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Showing papers in "Microfluidics and Nanofluidics in 2019"


Journal ArticleDOI
TL;DR: Wang et al. as discussed by the authors summarized the recent research progress on liquid-liquid two-phase flow in microchannel, especially focusing on flow pattern and mass transfer, and future needs are proposed for extending the researches on liquid -liquid twophase flow and enlarging its application fields.
Abstract: Liquid–liquid two-phase flow in microchannel is very common in micro-chemical and micro-biological system, etc. Deep understanding of the liquid–liquid two-phase flow mechanisms and mass transfer in microchannel can promote industrial applications significantly. To summarize the recent research progress on the liquid–liquid two-phase flow in microchannel, this paper collects research work about this topic, especially focusing on flow pattern and mass transfer. To begin with, flow patterns observed in various conditions are identified and factors which influence the flow patterns are analyzed. Then, mass transfer in liquid–liquid two-phase flow is discussed, especially the mass transfer during droplet flow, with both experiments and simulations. Furthermore, energy dissipation involved in liquid–liquid two-phase flow in microchannel is also briefly discussed. Finally, future needs are proposed for extending the researches on liquid–liquid two-phase flow and enlarging its application fields.

53 citations


Journal ArticleDOI
TL;DR: The potential of centrifugal microfluidic platforms to perform complex bioanalytical assays in an automated fashion is illustrated by several examples, which include on-chip preparation of aliquot libraries, nucleic acid purification, amplification and analysis as well as blood separation.
Abstract: This review is an account of centrifugal microfluidic systems that use various actuation strategies in addition to intrinsic centrifugal forces to accurately regulate the motion of fluids during rotation. Platforms that integrate active methods of pumping and flow control render centrifugal microfluidics more versatile as they facilitate integration and process automation by enabling (or improving the reliability of) important fluidic functions, such as metering, aliquoting, valving, flow switching, mixing, and inward pumping. Principles and working mechanisms underlying these strategies are described in the context of recent trends in instrument design and development where centrifugal platforms have been equipped with pneumatic, magnetic or electromechanical actuators serving as pumping and valving elements. The potential of these platforms to perform complex bioanalytical assays in an automated fashion is illustrated by several examples, which include on-chip preparation of aliquot libraries, nucleic acid purification, amplification and analysis as well as blood separation.

38 citations


Journal ArticleDOI
TL;DR: In this article, a series of aqueous dispersed phases were used with a viscosity ratio between continuous and dispersed phases of close to unity to study drop generation in a Dolomite microfluidic device.
Abstract: The regimes of drop generation were studied in a Dolomite microfluidic device which combined both hydrodynamic and geometrical flow focusing over a broad range of flow rates. A series of aqueous dispersed phases were used with a viscosity ratio between continuous and dispersed phases of close to unity. Surfactants were added to alter the interfacial tension. It was shown that the transition from dripping to jetting is well described by the capillary numbers of both the dispersed and continuous phases. Only the jetting regime was observed if the capillary number of the dispersed phase was above a critical value, whereas at smaller values of this parameter a jetting → dripping → jetting transition was observed by increasing the capillary number of the continuous phase. The analysis performed has shown that the conditions for a dripping to jetting transition at moderate and large values of the capillary number of the continuous phase can be predicted theoretically by comparison of the characteristic time scales for drop pinch-off and jet growth, whereas the transition at small values cannot. It is suggested that this transition is geometry mediated and is a result of the interplay of jet confinement in the focusing part and a decrease of confinement following entry into the main channel. The flow fields inside the jet of the dispersed phase were qualitatively different for small and large values of the capillary number of the continuous phase revealing the relative contribution of the dispersed phase flow in jet formation. The volume of the drops formed in the jetting regime increased as a power law function of the flow rate ratio of the dispersed to continuous phase, independent of the interfacial tension.

37 citations


Journal ArticleDOI
TL;DR: In this article, the influence of the sharp structure and vibration velocity on the streaming flow is investigated by directly visualizing the displacement of tracing particles and the generated acoustic streaming is observed using particle image velocimetry, under various operating conditions.
Abstract: Acoustic streaming can be generated in microchannels by low-frequency acoustic transducer in the vicinity of sharp structures. Close to the tip, the strong curvature induces bent trajectories on the time-periodic acoustic flow, locally enhancing the streaming-generating force. In this study, we investigate the influence of the sharp structure and vibration velocity on the streaming flow. The vibration velocities are characterized by directly visualizing the displacement of tracing particles and the generated acoustic streaming is observed using particle image velocimetry, under various operating conditions. By measuring the concentration of a fluorescence dye, we evaluate the mixing performance for different values of tip angle, vibration amplitude, and flow rate through the microchannel. Our results confirm that intense streaming is generated under low-frequency (2.5 kHz) acoustic condition when the local curvature of the boundary is close to or smaller than the viscous boundary-layer thickness. It is shown that the sharpest the edge tip, the largest the vortices size and the spatial extent of the induced streaming, therefore greatly enhancing the mixing between two miscible liquids. The mixing index, linearly characterizing the mixing degree between 1 (totally separated) and 0 (perfectly mixed), jumps from 0.73 (without acoustic excitation) to 0.38 (with acoustic excitation), resulting in a highly mixed homogeneous fluid just after the sharp edge. This emphasizes the promising potential of acoustic streaming to enhance mass transfer inside microchannels which is usually limited by the laminar flow conditions.

36 citations


Journal ArticleDOI
TL;DR: In this paper, a comprehensive analysis of the geometrical parameters influencing the sensitivity of a coplanar electrode layout for electrical impedance flow cytometry is presented, which is used for sizing and characterizing particles from single cells to cell aggregates.
Abstract: This paper describes a comprehensive analysis of the geometrical parameters influencing the sensitivity of a coplanar electrode layout for electrical impedance flow cytometry. The designs presented in this work have been simulated, fabricated, and tested. 3D finite element method was applied to simulate and improve the sensitivity of the coplanar designs for two spacings between electrodes. The proposed model uses conditional expressions to define spatially dependent material properties. The vertical and lateral sensitivities were evaluated for all the designs. The experimental results obtained with polystyrene beads show good agreement with the simulations. Precentering particles with dielectrophoresis allowed to control their position in the microchannel. The optimized designs are envisioned to be used for sizing and characterizing particles from single cells to cell aggregates.

35 citations


Journal ArticleDOI
TL;DR: A bone-chip system to study osteogenic differentiation in vitro, coupled with optical imaging approach which provides the opportunity of monitoring cell survival, proliferation and differentiation in vivo without the need to terminate the culture, is developed.
Abstract: Human organoids and organ-on-chip systems to predict human responses to new therapies and for the understanding of disease mechanisms are being more commonly used in translational research. We have developed a bone-chip system to study osteogenic differentiation in vitro, coupled with optical imaging approach which provides the opportunity of monitoring cell survival, proliferation and differentiation in vitro without the need to terminate the culture. We used the mesenchymal stem cell (MSC) line over-expressing bone morphogenetic protein-2 (BMP-2), under Tet-Off system, and luciferase reporter gene under constitutive promoter. Cells were seeded on chips and supplemented with osteogenic medium. Flow of media was started 24 h later, while static cultures were performed using media reservoirs. Cells grown on the bone-chips under constant flow of media showed enhanced survival/proliferation, comparing to the cells grown in static conditions; luciferase reporter gene expression and activity, reflecting the cell survival and proliferation, was quantified using bioluminescence imaging and a significant advantage to the flow system was observed. In addition, the flow had positive effect on osteogenic differentiation, when compared with static cultures. Quantitative fluorescent imaging, performed using the osteogenic extra-cellular matrix-targeted probes, showed higher osteogenic differentiation of the cells under the flow conditions. Gene expression analysis of osteogenic markers confirmed the osteogenic differentiation of the MSC-BMP2 cells. Immunofluorescent staining performed against the Osteocalcin, Col1, and BSP markers illustrated robust osteogenic differentiation in the flow culture and lessened differentiation in the static culture. To sum, the bone-chip allows monitoring cell survival, proliferation, and osteogenic differentiation using optical imaging.

35 citations


Journal ArticleDOI
TL;DR: In this paper, a detailed parametric analysis of wax printing technique for fabricating µPADs is presented, and experimental results show that the wax spreading in the paper porous structure depends on the initially deposited wax line thickness, a threshold melting temperature and melting time.
Abstract: Accurate prediction of hydrophobic–hydrophilic channel barriers is essential in the fabrication of paper-based microfluidic devices. This research presents a detailed parametric analysis of wax printing technique for fabricating µPADs. Utilizing commonly used Grade 1 filter paper, experimental results show that the wax spreading in the paper porous structure depends on the initially deposited wax line thickness, a threshold melting temperature and melting time. Initial width of the printed line has a linear relationship with the final width of the barrier; however, a less pronounced effect of temperature was observed. Based on the spreading behavior of the molten wax at different parameters, a generalized regression model has been developed and validated experimentally. The developed model accurately predicts wax spreading in Whatman filter paper: a non-uniform distribution of pores and fibers. Finally, tests were carried out for calorimetric detection of commonly used adulterants present in milk samples.

35 citations


Journal ArticleDOI
TL;DR: In this article, a modular microfluidic system for generating emulsion droplets using a 3D printer is presented, which can be applied to bioassays, material synthesis, and other applications.
Abstract: We designed a modular microfluidic system for generating droplets using a three-dimensional (3D) printer. This system was manufactured as a modular system with multipurpose droplet generation flexibility. The various types of emulsion droplets can be generated by changing the combination of the incorporated modules. All modules are interconnected based on a novel coupling system that facilitates assembly and disassembly, and leakages do not occur even for pressures of the order of ~ 40 kPa. We demonstrate the capacity of the system to generate emulsion droplets, ranging from single to complicated dual-core double-emulsion droplets. Droplet sizes in the range of 50–500 μm were obtained by controlling the flow rate and the generation frequency in the range of 1–100 Hz. Furthermore, an electrode module was developed to demonstrate different electrohydrodynamic phenomena, such as the shape deformation, coalescence, breakup, and others. This 3D printed modular microfluidic system makes it possible to meet the needs of the end-user, and can be applied to bioassays, material synthesis, and other applications.

31 citations


Journal ArticleDOI
TL;DR: In this paper, the elasto-inertial particle focusing in 3D-printed microchannels with unconventional cross-sections was studied, and the mechanisms of particle focusing were explored by comparing the particle migrations in 0.3-wt% HA solution and PBS solution.
Abstract: In this paper, elasto-inertial particle focusing in 3D-printed microchannels with unconventional cross sections was studied. A novel 3D-printed mold-removal method was proposed to fabricate the microchannels. By modifying the orifice shape of the extrusion nozzle, the microchannel molds with arbitrary cross sections could be printed using an easily accessible fused deposition modeling (FDM) printer. After the routine PDMS casting procedure, the channel molds were dissolved to produce all-PDMS microfluidic chips, thereby eliminating the complex bonding process. The mechanisms of elasto-inertial focusing in the semielliptical and triangular microchannels were explored by comparing the particle migrations in 0.3 wt% HA solution and PBS solution, and the effects of flow rate on particle focusing position and focusing width were also investigated. We found that the single-line particle focusing in the triangular microchannel was more stable and closer to the channel bottom than that in the semielliptical microchannel, which is of great value to improve the detection sensitivity of microfluidic impedance cytometer with coplanar electrodes fabricated on the channel bottom.

30 citations


Journal ArticleDOI
TL;DR: This review presents recent advances in focusing and sorting of bio-micro/nanoparticles by non-Newtonian microfluidics, and principle and examples for passive and active manipulation of bioparticles in non- newtonian and non-newtonian/Newtonians hybrid microflows are highlighted.
Abstract: Most bio-micro/nanoparticles, including cells, platelets, bacteria, and extracellular vesicles, are inherently suspended in biofluids (i.e., blood) with non-Newtonian fluid characteristics. Understanding migration behaviors of bioparticles in non-Newtonian microfluidics is of significance in label-free manipulation of bioparticles, playing important roles in cell analysis and disease diagnostics. This review presents recent advances in focusing and sorting of bio-micro/nanoparticles by non-Newtonian microfluidics. Principle and examples for passive and active manipulation of bioparticles in non-Newtonian and non-Newtonian/Newtonian hybrid microflows are highlighted. Limitations and perspectives of non-Newtonian microfluidics for clinical applications are discussed.

29 citations


Journal ArticleDOI
TL;DR: A format of particle-based immunoassays relying on digital microfluidics (DMF) and magnetic forces to separate and resuspend HCG antibody-coated paramagnetic particles to solve the biofouling problem and has great potential for eventual use in a fast, low-waste, and inexpensive instrument for the quantitative analysis of proteins and small molecules in low sample volumes.
Abstract: Determinations of Human chorionic gonadotropin (HCG) are important for diagnosis and monitoring of pregnancy, pregnancy-related diseases and several types of cancers. As a step toward decentralized diagnostic systems, we introduce a format of particle-based immunoassays relying on digital microfluidics (DMF) and magnetic forces to separate and resuspend HCG antibody-coated paramagnetic particles. On this basis, we developed DMF diagnostic platform for automated HCG detection and realized droplet operations at 20 Hz. Using this platform, 10–50 µg/mL of HCG was detected by chemiluminescence method and the linear relationship between HCG concentrations and chemiluminescence signals was obtained. To solve the biofouling problem, we use pluronic additives in reagent droplets. The effect of different additive concentrations on droplet actuation was tested. The DMF immunoassays only take 20 min to finish the whole sample detection process. We propose that the new technique has great potential for eventual use in a fast, low-waste, and inexpensive instrument for the quantitative analysis of proteins and small molecules in low sample volumes.

Journal ArticleDOI
TL;DR: In this article, high-speed bright-field imaging was used to experimentally analyse the behavior of model bidisperse suspensions and the influences of bidispersity on the lateral inertial migration of the particles towards equilibrium positions within the channel cross-section and their longitudinal ordering into trains in the flow direction, under different conditions by varying the Reynolds number, the particles' size ratios and concentrations.
Abstract: Inertial focusing of particles in microchannels has demonstrated a great potential for a wide range of applications addressing various challenges, such as clinical diagnosis, biological assay, water treatment, etc. Even though numerous theoretical, numerical and experimental studies have been performed to identify the physical mechanisms underlying the migration of particles in confined environments, only a few works, up to now, have been devoted to the effects resulting from the interactions between particles of different sizes in polydisperse suspensions. In this work, high-speed bright-field imaging was used to experimentally analyse the behaviour of model bidisperse suspensions. The influences of bidispersity on (1) the lateral inertial migration of the particles towards equilibrium positions within the channel cross-section and (2) their longitudinal ordering into trains in the flow direction, were investigated under different conditions by varying the Reynolds number, the particles’ size ratios and concentrations. The quantitative measurements and statistical analysis of the experimental data show that the bidispersity can modify not only the lateral migration process but also the sequential particle-ordering phenomenon.

Journal ArticleDOI
TL;DR: Femtosecond laser microfabrication (FLM) of a poly(methyl methacrylate) (PMMA) inertial microfluidic sorter is reported on, separating particles based on their size and providing an enhanced-throughput capability.
Abstract: In biology and medicine, the application of microfluidics filtration technologies to the separation of rare particles requires processing large amounts of liquid in a short time to achieve an effective separation yield. In this direction, the parallelization of the sorting process is desirable, but not so easy to implement in a lab on a chip (LoC) device, especially if it is fully inertial. In this work, we report on femtosecond laser microfabrication (FLM) of a poly(methyl methacrylate) (PMMA) inertial microfluidic sorter, separating particles based on their size and providing an enhanced-throughput capability. The LoC device consists of a microchannel with expansion chambers provided with siphoning outlets, for a continuous sorting process. Different from soft lithography, which is the most used technique for LoC prototyping, FLM allows developing 3D microfluidic networks connecting both sides of the chip. Exploiting this capability, we are able to parallelize the circuit while keeping a single output for the sorted particles and one for the remaining sample, thus increasing the number of processed particles per unit time without compromising the simplicity of the chip connections. We investigated several device layouts (at different flow rates) to define a configuration that maximizes the selectivity and the throughput.

Journal ArticleDOI
TL;DR: In this paper, a small amount of polymers were added to the sample solution to tune the fluid elasticity, and allow particles to migrate laterally and reach their equilibriums at the centerline of a symmetric serpentine channel under the synthesis effect of elastic, inertial and Dean-flow forces.
Abstract: This work investigates particle focusing under Dean-flow-coupled elasto-inertial effects in symmetric serpentine microchannels. A small amount of polymers were added to the sample solution to tune the fluid elasticity, and allow particles to migrate laterally and reach their equilibriums at the centerline of a symmetric serpentine channel under the synthesis effect of elastic, inertial and Dean-flow forces. First, the effects of the flow rates on particle focusing in viscoelastic fluid in serpentine channels were investigated. Then, comparisons with particle focusing in the Newtonian fluid in the serpentine channel and in the viscoelastic fluid in the straight channel were conducted. The elastic effect and the serpentine channel structure could accelerate the particle focusing as well as reduce the channel length. This focusing technique has the potential as a pre-ordering unit in flow cytometry for cell counting, sorting, and analysis. Moreover, focusing behaviour of Jurkat cells in the viscoelastic fluid in this serpentine channel was studied. Finally, the cell viability in the culture medium containing a dissolved polymer and after processing through the serpentine channel was tested. The polymer within this viscoelastic fluid has a negligible effect on cell viability.

Journal ArticleDOI
TL;DR: In this paper, the authors investigate the inertialess secondary flow of viscoelastic fluids in curved microchan-nels of rectangular cross-section and constant but alternating curvature, and present the first experimental visualization evidence and characterization of these steady secondary flows, using a complementarity of µPIV in the plane of the channel.
Abstract: Secondary flows are ubiquitous in channel flows, where small velocity components perpendicular to the main velocity appear due to the complexity of the channel geometry and/or that of the flow itself such as from inertial or non-Newtonian effects, etc. We investigate here the inertialess secondary flow of viscoelastic fluids in curved microchan-nels of rectangular cross-section and constant but alternating curvature: the so-called "serpentine channel" geometry. Numerical calculations (Poole et al, 2013) have shown that in this geometry, in the absence of elastic instabilities, a steady secondary flow develops that takes the shape of two counter-rotating vortices in the plane of the channel cross-section. We present the first experimental visualization evidence and characterization of these steady secondary flows, using a complementarity of µPIV in the plane of the channel, and L. Ducloue · L. Casanellas · A. Lindner confocal visualisation of dye-stream transport in the cross-sectional plane. We show that the measured streamlines and the relative velocity magnitude of the secondary flows are in qualitative agreement with the numerical results. In addition to our techniques being broadly applicable to the character-isation of three-dimensional flow structures in microchan-nels, our results are important for understanding the onset of instability in serpentine viscoelastic flows.

Journal ArticleDOI
TL;DR: In this article, the authors present the properties of an electrical double layer formed by ions inside a charged cylindrical pore studied by the grand canonical Monte Carlo simulation and classical density functional theory.
Abstract: We present the properties of an electrical double layer formed by ions inside a charged cylindrical pore studied by the grand canonical Monte Carlo simulation and classical density functional theory. The cylinder radius is 3000 pm. The wall is hard, perfectly smooth. The ions are modelled by hard spheres with a point electric charge at the centre. The hard sphere diameter is fixed at 400 pm. The monovalent ions are immersed in a continuous dielectric medium of the relative permittivity er. The temperature is 298.15 K and the electrolyte concentration takes the following values: 1.0, 2.5 and 4.0 M. The surface charge density varies in the range from − 1.0 to + 1.0 C/m2. The ion singlet distribution results show adsorption of counter-ions and desorption of co-ions from the cylindrical electrode. At high electrode charges the second layer of counter-ions is formed, while for high electrolyte concentration the co-ion distribution curve has a small maximum at some distance from the electrode surface. In comparison to the planar electrode, the concave one attracts stronger the counter-ions and repels the co-ions. At high electrolyte concentration, the profiles of the volume charge density have a positive hump, while those of the mean electrostatic potential have a negative minimum, which indicates the overscreening effect. For low electrolyte concentrations, the differential capacitance curve has a minimum at σ = 0 surrounded by two maxima. With increasing concentration, the minimum transforms into a maximum. The differential capacitance curves run above the curves for the planar electrode at small electrode charges and below them for high negative and positive charges. The very good agreement of all the grand canonical Monte Carlo to the classical density functional theory results presented in the paper indicates the reliability of the latter approach in cylindrical pore as well as planar geometry.

Journal ArticleDOI
TL;DR: In this paper, the authors investigate the cross-sectional arrangement of the particles is fundamental in determining the characteristics of the resulting particle pair, and show that the particle pair formation, robustness and the stability of particle pairs, and the precision of the inter-particle distance in an oscillatory flow field, in microchannels with a rectangular cross section.
Abstract: Particles suspended in conduit flows at small and intermediate Reynolds numbers cluster on specific focal positions while also forming particle pairs and trains due to flow-mediated interactions. The recent introduction of oscillatory inertial microfluidics has enabled the creation of virtually infinite channels, allowing the manipulation of particles at extremely low particle Reynolds numbers (Rep ≪ 1). Here, we investigate experimentally the dynamics of formation, the robustness and the stability of particle pairs, and the precision of the inter-particle distance in an oscillatory flow field, in microchannels with a rectangular cross section. Our results indicate that the cross-sectional arrangement of the particles is fundamental in determining the characteristics of the resulting particle pair.

Journal ArticleDOI
TL;DR: This paper optimizes the micromixer with the concave grooves and reveals the different properties of the mixing, which is a novel approach for fluid topology optimization using genetic algorithm.
Abstract: This paper proposes a novel approach for fluid topology optimization using genetic algorithm. In this study, the enhancement of mixing in the passive micromixers is considered. The efficient mixing is achieved by the grooves attached on the bottom of the microchannel and the optimal configuration of grooves is investigated. The grooves are represented based on the graph theory. The mixing performance is analyzed by a CFD solver and the exploration by genetic algorithm is assisted by the Kriging model to reduce the computational cost. The characteristics of the convex and the concave grooves are compared. To balance the global exploration and the reasonable computational cost, this paper investigates three cases with the convex grooves subject to constraint that differs in handling of design variables. In each case, genetic algorithm finds several local optima since the objective function is a multi-modal function, and these optima reveal the specific characteristic for efficient mixing. Moreover, this paper optimizes the micromixer with the concave grooves and reveals the different properties of the mixing. Finally, to guarantee the obtained solutions competitive, the sensitivity analysis is performed to the best solution in each case.

Journal ArticleDOI
TL;DR: In this article, the particle migration characters in contractionexpansion channels with contraction-expansion ratio γ = 1.0 and γ= 2.0 through numerical simulation and corresponding validation experiments.
Abstract: Inertial microfluidic device has been widely used for particle/cell manipulation in recent years, due to the attractive advantages of high throughput, low cost and simple operating. As a typical inertial microfluidic microchannel pattern, the contraction–expansion microchannel is usually applied for particle focusing or separation because of the ability to be easily parallelized. However, the mechanism of particle focusing in this channel is still vague and the effects of microchannel dimension have not been considered in the former experimental researches. This paper reports the particle migration characters in microfluidic channels with contraction–expansion ratio γ = 1.0 and γ = 2.0 through numerical simulation and corresponding validation experiments. Based on lattice-Boltzmann method (LBM)–immersed boundary method (IBM) model, which numerically describes the particle behavior in the microfluid, we study the particle-focusing mechanics in contraction–expansion microchannels further with the particle trajectory and rotation data which are not easily observed in experiments. With the simulation results, it can be found that contraction–expansion ratio can obviously influence the particles on their focusing patterns. A large γ continuous contraction–expansion microchannel needs higher flow rate to keep different-sized particles separated and has better focusing performance. The secondary flow in the cross section plays an important role to focus different size particles at different equilibrium positions. Research results of these sheathless and easily paralleled contraction–expansion microchannels can provide helpful insight for particle/cell detection chip design in the future.

Journal ArticleDOI
TL;DR: In this article, the authors demonstrate the use of normal stress differences for propulsion in a Boger fluid environment and show that when the dumbbell is asymmetric (snowman geometry), non-Newtonian normal stress difference leads to net propulsion in the direction of the smaller sphere.
Abstract: Viscoelastic fluids impact the locomotion of swimming microorganisms and can be harnessed to devise new types of self-propelling devices. Here we report on experiments demonstrating the use of normal stress differences for propulsion. Rigid dumbbells are rotated by an external magnetic field along their axis of symmetry in a Boger fluid. When the dumbbell is asymmetric (snowman geometry), non-Newtonian normal stress differences lead to net propulsion in the direction of the smaller sphere. The use of a simple model allows to rationalise the experimental results and to predict the dependence of the snowman swimming speed on the size ratio between the two spheres.

Journal ArticleDOI
TL;DR: In this article, the authors investigated the aggregation of a dense suspension of particles (volume fraction, = 0.1 ) in a PDMS microwell by employing surface acoustic wave (SAW) microcentrifugation.
Abstract: We investigate the aggregation of a dense suspension of particles (volume fraction, $$\varphi \sim 0.1$$ ) in a PDMS microwell by employing surface acoustic wave (SAW) microcentrifugation. In spite of acoustic attenuation at the LiNbO3–PDMS interface, a significant portion of the energy (> 80%) is available for driving fluid actuation, and, in particular, microcentrifugation in the microwell via acoustic streaming. Rapid particle aggregation can then be affected in the microcentrifugation flow, arising as a consequence of the interplay between the hydrodynamic pressure gradient force $$F_{\text{p}}$$ responsible for the migration of particles to the center of the microwell and shear-induced diffusion force $$F_{\text{SID}}$$ that opposes their aggregation. Herein, we experimentally investigated the combined effect of the particle size $$a$$ and sample concentration $$c$$ on these microcentrifugation flows. The experimental results show that particles of smaller size and lower sample concentration (such that $$F_{\text{p}} > F_{\text{SID}}$$ ) are concentrated efficiently into an equilibrium spot, whose diameter scales with the initial particle volume fraction as $$d_{\text{cs}} \sim \varphi^{0.3}$$ . In contrast, we found that as the local particle volume fraction at the center of the microwell approaches $$\varphi \sim 0.1$$ such that $$F_{\text{SID}} \ge F_{\text{p}}$$ , the particle aggregation fails. Additionally, we also investigate the effects of the well diameter, and the height, lateral positioning of microwell and the liquid volume on the microcentrifugation.

Journal ArticleDOI
TL;DR: In this paper, a real-time, capillary, convective polymerase chain reaction (PCR) system based on horizontal convection is developed and analyzed, where the capillary tube reactor is heated at one end in a pseudo-isothermal manner to achieve efficient thermal cycling.
Abstract: A real-time, capillary, convective polymerase chain reaction (PCR) system based on horizontal convection is developed and analyzed. The capillary tube reactor is heated at one end in a pseudo-isothermal manner to achieve efficient thermal cycling based on horizontal thermal convection. Mathematical modeling and the in silico simulations indicate that, once consistent temperature gradient along the horizontal capillary tube has been established, a repeatable and continuous circulatory flow in the horizontal directions is created. The formed convection is able to transport PCR reagents through different temperature zones inside the horizontal capillary tube for different reaction stages, that is, DNA denaturing, annealing, and extension in a typical PCR cycle. Furthermore, the effectiveness and efficiency of the horizontal convection for PCR thermal cycling in a capillary tube is confirmed by experimentation. To evaluate the concept of horizontal convective PCR, a compact system, which is able to heat the capillary tube from one end and monitor the fluorescence in situ with a smartphone camera, is developed for real-time amplification. With horizontal thermal convection, influenza A (H1N1) virus nucleic acid targets with a limit of detection (LOD) of 1.0 TCID50/mL can be successfully amplified and detected in 30 min, which is promising for efficient nucleic acid analysis in point-of-care testing.

Journal ArticleDOI
TL;DR: In this paper, the dynamics of bubble formation in a highly viscous liquid in a co-flowing microfluidic device is experimentally investigated using a high-speed camera.
Abstract: In this work, the dynamics of bubble formation in a highly viscous liquid in a co-flowing microfluidic device is experimentally investigated. The evolution of gaseous thread in the co-flowing device is recorded using a high-speed camera. The bubble formation process can be divided into three stages: retraction stage, expansion stage, and collapse stage. According to an analysis of the forces acting on the gaseous thread, the bubble formation in the co-flowing device is a competitive result of the surface tension, pressure difference and shearing effects. The surface tension effect plays an important role in the retraction stage. In the expansion stage, the pressure difference effect dominates the bubble’s growth. While in the collapse stage, the shearing effect leads to the interface breakup. Three empirical correlations are proposed according to the experimental data and can be used to predict bubble formation frequency, the diameter and length of the generated bubbles.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the fluid flow characteristics spanning a variety of distinct regimes from small wall deflections, where the deformable microchannel resembles its corresponding rigid one, to wall deflection much larger than the original height.
Abstract: The emerging field of deformable microfluidics widely employed in the Lab-on-a-Chip and MEMS communities offers an opportunity to study a relatively under-examined physics The main objective of this work is to provide a deeper insight into the underlying coupled fluid–solid interactions of a low-Reynolds-number, ie $$Re \sim O(10^{-2}$$ – $$10^{+1})$$ , fluid flow through a shallow deformable microchannel with ultra-low height-to-width-ratios, ie $$O(10^{-3})$$ The fabricated deformable microchannels of several microns in height and few millimeters in width, whose aspect ratio is about two orders of magnitude smaller than that of the previous reports, allow us to investigate the fluid flow characteristics spanning a variety of distinct regimes from small wall deflections, where the deformable microchannel resembles its corresponding rigid one, to wall deflections much larger than the original height, where the height-independent characteristic behavior emerges The effects of the microchannel geometry, membrane properties, and pressure difference across the channel are represented by a lumped variable called flexibility parameter Under the same pressure drop across different channels, any difference in their geometries is reflected into the flexibility parameter of the channels, which can potentially cause the devices to operate under distinct regimes of the fluid–solid characteristics For a fabricated microchannel with given membrane properties and channel geometry, on the other hand, a sufficiently large change in the applied pressure difference can alter the flow-structure behavior from one characteristic regime to another By appropriately introducing the flexibility parameter and the dimensionless volumetric flow rate, a master curve is found for the fluid flow through any long and shallow deformable microchannel A criterion is also suggested for determining whether the coupled or decoupled fluid–solid mechanics should be considered

Journal ArticleDOI
TL;DR: In this article, a protein detection method was proposed based on online ICP stacking and successfully used for the detection of total protein from urine samples, where proteins from physiological samples can be directly loaded onto the depletion region of the ICP interface established by a piece of cation exchange membrane on a paper fluidic channel, and the protein content can be cumulatively stacked as a narrow band as visually observed by smartphone camera.
Abstract: Charged species can be effectively stacked on paper-based analytical device (PAD) taking advantage of ion concentration polarization (ICP) effect. Protein, as ampholyte species, could also be stacked using this effect to improve its detection sensitivity. In this work, a protein detection method was proposed based on online ICP stacking and successfully used for the detection of total protein from urine samples. We showed that proteins from physiological samples can be directly and repeatedly loaded onto the depletion region of the ICP interface established by a piece of cation exchange membrane on a paper fluidic channel, and the protein content can be cumulatively stacked as a narrow band as visually observed by smartphone camera. Colorimetric detection of model protein (phyco) showed that at least 60-fold preconcentration could be achieved with this method. With post-staining of the stacked albumin from artificial urine, a linear response in the diagnostic meaningful range of 50–350 mg/L (R2 = 0.994) was achieved. Total protein from clinical urine samples was detected, and the recovery rate was found in the range of 93–108%, and the RSD was less than 11%. Comparative assays showed no significant difference between the results of this and that of the clinical method. This paper demonstrated the feasibility of online stacking and sensitive detection of proteins from physiological samples using PAD-ICP platform.

Journal ArticleDOI
TL;DR: The results suggest that the use of constant-viscosity viscoelastic fluid pushes the cells toward the channel centerline which can be used in microfluidic devices used for cell focusing such as cytometers.
Abstract: In this paper, we study a suspension of cells at a moderate volume fraction flowing in a microchannel filled with Newtonian or viscoelastic fluids and investigate the role of cell size, cell volume fraction, inertia, deformability, and fluid elasticity on the cell distribution. Our results suggest that the use of constant-viscosity viscoelastic fluid pushes the cells toward the channel centerline which can be used in microfluidic devices used for cell focusing such as cytometers. The cell-free layer increases which provides larger gap for separating rare cells in microfluidic devices. Furthermore, we show that the volumetric flow rate can be significantly enhanced with the addition of polymers in the suspending fluid. This effect enhances the processing speed which is of interest in designing microfluidic devices. This fundamental study can provide insight on the role of rheological properties of the fluid that can be tuned to control the motion of the cells for efficient design of microfluidic devices.

Journal ArticleDOI
TL;DR: In this article, a coupled continuum model incorporating size influences and geometric nonlinearity is presented for the coupled motions of viscoelastic nonlinear nanotubes conveying nanofluid.
Abstract: A coupled continuum model incorporating size influences and geometric nonlinearity is presented for the coupled motions of viscoelastic nonlinear nanotubes conveying nanofluid. A modified model of nanobeams incorporating nonlocal strain gradient effects is utilised for describing size influences on the bifurcation behaviour of the fluid-conveying nanotube. Furthermore, size influences on the nanofluid are taken into account via Beskok–Karniadakis theory. To model the geometric nonlinearity, nonlinear strain–displacement relations are employed. Utilising Hamilton’s principle and the Kelvin–Voigt model, the coupled equations of nonlinear motions capturing the internal energy loss are derived. A Galerkin procedure with a high number of shape functions and a direct time-integration scheme are then employed to extract the bifurcation characteristics of the nanofluid-conveying nanotube with viscoelastic properties. A specific attention is paid to the chaotic response of the viscoelastic nanosystem. It is found that the coupled viscoelastic bifurcation behaviour is very sensitive to the flow velocity.

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Guojun Liu1, Fang He1, Xinbo Li1, Hong Zhao1, Zhang Yanyan1, Zhiqiang Li1, Zhigang Yang1 
TL;DR: In this paper, a microfluidic chip is proposed to achieve multi-level particle separation by using the sheath flow on both sides to align the mixed particles in the set area (near the side of the channel) of the separation channel.
Abstract: Combined with acoustic separation and hydraulic separation technology, a microfluidic chip, which can achieve multi-level particle separation, is proposed in this work. The chip uses the sheath flow on both sides to align the mixed particles in the set area (near the side of the channel) of the separation channel. And then, the mixed particles successively pass through the acoustic surface wave and hydraulic action area, which are generated by modulating interdigital transducers and adjusting the flow ratio, respectively, and finally realize multiple particle separation under the acoustic radiation and hydraulic force. The corresponding separation experiments were carried out using polystyrene (PS) microparticles with diameters of 1 µm, 5 µm, and 10 µm, respectively. Moreover, we explored the influence of the peak-to-peak voltage (Vpp) and flow ratio on the PS microparticles separation effect, and the separation effect is optimal at the flowrate in the main channel is 4 mm/s, Vpp = 25 V, A1 = 0.2, A2 = 0.5. Under these conditions, the separation purity of 1 µm, 5 µm, and 10 µm PS microparticles are 95.60%, 91.67%, 93.75%, respectively, and their separation rates are 96.67%, 89.19%, and 96.77%, respectively. The combined multi-level separation chip has the advantages of simple structure, high separation accuracy, high separation efficiency, and the ability to sort multiple particles, which can be applied to chemical analysis, cell sorting, biomedicine.

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TL;DR: In this paper, the DEP forces caused by the electrode pair effectively trapped the floating liquid marble between the two electrodes, and the effects of electrode arrangements on positioning capability were studied by measuring the relative position of the floating marble to the electrodes at different voltage ratios.
Abstract: Manipulation of a floating liquid marble (LM) plays an important role in LM-based digital microfluidics for three-dimensional cell culture. Dielectrophoretic (DEP) actuation is a simple yet versatile manipulation technique that enables small droplets to be delivered across an open liquid surface. This paper reports the concept of accurately positioning a floating LM using a pair of electrodes. The experimental scheme consists of a small LM floating on an open water surface with two identical electrodes suspended above it. High voltages applied to each electrode generated a non-uniform electric field, which attracted the floating LM towards the corresponding electrode by a DEP force. The combined DEP forces caused by the electrode pair effectively trapped the floating LM between the two electrodes. By controlling the voltages of two individual electrodes respectively, the DEP forces could be tuned to accurately position the floating LM. We also studied the effects of electrode arrangements on positioning capability by measuring the relative position of the LM to the electrodes at different voltage ratios. We formulated an analytical model to describe the DEP force and obtained a governing equation that determines the LM position for various electrode configurations. In addition, we determined the effective working range of this setup and discussed future work with three or more electrodes for positioning a floating LM in two dimensions. This manipulation technique uses a simple and inexpensive setup without moving parts, which fills the gap in knowledge about controlled manipulation of LMs.

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TL;DR: This article characterizes different cell encapsulation modes and presents the droplet volume distribution, frequency of encapsulation and cell population in terms of inner and outer fluid capillary ratios and viscosity of the shell fluid.
Abstract: Flow-focusing microencapsulation is an important process to protect the cells in biomedical applications. This article characterizes different cell encapsulation modes and presents the droplet volume distribution, frequency of encapsulation and cell population in terms of inner and outer fluid capillary ratios and viscosity of the shell fluid. The desired mode of at least one cell in a droplet is determined for different capillary number ranges and each viscosity ratios. The droplet volume and frequency of droplet generation are normalized for a combined non-dimensional parameter to classify different patterns of compound droplet formation which helps us to improve single-cell encapsulation process. With increase in orifice radius, the droplet volume increases, and the success rate of cell encapsulation increases. Above a critical radius, the encapsulation mode transitions from one cell to multiple cells captured inside the droplet.