Deterministic lateral displacement (DLD) in the high Reynolds number regime: high-throughput and dynamic separation characteristics

Recent progress in the development of biosensors has created a demand for high-throughput sample preparation techniques that can be easily integrated into microfluidic or lab-on-a-chip platforms. One mechanism that may satisfy this demand is deterministic lateral displacement (DLD), which uses hydrodynamic forces to separate particles based on size. Numerous medically relevant cellular organisms, such as circulating tumor cells (10–15 µm) and red blood cells (6–8 µm), can be manipulated using microscale DLD devices. In general, these often-viscous samples require some form of dilution or other treatment prior to microfluidic transport, further increasing the need for high-throughput operation to compensate for the increased sample volume. However, high-throughput DLD devices will require a high flow rate, leading to an increase in Reynolds numbers (Re) much higher than those covered by existing studies for microscale (≤?100 µm) DLD devices. This study characterizes the separation performance for microscale DLD devices in the high-Re regime (10?<?Re?<?60) through numerical simulation and experimental validation. As Re increases, streamlines evolve and microvortices emerge in the wake of the pillars, resulting in a particle trajectory shift within the DLD array. This differs from previous DLD works, in that traditional models only account for streamlines that are characteristic of low-Re flow, with no consideration for the transformation of these streamlines with increasing Re. We have established a trend through numerical modeling, which agrees with our experimental findings, to serve as a guideline for microscale DLD performance in the high-Re regime. Finally, this new phenomenon could be exploited to design passive DLD devices with a dynamic separation range, controlled simply by adjusting the device flow rate.     

Capabilities and limitations of 2-dimensional and 3-dimensional numerical methods in modeling the fluid flow in sudden expansion microchannels

This paper deals with computational and experimental investigations into pressure-driven flow in sudden expansion microfluidic channels. Improving the design and operation of microfluidic systems requires that the capabilities and limitations of 2-dimensional (2-D) and 3-dimensional (3-D) numerical methods in simulating the flow field in a sudden expansion microchannel be well understood. The present 2-D simulation results indicate that a flow separation vortex forms in the corner behind the sudden expansion microchannel when the Reynolds number is very low (Re∼0.1). However, the experimental results indicate that this prediction is valid only in the case of a sudden expansion microchannel with a high aspect ratio (aspect ratio >> 1). 3-D computational fluid dynamics simulations are performed to predict the critical value of Re at which the flow separation vortex phenomenon is induced in sudden expansion microchannels of different aspect ratios. The experimental flow visualization results are found to be in good agreement with the 3-D numerical predictions. The present results provide designers with a valuable guideline when choosing between 2-D or 3-D numerical simulations as a means of improving the design and operation of microfluidic devices.     

An efficient micromixer actuated by induced-charge electroosmosis using asymmetrical floating electrodes

Efficient microfluid mixing is an important process for various microfluidic-based biological and chemical reactions. Herein we propose an efficient micromixer actuated by induced-charge electroosmosis (ICEO). The microchannel of this device is easy to fabricate for its simple straight channel structure. Importantly, unlike previous design featuring complicated three-dimensional conducting posts, we utilize the simpler asymmetrical planar floating-electrodes to induce asymmetrical microvortices. For evaluating the mixing performance of this micromixer, we conducted a series of simulations and experiments. The mixing performance was quantified using the mixing index, specifically, the mixing efficiency can reach 94.7% at a flow rate of 1500 µm/s under a sinusoidal wave with a peak voltage of 14 V and a frequency of 400 Hz. Finally, we compared this micromixer with different micromixing devices using a comparative mixing index, demonstrating that this micromixer remains competitive among these existing designs. Therefore, the method proposed herein can offer a simple solution for efficient fluids mixing in microfluidic systems.     

Engineering droplet navigation through tertiary-junction microchannels

We present an experimental and in silico investigation of path selection by a single droplet inside a tertiary-junction microchannel using oil-in-water as a model system. The droplet was generated at a T-junction inside a microfluidic chip, and its flow behavior as a function of droplet size, streamline position, viscosity, and Reynolds number (Re) of the continuous phase was studied downstream at a tertiary junction having perpendicular channels of uniform square cross section and internal fluidic resistance proportional to their lengths. Numerical studies were performed using the multicomponent lattice Boltzmann method. Both the experimental and numerical results showed good agreement and suggested that at higher Re equal to 3, the flow was dominated by inertial forces resulting in the droplets choosing a path based on their center position in the flow streamline. At lower Re of 0.3, the streamline-assisted path selection became viscous force-assisted above a critical droplet size. As the Re was further reduced to 0.03, or when the viscosity of the dispersed phase was increased, the critical droplet size for transition also decreased. This multivariate approach can in future be used to engineer sorting of cells, e.g., circulating tumor cells (CTCs) allowing early-stage detection of life-threatening diseases.     

Inertial migration of single particle in a square microchannel over wide ranges of <Emphasis Type="Italic">Re</Emphasis> and particle sizes

Inertial migration of particles has been widely used in inertial microfluidic systems to passively manipulate cells/particles. However, the migration behaviors and the underlying mechanisms, especially in a square microchannel, are still not very clear. In this paper, the immersed boundary-lattice Boltzmann method (IB-LBM) was introduced and validated to explore the migration characteristics and the underlying mechanisms of an inertial focusing single particle in a square microchannel. The grid-independence analysis was made first to highlight that the grid number across the thin liquid film (between a particle and its neighboring channel wall) was of significant importance in accurately capturing the migrating particle’s dynamics. Then, the inertial migration of a single particle was numerically investigated over wide ranges of Reynolds number (Re, from 10 to 500) and particle sizes (diameter-to-height ratio a/H, from 0.16 to 0.5). It was interesting to find that as Re increased, the channel face equilibrium (CFE) position moved outward to channel walls at first, and then inflected inwards to the channel center at high Re (Re?>?200). To account for the physical mechanisms behind this behavior, the secondary flow induced by the inertial focusing single particle was further investigated. It was found that as Re increased, two vortices appeared around the particle and grew gradually, which pushed the particle away from the channel wall at high Re. Finally, a correlation was proposed based on the numerical data to predict the critical length L_c (defined to describe the size of fluid domain that was strongly influenced by the particle) according to the particle size a/H and Re.     

微流控芯片中电渗流的数值模拟与仿真研究

从电渗流形成的基本理论入手,推导了电场和流场双物理场耦合的控制方程.运用多物理场数值计算分析软件建立了长为1000μm,宽为100μm的二维流道,在微流道中间250~750μm的区域施加了直流电压,并在数值模拟中还原了微流道内壁和微流体的物理属性,计算得出了各段流体的速度场,进而得出了各段流体的流型.通过二维流道压力分布分析了微流道中各段产生不同流型的原因.对微流控芯片中的电动流动的功能原理分析及优化设计具有借鉴意义.     

Numerical simulation of flow and heat transfer in radially rotating microchannels

Investigation of fluid flow and heat transfer in rotating microchannels is important for centrifugal microfluidics, which has emerged as an advanced technique in biomedical applications and chemical separations. The centrifugal force and Coriolis force, arising as a consequence of the microchannel rotation, change the flow pattern significantly from the symmetric profile of a non-rotating channel. Successful design of microfluidic devices in centrifugal microfluidics depends on effectively regulating these forces in rotating microchannels. In this work, we have numerically investigated the flow and heat transfer in rotating rectangular microchannel with continuum assumption. A pressure-based finite-volume technique with a staggered grid was applied to solve the steady incompressible Navier–Stokes and energy equations. It was observed that the effect of Coriolis force was determined by the value of the non-dimensional rotational Reynolds number (Re _ω ). By comparing the root mean square deviation of the axial velocity profiles with the approximate analytical results of purely centrifugal flow for different aspect ratios (AR = width/height), a critical rotational Reynolds number (Re _ω,cr) was computed. Above this value of (Re _ω,cr), the effect of secondary flow becomes dominant. For aspect ratios of 0.25, 0.5, 1.0, 2.0, 4.0 and 9.09, this critical rotational Reynolds number (Re _ω,cr) was found to be 14.0, 5.5, 3.8, 4.7, 6.5 and 10.0, respectively.     

Enhanced size-dependent trapping of particles using microvortices

Inertial microfluidics has been attracting considerable interest for size-based separation of particles and cells. The inertial forces can be manipulated by expanding the microchannel geometry, leading to formation of microvortices for selective isolation and trapping of particles or cells from a mixture. In this work, we aim to enhance our understanding of particle trapping in such microvortices by developing a model of selective particle entrapment. Design and operational parameters including flow conditions, size of the trapping region, and target particle concentration are explored to elucidate their influence on trapping behavior. Our results show that the size dependence of trapping is characterized by a threshold Reynolds number, which governs the selective entry of particles into microvortices from the main flow. We show that concentration enhancement on the order of 100,000× and isolation of targets at concentrations as low as 1/mL is possible. Ultimately, the insights gained from our systematic investigation suggest optimization solutions that enhance device performance (efficiency, size selectivity, and yield) and are applicable to selective isolation and trapping of large rare cells as well as other applications.     

Numerical simulation of the capillary flow in the meander microchannel

Pumping in microfluidic devices is an important issue in actuating fluid flow in microchannel, especially that capillary force has received more and more attractions due to the self-driven motion without external power input. However, less 2D simulation was done on the capillary flow in microchannel especially the meander microchannel which can be used for mixing and lab-on-a-chip (LOC) application. In this paper, the numerical simulation of the capillary flow in the meander microchannel has been studied using computer fluid dynamic simulation software CFD-ACE⁺. Different combinations of channel width in the X-direction denoted as W_x and Y-direction denoted as W_y were designed for simulating capillary flow behavior and pressure drop. The designed four types of meander microchannels (W_x × W_y) were 100 × 100 μm, 100 × 200 μm, 50 × 200 μm, and 50 × 400 μm. In this simulation results, it is found that the capillary pumping speed is highly depending on the channel width. The large speed change occurs at the turning angle of channel width change from W_x to W_y. The fastest pumping effect is found in the meander channel of 100 × 100 μm, which has an average pumping speed of 0.439 mm/s. The slowest average flow speed of 0.205 mm/s occurs in the meander channel of 50 × 400 μm. Changing the meander channel width may vary the capillary flow behavior including the pumping speed and the flow resistance as well as pressure drop which will be a good reference in designing the meander microchannels for microfluidic and LOC application.     

Configurable AC electroosmotic generated in-plane microvortices and pumping flow in microchannels

This paper proposes the patterned AC electroosmotic flows (AC-EOF) by simply grouping discrete electrodes together to form various electrode configurations for generation of in-plane microvortices with clockwise/counter-clockwise rotation, and pumping flow in a microchannel. The rotational direction of in-plane microvortices and pumping flow direction can be controlled using the same electrode pattern by simple switching of the voltages on the electrodes. Microparticle image velocimetry (μPIV) was used to characterize the flow fields of the generated in-plane microvortices and pumping flow. The rotational strength of microvortices and flow rates of pumping flows were found to increase with the increase of the applied voltages, and an optimal value was achieved at an appropriately applied frequency. Moreover, the dependency of the applied voltages, frequencies, and the heights of the measured planes on the rotational strength of in-plane microvortices between the interdigitated and discrete electrode configurations were examined. The discrepancy in electrode geometry results in a small performance reduction, whereas it can be compensated for the ability of switching the rotational direction of in-plane microvortices using the same device. The configurable in-plane microvortices and pumping flow in microchannels provide the potential for micromixing applications and for the integration into a lab-on-a-chip system.     

Efficient heat transfer enhancement by elastic turbulence with polymer solution in a curved microchannel

Heat and mass transfer in microscale flows are limited due to extremely low Reynolds number (Re). In a curved microchannel, however, complex flow behaviors, such as elastic instability and elastic turbulence, can be induced via viscoelastic fluid at vanishingly low-Re conditions, which is of great potential to enhance the heat transfer performance. The influence of elastic instabilities and turbulence on heat dissipation of exothermic components is experimentally investigated in this study. The heat transfer performance of both viscoelastic (polymer solutions) and Newtonian (sucrose solutions) fluid flows in a curved microchannel with a square cross section is experimentally characterized. Titanium–platinum (Ti–Pt) thin films embedded at the bottom wall of the polydimethylsiloxane (PDMS) microchannel serve as both microheater and temperature sensor. For viscoelastic fluids, the spectrum of outlet temperature fluctuation in broad frequency (f) region fits the power law of f ^?1.1. Heat transfer enhancement due to the elastic turbulence in a curved microchannel is thereby identified by the drastic growth of the Nusselt number (Nu, the ratio of convective to conductive heat transfer normal to the boundary) with the increase in the Weissenberg number (Wi, the ratio of elastic stress to viscous stress). The mechanism of heat transfer enhanced by the convection effect of elastic turbulence is also elucidated.     

Design optimization of capillary-driven micromixer with square-wave microchannel for blood plasma mixing

A numerical and experimental investigation is performed into the flow characteristics and mixing performance of three microfluidic polydimethylsiloxane blood plasma mixing devices incorporating square-wave, curved and zigzag microchannels, respectively. For each device, the plasma is introduced into the microfluidic channel under the effects of capillary action alone. Of the three devices, that with the square-wave microchannel is found to yield the best mixing performance, and is therefore selected for design optimization. Four microfluidic micromixers incorporating square-wave microchannels with different widths in the x- and y-directions are fabricated using conventional photolithography techniques. The mixing performance of the four microchannels is investigated both numerically and experimentally. The results show that given an appropriate specification of the microchannel geometry, a mixing efficiency of approximately 76 % can be obtained within 4 s. The practical feasibility of the micromixer is demonstrated by performing prothrombin time (PT) tests using a total liquid volume of 4.0 μL (2.0 μL of plasma and 2.0 μL of PT reagent). It is shown that the mean time required to complete the entire PT test (including loading, mixing and coagulation) is less than 30 s.

     

Developing heatable microfluidic chip to generate gelatin emulsions and microcapsules

The heatable microfluidic chip developed herein successfully integrates a microheater and flow-focusing device to generate uniform-sized gelatin emulsions under various flow rate ratios (sample phase/oil phase, Q _s/Q _o) and driven voltages. The gelatin emulsions can be applied to encapsulate vitamin C for drug release. Our goal is to create the thermal conditions for thermo-sensitive hydrogel materials in the microfluidic chip and generate continuous and uniform emulsions under any external environment. The gelatin emulsion sizes have a coefficient of variation of <5 % and can be precisely controlled by altering the flow rate ratio (Q _s/Q _o) and driven voltage. The gelatin emulsion diameters range from 45 to 120 μm. Moreover, various sizes of these gelatin microcapsules containing vitamin C were used for drug release. The developed microfluidic chip has the advantages of a heatable platform in the fluid device, active control over the emulsion diameter, the generation of uniform-sized emulsions, and simplicity. This new approach for gelatin microcapsules will provide many potential applications in drug delivery and pharmaceuticals.     

High-throughput,single-stream microparticle focusing using a microchannel with asymmetric sharp corners

A new microfluidic device for fast and high-throughput particle focusing is reported. The particle focusing is based on the combination of inertial lift force effect and centrifugal force effect generated in a microchannel with a series of repeated asymmetric sharp corners on one side of the channel wall. The inertial lift force induces two focused particle streams in the microchannel, and the centrifugal force generated at the sharp corner structures tends to drive the particles laterally away from the corner. With the use of a series of repeated asymmetric sharp corner structures, a single and highly focused particle stream was achieved near the straight channel wall at a wide range of flow rate. In comparison with other hydrodynamic particle focusing methods, this method is less sensitive to the flow rate and can work at a higher flow rate (up to 700 μL/min) and Reynolds number (Re = 129.5). With its simple structure and operation, and high throughput, this method can be potentially used in particle focusing processes in a variety of lab-on-a-chip applications.     

Flow rate-insensitive microparticle separation and filtration using a microchannel with arc-shaped groove arrays

Inertial microfluidics can separate microparticles in a continuous and high-throughput manner, and is very promising for a wide range of industrial, biomedical and clinical applications. However, most of the proposed inertial microfluidic devices only work effectively at a limited and narrow flow rate range because the performance of inertial particle focusing and separation is normally very sensitive to the flow rate (Reynolds number). In this work, an innovative particle separation method is proposed and developed by taking advantage of the secondary flow and particle inertial lift force in a straight channel (AR = 0.2) with arc-shaped groove arrays patterned on the channel top surface. Through the simulation results achieved, it can be found that a secondary flow is induced within the cross section of the microchannel and guides different-size particles to the corresponding equilibrium positions. On the other hand, the effects of the particle size, flow rate and particle concentration on particle focusing and separation quality were experimentally investigated. In the experiments, the performance of particle focusing, however, was found relatively insensitive to the variation of flow rate. According to this, a separation of 4.8 and 13 µm particle suspensions was designed and successfully achieved in the proposed microchannel, and the results show that a qualified particle separation can be achieved at a wide range of flow rate. This flow rate-insensitive microfluidic separation (filtration) method is able to potentially serve as a reliable biosample preparation processing step for downstream bioassays.     

Immunochromatographic thread-based test platform for diagnosis of infectious diseases

Patterning is an important step in fabrication of multiplexed microfluidic devices. Various approaches including cutting, photolithography, wax-printing, plotting and etching have been developed and tested. Recently, using threads has emerged as a convenient and low-cost approach for fabrication of microfluidic devices. We explored the application of threads in combination with nitrocellulose membrane to fabricate multi-channel immunochromatographic diagnostic devices. Microfluidic channels were made using hydrophilic threads and nitrocellulose membrane strips. Household sewing needle was used to weave hydrophilic thread into desired patterns through a double-sided mounting tape. Glass fibre discs were used as conjugate pads while nitrocellulose membrane was used for immobilisation of capture antibodies. Patterned threads were linked to nitrocellulose membrane strips by overlapping so that reagents flowing through threads were eventually transferred to the membrane. The design was tested using IgG, H. pylori and Hepatitis B surface antigen. Continuous flow was observed from hydrophilic threads to the nitrocellulose membrane, and a positive signal was visualised on the membrane within 5 min of sample application. The observed limit of detection ranged between 30 and 300 ng/ml for H. pylori and Hepatitis B, respectively. Using thread and tape offers a promising alternative for patterning of simple, low-cost multiplexed microfluidic diagnostic devices with potential point-of-care applications in resource-limited settings.     

Droplet generation in a microchannel with a controllable deformable wall

We report the droplet generation behavior of a microfluidic droplet generator with a controllable deformable membrane wall using experiments and analytical model. The confinement at the droplet generation junction is controlled by using external pressure, which acts on the membrane, to generate droplets smaller than junction size (with other parameters fixed) and stable and monodispersed droplets even at higher capillary numbers. A non-dimensional parameter, i.e., controlling parameter K _p, is used to represent the membrane deformation characteristics due to the external pressure. We investigate the effect of the controlled membrane deformation (in terms of K _p), viscosity ratio λ and flow rate ratio r on the droplet size and mobility. A correlation is developed to predict droplet size in the controllable deformable microchannel in terms of the controlling parameter K _p, viscosity ratio λ and flow rate ratio r. Due to the deflection of the membrane wall, we demonstrate that the transition from the stable dripping regime to the unstable jetting regime is delayed to a higher capillary number Ca (as compared to rigid droplet generators), thus pushing the high throughput limit. The droplet generator also enables generation of droplets of sizes smaller than the junction size by adjusting the controlling parameter.     

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.     

Scaling the formation of slug bubbles in microfluidic flow-focusing devices

The present study aims at scaling the formation of slug bubbles in flow-focusing microfluidic devices using a high-speed digital camera and a micro particle image velocimetry (μ-PIV) system. Experiments were conducted in two different polymethyl methacrylate square microchannels of respectively 600 × 600 and 400 × 400 μm. N₂ bubbles were generated in glycerol–water mixtures with several concentrations of surfactant sodium dodecyl sulfate. The influence of gas and liquid flow rates, the viscosity of the liquid phase and the width of the microchannel on the bubble size were explored. The bubble size was correlated as a function of the width of the microchannel W _c, the ratio of the gas/liquid flow rates Q _g/Q _l and the liquid Reynolds number. During the pinch-off stage, the variation of the minimum width of the gaseous thread W _m with the remaining time could be scaled as _boxclose_boxclose ()^ - 0.15 (T - t)^1/3 . W_{\text{m}} \propto ({\frac{{Q_{\text{g}} }}{{Q_{\text{l}} }}})^{ - 0.15} (T - t)^{1/3} . The velocity fields in the liquid phase around the thread, determined by μ-PIV measurements, were obtained around a forming bubble to reveal the role of the liquid phase.     

Soft lithography fabrication of index-matched microfluidic devices for reducing artifacts in fluorescence and quantitative phase imaging

Microfluidic devices are widely used for biomedical applications based on microscopy or other optical detection methods. However, the materials commonly used for microfabrication typically have a high refractive index relative to water, which can create artifacts at device edges and limit applicability to applications requiring high-precision imaging or morphological feature detection. Here we present a soft lithography method to fabricate microfluidic devices out of MY133-V2000, a UV-curable, fluorinated polymer with low refractive index that is close to that of water (n = 1.33). The primary challenge in the use of this material (and fluorinated materials in general) is the low adhesion of the fluorinated material; we present several alternative fabrication methods we have tested to improve inter-layer adhesion. The close match between the refractive index of this material and aqueous solutions commonly used in biomedical applications enables fluorescence imaging at microchannel or other microfabricated edges without distortion. The close match in refractive index also enables quantitative phase microscopy imaging across the full width of microchannels without error-inducing artifacts for measurement of cell biomass. Overall, our results demonstrate the utility of low-refractive index microfluidics for biological applications requiring high-precision optical imaging.