芯片毛细管电泳的系统级建模与仿真技术研究

芯片毛细管电泳分离是微流控芯片系统中的重要组成部分,其电泳分离效率直接影响着芯片的整体功能。本文运用多端口组件模型技术建立了逶迤型芯片毛细管电泳分离的参数化行为模型及系统级模型。模型仿真结果与有限元仿真软件的仿真结果相比较,仿真速度提高了100多倍,而相对误差小于3.8%,表明论文所建立的芯片毛细管电泳分离行为模型,能够在不降低系统仿真精度的同时更加快速高效地对系统性能做出评价。     

基于虚拟仪器的电渗流检测系统的设计

为实现微流控芯片的高精度分析,设计了一种基于虚拟仪器的微通道电渗流检测系统.介绍了电渗流测定的常用方法及其优缺点,基于电流监测法原理设计了微通道电渗流检测系统的硬件结构,采用LabVIEW软件开发了人-机界面.并在不同电场强度作用下,完成了微通道电渗流的测定.实验表明:该设计的检测系统能很好地满足微通道内部电渗流检测的需求.     

微流控芯片微通道热压成形中塑料流动的仿真

目前,PMMA微流控芯片微通道成形过程中热压参数的调整周期很长.针对这一问题,本文基于热粘弹性理论建立微通道成形过程中的热-应力耦合场模型,利用有限元软件对微通道热压成形过程进行了仿真,通过对不同压力、温度和时间下微通道成形的仿真,得出了最优化的工艺参数.实验结果验证了仿真结论,可以实现对微流控芯片微通道热压成形过程的快速有效的控制.     

基于激光诱导的细胞荧光成像系统研制

分析了激光诱导荧光法检测钙离子浓度的原理.并利用微流控芯片在细胞培养和检测上的独特优越性,设计实现了基于微流控芯片的测量细胞内钙离子浓度变化的显微荧光成像系统.在对微流控芯片技术研究的基础上设计制作了微流控芯片,并设计了显微系统、快速波长切换系统、CCD成像系统等.利用这套显微荧光成像系统对活体细胞的荧光图像进行采集....     

适用于暗场生化传感系统的微流控芯片的研制与验证

为了提高暗场检测的效率、获取高质量的传感信息,基于实验设备的物理尺寸以及实验环境,通过COMSOL Multiphysics仿真,并采取键合工艺,研制了一种适用于暗场生化传感系统的微流控芯片。该芯片可在同一暗场视野下观察到四个反应区域,实现对多种样品的并行检测。同时由于该设计的连通性,四个反应区域可以两两进行精确对照,对样本检测结果进行定性定量对比。实验中,在暗场显微成像系统下捕获到微流控芯片通入各反应区域的传感单元纳米粒子,测出散射光谱,验证其可行性。暗场显微成像系统和微流控芯片的结合,实现了自动化、集成化的实时原位并行检测,极大地提高了实验效率。     

梳齿谐振器宏模型的系统级应用

宏模型的获取是由Krylov子空间投影法结合器件级有限元分析的宏建模方法来实现,利用此模型和基于可重用IP设计思想的系统级组件建模方法建立由VHDL-AMS语言描述的梳齿谐振器系统级模型,在华大VDE仿真平台上搭建出了梳齿谐振器的系统模型,并进行一系列的仿真,包括时域阶跃、交流电压信号仿真和频域交流小信号仿真,仿真结果与商用仿真工具ANSYS仿真结果保持良好的一致.     

用于微流控PCR的TEC温控系统结构优化设计

为了实现微流控聚合酶链式反应(PCR)的快速升降温,设计了一种基于半导体制冷片(TEC)的温度控制系统.通过对控温对象微流控PCR芯片的热分析,确定了TEC的参数,并且研究了TEC效率与散热性能之间的关系.在此基础上,设计了一种热管鳍片式高性能散热器,对其传热机理、传热路线及热阻进行了深入分析,建立了有限元模型,并对该热管散热器进行了实验测试.实验结果表明:该温控系统的平均升降温速率达到7.48℃/s,为实现微流控PCR系统的快速精确升降温控制奠定了良好基础.     

基于小波能量元和改进双阈值函数的微流控芯片信号去噪方法研究

微流控芯片技术是一种新型的分析检测技术,可广泛应用于生物、化学、医学等领域。为提高微流控芯片信号去噪效果,本文提出了一种基于小波能量元和改进双阈值函数的去噪方法。构建了基于指数和对数函数的小波能量元双阈值函数,继而设计了微流控芯片信号去噪算法。以模拟的微流控芯片信号为研究对象,对比选择db4小波基进行了4层分解去噪仿真实验。仿真结果表明,本文方法优于现有的普通阈值法、空域相关法和能量元浮动阈值法。该方法已应用于自主研发的非接触式微流控芯片便携式分析诊断仪,去噪效果良好,有效提升了设备性能。     

低成本聚合物微流控芯片加工技术综述

针对传统微流控芯片加工方法成本高昂、耗时长的问题,近年来出现了多种低成本的微流控芯片加工方法,在聚合物、纸等材料上加工、完成了能够满足其应用需求的微流控芯片。对当前各类基于聚合材料的低成本微流控芯片加工技术进行了梳理和总结,并对未来低成本微流控芯片的发展进行了展望。     

基于图像处理的微流控芯片智能定位系统

针对微流控芯片分析系统中微管道检测手动定位方式定位精度低、耗时费力及无法完成跟踪定位等缺点，设计了一种基于图像处理技术的微流控芯片智能定位系统。系统采用形态学方法、细化算法及Radon变换等相关图像处理方法将芯片平面图上微管道的节点提取出来，生成邻接表，以完成对微流控芯片的智能跟踪定位，并通过定位结果对邻接表进行反馈修正。实验表明所提出的智能跟踪定位方法在对微流控芯片进行跟踪定位时效果良好。     

Surface tension driven and 3-D vortex enhanced rapid mixing microchamber

This paper proposes a novel passive micromixer design for mixing enhancement by forming a large three-dimensional (3-D) flow vortex in a counterflow microfluidic system. The counterflow fluids are self-driven by surface tension to perform mixing in an open chamber. The chamber design consists of two rectangular bars to house the chamber and to form two opening inlets from opposite directions. The best design is selected from various versions of mixing chambers. The mixing effectiveness is tremendously increased by folds of contacting surface between two fluids induced and enhanced due to the stretching of two fluid contacting interfaces by the formation of a 3-D large size vortex structure inside the mixing chamber itself with unaccountable numbers of fluid layers. Both numerical simulations and experiments are performed and compared to identify the design parameters for maximum utilization in this microfluidic system, such as the length of rectangular bar, microchannel wall height, and mixing chamber size. Compared to traditional micromixers operated by two-dimensional (2-D) vortex, this passive mixer can greatly enhance mixing efficiency and reduce mixing time by tenfold from around 10 s to less than 10 ms by 3-D effective chaotic flow structures in a more compact size. This mixing chamber is also suitable for an H-shape digital fluidic system for parallel mixing process in different mixing ratio simultaneously as a lab-on-a-chip system.     

Analysis of passive microfluidic mixers incorporating 2D and 3D baffle geometries fabricated using an excimer laser

We present new passive microfluidic mixing structures based on 2D and 3D geometries. The primary mechanism of mixing in these devices is based on chaotic advection. The mixers which incorporate 3D structures introduce transverse flow rotation greatly enhancing performance. Simulations and experimental tests were performed over a Reynolds number (Re) range from 0.1 to 20 and showed good agreement. At an Re of 0.1, 90% mixing was achieved in a path length of 32 and 7 mm, for the 2D and 3D geometrical mixers, respectively. This represents an improvement in performance over a standard T-mixer of 20% for the 2D mixer and 82.5% for the 3D mixer. An inflection point in the mixing efficiency was observed for both mixer types around an Re of 1. The devices were fabricated on a polymethylmethacrylate (PMMA) substrate, using an excimer laser beam incorporating an intelligent pinhole mask. Initially, structures were developed off-line using a laser simulation tool. A design-of- experiments (DOE) approach along with computational fluid dynamic (CFD) analysis was used to optimise mixing element geometry. This precursor to the fabrication step greatly reduces the time between the design stage and device realisation.     

Evaluation of passive mixing behaviors in a pillar obstruction poly(dimethylsiloxane) microfluidic mixer using fluorescence microscopy

The rapid mixing of fluids passing through a microfluidic channel is very important for various applications of microfluidic systems. It has been a great challenge to achieve highly efficient mixing in a microfluidic system because it is very difficult to generate turbulence in a submillimeter-size channel at low Reynolds numbers (Re). In this paper, we fabricated a pillar obstruction microfluidic mixer and evaluated its mixing efficiency at various flow rates. The mixing behavior of confluent streams was estimated using a fluorescence microscope. Three different sets of miscible solutions (phosphate-buffered solution, gold nanocolloids and 20% glycerol), with Rhodamine 6G aqueous solution, were used as sample laminar flows. According to our experimental results, the pillar obstruction microfluidic mixer shows an excellent mixing performance in the low Re range. Here, the mixing performance was strongly dependent on the characteristic viscosity changes of different sets of miscible solutions. The pillar obstruction microfluidic mixer designed here is expected to benefit a wide range of lab-on-a-chip applications because fabrication is very simple and the mixing efficiency is excellent at low Re.     

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.     

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.     

Convective–diffusive transport in parallel lamination micromixers

Effective mixing and a controllable concentration gradient are important in microfluidic applications. From the scaling law, decreasing the mixing length can shorten the mixing time and enhance the mixing quality. The small sizes lead to small Reynolds numbers and a laminar flow in microfluidic devices. Under these conditions, molecular diffusion is the main transport effect during the mixing process. In this paper, we present complete 2D analytical models of convective–diffusive transport in parallel lamination micromixers for a binary system. An arbitrary mixing ratio between solute and solvent is considered. The analytical solution indicates the two important parameters for convective–diffusive transport in microchannels: the Peclet number and the dimensionless mixing length. Furthermore, the model can also be extended to the mixing of multiple streams—a common and effective concept of parallel mixing in microchannels. Using laser machining and adhesive bonding, polymeric micromixers were fabricated and tested to verify the analytical results. The experimental results agree well with the analytical models.This revised version was published online in March 2005 with corrections to Eq. 12.     

Leveraging stimuli responsive hydrogels for on/off control of mixing

Microfluidic mixers are an important component in microfluidic devices. This paper presents a micromixer which can control mixing with responsive hydrogel actuators to modulate mixing between two adjacent fluids dependant on the chemistries of the fluid. This is achieved by the responsive hydrogels swelling or contracting under different stimuli, which alters the mixing between the two fluids. We present this device using standard pH responsive hydrogels for two different device designs and demonstrate altered mixing profiles based on the pH of the fluid streams. For the T-shaped device an increase in mixing efficiency from 18.3% to 34.5% is observed between the contracted and expanded hydrogel states. For the modified T-shaped device mixing efficiency in the contracted state is 25.0% while in the expanded state efficiency increases to 72.9%. This can be used as a mixer that has on/off functionality of an active mixer, based on the pH of the mixing streams, with the advantages a passive mixer offers. Other responsive hydrogel chemistries could be substituted into the device to achieve many different triggers for mixing.     

Electrokinetically driven flow mixing utilizing chaotic electric fields

This paper presents a novel microfluidic mixing scheme in which the species streams are mixed via the application of chaotic electric fields to four electrodes mounted on the upper and lower surfaces of the mixing chamber. Numerical simulations are performed to analyze the effects of the resulting chaotic electrokinetic driving forces on the fluid flow characteristics within the micromixer and the corresponding mixing performance. During simulation, chaotic oscillating electric potentials are derived using a Duffing–Holmes chaos system. Simulation results indicate that the chaotic electrokinetic driving forces induce a complex flow behavior within the micromixer which results in efficient mixing of the two species streams. It is shown that mixing efficiencies up to 95% can be obtained in the novel micromixer.     

Quantification of the performance of chaotic micromixers on the basis of finite time Lyapunov exponents

Chaotic micromixers such as the staggered herringbone mixer developed by Stroock et?al. allow efficient mixing of fluids even at low Reynolds number by repeated stretching and folding of the fluid interfaces. The ability of the fluid to mix well depends on the rate at which ??chaotic advection?? occurs in the mixer. An optimization of mixer geometries is a non-trivial task which is often performed by time consuming and expensive trial and error experiments. In this paper an algorithm is presented that applies the concept of finite-time Lyapunov exponents to obtain a quantitative measure of the chaotic advection of the flow and hence the performance of micromixers. By performing lattice Boltzmann simulations of the flow inside a mixer geometry, introducing massless and non-interacting tracer particles and following their trajectories the finite time Lyapunov exponents can be calculated. The applicability of the method is demonstrated by a comparison of the improved geometrical structure of the staggered herringbone mixer with available literature data.