微流控芯片上的颗粒被动聚焦技术

微流控芯片上的颗粒聚焦技术已广泛用于生物、化学、工程和医疗等领域。精确的聚焦过程是计数、检测或分选等应用的关键预处理步骤。颗粒聚焦技术根据是否引入外部能场和鞘流,分为主动聚焦、被动聚焦和鞘流辅助聚焦。被动聚焦利用流体的惯性、黏弹性等特性操控颗粒在流体中的平衡位置,拥有结构简单、高通量、生物兼容、低成本和无标记等多重优点。已有大量文献针对微流控芯片上的颗粒被动聚焦技术,从芯片的结构拓展、微流体特性和微粒特性等方面,开展了实验和数值计算研究。本文对微流控芯片上的颗粒被动聚焦技术最新研究进展进行了综述,首先对流体中颗粒受到的水动力和聚焦相关原则进行阐述,进一步详细综述被动聚焦技术进展,最后对该技术的未来发展作出了展望。     

黏弹性流体在微粒被动操控技术中的应用

因能实现微米尺度粒子的精确操控,微流控技术已被广泛运用于医学、制药、生物和化学等领域,其中无需外场作用的被动操控技术由于其简单性和自主性更是成为研究热点。与其他被动操控技术相比,黏弹性聚焦技术更易实现微粒的三维聚焦且能操控微粒的尺度跨度大、流体流量范围广。因此,本文综述了黏弹性流体在微粒被动操控应用中的最新研究进展。首先,介绍了微粒在不同结构流道内的黏弹性流体中进行迁移的受力机理,进一步详细阐述了黏弹性聚焦、黏弹性分选、黏弹性混合以及其他黏弹性微粒操控应用研究进展,最后对研究黏弹性流体流动特性和在其内微粒迁移运动规律的数值模拟方法进行了介绍,并在分析现有问题的基础上对黏弹性微流控技术未来的发展作出了展望。     

螺旋通道中稳定增强的二次流构建及其粒子聚焦研究

惯性微流是一种具有高通量精确操控粒子和细胞能力的微流控技术,近年来受到广泛关注。然而,由于惯性微流芯片内二次流的不稳定性,在大尺寸管道内实现粒子流速不敏感的聚焦仍存在挑战。本研究开发了一种微结构辅助的超低高宽比螺旋微通道,利用二次流的稳定和加速实现了粒子的惯性聚焦。研究结果表明,在大的流速灌注范围（0.5～3.0 mL/min）内成功实现了粒径分别为7.3和15.5μm的荧光粒子在1 mm宽的螺旋通道芯片内的聚焦,聚焦效率分别达到94%和99%以上。此外,粒子聚焦位置距离管道内壁高达100μm,远大于其它惯性聚焦芯片。因此,通过在螺旋通道芯片内设置等序列的微结构,促使二次流的稳定和增强,完成了流量和粒径不敏感的惯性聚焦。与传统的惯性聚焦方法相比,本方法无需额外的鞘流操作,具有高通量和易于制造的特点。这种创新的结构为便携式惯性微流控芯片的开发提供了更多的选择,可应用于细胞分析与检测、流式细胞仪和在线样品处理等领域。     

磁场控制技术在微流控芯片中的应用*

磁场作为除了电场和力场之外的另一个有力的驱动和控制手段,由于不需与溶液接触即可实现对被分析物的操纵,极大降低污染的可能,近年来被越来越广泛地用于微流控芯片系统,尤其在细胞、病毒甚至单分子的捕获、分选以及操纵等方面显示出较大优势。本文综述了微流控芯片系统中磁场控制技术的最新进展,分别从理论分析,磁场加工技术、泵阀的实现,微流体控制和磁分离等方面介绍了该领域近几年的发展状况,并重点分析了微流控芯片磁场操控技术在临床分析和现场检测方面的应用,及其未来发展趋势和需解决的主要问题。     

微液滴微流控芯片:微液滴的形成、操纵和应用

微流控芯片中形成的微液滴粒径均一、可控,与传统的连续流体系相比,具有能实现试剂的快速混合、通量更高等优点.本文介绍了微流控芯片中由微通道控制的微液滴的形成、分裂、合并、混合、分选和捕获等微液滴操纵技术,以及微液滴技术在纳米粒子、聚合物微粒的合成、纳米粒子自组装、蛋白质结晶研究和DNA、细胞分析等领域的研究进展.     

精准入微——将微流控技术引入分析化学教学的探讨

微流控技术凭借其优异的微尺度操控能力,在分析化学和其他诸多领域得到了广泛而快速的发展。在本科阶段的分析化学课程引入微流控技术有助于提高分析化学教学的前沿性和趣味性,促进创新型人才的培养。本文回顾了微流控技术的发展史并挖掘了其中蕴含的课程思政元素,简要介绍了微流控技术的重要理论和微流控芯片的基本制作方法,讨论了微流控技术与分析化学的联系。在此基础上介绍了近年来微流控技术在分析化学领域,尤其是生命分析科学领域的研究进展,以期为分析化学教学引入微流控技术提供参考。     

基于表面增强拉曼光谱微流控芯片的研究进展

微流控芯片实验室是一种以在微米尺度的空间中对流体进行操控为主要特征的技术,具有灵活集成多种单元技术,降低样品消耗量等优势。拉曼光谱是一项重要的现代光谱技术,被广泛应用于化学、物理和生物科学等诸多学科领域,基于纳米银或金粒子的表面增强拉曼(SERS)技术具有非常高的灵敏度,可对环境中的污染物和生物分析样品进行痕量分析。该文主要对表面增强拉曼光谱微流控芯片领域的研究进展进行总结,包括纳米粒子合成、芯片设计以及常见的传感器类型,介绍了其在生命科学、环境监测等领域的应用,显示了其广阔的应用前景。     

微流控芯片液滴生成与检测技术研究进展

微流控芯片液滴技术是一种操控微小体积液体的新技术,既可实现高通量微观样本的生成及控制,也可进行独立液滴的操作.分散的微液滴单元可作为理想的微反应器,在生物医药中的药物筛选、材料筛选和高附加值微颗粒材料合成领域展现出巨大的应用潜力.液滴微流控芯片是利用流体剪切力的改变,使互不相溶的两相流体在其界面处生成稳定、有序的液滴,...     

微流控芯片上的免疫分析

近20年来,随着微流控芯片加工技术的不断发展,微流控分析已从一个概念发展为当前世界上最前沿的科技领域之一,微流控芯片上免疫分析的方法研究也取得重要进展。这些芯片包含传输流体的微通道和免疫分析程序中部分或全部的必要组件。微流控技术用于免疫分析在减少试剂用量、缩短分析时间、自动化等方面提高了分析性能。本文综述了微流控芯片上免疫分析的发展、分类,并评述了各类微流控免疫分析芯片的性能及优缺点。     

微流控液滴技术及其在生物医学分析中的应用进展

微流控芯片微滴技术作为一种基于微流控芯片的操控微小体积液体的新技术,以分散的微滴单元作为微反应器,它大大强化了微流控芯片的高灵敏度、低消耗、高通量和自动化等优点,受到日益广泛的重视,并在物理学、化学和生物学等领域中显示出巨大的应用潜力。文章叙述了微流控微滴领域的最新进展,对新的微滴生成技术及操控技术进行介绍,最后阐述了微滴技术在生物医学分析中的最新研究进展。     

A smart and portable micropump for stable liquid delivery

Precise and reliable liquid delivery is vital for microfluidic applications. Here, we illustrate the design, fabrication, characterization, and application of a portable, low cost, and robust micropump, which brings solution to stable liquid delivery in microfluidic environment. The pump is designed with three optional speeds of different pumping flow rates, and it can be simply actuated by spring‐driven mechanism. The different flow rates of the pump are realized via passive microvalves in a compact microfluidic chip, which is installed in the pump. Importantly, the membrane structures of the microvalves allow accurate liquid control, and stable flow rates can be achieved via a spring setup. The proposed pump is applied to continuously and stably infuse microbead suspension into an inertial microfluidic chip, and good particle focusing is realized in the spiral channel of the inertial microfluidic chip. The proposed portable, self‐powered, and cost‐efficient pump is crucial for microfluidic lab‐on‐a‐chip system integration, which may facilitate microfluidic application for precise liquid delivery, control, measurement, and analysis.     

Low-cost multi-core inertial microfluidic centrifuge for high-throughput cell concentration

We developed a low-cost multi-core inertial microfluidic centrifuge (IM-centrifuge) to achieve a continuous-flow cell/particle concentration at a throughput of up to 20 mL/min. To lower the cost of our IM-centrifuge, we clamped a disposable multilayer film-based inertial microfluidic (MFIM) chip with two reusable plastic housings. The key MFIM chip was fabricated in low-cost materials by stacking different polymer-film channel layers and double-sided tape. To increase processing throughput, multiplexing spiral inertial microfluidic channels were integrated within an all-in-one MFIM chip, and a novel sample distribution strategy was employed to equally distribute the sample into each channel layer. Then, we characterized the focusing performance in the MFIM chip over a wide flow-rate range. The experimental results showed that our IM-centrifuge was able to focus various-sized particles/cells to achieve volume reduction. The sample distribution strategy also effectively ensured identical focusing and concentration performances in different cores. Finally, our IM-centrifuge was successfully applied to concentrate microalgae cells with irregular shapes and highly polydisperse sizes. Thus, our IM-centrifuge holds the potential to be employed as a low-cost, high-throughput centrifuge for disposable use in low-resource settings.     

Improvement of size-based particle separation throughput in slanted spiral microchannel by modifying outlet geometry

The inertial microfluidic technique, as a powerful new tool for accurate cell/particle separation based on the hydrodynamic phenomenon, has drawn considerable interest in recent years. Despite numerous microfluidic techniques of particle separation, there are few articles in the literature on separation techniques addressing external outlet geometry to increase the throughput efficiency and purity. In this work, we report on a spiral inertial microfluidic device with high efficiency (>98%). Herein, we demonstrate how changing the outlet geometry can improve the particle separation throughput. We present a complete separation of 4 and 6 μm from 10 μm particles potentially applicable to separate microalgae (Tetraselmis suecica from Phaeodactylum tricornutum). Two spiral microchannels with the same cross section dimension but different outlet geometry were considered and tested to investigate the particle focusing behavior and separation efficiency. As compared with particle focusing observed in channels with a simple outlet, the particle focusing in a modified outlet geometry appears in a more successful focusing manner with complete separation. This simple approach of particle separation makes it attractive for lab-on-a-chip devices for continuous extraction and filtration of a wide range of cell/particle sizes.     

Inertial separation in a contraction-expansion array microchannel

We report a contraction-expansion array (CEA) microchannel that allows inertial size separation by a force balance between inertial lift and Dean drag forces in fluid regimes in which inertial fluid effects become significant. An abrupt change of the cross-sectional area of the channel curves fluid streams and produces a similar effect compared to Dean flows in a curved microchannel of constant cross-section, thereby inducing Dean drag forces acting on particles. In addition, the particles are influenced by inertial lift forces throughout the contraction regions. These two forces act in opposite directions each other throughout the CEA microchannel, and their force balancing determines whether the particles cross the channel, following Dean flows. Here we describe the physics and design of the CEA microfluidic device, and demonstrate complete separation of microparticles (polystyrene beads of 4 and 10 μm in diameter) and efficient exchange of the carrier medium while retaining 10 μm beads.     

Inertial microfluidics: Recent advances

Inertial microfluidics has attracted significant attentions in last decade due to its superior advantages of high throughput, label- and external field-free operation, simplicity, and low cost. A wide variety of channel geometry designs were demonstrated for focusing, concentrating, isolating, or separating of various bioparticles such as blood components, circulating tumor cells, bacteria, and microalgae. In this review, we first briefly introduce the physics of inertial migration and Dean flow for allowing the readers with diverse backgrounds to have a better understanding of the fundamental mechanisms of inertial microfluidics. Then, we present a comprehensive review of the recent advances and applications of inertial microfluidic devices according to different channel geometries ranging from straight channels, curved channels to contraction-expansion-array channels. Finally, the challenges and future perspective of inertial microfluidics are discussed. Owing to its superior benefit for particle manipulation, the inertial microfluidics will play a more important role in biology and medicine applications.     

Impedance‐based viscoelastic flow cytometry

Elastic nature of the viscoelastic fluids induces lateral migration of particles into a single streamline and can be used by microfluidic based flow cytometry devices. In this study, we investigated focusing efficiency of polyethylene oxide based viscoelastic solutions at varying ionic concentration to demonstrate their use in impedimetric particle characterization systems. Rheological properties of the viscoelastic fluid and particle focusing performance are not affected by ionic concentration. We investigated the viscoelastic focusing dynamics using polystyrene (PS) beads and human red blood cells (RBCs) suspended in the viscoelastic fluid. Elasto‐inertial focusing of PS beads was achieved with the combination of inertial and viscoelastic effects. RBCs were aligned along the channel centerline in parachute shape which yielded consistent impedimetric signals. We compared our impedance‐based microfluidic flow cytometry results for RBCs and PS beads by analyzing particle transit time and peak amplitude at varying viscoelastic focusing conditions obtained at different flow rates. We showed that single orientation, single train focusing of nonspherical RBCs can be achieved with polyethylene oxide based viscoelastic solution that has been shown to be a good candidate as a carrier fluid for impedance cytometry.     

Concentration‐controlled particle focusing in spiral elasto‐inertial microfluidic devices

Herein, we proposed a strategy for controlling the particle focusing position in Dean‐coupled elasto‐inertial flows via adjusting the polymer concentration of viscoelastic fluids. The physics behind the control strategy was then explored and discussed. At high polymer concentrations, the flowing particles could be single‐line focused exactly at the channel centerline under the dominated elastic force. The center‐line focusing in our spiral channel may employed as a potential pretreatment scheme for microflow cytometry detection. With further decreasing polymer concentrations, the particles would shift into the outer channel region under the comparable competition between inertial lift force, elastic force and Dean drag force. Finally, the observed position‐shifting was successfully employed for particle concentration at a throughput much higher than most existing elasto‐inertial microfluidics.     

A method for DNA detection in a microchannel: fluid dynamics phenomena and optimization of microchannel structure

A simple DNA diagnosis method using microfluidics has been developed which requires simple and straightforward procedures such as injection of sample and probe DNA solutions. This method takes advantage of the highly accurate control of fluids in microchannels, and is superior to DNA microarray diagnosis methods due to its simplicity, highly quantitative determination, and high-sensitivity. The method is capable of detecting DNA hybridization for molecules as small as a 20 mer. This suggests the difference in microfluidic behavior between single strand DNA (ssDNA) and double stranded DNA (dsDNA). In this work, influence of both the inertial force exerted on DNA molecules and the diffusion of DNA molecules was investigated. Based on the determination of these parameters for both ssDNA and dsDNA by experiments, a numerical model describing the phenomena in the microchannel was designed. Computational simulation results using this model were in good agreement with previously reported experimental results. The simulation results showed that appropriate selection of the analysis point and the design of microchannel structure are important to bring out the diffusion and inertial force effects suitably and increase the sensitivity of the detection of DNA hybridization, that is, the analytical performance of the microfluidic DNA chip.     

Numerical study of dielectrophoresis-modified inertial migration for overlapping sized cell separation

Circulating tumor cells (CTCs) have been proven to have significant prognostic, diagnostic, and clinical values in early-stage cancer detection and treatment. The efficient separation of CTCs from peripheral blood can ensure intact and viable CTCs and can, thus, give proper genetic characterization and drug innovation. In this study, continuous and high-throughput separation of MDA-231 CTCs from overlapping sized white blood cells (WBCs) is achieved by modifying inertial cell focusing with dielectrophoresis (DEP) in a single-stage microfluidic platform by numeric simulation. The DEP is enabled by embedding interdigitated electrodes with alternating field control on a serpentine microchannel to avoid creating two-stage separation. Rather than using the electrokinetic migration of cells which slows down the throughput, the system leverages the inertial microfluidic flow to achieve high-speed continuous separation. The cell migration and cell positioning characteristics are quantified through coupled physics analyses to evaluate the effects of the applied voltages and Reynolds numbers (Re) on the separation performance. The results indicate that the introduction of DEP successfully migrates WBCs away from CTCs and that separation of MDA-231 CTCs from similar sized WBCs at a high Re of 100 can be achieved with a low voltage of magnitude 4 ×10⁶ V/m. Additionally, the viability of MDA-231 CTCs is expected to be sustained after separation due to the short-term DEP exposure. The developed technique could be exploited to design active microchips for high-throughput separation of mixed cell beads despite their significant size overlap, using DEP-modified inertial focusing controlled simply by adjusting the applied external field.     

Continuous particle separation in spiral microchannels using Dean flows and differential migration

Microparticle separation and concentration based on size has become indispensable in many biomedical and environmental applications. In this paper we describe a passive microfluidic device with spiral microchannel geometry for complete separation of particles. The design takes advantage of the inertial lift and viscous drag forces acting on particles of various sizes to achieve differential migration, and hence separation, of microparticles. The dominant inertial forces and the Dean rotation force due to the spiral microchannel geometry cause the larger particles to occupy a single equilibrium position near the inner microchannel wall. The smaller particles migrate to the outer half of the channel under the influence of Dean forces resulting in the formation of two distinct particle streams which are collected in two separate outputs. This is the first demonstration that takes advantage of the dual role of Dean forces for focusing larger particles in a single equilibrium position and transposing the smaller particles from the inner half to the outer half of the microchannel cross-section. The 5-loop spiral microchannel 100 microm wide and 50 microm high was used to successfully demonstrate a complete separation of 7.32 microm and 1.9 microm particles at Dean number De = 0.47. Analytical analysis supporting the experiments and models is also presented. The simple planar structure of the separator offers simple fabrication and makes it ideal for integration with on-chip microfluidic systems, such as micro total analysis systems (muTAS) or lab-on-a-chip (LOC) for continuous filtration and separation applications.