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.     

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.     

Analysis and experiment of capillary valves for microfluidics on a rotating disk

This paper presents an analytical expression of the pressure barrier in a capillary-burst valve for flow regulation in centrifugal microfluidics. The analysis considers variations of the interfacial energies at the meniscus of three-dimensional (3D) configuration in a rectangular microchannel with a sudden expansion in cross-section. We derive a simple expression that predicts the critical burst pressure or rotational speed to overcome the capillary valve. Experiments were carried out for capillary valves that were integrated with microchannels on a rotating disk having various cross-sectional dimensions (300 and 400 μm in width and 80–600 μm in depth) and wedge angles (30°–100°) of sudden expansion. The flow visualization of the meniscus development across the capillary valve supports the assumptions made for the present analysis. The measurements of burst rotational speeds for the capillary valves are in good agreement with the predictions by the simple expression except that those with a larger channel width and wider wedge angles are nearly 10% lower than the predicted values.     

Scaling the formation of slug bubbles in microfluidic flow-focusing devices

The present study aims at scaling the formation of slug bubbles in flow-focusing microfluidic devices using a high-speed digital camera and a micro particle image velocimetry (μ-PIV) system. Experiments were conducted in two different polymethyl methacrylate square microchannels of respectively 600 × 600 and 400 × 400 μm. N₂ bubbles were generated in glycerol–water mixtures with several concentrations of surfactant sodium dodecyl sulfate. The influence of gas and liquid flow rates, the viscosity of the liquid phase and the width of the microchannel on the bubble size were explored. The bubble size was correlated as a function of the width of the microchannel W _c, the ratio of the gas/liquid flow rates Q _g/Q _l and the liquid Reynolds number. During the pinch-off stage, the variation of the minimum width of the gaseous thread W _m with the remaining time could be scaled as _boxclose_boxclose ()^ - 0.15 (T - t)^1/3 . W_{\text{m}} \propto ({\frac{{Q_{\text{g}} }}{{Q_{\text{l}} }}})^{ - 0.15} (T - t)^{1/3} . The velocity fields in the liquid phase around the thread, determined by μ-PIV measurements, were obtained around a forming bubble to reveal the role of the liquid phase.     

Liquid film thickness measurement underneath a gas slug with miniaturized sensor matrix in a microchannel

Measurement of liquid film thickness is essential for understanding the dynamics of two-phase flow in microchannels. In this work, a miniaturized sensor matrix with impedance measurement and MEMS technology to measure the thin liquid film underneath a bubble in the air–water flow in a horizontal microchannel has been developed. This miniaturized sensor matrix consists of 5 × 5 sensors where each sensor is comprised of a transmitter and a receiver electrode concentrically. The dimension and performance of the sensor electrodes were optimized with simulation results. The maximum diameter of the sensor ring is 310 µm, allowing a measurable range of liquid film thickness up to 83 µm. These sensors were distributed on the surface of a wafer with photolithography technology, covering a total length of 8 mm and a width of 2 mm. A spatial resolution of 0.5 × 2.0 mm² and a temporal resolution of 5 kHz were achieved for this sensor matrix with a measurement accuracy of 0.5 µm. A series of microchannels with different heights were used in the calibration in order to achieve the signal-to-thickness characteristics of each sensor. This delicate sensor matrix can provide detailed information on the variation of film thickness underneath gas–water slug directly, accurately and dynamically.     

Integrated structure of PMMA microchannels for DNA separation by microchip capillary electrophoresis

We proposed and fabricated an integrated structure of microchannels consists of three different functional PMMA layers for post-genome analysis, gene diagnosis, and screenings of useful materials for pharmaceutical. This integrated structure with 96 microchip capillary electrophoresis units in one chip is characterized as the simple structure with low cost and new aspects of the serial unit bio-chemical operation from DNA amplification to their analysis using microchip capillary electrophoresis. The design of the structure was performed using computational fluid dynamics, heat transmission, and electrophoresis simulation. To improve DNA separation resolution, microchannel with narrow width at the corner was adapted. The deep X-ray lithography process using synchrotron radiation “New SUBARU”, nano-imprint, and fusion bonding without bonding adhesive was applied for the fabrication of the integrated structure of microchannels. It was demonstrated that the proposed integrated structure of microchannels results in a good performance of the on-chip DNA amplification and separation in a small MCE unit area of 9 mm × 9 mm.     

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.     

Persistence of turbulent flow in microchannels at very low Reynolds numbers

A fully resolved numerical simulation of a turbulent microchannel flow, with uniformly spaced two-dimensional obstruction elements mounted at the wall and normal to the flow direction, was carried out at a very low Reynolds number of Re ≃ 970 based on the centerline velocity and the microchannel height. Employing the lattice Boltzmann numerical technique, all energetic scales of turbulence were resolved with about 19 × 10⁶ grid points (1261 × 129 × 128 in the x ₁, x ₂, and x ₃ directions). The simulated results confirm the self-maintenance of turbulence at such a low Reynolds number. Turbulence persisted over more than 1,000 turnover times, which was sufficiently long to prove its self-maintenance. These findings support the conjecture that turbulence developing in microchannels having rough walls can not only be initiated but also maintained at very low Reynolds numbers.     

A microfluidic platform with permeable walls for the analysis of vascular and extravascular mass transport

The interface between the blood pool and the extravascular matrix is fundamental in regulating the transport of molecules, nanoparticles and cells under physiological and pathological conditions. In this work, a microfluidic chip is presented comprising two parallel microchannels connected laterally via an array of high aspect ratio micropillars, constituting the permeable vascular membrane. A double-step lithographic process combined with a replica molding approach is employed to realize 80 different arrays of micropillars exhibiting three cross-sectional geometries (rectangular, elliptical and curved); two orientations (normal and parallel) with respect to the flow; and a variety of width and gap sizes, respectively, ranging from 10 to 20 μm and 2 to 5 μm. As compared to conventional rectangular structures, the curved pillars provide higher bending stiffness, lower adhesive interactions, and smaller intra-channel separation distances. Specifically, 10-μm-wide curved pillars, laying parallel to the flow, offered the highest mechanical stability. To assess vascular permeability, the extravascular channel was filled with a hyaluronic acid hydrogel, while fluorescent Dextran molecules and calibrated polystyrene beads were injected in the vascular channel. Membrane permeability was observed to reduce with the molecular weight of Dextran and diameter of the beads, ranging from about 6 × 10^?5 to 2 × 10^?5 cm/s for 40 and 250 kDa Dextran and up to zero for 1.5 μm beads. The presented data demonstrate the potential of the proposed microfluidic chip for analyzing the vascular and extravascular mass transport, over multiple spatial and temporal scales, in a variety of diseases involving differential permeation across vascular walls.     

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.     

Development of a nanofluidic preconcentrator with precise sample positioning and multi-channel preconcentration

A nanofluidic preconcentrator with the capability of rapidly preconcentrating and precisely positioning protein bands in multiple microchannels has been developed for highly sensitive detection of biomolecules. A novel electrical resistive network model is developed to guide the design of the nanofluidic preconcentrator which consists of a PDMS slab bonded with a glass slide. In the prototype design, two microchannels (23 mm long, 25–50 μm wide, and 5–15 μm deep), one preconcentration microchannel and one ground microchannel are connected in the middle via 16 nanochannels (25–50 μm long, 25 μm wide, and 50–80 nm deep). With two sets of optimal voltage settings applied on the opposite ends of the nanofluidic chip, the ion depletion region and electrokinetic trapping were generated to carry out the preconcentration. With the optimal voltage settings (30–30 V) predicted by the model, the ionic current of the nanochannel in our optimized preconcentrator was adjusted to be greater than the threshold value (3.9 nA) needed for the occurrence of the preconcentration, and a preconcentration factor >10⁵ was achieved in 5 min. The sample positioning capability of the preconcentrator was demonstrated by adjusting the applied voltages and moving the preconcentrated protein bands to multiple sites by a distance from several micrometers to several millimeters in the preconcentration channel. The multi-channel preconcentration capability was also demonstrated by preconcentrating two protein bands in two separate microchannels. In this work, the resistive network model was developed and validated to optimize nanofluidic preconcentrators for rapid, high throughput and highly sensitive sensing of low abundance analytes.     

Analytical investigation of the feasibility of sacrificial microchannel sealing for Chip-Scale Atomic Magnetometers

An alkali metal vapor cell is a crucial component of the highly sensitive Chip Scale Atomic Magnetometers (CSAMs) that are increasingly deployed in a variety of electronic devices. Herein, we propose a novel microfabrication technique utilizing an array of microchannels at a bonded interface, to enable gas feedthrough for evacuation of unwanted gases from a vapor cell and subsequent introduction of an inert gas, followed by permanent sealing of the microchannels by reflow of a glass frit. The characteristics of glass frit reflow are analyzed to investigate the feasibility of using microchannels formed either on a silicon substrate, or embedded in a glass frit layer, with four different cross-sectional shapes considered. Prior to modeling the microchannels for simulation, the minimum cross-sectional size of a microchannel that fulfills gas feedthrough requirements was calculated and a value of 10 μm was determined based on a flow conductance model. The sealing of the microchannels was simulated using the finite element method (FEM) and the results revealed that flow resistance is a crucial design factor. Thus, embedded microchannel designs were more suitable for the proposed sealing technique than microchannel designs fabricated in silicon.     

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).     

微流控芯片中电渗流的数值模拟与仿真研究

从电渗流形成的基本理论入手,推导了电场和流场双物理场耦合的控制方程.运用多物理场数值计算分析软件建立了长为1000μm,宽为100μm的二维流道,在微流道中间250~750μm的区域施加了直流电压,并在数值模拟中还原了微流道内壁和微流体的物理属性,计算得出了各段流体的速度场,进而得出了各段流体的流型.通过二维流道压力分布分析了微流道中各段产生不同流型的原因.对微流控芯片中的电动流动的功能原理分析及优化设计具有借鉴意义.     

The manufacturing of packaged capillary action microfluidic systems by means of CO2 laser processing

In this article we demonstrate a simple yet robust rapid prototyping manufacturing technique for the construction of autonomous microfluidic capillary systems by means of CO₂ laser processing. The final packaging of the microfluidic device is demonstrated using thermal lamination bonding and allows for a turnaround time of approximately 30 min to 3 h from activation of the laser system to device use. The low-cost CO₂ laser system is capable of producing repeatable microfluidic structures with minimum feature sizes superior than 100–150 μm over channel depths of more than 100 μm. This system is utilised to create capillary pump and valve designs within poly (methyl methacrylate) (PMMA) substrates. Such components are part of advanced systems that can self initiate and maintain the flow of various volumes of fluids from an input to a collection reservoir, whilst also controlling the progression of the flow through the various demonstrated valve type structures. The resulting systems could prove a very useful alternative to traditional, non-integrated, fluidic actuation and flow control systems found on-chip, which generally require some form of energy input, have limited portable capabilities and require more complex fabrication procedures.     

Fabrication of 1D nanochannels on thermoplastic substrates using microchannel compression

We present a new method to fabricate one-dimensional (1D) nanochannels on a thermoplastic substrate. This method has two main steps. First, a mold with microscale features is used to replicate microchannels on a thermoplastic substrate. Second, the fabricated microchannel is compressed to a 1D nanochannel at a temperature above the glass transition temperature (T_g) of the themoplastics. The effects of compression temperature, compression pressure, retaining time and loading rate on microchannel compression have been studied. Results have shown that a 1D nanochannel of 1–30 μm wide and 200–300 nm deep can be readily fabricated by using this method.     

Effects of geometry factors on microvortices evolution in confined square microcavities

Recently, microcavities have become a central feature of diverse microfluidic devices for many biological applications. Thus, the flow and transport phenomena in microcavities characterized by microvortices have received increasing research attention. It is important to understand thoroughly the geometry factors on the flow behaviors in microcavities. In an effort to provide a design guideline for optimizing the microcavity configuration and better utilizing microvortices for different applications, we investigated quantitatively the liquid flow characteristics in different square microcavities located on one side of a main straight microchannel by using both microparticle image velocimetry (micro-PIV) and numerical simulation. The influences of the inlet Reynolds numbers (with relatively wider values Re?=?1–400) and the hydraulic diameter of the main microchannel (D_H?=?100, 133 μm) on the evolution of microvortices in different square microcavities (100, 200, 400 and 800 μm) were studied. The evolution and characteristic of the microvortices were investigated in detail. Moreover, the critical Reynolds numbers for the emergence of microvortices and the transformation of flow patterns in different microcavities were determined. The results will provide a useful guideline for the design of microcavity-featured microfluidic devices and their applications.     

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.     

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.