A suction-type, pneumatic microfluidic device for liquid transport and mixing

This study presents a new suction-type, pneumatically driven microfluidic device for liquid delivery and mixing. The three major components, including two symmetrical, normally closed micro-valves and a sample transport/mixing unit, are integrated in this device. Liquid samples can be transported by the suction-type sample transport/mixing unit, which comprised a circular air chamber and a fluidic reservoir. Experimental results show that volume flow rates ranging from 50 to 300 μl/min can be precisely controlled during the sample transportation processes. Moreover, the transport/mixing unit can also be used as a micro-mixer to generate efficient mixing between two reaction chambers by regulating the time-phased deformation of the polydimethylsiloxane (PDMS) membranes. A mixing efficiency as high as 98.4% can be achieved within 5 s utilizing this prototype pneumatic microfluidic device. Consequently, the development of this new suction-type, pneumatic microfluidic device can be a promising tool for further biological applications and for chemical analysis when integrated into a micro-total analysis system (μ-TAS) device.     

Chaotic mixing using source�Csink microfluidic flows in a PDMS chip

We present an active fixed-volume mixer based on the creation of multiple source–sink microfluidic flows in a polydimethylsiloxane (PDMS) chip without the need of external or internal pumps. To do so, four different pressure-controlled actuation chambers are arranged on top of the 5 μl volume of the mixing chamber. After the mixing volume is sealed/fixed by microfluidic valves made using ‘microplumbing technology’, a virtual source–sink pair is created by pressurizing one of the membranes and, at the same time, releasing the pressure of a neighboring one. The pressurized air deforms the thin membrane between the mixing and control chambers and creates microfluidic flows from the squeezed region (source) to the released region (sink) where the PDMS membrane is turned into the initial state. Several schemes of operation of virtual source–sink pairs are studied. In the optimized protocol, mixing is realized in just a sub-second time interval, thanks to the implementation of chaotic advection.     

Micromachining of passive planar micromixer on poly (methyl methacrylate) substrate with excimer laser ablation

Excimer laser ablation technique was introduced into this work to fabricate a passive planar micromixer on the PMMA substrate. T-junction shaped and width-changed S-shaped microchannels were both designed in this micromixer to enhance mixing effect. The mixing experiment of distilled water and Rhodamine B with injection flow rate of 500 and 1,500 μm/s validates the mixing effectivity of this micromixer, and indicates the feasibility of excimer laser ablation in the microfabrication of μ-TAS device.     

Electrokinetically driven flow mixing utilizing chaotic electric fields

This paper presents a novel microfluidic mixing scheme in which the species streams are mixed via the application of chaotic electric fields to four electrodes mounted on the upper and lower surfaces of the mixing chamber. Numerical simulations are performed to analyze the effects of the resulting chaotic electrokinetic driving forces on the fluid flow characteristics within the micromixer and the corresponding mixing performance. During simulation, chaotic oscillating electric potentials are derived using a Duffing–Holmes chaos system. Simulation results indicate that the chaotic electrokinetic driving forces induce a complex flow behavior within the micromixer which results in efficient mixing of the two species streams. It is shown that mixing efficiencies up to 95% can be obtained in the novel micromixer.     

Mixing and hydrodynamic analysis of a droplet in a planar serpentine micromixer

In this work we combined numerical simulation with molecular-diffusion effect, high-tempo micro-particle image velocimetry (μ-PIV), and probability distribution function (PDF) analysis to investigate the chaotic mixing and hydrodynamics inside a droplet moving through a planar serpentine micromixer (PSM). Robust solutions for the distributions of interface and concentration of the droplets were obtained via computational fluid dynamics. The simulated fluid patterns are consistent with those measured with μ-PIV, which serves as a powerful nonintrusive diagnostic approach to observe the droplets. Two mechanisms are proposed to enhance the performance of mixing in a PSM—the deformation of droplets and the asymmetric recirculation within the droplets. On introducing alternating cross sections into a winding channel, this specific design of PSM is found to amplify the fluid disturbance and maximum vorticity difference. Data show that the PDF of the vorticity fields is modified and the fraction with larger vorticity is increased. Accordingly, the PSM is capable of achieving a mixing index 90% within 700 μm (Re = 2), which is eight times better than for a straight microchannel. The results not only demonstrate explicitly the fluid patterns within the droplets but also provide significant insight into the factors dominating the mixing efficiency.     

Microfluidic inverse phase ELISA via manipulation of magnetic beads

We report a new technique for conducting immuno-diagnostics on a microfluidic platform. Rather than handling fluid reagents against a stationary solid phase, the platform manipulates analyte-coated magnetic beads through stationary plugs of fluid reagents to detect an antigenic analyte. These isolated but accessible plugs are pre-encapsulated in a microchannel by capillary force. We call this platform microfluidic inverse phase enzyme-linked immunosorbent assay (μIPELISA). μIPELISA has distinctive advantages in the family of microfluidic immunoassay. In particular, it avoids pumping and valving fluid reagents during assaying, thus leading to a lab-on-a-chip format that is free of instrumentation for fluid actuation and control. We use μIPELISA to detect digoxigenin-labeled DNA segments amplified from E. coli O157:H7 by polymerase chain reaction (PCR), and compare its detection capability with that of microplate ELISA. For 0.259 ng μl⁻¹ of digoxigenin-labeled amplicon, μIPELISA is as responsive as the microplate ELISA. Also, we simultaneously conduct μIPELISA in two parallel microchannels.     

DNA ligation using a disposable microfluidic device combined with a micromixer and microchannel reactor

A novel PDMS and glass-based microfluidic device consisting of a micromixer and microreactor for DNA ligation is described in this article. The new passive type planar micromixer is 10.33 mm long and composed of a straight channel integrated with nozzles and pillars, and the microreactor is composed of a serpentine channel. Mixing was enhanced by convective diffusion facilitated by the nozzles and pillars. The performance of the micromixer was analytically simulated and experimentally evaluated. The micromixer showed a good mixing efficiency of 87.7% at a 500 μL/min flow rate (Re = 66.5). DNA ligation was successfully performed using the new microfluidic device, and ligation time was shortened from 4 h to 5 min. When used for on-chip ligation, this new micromixer offers advantages of disposability and portability.     

Development and characterisation of integrated microfluidics on waveguide-based photonic platforms fabricated from hybrid materials

This article reports on a detailed investigation of sol–gel processed hybrid organic–inorganic materials for use in lab-on-a-chip (LoC) applications. A particular focus on this research was the implementation of integrated microfluidic circuitry in waveguide-based photonic sensing platforms. This objective is not possible using other fabrication technologies that are typically used for microfluidic platforms. Significant results on the surface characterisation of hybrid sol–gel processed materials have been obtained which highlight the ability to tune the hydrophilicity of the materials by careful adjustment of material constituents and processing conditions. A proof-of-principle microfluidic platform was designed and a fabrication process was established which addressed requirements for refractive index tuning (essential for waveguiding), bonding of a transparent cover layer to the device, optimized sol–gel deposition process, and a photolithography process to form the microchannels. Characterisation of fluid flow in the resulting microchannels revealed volumetric flow rates between 0.012 and 0.018 μl/min which is characteristic of capillary-driven fluid flow. As proof of the integration of optical and microfluidic functionality, a microchannel was fabricated crossing an optical waveguide which demonstrated that the presence of optical waveguides does not significantly disrupt capillary-driven fluid flow. These results represent the first comprehensive evaluation of photocurable hybrid sol–gel materials for use in waveguide-based photonic platforms for lab-on-a-chip applications.     

Analysis of a chaotic micromixer by novel methods of particle tracking and FRET

Two novel numerical and experimental methods are proposed for quantitatively analyzing the chaotic mixing in a circulation-disturbance micromixer (CDM). A particle-tracking approach incorporated with the geometric distribution of particles is derived to evaluate the mixing performance. This method provides additional evaluation about the degree of particles scattering, when compared to the Shannon entropy method. In addition, the fluorescence resonance energy transfer (FRET) method using R-Phycoerythrin (RPE) and cross-linked allophycocyanin (clAPC) is developed to demonstrate both the mixing performance and the applicability of CDM for biochemical reaction. The two proposed indices, including the particle-tracking distribution and FRET factor, are verified to sufficiently reveal the periodic constructive interference of the vortices in a CDM and a slanted groove micromixer. They also explicitly indicate the mixing performance of the chaotic micromixers. The methodologies are expected to be applied successfully for performance analysis of various micromixers or microreactors, and thus have a great potential for μTAS applications.     

Surface tension driven and 3-D vortex enhanced rapid mixing microchamber

This paper proposes a novel passive micromixer design for mixing enhancement by forming a large three-dimensional (3-D) flow vortex in a counterflow microfluidic system. The counterflow fluids are self-driven by surface tension to perform mixing in an open chamber. The chamber design consists of two rectangular bars to house the chamber and to form two opening inlets from opposite directions. The best design is selected from various versions of mixing chambers. The mixing effectiveness is tremendously increased by folds of contacting surface between two fluids induced and enhanced due to the stretching of two fluid contacting interfaces by the formation of a 3-D large size vortex structure inside the mixing chamber itself with unaccountable numbers of fluid layers. Both numerical simulations and experiments are performed and compared to identify the design parameters for maximum utilization in this microfluidic system, such as the length of rectangular bar, microchannel wall height, and mixing chamber size. Compared to traditional micromixers operated by two-dimensional (2-D) vortex, this passive mixer can greatly enhance mixing efficiency and reduce mixing time by tenfold from around 10 s to less than 10 ms by 3-D effective chaotic flow structures in a more compact size. This mixing chamber is also suitable for an H-shape digital fluidic system for parallel mixing process in different mixing ratio simultaneously as a lab-on-a-chip system.     

Electrokinetic mixing in microfluidic systems

The applications of electrokinetics in the development of microfluidic devices have been widely attractive in the past decade. Electrokinetic devices generally require no external mechanical moving parts and can be made portable by replacing the power supply by small battery. Therefore, electrokinetic-based microfluidic systems can serve as a viable tool in creating a lab-on-a-chip (LOC) or micro-total analysis system (μTAS) for use in biological and chemical assays. Mixing of analytes and reagents is a critical step in realizing lab-on-a-chip. This step is difficult due to the low Reynolds numbers flows in microscale devices. Hence, various schemes to enhance micro-mixing have been proposed in the past years. This review reports recent developments in the micro-mixing schemes based on DC and AC electrokinetics, including electrowetting-on-dielectric (EWOD), dielectrophoresis (DEP), and electroosmosis (EO). These electrokinetic-based mixing approaches are generally categorized as either active or passive in nature. Active mixers either use time-dependent (AC or DC field switching) or time-independent (DC field) external electric fields to achieve mixing, while passive mixers achieve mixing in DC fields simply by virtue of their geometric topology and surface properties, or electrokinetic instability flows. Typically, chaotic mixing can be achieved in some ways and is helpful to mixing under large Péclet number regimes. The overview given in this article provides a potential user or researcher of electrokinetic-based technology to select the most favorable mixing scheme for applications in the field of micro-total analysis systems.     

A highly uniform lamination micromixer with wedge shaped inlet channels for time resolved infrared spectroscopy

We present a horizontal multi-lamination micromixer with specially wedge shaped vertical fluid inlets for fast and highly uniform fluid mixing in the low millisecond range. The four-layer laminar flow is created by a fluidic distribution network, reducing the amount of fluid connectors to the macroscopic world to two. All the geometries of the channel inlets and the distribution network were optimized for low flow rates and hence for low sample consumption using CFD simulations. The device materials applied feature low absorption in the mid-infrared (wavelength 3--10 μm) allowing to use this device for time resolved infrared spectroscopy. The micromixer itself can be built by silicon micromachining techniques without the need of complicated fabrication steps. Due to a transparent calcium fluoride cover optical measurements are possible as well which were used to characterize the device. Mixing times in the range of 1 ms with optical color measurements of aqueous solutions and with time resolved infrared measurement of the proton exchange reaction of H₂O and D₂O are achieved.     

A numerical study of an electrothermal vortex enhanced micromixer

Temperature gradients aroused from the Joule heating in a non-uniform electrical field can induce inhomogeneities of electric conductivity and permittivity of the electrolyte, thus causing an electrothermal force that generates flow motion. A 2D numerical investigation of a micromixer, utilizing electrothermal effect to enhance its mixing efficiency, is proposed in this paper. Results for temperature and velocity distributions, as well as sample concentration distribution are obtained for an electrolyte solution in a microchannel with different pairs of electrodes under AC potentials with various frequencies. Numerical solutions were first carried out for one pair of electrodes, with a length of 10 μm separated by a gap of 10 μm, on one side wall of a microchannel having a length of 200 μm and a height of 50 μm. It is found that the electrothermal flow effect, in the frequency range for which Coulomb force is predominant, induces vortex motion near the electrodes, thus stirring the flow streams and enhancing its mixing efficiency. If more than one pair of electrodes is located on the opposite walls of the microchannel, the mixing efficiency depends on the AC potential applied pattern and the electrodes arrangement pattern. The distance between two pairs of electrodes on two opposite walls is then optimized numerically. Sample mixing efficiencies, using KCl solutions as the working fluid in microchannels with different number of electrodes pairs at optimal electrodes arrangement pattern, are also investigated. If root mean squared voltages of 10 V in an AC frequency range of 0.1–10 MHz are imposed on 16 pairs of electrodes separated at an optimal distance, the numerical results show that a mixing efficiency of 98% can be achieved at the end of the microchannel having a length of 700 μm and a height of 50 μm at Re = 0.01 Pe _C = 100, and Pe _T = 0.07. However, the mixing efficiency decreases sharply at a frequency higher than 10 MHz owing to the drastically decrease in the Coulomb force.     

Improved serpentine laminating micromixer with enhanced local advection

It is a complicated task to achieve high level of mixing inside a microchannel because the flow is characterized by low Reynolds number (Re). Recently, the serpentine laminating micromixer (SLM) was reported to achieve efficient chaotic mixing by introducing “F”-shape mixing units successively in two layers such that two mixing mechanisms, namely splitting/recombination and chaotic advection, enhance the mixing performance in combination. The present paper proposes an improved serpentine laminating micromixer (ISLM) with a novel redesign of the “F”-shape mixing unit: reduced cross-sectional area at the recombination region locally enhances advection effect which helps better vertical lamination, resulting in improved mixing performance. Flow characteristics and mixing performances of SLM and ISLM are investigated numerically and verified experimentally. Numerical analysis system is developed based on a finite element method and a colored particle tracking method, while mixing entropy is adopted as a mixing measure. Numerical analysis result confirms enhanced vertical lamination performance and consequently improved mixing performance of ISLM. SLM and ISLM were fabricated by polydimethylsiloxane (PDMS) casting against SU-8 patterned masters. Mixing performance is observed by normalized purple color intensity change of phenolphthalein along the downchannel. Flow characteristics of SLM and ISLM are investigated by tracing the purple interface of two streams via optical micrograph. The normalized mixing intensity behavior confirms improved mixing performance of ISLM, which is consistent with numerical analysis result.     

Micro-light distribution system via optofluidic cascading prisms

This article reports a micro-light distribution system realized by altering the reflective indices of two optofluidic cascading prisms. Different micron scale light distribution configurations can be tuned via the imposed flow rates of the microfluidic mixers. The variable optical interface’s reflectivity of the cascading prisms is based on the tuning of refractive indices of micromixed fluids within the cascading prisms. The microscale light distribution is achieved via total internal reflection and partial refraction occurs at the fluid–solid optical interfaces. 1 × 3 light switching denotes one optical inlet while the light can be guided via any one of the three optical outlets. The 1 × 3 light switching capability is demonstrated. The light splitting capability to achieve different proportion of light power distribution is also demonstrated and characterized. The optofluidic cascading prisms are integrated with micromixer, prolonging the working life of the optical compartment considerably as the fluids are only consumed when optical tuning is required. The proposed technique eliminates the disadvantage of optofluidic compartments based on liquid–liquid interfaces as liquid–liquid interface possess weaker mechanical stability than solid–liquid interface. The proposed design also does not require continuous supply of fluids as in optofluidic compartments based on liquid–liquid interfaces. The optofluidic cascading prisms can be cascaded further to form a complex planar light distribution system for seamless light distribution in lab-on-a-chip excitation and sensing applications.     

Aliquoting on the centrifugal microfluidic platform based on centrifugo-pneumatic valves

We present a new method for aliquoting liquids on the centrifugal microfluidic platform. Aliquoting is an essential unit operation to perform multiple parallel assays (“geometric multiplexing”) from one individual sample, such as genotyping by real-time polymerase chain reactions (PCR), or homogeneous immunoassay panels. Our method is a two-stage process with an initial metering phase and a subsequent transport phase initiated by switching a centrifugo-pneumatic valve. The method enables aliquoting liquids into completely separated reaction cavities. It includes precise metering that is independent on the volume of pre-stored reagents in the receiving cavities. It further excludes any cross-contamination between the receiving cavities. We characterized the performance for prototypes fabricated by three different technologies: micro-milling, thermoforming of foils, and injection molding. An initial volume of ~90 μl was split into 8 aliquots of 10 μl volume each plus a waste reservoir on a thermoformed foil disk resulting in a coefficient of variation (CV) of the metered volumes of 3.6%. A similar volume of ~105 μl was split into 16 aliquots of 6 μl volume each on micro-milled and injection-molded disks and the corresponding CVs were 2.8 and 2.2%, respectively. Thus, the compatibility of the novel aliquoting structure to the aforementioned prototyping and production technologies is demonstrated. Additionally, the important question of achievable volume precision of the aliquoting structure with respect to the production tolerances inherent to each of these production technologies is addressed experimentally and theoretically. The new method is amenable to low cost mass production, since it does not require any post-replication surface modifications like hydrophobic patches.     

Acoustically induced bubbles in a microfluidic channel for mixing enhancement

Due to small dimensions and low fluid velocity, mixing in microfluidic systems is usually poor. In this study, we report a method of enhancing microfluidic mixing using acoustically induced gas bubbles. The effect of applied frequency on mixing was investigated over the range 0.5–10 kHz. Under either low frequency 0.5 kHz or high frequency 10 kHz, no noticeable improvement in the present mixer was observed. However, a significant increase in the mixing efficiency was achieved within a window of the frequencies between 1.0 and 5.0 kHz. It was found in our present microfluidic structure, single (or multi-) bubble(s) could be acoustically generated under the frequency ranging from 1.0 to 5.0 kHz by a piezoelectric disc. The interaction between bubble and acoustic field causes bubble oscillation which in turn could disturb local flow field to result in mixing enhancement.     

Integrated microfluidic system for electrochemical sensing of glycosylated hemoglobin

This article reports a new miniature electrochemical detection system integrating a sample pretreatment device for fast detection of glycosylated hemoglobin (HbA_1C), which is a common indicator for diabetes mellitus. In this system, circular micropumps, normally closed microvalves, dielectrophoretic (DEP) electrodes, and electrochemical sensing electrode are integrated to perform several crucial processes. These processes include separation of red blood cells (RBCs), sample/reagent transportation, mixing, cell lysis, and electrochemical sensing. For the HbA_1C measurement, the RBCs are separated and are collected from whole human blood by using a positive DEP force generated by the DEP electrodes. The collected RBCs are then lysed to release HbA_1C for the subsequent electrochemical detection processes. Experimental data show that the RBCs are successfully separated and are collected using the developed system with a RBCs capture rate of 84.2%. The subsequent detection of HbA_1C is automatically completed by utilizing electrochemical sensing electrode. The microfluidic system only consumes a sample volume of 200 μl. The entire process is automatically performed within a short period of time (10 min). The development of this integrated microfluidic system may be promising for the clinical monitoring of diabetes mellitus.     

A rapid magnetic particle driven micromixer

Performances of a magnetic particle driven micromixer are predicted numerically. This micromixer takes advantages of mixing enhancements induced by alternating actuation of magnetic particles suspended in the fluid. Effects of magnetic actuation force, switching frequency and channel’s lateral dimension have been investigated. Numerical results show that the magnetic particle actuation at an appropriate frequency causes effective mixing and the optimum switching frequency depends on the channel’s lateral dimension and the applied magnetic force. The maximum efficiency is obtained at a relatively high operating frequency for large magnetic actuation forces and narrow microchannels. If the magnetic particles are actuated with a much higher or lower frequency than the optimum switching frequency, they tend to add limited agitation to the fluid flow and do not enhance the mixing significantly. The optimum switching frequency obtained from the present numerical prediction is in good agreement with the theoretical analysis. The proposed mixing scheme not only provides an excellent mixing, even in simple microchannel, but also can be easily applied to lab-on-a-chip applications with a pair of external electromagnets.     

A numerical design study of chaotic mixing of magnetic particles in a microfluidic bio-separator

A two-dimensional numerical investigation into the mixing of magnetic microparticles with bio-cells in a chaotic micromixer is carried out by using a multiphysics finite element analysis package. Fluid and magnetic problems are simulated in steady-state and time-dependent modes, respectively. Intensity of segregation is utilized as the main index to examine the efficiency of the mixer. Trajectories of the particles are used in order to detect chaos in their motion and quantify its extent. Moreover, probability of the collision between particles and target bio-cells is examined as a supplemental index to study the effects of driving parameters on the mixing process. Simulation results reveal that while in some ranges of operating conditions all indices are in good agreement, there are some ranges where they appear to predict contradicting results which is discussed in details. It is found that optimum operating conditions for the system is obtained when the Strouhal number is less than 0.6, which corresponds to the efficiency of about 85% in a mixing length of 500 μm (The mixer design described here is patent pending).