Liquid Microjunction Surface Sampling Probe Fluid Dynamics: Characterization and Application of an Analyte Plug Formation Operational Mode

The recently discovered sample plug formation and injection operational mode of a continuous flow, coaxial tube geometry, liquid microjunction surface sampling probe (LMJ-SSP) was further characterized and applied for concentration and mixing of analyte extracted from multiple areas on a surface and for nanoliter-scale chemical reactions of sampled material. A transparent LMJ-SSP was constructed and colored analytes were used so that the surface sampling process, plug formation, and the chemical reactions could be visually monitored at the sampling end of the probe before being analyzed by mass spectrometry of the injected sample plug. Injection plug peak widths were consistent for plug hold times as long as the 8 min maximum attempted (RSD below 1.5%). Furthermore, integrated injection peak signals were not significantly different for the range of hold times investigated. The ability to extract and completely mix individual samples within a fixed volume at the sampling end of the probe was demonstrated and a linear mass spectral response to the number of equivalent analyte spots sampled was observed. Using the color and mass changing chemical reduction of the redox dye 2,6-dichlorophenol-indophenol with ascorbic acid, the ability to sample, concentrate, and efficiently run reactions within the same plug volume within the probe was demonstrated.     

Novel electroosmotic micromixer configuration based on ion-selective microsphere

In this paper, a micromixer of a new configuration is presented, consisting of a spherical chamber in the center of which an ion-selective microsphere is placed. Stratified liquid is introduced through the chamber via inlet and outlet holes under an external pressure gradient and an external electric field is directed in such a way that the resulting electroosmotic flow is directed against the pressure-driven flow, resulting in mixing. The investigation is carried out by direct numerical simulation on a super-computer. Optimal values of the applied electric field are determined to yield strong mixing. Above this optimal mixing regime, a number of instabilities and bifurcations are realized, which qualitatively coincide with those occurring during electrophoresis of an ion-selective microgranule. As shown by our calculation, these instabilities do not lead to an enhanced mixing. The resulting electroconvective vortices remain confined near the surface of the microgranule, and do not sufficiently perturb the stratified fluid flow further from the granule. On the other hand, another type of instability caused by the salt concentration gradient can generate sufficiently strong oscillations to enhance mixing. However, this only occurs when the external electric field is sufficiently high that the electroosmotic flow is comparable to the pressure-driven flow. This ultimately leads to creation of reverse flows of the liquid and cessation of the device operation. Thus, it was shown that the best mixing occurs in the absence of electrokinetic instability. Based on the data obtained, it is possible to select the necessary geometric characteristics of the micromixer to achieve the optimal mixing mode for a given set of liquids, which may be ten times more effective than passive mixers at the same flow rates. A comparison with the experimental data of the other authors confirms the effectiveness of this device and its other capabilities. Furthermore, the basic device design can be operated in other modes, for example, an electrohydrodynamic pump, a streaming current generator, or even a micro-reactor, depending on the system parameters and choice of an ion-selective granule.     

Numerical study of a novel induced-charge electrokinetic micro-mixer

A novel micro-mixer based on the induced-charge electrokinetic motion of an electrically conducting particle is proposed and numerically demonstrated in this paper. For most microfluidic applications, it is desired to mix different streams of solutions rapidly in a continuous flow mode. Therefore, in this work, we consider a mixing chamber containing an electrically conducting particle and the mixing chamber is located in the middle of a microchannel. Vortices are generated around the electrically conducting particle in an aqueous solution due to the interaction of the applied electric field and the induced surface charge on the particle. These vortices will enhance significantly the mixing of different solutions around the particle. The effectiveness of mixing the two streams entering the mixing chamber is numerically studied as functions of the applied electric field. Excellent mixing can be achieved in this system under two perpendicularly applied electric fields. The proposed micro-mixer is simple and easy to be fabricated for lab-on-a-chip applications.     

Microfluidic mixing using contactless dielectrophoresis

The first experimental evidence of mixing enhancement in a microfluidic system using contactless dielectrophoresis (cDEP) is presented in this work. Pressure-driven flow of deionized water containing 0.5?μm beads was mixed in various chamber geometries by imposing a dielectrophoresis (DEP) force on the beads. In cDEP the electrodes are not in direct contact with the fluid sample but are instead capacitively coupled to the mixing chamber through thin dielectric barriers, which eliminates many of the problems encountered with standard DEP. Four system designs with rectangular and circular mixing chambers were fabricated in PDMS. Mixing tests were conducted for flow rates from 0.005 to 1?mL/h subject to an alternating current signal range of 0-300?V at 100-600 kHz. When the time scales of the bulk fluid motion and the DEP motion were commensurate, rapid mixing was observed. The rectangular mixing chambers were found to be more efficient than the circular chambers. This approach shows potential for mixing low diffusivity biological samples, which is a very challenging problem in laminar flows at small scales.     

Mixing with EOF for a Precipitation Reaction

Microfluidics is becoming increasingly more interesting for chemical engineering applications. This article takes a closer look at the possibilities of performing a precipitation reaction in a microfluidic device. This specific type of reaction demands for instance fast mixing. We take sodium chloride precipitation as a model anti‐solvent precipitation reaction. Effective mixing is achieved by applying an electric field over the fluid. The dispersion of a plug is measured when it is transported by pressure driven flow or electroosmotic flow. These two different types of transportation are investigated.     

Continuous cell washing and mixing driven by an ultrasound standing wave within a microfluidic channel

Ultrasound standing wave radiation force and laminar flow have been used to transfer yeast cells from one liquid medium to another (washing) by a continuous field-flow fractionation (FFF) approach. Two co-flowing streams, a cell-free suspending phase (flow rate > 50% of the total flow-through volume) and a yeast suspension, were introduced parallel to the nodal plane of a 3 MHz standing wave resonator. The resonator was fabricated to have a single pressure nodal plane at the centre line of the chamber. Laminar flow ensured a stable interface was maintained as the two suspending phases flowed through the sound field. Initiation of the ultrasound transferred cells to the cell-free phase within 0.5 s. This particle transfer procedure circumvents the pellet formation and re-suspension steps of centrifuge based washing procedures. In addition, fluid mixing was demonstrated in the same chamber at higher sound pressures. The channel operates under negligible back-pressure (cross-section, 0.25 [times] 10 mm) and with only one flow convergence and one flow division step, the channel cannot be easily blocked. The force acting on the cells is small; less than that experienced in a centrifuge generating 100g. The acoustically-driven cell transfer and mixing procedures described may be particularly appropriate for the increasingly complex operations required in molecular biology and microbiology and especially for their conversion to continuous flow processes.     

Characterization and optimization of slanted well designs for microfluidic mixing under electroosmotic flow

Recently, a series of slanted wells on the floor of a microfluidic channel were experimentally shown to successfully induce off-axis transport and mixing of two confluent streams when operating under electroosmotic (EO) flow. This paper will further explore, through numerical simulations, the parameters that affect off-axis transport under EO flow with an emphasis on optimizing the mixing rate of (a). two confluent streams in steady-state or (b). the transient scenario of two confluent plugs of material, which simulates mixing after an injection. For the steady-state scenario, the degree of mixing was determined to increase by changing any of the following parameters: (1). increasing the well depth, (2). decreasing the well angle relative to the axis of the channel, and (3). increasing the EO mobility of the well walls relative to the mobility of the main channel. Also, it will be shown that folding of the fluid can occur when the well angle is sufficiently reduced and/or when the EO mobility of the wells is increased relative to the channel. The optimum configuration for the transient problem of mixing two confluent plugs includes shallow wells to minimize the well residence time, and an increased EO mobility of the well walls relative to the main channel as well as small well angles to maximize off-axis transport. The final design reported here for the transient study reduces the standard deviation of the concentration across the channel by 72% while only increasing the axial dispersion of the injected plug by 8.6 % when compared to a plug injected into a channel with no wells present. These results indicate that a series of slanted wells on the wall of a microchannel provides a means for controlling and achieving a high degree of off-axis transport and mixing in a passive manner for micro total analysis system (microTAS) devices that are driven by electroosmosis.     

Mixing chambers in flow analysis: A review

Inclusion of a mixing chamber in a flow system is critically rev—iewed in-relation to sample dilution, improvement of mixing conditions and exploitation of exponential concentration lessening. Analytical perspectives related to the use of a mixing chamber such as time-based flow analysis, flow titrations, and analyte separation/concentration are also discussed along with the examination of several ordinary manifold components that might act as mixing chambers. The possibility of using the mixing chamber in order to accommodate or to carry out the multiple steps inherent to the specific analytical procedure or, in other words, to behave as a mini-laboratory, is also highlighted. This aspect is foreseen as a logical evolution of the lab-on-a-valve and the flow-batch concepts. The article is published in the original.     

Comparison of several spray chambers operating at very low liquid flow rates in inductively coupled plasma atomic emission spectrometry

Four different spray chambers were evaluated in ICP-AES at very low liquid flow rates: a double-pass (Scott type), a conventional cyclonic, and two low-volume cyclonic-type spray chambers (i.e., Cinnabar and Genie). A glass concentric pneumatic micro nebulizer (Atom Mist) was used in conjunction with all four chambers. The liquid flow rate was varied from 10 to 160 microL min(-1). The conventional cyclonic spray chamber gave rise to coarser tertiary aerosols, higher analyte and solvent transport rates, higher sensitivity and lower limits of detection than the remaining ones. The low-volume spray chambers afforded analytical figures of merit similar to the double-pass one, despite their very different designs. However, these spray chambers exhibited shorter wash-out times. The matrix effects were significant only for the double-pass. This fact allowed the analysis of reference samples by employing aqueous standards at a minimum level of sample consumption. The recoveries obtained for the cyclonic spray chambers and several certified samples were close to 100%, being always lower in the case of the double-pass spray chamber.     

Batch-mode mixing on centrifugal microfluidic platforms

We present two novel fluidic concepts to drastically accelerate the process of mixing in batch-mode (stopped-flow) on centrifugal microfluidic platforms. The core of our simple and robust setup exhibits a microstructured disk with a round mixing chamber rotating on a macroscopic drive unit. In the first approach, magnetic beads which are prefilled into the mixing chamber are periodically deflected by a set of permanent magnets equidistantly aligned at spatially fixed positions in the lab-frame. Their radial positions alternatingly deviate by a slight positive and negative offset from the mean orbit of the chamber to periodically deflect the beads inbound and outbound during rotation. Advection is induced by the relative motion of the beads with respect to the liquid which results from the magnetic and centrifugal forces, as well as inertia. In a second approach--without magnetic beads--the disk is spun upon periodic changes in the sense of rotation. This way, inertia effects induce stirring of the liquids. As a result, both strategies accelerate mixing from about 7 minutes for mere diffusion to less than five seconds. Combining both effects, an ultimate mixing time of less than one second could be achieved.     

Identification of micro-scale calorimetric devicesIV. Descriptive models in 3-D

The experimental analysis of conventional conduction calorimeters shows excellent reproducibility and relevant systematic errors in comparison with thermodynamic values established via adiabatic calorimeters. Two examples: a DSC and a liquid flow device are schematically analyzed. When an increased accuracy will be obtained the positional effects on the experimental set-up and on the measurement process need to be modelled. From experimental measurements realized on the Xensor liquid nano-calorimeter representative models can be built. To evaluate the reliability of measurement routines, established from experimental basis, several different dissipation structures inside the working space can be simulated. Two experimental configurations related to drop to drop reaction and to continuous mixing are modelled via RC approach. The RC formalism is extended to evaluate the carried energy effect produced by the continuous inflow/outflow of reactants in the mixing enthalpy chamber. This revised version was published online in July 2006 with corrections to the Cover Date.     

Micromixing of miscible liquids in segmented gas-liquid flow

We present an integrated microfluidic system that achieves efficient mixing between two miscible liquid streams by introducing a gas phase, forming a segmented gas-liquid (slug) flow, and completely separating the mixed liquid and gas streams in a planar capillary separator. The recirculation motion associated with segmented flow enhances advection in straight microchannels without requiring additional fabrication steps. Instantaneous velocity fields are quantified by microscopic particle image velocimetry (muPIV). Velocities in the direction normal to the channel amount to approximately 30% of the bulk liquid velocity inside a liquid segment. This value depends only weakly on the length of a liquid segment. Spatial concentration fields and the extent of mixing (EOM) are obtained from pulsed-laser fluorescence microscopy and confocal scanning microscopy measurements. The mixing length is reduced 2-3-fold in comparison with previously reported chaotic micromixers that use three-dimensional microchannel networks or patterned walls. Segmented gas-liquid microflows allow mixing times to be varied over several orders of magnitude between milliseconds and second time scales.     

Design, simulation and application of a new micromixing device for time resolved infrared spectroscopy of chemical reactions in solution

We present a novel micromachined fast diffusion based mixing unit for the study of rapid chemical reactions in solution with stopped-flow time resolved Fourier transform infrared spectroscopy (TR-FTIR). The presented approach is based on a chip for achieving lamination of two liquid sheets of 10 microm thickness and approximately 1 mm width on top of each other and operation in the stopped-flow mode. The microstructure is made on infrared transmitting calcium fluoride discs and built up with two epoxy negative photoresist layers and one silver layer in between. Due to the highly laminar flow conditions and the short residence time in the mixer there is hardly any mixing when the two liquid streamlines pass through the mixing unit, which allows one to record a mid-IR transmission spectrum of the analytes prior to reaction. When the flow is stopped, the reactant streams are arrested in the flow-cell and rapidly mixed by diffusion due to the reduced interstream distances and the reaction can be directly followed with hardly any dead time. On the basis of two model reactions-neutralisation of acetic acid with sodium hydroxide as well as saponification of methyl monochloroacetate-the performance of the mixing device was tested revealing proper functioning of the device with a time for complete mixing of less than 100 ms. The experimental results were supported by numerical simulations using computational fluid dynamics (CFD), which allowed a reliable, quantitative analysis of concentration, pressure and flow profiles in the course of the mixing process.     

Reducing the Background Level of a Mass-Spectrometric Hollow Cathode Glow Discharge Ion Source

Glow discharge mass spectrometry was used for the direct elemental analysis of solids with gas inclusions. The background signal of a glow discharge, which converts the analyte into ions, is higher than the background signals of other plasma sources by several orders of magnitude. The structure and sources of background contamination were analyzed in this work. It was found that hydrocarbon and water impurities, which are adsorbed on the inner surfaces of the discharge chamber, make the major contribution to the background signal of a glow discharge source. A glow discharge plasma licked the walls of the discharge chamber to desorb contaminants. We proposed using a hollow cathode with a holed cap arranged at the vertex. On the appearance of a discharge, a plasma plug is formed in the cathode hole in front of the orifice. This plasma plug prevents a gas flow from the hole to the source chamber. As a result, a gas pressure drop is formed whose magnitude depends on the orifice diameter in the cap.     

A passive pumping method for microfluidic devices

The surface energy present in a small drop of liquid is used to pump the liquid through a microchannel. The flow rate is determined by the volume of the drop present on the pumping port of the microchannel. A flow rate of 1.25 microL s(-1) is demonstrated using 0.5 microL drops of water. Two other fluid manipulations are demonstrated using the passive pumping method: pumping liquid to a higher gravitational potential energy and creating a plug within a microchannel.     

Development of the continuously variable volume reactor for flow injection analysis: Part 1. Design, capabilities and testing

A new apparatus for mixing sample and reagent in flow injection analysis (FIA) is described. The continuously variable volume reactor (CVVR) replaces the conventional mixing coil in a flow injection (FI) manifold to provide mixing and dilution. A linear actuator motor allows control of the chamber volume via LabVIEW software. The chamber volume can be incremented in steps of 1 μl over the range 68-1704 μl. In addition, the chamber has an integral variable-speed stirring unit that is also under computer control. Experiments were performed to evaluate the dispersion characteristics of this new device, evaluate the volume reproducibility, and understand the mixing characteristics. Use of the chamber is shown in the determination of iron(II) in pond water, and in NIST SRM 1643d with excellent results and a detection limit of 3.7 μg/l iron(II). Advantages of the CVVR and future research activities using the device are discussed.     

Mass Exchange in Absorption in Fluid-Gas Jet Apparatus with Elongated Mixing Chamber

Mass exchange in absorbers having the form of fluid-gas jet apparatus with elongated mixing chamber is considered. An approach to calculation of the mass-exchange coefficients and gas absorption rate in a flow of a gas-fluid emulsion in the mixing chamber is proposed. Results obtained in industrial operation of the absorber are presented.     

Applicability of two-membrane reactors for reversible gas phase reaction. Effects of flow patterns and inerts

The objective of this study is a comparative analysis of single and two-membrane reactor performances for isothermal reversible gas phase reaction. The effects of flow patterns (ideal mixing, cocurrent and countercurrent plug flow) and the presence of inert components were investigated. It is shown by simulation that for the pure reactant feed in absence of inerts, the performance of a two-membrane reactor is not significantly affected by the flow patterns, providing the pressure ratio is kept close to zero. Concerning the conversion efficiency in the case when the reactant is the slowest permeating component, the advantage of a two-membrane reactor is evident, it being least significant for countercurrent plug flow. In the presence of inerts in the separation zone, the advantage of a two-membrane reactor is maintained, while it is diminished by increasing inert flow rate in the reaction zone.     

Surface tension drawing of liquid from microplate capillary wells

Pressure differentials are routinely used to actuate flow in capillaries. We advance here an alternative means of flow generation that capitalizes on the extension of a liquid bridge achieved by the drawing of a rod through the action of surface tension. This meets the exigencies of creating controllable flow using simpler and more compact means. We found the ability to generate controllable flow to be strongly affected by the liquid bridge sustaining features, and that the use of rod diameters larger than the capillary was more conducive. The extensional flow resulting from the rupture of the liquid bridge was also found to have a strong circulation component which facilitated mixing. The approach here is highly amenable for use in capillary well microplates which have significant advantages over standard microplates. The features of this approach offer usage possibilities in biochemical applications in the field, such as in the leukocyte cell adhesion and hemagglutination tests of blood samples.     

Fast DNA hybridization on a microfluidic mixing device based on pneumatic driving

A novel fluid mixing strategy was developed which significantly enhanced the efficiency of DNA hybridization. A pneumatic micro-mixing device consisting of two pneumatic chambers and an underneath DNA microarray chamber was built up. The fluid in the array chamber was pneumatically pumped alternately by the two pneumatic chambers. The chaotic oscillatory flow caused by the pumping greatly intensified the fluidic mixing. A homogeneous distribution of the tracer dye solution in the microarray chamber was observed after 2 s mixing with a pumping frequency of 24 Hz. Microarray DNA hybridization was substantially accelerated using this device, and the fluorescence intensity showed a plateau after oscillating 30 s at room temperature. The corresponding signal level of the dynamic hybridization was 12.5-fold higher than that of the static hybridization performed at 42 °C. A signal-to-noise ratio of 117 was achieved and the nonspecific adsorption of the targets to the sample array was minimized, which might be attributed to the strong shearing force generated during the pneumatic mixing process.