Pre-programmable polymer transformers as on-chip microfluidic vacuum generators

This paper develops novel polymer transformers using thermally actuated shape memory polymer (SMP) materials. This paper applies SMPs with thermally induced shape memory effect to the proposed novel polymer transformers as on-chip microfluidic vacuum generators. In this type of SMPs, the morphology of the materials changes when the temperature of materials reaches its glass transition temperature (T _g). The structure of the polymer transformer can be pre-programmed to define its functions, which the structure is reset to the temporary shape, using shape memory effects. When subjected to heat, the polymer transformer returns to its pre-memory morphology. The morphological change can produce a vacuum generation function in microfluidic channels. Vacuum pressure is generated to suck liquids into the microfluidic chip from fluidic inlets and drive liquids in the microchannel due to the morphological change of the polymer transformer. This study adopts a new smart polymer with high shape memory effects to achieve fluid movement using an on-chip vacuum generation source. Experimental measurements show that the polymer transformer, which uses SMP with a T _g of 40°C, can deform 310 μm (recover to the permanent shape from the temporary shape) within 40 s at 65°C. The polymer transformer with an effective cavity volume of 155 μl achieved negative pressures of −0.98 psi. The maximum negative up to −1.8 psi can be achieved with an effective cavity volume of 268 μl. A maximum flow rate of 24 μl/min was produced in the microfluidic chip with a 180 mm long channel using this technique. The response times of the polymer transformers presented here are within 36 s for driving liquids to the end of the detection chamber. The proposed design has the advantages of compact size, ease of fabrication and integration, ease of actuation, and on-demand negative pressure generation. Thus, this design is suitable for disposable biochips that need two liquid samples control. The polymer transformer presented in this study is applicable to numerous disposable microfluidic biochips.     

Liquid�Cliquid fluorescent waveguides using microfluidic-drifting-induced hydrodynamic focusing

We demonstrate fluorescent liquid-core/liquid-cladding (L ²) waveguides focused in three-dimensional (3-D) space based on a 3-D hydrodynamic focusing technique. In the proposed system, the core and vertical cladding streams are passed through a curved 90° corner in a microfluidic channel, leading to the formation of a pair of counter rotating vortices known as the Dean vortex. As a result, the core fluid is completely confined within the cladding fluid and does not touch the top and bottom poly(dimethylsiloxane) (PDMS) surfaces of the microfluidic channel. Because the core stream was not in contact with the PDMS channel, whose refractive index contrast and optical smoothness with the core fluid are lower than that between the core and the cladding fluids, the 3-D focused L ² waveguide exhibited a higher captured fraction (η) and lower propagation loss when compared to conventional two-dimensional (2-D) focused L ² waveguides. Because the proposed 3-D focused L ² waveguides can be generated in planar PDMS microfluidic devices, such optofluidic waveguides can be integrated with precise alignment together with other in-plane microfluidic and optical components to achieve micro-total analysis systems (μ-TAS).     

Parameters affecting the shape of a hydrodynamically focused stream

Even at low Reynolds numbers, momentum can impact the shape of hydrodynamically focused flow. Both theoretical and experimental characterization of hydrodynamic focusing in microchannels at Reynolds numbers ≤25 revealed the important parameters that affect the shape of the focused layer. A series of symmetric and asymmetric microfluidic channels with two converging streams were fabricated with different angles of confluence at the junction. The channels were used to study the characteristics of Y-type microchannels for flow-focusing. Computational analysis and experimental results gathered using confocal microscopy and particle image velocimetry indicated that the orientation of the sheath and the sample stream inlets, as well as the absolute flow velocities, determine the curvature in the concentration distribution of the focused stream. Decreasing the angle of confluence between sheath and sample, as well as reducing the overall Reynolds number, resulted in a flat interface between sheath and focused fluids. Alignment of the faster flowing sheath fluid channel with the main channel also reduced the inertial effects and produced a focused stream with a flat concentration profile. Control over the shape of the focused stream is important in many biosensors and lab-on-a-chip devices that rely on hydrodynamic focusing for increased detection sensitivity.     

Electrospinning hollow and core/sheath nanofibers using hydrodynamic fluid focusing

Hollow poly (vinylpyrrolidone) (PVP) + TiO₂ and polypyrrole (core)/PVP (sheath) nanofibers were successfully electrospun using hydrodynamic fluid focusing. Utilizing a two-dimensional fluid focusing technique previously applied to aqueous solutions, intersecting microchannels cast in (poly)dimethylsiloxane were utilized to dynamically center core fluids in immiscible sheath fluids prior to electrospinning at the channel outlet. Advantages of using microfluidic channel networks for the electrospinning of composite nanofibers include spatiotemporal control over input reagents, ease of fabrication and the ability to focus the core stream into sheath layer without the need of complex co-annular nozzles.     

Controlled counter-flow motion of magnetic bead chains rolling along microchannels

We demonstrate controlled transport of superparamagnetic beads in the opposite direction of a laminar flow. A permanent magnet assembles 200 nm magnetic particles into about 200 μm long bead chains that are aligned in parallel to the magnetic field lines. Due to a magnetic field gradient, the bead chains are attracted towards the wall of a microfluidic channel. A rotation of the permanent magnet results in a rotation of the bead chains in the opposite direction to the magnet. Due to friction on the surface, the bead chains roll along the channel wall, even in counter-flow direction, up to at a maximum counter-flow velocity of 8 mm s⁻¹. Based on this approach, magnetic beads can be accurately manoeuvred within microfluidic channels. This counter-flow motion can be efficiently be used in Lab-on-a-Chip systems, e.g. for implementing washing steps in DNA purification.     

In-channel focusing of flowing microparticles utilizing hydrodynamic filtration

We present herein microfluidic systems to continuously focus the positions of flowing particles onto the center of a microchannel, which is indispensable to various applications for manipulating particles or cells such as flow cytometry and particle-based bioassay. A scheme called ‘hydrodynamic filtration’ is employed to repeatedly split fluid flows from a main stream, while remaining particles in the main stream. By re-injecting the split flows into the main channel, these flows work as sheath flows, focusing the positions of the particles onto the center of the microchannel without the help of sheath flows or complicated devices generating physical forces. In this study, we proposed two schemes, and compared the focusing efficiencies between the two schemes using particles 5.0 μm in diameter. Also, we confirmed that the flow speed did not affect the focusing efficiency, demonstrating the versatility and applicability of the presented systems. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Decreasing microfluidic evaporation loss using the HMDL method: open systems for nucleic acid amplification and analysis

Evaporation is of great importance when dealing with microfluidic devices with open air/liquid interfaces due to the large surface-to-volume ratio. For devices utilizing a thermal reaction (TR) reservoir to perform a series of biological and chemical reactions, excessive heat-induced microfluidic evaporation can quickly lead to reaction reservoir dry out and failure of the overall device. In this study, we present a simple, novel method to decrease heat-induced fluid evaporation within microfluidic systems, which is termed as heat-mediated diffusion-limited (HMDL) method. This method does not need complicated thermal isolation to reduce the interfacial temperature, or external pure water to be added continuously to the TR chamber to compensate for evaporation loss. The principle of the HMDL method is to make use of the evaporated reaction content to increase the vapor concentration in the diffusion channel. The experimental results have shown that the relative evaporation loss (V _loss/V _ini) based on the HMDL method is not only dependent on the HMDL and TR region’s temperatures (T _HMDL and T _TR), but also on the HMDL and TR’s channel geometries. Using the U-shaped uniform channel with a diameter of 200 μm, the V _loss/V _ini within 60 min is low to 5% (T _HMDL = 105°C, T _TR = 95°C). The HMDL method can be used to design open microfluidic systems for nucleic acid amplification and analysis such as isothermal amplification and PCR thermocycling amplification, and a PCR process has been demonstrated by amplifying a 135-bp fragment from Listeria monocytogenes genomic DNA.     

Dynamic coating for protein separation in cyclic olefin copolymer microfluidic devices

We report our study on using hydroxyethyl cellulose (HEC) as a dynamic coating for protein separation in microfluidic devices made from cyclic olefin copolymer (COC). The coating significantly enhances hydrophilicity of COC surface, evident from the decrease in contact angle of water in a COC channel. Surface treatment of COC channels with HEC also results in a 72% drop in electroosmotic (EO) mobility and a significant reduction in protein adsorption on the channel wall. Using bovine serum albumin as a model protein, the number of theoretical plates of 1.1 × 10⁴ was achieved in a separation distance of 3.3 cm using free solution electrophoresis. Hydroxyethyl cellulose dynamic coating is also found to have an effect on isoelectric focusing (IEF) of proteins. It not only prevents proteins from adsorption, but also reduces EO flow, both of which help achieve IEF of proteins with a difference of 0.1 pH values in isoelectric points (pI).     

Fabrication and testing of embedded microvalves within PMMA microfluidic devices

The integration of a PDMS membrane within orthogonally placed PMMA microfluidic channels enables the pneumatic actuation of valves within bonded PMMA–PDMS–PMMA multilayer devices. Here, surface functionalization of PMMA substrates via acid catalyzed hydrolysis and air plasma corona treatment were investigated as possible techniques to permanently bond PMMA microfluidic channels to PDMS surfaces. FTIR and water contact angle analysis of functionalized PMMA substrates showed that air plasma corona treatment was most effective in inducing PMMA hydrophilicity. Subsequent fluidic tests showed that air plasma modified and bonded PMMA multilayer devices could withstand fluid leakage at an operational flow rate of 9 μl/min. The pneumatic actuation of the embedded PDMS membrane was observed through optical microscopy and an electrical resistance based technique. PDMS membrane actuation occurred at pneumatic pressures of as low as 10 kPa and complete valving occurred at 14 kPa for ~100 μm by 100 μm channel cross-sections.     

Fabrication and electrical characterization of integrated nano-scale fluidic channels

We present the fabrication and characterization of nanoscale fluidic channels with embedded electrodes. Arrays of 2.25 μm long and 60 nm tall nanochannels with widths ranging from 60 to 500 nm were microfabricated in SiO₂ with Au electrodes embedded inside and outside of the nanochannels. The built-in electrodes were able to probe nanochannel conductance via a redox reaction of \textFe(\textCN)₆^{3 - /4 -} {\text{Fe}}({\text{CN}})_{6}^{3 - /4 - } . Amperometric characterization showed that conductance of nanochannel arrays varied linearly both with the width and number of nanochannels and was in the 10–100 pS range. Further, we show that electrical current was largely diffusion based and could be predicted from channel geometry using standard diffusion equations. We also discuss the potential of such nanochannel arrays as electronic biomolecular sensors and show preliminary streptavidin detection results.     

An electrokinetic mixer driven by oscillatory cross flow

An electrokinetic mixer driven by oscillatory cross flow has been studied numerically as a means for generating chaotic mixing in microfluidic devices for both confined and throughput mixing configurations. The flow is analyzed using numerical simulation of the unsteady Navier–Stokes equations combined with the tracking of single and multi-species passive tracer particles. First, the case of confined flow mixing is studied in which flow in the perpendicular channels of the oscillatory mixing element is driven sinusoidally, and 90° out of phase. The flow is shown to be chaotic by means of positive effective (finite time) Lyapunov exponents, and the stretching and folding of material lines leading to Lagrangian tracer particle dispersion. The transition to chaotic flow in this case depends strongly on the Strouhal number (St), and weakly on the ratio of the cross flow channel length to width (L/W). For L/W = 2, the flow becomes appreciably chaotic as evidenced by visual particle dispersion at approximately St = 0.32, and the transitional value of St increases slightly with increasing aspect ratio. A peak degree of mixing on the order of 85% is obtained for the range of parameter values explored here. In the second phase of the analysis, the effect of combining a fixed throughput flow with the oscillatory cross channel motion for use in a continuous mixing operation is examined in a star cell geometry. Chaotic mixing is again observed, and the characteristics of the downstream dispersion patterns depend mainly on the Strouhal number and the (dimensionless) throughput rate. In the star cell, the flow becomes appreciably chaotic as evidenced by visual particle dispersion at approximately St = 1, slightly higher than for the case of cross cell. The star cell mixing behavior is marked by the convergence of the degree of mixing to a plateau level as the Strouhal number is increased at fixed flow rate. Degree of mixing values from 70 to 80% are obtained indicating that the continuous flow is bounded by the maximum degree of mixing obtained from the confined flow configuration.

Chitosan microfiber fabrication using a microfluidic chip and its application to cell cultures

In this study, a poly-methyl-methacrylate (PMMA) microfluidic chip with a 45° cross-junction microchannel is fabricated using a CO₂ laser machine to generate chitosan microfibers. Chitosan solution and sodium tripolyphosphate (STPP) solution were injected into the cross-junction microchannel of the microfluidic chip. The laminar flow of the chitosan solution was generated by hydrodynamic focusing. The diameter of laminar flow, which ranged from 30 to 50 μm, was controlled by changing the ratio between chitosan solution and STPP solution flow rates in the PMMA microfluidic chip. The laminar flow of the chitosan solution was converted into chitosan microfibers with STPP solution via the cross-linking reaction; the diameter of chitosan microfibers was in the range of 50–200 μm. The chitosan microfibers were then coated with collagen for cell cultivation. The results show that the chitosan microfibers provide good growth conditions for cells. They could be used as a scaffold for cell cultures in tissue engineering applications. This novel method has advantages of ease of fabrication, simple and low-cost process.     

Experimental study of diffusion-based extraction from a cell suspension

A recently proposed application of microfluidics is the post-thaw processing of biological cells. Numerical simulations suggest that diffusion-based extraction of the cryoprotective agent dimethyl sulfoxide (DMSO) from blood cells is viable and more efficient than centrifugation, the conventional method of DMSO removal. In order to validate the theoretical model used in these simulations, a prototype was built and the flow of two parallel streams, a suspension of Jurkat cells containing DMSO and a wash stream that contained neither cells nor DMSO, was characterized experimentally. DMSO transport in a rectangular channel (depth 500 μm, width 25 mm and overall length 125 mm) was studied as a function of three dimensionless parameters: depth ratio of the streams, cell volume fraction in the cell solution, and the Peclet number (Pe) based on channel depth, average flow rate and the diffusion coefficient for DMSO in water. In our studies, values of Pe ranged from O(10³) to O(10⁴). Laminar flow was ensured by keeping the Reynolds number between O(1) and O(10). Experimental results based on visual and quantitative data demonstrate conclusively that a microfluidic device can effectively remove DMSO from liquid and cell laden streams without compromising cell recovery. Also, flow conditions in the microfluidic device appear to have no adverse effect on cell viability at the outlet. Further, the results demonstrate that we can predict the amount of DMSO removed from a given device with the theoretical model mentioned previously.     

Effect of dispersed phase viscosity on maximum droplet generation frequency in microchannel emulsification using asymmetric straight-through channels

Uniformly sized droplets of soybean oil, MCT (medium-chain fatty acid triglyceride) oil and n-tetradecane with a Sauter mean diameter of d _3,2 = 26–35 μm and a distribution span of 0.21–0.25 have been produced at high throughputs using a 24 × 24 mm silicon microchannel plate consisting of 23,348 asymmetric channels fabricated by photolithography and deep reactive ion etching. Each channel consisted of a 10-μm diameter straight-through micro-hole with a length of 70 μm and a 50 × 10 μm micro-slot with a depth of 30 μm at the outlet of each channel. The maximum dispersed phase flux for monodisperse emulsion generation increased with decreasing dispersed phase viscosity and ranged from over 120 L m⁻² h⁻¹ for soybean oil to 2,700 L m⁻² h⁻¹ for n-tetradecane. The droplet generation frequency showed significant channel to channel variations and increased with decreasing viscosity of the dispersed phase. For n-tetradecane, the maximum mean droplet generation frequency was 250 Hz per single active channel, corresponding to the overall throughput in the device of 3.2 million droplets per second. The proportion of active channels at high throughputs approached 100% for soybean oil and MCT oil, and 50% for n-tetradecane. The agreement between the experimental and CFD (Computational Fluid Dynamics) results was excellent for soybean oil and the poorest for n-tetradecane.     

High-throughput electrokinetic bioparticle focusing based on a travelling-wave dielectrophoretic field

This study presents a sheathless and portable microfluidic chip that is capable of high-throughput focusing bioparticles based on 3D travelling-wave dielectrophoresis (twDEP). High-throughput focusing is achieved by sustaining a centralized twDEP field normal to the continuous through-flow direction. Two twDEP electrode arrays are formed from upper and lower walls of the microchannel and extend to its center, which induce twDEP forces to provide the lateral displacements in two directions for focusing the bioparticles. Bioparticles can be focused to the center of the microchannel effectively by twDEP conveyance when the characteristic time due to twDEP conveying in the y direction is shorter than the residence time of the particles within twDEP electrode array. Red blood cells can be effectively focused into a narrow particle stream (~10 μm) below a critical flow rate of 10 μl/min (linear flow velocity ~5 mm/s), when under a voltage of 14 V_p–p at a frequency of 500 kHz is applied. Approximately 90% focusing efficiency for red blood cells can be achieved within two 6-mm-long electrode arrays when the flow rate is below 12 μl/min. Blood cells and Candida cells were also focused and sorted successfully based on their different twDEP mobilities. Compared to conventional 3D-paired DEP focusing, velocity is enhanced nearly four folds of magnitude. 3D twDEP provides the lateral displacements of particles and long residence time for migrating particles in a high-speed continuous flow, which breaks through the limitation of many electrokinetic cell manipulation techniques.     

Effects of channel surface finish on blood flow in microfluidic devices

The behaviour of blood flow in relation to microchannel surface roughness has been investigated. Special attention was focused on the techniques used to fabricate the microchannels and on the apparent viscosity of the blood as it flowed through these microchannels. For the experimental comparison of smooth and rough surface channels, each channel was designed to be 10 mm long and rectangular in cross-section with aspect ratios of ≥100:1 for channel heights of 50 and 100 μm. Polycarbonate was used as the material for the device construction. The shims, which created the heights of the channels, were made of polyethylene terephthalate. Surface roughnesses of the channels were varied from R _z of 60 nm to 1.8 μm. Whole horse blood and filtered water were used as the test fluids and differential pressures ranged from 200 to 5,000 Pa. The defibrinated horse blood was treated further to prevent coagulation. The results indicate that a surface roughness above an unknown value lowers the apparent viscosity of blood dramatically due to boundary effects. Furthermore, the roughness seemed to influence both water and whole blood almost equally. A set of design rules for channel fabrication is also presented in accordance with the experiments performed.     

Magnetically controlled valve for flow manipulation in polymer microfluidic devices

A simple, external in-line valve for use in microfluidic devices constructed of polydimethylsiloxane (PDMS) is described. The actuation of the valve is based on the principle that flexible polymer walls of a liquid channel can be pressed together by the aid of a permanent magnet and a small metal bar. In the presence of a small NdFeB magnet lying below the channel of interest, the metal bar is pulled downward simultaneously pushing the thin layer of PDMS down thereby closing the channel stopping any flow of fluid. The operation of the valve is dependent on the thickness of the PDMS layer, the height of the channel, the gap between the chip and the magnet and the strength of the magnet. The microfluidic channels are completely closed to fluid flows ranging from 0.1 to 1.0 μL/min commonly used in microfluidic applications.     

Computational modeling and comparison of three co-laminar microfluidic mixing techniques

This study compares three common microfluidic mixing techniques: electroosmosis with patterned zeta potential, hydrodynamic focusing and physical constrictions. All three techniques provide a higher degree of mixing than a comparable channel without a mixer, but at the cost of higher power requirements. Of the three techniques, the electroosmotic mixer requires the greatest amount of power to produce a high degree of mixing, unless the channels are much smaller than those typical for microfluidic devices. The power requirement of the physical constriction mixer may be lowered by using multiple constrictions, with only a small loss in mixing effectiveness. The physical constriction mixer is recommended, since it has power requirements similar to the hydrodynamic focusing mixer but only requires the use of a single pump. However, if the mixing liquids contain particulates, a hydrodynamic focusing mixer may be preferred, because the physical constriction mixer may clog, depending on the particulate size.     

Experimental and numerical investigation into the joule heating effect for electrokinetically driven microfluidic chips utilizing total internal reflection fluorescence microscopy

This paper presents a detection scheme for analyzing the temperature distribution nearby the channel wall in a microfluidic chip utilizing a temperature-dependent fluorescence dye. An advanced optical microscope system—total internal reflection fluorescence microscope (TIRFM) is used for measuring the temperature distribution on the channel wall at the point of electroosmotic flow in an electrokinetically driven microfluidic chip. In order to meet the short working distance of the objective type TIRFM scheme, microscope cover glass slits are used to fabricate the microfluidic chips. The short fluorescence excitation depth from a TIRFM system makes the intensity information obtained using TIRFM is not sensitive to the channel depth variation which ususally biases the measured results while using a conventional Epi-fluorescence microscope (EPI-FM). Therefore, a TIRFM can precisely describe the temperature profile of the distance within 100 nm of the channel wall where consists of the Stern layer and the diffusion layer for an electrokinetic microfluidic system. Results indicate the proposed TIRFM provides higher measurement sensitivity over the EPI-FM. Significant temperature gradient along the channel depth is experimentally observed. In addition, the measured wall temperature distributions can be the boundary conditions for numerical investigation into the joule heating effect. The proposed method gives a precise temperature profile of microfluidic channels and shows the substantial impact on developing a numerical simulation model for precisely predicting the joule heating effect in microfluidic chips.     

Hybrid molecular dynamics-continuum simulation for nano/mesoscale channel flows

The present study deals with multiscale simulation of the fluid flows in nano/mesoscale channels. A hybrid molecular dynamics (MD)-continuum simulation with the principle of crude constrained Lagrangian dynamics for data exchange between continuum and MD regions is performed to resolve the Couette and Poiseuille flows. Unlike the smaller channel heights, H < 50σ (σ is the molecular length scale, σ ≈ 0.34 nm for liquid Ar), considered in the previous works, this study deals with nano/mesoscale channels with height falling into the range of 44σ ≤ H ≤ 400σ, i.e., O(10)–O(10²) nm. The major concerns are: (1) to alleviate statistic fluctuations so as to improve convergence characteristics of the hybrid simulation—a novel treatment for evaluation of force exerted on individual particle is proposed and its effectiveness is demonstrated; (2) to explore the appropriate sizes of the pure MD region and the overlap region for hybrid MD-continuum simulations—the results disclosed that, the pure MD region of at least 12σ and the overlap region of the height 10σ have to be used in this class of hybrid MD-continuum simulations; and (3) to investigate the influences of channel height on the predictions of the flow field and the slip length—a slip length correlation is formulated and the effects of channel size on the flow field and the slip length are discussed. An erratum to this article can be found at