Acoustically induced bubbles in a microfluidic channel for mixing enhancement

Due to small dimensions and low fluid velocity, mixing in microfluidic systems is usually poor. In this study, we report a method of enhancing microfluidic mixing using acoustically induced gas bubbles. The effect of applied frequency on mixing was investigated over the range 0.5–10 kHz. Under either low frequency 0.5 kHz or high frequency 10 kHz, no noticeable improvement in the present mixer was observed. However, a significant increase in the mixing efficiency was achieved within a window of the frequencies between 1.0 and 5.0 kHz. It was found in our present microfluidic structure, single (or multi-) bubble(s) could be acoustically generated under the frequency ranging from 1.0 to 5.0 kHz by a piezoelectric disc. The interaction between bubble and acoustic field causes bubble oscillation which in turn could disturb local flow field to result in mixing enhancement.     

A magnetic microstirrer and array for microfluidic mixing

We report the development of a micromachined magnetic-bar micromixer for microscale fluid mixing in biological laboratory-on-a-chip applications. The mixer design is inspired by large scale magnetic bar mixers. A rotating magnetic field causes a single magnetic bar or an array of them to rotate rapidly within a fluid environment. A fabrication process of the magnetic bar mixer is developed. Results of fluid mixing in micro channels and chambers are investigated using experimental means and computer-aided fluid simulation.     

Cell separation in a microfluidic channel using magnetic microspheres

Magnetophoretic isolation of biological cells in a microfluidic environment has strong relevance in biomedicine and biotechnology. A numerical analysis of magnetophoretic cell separation using magnetic microspheres in a straight and a T-shaped microfluidic channel under the influence of a line dipole is presented. The effect of coupled particle–fluid interactions on the fluid flow and particle trajectories are investigated under different particle loading and dipole strengths. Microchannel flow and particle trajectories are simulated for different values of dipole strength and position, particle diameter and magnetic susceptibility, fluid viscosity and flow velocity in both the microchannel configurations. Residence times of the captured particles within the channel are also computed. The capture efficiency is found to be a function of two nondimensional parameters, α and β. The first parameter denotes the ratio of magnetic to viscous forces, while the second one represents the ratio of channel height to the distance of the dipole from the channel wall. Two additional nondimensional parameters γ (representing the inverse of normalized offset distance of the dipole from the line of symmetry) and σ (representing the inverse of normalized width of the outlet limbs) are found to influence the capture efficiency in the T-channel. Results of this investigation can be applied for the selection of a wide range of operating and design parameters for practical microfluidic cell separators.     

Size-selective separation of magnetic nanospheres in a microfluidic channel

This paper reported an efficient method to size-selective separate magnetic nanospheres using a self-focusing microfluidic channel equipped with a permanent magnet. Under external magnetic field, the magnetophoresis force exerted on particles leads to size-dependent deflections from their laminar flow paths and results in effective particles separation. By adjusting the distance between magnet and main path of channel, we obtained two monodisperse nanosphere samples (Ca. 90 nm, Ca. 160 nm) from polydispersing particles solution whose diameters varied from 40 to 280 nm. Based on the magnetostatic and laminar flow models, numerical simulations were also used to predict and optimize the nanospheres migrations. Two thresholds of particles diameters were obtained by the simulations and diverse at each position of magnet. Therefore, appropriate position of the magnet could be determined at a certain particle sizes’ range when the flow rate of the two inlets remains unchanged.     

Orbiting magnetic microbeads enable rapid microfluidic mixing

We use three-dimensional numerical simulations and experiments to examine microfluidic mixing induced by orbiting magnetic microbeads in a microfluidic channel. We show that orbiting microbeads can lead to rapid fluid mixing in low Reynolds number flow, and identify two distinct mixing mechanisms. Bulk advection of fluid across the channel occurs due to the flow pattern that is developed when the ratio of flow velocity to bead velocity is low, and leads to rapid mixing. At higher velocity ratios, dispersion of small amounts of fluid across the channel occurs and results in increased mixing. We use simulations to investigate the effect of system parameters on the distance required to achieve a desired mixing level. We develop an experimental continuous-flow device and use it to validate our simulations and to demonstrate rapid microfluidic mixing. This device has the flexibility to also be applied to a mixing chamber or to stop-flow applications for rapid and controllable mixing. In addition to rapid mixing, the use of orbiting magnetic microbeads has the added benefit that functionalized microbeads can be used to capture particles from the fluid solution during mixing, and that they can be extracted from the device for analysis, thus serving multiple functionalities in a single device.     

Continuous generation of hydrogel beads and encapsulation of biological materials using a microfluidic droplet-merging channel

In this paper, we describe a method for encapsulation of biomaterials in hydrogel beads using a microfluidic droplet-merging channel. We devised a double T-junction in a microfluidic channel for alternate injection of aqueous fluids inside a droplet unit carried within immiscible oil. With this device, hydrogel beads with diameter <100 μm are produced, and various solutions containing cells, proteins and reagents for gelation could merge with the gel droplets with high efficiency in the broad range of flow rates. Mixing of reagents and reactions inside the hydrogel beads are continuously observed in a microchannel through a microscope. By enabling serial injection of each liquid with the dispersed gel droplets after they are produced from the oil-focusing channel, the device simplifies the sample preparation process, and gel-bead fabrication can be coupled with further assay continuously in a single channel. Instantaneous reactions of enzyme inside hydrogel and in-situ formation of cell-containing beads with high viability are demonstrated in this report.     

A numerical design study of chaotic mixing of magnetic particles in a microfluidic bio-separator

A two-dimensional numerical investigation into the mixing of magnetic microparticles with bio-cells in a chaotic micromixer is carried out by using a multiphysics finite element analysis package. Fluid and magnetic problems are simulated in steady-state and time-dependent modes, respectively. Intensity of segregation is utilized as the main index to examine the efficiency of the mixer. Trajectories of the particles are used in order to detect chaos in their motion and quantify its extent. Moreover, probability of the collision between particles and target bio-cells is examined as a supplemental index to study the effects of driving parameters on the mixing process. Simulation results reveal that while in some ranges of operating conditions all indices are in good agreement, there are some ranges where they appear to predict contradicting results which is discussed in details. It is found that optimum operating conditions for the system is obtained when the Strouhal number is less than 0.6, which corresponds to the efficiency of about 85% in a mixing length of 500 μm (The mixer design described here is patent pending).     

Influence of adjusting the inlet channel confluence angle on mixing behaviour in inertial microfluidic mixers

Recent drive for high-throughput microfluidic systems has triggered tremendous research effort to develop efficient, high-throughput microfluidic mixers. In particular, inducing a fluid–fluid collision at high flow rate in microfluidic channel has been suggested as an effective strategy to enhance mixing. However, previous studies using T-shaped microfluidic mixers showed that, in addition to fluid–fluid collision, the confluence angle of fluid stream in microfluidic channel also has a dramatic effect on mixing. This study suggests the possibility to enhance mixing by simply changing the inlet confluence angle of the streams. In this work, we assess the mixing behaviour of microfluidic mixers with variable inlet confluence angle with the Reynolds number (Re) range of 2.83–566. It is shown that the increase in inlet confluence angle enables the reduction of Re required for complete mixing. Simulation results demonstrate that increasing the confluence angle facilitates the interaction of vortices in mixers to induce an enhanced mixing. We further demonstrate that the increased interaction of vortices also prompts the turbulent emulsification where a significant reduction in emulsion size is observed for each mixer with increased inlet confluence angle at same Re.     

Residence time distribution analysis of magnetic nanoparticle-enhanced mixing using time-dependent magnetic actuation in microfluidic system

The dynamics of an innovative time-dependent magnetic nanoparticle (MNP)-based mixing strategy is demonstrated in this study using a multiphysics finite element model. Residence time distribution (RTD) analysis, for the first time, is successfully applied to predict the performance as well as investigate and optimize a wide range of design parameters used in the magnetically actuated mixing process. Orientation of electrodes as well as the direction of current to produce desirable magnetic field are found to play a major role on mixing performance. It is also found that a two-electrode system with an optimized current can be as effective as a four-electrode system. For effective mixing, an optimum switching frequency of current supplied to electrodes is predicted. Effect of MNP size, flow condition on mixing performance is also studied using RTD analysis and optimized values are predicted. Overall, the developed “numerical prototype” in conjunction with RTD analysis demonstrates that time-dependent magnetic actuation can be effectively used to mix or tag MNPs with biomolecules in situ for further processing and the numerical model can be used as a predictive tool in the design and optimization of mixing strategy for developing efficient lab-on-a-chip systems.     

Electrokinetic mixing in microfluidic systems

The applications of electrokinetics in the development of microfluidic devices have been widely attractive in the past decade. Electrokinetic devices generally require no external mechanical moving parts and can be made portable by replacing the power supply by small battery. Therefore, electrokinetic-based microfluidic systems can serve as a viable tool in creating a lab-on-a-chip (LOC) or micro-total analysis system (μTAS) for use in biological and chemical assays. Mixing of analytes and reagents is a critical step in realizing lab-on-a-chip. This step is difficult due to the low Reynolds numbers flows in microscale devices. Hence, various schemes to enhance micro-mixing have been proposed in the past years. This review reports recent developments in the micro-mixing schemes based on DC and AC electrokinetics, including electrowetting-on-dielectric (EWOD), dielectrophoresis (DEP), and electroosmosis (EO). These electrokinetic-based mixing approaches are generally categorized as either active or passive in nature. Active mixers either use time-dependent (AC or DC field switching) or time-independent (DC field) external electric fields to achieve mixing, while passive mixers achieve mixing in DC fields simply by virtue of their geometric topology and surface properties, or electrokinetic instability flows. Typically, chaotic mixing can be achieved in some ways and is helpful to mixing under large Péclet number regimes. The overview given in this article provides a potential user or researcher of electrokinetic-based technology to select the most favorable mixing scheme for applications in the field of micro-total analysis systems.     

Evolution of mixing in a microfluidic reverse-staggered herringbone micromixer

Microfluidic platforms offer a variety of advantages including improved heat transfer, low working volumes, ease of scale-up, and stronger user control on operating parameters. However, flow within microfluidic channels occurs at low Reynolds number (Re), which makes mixing difficult to accomplish. Adding V-shaped ridges to channel walls, a pattern called the staggered herringbone design (SHB), alleviates this problem by introducing transverse flow patterns that enable enhanced mixing. Building on our prior work, we here developed a microfluidic mixer utilizing the SHB geometry and characterized using CFD simulations and complimentary experiments. Specifically, we investigated the performance of this type of mixer for unequal species diffusivities and inlet flows. A channel design with SHB ridges was simulated in COMSOL Multiphysics® software under a variety of operating conditions to evaluate its mixing capabilities. The device was fabricated using soft-lithography techniques to experimentally visualize the mixing process. Mixing within the device was enabled by injecting fluorescent dyes through the device and imaging using a confocal microscope. The device was found to efficiently mix fluids rapidly, based on both simulations and experiments. Varying Re or species diffusion coefficients had a weak effect on the mixing profile, due to the laminar flow regime and insufficient residence time, respectively. Mixing effectiveness increased as the species flow rate ratio increased. Fluid flow patterns visualized in confocal microscope images for selective cases were strikingly similar to CFD results, suggesting that the simulations serve as good predictors of device performance. This SHB mixer design would be a good candidate for further implementation as a microfluidic reactor.     

Electrohydrodynamics around single ion-permselective glass beads fixed in a microfluidic device

This work demonstrates by direct visualization using confocal laser scanning microscopy that the application of electrical fields to a single-fixed, ion-permselective glass bead produces a remarkable complexity in both the coupled mass and charge transport through the bead and the coupled electrokinetics and hydrodynamics in the adjoining bulk electrolyte. The visualization approach enables the acquisition of a wealth of information, forming the basis for a detailed analysis of the underlying effects (e.g., ion-permselectivity, concentration polarization, nonequilibrium electroosmotic slip) and an understanding of electrohydrodynamic phenomena at charge-selective interfaces under more general conditions. The device used for fixing single beads in a microfluidic channel is flexible and allows to investigate the electrohydrodynamics in both transient and stationary regimes under the influence of bead shape, pore size and surface charge density, mobile phase composition, and applied volume forces. This insight is relevant for the design of microfluidic/nanofluidic interconnections and addresses the ionic conductance of discrete nanochannels, as well as nanoporous separation and preconcentration units contained as hybrid configurations, membranes, packed beds, or monoliths in lab-on-a-chip devices.     

Focusing microparticles in a microfluidic channel with ferrofluids

We report a novel on-chip microparticles focusing technique using stable magnetic nanoparticles suspension (i.e., ferrofluids). The principle of focusing is based on magnetic buoyancy forces exerted on non-magnetic particles within ferrofluids under non-uniform magnetic field. The design, modeling, fabrication, and characterization of the focusing scheme are presented. Focusing of 4.8, 5.8, and 7.3 ??m microparticles at various flow rates are demonstrated in a microfluidic channel. Our scheme is simple, low-cost, and label-free compared to other existing techniques.     

Controlling capillary-driven surface flow on a paper-based microfluidic channel

This paper describes two methods for controlling capillary-driven liquid flow on microfluidic channels. Unlike flow driven by external forces, capillary-driven flow is dominated by interfacial phenomena and, therefore, is sensitive to the channel geometry and chemical composition (surface energy) along the channel. The first method to control fluid flow is based on altering surface energy along the channel through regulation of UV irradiation time, which enables adjusting the contact angle along the fluid path. The slowing down (delay) of the liquid flow depends on the stripe length and its position in the channel. Using this technique, we generated flow delays spanning from a second to over 3 min. In the second approach, we manipulated the flow velocity by introducing contractions and expansions in the channel. The methods used herein are inexpensive and can be incorporated to the microfluidic channel fabrication step. They are capable of controlling liquid flow with precise time delays without introducing the foreign matter in the fluidic device.     

数字微流控生化芯片多液滴稀释方法的研究

生化试验中如何将样品试剂配备过程转化成有效的数字生化芯片实现的协议,并给出相应的操作过程中的稀释/混合操作优化算法非常关键,是样品试剂配备过程的一个挑战。为减少操作步骤和节省药品,提出针对数字微流控生物芯片多液滴混合器稀释/混合操作优化算法,该算法允许多个液体参与混合分离操作,可以在误差允许范围内利用片上多液滴混合器用较少的操作步骤获得目标浓度的液滴。相对传统的两液滴混合方法,减少了稀疏/混合的步骤和稀释/混合时间,同时减少中间废弃液滴的数目。实验结果也表明可以在允许的误差范围内高效地进行混合/分离操作,获得目标浓度的液滴。     

Effective mixing in a microfluidic oscillator using an impinging jet on a concave surface

In this study, we present a microfluidic oscillator design that employs an impinging jet on a concave surface to enhance the microscale mixing process. The Coand? effect along with the G?rtler instability proves to incite sustainable flapping motion beyond the obstacle and mixing is profoundly improved. From the flow visualization results, four different regimes are identified and we find that the primary enhancement of mixing performance is always linked to the transition of flow regime. Moreover, incorporating a sudden-expansion confluence provokes flow three dimensionality and elevates the mixing level significantly at low Reynolds numbers. For a Reynolds number as low as 70, the tail flow behind the concave obstacle successfully exhibits a periodic oscillation and Hopf bifurcation is induced, leading to a drastic augmentation in the time-average mixing efficiency. By utilizing the spectrum analysis, the characteristic frequency of flapping motion is found to vary linearly with the throat velocity, resulting in a constant Strouhal number of 3.8?×?10^?5.     

Magnetic particle dosing and size separation in a microfluidic channel

Separation of functional magnetic particles or magnetically labeled entities is a key feature for bioanalytical or biomedical applications and therefore also an important component of lab-on-a-chip devices for biological applications. We present a novel integrated microfluidic magnetic bead manipulation device, comprising dosing of magnetic particles, controlled release and subsequent magnetophoretic size separation with high resolution. The system is designed to meet the requirements of specific bioassays, in particular of on-chip agglutination assays for the detection of rare analytes by particle coupling as doublets. Integrated soft-magnetic microtips with different shapes provide the magnetic driving force of the bead manipulation protocol. The magnetic tips that serve as field concentrators of an external electromagnetic field, are positioned in close contact to a microfluidic channel in order to generate high magnetic actuation forces. Mixtures of 1.0 μm and 2.8 μm superparamagnetic beads have been used to characterize the system. Magnetophoretic size separation with high resolution was performed in static conditions and in continuous flow mode. In particular, we could demonstrate the separation of 1.0 μm single beads and doublets in a sample flow.     

Characterization of DNA hybridization kinetics in a microfluidic flow channel

In this investigation we report on the influence of volumetric flow rate, flow velocity, complementary DNA concentration, height of a microfluidic flow channel and time on DNA hybridization kinetics. A syringe pump was used to drive Cy3-labeled target DNA through a polydimethylsiloxane (PDMS) microfluidic flow channel to hybridize with immobilized DNA from the West Nile Virus. We demonstrate that a reduction of channel height, while keeping a fixed volumetric flow rate or a fixed flow velocity, enhances mass transport of target DNA to the capture probes. Compared to a passive hybridization, the DNA hybridization in the microfluidic flow channel generates higher fluorescence intensities for lower concentration of target DNA during the same fixed period of time. Within a fixed 2 min time period the fastest DNA hybridization at a 50 pM concentration of target DNA is achieved with a continuous flow of target DNA at the highest flow rate and the lowest channel height.     

Free-floating amphiphilic picoliter droplet carriers for multiplexed liquid loading in a microfluidic channel

We present free-floating amphiphilic picoliter microcarriers for multiplexed loading in a microfluidic device. The amphiphilic microcarrier is composed of encoded hydrophobic hexagonal outer structure and hydrophilic inner structure. We fabricate these free-floating droplet carriers and assemble them in a microfluidic device for a demonstration of multiplexed liquid loading. Picoliter loading is performed by serial solution exchange of aqueous and oil phase solution. We are able to precisely adjust the loaded volume by varying the diameter and depth of the microcarrier. We also fabricate arbitrary shaped microwells and load picoliter droplets into?them. A microbead suspension is also used to demonstrate mixing via continuous oil flow. Further development of this work may be applicable to high-throughput multiplexed assays using quantized liquid loading in a microfluidic environment.