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.     

Automating fluid delivery in a capillary microfluidic device using low-voltage electrowetting valves

A multilayer capillary polymeric microfluidic device integrated with three normally closed electrowetting valves for timed fluidic delivery was developed. The microfluidic channel consisted two flexible layers of poly (ethylene terephthalate) bonded by a pressure-sensitive adhesive spacer tape. Channels were patterned in the spacer tape using laser ablation. Each valve contained two inkjet-printed silver electrodes in series. Capillary flow within the microchannel was stopped at the second electrode which was modified with a hydrophobic monolayer (valve closed). When a potential was applied across the electrodes, the hydrophobic monolayer became hydrophilic and allowed flow to continue (valve opened). The relationship between the actuation voltage, the actuation time, and the distance between two electrodes was performed using a microfluidic chip containing a single microchannel design. The results showed that a low voltage (4.5 V) was able to open the valve within 1 s when the distance between two electrodes was 1 mm. Increased voltages were needed to open the valves when the distance between two electrodes was increased. Additionally, the actuation time required to open the valve increased when voltage was decreased. A multichannel device was fabricated to demonstrate timed fluid delivery between three solutions. Our electrowetting valve system was fabricated using low-cost materials and techniques, can be actuated by a battery, and can be integrated into portable microfluidic devices suitable for point-of-care analysis in resource-limited settings.     

Development and characterization of a capillary-flow microfluidic device for nucleic acid detection

We have developed a capillary flow-driven microfluidic biosensor to meet the needs of diagnostics for resource-limited areas. The device combined elements of lateral flow assays and microfluidic technology resulting in a hybrid with benefits of both formats. The biosensor was achieved by bonding two pieces of polymethyl methacrylate with channels ablated by a CO₂ laser, and enclosing an absorbent pad. The channels were UV/ozone treated to increase hydrophilicity which enabled capillary flow. The absorbent pad allowed for continuous flow in the channels once filled. The application of biosensor was demonstrated by detection of DNA with a sandwich assay. The target DNA was hybridized with nucleic acid modified magnetic beads as well as Ru(bpy) ₃ ²⁺ doped silica nanoparticles. Fluorescent signals were quantified in a holder fabricated to fit in a fluorescent microtiter plate reader. The capillary flow microfluidic was capable to detect 1?pmol target. The assay format which features rapid analysis and does not require the use of pumps could allow for inexpensive point of care diagnostics in the future.     

Micro-optofluidic switch realized by 3D printing technology

This paper presents a PDMS micro-optofluidic chip that allows a laser beam to be driven directly toward a two-phase flow stream in a micro-channel while at the same time automatically, detecting the slug’s passage and stirring the laser light, without the use of any external optical devices. When the laser beam interacts with the microfluidic flow, depending on the fluid in the channel and the laser angle of incidence, a different signal level is detected. So a continuous air–water segmented flow will generate a signal that switches between two values. The device consists of a T-junction, which generates the two-phase flow, and three optical fiber insertions, which drive the input laser beam toward a selected area of the micro-channel and detects the flow stream. Three micro-channel sections of different widths were considered: 130, 250, 420 μm and the performance of the models was obtained by comparing ray-tracing simulations. The master of the device has been realized by 3D printing technology and a protocol which realizes the PDMS chip is presented. The static and dynamic characterizations, considering both single flows and two-phase flows, were carried out, and in spite of the device’s design simplicity, the sensitivity of the system to capture changes in the segmented flows and to stir the laser light in different directions was fully confirmed. The experimental tests show the possibility of obtaining satisfactory results with channel diameters in the order of 200 μm.     

Fast and inexpensive method for the fabrication of transparent pressure-resistant microfluidic chips

The recent rise of high-pressure applications in microfluidics has led to the development of different types of pressure-resistant microfluidic chips. For the most part, however, the fabrication methods require clean room facilities, as well as specific equipment and expertise. Furthermore, the resulting microfluidic chips are not always well suited to flow visualization and optical measurements. Herein, we present a method that allows rapid and inexpensive prototyping of optically transparent microfluidic chips that resist pressures of at least 200 bar. The fabrication method is based on UV-curable off-stoichiometry thiol-ene epoxy (OSTE+) polymer, which is chemically bonded to glass. The reliability of the device was verified by pressure tests using CO₂, showing resistance without failure up to at least 200 bar at ambient temperature. The microchips also resisted operation at high pressure for several hours at a temperature of 40 °C. These results show that the polymer structure and the chemical bond with the glass are not affected by high-pressure CO₂. Opportunities for flow visualization are illustrated by high-pressure two-phase flow shadowgraphy experiments. These microfluidic chips are of specific interest for use with supercritical CO₂ and for optical characterization of phase transitions and multiphase flow under near-critical and critical CO₂ conditions.     

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.     

A facile strategy to integrate robust porous aluminum foil into microfluidic chip for sorting particles

High efficiency integration of functional microdevices into microchips is crucial for broad microfluidic applications. Here, a device-insertion and pressure sealing method was proposed to integrate robust porous aluminum foil into a microchannel for microchip functionalization which demonstrate the advantage of high efficient foil microfabrication and facile integration into the microfluidic chip. The porous aluminum foil with large area (10 × 10 mm²) was realized by one-step femtosecond laser perforating technique within few minutes and its pores size could be precisely controlled from 3 μm to millimeter scale by adjusting the laser pulse energy and pulse number. To verify the versatility and flexibility of this method, two kinds of different microchips were designed and fabricated. The vertical-sieve 3D microfluidic chip can separate silicon dioxide (SiO₂) microspheres of two different sizes (20 and 5 μm), whereas the complex stacking multilayered structures (sandwich-like) microfluidic chip can be used to sort three different kinds of SiO₂ particles (20, 10 and 5 μm) with ultrahigh separation efficiency of more than 92%. Furthermore, these robust filters can be reused via cleaning by backflow (mild clogging) or disassembling (heavy clogging).     

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.     

Manufacture of microfluidic glass chips by deep plasma etching, femtosecond laser ablation, and anodic bonding

Two dry subtractive techniques for the fabrication of microchannels in borosilicate glass were investigated, plasma etching and laser ablation. Inductively coupled plasma reactive ion etching was carried out in a fluorine plasma (C₄F₈/O₂) using an electroplated Ni mask. Depth up to 100 μm with a profile angle of 83°–88° and a smooth bottom of the etched structure (Ra below 3 nm) were achieved at an etch rate of 0.9 μm/min. An ultrashort pulse Ti:sapphire laser operating at the wavelength of 800 nm and 5 kHz repetition rate was used for micromachining. Channels of 100 μm width and 140 μm height with a profile angle of 80–85° were obtained in 3 min using an average power of 160 mW and a pulse duration of 120 fs. A novel process for glass–glass anodic bonding using a conductive interlayer of Si/Al/Si has been developed to seal microfluidic components with good optical transparency using a relatively low temperature (350°C).     

One-step rapid fabrication of paper-based microfluidic devices using fluorocarbon plasma polymerization

In this work, we demonstrated an all-dry, top-down, and one-step rapid process to fabricate paper-based microfluidic devices using fluorocarbon plasma polymerization. This process is able to create fluorocarbon-coated hydrophobic patterns on filter paper substrates while maintaining the trench and detection regions intact and free of contamination after the fabrication process, as confirmed by attenuated total reflectance–Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We have shown that the processing time is one critical factor that influences the device performance. For the device fabricated with a sufficiently long processing time (180 s), the sample fluid flow can be well confined in the patterned trenches. By testing the device with an 800 μm channel width, a sample solution amount as small as 4.5 μL is sufficient to perform the test. NO₂ ^? assay is also performed and shows that such a device is capable for biochemical analysis.     

A novel filtration method integrated on centrifugal microfluidic devices

A method has been developed that integrates filters directly into centrifugal microfluidic devices. This technique is suitable for both rapid prototyping and commercial applications. Commercially available filter paper was sealed into the centrifugal microfluidic device with a simple manual fabrication procedure. The method was validated using soil slurry in water and a variety of filter papers with pore sizes ranging from 0.7 to 11 μm. Filtration times of 4 s to several minutes were obtained for 100 μL samples depending on the type of filter paper and rotation rate utilized. The validity of the method was demonstrated by assessing the amount of light lost due to the scatter or absorption caused by particles in the filtered sample while the device was in motion. Filtration and sedimentation were compared and after 30 min of centrifugation, sedimentation had not removed particles as well as filtration. This technique opens up centrifugal microfluidic devices to a wide range of samples.     

Effect of operating conditions and liquid physical properties on the size of monodisperse microbubbles produced in a capillary embedded T-junction device

The aim of this study was to investigate the effect of operating parameters such as liquid flow rate, gas inlet pressure, and capillary diameter as well as the influence of the physical properties of the liquid, in particular viscosity, on the generation of monodisperse microbubbles in a circular cross section T-junction device. Aqueous glycerol solutions with viscosities ranging from 1- to 100 mPa s were used in the experiments. The bubble diameter generated was studied for systematically varied combinations of gas inlet pressure, liquid flow rate, and liquid viscosity with a fixed capillary inner diameter of 150 μm for the liquid and gas inlet channels as well as the outlet channel. In addition, the effect of channel geometry on bubble size was studied using capillaries with inner diameters of first 100 and then 200 μm. In all the experiments the distance between the coaxial capillaries at the junction was set to be 200 μm. All the microbubbles produced in this study were highly monodisperse (polydispersity index <1 %) and it was found, as expected, that bubble formation and size were influenced by the ratio of liquid to gas flow rate, capillary size, and liquid viscosity. The experimental data were then compared with empirical scaling laws derived for rectangular cross-section junctions. In contrast with these previous studies, which have found bubble size to be dependent on either the flow rate ratio (the squeezing regime) or capillary number (the dripping regime), in this experimental study bubble size was found to depend on both capillary number and flow ratio.     

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.     

Normally closed plunger-membrane microvalve self-actuated electrically using a shape memory alloy wire

Various microfluidic architectures designed for in vivo and point-of-care diagnostic applications require larger channels, autonomous actuation, and portability. In this paper, we present a normally closed microvalve design capable of fully autonomous actuation for wide diameter microchannels (tens to hundreds of µm). We fabricated the multilayer plunger-membrane valve architecture using the silicone elastomer, poly-dimethylsiloxane (PDMS) and optimized it to reduce the force required to open the valve. A 50-µm Nitinol (NiTi) shape memory alloy wire is incorporated into the device and can operate the valve when actuated with 100-mA current delivered from a 3-V supply. We characterized the valve for its actuation kinetics using an electrochemical assay and tested its reliability at 1.5-s cycle duration for 1 million cycles during which we observed no operational degradation.     

Low-cost credit card-based microfluidic devices for magnetic bead immobilisation

We report a simple low-cost magnetic microfluidic device for magnetic bead separation and immobilisation. One dimensional arrays of localised high magnetic field gradients are constructed at the interfaces between regions magnetised with opposing polarities on the magnetic Fe₂O₃ composite stripes of credit cards. The localised high magnetic field gradients are employed to trap magnetic beads on the surface of the magnetic stripe, without the need for external magnetic components. A magnetic card writer was used to deterministically pattern the magnetic stripes of credit cards to define arrays of magnetic reversals. The fabrication of the device is based on PDMS to credit card bonding of simple flow channels. Experimental results demonstrate that magnetic beads can be captured with efficiencies of 85, 67 and 27 % at flow rates of 25, 50 and 100 μL min^?1, respectively. The results show that the credit card-based magnetic separator might offer an efficient, simple, low-cost alternative to traditional microfluidic magnetic separators for applications such as immunomagnetic cell separation.     

Cells adhered and cultured on microcantilevers

This paper shows a novel method to cultivate cells on a π-shape microcantilever inside a polydimethylsiloxane microfluidic system. Only one lithography step was needed to precisely align and pattern a poly(2-hydroxyethyl methacrylate) hydrogel microstructure, of size 200 × 200 μm, onto a silicon nitride microcantilever inside the PDMS microfluidic device. Gelatin was used as a sacrificial layer to resolve the issue of the microfluidic and hydrogel microstructure sticking together, successfully releasing the microcantilevers. BHK-21 cells were successfully laden and cultivated on the hydrogel microstructures of microcantilevers for 24 h. The optical system consisted of a He–Ne laser, a charge-coupled device camera, and a position-sensitive detector, which was used to measure the deflections of the microcantilevers due to the laden cells. The deflection increased continually during the cell-laden period. Meanwhile, the deflection increased with increasing cell concentration. By repeating the cell-laden and culture experiment three times, the magnitude and trend of deflection of microcantilevers were almost the same. It demonstrates that the microcantilever-based biochip has adequate stability and provides reliable measurement results for drug screening applications in the future.     

Transparent thin thermoplastic biochip by injection-moulding and laser transmission welding

Recently microfluidic devices have emerged as a viable technology for the miniaturization of high throughput tools for analytical tasks related to structural biology such as screening of crystallization conditions and structural analysis. This work reports the manufacture of microfluidic chips in transparent thermoplastic polymers [poly(methylmethacrylate) (PMMA), and cyclic olefin copolymer (COC)] using two complementary technologies, injection moulding for the fabrication of the fluidic level and laser transmission welding for the sealing of the cover. A steel mould insert was produced by laser micro caving using a solid state laser radiation source (Nd:YAG, wavelength 1,064 nm). Fluidic chips of ~670 μm thickness comprising channels of 50 μm depth and width down to 50 μm were injection moulded in PMMA and COC. Joining of transparent thin cover film to the micro-injected fluidic level was performed by laser transmission welding using high power diode laser radiation (wavelength 940 nm) and an intermediate thin absorbing layer with a thickness of about several nanometers.     

A microfluidic chip of multiple-channel array with various oxygen tensions for drug screening

Oxygen participates in numbers of cellular activities and behaviors in both normal and pathological tissues. In physiological microenvironment, oxygen tension is generally below 21 % and varies in different species, states and regions of organs. However, present studies of cellular behavior in vitro are performed in an ambient level, which is not conformity to the reality in vivo. In this study, a microfluidic device was developed to generate controllable oxygen tensions on a multiple-channel array chip for high-throughput drug screening. Controlling various concentrations of chemical reagents with confined flow rate, specific oxygen tensions can be established from 1.6 to 21 %, where the oxygen tension of each channel can be modulated in demand. When the concentrations of pyrogallol change from 100 to 700 μg/mL with the flow rate of 5 μL/min, oxygen tensions in cell chambers range from 12.5 to 3.87 %. Pyrogallol with the concentration of 0 μg/mL is used as the control group to obtain 20.9 % oxygen condition. The developed microfluidic chip was used to investigate the cytotoxicity of TPZ and cisplatin, and the results demonstrate different manners of two oxygen-sensitive anti-tumor drugs in oxygen-dependent cytotoxic responses. Due to its character, the microfluidic device is believed to establish any desired and measurable oxygen tension distribution for pharmacology development, which is promising to improve efficiency and reduce tedious operation for pharmaceutical studies.     

Design and fabrication of an electrochemically actuated microvalve

A microfluidic valve based on electrochemical (ECM) actuation was designed, fabricated using UV-LIGA microfabrication technologies. The valve consists of an ECM actuator, polydimethylsiloxane (PDMS) membrane and a micro chamber. The flow channels and chamber are made of cured SU-8 polymer. The hydrogen gas bubbles were generated in the valve microchamber with Pt black electrodes (coated with platinum nanoparticles) and filled with 1 M of NaCl solution. The nano particles coated on the working electrode helps to boost the surface-to-volume ratio of the electrode for faster reversible electrolysis and faster valve operation. To test the functionality of the microvalve, a simple micropump based on ECM principle was also integrated in the system to deliver a microscopic volume of fluid through the valve. The experimental results have showed that an approximately 300 μm deflection of valve membrane was achieved by applying a bias voltage of ?1.5 V across the electrodes. The pressure in the valve chamber was estimated to be about 200 KPa. Experimental results proved that the valve can be easily operated by controlling the electrical signals supplied to the ECM actuators.     

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.