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.     

基于微流控芯片的癌细胞分选仪硬件系统设计

设计了基于微流控芯片的癌细胞分选仪的硬件系统。系统采用光电倍增管(PMT)采集微流控芯片沟道内流动细胞的荧光信号,通过设计的微弱电流信号采集电路进行光电倍增管输出信号的处理,完成对细胞微弱荧光信号的检测。此外,设计了0~1 200 V范围幅值与脉宽可调的高压脉冲源,可产生随机高压脉冲用于癌细胞的分选。整个系统实现了微流控芯片上癌细胞检测、计数以及分选的结合。     

Novel continuous particle sorting in microfluidic chip utilizing cascaded squeeze effect

This article presents a novel technique for the continuous sorting and collection of microparticles in a microfluidic chip using a cascaded squeeze effect. In the proposed approach, microparticles of different sizes are separated from the sample stream using sheath flows and are then directed to specific side channels for collection. The sheath flows required to separate the particles are generated using a single high voltage supply integrated with a series of variable resistors designed to create electric fields of different intensities at different points of the microchip. Numerical simulations are performed to analyze the electrical potential contours and flow streamlines within the microchannel. Experimental trials show that the microchip is capable of continuously separating microparticles with diameters of 5, 10 and 20 μm, respectively. To further evaluate the performance of the microchip, a sample composed of yeast cells and polystyrene beads is sorted and collected. The results indicate that the microchip achieves a recovery ratio of 87.7% and a yield ratio of 94.1% for the yeast cells and therefore attains a comparable performance to that of a large-scale commercial flow cytometer. Importantly, the high performance of the microchip is achieved without the need for a complex control system or for sophisticated actuation mechanisms such as embedded microelectrodes, ultrasonic generators, or micropumps, and so forth.     

A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices

Recent advances in microfluidic devices put a high demand on small, robust and reliable pumps suitable for high-throughput applications. Here we demonstrate a compact, low-cost, directly attachable (clip-on) electroosmotic pump that couples with standard Luer connectors on a microfluidic device. The pump is easy to make and consists of a porous polycarbonate membrane and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) electrodes. The soft electrode and membrane materials make it possible to incorporate the pump into a standard syringe filter holder, which in turn can be attached to commercial chips. The pump is less than half the size of the microscope slide used for many commercial lab-on-a-chip devices, meaning that these pumps can be used to control fluid flow in individual reactors in highly parallelized chemistry and biology experiments. Flow rates at various electric current and device dimensions are reported. We demonstrate the feasibility and safety of the pump for biological experiments by exposing endothelial cells to oscillating shear stress (up to 5 dyn/cm²) and by controlling the movement of both micro- and macroparticles, generating steady or oscillatory flow rates up to ± 400 μL/min.     

Numerical simulation of a novel microfluidic electroosmotic micromixer with Cantor fractal structure

In this paper, we design a novel low voltage of electroosmotic micromixer with fractal structure. Because of the influence of high voltage on electrode and solution, we propose an electroosmotic micromixer of low voltage. In order to optimize the electrode position, we design the Cantor fractal according to Cantor principle, and arrange the electrode pairs on the fractal. Then we study the mixing effect of the electrode pairs length on the mixing performance, the effect of the electrode position and the effect of fractal electrode group spacing on the mixing efficiency. When the electroosmotic micromixer has three electrode groups at alternating voltage of 5 V and alternating frequency of 8 Hz, the best mixing efficiency can reach 95.2% in one second. We call this micromixer Cantor fractal electroosmotic micromixer (CFEM). At the same Re, the mixing efficiency of CFEM is higher than the electrodeless micromixer 50%.

     

基于MEMS细胞电融合芯片的设计与实验研究

基于MEMS技术,根据细胞电融合的工作条件,设计了一种可以在低电压驱动下工作的细胞电融合芯片。该芯片的外界驱动电压（包括排队与融合电压）仅为传统细胞电融合槽的1／100—1／20,可以显著降低外界驱动部分的设计、制造成本,扩展细胞电融合技术的应用。介绍了该芯片的设计思路,分析了原试制细胞电融合芯片存在的可靠性和氧化问题,提出了有效的改进方法,优化了芯片设计方案,制定了相应的加工工艺流程。给出了采用该芯片对部分细胞进行初步排队、融合实验的结果,实验结果表明：对原有芯片进行的优化设计是有效的。     

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).     

微流控芯片及其应用

单层BD碟片容量为25GB、双层为50GB,基本上可以满足完全高清节目的记录播放。但是随着3D技术和互动技术的介入以及超大容量数据存储需求的增长,目前的BD标准将面临挑战。本文以工程实践的角度介绍了3种BD碟片的物理结构,并以此为基础,结合当前光存储领域的最新技术,从存储密度和数据传输率两方面展望了BD技术的发展趋势。     

A cell electrofusion microfluidic chip with micro-cavity microelectrode array

A new cell electrofusion microfluidic chip with 19,000 pairs of micro-cavity structures patterned on vertical sidewalls of a serpentine-shaped microchannel has been designed and fabricated. In each micro-cavity structure, the two sidewalls perpendicular to the microchannel are made of SiO₂ insulator, and that parallel to the microchannel is made of silicon as the microelectrode. One purpose of the design with micro-cavity microelectrode array is to obtain high membrane voltage occurring at the contact point of two paired cells, where cell fusion takes place. The device was tested to electrofuse NIH3T3 and myoblast cells under a relatively low voltage (~9 V). Under an AC electric field applied between the pair of microelectrodes positioned in the opposite micro-cavities, about 85–90 % micro-cavities captured cells, and about 60 % micro-cavities are effectively capable of trapping the desired two-cell pairs. DC electric pulses of low voltage (~9 V) were subsequently applied between the micro-cavity microelectrode arrays to induce electrofusion. Due to the concentration of the local electric field near the micro-cavity structure, fusion efficiency reaches about 50 % of total cells loaded into the device. Multi-cell electrofusion and membrane rupture at the end of cell chains are eliminated through the present novel design.     

A portable,hand-powered microfluidic device for sorting of biological particles

Manually hand-powered portable microfluidic devices are cheap alternatives for point-of-care diagnostics. Currently, on-field tests are limited by the use of bulky syringe pumps, pressure controller and equipment. In this work, we present a manually operated microfluidic device incorporated with a groove-based channel. We show that the device is capable to effectively sort particles/cells by manual hand powering. First, the grooved-based channel with differently sized polystyrene particles was characterized using syringe pumps to study their distributions under various flow rate conditions. Afterward, the particle mixtures were sorted manually using hand power to verify the capability of this device. Finally, the manually operated device was used to sort platelets from peripheral blood mononuclear cells (PBMCs). The platelets were collected with a purity of ~ 100%. The purity of PBMCs was enhanced from 0.8 to 10.4% after multiple processes which results in an enrichment ratio of 13.8. During the process of manual hand pumping, the flow fluctuation caused by unstable injection will not influence the sorting performance. Due to its simplicity, this manually operated microfluidic chip is suitable for outfield settings.     

Human blood microfluidic test chip for imaging,label-free biosensor

We designed and evaluated a microfluidic test chip for human blood filtration and imaging label-free detection of multiple biomarkers. The microfluidic chip has a total size of 75 mm × 25 mm × 2 mm. It is realized as an assembly of a plastic chip and a functionalized photonic crystal slab on a glass substrate. The plastic chip contains capillary channels, a filter membrane and a cavity open on one side. The photonic crystal chip is bonded with an adhesive foil to the open cavity. Human blood filtration is demonstrated. We determined that fluorescently labelled particles of diameter 3 µm or larger are filtered out by the system. Refractometric measurements are performed with the test chip in combination with a compact imaging read-out system to investigate the system response to refractive index changes. Flow dynamics in the sensor cavity are imaged for replacing water by isopropanol. Finally, the binding of 500 nm biotin dissolved in phosphate buffer saline to a photonic crystal surface locally functionalized with streptavidin is demonstrated.     

聚二甲基硅氧烷微流控芯片的制备

采用印刷电路板技术加工出芯片模具,以聚二甲基硅氧烷(PDMS)为材料制作出微流控芯片。该芯片由基片和盖片组成,微流控沟道位于基片上,深度和宽度分别为75μm和100μm,由盖片对其进行密封。考察了有绝缘漆模具和无绝缘漆模具制作的芯片的电泳分离情况。在该PDMS微流控芯片上对用异硫氰酸酯荧光素标记的氨基酸进行了电泳分离,当信噪比S/N=3时,最小检测浓度达到0.8×10-11mol/L。     

Development of high throughput microfluidic cell culture chip for perfusion 3-dimensional cell culture-based chemosensitivity assay

This study reports a microfluidic cell culture chip encompassing 36 microbioreactors for high throughput perfusion 3-dimensional (3D) cell culture-based chemosensitivity assays. Its advantages include the capability for multiplexed medium delivery, and the function for both efficient and high throughput micro-scale 3D culture construct preparation and loading. The results showed that the proposed medium pumping mechanism was able to provide a uniform pumping rates ranging from 1.2 to 3.9 μl h⁻¹. In addition, the simple cell/hydrogel loading scheme has been proven to be able to carry out 3D cell culture construct preparation and loading precisely and efficiently. Furthermore, a chemosensitivity assay was successfully demonstrated using the proposed cell culture chip. The results obtained were also compared with the same evaluation based on a conventional 2D monolayer cell culture. It can be concluded that the choice of cell culture format can result in different chemosensitivity evaluation results. Overall, because of the nature of miniaturized perfusion 3D cell culture, the cell culture chip not only can provide stable, well-defined and more biologically relevant culture environments, but it also features low consumption of research resources. All these traits are found particularly useful for high-precision and high-throughput 3D cell culture-based assays.     

基于ACS运动控制的LED晶片分选系统设计

为了提高LED晶片分选机的分选速度和精度,设计了基于IPC+ ACS运动控制的LED晶片分选系统;分析了晶片分选过程直线电机定位、直驱电机旋转以及音圈电机拾取三部分的时序,并结合电机性能分别规划了3类电机的定位时间;以直驱电机为例分析了在SPiiPlus MMI软件环境中调试电机电流环、速度环和位置环以及频域稳定性的过程,并最终给出3类电机的定位时间和定位误差;设计了吸嘴和顶针接触式剥离拾取晶片的方案,利用ACSPL+语言编写拾取动作的程序,并在速度环和位置环曲线中加以验证;在ZKMY-P10型号的分选机分选平台进行了连续分选测试,实验结果表明,分选机的X/Y轴定位精度为±0.5 mil,晶片分选的平均速度为125 ms/片.     

聚二甲基硅氧烷微流体芯片的制作技术

基于MEMS技术的微流体芯片在分析化学和生物医学领域显示了巨大的应用潜力。作为构建微流体芯片的基底材料———聚二甲基硅氧烷(PDMS)已经表现出了许多的优点:良好的电绝缘性、较高的热稳定性、优良的光学特性以及简单的加工工艺等。采用浇注法制作了PDMS电泳微芯片,对PDMS微流体芯片的加工工艺、封装方法和结构特征进行了探讨,并提出了相应的解决方案。     

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.     

ITO薄膜微流体芯片的温控系统设计

设计了一种用于氧化铟锡(ITO)薄膜基材微流体芯片的恒温控制系统。系统采用数字温度传感器采集ITO薄膜温度,USB 2.0接口通信。用户通过PC机可实时监测微流体芯片温度变化情况,设定目标温度,以及存储温度数据。系统采用改进增量式PID控制算法实现温度控制,控制精度可达±0.2℃。     

复合式微流控脱水芯片的研制

报道了一种复合式微流控脱水芯片。采用玻璃、聚二甲氧基硅氧烷(PDMS)和聚碳酸酯(PC)三种材质,采用不可逆封接方法分别制得玻璃—PDMS液路半芯片、PC—PDMS气路半芯片,中间夹一层聚四氟乙烯(PTFE)多孔滤膜,将两个半芯片可逆封接形成玻璃—PDMS…PDMS—PC结构的全芯片。该制备方法简单可靠,其液路半芯片和气路半芯片可以单独更换,使得使用成本降低。实验表明:该芯片脱水性能良好,可用于有机合成步骤中含水试剂的高效除水。     

Using a cross-flow microfluidic chip for monodisperse UV-photopolymerized microparticles

In this paper, we report a microfluidic chip containing a cross-junction channel for the manipulation of UV-photopolymerized microparticles. Hydrodynamic-focusing is used to form a series of using 365 nm UV light to solidify the hydrogel droplets. We were able to control the size of the hydrogel droplets from 75 to 300 μm in diameter by altering the sample and by changing the flow rate ratio of the mineral oil in the center inlet channel to that of the side inlet channels. We found that the size of the emulsions increases with an increase in average velocity of the dispersed phase flow (polymer solution flow). The size of the emulsions decreases with an average velocity increase of the continuous phase flow (mineral oil flow). Experimental data show that the emulsions are very uniform. The developed microfluidic chip has the advantages of ease of fabrication, low cost, and high throughput. The emulsions generated are very uniform and have good regularity.