Continuous-flow ferrohydrodynamic sorting of particles and cells in microfluidic devices

A new sorting scheme based on ferrofluid hydrodynamics (ferrohydrodynamics) was used to separate mixtures of particles and live cells simultaneously. Two species of cells, including Escherichia coli and Saccharomyces cerevisiae, as well as fluorescent polystyrene microparticles were studied for their sorting throughput and efficiency. Ferrofluids are stable magnetic nanoparticles suspensions. Under external magnetic field gradients, magnetic buoyancy forces exerted on particles and cells lead to size-dependent deflections from their laminar flow paths and result in spatial separation. We report the design, modeling, fabrication and characterization of the sorting device. This scheme is simple, low-cost and label-free compared to other existing techniques.     

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).     

A microfluidic device for rapid concentration of particles in continuous flow by DC dielectrophoresis

This article presents a microfluidic device (so called concentrator) for rapid and efficient concentration of micro/nanoparticles using direct current dielectrophoresis (DC DEP) in continuous fluid flow. The concentrator is composed of a series of microchannels constructed with PDMS-insulating microstructures to focus efficiently the electric field in the flow direction to provide high field strength and gradient. Multiple trapping regions are formed within the concentrator. The location of particle trapping depends on the strength of the electric field applied. Under the experimental conditions, both streaming movement and DEP trapping of particles simultaneously take place within the concentrator at different regions. The former occurs upstream and is responsible for continuous transport of the particles, whereas the latter occurs downstream and rapidly traps the particles delivered from upstream. The observation agrees with the distribution of the simulated electric field and DEP force. The performance of the device is demonstrated by successfully and effectively concentrating fluorescent nanoparticles. At the sufficiently high electric field, the device demonstrates a trapping efficiency of 100%, which means downstream DEP traps and concentrates all (100%) the incoming particles from upstream. The trapping efficiency of the device is further studied by measuring the fluorescence intensity of concentrated particles in the channel. Typically, the fluorescence intensity becomes saturated in Trap 1 by applying the voltage (400 V) for >2 min, demonstrating that rapid concentration of the nanoparticles (10⁷ particles/ml) is achieved in the device. The microfluidic concentrator described can be implemented in applications where rapid concentration of targets is needed such as concentrating cells for sample preparation and concentrating molecular biomarkers for detection.     

Development of sorting, aligning, and orienting motile sperm using microfluidic device operated by hydrostatic pressure

In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are the most commonly used assisted reproductive technologies to overcome male infertility problems. One of the obstacles of IVF and ICSI procedures is separating motile sperm from non-motile sperm to select the most competent sperm population from any given sperm sample. In addition, orientation and separation of the head from the tail is another obstacle for ICSI. Using the self-movement of sperm against flow direction, motile and non-motile sperm can be separated with an inexpensive polymeric microfluidic system. In this paper, we describe the development of a microfluidic system obtained through low-cost fabrication processes. We report experimental results of sperm sorting using hydrostatic pressure of three different species: bull, mouse, and human. The movement of cells in these channels was observed under a microscope and recorded with a digital camera. It is shown that the hydrostatic pressure and self-movement of motile sperm can be used to solve separating, aligning and orienting sperm in the microchannel.     

Highly efficient dual-channel cytometric-detection of micron-sized particles in microfluidic device

To demonstrate the ability to efficiently count and identify suspended micron-sized particles by simultaneously detecting their fluorescence emission and light scattering in microfabricated channel, a compact configuration that used a polydimethylsiloxane (PDMS) microfabricated channel as interrogation component, hydrodynamic focusing for particle control, and a simple free-space optical setup for signal detection, was accordingly developed. Subsequently, a quantitative count of 1.013 μm diameter fluorescently labeled beads in suspension was implemented in a microfluidic device employing both fluorescence emission and light scattering at average particle throughput ranging from 83 to 416 particles/s. As a result, the detection efficiencies above 88% for both signals and correlation percentages above 97% between them were routinely achieved. In addition, it was shown that effective differentiation of 1.013 μm fluorescently labeled beads from various unlabeled beads in mixed populations of high mixing ratios had been successfully realized in this microfluidic-device-based instrumentation. Finally, the demonstrated system was used to detect fluorescein isothiocyanate (FITC) labeled nonpathogenic bacteria of Escherichia coli (E. coli) DH5α. The results showed the detection efficiencies above 89.7% for fluorescence emission and 94.5% for light scattering signals, and a correlation of 94.9% between the two signals at an average throughput of 350 cells/s have been obtained. As a comparison, the detection accuracies of the dual-channel cytometric detection of the FITC-labeled E. coli DH5α cells in the microfluidic device are approximately 84.3% and 88.8% for fluorescence emission and light scattering respectively when compared against a manual cell count using a haemocytometer as a standard.     

A microfluidic device for thermal particle detection

We demonstrate the use of heat to count microscopic particles. A thermal particle detector (TPD) was fabricated by combining a 500-nm-thick silicon nitride membrane containing a thin-film resistive temperature detector with a silicone elastomer microchannel. Particles with diameters of 90 and 200 μm created relative temperature changes of 0.11 and ?0.44 K, respectively, as they flowed by the sensor. A first-order lumped thermal model was developed to predict the temperature changes. Multiple particles were counted in series to demonstrate the utility of the TPD as a particle counter.     

Modular component design for portable microfluidic devices

A new modular design concept for microfluidic devices is proposed and demonstrated in this study. We designed three key modular microfluidic components: pumps, valves, and reservoirs, and demonstrated that a microfluidic device with specific functions can be easily assembled with those key modular components. Our pumps are man-powerable so that the assembled microfluidic devices require no any other power sources like expensive syringe pumps or air compressors. This feature makes the assembled microfluidic devices completely portable. We also combined our assembled device with other existing mixing microchannels to serve as the mixing and loading system in polymerase chain reaction experiment to amplify DNA successfully. This result shows that those modular components can be integrated into other microchannels, implying great potential applications of the modular design.     

A suction-type, pneumatic microfluidic device for liquid transport and mixing

This study presents a new suction-type, pneumatically driven microfluidic device for liquid delivery and mixing. The three major components, including two symmetrical, normally closed micro-valves and a sample transport/mixing unit, are integrated in this device. Liquid samples can be transported by the suction-type sample transport/mixing unit, which comprised a circular air chamber and a fluidic reservoir. Experimental results show that volume flow rates ranging from 50 to 300 μl/min can be precisely controlled during the sample transportation processes. Moreover, the transport/mixing unit can also be used as a micro-mixer to generate efficient mixing between two reaction chambers by regulating the time-phased deformation of the polydimethylsiloxane (PDMS) membranes. A mixing efficiency as high as 98.4% can be achieved within 5 s utilizing this prototype pneumatic microfluidic device. Consequently, the development of this new suction-type, pneumatic microfluidic device can be a promising tool for further biological applications and for chemical analysis when integrated into a micro-total analysis system (μ-TAS) device.     

A portable sample concentrator on paper-based microfluidic devices

Microfluidic paper-based analytical devices (µPADs) provide a promising solution for low-cost point-of-care diagnostic applications. However, much work remains to be done in optimizing their design and performance. Accordingly, this study investigates the preconcentration performance of µPADs comprising one, two and three convergent channels, respectively. The performance of the three devices is evaluated experimentally using fluorescein and a fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) sample with an initial concentration of 10^?5 M. It is shown that the single-channel µPAD achieves a 20-fold improvement in the sample concentration in approximately 2 min. By contrast, the double- and triple-channel µPADs achieve preconcentration factors of 60- and 140-fold, respectively. Finally, a portable concentrator device is proposed. The experimental results show that a 100-fold improvement in the FITC-BSA sample concentration can be obtained in approximately 110 s given the use of four 16-V batteries, yielding a practical point-of-care diagnostic device.     

A multilayer lateral-flow microfluidic device for particle separation

Particle separation technology plays an important role in a wide range of applications as a critical sample preprocessing step for analysis. In this work, we proposed and fabricated a multilayer lateral-flow particle filtration and separation device based on polydimethylsiloxane molding and transfer bonding techniques. Particle separation capability was demonstrated by 4.5-um polystyrene bead filtration and cancer cell (SK-BR-3) retrieving. This device exhibits higher throughput compared with most active particle separation methods and is less vulnerable to membrane clogging problem. This novel multilayer particle filtration and separation device is expected to find applications in biomedical, environmental and microanalysis fields.     

A microfluidic microwell device for immunomagnetic single-cell trapping

Single-cell analysis has been widely applied in various biomedical applications, such as cancer diagnostics, immune status monitoring, and drug screening. To perform an accurate and rapid cellular analysis, various magnetic-activated cell sorting techniques are available in the markets. However, large sample requirement and uneven magnetic field distribution limit its application in single-cell trapping and following analysis. To address these problems, we developed a microfluidic microwell device for immunomagnetic single-cell trapping. By adding a microwell layer between the microchannel and magnet, the magnetic field along the device becomes more uniform. Besides, magnetic beads can be retained in the array of microwell after the high-speed washing step, whereas untrapped beads would be flushed away, resulting in high single-particle trapping efficiency (62%) and purity (99.6%). To achieve large-area single-cell trapping, we introduced a “sweeping” loading protocol to further expand the single-particle trapping range. In the microwell region near to the edge of the magnet, over 3000 single magnetic beads were trapped in a 10 mm² area. Finally, we demonstrated immunomagnetic-labeled THP-1 cells can successfully be trapped at single-cell level in the microwell. The cell trapping process can be done in 10 min. We believe the platform with an accurate and efficient single-cell trapping functionality could potentially be used for various cellular analyses at the single-cell level.     

Synthesis of bio-functionalized copolymer particles bearing carboxyl groups via a microfluidic device

Monodisperse copolymer particles carrying surface carboxyl groups in the range of 50–200 μm were prepared by in situ UV polymerization of ethyleneglycol dimethacrylate (EGDMA) with acrylic acid (AA) via a microfluidic flow-focusing device (MFFD). The design of the coaxial orifices in the MFFD enables the confinement of the comonomer liquid thread to the central axis of the microchannel, which can avoid the wetting problem of comonomer liquid with the microchannel and can successfully produce monodisperse copolymer microspheres with coefficient of variance below 5%. The effects of concentration of EGDMA and AA on droplet diameters and the distribution of carboxyl group on particle surfaces were examined. It has been found that, increasing the concentration of AA would decrease particle sizes, but increase the distribution of carboxyl group on particle surfaces. Bioconjugation of the carboxylated copolymer particles with the anti-rabbit IgG–Cy3 conjugates was successfully demonstrated. By increasing the concentration of AA accompanied with decreasing the particle sizes, high efficiency of bioconjugation on carboxylated copolymer particles was achieved. The rapid continuous synthesis of carboxylated copolymer particles via a microfluidic device provides a reliable control of particle sizes and composition for massive production in biotechnological applications.     

Design,simulation and experiment of electroosmotic microfluidic chip for cell sorting

A microfluidic cell sorting chip has been developed using micromachining technology, where electroosmotic flow (EOF) is exploited to drive and switch cells. For this electroosmotically driven system, it is found that the effect of induced hydrostatic pressure caused by unequal levels in solution reservoirs is not negligible. In this work, the numerical simulation of EOF and opposing pressure induced flow in microchannels is presented and the velocity profiles in the microchannels are measured experimentally using microparticle imaging velocimetry (PIV) system. The result shows that the final resulting velocity is the superposition of the two flows. A total volume of 0.305 μl is transported in the 50 μm microchannel and the back flow occurs after 240 s transportation. The task of sorting cells is realized at the switching structure by adjusting the electric fields in the microchannels. The performance of the cell sorting chip is optimized by investigating the effect of different switching structures. A Y-junction switching structure with 90° switching angle is highly recommended with simulated leakage distance of 53 μm and switching time of 8 ms.     

一种便携式开关柜局部放电检测仪器的设计

为实现对开关柜内部局部放电的带电检测并保证其检测结果准确,提出了一种将超声波法(AE)与暂态对地电压法(TEV)相结合的同步联合检测方法,并研制了检测装置。该装置前端采用12位的ADS805模数转换器,主控部分采取FPGA+ARM的结构来实现,数据处理部分采用i MX257为核心,不但提高了检测系统的可靠性,并且具有丰富的人机交互界面。     

A portable device for the assessment of dynamic visual acuity

Dynamic visual acuity (DVA) thresholds are among the few visual functions predictive of automobile crashes. DVA is also sensitive to alcohol and aging. However, measuring DVA is awkward because there is no standardized, efficient, flexible apparatus for DVA assessment. In this project, we developed a prototype of an automated, portable DVA system using a low-energy laser, and we compared this laser DVA with the traditional device in two within-subjects, repeated measures designs. The two studies included 48 participants (22 males and 26 females with an average age of 18.33 years). The most important findings were that: (1) retest reliabilities of the two DVA devices were comparable and higher with the laser; (2) average correlations between the two devices were r = 0.62 (p < 0.01) and r = 0.65 (p < 0.01) for the two designs respectively; and (3) after correction for reliability attenuation these improved to r = 0.92 and r = 0.78. These findings indicate that a flexible DVA laser device can be developed to measure the same construct as the more traditional bulky DVA device.     

A microfluidic device for array patterning by perpendicular electrokinetic focusing

This paper describes a microfluidic chip in which two perpendicular laminar-flow streams can be operated to sequentially address the surface of a flow-chamber with semi-parallel sample streams. The sample streams can be controlled in position and width by the method of electrokinetic focusing. For this purpose, each of the two streams is sandwiched by two parallel sheath flow streams containing just a buffer solution. The streams are being electroosmotically pumped, allowing a simple chip design and a setup with no moving parts. Positioning of the streams was adjusted in real-time by controlling the applied voltages according to an analytical model. The perpendicular focusing gives rise to overlapping regions, which, by combinatorial (bio) chemistry, might be used for fabrication of spot arrays of immobilized proteins and other biomolecules. Since the patterning procedure is done in a closed, liquid filled flow-structure, array spots will never be exposed to air and are prevented from drying. With this device configuration, it was possible to visualize an array of 49 spots on a surface area of 1 mm². This article describes the principle, fabrication, experimental results, analytical modeling and numerical simulations of the microfluidic chip.     

一种用于电子产品的温湿度记录装置

环境的温湿度对电子产品的质量是致命的,如何有效管理存放电子产品的环境温湿度以减少企业损失是企业的重要任务.提出了一种用于电子产品温湿度记录的装置,可对温湿度进行实时显示及记录,并带有USB输出口对数据进行输出,获取装置采集的数据.系统具有体积小、功耗低、操作简单等特点,可以记录电子产品长期存储环境中的温度与湿度,也可以用于其他需要测量温湿度的场合,在结构设计上采用尽可能小的结构,并采用铁磁装置,便于记录装置的放置,具有广泛的应用前景.     

Miniaturized DNA amplification platform with soft-lithographically fabricated continuous-flow PCR microfluidic device on a portable temperature controller

Fabrication of 3D microfluidic devices is normally quite expensive and tedious. A strategy was established to rapidly and effectively produce multilayer 3D microfluidic chips which are made of two layers of poly(methyl methacrylate) (PMMA) sheets and three layers of double-sided pressure sensitive adhesive (PSA) tapes. The channel structures were cut in each layer by cutting plotter before assembly. The structured channels were covered by a PMMA sheet on top and a PMMA carrier which contained threads to connect with tubing. A large variety of PMMA slides and PSA tapes can easily be designed and cut with the help of a cutting plotter. The microfluidic chip was manually assembled by a simple lamination process.The complete fabrication process from device design concept to working device can be completed in minutes without the need of expensive equipment such as laser, thermal lamination, and cleanroom. This rapid frabrication method was applied for design of a 3D hydrodynamic focusing device for synthesis of gold nanoparticles (AuNPs) as proof-of-concept. The fouling of AuNPs was prevented by means of a sheath flow. Different parameters such as flow rate and concentration of reagents were controlled to achieve AuNPs of various sizes. The sheet-based fabrication method offers a possibility to create complex microfluidic devices in a rapid, cheap and easy way.

     

低功耗便携式心电仪的设计

介绍了一种低功耗便携式心电仪的设计与实现.采用MSP430F169作为核心控制器,配有心电信号采集调理电路、液晶显示模块和数据存储模块等.该心电仪能够对心电进行实时采集处理、显示,而且可以将存储在SD卡内的数据通过USB接口在上位机上进行显示、分析,功耗低、方便携带,有较强的通用性.