Microfluidic Mixing: A Review

The aim of microfluidic mixing is to achieve a thorough and rapid mixing of multiple samples in microscale devices. In such devices, sample mixing is essentially achieved by enhancing the diffusion effect between the different species flows. Broadly speaking, microfluidic mixing schemes can be categorized as either “active”, where an external energy force is applied to perturb the sample species, or “passive”, where the contact area and contact time of the species samples are increased through specially-designed microchannel configurations. Many mixers have been proposed to facilitate this task over the past 10 years. Accordingly, this paper commences by providing a high level overview of the field of microfluidic mixing devices before describing some of the more significant proposals for active and passive mixers

Induced-Charge Electro-Osmosis

We describe the general phenomenon of `induced-charge electro-osmosis' (ICEO) -- the nonlinear electro-osmotic slip that occurs when an applied field acts on the ionic charge it {\sl induces} around a polarizable surface. Motivated by a simple physical picture, we calculate ICEO flows around conducting cylinders in steady (DC), oscillatory (AC), and suddenly-applied electric fields. This picture, and these systems, represent perhaps the clearest example of nonlinear electrokinetic phenomena. We complement and verify this physically-motivated approach using a matched asymptotic expansion to the electrokinetic equations in the thin double-layer and low potential limits. ICEO slip velocities vary like $u_s \propto E_0^2 L$, where $E_0$ is the field strength and $L$ is a geometric length scale, and are set up on a time scale $\tau_c = \lambda_D L/D$, where $\lambda_D$ is the screening length and $D$ is the ionic diffusion constant. We propose and analyze ICEO microfluidic pumps and mixers that operate without moving parts under low applied potentials. Similar flows around metallic colloids with fixed total charge have been described in the Russian literature (largely unnoticed in the West). ICEO flows around conductors with fixed potential, on the other hand, have no colloidal analog and offer further possibilities for microfluidic applications.Comment: 36 pages, 8 figures, to appear in J. Fluid Mec

Numerical Simulations of Flow and Mass Transport in Micro-Fluidic Components for Modular Bio-Analytic Chip Applications

Microfluidics has received a great deal of attention in the past decade. The ability of modular microfluidic chips to miniaturize integrate chemical and biological systems (µTAS) can be greatly productive in terms of cost and efficiency. During the design of these modular devices, misalignment of materials, geometrical or both is one of the most common problems. These misalignments can have adverse effect in both pressure driven and electrokinetically driven flows. In the present work, Numerical Simulations have been performed to study the effect of material and geometrical mismatch on the flow behavior and species progression in microfluidic interconnects. In the case of electrokinetic flows, simulations were performed for 13%, 50%, 58% and 75% reduction in the available flow area at the mismatch plane. Correlations were developed to predict the flow rate reduction due to the geometrical mismatch in electrokinetic flows. A 13% flow area reduction was found to be insignificant and did not cause an appreciable sample loss. As the amount of geometrical mismatch increases (i.e. area reduction is more than 40%), it can have a significant effect on the sample resolution and on the flow behavior. In the case of pressure driven flows, Numerical Simulations have been performed for three types of interconnection methods: End-to-End, Channel Overlap, and Tube-in- Reservoir interconnection. The effects of geometrical misalignments in these three interconnection methods have been investigated and the results were interpreted in terms of the pressure drop and equivalent length. The amount of misalignment was varied by changing the available flow area ratios. All the configurations were simulated for practically relevant Reynolds numbers ranging from 0.075 to 75. Correlations were developed to predict the pressure drop for any given misalignment area ratio. It was found that for the misalignment area ratio of 2:1 or more, the increase in pressure drop can be drastic. Numerical simulations of Injection and separation were also performed to study the effect of curvatures on the elongation of generated plugs. These end curvatures are commonly encountered during high precision micromilling process as a method to fabricate polymer microfluidic devices. The effect of pinching and pullback voltages on the generation of the sample plugs was investigated and optimum conditions to minimize plug dispersion were found

Microfluidics: Fluid physics at the nanoliter scale

Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Péclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world

ELECTROKINETIC PARTICLE MANIPULATIONS IN SPIRAL MICROCHANNELS

Recent developments in the field of microfluidics have created a multitude of new useful techniques for practical particle and cellular assays. Among them is the use of dielectrophoretic forces in \u27lab-on-a-chip\u27 devices. This sub-domain of electrokinetic flow is particularly popular due to its advantages in simplicity and versatility. This thesis makes use of dielectrophoretic particle manipulations in three distinct spiral microchannels. In the first of these experiments, we demonstrate the utility of a novel single-spiral curved microchannel with a single inlet reservoir and a single outlet reservoir for the continuous focusing and filtration of particles. The insulator-based negative-dielectrophoretic (repulsive) force is used in a parametric study of the effects of electric field strength, particle size, and solution concentration on particle focusing abilities. It was summarily determined that all three factors are positively correlated with increased particle focusing ability. From these results, a partial filtration of 10 μm particles from a binary solution of 3 and 10 μm particles was demonstrated. Also observed was a balance between dielectrophoretic and repulsive particle-wall interactions; thus yielding a novel approach for particle manipulation. Following the results of the first, we demonstrate in the second experiment a continuous-flow electrokinetic separation of both a binary mixture and a ternary mixture of colloidal particles based on size in a single-spiral microchannel with a single inlet reservoir and triple outlet reservoirs. This method also utilizes both curvature-induced dielectrophoresis to focus particles to a tight stream and the previously observed wall-induced electric lift to manipulate the aligned particles to size-dependent equilibrium positions. Due to the continuous nature of the flow through concentric spiral loops, both focusing forces influence particles simultaneously. This novel technique is useful for its compact geometry, robust structure, ease of manufacture, and ease of use in the manipulation of independent particle species. A theoretical model is also developed to understand this separation, and the obtained analytical formula predicts the experimentally measured particle center-wall distance in the spiral with a close agreement. We demonstrate in the third experiment a continuous-flow electrical sorting of spherical and peanut-shaped particles of similar volumes in an asymmetric double-spiral microchannel with a single inlet reservoir and triple outlet reservoirs. This experiment, unlike the first two, differentiates particle species based principally on shape. Shape is an intrinsic marker of cell cycle, an important factor for identifying a bio-particle, and also a useful indicator of cell state for disease diagnostics; therefore, shape can be a specific marker in label-free particle and cell separation for various chemical and biological applications. The double-spiral geometry exploits curvature-induced dielectrophoresis to initially focus particles to a tight stream in the first spiral without any sheath flow. Particles are subsequently displaced to shape-dependent flow paths in the second spiral without any external force. We also develop a numerical model to simulate and understand this shape-based particle sorting in spiral microchannels. The predicted particle trajectories agree qualitatively with the experimental observation

Numerical Simulation of Electroosmotic Flow of Viscoelastic Fluid in Microchannel

Electroosmotic flow (EOF) has been widely used in various biochemical microfluidic applications, many of which often involve the use of viscoelastic non-Newtonian fluids. Due to the existence of the elastic effect, the viscoelastic EOF develops into chaotic flow under extremely low Reynolds numbers, which is known as elastic turbulence. The mechanism of elastic turbulence in electroosmotic flow remains unclear. Numerical simulation plays an important role in understanding the mechanisms of elastic turbulence. This dissertation is aimed to study the EOF of viscoelastic fluids in constriction microchannels under various direct current (DC) and alternating current (AC) electric fields. First, the EOF of viscoelastic fluid in a straight contraction microchannel is investigated. The influences of the polymer concentration and the applied DC electric field on the elastic instabilities are analyzed. The flow fluctuations and secondary upstream vortices before the entrance of the microchannel are found to be related to the induced elastic stress within the microchannel. The polymer concentration shows a more significant influence on the elastic instability. A flow map in polymer concentration and electric field domain is formed as guidance for further studies. Then, the study is extended to the viscoelastic EOF in a microchannel with 90◦ bends under the combination of DC and AC electric fields. The elastic turbulence is identified from the fluctuation of the velocity field and upstream vortices. The energy spectra of the velocity fluctuation show power-law decay over a wide range of frequencies, which is a typical characteristic of elastic turbulence. The 90◦ bends show influence on the dye concentration profile in cross sections of the microchannel. A more even dye concentration distribution is obtained with an increasing number of 90◦ bends. Moreover, the opening angle of the particle trace at the exit of the contraction microchannel show dependency on the frequency of the AC electric field, which is related to the characteristic frequency of the viscoelastic EOF. The study is then focused on the influence of the frequency of the AC electric field on the viscoelastic EOF. Short contraction microchannels are adopted for the frequency study. The peak in the energy spectra of the velocity fluctuation under DC electric field indicates the characteristic frequency of the viscoelastic EOF. Under AC electric field, the highest amplitude of the energy spectra is obtained when the frequency of AC electric field is close to the characteristic frequency. The same trend is also observed in the statistical results of the average velocity. However, when the frequency is relatively high, both the amplitude of the energy spectra and the average velocity decrease to a level even lower than under a DC electric field, which indicates the existence of an optimal frequency of the AC electric field in order to achieve the highest flow rate

Driving microfluidic flows with three dimensional electrodes.

Most of the structures in submillimeter-scale engineering are created from thin films, making them essentially two-dimensional (2D). Significant work has been done to fabricate 3D structures using self-folding, a deterministic form of self-assembly, and three dimensional lithographic and non-lithographic patterning. The objective of this work is to propose different fabrication and patterning strategies of 3D structures used as pumping electrodes for micro fluidic applications. 3D electrodes drive flows over the whole channel height while 2D electrodes stay near one wall. The first application of the 3D electrodes is mixing chemical or biological samples with reagents for chemical analysis which is one of the most time consuming operations in microfluidic platforms. The mixer used is based on the electrokinetic phenomenon of induced charge electro-osmosis (ICEO). ICEO creates microvortices around polarized posts with gold coated sidewalls, connected to embedded electrodes, by application of alternating current (AC) electric fields. These microvortices around posts help in mixing the two reagents very quickly. These vertical sidewall gold coated posts and embedded electrodes are fabricated using 3D photolithographic patterning and an ion milling fabrication technique. The second application is fast ac electro-osmotic (ACEO) pumps using 3D electrodes. These 3D electrodes dramatically improve the flow rate and frequency range of ACEO pumps over the planar electrodes. A non-photolithographic electrode patterning method is proposed to fabricate such electrodes. The method is based on shadowed evaporation of metal on an insulating substrate. This method is considered to be simple and cost effective compared to others used to create these stepped 3D electrodes. Finally, a self-folding technique is proposed to create out-of plane three dimensional electrodes for ACEO tube pumps. The technique depends on the strain mismatch between two different layered sheets of material. One layer usually has compressive stress, i.e. thermally grown Si02, and the other has relatively tensile stress, i.e. metals. The design is similar to the planar electrodes design in the literature, except as a 3D electrode it interacts with a larger volume of fluid for a more efficient pump

Passive Micromixers

Micro-total analysis systems and lab-on-a-chip platforms are widely used for sample preparation and analysis, drug delivery, and biological and chemical syntheses. A micromixer is an important component in these applications. Rapid and efficient mixing is a challenging task in the design and development of micromixers. The flow in micromixers is laminar, and, thus, the mixing is primarily dominated by diffusion. Recently, diverse techniques have been developed to promote mixing by enlarging the interfacial area between the fluids or by increasing the residential time of fluids in the micromixer. Based on their mixing mechanism, micromixers are classified into two types: active and passive. Passive micromixers are easy to fabricate and generally use geometry modification to cause chaotic advection or lamination to promote the mixing of the fluid samples, unlike active micromixers, which use moving parts or some external agitation/energy for the mixing. Many researchers have studied various geometries to design efficient passive micromixers. Recently, numerical optimization techniques based on computational fluid dynamic analysis have been proven to be efficient tools in the design of micromixers. The current Special Issue covers new mechanisms, design, numerical and/or experimental mixing analysis, and design optimization of various passive micromixers

ELECTROKINETIC TRANSPORT AND MANIPULATION OF PARTICLES IN CURVED MICROCHANNELS

The investigation of electrokinetic particle transport in confined microchannels has practical significances in a variety of applications ranging from traditional gel electrophoresis to electrokinetic microfluidics-based lab-on-a-chip devices. To date, however, studies on particle electrokinetics have been limited to primarily theoretical or numerical analyses in straight microchannels of simple geometries. Very little work has been done on electrokinetic particle motions in real microchannels which usually consist of one or multiple turns. This thesis is dedicated to the fundamental and applied studies of electrokinetic transport and manipulation of particles in various curved microchannels using a combined experimental, theoretical, and numerical method. First, a fundamental study of particle electrokinetics in a microchannel U-turn, a typical unit in LOC devices, was investigated. A 2-D numerical model based on finite element method was developed to understand and predict the particle motion within the U-turn. It is demonstrated that particles are deflected to the outer wall of the turn by curvature-induced dielectrophoresis (termed cDEP) due to the locally intrinsic electric field gradients. Moreover, this lateral displacement increases with the rise of either the applied electric field or the particle size. Next, we utilize the cDEP in microchannel turns to implement a continuous electrokinetic focusing of particles in serpentine microchannels. Particles are demonstrated to gradually migrate to the centerline due to the periodically switched dielectrophoretic force they experience in a serpentine microchannel. This electrokinetic focusing favors large electric fields and large particles, and also increases when the number of serpentine periods increases. Such focusing also takes place in a spiral microchannel, where, however, particles are eventually focused to a stream flowing near the outer sidewall of the channel. Then, we explore the applications of cDEP to continuous electrokinetic separation of particles in curved microchannels. We develop two different approaches based on what we have acquired from the studies of particle electrokinetics in serpentine and spiral microchannels. The first approach employs a sheath flow to focus particles to one sidewall of a serpentine microchannel, where particles are then deflected to different flow paths by cDEP and thus sorted at the exit of serpentine section. We use this method to separate particles and cells by size at low DC electric fields. The second approach eliminates the sheath flow focusing of particles by the use of particle deflection and focusing in a double-spiral microchannel. Specifically, particles are focused by cDEP to one single stream near the outer wall of the first spiral, which is then displaced by cDEP and divided into two or more sub-streams in the second spiral, enabling the continuous sorting. We use this approach to implement the separation of particles by size and by charge, respectively. Moreover, we also demonstrate a continuous ternary separation of particle by size and charge simultaneously