Design optimization of capillary-driven micromixer with square-wave microchannel for blood plasma mixing

A numerical and experimental investigation is performed into the flow characteristics and mixing performance of three microfluidic polydimethylsiloxane blood plasma mixing devices incorporating square-wave, curved and zigzag microchannels, respectively. For each device, the plasma is introduced into the microfluidic channel under the effects of capillary action alone. Of the three devices, that with the square-wave microchannel is found to yield the best mixing performance, and is therefore selected for design optimization. Four microfluidic micromixers incorporating square-wave microchannels with different widths in the x- and y-directions are fabricated using conventional photolithography techniques. The mixing performance of the four microchannels is investigated both numerically and experimentally. The results show that given an appropriate specification of the microchannel geometry, a mixing efficiency of approximately 76 % can be obtained within 4 s. The practical feasibility of the micromixer is demonstrated by performing prothrombin time (PT) tests using a total liquid volume of 4.0 μL (2.0 μL of plasma and 2.0 μL of PT reagent). It is shown that the mean time required to complete the entire PT test (including loading, mixing and coagulation) is less than 30 s.

     

Centrifuge-based micromixer with three-dimensional square-wave microchannel for blood plasma mixing

A numerical and experimental investigation is performed into the flow characteristics and mixing performance of four centrifuge-based compact disk (CD) microfluidic mixers with square-wave microchannels and different numbers and arrangements of inlet channels. Of the four micromixers, the 3 × 1 3D mixer (three inlet channels, one outlet channel, and a two-layer mixing channel) is found to yield the best mixing performance. The superior mixing performance is attributed to the formation of transverse secondary flows and a 3D stirring effect at the corners of the square-wave channel. The experimental results show that given a CD rotation speed of 1000 rpm, a mixing efficiency of more than 91 % can be obtained within 5 s. The practical feasibility of the micromixer is demonstrated by performing prothrombin time (PT) tests. It is shown that the mean time required to complete the entire PT test (including loading, mixing and coagulation) is less than 45 s.

     

Disposable microfluidic blood cuvette for measuring hemoglobin concentration

This paper presents a new air-bubble free microfluidic blood cuvette for the measurement of hemoglobin concentration. The microfluidic blood cuvette was filled with blood samples by capillary force, and hemoglobin levels in the blood were determined by measuring absorbance at the wavelength of 530 nm. Two different microfluidic blood cuvettes with dual and single sidewall microchannels were investigated. The microfluidic blood cuvette was fabricated using a polymethyl methacrylate substrate and a dry film photoresist. During the blood-filling process, air was trapped in the dual-sided wall-type cuvettes, while no air trapping occurred in the single sidewall-type cuvettes. The sensitivity of the hemoglobin measurements was more linear in a 105 μm deep microchannel than in a 35 μm deep microchannel.     

Numerical simulation of the capillary flow in the meander microchannel

Pumping in microfluidic devices is an important issue in actuating fluid flow in microchannel, especially that capillary force has received more and more attractions due to the self-driven motion without external power input. However, less 2D simulation was done on the capillary flow in microchannel especially the meander microchannel which can be used for mixing and lab-on-a-chip (LOC) application. In this paper, the numerical simulation of the capillary flow in the meander microchannel has been studied using computer fluid dynamic simulation software CFD-ACE⁺. Different combinations of channel width in the X-direction denoted as W_x and Y-direction denoted as W_y were designed for simulating capillary flow behavior and pressure drop. The designed four types of meander microchannels (W_x × W_y) were 100 × 100 μm, 100 × 200 μm, 50 × 200 μm, and 50 × 400 μm. In this simulation results, it is found that the capillary pumping speed is highly depending on the channel width. The large speed change occurs at the turning angle of channel width change from W_x to W_y. The fastest pumping effect is found in the meander channel of 100 × 100 μm, which has an average pumping speed of 0.439 mm/s. The slowest average flow speed of 0.205 mm/s occurs in the meander channel of 50 × 400 μm. Changing the meander channel width may vary the capillary flow behavior including the pumping speed and the flow resistance as well as pressure drop which will be a good reference in designing the meander microchannels for microfluidic and LOC application.     

Numerical study of the effect on mixing of the position of fluid stream interfaces in a rectangular microchannel

A numerical study has been carried out to investigate the effect on mixing of the position of fluid stream interfaces in a rectangular microchannel. The velocity profile in a microchannel has a parabolic shape which shows maximum local velocity at the center of the channel and minimum velocity near the wall. This velocity profile governs the residence time of the fluid streams and hence effects on the mixing of fluid streams. Single and double interfaces of the fluid streams have been studied in rectangular microchannels for the range of Reynolds numbers (0.1 ≤ Re ≤ 10) where mixing is mainly governed by molecular diffusion. Significant variations in the mixing performance have been shown at various positions of the interfaces at different Reynolds number.     

Rapid prototyping of glass-based microfluidic chips utilizing two-pass defocused CO2 laser beam method

A method is proposed for the scribing of glass substrates utilizing a commercial CO₂ laser system. In the proposed approach, the substrate is placed on a hotplate and the microchannel is then ablated using two passes of a defocused laser beam. The aspect ratio and surface quality of the microchannels formed after the first and second laser passes are examined using scanning electron microscopy and atomic force microscopy. The observation results show that the second laser pass yields an effective reduction in the surface roughness. The practicality of the proposed approach is demonstrated by fabricating a microfluidic chip for formaldehyde concentration detection. It is shown that the detection results obtained for five Chinese herbs with formaldehyde concentrations ranging from 5 to 55 ppm deviate by no more than 5.5 % from those obtained using a commercial macroscale device. In other words, the results confirm that the proposed defocused ablation technique represents a viable solution for the rapid and low-cost fabrication of a wide variety of glass-based microfluidic chips.     

Laser polishing and 2PP structuring of inside microfluidic channels in fused silica

This study presents the development of post-processing steps for microfluidics fabricated with selective laser etching (SLE) in fused silica. In a first step, the SLE surface—even inner walls of microfluidic channels—can be smoothed by laser polishing. In addition, two-photon polymerization (2PP) can be used to manufacture polymer microstructures and microcomponents inside the microfluidic channels. The reduction in the surface roughness by laser polishing is a remelting process. While heating the glass surface above softening temperature, laser radiation relocates material thanks to the surface tension. With laser polishing, the RMS roughness of SLE surfaces can be reduced from 12 µm down to 3 nm for spatial wavelength λ < 400 µm. Thanks to the laser polishing, fluidic processes as well as particles in microchannels can be observed with microscopy. A manufactured microfluidic demonstrates that SLE and laser polishing can be combined successfully. By developing two-photon polymerization (2PP) processing in microchannels we aim to enable new applications with sophisticated 3D structures inside the microchannel. With 2PP, lenses with a diameter of 50 µm are processed with a form accuracy rms of 70 nm. In addition, this study demonstrates that 3D structures can be fabricated inside the microchannels manufactured with SLE. Thanks to the combination of SLE, laser polishing and 2PP, research is pioneering new applications for microfluidics made of fused silica.     

Numerical simulation of flow and heat transfer in radially rotating microchannels

Investigation of fluid flow and heat transfer in rotating microchannels is important for centrifugal microfluidics, which has emerged as an advanced technique in biomedical applications and chemical separations. The centrifugal force and Coriolis force, arising as a consequence of the microchannel rotation, change the flow pattern significantly from the symmetric profile of a non-rotating channel. Successful design of microfluidic devices in centrifugal microfluidics depends on effectively regulating these forces in rotating microchannels. In this work, we have numerically investigated the flow and heat transfer in rotating rectangular microchannel with continuum assumption. A pressure-based finite-volume technique with a staggered grid was applied to solve the steady incompressible Navier–Stokes and energy equations. It was observed that the effect of Coriolis force was determined by the value of the non-dimensional rotational Reynolds number (Re _ω ). By comparing the root mean square deviation of the axial velocity profiles with the approximate analytical results of purely centrifugal flow for different aspect ratios (AR = width/height), a critical rotational Reynolds number (Re _ω,cr) was computed. Above this value of (Re _ω,cr), the effect of secondary flow becomes dominant. For aspect ratios of 0.25, 0.5, 1.0, 2.0, 4.0 and 9.09, this critical rotational Reynolds number (Re _ω,cr) was found to be 14.0, 5.5, 3.8, 4.7, 6.5 and 10.0, respectively.     

Application of metal film protection to microfluidic chip fabrication using CO2 laser ablation

The CO₂ laser ablation is a common technique for patterning the microchannels and holes used in microfluidic devices. However, the ablation process frequently results in an accumulation of resolidified material around the rims of the ablated features and a clogging of the base of the microchannel. In the article, these problems are resolved by means of a proposed metal-film-protected CO₂ laser ablation technique. In the approach, the substrate is patterned with a thin metallic mask prior to the ablation process and the mask is then stripped away once the ablation process is complete. The feasibility of the proposed approach is demonstrated by fabricating two micromixers with Y-shaped and T-shaped microchannels, respectively. It shows that for a designed channel width of 100 μm, the metallic mask reduces the ablated channel width from 268 to 103 μm. Moreover, the bulge height around the rims of the channel is reduced from 8.3 to <0.2 μm. Finally, the metallic mask also prevents clogging in the intersection regions of the two devices. The experimental mixing results obtained using red and green pigment dyes confirm the practical feasibility of the proposed approach.     

Arrays of high-aspect ratio microchannels for high-throughput isolation of circulating tumor cells (CTCs)

Microsystem-based technologies are providing new opportunities in the area of in vitro diagnostics due to their ability to provide process automation enabling point-of-care operation. As an example, microsystems used for the isolation and analysis of circulating tumor cells (CTCs) from complex, heterogeneous samples in an automated fashion with improved recoveries and selectivity are providing new opportunities for this important biomarker. Unfortunately, many of the existing microfluidic systems lack the throughput capabilities and/or are too expensive to manufacture to warrant their widespread use in clinical testing scenarios. Here, we describe a disposable, all-polymer, microfluidic system for the high-throughput (HT) isolation of CTCs directly from whole blood inputs. The device employs an array of high aspect ratio (HAR), parallel, sinusoidal microchannels (25 × 150 μm; W × D; AR = 6.0) with walls covalently decorated with anti-EpCAM antibodies to provide affinity-based isolation of CTCs. Channel width, which is similar to an average CTC diameter (10–20 μm), plays a critical role in maximizing the probability of cell/wall interactions and allows for achieving high CTC recovery. The extended channel depth allows for increased throughput at the optimized flow velocity (2 mm/s in a microchannel); maximizes cell recovery, and prevents clogging of the microfluidic channels during blood processing. Fluidic addressing of the microchannel array with a minimal device footprint is provided by large cross-sectional area feed and exit channels poised orthogonal to the network of the sinusoidal capillary channels (so-called Z-geometry). Computational modeling was used to confirm uniform addressing of the channels in the isolation bed. Devices with various numbers of parallel microchannels ranging from 50 to 320 have been successfully constructed. Cyclic olefin copolymer (COC) was chosen as the substrate material due to its superior properties during UV-activation of the HAR microchannels surfaces prior to antibody attachment. Operation of the HT-CTC device has been validated by isolation of CTCs directly from blood secured from patients with metastatic prostate cancer. High CTC sample purities (low number of contaminating white blood cells) allowed for direct lysis and molecular profiling of isolated CTCs.     

Flow characteristics of polar liquids in microfluidic immunosensors

There is an interest in microfluidic devices for disease detection. In microfluidic immunosensors, the microchannel surfaces are functionalized with a stack of intermediate linker molecules to the specific antibodies. The efficiency of these immunosensors depends on the effective capture of antigens flowing in the carrier fluid by the surface-immobilized antibodies. The diffusion of these antigens to these antibody-immobilized surfaces is governed by the velocity profile, which in turn is governed by the interaction of the carrier fluid molecules with the surface antibodies. We report a systematic study to characterize fluid flow of different polar liquids (water, methanol and isopropyl alcohol) in trapezoidal Si microchannels, of about 100 μm hydraulic diameter, functionalized with intermediate molecular layers along with three different antibodies immobilized via these molecular layers. The friction constants were calculated from the pressure drop measurements. We attempted to understand the solid–liquid interactions in terms of the friction constants as a function of the solid surface free energies of the terminal antibody layers (which are affected by the energetics of the underlying layers) immobilized on to the microchannels, and the polarities of the liquids flowing through these microchannels. Correlations of liquid polarities with the friction constants were seen for almost all the functionalized surfaces. A reasonable correlation of the surface energies with the friction constants was seen for most of the surfaces studied. Possible reasons for the behaviors are discussed. The measured friction constants and the knowledge of the solid–liquid interactions could facilitate improved designs of microfluidic immunosensors.     

An efficient micromixer actuated by induced-charge electroosmosis using asymmetrical floating electrodes

Efficient microfluid mixing is an important process for various microfluidic-based biological and chemical reactions. Herein we propose an efficient micromixer actuated by induced-charge electroosmosis (ICEO). The microchannel of this device is easy to fabricate for its simple straight channel structure. Importantly, unlike previous design featuring complicated three-dimensional conducting posts, we utilize the simpler asymmetrical planar floating-electrodes to induce asymmetrical microvortices. For evaluating the mixing performance of this micromixer, we conducted a series of simulations and experiments. The mixing performance was quantified using the mixing index, specifically, the mixing efficiency can reach 94.7% at a flow rate of 1500 µm/s under a sinusoidal wave with a peak voltage of 14 V and a frequency of 400 Hz. Finally, we compared this micromixer with different micromixing devices using a comparative mixing index, demonstrating that this micromixer remains competitive among these existing designs. Therefore, the method proposed herein can offer a simple solution for efficient fluids mixing in microfluidic systems.     

Fabrication of circular microfluidic channels through grayscale dual-projection lithography

Circular microfluidic channels are in great demand since they are more realistic in mimicking physiological flow systems, generating axis-symmetrical flow, and achieving uniform shear stress. A typical microchannel with rectangular cross section can induce non-physiological gradients of shear rate, pressure, and velocity. This paper presents a novel method of fabricating microfluidic channels with circular and elliptical cross sections through grayscale dual-projection lithography. Our method utilizes two projecting systems to expose grayscale image face-to-face and simultaneously polymerize the photocurable material. The cross-sectional profiles of the fabricated microchannels are consistent with mathematical predictions and, therefore, demonstrate the capability of controlling the channel shapes precisely. Customized circular microchannels can be generated with complex features such as junctions, bifurcations, hierarchies, and gradually changed diameters. This method is capable of fabricating circular channels with a wide range of diameters (39 μm–2 mm) as well as elliptical channels with a major-to-minor axis ratio up to 600%. Microfluidic devices with circular cross sections suitable for particle analysis were made as a demonstrative application in nanoparticle binding and distribution within a mimetic blood vessel. A ready-to-use microfluidic device with customized circular channels can be fabricated within 1 h without the need of clean room or expensive photolithography devices.     

Experimental study on self-flowing speed in microchannel related to micro-/nanoscale surface topographies

The microfluidic flowing on chip surface depends on the external load such as centrifugal force, magnetic force and bubbles, but it leads to the complexity of microsystem. Hence, a self-flowing is proposed inside microchannel on chip surface without any external load. The objective is to explore how micro-/nanoscale surface topographies of microchannel influence the microfluidic flowing. First, the microgrinding with a diamond wheel microtip was employed to fabricate the accurate and smooth V-shaped microchannel with the height of 300 µm and less; then, the microfluidic flowing state was modeled by the flowing concave with the parameterization of flow-end height; finally, the microfluidic flowing speed was experimentally investigated with reference to microchannel angle, gradient, surface roughness and chip material. It is shown that the microfluidic self-flowing is mainly induced by the microchannel tip and the nanometer-scale surface cracks around the microchannel tip. Small microchannel angle, large microchannel gradient and smooth microchannel surface may enhance the flowing speed on chip surface. The brittle quartz glass produces the nanometer-scale surface cracks around the microchannel tip, leading to an increase about 40 times in the self-flowing speed compared with the ductile polymer. It is confirmed that the self-flowing speed in dynamic state may be characterized by the proposed concave flow-end height.     

The effect of asymmetry on micromixing in curvilinear microchannels

The necessity of microscale mixing processes has been tremendously increasing in most of the microsize chemical and biochemical devices during recent years, particularly in the design of lab-on-a-chip and micrototal analysis systems. Different approaches were implemented in the available micromixers in the literature for improving the mixing performance. Due to the absence of any external source, mixing by utilizing passive mixing techniques is more economical. In curvilinear microchannels, which offer effective passive mixing, chaotic advection results in continuous radial perforation of inter-diffusion layer between the fluid streams due to the transverse secondary flows. In this study, the effects of Dean vortices and secondary flows were investigated in asymmetrical polydimethylsiloxane curvilinear rectangular microchannels, which were fabricated by one-step lithography process and had repeated S-shape patterns with a curvature of 280° along the channel. Moreover, the effect of asymmetry was assessed by comparing the mixing results with symmetrical microchannels. Mixing performance was analyzed by using NaOH and phenolphthalein solutions as mixing fluids, which entered from the channel inlets. According to the results, the significant effects of stretching and contracting motion of Dean vortices revealed themselves above a certain Dean number value, thereby making the asymmetrical microchannel outperform the symmetrical channel in the mixing performance. Below this threshold, the symmetrical microchannel was observed to be superior to the asymmetrical microchannel.     

Superhydrophobic, hierarchical, plasma-nanotextured polymeric microchannels sustaining high-pressure flows

We fabricated superhydrophilic and superhydrophobic polymeric microfluidic devices with controlled hierarchical, random roughness, using plasma processing. We implemented a dye staining technique to visually demonstrate the persistence of the superhydrophobic state under flow for pressures in excess of 2.5 bar inside the microchannel. We further confirmed the stability of superhydrophobicity by pressure drop measurements, friction factor and slip length calculations under laminar flow conditions. We also compared identical rough superhydrophilic and superhydrophobic microchannels showing reduced pressure drop in the latter by as much as 22 %. Plasma etching and simultaneous nanotexturing (followed by optional fluorocarbon plasma deposition) are thus shown as an easy-to-implement method for attaining robust Cassie-state against high-pressure microchannel flows.     

Superhydrophobic,passive microvalves with controllable opening threshold: exploiting plasma nanotextured microfluidics for a programmable flow switchboard

Plasma processing is used to create passive superhydrophobic on–off valves with tailored opening pressure inside microfluidic devices. First, anisotropic O₂ plasma etching on polymeric microchannels is utilized to controllably roughen (nanotexture) the bottom of the microchannel. Second, the nanotextured surfaces are hydrophobized by means of a C₄F₈ plasma deposition step through a stencil mask creating superhydrophobic stripes or patches. The superhydrophobic patches play the role of on/off valves with predesigned opening pressure threshold (in the range 40–110 mbar), determined by the microchannel dimensions and the size of the nanotexture on the patch. These valves are integrated inside microchannel networks paving the way to autonomous microfluidic devices. To this aim, we present a novel preprogrammable flow switchboard that can split and control the liquid flow for multiple analysis purposes. The proposed valves present an example of how effectively plasma nanoscience and nanotechnology can be applied to microfluidics/nanofluidics and analytical chemistry.     

Analysis and experiment of transient filling flow into a rectangular microchannel on a rotating disk

In order to predict the time-dependent behaviors of the moving front in lab-on-a-CD systems or centrifugal pumping, an analytical expression and experimental methods of centrifugal-force-driven transient filling flow into a rectangular microchannel in centrifugal microfluidics are presented in this paper. Considering the effect of surface tension, and neglecting the effect of Coriolis force, the velocity profile, flow rate, the moving front displacement and the pressure distribution along the microchannel are characterized. Experiments are carried out using the image-capturing unit to measure the shift of the flow in rectangular microchannels. The flow characteristics in rectangular microchannels with different cross-sectional dimensions (200, 300 and 400 μm in width and 140, 240 and 300 μm in depth) and length (18 and 25 mm) under different rotational speed are investigated. According to the experimental data, the model can be more reasonable to predict the flow displacement with time, and the errors between theoretical and the experimental will decrease with increasing the cross-section size of the microchannel.     

Fabrication of polyimide microfluidic devices by laser ablation based additive manufacturing

Polyimide microfluidic devices (MFDs) have been attached enormous significance because of its excellent organic-solvent inertness, biocompatibility, and thermal stability. In this paper, a novel fabrication method based on the thought of additive manufacturing, which is adding materials layer by layer from bottom to top, was used to construct a multilayer polyimide MFD. The MFD has sophisticated three-dimensional (3D) microchannels with adjustable cross-sectional geometries and high bonding strength, which leads to good reagent mixing performance, large surface-to-volume ratio, and great durability. Starting from a single polyimide film, ultraviolet (UV) laser was utilized to ablate microchannels on the film. Due to the studies over the influence of UV laser on the channel width, the microchannel edge shape is under control, varying from trapezoid to rectangle. From monolayer to multilayer MFDs, thermal bonding with fluorinated ethylene propylene (FEP) nanoparticle dispersion as the adhesive was adopted to stack polyimide films tightly with precise alignment. In this way, microchannels can be connected vertically between layers to form 3D structures. Besides, a homogeneous adhesive interlayer and polyimide-FEP mixing regime were formed, which can provide high bonding strength. Results of computational fluid dynamics simulation of 3D microchannel structures and organic synthesis experiment revealed that our device has great reagent mixing efficiency and promising application prospects in diverse research fields, especially organic chemical and biological studies.

     

Liquid flow through a diverging microchannel

In this work, experiments and three-dimensional numerical calculations of fluid flow through diverging microchannels were carried out with the aim of bringing out differences between flow in uniform and nonuniform passages. Deionized water was used as the working fluid in the experiments where the effects of mass flow rate (8.33 × 10^?6 to 8.33 × 10^?5 kg/s), microchannel hydraulic diameter (118–177 µm), length (10–30 mm) and divergence angle (4°–16°) on pressure drop were studied. The results are analyzed in detail with the help of numerical data. The pressure drop exhibits a linear dependence on the mass flow rate, whereas it is inversely proportional to the divergence angle and square of the hydraulic diameter. The pressure drop increases anomalously at 16°, suggesting that flow reversal occurs between 12° and 16°, which agrees with the corresponding value at the conventional scale. For the purpose of predicting pressure drop using straight microchannel theory, an equivalent hydraulic diameter was defined. It is observed that the equivalent hydraulic diameter, located at one-third of the diverging microchannel length from the inlet, becomes mostly independent of the mass flow rate, microchannel hydraulic diameter, length and divergence angle. The pressure drop for a diverging microchannel becomes equal to an equivalent hydraulic diameter uniform cross-section microchannel, suggesting that conventional correlations for straight microchannels can also be applied to diverging microchannels. The data presented in this work are of fundamental importance and can help in optimization of diffuser design used for example in valveless micropumps.