The synergistic effect of periodic immunomagnetics and microfluidics on universally capturing circulating tumor cells

Efficient capture data on circulating tumor cells (CTCs) determines early-stage cancer diagnosis and contributes to timely clinical treatment. We present an enhanced method of capturing CTCs accomplished by a microfluidic device integrated with magnetic field to activate the kinetic motion of in-device magnetic beads. The device, consisting of a microfluidic chamber and two electrode chips applied with pulsatile alternating current in both, is designed based on simulations on the periodicity characteristic of magnetic beads as well as the effect of heat dissipation on cell culture medium manifest. Using MEMS technologies, the prototype is fabricated and assembled. The cell capture experiments based on active magnetic beads are achieved in separation of rare cancer cells (MCF7 cells) with low concentration. The capture rate is estimated up to 88 %, with great potential of dramatically improving detection efficiency in disease diagnostics.     

A chaotic mixer for magnetic bead-based micro cell sorter

An efficient magnetic force driven mixer with simple configuration is designed, fabricated, and tested. It is designed to facilitate the mixing of magnetic beads and biomolecules in a microchannel, where mixing is unavoidably inefficient due to its low Reynolds number. With appropriate temporal variations of the force field, chaotic mixing is achieved, hence the mixing becomes effective. The mixing device consists of embedded microconductors as a magnetic field source and a microchannel that guides the streams of working fluid. It is demonstrated that a pair of integrated micro conductors provides a local magnetic field strong enough to attract nearby magnetic beads. Mixing of magnetic beads is accomplished by applying a time-dependent control signal to a row of conductors, at the Reynolds number of as low as 10/sup -2/. Two-dimensional numerical simulation has been performed to design the configuration of the channel and electrodes, which creates chaotic motion of beads. It is found that a simple two-dimensional serpentine channel geometry with the transverse electrodes is able to create the stretching and folding of material lines, which is a manifestation of chaos. The mixing pattern predicted by the simulation has been confirmed by both flow visualization and PTV (particle tracking velocimetry) in the chaotic mixer fabricated, which should greatly increase the attachment of beads onto the target biomolecules. The optimum frequency of applied control signal is searched by evaluating the Lyapunov exponent in both numerical and experimental particle tracking. It is found that the range of optimum Strouhal number is 5相似文献   

A rapid magnetic particle driven micromixer

Performances of a magnetic particle driven micromixer are predicted numerically. This micromixer takes advantages of mixing enhancements induced by alternating actuation of magnetic particles suspended in the fluid. Effects of magnetic actuation force, switching frequency and channel’s lateral dimension have been investigated. Numerical results show that the magnetic particle actuation at an appropriate frequency causes effective mixing and the optimum switching frequency depends on the channel’s lateral dimension and the applied magnetic force. The maximum efficiency is obtained at a relatively high operating frequency for large magnetic actuation forces and narrow microchannels. If the magnetic particles are actuated with a much higher or lower frequency than the optimum switching frequency, they tend to add limited agitation to the fluid flow and do not enhance the mixing significantly. The optimum switching frequency obtained from the present numerical prediction is in good agreement with the theoretical analysis. The proposed mixing scheme not only provides an excellent mixing, even in simple microchannel, but also can be easily applied to lab-on-a-chip applications with a pair of external electromagnets.     

Local control of magnetic objects in microfluidic channels

The application of magnetic fields in microfluidics is of growing interest and the localisation of the applied field emerges as a key requisite for future integration with other micro-platforms. In this paper, we present a novel strategy of fabrication of an integrated microchannel, which combines the advantages of localisation of the magnetic field with simplicity of design and fabrication. The circuit is fabricated in one single step using a copper plate dedicated to microelectronics. We determine the magnetic field inside the microchannel by numerical simulations computed for this novel design. Magnetic beads in the microchannel are driven into movement by a magnetic force in the range of a few picoNewtons. We have checked that the magnetic force is well localised by following bead trajectories when they approach the magnetic area. Moreover, as a proof of concept, quantitative magnetic cell sorting was successfully performed in the microchannel.     

High-throughput micromixers based on acoustic streaming induced by surface acoustic wave

Flow characteristics in microfluidic devices is naturally laminar due to the small channel dimensions. Mixing based on molecular diffusion is generally poor. In this article, we report the fabrication and characterization of active surface-acousticwave-driven micromixers which exploit the acoustic streaming effect to significantly improve the mixing efficiency. A side-by-side flow of water and fluorescent dye solution was driven by a syringe pump. Surface wave with a frequency of 13 MHz was launched perpendicular to the flow. The wave was generated by two designs of interdigitated electrodes on LiNbO₃ substrate: parallel electrodes and focusing electrodes. The mixing efficiency was observed to be proportional to the square of the applied voltage. Under the same applied voltage, the focusing type offers a better mixing efficiency. The fabrication of the micromixer is compatible to current technology such as soft lithography and deep reactive ion etching. Despite the high throughput and fast mixing time, the mixer design is simple and could be integrated into any microfluidic platform.     

谐振频率转换机制振动能采集器研究进展

环境振动能采集器可为低功耗系统提供绿色环保、可再生能源,具有寿命长久、能量密度高、微型、易集成等优势.能量采集环境具有随机振动频率低、频域广、振源幅值小且多方向性等特点,频率转换机制可有效解决采集器与环境振动频率不匹配问题,提高其能量转换效率.发电装置中的拾振结构频变方式主要分为接触式和非接触式,具体操作方法包括直接或间接碰撞拾振体、驱使振动体形变、磁力耦合调频等.综合比较了各类频率转换机制的优缺点及其实用性,指出了低宽频、高效能、智能化是未来振动能采集微电源的研究趋势.     

Microfluidic multi-target sorting by magnetic repulsion

In magnetophoresis-based microfluidic systems, the free-flow sorting is achieved by incrementally navigating the magnetic target toward a designated outlet. This is typically enabled using high-gradient magnetic concentrators (HGMCs), axially aligned or slightly slanted with the streaming sample flow. Such axial and incremental magnetic manipulation critically constraints the throughput and the number of targets that can be sorted simultaneously. To overcome these constraints, we present an alternative repulsion-based sorting method. The repulsion force is due that induced, over a limited angular expanse, around a single ferromagnetic wire. The wire is positioned transversally against the focused sample flow. Differentially repelled by the repulsive force, each target deflects from its focused path to follow a ribbon-like trajectory that leads to a spatially addressable outlet. The mediated sorting takes place more rapidly and is confined to the region facing the transversal wire. More importantly, the introduced concept design allows for a throughput that is geometrically scalable with the length of the wire. The functionality of the systems is demonstrated experimentally and numerically to yield the simultaneous and complete multi-target sorting of two and more magnetic beads.     

Hydrodynamic trap-and-release of single particles using dual-function elastomeric valves: design, fabrication, and characterization

This paper introduces a simple method for trapping and releasing single particles, such as microbeads and living cells, using dual-function elastomeric valves. Our key technique is the utilization of the elastomeric valve as a dual-function removable trap instead of a fixed trap and a separate component for releasing trapped particles, thereby enabling a simple yet effective trap-and-release of particles. We designed, fabricated, and characterized a microfluidic-based device for trapping and releasing single beads by controlling elastomeric valves driven by pneumatic pressure and a fluid flow action. The fluid flow is controlled to ensure that beads flowing in a main stream enter into a branch channel. A bead is trapped by deflected elastomeric valves positioned at the entrance of a branch channel. The trapped bead is easily released by removing the applied pressure. The trapping and releasing of single beads of 21?μm in diameter were successfully performed under an optimized pressure and flow rate ratio. Moreover, we confirmed that continuous trapping and releasing of single beads by repeatedly switching elastomeric valves enables the collection of a controllable number of beads. Our simple method can be integrated into microfluidic systems that require single or multiple particle arrays for quantitative and high-throughput assays in applications within the fields of biology and chemistry.     

MMC电容电压排序优化算法研究

根据模块化多电平换流器的运行原理,研究了传统电容电压排序算法导致器件开关频率增大的根本原因;为降低器件的开关频率,提高系统运行效率,提出了一种电容电压排序优化算法。该算法对传统排序算法进行了优化改进,给定3个电压参考值,将已投入的子模块电容电压值与参考值进行比较,判断是否继续保持投入状态。在Matlab中搭建了每相60个子模块的MMC电容电压排序优化算法仿真模型,仿真结果表明,该算法能显著降低功率器件的开关频率,减小换流器的功率耗损。     

Method for flow measurement in microfluidic channels based on electrical impedance spectroscopy

We have developed and characterized two novel micro flow sensors based on measuring the electrical impedance of the interface between the flowing liquid and metallic electrodes embedded on the channel walls. These flow sensors are very simple to fabricate and use, are extremely compact and can easily be integrated into most microfluidic systems. One of these devices is a micropore with two tantalum/platinum electrodes on its edges; the other is a micro channel with two tantalum/platinum electrodes placed perpendicular to the channel on its walls. In both sensors the flow rate is measured via the electrical impedance between the two metallic electrodes, which is the impedance of two metal–liquid junctions in series. The dependency of the metal–liquid junction impedance on the flow rate of the liquid has been studied. The effects of different parameters on the sensor’s outputs and its noise behavior are investigated. Design guidelines are extracted and applied to achieve highly sensitive micro flow sensors with low noise.     

Investigation of active interface control of pressure driven two-fluid flow in microchannels

We report a novel concept to control the interface location of a pressure-driven multi-phase flow in a microchannel by using electroosmotic flow effects. This concept has potential applications in flow switching and cell sorting in bio-analytical systems. In an H-shaped microchannel structure, aqueous sodium chloride (NaCl) solution and glycerol diluted with water were pumped through two inlets at the same flow rate. The electric field was applied on the electrolyte solution side. Adjusting the magnitude and direction of electric field has successfully controlled the interface position between the two phases. This technique provides a new approach to control the interface position between the two fluids.     

基于纳米磁珠技术的新型微全分析DNA芯片的研究

在微全分析系统的研究中,样品提取及DNA分析技术是非常重要的一个环节.也是目前国内外研究的热点之一.文中介绍了一种新型的基于单芯片的样品制备和扩增方法.采用多层微加工技术制作SU-8模具,通过注模成型,制作出有立体微柱结构的PDMS(聚二甲基硅氧烷)芯片,在芯片微池内填充超顺磁性磁珠,利用固相提取(solid phase extraction,SPE)法,将细胞裂解、DNA提取、PCR反应等功能集成在一个PDMS芯片上.整个流程快速有效,操作简便且易于芯片系统集成,提取产物可以不必洗脱,直接作为下一步PCR反应的模板,在同一芯片上进行扩增反应,实现了样品预处理、DNA提取和PCR扩增的集成.     

A PMMA valveless micropump using electromagnetic actuation

We have fabricated and characterized a polymethylmethacrylate (PMMA) valveless micropump. The pump consists of two diffuser elements and a polydimethylsiloxane (PDMS) membrane with an integrated composite magnet made of NdFeB magnetic powder. A large-stroke membrane deflection (~200 m) is obtained using external actuation by an electromagnet. We present a detailed analysis of the magnetic actuation force and the flow rate of the micropump. Water is pumped at flow rates of up to 400 µl/min and backpressures of up to 12 mbar. We study the frequency-dependent flow rate and determine a resonance frequency of 12 and 200 Hz for pumping of water and air, respectively. Our experiments show that the models for valveless micropumps of A. Olsson et al. (J Micromech Microeng 9:34, 1999) and L.S. Pan et al. (J Micromech Microeng 13:390, 2003) correctly predict the resonance frequency, although additional modeling of losses is necessary.     

3D-printed microfluidic manipulation device integrated with magnetic array

This paper reported a transparent, high-precision 3D-printed microfluidic device integrated with magnet array for magnetic manipulation. A reserved groove in the device can well constrain the Halbach array or conventional alternating array. Numerical simulations and experimental data indicate that the magnetic flux density ranges from 30 to 400 mT and its gradient is about 0.2–0.4 T/m in the manipulation channel. The magnetic field parameters of Halbach array in the same location are better than the other array. Diamagnetic polystyrene beads experience a repulsive force and move away from the magnetic field source under the effect of negative magnetophoresis. It is undeniable that as the flow rate increases, the ability of Halbach array to screen particle sizes decreases. Even so, it has a good particle size discrimination at a volumetric flow rate of 1.08 mL/h, which is much larger than that of a conventional PDMS device with a single magnet. The observed particle trajectories also confirm these statements. The deflection angle is related to the magnetic field, flow rate, and particle size. This 3D-printed device integrated with Halbach array offers excellent magnetic manipulation performance.     

基于ARM的超磁致伸缩微驱动器的偏置与驱动电路设计

超磁致伸缩微驱动器的工作主要需要提供一个可控的偏置磁场和驱动磁场,前者使超磁致伸缩材料的磁致伸缩特性得到优化,消除倍频效应,后者实现对微驱动器的输出位移控制;设计一个可控电流源,采用悬浮负载功率放大恒流电路,并通过ARM处理器的数模控制,使指定电流通过电磁线圈以产生所需磁场强度;该设计的可控电源,可输出最大±5A的电流,提供给偏置和驱动线圈,实现微驱动器的直观、灵活的控制。     

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.     

A novel integrated microfluidic platform based on micro-magnetic sensor for magnetic bead manipulation and detection

We present a novel integrated microfluidic platform based on micro-magnetic sensor for manipulating and detecting magnetic beads (MB). A micro-spiral planar coil in MB manipulating system microfabricated by micro-electro-mechanical system technology is implemented to manipulate MB, and a giant magnetoimpedance (GMI) based micro-magnetic sensor is employed to detect the trapped MB. In our work, MB can be efficiently trapped by trapping force generated from micro-coil in microchannel. Next, trapped MB are detected by the changing ratio of impedance, as well as the variation of resistance and reactance in GMI sensor for trapped MB induce weak stray magnetic field under the magnetization by external magnetic field. The maximum difference of GMI ratio between with beads condition and without beads condition is 4.0% at the optimum driving frequency of 20 MHz under the external magnetic field of 15 Oe, and resistance ratio varies more significantly than reactance ratio. In comparison with traditional MB detecting methods by GMI sensor, the integrated microfluidic platform based on GMI sensor can not only manipulate and detect MB signal sensitively, but also enhance detection efficiency and decrease the experiment errors. Furthermore, this platform avoids contamination from the solutions in chemically reactive layers and reduces assay time in future biomarker detection. In our work, the microfluidic platform based on GMI sensor has potential applications in biomarker detection via MB manipulation and detection.     

磁力驱动串联式双腔微泵设计及性能测试

针对无阀微泵背压能力较弱等问题,采用MEMS技术制作出不同结构参数的双腔和单腔微泵体,构建了基于电机驱动的磁力式双腔串联无阀微泵测控系统.实验结果表明,泵腔面积相等的情况下,圆形泵腔的微泵流量大于椭圆形泵腔的流量;随着驱动频率的升高,双腔串联微泵的流量呈现高斯分布,并在20 Hz附近处出现流量峰值,微泵的最大流量可达1.5 mL/min,微泵的截止背压为170 mmH2O,双腔串联微泵比单腔微泵的流量增大约80％.     

DSP的有源钳位反激式光伏并网逆变器设计

本文设计了一套以TI公司的TMS320F28335浮点型DSP为控制核心的单相光伏并网微型逆变器,光伏电池输出的直流电经交错并联反激式变换器转换为2倍于电网频率的正弦双半波电流,再用极性反转桥将正弦双半波电流转换为与电网同频同相的交流电并入电网.采用有源钳位电路能使MOSFET管实现零电压开关(ZVS).提出的一种改进型扰动观察法,可提高MPPT效率.样机实验波形表明,该光伏逆变器输出电流谐波含量较少,能够向电网输送高质量的电能.     

开关电源在变频器中的应用

本文介绍了开关电源的基本原理,以及变频器里开关电源的特点。比较详细地分析了作为开关电源里核心部件的集成振荡心片的结构和原理。最后介绍了一个在变频器里具体应用的实例。