Design Of Microfluidic Devices Research Articles

Synchronous volume and color self-oscillating gels based on chemomechanical coupling

A novel Belousov-Zhabotinsky (BZ) gels which were observed volume and color self-oscillating periodically and autonomously in a closed homogeneous solution free of acid without any external stimuli were prepared successfully and the self-oscillating could last more than 3 h. The cross-linked gels are composed of a non-thermoresponsive and biocompatible poly(vinylpyrrolidone) (PVP), acrylic acid (AA) and 5-acrylamide-1,10-phenanthroline bis(1,10-phenanthroline) iron(II) (Fe(phen)3), which act as the catalyst for the BZ reaction. The amplitude of the diameter oscillation for cylindrical gels was about 20 μm to approximately 5% of its initial diameter. The period of the volume oscillation was about 250 s. A moving chemical wave was observed directly propagation across cylindrical gels. The reversible changes in volume and color, the moving chemical wave in the gels have potential applications in the design of microfluidic devices and mass-transport systems under mild pH conditions.

An Open Software Platform for the Automated Design of Paper-Based Microfluidic Devices

Paper-based microfluidic devices have many applications in biomedical and environmental analysis. However, the process of prototyping device designs can be tedious, error-prone, and time-consuming. Here, we present a cross-platform, open-source software tool—AutoPAD—developed to quickly create and modify device designs and provide a free alternative to commercial design software. The capabilities that we designed to be inherent to AutoPAD (e.g., automatic zone alignment and design refactoring) highlight its potential use in nearly any paper-based microfluidic device application and for creating nearly any desired design, which we demonstrate through the recreation of numerous device designs from the literature.

Self-Similar Interfacial Impedance of Electrodes in High Conductivity Media.

Electrode polarization (EP) happening due to accumulation of ions at the electrode/electrolyte interface is an inevitable phenomenon while measuring impedance spectrum in high conductivity buffers and at low RF spectrum. Well-characterized time scales elucidating the EP effect are important for the rational design of microfluidic devices and impedance sensors. In this Article, interfacial impedance at the electrode/electrolyte interface is investigated considering channel height and Debye length effects on characteristic time scale in a binary electrolyte solution using parallel plate electrode configuration. Experimental results reveal self-similarity of normalized electrical impedance as a function of the normalized frequency. The experimental results also match with numerical solutions obtained by finite element simulation of unsteady fully coupled Poisson-Nernst-Planck (PNP) equations. Furthermore, fractal shaped gold nanostructured electrodes are examined, and it has been proven that electric double layer (EDL) formed on porous electrode surfaces acts as a thick EDL and modifications to the characteristic time scale is necessary for porous electrodes. Finally, a constant phase element (CPE) model is proposed to account for the self-similar impedance spectrum, which can be used for different channel heights and solution conductivities.

Numerical design of a T-shaped microfluidic device for deformability-based separation of elastic capsules and soft beads.

We propose a square cross-section microfluidic channel with an orthogonal side branch (asymmetric T-shaped bifurcation) for the separation of elastic capsules and soft beads suspended in a Newtonian liquid on the basis of their mechanical properties. The design is performed through three-dimensional direct numerical simulations. When suspended objects start near the inflow channel centerline and the carrier fluid is equally partitioned between the two outflow branches, particle separation can be achieved based on their deformability, with the stiffer ones going "straight" and the softer ones being deviated to the "side" branch. The effects of the geometrical and physical parameters of the system on the phenomenon are investigated. Since cell deformability can be significantly modified by pathology, we give a proof of concept on the possibility of separating diseased cells from healthy ones, thus leading to illness diagnosis.

Polymer-based microfluidic chips for isothermal amplification of nucleic acids

Creation of low-cost compact devices based on microfluidic platforms for biological and medical research depends on the degree of development and enhancement of prototyping technologies. Two designs of polymer and hybrid microfluidic devices fabricated by soft lithography and intended for isothermal amplification and polymerase chain reaction are presented in this paper. The digital helicase-dependent isothermal amplification was tested in the device containing a droplet generator. Polymerase chain reaction was carried out in the hybrid microfluidic device having ten reaction chambers. A synthesized cDNA fragment of GAPDH housekeeping gene was used as a target.

Multiple Myeloma Cell Drug Responses Differ in Thermoplastic vs PDMS Microfluidic Devices.

Poly(dimethylsiloxane) (PDMS) is a commonly used elastomer for fabricating microfluidic devices, but it has previously been shown to absorb hydrophobic molecules. Although this has been demonstrated for molecules such as estrogen and Nile Red, the absorption of small hydrophobic molecules in PDMS specifically used to treat cancer and its subsequent impact on cytotoxicity measurements and assays have not been investigated. This is critical for the development of microfluidic chemosensitivity and resistance assay (CSRA) platforms that have shown potential to help guide clinical therapy selection and whichrely on the accuracy of the readout involving interactions between patient-derived cells and cancer drugs. It is thus important to address the issue of drug absorption into device material. We investigated drug absorption into microfluidic devices by treating multiple myeloma (MM) tumor cells with two MM drugs (bortezomib (BTZ) and carfilzomib (CFZ)) in devices fabricated using three different materials (polystyrene (PS), cyclo-olefin polymer (COP), and PDMS). Half-maximal inhibitory concentrations (IC50) were obtained for each drug-material combination, and an increase in IC50 of ∼4.3× was observed in PDMS devices compared to both thermoplastic devices. Additionally, each MM drug was exposed to polymer samples, and samples were analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS) to characterize adsorption and absorption of the drugs into each material. ToF-SIMS data showed the bias observed in IC50 values found in PDMS devices was directly related to the absorption of drug during dose-response experiments. Specifically, BTZ and CFZ absorption in both PS and COP were all in the range of ∼100-300 nm, whereas BTZ and CFZ absorption in PDMS was ∼5.0 and ∼3.5 μm, respectively. These results highlight the biases that exist in PDMS devices and the importance of material selection in microfluidic device design, especially in applications involving drug cytotoxicity and hydrophobic molecules.

Control of molecular shuttles by designing electrical and mechanical properties of microtubules.

Kinesin-driven microtubules have been focused on to serve as molecular transporters, called "molecular shuttles," to replace micro/nanoscale molecular manipulations necessitated in micro total analysis systems. Although transport, concentration, and detection of target molecules have been demonstrated, controllability of the transport directions is still a major challenge. Toward broad applications of molecular shuttles by defining multiple moving directions for selective molecular transport, we integrated a bottom-up molecular design of microtubules and a top-down design of a microfluidic device. The surface charge density and stiffness of microtubules were controlled, allowing us to create three different types of microtubules, each with different gliding directions corresponding to their electrical and mechanical properties. The measured curvature of the gliding microtubules enabled us to optimize the size and design of the device for molecular sorting in a top-down approach. The integrated bottom-up and top-down design achieved separation of stiff microtubules from negatively charged, soft microtubules under an electric field. Our method guides multiple microtubules by integrating molecular control and microfluidic device design; it is not only limited to molecular sorters but is also applicable to various molecular shuttles with the high controllability in their movement directions.

Simulation analysis of rectifying microfluidic mixing with field-effect-tunable electrothermal induced flow.

We report herein field-effect control on in-phase electrothermal streaming from a theoretical point of view, a phenomenon termed "alternating-current electrothermal-flow field effect transistor" (ACET-FFET), in the context of a new technology for handing analytes in microfluidics. Field-effect control through a gate terminal endows ACET-FFET the ability to generate arbitrary symmetry breaking in the transverse vortex flow pattern, which makes it attractive for mixing microfluidic samples. A computational model is developed to study the feasibility of this new microfluidic device design for micromixing. The influence of various parameters on developing an efficient mixer is investigated, and an integrated layout of discrete electrode array is suggested for achieving high-throughput mixing. Our physical demonstration with field-effect electrothermal flow control using a simple electrode structure proves invaluable for designing active micromixers for modern micro total analytical system.

Tunable backflow in chiral nematic liquid crystals via twist-bend nematogens and surface-localised in-situ polymer protrusions

ABSTRACTDynamic electro-optic response of the liquid crystal (LC) director shows a backflow effect that is manifested as an optical bounce in chiral nematic LCs (N*LC) during field-induced homeotropic-twisted transition. The bend elastic constant (K33) strongly influences the dynamics of backflow at the N*LC in homeotropic-twisted transition. The cyanobiphenyl LC dimers – CB7CB, CB9CB and CB11CB – possess a unique characteristic of inherent bend molecular configuration that lowers K33. With the modulation of the effective K33 in dimer-doped N*LCs, we report the tunability of the optical bounce that decreases with the increase in the length of flexible spacers in LC dimers. The doped LC dimers with short spacer lengths not only generate a strong backflow with an enhanced twist degeneracy of the LC director across the cell, but also prolong the time of disappearance of the optical bounce. Furthermore, we demonstrate the suppression of the optical bounce with surface localised polymer protrusions having 50–100 nm diameters, which allow faster dynamic relaxation process and reduced backflow. We envision a novel design of a tunable microfluidic device for precise flow control of organic or inorganic matter in LC medium that exploits the tunable backflow in LC dimer-doped N*LCs.

Hydrodynamic interaction of blood cells with micro-rough surfaces in a shear flow

In this paper, we address hydrodynamic interactions of individual red blood cells (erythrocytes) with micro-rough surfaces in a shear flow of a viscous fluid using computer simulations. We study the influence of the microrelief on the dynamics of cell movement. It has been shown that periodic microrelief with typical length scale comparable with the size of an erythrocyte may cause an increase of the repulsive hydrodynamic force directed outwards on the micro-rough wall. The results can be used in the design of microfluidic devices that are intended to operate with whole blood samples.

Hydrodynamic front-like swarming of phoretically active dimeric colloids

Self-propelled phoretic colloids have recently emerged as a promising avenue for the design of artificial microswimmers. Here we show how systems of thermophobic dimeric swimmers can form swarms, in the sense of clusters with an ordered collective net motion. The interplay of attractive hydrodynamic with repulsive phoretic interactions leads to the formation of swarming structures with a flattened geometry in three-dimensional systems. The design of microfluidic devices and of bio-compatible microrobots can benefit from these dynamic and controllable systems.

Magnetohydrodynamic flow with slippage in an annular duct for microfluidic applications

In this paper, we investigate theoretically the 3D laminar flow of an electrolyte in an annular duct driven by a Lorentz force. The duct is formed by two concentric electrically conducting cylinders limited by insulating bottom and top walls. A uniform magnetic field acts along the axial direction, while a potential difference is applied between the cylinders so that a radial electric current traverses the fluid. The interaction of the current and the magnetic field produces a Lorentz force that drives an azimuthal flow. The steady flow is solved using a Galerkin method with Bessel–Fourier series in the radial direction and trigonometric series along the vertical direction, allowing different combinations of slip conditions at the walls. The orthogonality of both series with the general boundary conditions of the third kind is used to find an analytic approximation. Velocity patterns and flow rates are explored by varying the aspect ratio of the duct and the gap between the cylinders, as well as the slippage at the walls. Results can provide useful information for optimization and design of annular microfluidic devices.

Magnetic-field-driven alteration in capillary filling dynamics in a narrow fluidic channel.

We investigated pressure-driven transport of an immiscible binary system, constituted by two electrically conducting liquids, in a narrow fluidic channel under the influence of an externally applied magnetic field. The surface wettability was taken into account in the analysis considering that the walls of the channel are chemically treated to obtain various predefined contact angles as required for the study. Alterations in the capillary filling and wetting dynamics in the channel stemming from a complex interplay among different forces acting over the interface were investigated. It was shown that an alteration in the strength of the magnetic field leads to an alteration in the dynamics of the interface, which in turn, alters the filling and wetting dynamics nontrivially upon interaction with the surface tension force due to the wetted walls of the channel. It is emphasized that a contrast in properties of constituents of the binary system gives rise to an alteration in the forces being applied across the interface, leading to an intricate control over the filling and wetting dynamics for a given flow configuration and an applied field strength. We believe that the results obtained from this analysis may aid the design of microfluidic devices used for multiphase transport.

Investigation into the Effect of Acoustic Radiation Force and Acoustic Streaming on Particle Patterning in Acoustic Standing Wave Fields.

Acoustic standing waves have been widely used in trapping, patterning, and manipulating particles, whereas one barrier remains: the lack of understanding of force conditions on particles which mainly include acoustic radiation force (ARF) and acoustic streaming (AS). In this paper, force conditions on micrometer size polystyrene microspheres in acoustic standing wave fields were investigated. The COMSOL® Mutiphysics particle tracing module was used to numerically simulate force conditions on various particles as a function of time. The velocity of particle movement was experimentally measured using particle imaging velocimetry (PIV). Through experimental and numerical simulation, the functions of ARF and AS in trapping and patterning were analyzed. It is shown that ARF is dominant in trapping and patterning large particles while the impact of AS increases rapidly with decreasing particle size. The combination of using both ARF and AS for medium size particles can obtain different patterns with only using ARF. Findings of the present study will aid the design of acoustic-driven microfluidic devices to increase the diversity of particle patterning.

A new microfluidic device design for a defined positioning of neurons in vitro.

A new triangle-shaped microfluidic channel system for defined cell trapping is presented. Different variants of the same basic geometry were produced to reveal the best fitting parameter combinations regarding efficiency and sensitivity. Variants with differences in the trap gap width and the inter-trap distance were analyzed in detail by Computational Fluid Dynamics simulations and in experiments with artificial beads of different sizes (30, 60, 80 μm). Simulation analysis of flow dynamics and pressure profiles revealed strongly reduced pressure conditions and balanced flow rates inside the microfluidic channels compared to commonly used systems with meandering channels. Quantitative experiments with beads showed very good trapping results in all channel types with slight variations due to geometrical differences. Highest efficiency in terms of fast trap filling and low particle loss was shown with channel types having a larger trap gap width (20 μm) and/or a larger inter-trap distance (400 μm). Here, experimental success was achieved in almost 85% to 100% of all cases. Particle loss appeared significantly more often with large beads than with small beads. A significantly reduced trapping efficiency of about 50% was determined by using narrow trap gaps and a small inter-trap distance in combination with large 80 μm beads. The combination of the same parameters with small and medium beads led to an only slight decrease in trapping efficiency (80%). All channel types were tested qualitatively with invertebrate neurons from the pond snail Lymnaea stagnalis. The systems were appropriate to trap those sensitive neurons and to keep their viability in the trapping area at the same time.

Design and Verification of a Blood Cell Separation Microfluidic Device

Blood cell separation microdevices are designed in biomedical engineering for the separation of particular cells from blood, such as cancer cells. The movement of blood microparticles, specially these cancer cells, in a continuous flow microfluidic device is controlled by several forces, as a result, understanding and guiding the movement of these microparticles is a challenging problem. These cells are subject to different types of forces that result from natural or external effects. These forces include gravity, and virtual mass, buoyancy, dielectrophoresis and, inertia force. Therefore, all of these are to be accounted for in any design or implementation of a system. This paper we use formal analysis of a separation microdevice in order to model and verify the the microparticle movement and behavior at high level of abstraction while considering different types of forces. The the dynamic behavior of the particle can be modeled as a Markovian decision process in order to predict the trajectory of microparticles. This model can be used to provide probabilistic analysis for the particle movement in the microdevice under the effect of different types of forces.

Virtualization of fluid-dynamics in micro-air assisted extruders for food microfluidic based encapsulation

Microfluidic technique represents an interesting technological solution for the production of alginate microbeads in pharmaceutical, food and cosmetics industry. Given the characteristic small size of microfluidic devices and the extremely complex dynamics which are at the base of transport phenomena involved in this process, a purely experimental approach is not able to provide all significant data to design cheap but trustable devices. In this work, a virtual approach – based on computational fluid dynamics analysis – has been proposed to analyze the behavior of a micro air-assisted extruder and to provide mechanistic insight into the particle formation dynamics. The particle formation was characterized by a complex periodic dynamics, during which elongations and instabilities brought to merging of liquid droplets, of different main size, into bigger drops.Jet instabilities dominating the drops break-up dynamics were greatly influenced by geometric parameters: the fluid-dynamic analysis showed that small misalignment can dramatically change the jet breakup dynamics, introducing a completely different framework.The analysis proposed in this work represents a powerful tool for the design of simple and cheap microfluidic devices, capable of mass production of small (around 300 μm of diameter) and regular alginate microbeads, at least for matrix encapsulation.

Influence of combined electromagnetohydrodynamics on microchannel flow with electrokinetic effect and interfacial slip

We investigate analytically the combined consequences of electromagnetohydrodynamic forces and interfacial slip on streaming potential mediated pressuredriven flow in a microchannel. Going beyond traditional Debye-Huckel limit, we first derive a closed-form analytical solution for velocity field by considering nonlinear electrical potential distribution, wall slip effects, externally imposed transverse magnetic field, and laterally applied electric field in the plane of flow. The effects of electrical double-layer (EDL) formation and the consequent interfacial phenomena are critically examined under such situations. An expression for induced streaming potential in the microchannel is deduced considering EDL formation and the consequences of finite conductance of the immobilized Stern layer. This simplified analytical expression is later on critically assessed against three-dimensional simulation paradigm of streaming potential mediated flows, which is a first effort of this kind. We demonstrate that flow rate increases progressively with increasing surface potential and eventually approaches to a limiting value. Combination of electromagnetohydrodynamic effect with liquid slip is shown to amplify the flow rate, even at lower values of surface potential. Our study brings out the possibility of achieving an optimum flow rate by judicious application of combined electromagnetohydrodynamics. The present analysis has significant consequence in the design of advanced microfluidic devices with improved efficiency and functionality.

Design and characterization of hydrogel-based microfluidic devices with biomimetic solute transport networks.

Hydrogel could serve as a matrix material of new classes of solar cells and photoreactors with embedded microfluidic networks. These devices mimic the structure and function of plant leaves, which are a natural soft matter based microfluidic system. These unusual microfluidic-hydrogel devices with fluid-penetrable medium operate on the basis of convective-diffusive mechanism, where the liquid is transported between the non-connected channels via molecular permeation through the hydrogel. We define three key designs of such hydrogel devices, having linear, T-shaped, and branched channels and report results of numerical simulation of the process of their infusion with solute carried by the incoming fluid. The computational procedure takes into account both pressure-driven convection and concentration gradient-driven diffusion in the permeable gel matrix. We define the criteria for evaluation of the fluid infusion rate, uniformity, solute loss by outflow and overall performance. The T-shaped channel network was identified as the most efficient one and was improved further by investigating the effect of the channel-end secondary branches. Our parallel experimental data on the pattern of solute infusions are in excellent agreement with the simulation. These network designs can be applied to a broad range of novel microfluidic materials and soft matter devices with distributed microchannel networks.

Modeling of dielectrophoretic particle motion: Point particle versus finite-sized particle.

Dielectrophoresis (DEP) is a very popular technique for microfluidic bio-particle manipulation. For the design of a DEP-based microfluidic device, simulation of the particle trajectory within the microchannel network is crucial. There are basically two approaches: (i) point-particle approach and (ii) finite-sized particle approach. In this study, many aspects of both approaches are discussed for the simulation of direct current DEP, alternating current DEP, and traveling-wave DEP applications. Point-particle approach is implemented using Lagrangian tracking method, and finite-sized particle is implemented using boundary element method. The comparison of the point-particle approach and finite-sized particle approach is presented for different DEP applications. Moreover, the effect of particle-particle interaction is explored by simulating the motion of closely packed multiple particles for the same applications, and anomalous-DEP, which is a result of particle-wall interaction at the close vicinity of electrode surface, is illustrated.