Characterizing electroosmotic flow in microfluidic devices

The current-monitoring method was used to measure the electroosmotic flow (EOF) in borosilicate glass capillaries and zeonor plastic microfluidic devices. The surface of the zeonor devices must be oxidized to support EOF and this treatment shows signs of aging within 6 days. Oxidized zeonor devices showed the same response to changes in applied field, pH, and ionic concentration as the capillaries. The effects of several common dynamic surfactant coatings on the walls were also studied (0.1%, v/v solutions of POP-6, POP4, Pluronics L81, and NP-40). These generally significantly suppressed the EOF but required several days to stabilize.     

Surfactant-induced electroosmotic flow in microfluidic capillaries

Control of EOF in microfluidic devices is essential in applications such as protein/DNA sizing and high‐throughput drug screening. With the growing popularity of poly(methyl methacrylate) (PMMA) as the substrate for polymeric‐based microfludics, it is important to understand the effect of surfactants on EOF in these devices. In this article, we present an extensive investigation exploring changes in EOF rate induced by SDS, polyoxyethylene lauryl ether (Brij35) and CTAB in PMMA microfluidic capillaries. In a standard protein buffer (Tris‐Glycine), PMMA capillaries exhibited a cathodic EOF with measured mobility of 1.54 ± 0.1 (× 10^?4 cm²/V.s). In the presence of surfactant below a critical concentration, EOF was independent of surfactant concentration. At high concentrations of surfactants, the electroosmotic mobility was found to linearly increase/decrease as the logarithm of concentration before reaching a constant value. With SDS, the EOF increased by 257% (compared to buffer), while it was decreased by 238% with CTAB. In the case of Brij35, the electroosmotic mobility was reduced by 70%. In a binary surfactant system of SDS/CTAB and SDS/Brij35, addition of oppositely charged CTAB reduced the SDS‐induced EOF more effectively compared to nonionic Brij35. We propose possible mechanisms that explain the observed changes in EOF and zeta potential values. Use of neutral polymer coatings in combination with SDS resulted in 50% reduction in the electroosmotic mobility with 0.1% hydroxypropyl methyl cellulose (HPMC), while including 2% poly (N,N‐dimethylacrylamide) (PDMA) had no effect. These results will potentially contribute to the development of PMMA‐based microfluidic devices.     

Interfacial thermocapillary vortical flow for microfluidic mixing

We present a method for the mixing of fluids in a quasi two-dimensional system with low Reynolds number by means of generating a vortical flow. A two-dimensional cavitation bubble is induced in liquid-expanded phase by locally heating a Langmuir monolayer at the air/liquid interface with an IR laser. The laser-induced cavitation bubble works as a microfluidic pump and generates a thermocapillary flow around the pump. As a result, the surrounding liquid-expanded phase flows in one direction. Perturbing the thermocapillary flow with solid folds that are created by compression and reexpansion of the monolayer induces the vortical flow behind the folds. Applying the equation of creeping flow, we find a torque halfway from the center causing the vortical flow. The vorticity created in this way stretches the liquid-expanded and gaseous phase in the azimuthal direction and at the same time thins both phases in the radial direction. If the vortical flow could be maintained long enough to reach a radial thinning that would allow the interdiffusion of surfactants at the surface, then this technique would open a route for the effective two-dimensional microfluidic mixing at low Reynolds numbers.     

Two simple and rugged designs for creating microfluidic sheath flow

A simple design capable of 2-dimensional hydrodynamic focusing is proposed and successfully demonstrated. In the past, most microfluidic sheath flow systems have often only confined the sample solution on the sides, leaving the top and bottom of the sample stream in contact with the floor and ceiling of the channel. While relatively simple to build, these designs increase the risk of adsorption of sample components to the top and bottom of the channel. A few designs have been successful in completely sheathing the sample stream, but these typically require multiple sheath inputs and several alignment steps. In the designs presented here, full sheathing is accomplished using as few as one sheath input, which eliminates the need to carefully balance the flow of two or more sheath inlets. The design is easily manufactured using current microfabrication techniques. Furthermore, the sample and sheath fluid can be subsequently separated for recapture of the sample fluid or re-use of the sheath fluid. Designs were demonstrated in poly(dimethylsiloxane) (PDMS) using soft lithography and poly(methyl methacrylate) (PMMA) using micromilling and laser ablation.     

Continuous and precise particle separation by electroosmotic flow control in microfluidic devices

A new scheme has been described for continuous particle separation using EOF in microfluidic devices. We have previously reported a method for particle separation, called "pinched flow fractionation (PFF)", in which size-dependent and continuous particle separation can be achieved by introducing pressure-driven flows with and without particles into a pinched microchannel. In this study, EOF was employed to transport fluid flows inside a microchannel. By controlling the applied voltage to electrodes inserted in each inlet/outlet port, the flow rates from both inlets, and flow rates distributed to each outlet could be accurately tuned, thus enabling more effective separation compared to the pressure-driven scheme. In the experiment, the particle behaviors were compared between EOF and pressure-driven flow schemes. In addition, micrometer- and submicrometer-sized particles were accurately separated and individually collected using a microchannel with multiple outlet branch channels, demonstrating the high efficiency of the presented scheme.     

Electric field-decoupled electroosmotic pump for microfluidic devices

An electric field-free electroosmotic pump has been constructed and its pumping rate has been measured under various experimental conditions. The key component of the pump is an ion-exchange membrane grounding joint that serves two major functions: (i) to maintain fluid continuity between pump channels and microfluidic conduit and (ii) to ground the solution in the microfluidic channel at the joint through an external electrode, and hence to decouple the electric field applied to the pump channels from the rest of the microfluidic system. A theoretical model has been developed to calculate the pumping rates and its validity has been demonstrated.     

Tradeoff between mixing and transport for electroosmotic flow in heterogeneous microchannels with nonuniform surface potentials

Electroosmotic flow (EOF) is a phenomenon associated with the movement of an aqueous solution induced by the application of an electric field in microchannels. The characteristics of EOF depend on the nature of the surface potential, i.e., whether it is uniform or nonuniform. In this paper, a lattice Boltzmann model (LBM) combined with the Poisson-Boltzmann equation is used to simulate flow field in a rectangular microchannel with nonuniform (step change) surface potentials. The simulation results indicate that local circulations can occur near a heterogeneous region with nonuniform surface potentials, in agreement with those by other authors. Largest circulations, which imply a highest mixing efficiency due to convection and short-range diffusion, were found when the average surface potential is zero, regardless of whether the distribution of the heterogeneous patches is symmetric or asymmetric. In this work, we have illustrated that there is a trade-off between the mixing and liquid transport in EOF microfluidics. One should not simply focus on mixing and neglect liquid transport, as performed in the literature. Excellent mixing could lead to a poor transport of electroosmotic flow in microchannels.     

Numerical calculation of the electroosmotic flow at the cross region in microfluidic chips.

A numerical study is presented for the electroosmotic flow (EOF) at the cross region in microfluidic chips. The distributions of the electric potential due to the electric double layer (EDL) and the external electric field are discussed and the calculation of the latter can give rough speculations on the flow tendencies in the channels during various operation modes. Simplification of the two-dimensional Navier-Stokes (N-S) equations is obtained by focusing on the solution of interior flows, and the numerical calculation results show good agreement with the experimental images. The sample leakage to the separation channel during the "float" sampling proved to be caused not only by the sample diffusion, but also by the weak extension of the sampling electric field. It is also verified that with suitable voltage configuration, the "pinch" sampling mode is better than the "float" mode in sample plug control.     

Covalent anionic copolymer coatings with tunable electroosmotic flow for optimization of capillary electrophoretic separations

We present a method for finely adjustable electroosmotic flow (EOF) velocity in cathodic direction for the optimization of separations in capillary electrophoresis. To this end, we use surface modification of the separation fused silica capillary by the covalently attached copolymer of acrylamide (AM) and 2-acrylamido-2-methyl-1-propanesulfonate (AMPS), that is, poly(AM-co-AMPS) or PAMAMPS. Coatings were formed by the in-capillary polymerization of a mixture of the neutral AM and anionic AMPS monomers premixed in various ratios in order to control the charge density of the copolymer. EOF mobility varies in the 0 to ∼40 × 10⁻⁹ m² V⁻¹ s⁻¹ interval for PAMAMPS coatings ranging from 0 to 60 mol.% of charged AMPS monomer. For EOF in PAMAMPS-treated capillaries, we observed (i) a negligible dependence on pH in the 2–10 interval, (ii) a minor variance among background electrolytes (BGEs) in function of their components and (iii) its standard decrease with increasing ionic strength of the BGE. Interest in variable cathodic EOF was demonstrated by the amelioration of separation of two kinds of isomeric anionic analytes, that is, monosaccharides phosphates and helquat enantiomers, in counter-EOF mode.     

Assessment of Joule heating and its effects on electroosmotic flow and electrophoretic transport of solutes in microfluidic channels

Joule heating is inevitable when an electric field is applied across a conducting medium. It would impose limitations on the performance of electrokinetic microfluidic devices. This article presents a 3-D mathematical model for Joule heating and its effects on the EOF and electrophoretic transport of solutes in microfluidic channels. The governing equations were numerically solved using the finite-volume method. Experiments were carried out to investigate the Joule heating associated phenomena and to verify the numerical models. A rhodamine B-based thermometry technique was employed to measure the solution temperature distributions in microfluidic channels. The microparticle image velocimetry technique was used to measure the velocity profiles of EOF under the influence of Joule heating. The numerical solutions were compared with experimental results, and reasonable agreement was found. It is found that with the presence of Joule heating, the EOF velocity deviates from its normal "plug-like" profile. The numerical simulations show that Joule heating not only accelerates the sample transport but also distorts the shape of the sample band.     

Role of streaming potential on pulsating mass flow rate control in combined electroosmotic and pressure-driven microfluidic devices

In the present study, we investigate the implications of streaming potential on the mass flow rate control in a microfluidic device actuated by the combined application of a pulsating pressure gradient and a pulsating, externally applied, electric field. We demonstrate that the temporal dynamics due to streaming potential effects may lead to interesting non-trivial aspects of the resultant transport characteristics. Our results highlight the importance of an adequate accounting of the streaming potential effects for temporally tunable mass flow rate control strategies, which may act as a useful design artifice to augment mass flow rates in practical scenarios.     

Nanosized drug formulations under microfluidic continuous flow

We present a simple method involving a rotating tube processor to fabricate ultrafine crystalline drug nanoparticles under microfluidic continuous flow with precise control over particle size, with significantly enhanced dissolution of the drug.     

System peaks and optimization of anion separation in capillary electrophoresis with non-reversed electroosmotic flow

We studied system peaks present in the electropherograms obtained in the separation of anions by capillary electrophoresis with indirect spectrophotometric detection and cathode electroosmotic flow (EOF) with a chromate background electrolyte. The system peaks correspond to the zones with changed concentration of the background electrolyte; they formed when the zones of each analyte passed through the outlet of the capillary and then moved towards the EOF detector. It has been revealed that the height and area of the system peaks linearly depends on the concentration of the corresponding anion and the areas of the system peaks can achieve 10% of the anion peak area. An algorithm has been proposed for the determination of the optimal conditions for anion separation using hydrodynamic pressure for the regulation of the EOF flow rate. This algorithm prevents the overlapping of the anion and system peaks.     

Combinatorial mixing of microfluidic streams

We have devised a microfluidic mixer design that produces all the mixture combinations of a given number of dilutions of the input compounds. As proof of the concept, we present a device that generates four titrations of two dye solutions, blue and yellow, and combinatorially mixes the blue titrations with the yellow titrations to deliver the sixteen mixture combinations in separate outlet microchannels. Our device features four different flow levels made by stacking nine laser-cut Mylar laminates. The fluidic network has a symmetric design that guarantees that the flow rates are the same at all the outlets, with deviations attributable to imperfections in the fabrication, assembly, or perfusion processes. Design rules for scaling up the number of compounds and/or dilutions are presented. The mixing scheme has broad applicability in high-throughput combinatorial testing applications such as drug screening, cell-based biochemical assays, lab-on-a-chip devices, and biosensors.     

Hydrodynamic flow and electroosmotic flow in zirconia-packed capillaries

Fused-silica capillaries were packed with Zirchrom-PBD stationary phase for application in CEC, nanoLC and pseudoelectrochromatography (PEC). Acido-basic properties of zirconia can be used to control the EOF even if the zirconia particles were coated by polybutadiene. As for native zirconia, the EOF is pH-dependent and the pI is close to pH 5. The mixed-mode pressure-voltage technique induced a modulation of the mobile-phase velocity as well as an electrophoretic migration of the solutes in order to improve the resolution of the separation. A significant increase of the flow appeared when both hydrodynamic and EOFs were in the same direction. But an important reduction of the electroosmotic velocity was observed when the hydrodynamic flow and EOF were opposed in Zirchrom-PBD columns. This behaviour has been observed at high or low pH on several columns. Separations of neutral and charged compounds have been performed with these columns in PEC mode.     

Sample stacking and sweeping in microemulsion electrokinetic chromatography under pH-suppressed electroosmotic flow

Two on-line sample concentration techniques, sample stacking and sweeping under pH-suppressed electroosmotic flow, were evaluated in microemulsion electrokinetic chromatography. The concept of stacking with anion selective electrokinetic injection and a water plug in a reverse-migrating microemulsion (SASIW-RMME) was brought forward in this article. Six flavonoids were concentrated using a microemulsion consisting of 80 mM sodium dodecyl sulfate, 1.2% (v/v) ethyl acetate, 0.6% (v/v) 1-butanol, 10% acetonitrile (v/v) and 50 mM phosphoric acid (pH* 1.8). Significant detector response improvements were achieved. The limits of detection were in the low ng/ml level. Finally, the sample of Fructus aurantii Immaturus was analyzed using sweeping technique.     

Separation of dsDNA in the presence of electroosmotic flow under discontinuous conditions

Separations of phiX-174/HaeIII DNA restriction fragments have been performed in the presence of electroosmotic flow (EOF) using five different polymer solutions, including linear polyacrylamide (LPA), poly(ethylene oxide) (PEO), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), and agarose. During the separation, polymer solutions entered the capillary by EOF. When using LPA solutions, bulk EOF is small due to adsorption on the capillary wall. On the other hand, separation is faster and better for the large DNA fragments (> 872 base pairs, bp) using derivative celluloses and PEO solutions. Several approaches to optimum resolution and speed by controlling EOF and/or altering electrophoretic mobility of DNA have been developed, including (i) stepwise changes of ethidium bromide (0.5-5 microg/mL), (ii) voltage programming (125-375 V/cm), (iii) use of mixed polymer solutions, and (iv) use of high concentrations of Tris-borate (TB) buffers. The DNA fragments ranging from 434 to 653 bp that were not separated using 2% PEO (8,000,000) under isocratic conditions have been completely resolved by either stepwise changes of ethidium bromide or voltage programming. Compared to PEO solutions, mixed polymer solutions prepared from PEO and HEC provide higher resolving power. Using a capillary filled with 600 mM TB buffers, pH 10.0, high-speed (< 15 min) separation of DNA (pBR 322/HaeIII digest, pBR 328/ Bg/l digest and pBR 328/Hinfl digest) has been achieved in 1.5% PEO.     

Transient isotachophoresis of highly saline trace metals under strong electroosmotic flow conditions

Transient isotachophoresis (TITP) is usually performed under low-electroosmotic flow (EOF) conditions using a coated capillary or a low pH background electrolyte. We used a bare fused-silica capillary for TITP stacking of anionic complexes of some heavy metals under high-EOF conditions (pH 9.0). The sample component chloride as a leading electrolyte induced stacking by an isotachophoretic mechanism and the complexing agent 4-(2-pyridylazo) resorcinol (PAR) acted as a terminating electrolyte. The optimized background electrolyte was composed of 150 mM N-tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid, 127 mM triethylamine, and 0.1 mM PAR at pH 9.0. The strong EOF at pH 9.0 pulled the analytes against their mobilities toward the outlet side, allowing a separation in the normal polarity mode. The stacking efficiency, reproducibility, analysis time, and sample loading capacity in coated and bare capillaries were compared. The stacking efficiency and reproducibility were higher and the analysis time was shorter in the coated capillary. However, a larger volume of a sample could be injected in the bare capillary to achieve detection limits comparable to those for the coated one without compromising the resolution between the analyte peaks. The limits of detection (S/N = 3) were in the sub-ppb range for the selected metals (Fe2+, 0.3 ppb; Ni2+, 0.16 ppb; and Zn2+, 0.8 ppb) in a standard saline sample with 250 mM NaCl matrix. The proposed method was successfully applied to the analysis of reference urine samples and human urine samples.     

Generation of concentration gradient by controlled flow distribution and diffusive mixing in a microfluidic chip

We have developed a simple method to generate a concentration gradient in a microfluidic device. This method is based on the combination of controlled fluid distribution at each intersection of a microfluidic network by liquid pressure and subsequent diffusion between laminas in the downstream microchannel. A fluid dynamic model taking into account the diffusion coefficient was established to simulate the on-chip flow distribution and diffusion. Concentration gradients along a distance of a few hundred micrometers were generated in a series of microchannels. The gradients could be varied by carefully regulating the liquid pressure applied to the sample injection vials. The observed concentration gradients of fluorescent dyes generated on the microfluidic channel are consistent with the theoretically predicted results. The microfluidic design described in this study may provide a new tool for applications based on concentration gradients, including many biological and chemical analyses such as cellular reaction monitoring and drug screening.