodamine 6G and PBS at pH 7.4 when the flow rate was under 6 mm s(-1). In addition to the solution-solution mixing, the micromixer can effectively mix suspended microparticles with solution. As a representative example, rapid and efficient lysis of human red blood cells was demonstrated allowing minimal damage of the white blood cells.     

Design and Fabrication of a Three Dimensional Spiral Micromixer

In this work, we present a three dimensional micromixer which consists of two layers of spiral channels overlapped together in the vertical direction. This micromixer is designed by using a smooth channel twisted into double‐layer spiral geometry with simple topological structure. Based on the principle of Dean effects, this kind of structure is beneficial to produce, enhance and sustain the Dean vortices, which can perturb the laminar fluid effectively. In order to improve the mixing performance, the detailed parameters have been optimized by using the computational fluid dynamics software. The results indicate that the erect channel which is connected with the two layers of spiral channels plays a critical role for well mixing. Meanwhile, the effect of mixing has been identified in a fabricated glass‐micromixer. The mixing ef?ciency of 90% has been achieved by optimizing the flow rate and the structure of the erect channel. Thus, this micromixer has manifested high mixing efficiency and presents good practicability in the versatile microfluidic systems.     

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.     

Mixing in microchannels based on hydrodynamic focusing and time-interleaved segmentation: modelling and experiment

This paper theoretically and experimentally investigates a micromixer based on combined hydrodynamic focusing and time-interleaved segmentation. Both hydrodynamic focusing and time-interleaved segmentation are used in the present study to reduce mixing path, to shorten mixing time, and to enhance mixing quality. While hydrodynamic focusing reduces the transversal mixing path, time-interleaved sequential segmentation shortens the axial mixing path. With the same viscosity in the different streams, the focused width can be adjusted by the flow rate ratio. The axial mixing path or the segment length can be controlled by the switching frequency and the mean velocity of the flow. Mixing ratio can be controlled by both flow rate ratio and pulse width modulation of the switching signal. This paper first presents a time-dependent two-dimensional analytical model for the mixing concept. The model considers an arbitrary mixing ratio between solute and solvent as well as the axial Taylor-Aris dispersion. A micromixer was designed and fabricated based on lamination of four polymer layers. The layers were machined using a CO2 laser. Time-interleaved segmentation was realized by two piezoelectric valves. The sheath streams for hydrodynamic focusing are introduced through the other two inlets. A special measurement set-up was designed with synchronization of the mixer's switching signal and the camera's trigger signal. The set-up allows a relatively slow and low-resolution CCD camera to freeze and to capture a large transient concentration field. The concentration profile along the mixing channel agrees qualitatively well with the analytical model. The analytical model and the device promise to be suitable tools for studying Taylor-Aris dispersion near the entrance of a flat microchannel.     

A novel in-plane passive microfluidic mixer with modified Tesla structures

An innovative in-plane passive micromixer using modified Tesla structures, which are used as passive valves, has been designed, simulated, fabricated and successfully characterized in this paper. Simulation and experimental results of the developed novel micromixer have shown excellent mixing performance over a wide range of flow conditions in the micro scale. The micromixer realized in this work has achieved even better mixing performance at a higher flow rate, and its pressure drop is less than 10 KPa at the flow rate of 100 microl min(-1). This micromixer shows characteristics similar to Taylor dispersion, with contributions from both diffusion and convection. The mixer has a diffusion domain region at low flow rate, but it moves to a convection domain region at high flow rate. Due to the simple in-plane structure of the novel micromixer explored in this work, the mixer can be easily realized and integrated with on-chip microfluidic devices and micro total analysis systems (micro-TAS).     

Numerical study of the vortex-induced electroosmotic mixing of non-Newtonian biofluids in a nonuniformly charged wavy microchannel: Effect of finite ion size

We propose a micromixer for obtaining better efficiency of vortex induced electroosmotic mixing of non-Newtonian bio-fluids at a relatively higher flow rate, which finds relevance in many biomedical and biological applications. To represent the rheology of non-Newtonian fluid, we consider the Carreau model in this study, while the applied electric field drives the constituent components in the micromixer. We show that the spatial variation of the applied field, triggered by the topological change of the bounding surfaces, upon interacting with the non-uniform surface potential gives rise to efficient mixing as realized by the formation of vortices in the proposed micromixer. Also, we show that the phase-lag between surface potential leads to the formation of asymmetric vortices. This behavior offers better mixing performance following the appearance of undulation on the flow pattern. Finally, we establish that the assumption of a point charge in the paradigm of electroosmotic mixing, which is not realistic as well, under-predicts the mixing efficiency at higher amplitude of the non-uniform zeta potential. The inferences of the present analysis may guide as a design tool for micromixer where rheological properties of the fluid and flow actuation parameters can be simultaneously tuned to obtain phenomenal enhancement in mixing efficiency.     

A pneumatic micromixer facilitating fluid mixing at a wide range flow rate for the preparation of quantum dots

A novel fluid micromixer based on pneumatic perturbation and passive structures was developed. This micromixer facilitates integration and is applicable to fluid mixing over a wide range of flow rates. The microfluidic mixing device consists of an S-shaped structure with two mixing chambers and two barriers, and two pneumatic chambers designed over the S-shaped channel. The performance of the micromixer for fluids with wide variation of flow rates was significantly improved owing to the integration of the pneumatic mixing components with the passive mixing structures. The mixing mechanism of the passive mixing structures was explored by numerical simulation, and the influencing factors on the mixing efficiency were investigated. The results showed that when using a gas pressure of 0.26 MPa and a 100 m-thick polydimethylsiloxane (PDMS) pneumatic diaphragm, the mixing of fluids with flow rates ranging from 1 to 650 L/min was achieved with a pumping frequency of 50 Hz. Fast synthesis of CdS quantum dots was realized using this device. Smaller particles were obtained, and the size distribution was greatly improved compared with those obtained using conventional methods.     

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.     

Electroosmotic flow mixing in zigzag microchannels

In this study we performed numerical and experimental investigations into the mixing of EOFs in zigzag microchannels with two different corner geometries, namely sharp corners and flat corners. In the zigzag microchannel with sharp corners, the flow travels more rapidly near the inner wall of the corner than near the outer wall as a result of the higher electric potential drop. The resulting velocity gradient induces a racetrack effect, which enhances diffusion within the fluid and hence improves the mixing performance. The simulation results reveal that the mixing index is approximately 88.83%. However, the sharp-corner geometry causes residual liquid or bubbles to become trapped in the channel at the point where the flow is almost stationary, when the channel is in the process of cleaning. Accordingly, a zigzag microchannel with flat-corner geometry is developed. The flat-corner geometry forms a convergent-divergent type nozzle which not only enhances the mixing performance in the channel, but also prevents the accumulation of residual liquid or bubbles. Scaling analysis reveals that this corner geometry leads to an effective increase in the mixing length. The experimental results reveal that the mixing index is increased to 94.30% in the flat-corner zigzag channel. Hence, the results demonstrate that the mixing index of the flat-corner zigzag channel is better than that of the conventional sharp-corner microchannel. Finally, the results of Taguchi analysis indicate that the attainable mixing index is determined primarily by the number of corners in the microchannel and by the flow passing height at each corner.     

Microfluidic baker's transformation device for three-dimensional rapid mixing

We developed a new passive-type micromixer based on the baker's transformation and realized a fast mixing of a protein solution, which has lower diffusion constant. The baker's transformation is an ideal mixing method, but there is no report on the microfluidic baker's transformation (MBT), since it is required to fabricate the complicated three-dimensional (3D) structure to realize the MBT device. In this note, we successfully fabricate the MBT device by using precision diamond cutting of an oxygen-free copper substrate for the mould fabrication and PDMS replication. The MBT device with 10.4 mm mixing length enables us to achieve complete mixing of a FITC solution (D = 2.6 × 10(-10) m(2) s(-1)) within 51 ms and an IgG solution (D = 4.6 × 10(-11) m(2) s(-1)) within 306 ms. Its mixing speed is 70-fold higher for a FITC solution and 900-fold higher for an IgG solution than the mixing speed by the microchannel without MBT structures. The Péclet number to attain complete mixing in the MBT device is estimated to be 6.9 × 10(4).     

A three-dimensional vortex microsystem designed and fabricated for controllable mixing

A three-dimensional micromixer is designed and fabricated by using glass-poly(dimethylsiloxane) (PDMS) hybridized materials. The improvement of the fabrication process makes the micromixer endure much higher flow rate. Based on the self-rotation effect of the fluid, the fast mixing can be achieved. The mixing process is evaluated by connecting the micromixer to a UV-Vis detector. The results show that by adjusting the infuse flow rate, the mixing process can be accurately controlled. Supported by the National Natural Science Foundation of China (Grant Nos. 20735002 & 29877019) and the Key Natural Science Foundation of Fujian Province, China (Grant No. D0520001)     

Electrokinetically-driven flow mixing in microchannels with wavy surface

This paper investigates the mixing characteristics of electrokinetically-driven flow in microchannels with different wavy surface configurations. Numerical simulations are performed to analyze the influence of the wave amplitude and the length of the wavy section on the mixing efficiency within the microchannel. Typically, straight channels have a poor mixing performance because the fluid flow is restricted to the low Reynolds number regime, and hence mixing takes place primarily as a result of diffusion effects. However, the wavy surfaces employed in the current microchannels increase the interfacial contact area between the two species in the microchannel and therefore improve the mixing efficiency. The mixing performance is further enhanced by the application of a heterogeneous charge pattern on the wavy surfaces. The numerical results show that the heterogeneous charge pattern generates flow circulations near the microchannel walls. These circulations are shown to provide an effective enhancement in the mixing performance. Overall, the present results show that the mixing performance is improved by increasing the magnitude of the heterogeneous surface zeta potential upon the wavy surface or by increasing the wave amplitude or the length of the wavy section in 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.     

Design of passive mixers utilizing microfluidic self-circulation in the mixing chamber

This paper proposes the design of a passive micromixer that utilizes the self-circulation of the fluid in the mixing chamber for applications in the Micro Total Analysis Systems (microTAS). The micromixer with a total volume of about 20 microL and consisting of an inlet port, a circular mixing chamber and an outlet port was designed. The device was actuated by a pneumatic pump to induce self-circulation of the fluid. The self-circulation phenomenon in the micromixer was predicted by the computational simulation of the microfluidic dynamics. Flow visualization with fluorescence tracer was used to verify the numerical simulations and indicated that the simulated and the experimental results were in good agreement. Besides, an index for quantifying the mixing performance was employed to compare different situations and to demonstrate the advantages of the self-circulation mixer. The mixing efficiencies in the mixer under different Reynolds numbers (Re) were evaluated numerically. The numerical results revealed that the mixing efficiency of the mixer with self-circulation was 1.7 to 2 times higher than that of the straight channel without a mixing chamber at Re= 150. When Re was as low as 50, the mixing efficiency of the mixer with self-circulation in the mixing chamber was improved approximately 30% higher than that in the straight channel. The results indicated that the self-circulation in the mixer could enhance the mixing even at low Re. The features of simple mixing method and fabrication process make this micromixer ideally suitable for microTAS applications.