Femtosecond laser-induced modification of surface wettability of PMMA for fluid separation in microchannels

The modification of polymer surface wettability is receiving increasing interest in recent years. As surface wettability affects the flowing resistance, and thus the separation ratio and/or mixing ratio of samples in different microchannels, the controlled modification of surface wettability is highly desirable. In this study, microfluidic channels with controlled surface wettability were achieved and fabricated using femtosecond (fs) laser direct ablation of polymethyl methacrylate at various fluences. Varied flow velocities and separation ratio of water in microfluidic channels have been successfully obtained through fs laser-induced modification in wetting characteristics of the microchannel surfaces. A concave flow front was observed in a microchannel with hydrophilic surface. Correspondingly, a convex flow front was observed with hydrophobic surface. For an untreated channel, a straight flow front was observed. These results would be attractive for various microfluidic chip applications, such as control of the reagent reaction through controlling liquid medium separation or control of mixing ratio in different channels.     

Rapid prototyping of PMMA microfluidic chips utilizing a CO<Subscript>2</Subscript> laser

A commercially available CO₂ laser scriber is used to perform the direct-writing ablation of polymethyl-methacrylate (PMMA) substrates for microfluidic applications. The microfluidic designs are created using commercial layout software and are converted into the command signals required to drive the laser scriber in such a way as to reproduce the desired microchannel configuration on the surface of a PMMA substrate. The aspect ratio and surface quality of the ablated microchannels are examined using scanning electron microscopy and atomic force microscopy surface measurement techniques. The results show that a smooth channel wall can be obtained without the need for a post-machining annealing operation by performing the scribing process with the CO₂ laser beam in an unfocused condition. The practicality of the proposed approach is demonstrated by fabricating two microfluidic chips, namely a cytometer, and an integrating microfluidic chip for methanol detection, respectively. The results confirm that the proposed unfocused ablation technique represents a viable solution for the rapid and economic fabrication of a wide variety of PMMA-based microfluidic chips.     

On-chip whole blood plasma separator based on microfiltration,sedimentation and wetting contrast

Miniaturized on-chip blood separators have a great value for point-of-care diagnosis. In our work, a combined design strategy—microfiltration, sedimentation in a retarded flow, and wetting contrast—was taken to overcome the known limitations of on-chip blood separators. Our microfluidic chip consists of a polydimethylsiloxane micropillar array and an etched glass with microchannel branches. The red blood cells are significantly slowed and gradually settled down due to micropillars and enlarged dimension of a chamber. An etched glass microchannel allows the extraction of blood plasma exclusively due to the capillary effect. The fabricated microfluidic device can separate blood plasma from a whole blood sample without any external driving force or dilution. The measured plasma separation efficiency was close to 100 % from human whole blood. Autonomous on-chip separation and collection of blood plasma was demonstrated.     

Optimized design and fabrication of a microfluidic platform to study single cells and multicellular aggregates in 3D

A microfluidic platform for cell motility analysis in a three-dimensional environment is presented. The microfluidic device is designed to study migration of both single cells and cell spheroids, in particular under spatially and temporally controlled chemical stimuli. A layout based on a central microchannel confined by micropillars and two lateral reservoirs was selected as the most effective. The microfluidics have an internal height of 350 μm to accommodate cell spheroids of a considerable size. The chip is fabricated using well-established micromachining techniques, by obtaining the polydimethylsiloxane replica from a Si/SU-8 master. The chip is then bonded on a 170-μm-thick microscope glass slide to allow high spatial resolution live microscopy. In order to allow the cost-effective and highly repeatable production of chips with high aspect ratio (5:1) micropillars, specific design and fabrication processes were optimized. This design permits spatial confinement of the gel where cells are grown, the creation of a stable gel–liquid interface and the formation of a diffusive gradient of a chemoattractant (>48 h). The chip accomplishes both the tasks of a microfluidic bioreactor system and a cell analysis platform avoiding critical handling of the sample. The experimental fluidic tests confirm the easy handling of the chip and in particular the effectiveness of the micropillars to separate the Matrigel? from the culture media. Experimental tests of (i) the stability of the gradient, (ii) the biocompatibility and (iii) the suitability for microscopy are presented.     

Sequential Field-Flow Cell Separation Method in a Dielectrophoretic Chip With 3-D Electrodes

This paper presents a sequential dielectrophoretic field-flow separation method for particle populations using a chip with a 3-D electrode structure. A unique characteristic of our chip is that the walls of the microfluidic channels also constitute the device's electrodes. This property confers the opportunity to use the electrodes' shape to generate not only the electric field gradient required for dielectrophoretic force but also a fluid velocity gradient. This interesting combination gives rise to a new solution for the dielectrophoretic separation of two particle populations. The proposed sequential field-flow separation method consists of four steps. First, the microchannel is filled with the mixture of the two populations of particle. Second, the particle populations are trapped in different locations of the microfluidic channels. The population, which exhibits positive dielectrophoresis (DEP), is trapped in the area where the distance between the electrodes is the minimum, while the other population that exhibits negative DEP is trapped in locations of maximum distance between electrodes. In the next step, increasing the flow in the microchannels will result in an increased hydrodynamic force that sweeps the cell population trapped by positive DEP out of the chip. In the last step, the electric field is removed, and the second population is swept out and collected at the outlet. For theoretical and experimental exemplification of the separation method, a population of viable and nonviable yeast cells was considered.     

New production method of convex microlens arrays for integrated fluorescence microfluidic detection systems

A new method for producing microlens array with large sag heights is proposed for integrated fluorescence microfluidic detection systems. Three steps in this production technique are included for concave microlens array formations to be integrated into microfluidic systems. First, using the photoresist SU-8 to produce hexagonal microchannel array is required. Second, UV curable glue is injected into the hexagonal microchannel array. Third, the surplus glue is rotated by a spinner at high velocity and exposed to a UV lamp to harden the glue. The micro concave lens molds are then finished and ready to produce convex microlens in poly methsiloxane (PDMS) material. This convex microlens in PDMS can be used for detecting fluorescence in microfluidic channels because a convex microlens plays the light convergence role for optical fiber detection.

     

Design optimization of micromixer with square-wave microchannel on compact disk microfluidic platform

This paper presents a passive micromixer on a compact disk (CD) microfluidic platform that performs plasma mixing function. The driving force of CD microfluidic platform including, the centrifugal force due to the system rotation, the Coriolis force as a function of the rotation angular frequency and velocity of liquid. Numerical simulations are performed to investigate the flow characteristics and mixing performance of three CD microfluidic mixers with square-wave, curved and zig-zag microchannels, respectively. Of the three microchannels, the square-wave microchannel is found to yield the best mixing performance, and is therefore selected for design optimization. Four CD microfluidic micromixers incorporating square-wave PDMS 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 and a CD rotation speed of 2,000 rpm, a mixing efficiency of more than 93 % can be obtained within 5 s.     

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.     

New production method of convex microlens arrays for integrated fluorescence microfluidic detection systems

A new method for producing microlens array with large sag heights is proposed for integrated fluorescence microfluidic detection systems. Three steps in this production technique are included for concave microlens array formations to be integrated into microfluidic systems. First, using the photoresist SU-8 to produce hexagonal microchannel array is required. Second, UV curable glue is injected into the hexagonal microchannel array. Third, the surplus glue is rotated by a spinner at high velocity and exposed to a UV lamp to harden the glue. The micro concave lens molds are then finished and ready to produce convex microlens in poly methsiloxane (PDMS) material. This convex microlens in PDMS can be used for detecting fluorescence in microfluidic channels because a convex microlens plays the light convergence role for optical fiber detection.     

Microfluidic bolus induced gradient generator for live cell signalling

Major events in cell biology are initiated by the binding of ligands to cell surface receptors and/or their transport into cells. We present a study of a simple microchannel system that integrates a bolus generator and surface-adhered cell culture domains. Our system allows the delivery of small packets or boluses of biomolecules to a cell population. Owing to pressure driven microfluidic flow of the bolus, a gradient of cell surface bound ligands is established along the length of the microchannel. Experimental data for the epidermal growth factor (EGF) binding to its receptor on A431 cells are presented. We highlight the effect of changing Peclet number (or flowrate), bolus shape, bolus volume and ligand concentration on the gradient formed longitudinally in the microchannel. A mathematical model describing the transient convection, diffusion, dispersion and binding of ligands to cell surface receptors is developed. The model provides essential design guidelines for our system with good qualitative agreement with experimental data. The results suggest ways to modulate the amount of bound ligand and the gradient independently. This simple microsystem is suitable for generating longer range gradients involving larger cell populations as compared to existing microfluidic systems.     

Replication of large scale micro pillar array with different diameters by micro injection molding

The capillary force is always used as the driving force of microfluidic chips. In this study, the capillary force of blood smart diagnostic microfluidic chip which fabricated by micro-injection molding (μ-IM) is offered by the structure of micro pillar array. And the detection effect of blood smart diagnostic microfluidic chips is affected by the replication and height distribution of large scale micro pillar array. So the effect of process parameters on the micro-structure and the height distribution of micro pillar is studied. The mold design is also an important factor affecting micro parts properties. In this study, a steel mold insert with almost 15,500 micro blind cavities was fabricated by milling, electrical discharge machine and Femtosecond Laser process. Polymethyl methacrylate -Polystyrene copolymer (SMMA NAS 30) was used as the molding material. The single factor trail and orthogonal experiment approach were adopted to investigate the effect of several process parameters and the significant effect factors affecting the replication of micro pillar. And the height distribution of micro pillar array was investigated by scanning electron microscope (SEM) and universal tool-measuring microscope to measure the replication quality. The results reveal that the replication of micro pillar is sensitive to the flow direction of the polymer melt. The height of micro pillar increases with the increase of mold temperature and injection speed. Moreover, the height distribution of micro pillar along and against flow direction was tightly related to the thermomechanical history of material during the molding process.

     

A dry film technology for the manufacturing of 3-D multi-layered microstructures and buried channels for lab-on-chip

The development of innovative and reliable techniques for devices miniaturization are enabling the massive growth of lab on chip (LOC) applications. In this article, we briefly review the technological options for LOC microfabrication, then we present the optimization of a process for the realization of tridimensional multi-layered structures and buried channels in a microfluidic network using a photo-patternable dry film, with a potential for LOC manufacturing. The tuning of all the fabrication parameters is widely discussed and micrographs and optical profiler images are reported to show fabrication results. The fabrication process is used for a Split-flow-thin (SPLITT) fractionation cell configuration. SPLITT is a particle fractionation technique based on the combined effect of two laminar streams (the sample containing the particles and a carrier) flowing inside a thin microchannel and the action of a vertical driving force for particle displacement. Since the SPLITT implemented in this work is electrically driven, patterned electrodes (thickness: 100 nm) are also integrated in the flow cell walls. The functionality of the cell was tested first verifying the presence of proper flow conditions for microfluidic SPLITT (absence of mixing between the streams) and then proving electrical fractionation with two different proteins (BSA and β-lactoglobulin) at different levels of ionic strength. The flow of the streams within the microfluidic channel was also simulated by a numerical 2-D model exactly reproducing the cell geometry, with a good accordance with experimental results.

     

Three-dimensional analysis and enhancement of continuous magnetic separation of particles in microfluidics

In continuous magnetic separation process, particles can be deflected and separated from the direction of laminar flow by means of magnetic force depending on their magnetic susceptibility and size as well as the flow rate. To analyze and control dynamic behavior of these particles flowing in microchannels, a three-dimensional numerical model was proposed and solved for obtaining the particle trajectories under the action of a gradient magnetic field and flow field. The magnetic force distribution and particle trajectories obtained were firstly verified by analytical and experimental results. Then, a detailed analysis for the enhancement of the continuous magnetic separation efficiency by optimizing the flow parameters and microchannel configurations was carried out. The results show that the separation efficiency can be greatly improved by controlling the flow rate ratio of the two fluid streams and introducing a broadened segment in the T-shaped microchannel. And it has been demonstrated to be effective through the sorting of 2-μm and 5-μm non-magnetic particles suspended in a dilute ferrofluid by a permanent magnet. The results reported could be encouraging for the design and optimization of efficient microfluidic separation systems.     

横风下桥梁高度对高速列车交会性能的影响

为研究横风下桥梁高度对高速列车会车性能的影响,基于空气动力学和列车系统动力学,分析指数风分布下不同高度桥梁周围的流场,建立高速列车多体系统动力学模型,模拟横风下列车在不同高度桥梁上会车时的表面压力特性和气动载荷特性.将得到的气动力作为外加载荷作用于列车上,分析桥梁高度对高速列车会车安全性能的影响.结果表明:当列车在环境风下交会时,背风侧列车的气动力波动大于迎风侧列车的气动力波动;当监测点风速固定且桥梁高度小于15 m时,随着桥梁高度的增加,列车的气动载荷最大幅值和安全指标最大幅值均有所减小;当桥梁高度为15～30 m时,随着桥梁高度的增加,列车的气动性能和动力学性能基本保持不变.     

A microfluidic chip for heterogeneous immunoassay using electrokinetical control

This article presents the development of a novel, automated, electrokinetically controlled heterogeneous immunoassay on a poly(dimethylsiloxane) (PDMS) microfluidic chip. A numerical method has been developed to simulate the electrokinetically driven, time-dependent delivery processes of reagents and washing solutions within the complex microchannel network. Based on the parameters determined from the numerical simulations, fully automated on-chip experiments to detect Helicobacter pylori were accomplished by sequentially changing the applied electric fields. Shortened assay time and much less reagent consumptions are achieved by using this microchannel chip while the detection limit is comparable to the conventional assay. There is a good agreement between the experimental result and numerical prediction, demonstrating the effectiveness of using CFD to assist the experimental studies of microfluidic immunoassay.     

Improved concentration and separation of particles in a 3D dielectrophoretic chip integrating focusing, aligning and trapping

This article presents a dielectrophoresis (DEP)-based microfluidic device with the three-dimensional (3D) microelectrode configuration for concentrating and separating particles in a continuous throughflow. The 3D electrode structure, where microelectrode array are patterned on both the top and bottom surfaces of the microchannel, is composed of three units: focusing, aligning and trapping. As particles flowing through the microfluidic channel, they are firstly focused and aligned by the funnel-shaped and parallel electrode array, respectively, before being captured at the trapping unit due to negative DEP force. For a mixture of two particle populations of different sizes or dielectric properties, with a careful selection of suspending medium and applied field, the population exhibits stronger negative DEP manipulated by the microelectrode array and, therefore, separated from the other population which is easily carried away toward the outlet due to hydrodynamic force. The functionality of the proposed microdevice was verified by concentrating different-sized polystyrene (PS) microparticles and yeast cells dynamically flowing in the microchannel. Moreover, separation based on size and dielectric properties was achieved by sorting PS microparticles, and isolating 5 μm PS particles from yeast cells, respectively. The performance of the proposed micro-concentrator and separator was also studied, including the threshold voltage at which particles begin to be trapped, variation of cell-trapping efficiency with respect to the applied voltage and flow rate, and the efficiency of separation experiments. The proposed microdevice has various advantages, including multi-functionality, improved manipulation efficiency and throughput, easy fabrication and operation, etc., which shows a great potential for biological, chemical and medical applications.     

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.     

Fabrication techniques to realize CMOS-compatible microfluidicmicrochannels

With microfluidic systems becoming more prominent, fabrication techniques for microfluidic systems are increasingly more important. An interesting alternative to existing fabrication techniques is to embed fluidic systems within an integrated circuit by micromachining materials in the integrated circuit itself. This paper describes novel methods for fabricating one component in the complementary metal-oxide-semiconductor (CMOS) microfluidic system, the microchannel. These techniques allow direct integration of sensors, actuators, or other electronics with the microchannel. This method expands the functional applications for microfluidic systems beyond their current abilities. By utilizing the methods described within this paper, a complete “smart” microfluidic system could be batch fabricated on a single integrated circuit (IC) chip     

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.     

An Electrolysis-Bubble-Actuated Micropump Based on the Roughness Gradient Design of Hydrophobic Surface

A novel electrolysis-bubble-actuated micropump based on the roughness gradient design in the microchannel is reported in this paper. This micropump is implemented by taking advantage of both the electrolysis actuation and the surface tension effect. The surface tension effect is controlled via the periodic generation of electrolytic bubbles and the roughness gradient design of microchannel surface, which results in the specified variation of liquid contact angle along the microchannel. Our proposed micropump could resolve the disadvantages that exist in the early reported micropumps, such as the complicated time-sequence power control, the need of long nozzle-diffuser structure, and the choking/sticking phenomena of electrolytic bubbles in a microchannel. Due to the features of large actuation force, low-power consumption, and room temperature operation, our micropump is suitable for the development of low-power consumption and compact micropumps for various applications. Experimental results show that the liquid displacement and the pumping rate could be easily and accurately controlled by adjusting the amplitude and frequency of the applied voltage. With the applied voltage of 15 V at 4.5 Hz, a maximum pumping rate of 114 nl/min is achieved for one of our micropump designs with a microchannel of 100 x 20 mum. In this paper, we report the theoretical analysis, design, micromachining process, operating principles, characterization, and experimental demonstration of these micropumps.