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Label-free cancer cell separation from whole blood on centrifugal microfluidic platform using hydrodynamic technique 利用流体力学技术在离心微流体平台上从全血中分离无标记癌细胞
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2024-01-11 DOI: 10.1007/s10404-023-02704-w
Chun-Chi Lin, Jui-Chi Tsai, Yi-Zhi Liu, Ju-Nan Kuo

The separation of cancer cells from blood samples is one of the most crucial tasks in cancer research. However, existing methods tend to be expensive and labor intensive. Accordingly, the present study proposes a low-cost platform that uses hydrodynamic effects for the label-free separation of cancer cells from whole blood samples using a simple centrifugal microfluidic device consisting of a Y-shaped microchannel, a contraction–expansion array (CEA) microchannel, and a bifurcation region. To enhance the separation efficiency, the input branches of the Y-shaped microchannel are designed with different widths to generate a sheath flow rate greater than the sample flow rate. As the sample flows through the CEA microchannel, the cancer cells are separated from the blood cells through inertial effects and the bifurcation law. Finally, the cancer cells are collected from the low-flow-rate branch of the bifurcation region. The feasibility of the device is first demonstrated by numerical simulations. Experimental trials are then performed to separate K562 cancer cells from blood samples with various hematocrit concentrations at disk rotational speeds ranging from 1000 to 3000 rpm. The experimental results show that the cancer cells can be successfully separated from a diluted blood sample with a ratio of 1:1.2 × 105 K562 cells to blood cells with a high efficiency of 90% at an angular velocity of 2000 rpm.

从血液样本中分离癌细胞是癌症研究中最关键的任务之一。然而,现有的方法往往成本高昂、劳动强度大。因此,本研究提出了一种利用流体力学效应从全血样本中无标记分离癌细胞的低成本平台,该平台由一个简单的离心微流控装置组成,包括一个 Y 型微通道、一个收缩膨胀阵列(CEA)微通道和一个分叉区。为了提高分离效率,Y 型微通道的输入分支设计成不同的宽度,以产生大于样品流速的鞘状流速。当样品流经 CEA 微通道时,癌细胞通过惯性效应和分叉规律从血细胞中分离出来。最后,从分叉区域的低流速分支收集癌细胞。首先通过数值模拟证明了该装置的可行性。然后进行实验,在圆盘转速为 1000 至 3000 转/分钟的条件下,从不同血细胞比容浓度的血液样本中分离 K562 癌细胞。实验结果表明,在角速度为 2000 rpm 时,可以成功地从 K562 细胞与血细胞比例为 1:1.2 × 105 的稀释血液样本中分离出癌细胞,分离效率高达 90%。
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引用次数: 0
Correction: Computation of flow rates in rarefied gas flow through circular tubes via machine learning techniques 更正:通过机器学习技术计算稀薄气体流经圆管时的流速
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2024-01-11 DOI: 10.1007/s10404-023-02706-8
F. Sofos, C. Dritselis, S. Misdanitis, T. Karakasidis, D. Valougeorgis
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引用次数: 0
Superhydrophobic treatment of PDMS-based microfluidic devices using CO2 laser ablation 利用二氧化碳激光烧蚀技术对基于 PDMS 的微流控设备进行超疏水处理
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2023-12-30 DOI: 10.1007/s10404-023-02698-5
Zhang Yajun, Liu Jingji, Yumeng Xie, Kunming Liang, Zhe Zhang, Chen Yang, Fan Yiqiang

This study proposed a two-step simple method for rapid superhydrophobic surface modification of PDMS for PDMS-based microfluidics. A laser-patterned PMMA plate was used as the mask for the following selective CO2 laser surface treatment on PDMS. The water contact angle, SEM and ATR-FTIR analysis were conducted for the characterization of the proposed superhydrophobic surface modification method for PDMS. The result shows that the water contact angle on the modified PDMS surface reaches around 160° with the laser power of 12 W and with a scanning speed of 60 mm/s. This method aims to develop a faster, easier, and low-cost method for selective superhydrophobic modification method for PDMS-based microfluidic devices. The proposed method could have wide applications potentials in the microfluidics field, especially for PDMS-based droplet microfluidics.

本研究提出了一种分两步对 PDMS 进行快速超疏水表面改性的简单方法,用于基于 PDMS 的微流控技术。以激光刻制的 PMMA 板为掩膜,对 PDMS 进行选择性 CO2 激光表面处理。对所提出的 PDMS 超疏水表面改性方法进行了水接触角、扫描电镜和 ATR-FTIR 分析。结果表明,在激光功率为 12 W、扫描速度为 60 mm/s 的条件下,改性后的 PDMS 表面的水接触角达到 160°左右。该方法旨在为基于 PDMS 的微流控器件开发一种更快、更简便、更低成本的选择性超疏水改性方法。该方法在微流控领域,尤其是基于 PDMS 的液滴微流控领域具有广泛的应用前景。
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引用次数: 0
Plane-symmetric co-flow capillary for the generation of monodisperse droplets 用于生成单分散液滴的平面对称共流毛细管
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2023-12-29 DOI: 10.1007/s10404-023-02703-x
Yao Gong, Lili Zou, Jang Min Park, Kai You, Xiang Yi, Bin Li

This study proposes a novel co-flow capillary microfluidic device that can generate highly monodisperse droplets and polymeric microspheres. The device mainly consists of two self-aligning special-shaped polymeric capillaries. The outer capillary features a gradually contracting and expanding geometry, and the inner has an elliptical cross section at the end. The elliptical nozzle of the inner capillary fits into the contraction region of the outer capillary, and so assembled device, namely a plane-symmetric co-flow capillary, benefits from the self-alignment of the capillaries. The design and manufacturing process of the device are outlined, including a discussion on how the processing conditions affect the capillary geometry. Subsequently, the proposed device is used for droplet generation tests, and the diameter distribution of generated droplets and their influencing factors are investigated. The droplet generation mechanism with the elliptical nozzle is discussed with the help of modeling and simulation. Furthermore, monodisperse porous polymeric microspheres are fabricated using the proposed device, and their porous features are characterized. The results show that the proposed device can produce monodisperse droplets with a mean diameter of a few hundred micrometers and a coefficient of variance (CV) of less than 1%, reflecting the stability of the device. Additionally, porous polymeric microspheres could be successfully produced, and the CV of the size distribution is only around 1%.

本研究提出了一种新型共流毛细管微流体装置,可产生高度单分散的液滴和聚合物微球。该装置主要由两个自对准的特殊形状聚合物毛细管组成。外层毛细管的几何形状是逐渐收缩和膨胀的,内层毛细管的末端是椭圆形截面。内侧毛细管的椭圆形喷嘴与外侧毛细管的收缩区域相吻合,这样组装起来的装置,即平面对称的共流毛细管,得益于毛细管的自对准。本文概述了该装置的设计和制造过程,包括对加工条件如何影响毛细管几何形状的讨论。随后,利用所提出的装置进行了液滴生成测试,并研究了生成液滴的直径分布及其影响因素。在建模和模拟的帮助下,讨论了椭圆形喷嘴的液滴生成机制。此外,还利用所提出的装置制造了单分散多孔聚合物微球,并对其多孔特征进行了表征。结果表明,所提出的装置可以制造出平均直径为几百微米的单分散液滴,方差系数(CV)小于 1%,这反映了该装置的稳定性。此外,还能成功制备多孔聚合物微球,其尺寸分布的 CV 值仅为 1%左右。
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引用次数: 0
Unidirectional particle transport in microfluidic chips operating in a tri-axial magnetic field for particle concentration and bio-analyte detection 在三轴磁场中运行的微流控芯片中的颗粒单向传输,用于颗粒浓缩和生物分析检测
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2023-12-24 DOI: 10.1007/s10404-023-02702-y
Negar Sadeghidelouei, Roozbeh Abedini-Nassab

The Controlled transport of tiny particles in a microfluidic environment has attracted the attention of numerous researchers in the field of lab-on-a-chip. In this work, for the first time, a fully operational microfluidic chip composed of asymmetric magnetic tracks that unidirectionally transport multiple magnetic particles synced with a general tri-axial magnetic field is proposed. In this innovative chip, the particle motion is analogous to the electron transport in electrical diodes, with similar controllability and automation levels not seen in other single-particle manipulation systems. The vertical bias component of the magnetic field by providing a repulsive force between the particles and preventing undesired cluster formation, makes the proposed chip even more similar to the electrical circuits. Additionally, the chip functions as a highly sensitive biosensor capable of detecting extremely low levels of DNA fragments using ligand-functionalized magnetic beads. The uniqueness of the proposed sensor lies in the introduction of a novel particle/analyte concentrator based on the proposed diodes, which enhances its detection sensitivity. This sensitivity is even further enhanced by a single-particle and pair detection image processing code. Furthermore, the background noise is reduced by eliminating the unwanted bead cluster formation commonly observed in previous works. The proposed device serves as a high-throughput unidirectional transport system at the single-particle resolution, offering sensitive bio-detection with many applications in biomedicine.

微流体环境中微小颗粒的可控传输吸引了芯片实验室领域众多研究人员的关注。在这项研究中,我们首次提出了一种完全可操作的微流控芯片,它由非对称磁轨组成,可在一般三轴磁场中同步单向传输多个磁性粒子。在这一创新芯片中,粒子运动类似于电子二极管中的电子传输,具有其他单粒子操纵系统所不具备的类似可控性和自动化水平。磁场的垂直偏置分量可在粒子之间产生排斥力,防止形成不必要的粒子簇,从而使拟议的芯片与电路更加相似。此外,该芯片还可用作高灵敏度生物传感器,利用配体功能化磁珠检测极低水平的 DNA 片段。该传感器的独特之处在于采用了基于二极管的新型粒子/分析物浓缩器,从而提高了检测灵敏度。单粒子和成对检测图像处理代码进一步提高了灵敏度。此外,由于消除了以往工作中常见的不需要的微珠簇形成,从而降低了背景噪声。所提出的装置可作为单粒子分辨率的高通量单向传输系统,提供灵敏的生物检测,在生物医学中有着广泛的应用。
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引用次数: 0
Experimental investigation of microparticle focusing in SiO2 nanofluids inside curvilinear microchannels 曲线微通道内 SiO2 纳米流体中微颗粒聚焦的实验研究
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2023-12-20 DOI: 10.1007/s10404-023-02700-0
Arsalan Nikdoost, Pouya Rezai

Curvilinear microchannels have enabled high throughput sized-based separation and manipulation of microparticles. Real life applications usually deal with fluid’s non-Newtonian behavior, where particles dynamics are altered compared to Newtonian mediums. Despite multiple reports on particle manipulation in shear-thinning fluids, no fundamental experimental investigation has been reported on microparticle focusing behavior inside shear-thickening fluids such as metallic oxide nanofluids in water (e.g., SiO2-water). These nanofluids pose unique thermal characteristics and exhibit a drastic increase in viscosity as the shear rate rises in the microchannel. Here, we investigate the particle focusing behavior of co-flows of SiO2 nanofluids inside curved microchannels with various channel widths and radii of curvature. We also report on the effect of nanofluid concentration, fluid axial velocity, and the particle size on particle migration. We observed a behavioral change in particle migration in SiO2 nanofluids, where the shear-dependent effect could enhance the particle focusing at lower flow rates. Moreover, the dominance of Dean drag at higher axial velocities would dominate the particle migration and transfer them towards two focusing peaks close to the sidewalls. A thorough investigation of particle behavior in nanofluids inside curved microchannels could enable future applications in heat exchangers, solar energy collectors, and nanoplastic detection.

曲线微通道实现了微颗粒的高通量大小分离和操作。现实生活中的应用通常涉及流体的非牛顿行为,与牛顿介质相比,粒子的动力学会发生改变。尽管有许多关于在剪切稀化流体中操纵微粒的报道,但还没有关于微粒在剪切增稠流体(如水中的金属氧化物纳米流体,如二氧化硅-水)中聚焦行为的基础实验研究报道。这些纳米流体具有独特的热特性,随着微通道中剪切速率的上升,粘度也会急剧增加。在此,我们研究了具有不同通道宽度和曲率半径的弯曲微通道内二氧化硅纳米流体共流的粒子聚焦行为。我们还报告了纳米流体浓度、流体轴向速度和颗粒大小对颗粒迁移的影响。我们观察到颗粒在二氧化硅纳米流体中的迁移行为发生了变化,其中剪切依赖效应可在较低流速下增强颗粒聚焦。此外,在较高的轴向速度下,迪安阻力将主导颗粒的迁移,并将颗粒向靠近侧壁的两个聚焦峰转移。对弯曲微通道内纳米流体中的粒子行为进行深入研究,有助于未来在热交换器、太阳能收集器和纳米塑料检测中的应用。
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引用次数: 0
Simulation of microfluidic intracellular delivery based on the synergy of cell squeezing and electrical field 基于细胞挤压和电场协同作用的微流体细胞内输送模拟
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2023-12-18 DOI: 10.1007/s10404-023-02701-z
Jianfeng Chen, Han Liu, Chuan Li, Xiaoxiao Chen, Yichuan Dai

In recent years, the microfluidic squeezing method for cell intracellular delivery has demonstrated high efficiency and generalizability. This approach, however, still faces difficulties in effectively transfecting large molecules. Integration of this method with other membrane disruption strategies can enhance intracellular delivery efficiency and cell viability. Notably, the combination of microchannel squeezing and electric fields emerges as the most crucial strategy. The cell membrane is rapidly perforated in a microfluidic device, and then an electric field is introduced to further improve the permeability of the plasma membrane, allowing transmembrane transit of impermeable molecules. Nevertheless, the underlying mechanism of the combined squeezing and electroporation method on cell membrane destabilization and material transport remains unclear. Thus, this paper aims to develop a computational model to investigate the intracellular delivery process influenced by various external stimuli and to examine the implications of mixing external stimuli as well as the distinct effects of electric and squeezing on intracellular delivery. Meanwhile, we modified the squeezing parameters (microchannel size and cell velocity) and the electric field parameters (pulse length, electric field strength, etc.) to optimize the cell’s absorption of foreign substances. The simulation results indicate that a decrease in the contraction width, an increase in the contraction length, and an increase in the average cell velocity could promote the squeezing deformation of the cell as well as the formation of pores on the cell membrane. And the joint action of cell squeezing and electric field enhances cellular absorption of substances. In addition, the change of electrical parameters also affects the results of cell squeezing in conjunction with the electric field. For example, the increased length of electric field pulses improves the cell membrane permeability. However, the electric field intensity must be set in a reasonable range (< several kV/cm) to prevent cell inactivation.

近年来,用于细胞内递送的微流体挤压法已显示出高效性和通用性。然而,这种方法在有效转染大分子方面仍面临困难。将这种方法与其他膜破坏策略相结合,可以提高细胞内递送效率和细胞活力。值得注意的是,微通道挤压和电场的结合是最关键的策略。细胞膜在微流体装置中迅速穿孔,然后引入电场,进一步提高质膜的通透性,使不通透的分子得以跨膜转运。然而,挤压和电穿孔相结合的方法对细胞膜失稳和物质转运的潜在机制仍不清楚。因此,本文旨在建立一个计算模型,研究各种外部刺激对细胞内输送过程的影响,并探讨混合外部刺激的影响以及电穿孔和挤压对细胞内输送的不同影响。同时,我们修改了挤压参数(微通道尺寸和细胞速度)和电场参数(脉冲长度、电场强度等),以优化细胞对外来物质的吸收。模拟结果表明,收缩宽度的减小、收缩长度的增加和细胞平均速度的提高可促进细胞的挤压变形以及细胞膜上孔隙的形成。细胞挤压和电场的共同作用增强了细胞对物质的吸收。此外,电参数的变化也会影响细胞挤压与电场共同作用的结果。例如,增加电场脉冲的长度可提高细胞膜的通透性。不过,电场强度必须设定在合理的范围内(几千伏/厘米),以防止细胞失活。
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引用次数: 0
Co-printing of micro/nanostructures integrated with preconcentration to enhance protein detection 集成预浓缩功能的微/纳米结构共打印技术可提高蛋白质检测能力
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2023-12-09 DOI: 10.1007/s10404-023-02699-4
Yi-Jung Lu, Han-Yun Hsieh, Wen-Fai Yang, Kuang-Chong Wu, Hidetoshi Tahara, Pei-Kuen Wei, Horn-Jiunn Sheen, Yu-Jui Fan

This paper reports a fabrication method that can make microstructures such as microfluidic channels and nanostructures to generate surface plasmon resonance (SPR) signals in one-step using hot embossing. We first made a micro/nanostructural mold on a silicon substrate through sequential e-beam lithography, reactive ion etching (RIE), photolithography, and inductively coupled plasma RIE. The fabricated mold and cyclo-olefin polymer (COP) film were pressed between two flat, heated metal bases under optimal conditions, and the micro/nanostructures were complementarily transferred to the COP film. After depositing a thin aluminum film onto the nanostructure, the device was completed by patterning Nafion that crossed two channels and a nearby nanostructure, and by bonding the COP film to a flat polydimethylsiloxane (PDMS) substrate with holes punched for the inlets and outlets. SPR signals of the nanostructures of the microfluidic channel were calibrated using glycerol solutions of different percentages, and a wavelength sensitivity of 393 nm/refractive index unit was found for the Al-based nanoslit SPR sensing chip. To detect macromolecules, we first modified bovine serum albumin (BSA) onto the surface of the SPR chip and then allowed different concentrations of anti-BSA samples to flow into the device. A calibration curve for detecting anti-BSA was constructed, and anti-BSA detection levels with and without preconcentration were compared.

本文报告了一种制造方法,该方法可以利用热压印技术一步制成微流体通道等微结构和纳米结构,从而产生表面等离子体共振(SPR)信号。我们首先通过电子束光刻、活性离子刻蚀(RIE)、光刻和电感耦合等离子体 RIE 在硅基底上制作了微/纳米结构模具。在最佳条件下,将制作好的模具和环烯烃聚合物(COP)薄膜压在两个平整、加热的金属基座之间,然后将微/纳米结构互补地转移到 COP 薄膜上。在纳米结构上沉积一层薄铝膜后,对穿过两个通道和附近纳米结构的 Nafion 进行图案化,并将 COP 薄膜粘合到平面聚二甲基硅氧烷(PDMS)基底上,在入口和出口处打孔,从而完成了该装置。使用不同比例的甘油溶液对微流体通道纳米结构的 SPR 信号进行了校准,发现铝基纳米光 SPR 传感芯片的波长灵敏度为 393 nm/折射率单位。为了检测大分子,我们首先在 SPR 芯片表面修饰了牛血清白蛋白(BSA),然后让不同浓度的抗 BSA 样品流入该装置。我们构建了检测抗 BSA 的校准曲线,并比较了有无预浓缩的抗 BSA 检测水平。
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引用次数: 0
Low-cost sheath-less microfluidic impedance cytometry for point-of-care applications 低成本的无护套微流控阻抗细胞术在护理点的应用
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2023-12-06 DOI: 10.1007/s10404-023-02697-6
Seied Ali Hosseini, Sanaz Bahrami, Leila Zolghadr, Nematollah Gheibi

The present study introduces a microfluidic device that employs impedance measurement to accurately enumerate cells in suspension. Prior to the development of this device, impedance cytometry microfluidic chips necessitated the use of planar electrodes and sheath fluids, which complicated the system, or utilized small constricted regions that impeded cell movement and reduced operational efficiency. This newly developed device is capable of sensitive and rapid cell enumeration without the need for sheath fluid or planar electrodes, making it suitable for point-of-care applications. Instead of thin-film electrodes, the same needles used for liquid injection were implemented for impedance measurement, thus simplifying the device. The physical parameters of the device were designed using analytical and computer-aided simulations to determine the maximum dimensions required for sensitive detection of human cells. Simulations were also employed to investigate the effects of flow rates, cell shape, and injection method on device performance, and results were compared with experimental findings. Finally, this novel device was tested for its ability to count MCF7 cells at various flow rates and concentrations, with a limit of detection of 32.3 cells per μL being achieved in 1 mL/hr flow rate.

本研究介绍了一种采用阻抗测量的微流控装置来精确计数悬浮细胞。在此设备开发之前,阻抗细胞术微流控芯片需要使用平面电极和鞘液,这使系统复杂化,或者使用阻碍细胞运动和降低操作效率的小收缩区域。这种新开发的设备能够灵敏和快速的细胞计数,而不需要鞘液或平面电极,使其适用于护理点应用。代替薄膜电极,使用与液体注射相同的针头进行阻抗测量,从而简化了设备。利用分析和计算机辅助模拟设计了该装置的物理参数,以确定灵敏检测人体细胞所需的最大尺寸。模拟研究了流速、电池形状和注射方式对器件性能的影响,并与实验结果进行了比较。最后,对该装置在不同流速和浓度下计数MCF7细胞的能力进行了测试,在1 mL/hr流速下,检测限为每μL 32.3个细胞。
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引用次数: 0
Quantitative analysis for sweat-absorbing times of paper-based microfluidic chips 纸基微流控芯片吸汗次数的定量分析
IF 2.8 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2023-12-02 DOI: 10.1007/s10404-023-02696-7
Heyue Huang, Chuanpei Xu, Peng Long, Yanzhang Chen, Xijun Huang, Zheng Liu, Hong Yang

Structures of paper-based microfluidic chips affect the sweat-absorbing time when they are used for sweat analysis. For the first time, we use COMSOL to establish two types of paper-based chip sweat-absorbing models that can quantitatively analyze this phenomenon. The standard model contains 1089 sweat glands, and the simplified model simplifies it according to the idea of finite element division, including 81 sweat glands. Sweat flows in from the bottom of the paper-based chip and out from the electrode contact surface (the upper surface of the central cylinder of the paper-based chip). Both models contain six paper-based chip structures, use Richards’ equation as the governing equation, set the outflow velocity to 0, and set the sweating rate of a sweat gland at 0.6 (mu)L/min. In the standard model, it takes only 46 s for the paper-based structure with the fastest sweat-absorbing speed to completely saturate the electrode contact surface with sweat (meaning the sweat-absorbing time is 46 s), which is 13.06(%) shorter than that of the slowest structure. In the simplified model, the top 3 structures of sweat-absorbing speed are consistent with the standard model. The simulation results show that the sweat-absorbing time is positively correlated with the H value of the bottom surface of the paper-based structure (defined as the area of the bottom surface /the area of sweat glands covered by the bottom surface), which can be proved by analytical and experimental methods. The analytical method proves that this conclusion can be generalized to other sweating rate conditions.

纸基微流控芯片在进行汗液分析时,其结构对吸汗时间有影响。我们首次使用COMSOL建立了两种纸基芯片吸汗模型,可以定量分析这一现象。标准模型包含1089个汗腺,简化模型根据有限元划分的思想进行简化,包括81个汗腺。汗液从纸基芯片的底部流入,从电极接触面(纸基芯片中心圆筒的上表面)流出。两种模型均包含6个基于纸张的芯片结构,采用Richards方程作为控制方程,将流出流速设为0,将汗腺排汗速率设为0.6 (mu) L/min。在标准模型中,吸汗速度最快的纸基结构将汗水完全浸透电极接触面只需要46 s(即吸汗时间为46 s),比吸汗速度最慢的纸基结构缩短了13.06 (%)。简化模型中吸汗速度的前3个结构与标准模型一致。仿真结果表明,吸汗时间与纸基结构底面的H值(定义为底面面积/底面覆盖的汗腺面积)呈正相关,可以通过分析和实验方法加以证明。分析方法证明,该结论可推广到其他出汗率条件。
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引用次数: 0
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Microfluidics and Nanofluidics
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