A picoliter-volume mixer for microfluidic analytical systems

Mixing confluent liquid streams is an important, but difficult operation in microfluidic systems. This paper reports the construction and characterization of a 100-pL mixer for liquids transported by electroosmotic flow. Mixing was achieved in a microfabricated device with multiple intersecting channels of varying lengths and a bimodal width distribution. All channels running parallel to the direction of flow were 5 microm in width whereas larger 27-microm-width channels ran back and forth through the parallel channel network at a 45 degrees angle. The channel network composing the mixer was approximately 10 microm deep. It was observed that little mixing of the confluent solvent streams occurred in the 100-microm-wide, 300-microm-long mixer inlet channel where mixing would be achieved almost exclusively by diffusion. In contrast, after passage through the channel network in the approximately 200-microm-length static mixer bed, mixing was complete as determined by confocal microscopy and CCD detection. Theoretical simulations were also performed in an attempt to describe the extent of mixing in microfabricated systems.     

Improvements in mixing time and mixing uniformity in devices designed for studies of protein folding kinetics

Using a microfluidic laminar flow mixer designed for studies of protein folding kinetics, we demonstrate a mixing time of 1 +/- 1 micros with sample consumption on the order of femtomoles. We recognize two limitations of previously proposed designs: (1) size and shape of the mixing region, which limits mixing uniformity and (2) the formation of Dean vortices at high flow rates, which limits the mixing time. We address these limitations by using a narrow shape-optimized nozzle and by reducing the bend of the side channel streamlines. The final design, which combines both of these features, achieves the best performance. We quantified the mixing performance of the different designs by numerical simulation of coupled Navier-Stokes and convection-diffusion equations and experiments using fluorescence resonance energy-transfer (FRET)-labeled DNA.     

An externally driven magnetic microstirrer

In this paper, an inexpensive, easy-to-fabricate active magnetic mixer is presented. This mixer functions on top of a common magnetic stir plate and is capable of mixing two streams, each at flow rates up to 5 ml min(-1). A liquid-phase photopolymerization technique is used to fabricate the device. An analysis of mixing efficiency is based on greyscale intensity measurements of two coloured streams passing through the mixer. A brief hypothesis of the mechanism of mixing is also presented.     

Optimization of a microfluidic mixer for studying protein folding kinetics

We have applied an optimization method in conjunction with numerical simulations to minimize the mixing time of a microfluidic mixer developed for protein folding studies. The optimization method uses a semideterministic algorithm to find the global minimum of the mixing time by varying the mixer geometry and flow conditions. We describe the minimization problem and constraints and give a brief overview of the optimization algorithm. We present results of the optimization, including the optimized geometry and parameter sensitivities, and we demonstrate the improvement in mixing performance with experiments using microfabricated mixers. The dye-quenching experiments of the original and optimized mixer designs show respective mixing times of 7 and 4 mus, a 40% reduction. The new design also provides more uniform mixing across streamlines that enter the mixer. The optimized mixer is the fastest reported continuous flow mixer for protein folding.     

Ultrasonic mixing in microfluidic channels using integrated transducers

This paper presents a microfluidic mixer that uses acoustic stirring created by ultrasonic waves. The ultrasound is introduced into the channel by integrated piezoelectric transducers. The transducers are made of a zinc oxide thin film, which is deposited on the bottom surface of a quartz substrate. The poly(dimethylsiloxane) channel is aligned to the transducers on the top surface of the substrate. The transducers are designed for operation around 450 MHz. The main mechanism of the mixing is the acoustic stirring of the fluid perpendicular to the flow direction. The radiation pressure that is generated by the transducer causes the stirring inside the microfluidic channel. The performance of the mixer is characterized by mixing phenolphthalein solution and sodium hydroxide dissolved in ethyl alcohol. Flow rates on the order of 1-100 microL/min are used. The transducers are driven by 1.2 V(rms) sinusoidal voltages at 450 MHz.     

通道式微混合器的设计及性能

利用计算流体力学和数字图像处理技术,研究"Y"型通道式微混合器的结构及混合性能,分析了混合器结构尺寸和流动条件对混合过程的影响.数值模拟结果表明,在混合通道入口夹角为60°、通道宽度为200μm、注入速度为0.02 m/s的流动条件下,可以取得比较满意的混合效果.利用数值模拟对比了扭曲通道混合器、导流块和直通道结构对混合过程的影响,结果表明使用导流块可以显著提高混合效果.依照模拟计算结果,设计并用MEMS工艺制作了双侧壁有内肋块的通道式微混合器,并进行了流体混合实验,观测了混合过程.拍摄混合实验图像,对比标准浓度-图像灰度关系曲线后识别出拍摄点混合指数.识别计算的结果也证实了所设计混合器性能上的优越性.最后对实验结果误差进行了分析,说明了误差来源并给出了相应的改进措施.     

Analysis of passive mixing behavior in a poly(dimethylsiloxane) microfluidic channel using confocal fluorescence and Raman microscopy

Confocal fluorescence microscopy (CFM) and confocal Raman microscopy (CRM) have been applied to monitor the laminar flow mixing behavior in a poly(dimethylsiloxane) (PDMS) microfluidic channel. Two passive PDMS micromixing devices were fabricated for this purpose: a two-dimensional round-wave channel and a three-dimensional serpentine channel. The microscale laminar flow mixing of ethanol and isopropanol was evaluated using the CFM and CRM at various flow rates. The mixing behavior of confluent streams in the microchannel was assessed by determining the degree of color change in Rhodamine 6G dye on mixing using the CFM. However, it was also possible to quantitatively evaluate the mixing process without employing a fluorescence label using the CRM. The results show a strong potential for CRM as a highly sensitive detection tool to measure fundamental fluid mixing processes and to provide detailed information on chemical changes of non-fluorescent reaction mixtures in a PDMS microfluidic channel.     

Design and Numerical Simulation of a Gas Mixer

A high precision gas mixer used to mix gases of small flow rapidly and uniformly was proposed in this paper. Nine simulation schemes were proposed based on orthogonal test. There were four factors including dilute gas flow rate, the length of mixing tube, the diameter of the mixing chamber and the width of the mixing chamber in orthogonal test and each factor had three levels. The numerical simulation was carried out to explore the relationship of the flow field and the four factors and to calculate the concentration of carbon monoxide at the mixer’s outlet. The primary factor that affected the mixing effectiveness was found out by means of range analysis. The heterogeneous degree of the distribution of carbon monoxide concentration at the mixer’s outlet was smaller than 0.002 under different conditions. The results reached uniform micromixing in engineering and met the requirement of measurement and detection.     

Mixing in the shear superposition micromixer: three-dimensional analysis

In this paper, we analyse mixing in an active chaotic advection micromixer. The micromixer consists of a main rectangular channel and three cross-stream secondary channels that provide ability for time-dependent actuation of the flow stream in the direction orthogonal to the main stream. Three-dimensional motion in the mixer is studied. Numerical simulations and modelling of the flow are pursued in order to understand the experiments. It is shown that for some values of parameters a simple model can be derived that clearly represents the flow nature. Particle image velocimetry measurements of the flow are compared with numerical simulations and the analytical model. A measure for mixing, the mixing variance coefficient (MVC), is analysed. It is shown that mixing is substantially improved with multiple side channels with oscillatory flows, whose frequencies are increasing downstream. The optimization of MVC results for single side-channel mixing is presented. It is shown that dependence of MVC on frequency is not monotone, and a local minimum is found. Residence time distributions derived from the analytical model are analysed. It is shown that, while the average Lagrangian velocity profile is flattened over the steady flow, Taylor-dispersion effects are still present for the current micromixer configuration.     

3D Printed Microfluidic Mixers—A Comparative Study on Mixing Unit Performances

One of the basic operations in microfluidic systems for biological and chemical applications is the rapid mixing of different fluids. However, flow profiles in microfluidic systems are laminar, which means molecular diffusion is the only mixing effect. Therefore, mixing structures are crucial to enable more efficient mixing in shorter times. Since traditional microfabrication methods remain laborious and expensive, 3D printing has emerged as a potential alternative for the fabrication of microfluidic devices. In this work, five different passive micromixers known from literature are redesigned in comparable dimensions and manufactured using high‐definition MultiJet 3D printing. Their mixing performance is evaluated experimentally, using sodium hydroxide and phenolphthalein solutions, and numerically via computational fluid dynamics. Both experimental and numerical analysis results show that HC and Tesla‐like mixers achieve complete mixing after 0.99 s and 0.78 s, respectively, at the highest flow rate (Reynolds number (Re) = 37.04). In comparison, Caterpillar mixers exhibit a lower mixing rate with complete mixing after 1.46 s and 1.9 s. Furthermore, the HC mixer achieves very good mixing performances over all flow rates (Re = 3.7 to 37.04), while other mixers show improved mixing only at higher flow rates.     

Comparative study of rhomboidal mixing sections using the boundary element method

The rhomboidal mixing section is becoming very popular in polymer extrusion to provide distributive mixing. Currently, several different designs are used but the details of the flow behavior and mixing efficiency is not well understood. This information is needed to be able to design and find the most efficient rhomboid geometry. In this research, nine different geometries with various pitches (helix of rhomboids) are analyzed using a three-dimensional boundary element method (BEM). The geometries are compared according to mixing efficiency, pressure and energy consumption. The investigation led to the conclusion that the most effective distributive mixing sections were the ones with neutral rhomboids (pineapple mixer). However, the neutral rhomboidal mixing section consumes the most pressure in the extruder.     

Mixing processes in a zigzag microchannel: finite element simulations and optical study

A finite element model has been used in order to study the mixing process of species in a 100-microm-wide zigzag microchannel integrating a "Y" inlet junction. The distribution of the concentration was obtained by solving successively the Navier-Stokes equation and the diffusion-convection equation in the steady state form. Because of the large range of Reynolds numbers studied (1 < Re < 800), the 2D diffusion-convection simulations are carried out with high diffusion coefficients. The results illustrated the effects of both flow rate and channel geometry on hydrodynamics and mixing efficiency. Below a critical Reynolds number of approximately 80, the mixing is entirely ensured by molecular diffusion. For higher Reynolds numbers, simulations revealed the mixing contribution of laminar flow recirculations. This effect increases for lower values of diffusion coefficients. Experimental studies on the mixing of species at different flow rates are reported showing the same hydrodynamic tendency.     

Acoustophoresis in wet-etched glass chips

Acoustophoresis in microfluidic structures has primarily been reported in silicon microfabricated devices. This paper demonstrates, for the first time, acoustophoresis performed in isotropically etched glass chips providing a performance that matches that of the corresponding silicon microdevices. The resonance mode characteristics of the glass chip were equal to those of the silicon chip at its fundamental resonance. At higher order resonance modes the glass chip displays resonances at lower frequencies than the silicon chip. The cross-sectional profiles of acoustically focused particle streams are also reported for the first time, displaying particles confined in a vertical band in the channel center for both glass and silicon chips. A particle extraction efficiency of 98% at flow rates up to 200 microL/min (2% particle concentration) is reported for the glass chip at the fundamental resonance. The glass and silicon chips displayed equal particle extraction performance when tested for increasing particle concentrations of 2-15%, at a flow velocity of 12.9 cm/s for the glass chip and 14.8 cm/s for the silicon chip.     

Electrokinetic fluid control in two-dimensional planar microfluidic devices

We present microfluidic device designs with a two-dimensional planar format and methods to facilitate efficient sample transport along both dimensions. The basic device design consisted of a single channel for the first dimension which orthogonally intersected a high-aspect ratio second-dimension channel. To minimize dispersion of sample moving into and through the sample transfer region, control channels were placed on both sides of the first-dimension channel, and the electrokinetic flow from these control channels was used to confine the sample stream. We used SIMION and COMSOL simulations of the electric fields and fluid flow to guide device design. First, devices with one, two, and four control channels were fabricated and tested, and four control channels provided the most effective sample confinement. The designs were evaluated by measuring the sample stream widths and concentration to width ratios as a function of the electric field strength ratio in the control channels and first-dimension (1D) channel (EC/E1D). Next, both a single open channel and an array of parallel channels were tested for the second dimension, and improved performance was observed for the parallel channel design, with stream widths as narrow as 120 microm. The ease with which fluids could be introduced into both the first and second dimensions was also illustrated. Sample plugs injected into the planar region were confined as effectively as sample streams and were easily routed into the planar region by reconfiguring the applied potentials.     

Investigation of the staggered herringbone mixer with a simple analytical model

An analytical model is presented for the three-dimensional flow in the recently introduced staggered herringbone mixer for microchannels. In this model, the flow in the cross-section of the channel is treated as a lid-driven cavity flow. The model is shown to reproduce the advection patterns that were observed experimentally in the staggered herringbone mixer. The model is then used to study the quality of mixing in this flow as a function of geometry. Analysis is performed with Poincaré maps, mixing simulations, and residence time distributions. A range of optimal geometries is identified.     

IMPINGEMENT CASTING PROCESS: TURBULENT MIXING IN AN IMPINGEMENT MIXER

Theoretical analysis for turbulent mixing in an isotropic turbulent field was carried out. Depending on the material properties and flow field, either viscous shear force or dynamic pressure force breaks-up the globules. From an order of magnitude analysis, generalized equations for predicting globule sizes were derived. Experimental work on turbulent impingement mixing of kerosene and water revealed that macromixing and micromixing vary dramatically depending on the mixing chamber geometry. Best mixing (fast macromixing and small globule sizes) was obtained in an arrow shaped mixing chamber where the incoming jets were opposite to each other and slanted upward toward the mixing head. The coefficients of the equation for predicting the maximum globule size of immiscible liquids were obtained from the experimental results of arrow-shaped impingement mixers.     

Time-resolved Fourier transform infrared spectroscopy of chemical reactions in solution using a focal plane array detector

A Fourier transform infrared (FT-IR) microscope equipped with a single as well as a 64 x 64 element focal plane array MCT detector was used to measure chemical reaction taking place in a microstructured flow cell designed for time-resolved FT-IR spectroscopy. The flow cell allows transmission measurements through aqueous solutions and incorporates a microstructured mixing unit. This unit achieves lamination of the two input streams with a cross-section of 300 x 5 microm each, resulting in fast diffusion-controlled mixing of the two input streams. Microscopic measurement at defined positions along the outlet channel allows time-resolved information of the reaction taking place in the flow cell to be obtained. In this paper we show experimental results on the model reaction between formaldehyde and sulfite. Using the single-point MCT detector, high-quality FT-IR spectra could be obtained from a spot size of 80 x 200 microm whereas the FPA detector allowed recording light from an area of 260 x 260 microm focused on its 64 x 64 detector elements. Therefore, more closely spaced features could be discerned at the expense of a significantly lower signal-to-noise (S/N) ratio per spectrum. Multivariate curve resolution-alternating least squares was used to extract concentration profiles of the reacting species along the outlet channel axis.     

Ultrafast microfluidic mixer and freeze-quenching device

The freeze-quenching technique is extremely useful for trapping meta-stable intermediates populated during fast chemical or biochemical reactions. The application of this technique, however, is limited by the long mixing time of conventional solution mixers and the slow freezing time of cryogenic fluids. To overcome these problems, we have designed and tested a novel microfluidic silicon mixer equipped with a new freeze-quenching device, with which reactions can be followed down to 50 micros. In the microfluidic silicon mixer, seven 10-microm-diameter vertical pillars are arranged perpendicular to the flow direction and in a staggered fashion in the 450-pL mixing chamber to enhance turbulent mixing. The mixed-solution jet, with a cross section of 10 microm x 100 microm, exits from the microfluidic silicon mixer with a linear flow velocity of 20 m/s. It instantaneously freezes on one of two rotating copper wheels maintained at 77 K and is subsequently ground into an ultrafine powder. The ultrafine frozen powder exhibits excellent spectral quality and high packing factor and can be readily transferred between spectroscopic observation cells. The microfluidic mixer was tested by the reaction between azide and myoglobin at pH 5.0. It was found that complete mixing was achieved within the mixing dead time of the mixer (20 micros), and the first observable point for this coupled device was determined to be 50 micros, which is approximately 2 orders of magnitude faster than commercially available instruments.     

Compact microfluidic structures for generating spatial and temporal gradients

We present an improved microfluidic design for generating spatial and temporal gradients. The basic functional elements are bifurcated and trifurcated channels used to split flow between two and three channels, respectively. We use bifurcated channels on the exterior of the channel manifold and trifurcated channels in the interior with mixing tees to recombine flows. For N gradient-forming levels, the number of discrete steps in the gradient is 2(N) + 1, allowing a compact gradient-forming structure that is only 1.6 mm long and 0.5 mm wide. Control of the relative sample concentration at the inlets enables generation of gradients with varying slopes and offsets. The small total channel length allows faster switching (only 2.6 s) between gradients of different compositions than did previous designs, allowing complex temporal sequences and reducing total displacement volume and reagent use. The design permits opposing-gradient experiments and generation of complex nonlinear gradients. We fabricated and tested three channel designs with either three or four gradient-forming levels, 20- or 40-microm channel widths, 60- or 120-microm center-to-center channel spacings, and 9 or 17 output steps. These devices produced essentially identical high-quality linear gradients using both pressure-driven and electrokinetic flow.     

Stability of internally mixing flow

Hydrodynamic stability of viscous shear flow resulting from the mixing of two parallel streams of fluid along the centre line of a channel is investigated. A linear stability analysis is employed and eigenvalues are extracted using a variational principle combined with a Rayleigh-Ritz procedure. Velocity profiles for the base flow are obtained from a numerical solution of the laminar mixing problem. Results show a sharp drop in critical Reynolds number as the streams start to mix. However, the flow is generally stable at the mean flow Reynolds number investigated here. These results have practical implications for enhancing mixing and heat or mass transfer in thermal systems of small characteristic dimensions, as found in microelectronic equipment packages.