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压力驱动双膜离子浓差极化系统中带电粒子分离与富集数值模拟研究

勾易行, 孙国伟, 孙润泽, 李子瑞

勾易行, 孙国伟, 孙润泽, 李子瑞. 压力驱动双膜离子浓差极化系统中带电粒子分离与富集数值模拟研究. 力学学报, 2024, 56(5): 1241-1250. DOI: 10.6052/0459-1879-23-601
引用本文: 勾易行, 孙国伟, 孙润泽, 李子瑞. 压力驱动双膜离子浓差极化系统中带电粒子分离与富集数值模拟研究. 力学学报, 2024, 56(5): 1241-1250. DOI: 10.6052/0459-1879-23-601
Gou Yixing, Sun Guowei, Sun Runze, Li Zirui. Numerical simulation of charged particle separation and enrichment in a pressure driven dual-membrane ion concentration polarization system. Chinese Journal of Theoretical and Applied Mechanics, 2024, 56(5): 1241-1250. DOI: 10.6052/0459-1879-23-601
Citation: Gou Yixing, Sun Guowei, Sun Runze, Li Zirui. Numerical simulation of charged particle separation and enrichment in a pressure driven dual-membrane ion concentration polarization system. Chinese Journal of Theoretical and Applied Mechanics, 2024, 56(5): 1241-1250. DOI: 10.6052/0459-1879-23-601

压力驱动双膜离子浓差极化系统中带电粒子分离与富集数值模拟研究

基金项目: 国家自然科学基金(12302353, 12072100), 河北省高等学校自然科学研究青年拔尖人才(BJK2023016)和中央引导地方科技发展资金(226Z1701G)资助项目
详细信息
    通讯作者:

    勾易行, 副教授, 主要研究方向为微纳尺度粒子操控. E-mail: gouyx@hebut.edu.cn

    李子瑞, 教授, 主要研究方向为计算力学及微纳流体力学. E-mail: lizirui@gmail.com

  • 中图分类号: O352

NUMERICAL SIMULATION OF CHARGED PARTICLE SEPARATION AND ENRICHMENT IN A PRESSURE DRIVEN DUAL-MEMBRANE ION CONCENTRATION POLARIZATION SYSTEM

  • 摘要: 微纳流体器件中的离子浓差极化现象可以高效富集低浓度粒子, 但多种粒子的富集与分离仍然存在分离效果差的问题. 文章提出了一种基于离子浓差极化现象的粒子分离与富集系统, 该系统通过设置两个离子交换膜构建两个微纳界面调控带电粒子所受的电场环境, 以DNA和牛血清白蛋白(BSA)为例, 依据不同淌度粒子所受电场力和流体曳力的竞争机制使得DNA和BSA在不同膜前富集, 进而实现二者的区位分离. 数值模拟分析了外部压力和不同离子交换膜跨膜电压的影响, 其中, 入口压力控制通道内的流体流速以影响粒子所受的流体曳力, 跨膜电压调节离子浓差极化现象以影响粒子所受的电场力. 数值模拟分析表明, 双膜系统的分离机制为不同耗尽区产生的高电场对两种粒子施加的电场力与其本身所受的流体曳力的竞争作用, 即在第一个膜前BSA所受的电场力小于流体曳力, 而DNA的受力则相反. 同时, 本文揭示了离子浓差极化形成下带电粒子在压力驱动双膜系统的富集机制. 结果表明, 当Vcm1 = 5VT, Vcm2 = 10VT, P0 = 400 Pa时, DNA和BSA可实现高效的区位分离且二者的富集倍数可分别达到1.2 × 105和6.0 × 104, 这将为多带电粒子的同时富集并分离及多级离子浓差极化级联系统设计提供新的思路和理论指导.
    Abstract: Ion concentration polarization phenomenon in micro-nano fluidic devices can efficiently enrich low-concentration particles, yet there remains an issue with the separation and enrichment of multiple particles with poor separation efficiency. In this paper, we propose a particle separation and enrichment system based on the ion concentration polarization phenomenon. This system constructs two micro-nano interfaces by employing two ion exchange membranes to regulate the electric field environment experienced by charged particles. This model takes DNA and BSA as examples, which enables the differential enrichment of DNA and bovine serum albumin (BSA) in front of different membranes, thus achieving their positional separation. Numerical simulations analyze the effects of external pressure and different transmembrane voltages of the ion exchange membranes. Specifically, inlet pressure controls the fluid velocity within the channel, affecting the fluid drag force experienced by particles. The transmembrane voltage regulates the ion concentration polarization phenomenon, affecting the electric field force experienced by particles. The numerical simulation analysis demonstrates that the separation mechanism of the dual-membrane system involves the competition between the high electric field generated in different depletion zones and the fluid drag force applied to the particles. This competition scenario indicates that in front of the first membrane, the electric field force on BSA is smaller than the fluid drag force, while the opposite is observed for DNA. Simultaneously, this paper reveals the mechanism of charged particle enrichment in a pressure-driven dual-membrane system formed under ion concentration polarization. The results indicate that under Vcm1 = 5VT, Vcm2 = 10VT, and P0 = 400 Pa, efficient positional separation of DNA and BSA is achievable. The enrichment multiples for DNA and BSA respectively reach 1.2 × 105 and 6.0 × 104. This offers a new perspective and theoretical guidance for simultaneously enriching and separating multiple charged particles and the design of multistage ion concentration polarization cascade system.
  • 微流控芯片也被称为片上实验室, 是一种以在微米尺度空间对流体进行操控为主要特征的科学技术. 与传统的大型仪器相比, 该技术将样品制备、富集、分离、收集和检测等流程集中于芯片上进行[1], 具有快速、高效、低消耗、集成化和微型化等优点, 因此已应用于细胞生物学[2]、药物筛选[3]、遗传分析[4]、化学组分鉴定[5]和食品检测[6]等多个领域.

    微流控芯片用于化学或者生物分析时, 给定的样本浓度一般很低, 因此能够有效地从低浓度样品中预浓缩分子, 具有重要价值. 目前实现样本的预浓缩的方法主要有场放大样品堆积(field amplified sample stacking, FASS)[7-8]、等电聚焦 (isoelectric focusing, IEF) [9-10]、等速电泳(isotachophoresis, ITP)[11-12]和离子浓差极化(ion concentration polarization, ICP )[13-14]. ICP是发生在微纳米流体界面的基本电化学传输现象, 在过去的几十年里引起了广泛研究. 为了更清楚地了解ICP的机理, 研究人员对其预浓缩的特性[15]和非线性电动流[16]做了大量的理论和实验研究. 早在2005年, ICP的富集效应已经得到实验验证, 其富集的蛋白质浓度可达百万倍[17]. 为了实现更高倍数的富集, 研究者研究了不同因素的影响, 如缓冲液浓度[18]、膜的厚度[19]、微通道形状[20-21]和施加的电压[22]等. 如Ouyang等[23]开发的一种分层微流控分子富集系统, 30 min内可以实现生物分子和蛋白质十亿倍的富集. 由于ICP在痕量粒子富集方面的优势, 近年来其应用也扩展到海水淡化[24-25]、能量收集[26-27]和生物传感[28]等领域.

    除了对粒子富集效果的研究, 研究者还试图通过ICP进行多物质富集和分离, 实现对复杂样本的提取检测. Song等[29]提出了一种基于Nafion薄膜的微纳流体装置, 利用ICP产生的梯度电场富集并分离, 成功将两种DNA富集在Nafion薄膜前的不同位置. Chiu等[30]提出一种结合收敛微通道和Nafion纳米多孔膜的流体微芯片, 利用收敛通道提高预富集效果和改进分离性能, 通过实验分离带负电荷的牛血清白蛋白(BSA)、四甲基罗丹明(TAMRA)和荧光聚合物珠子组成的混合样品, 证明了该装置的可行性. Choi等[31]在Nafion薄膜设计微腔结构并集成了气动微阀, 通过将不同分离物富集到不同腔室, 并控制微阀开关, 实现带电物质分离富集, 实验中成功将磺酰罗丹明B和Alexa Fluor 488富集在不同腔室, 并控制微阀收集到30倍的Alexa.

    尽管目前的研究已经证明了利用ICP效应在多带电粒子富集和分离的有效性, 但目前ICP系统多带电粒子分离也仅限于单一离子交换膜前的区位分离, 难以进行后续的提取. 基于此, 本文提出了一种基于ICP的压力驱动双膜富集系统实现带电离子的分离和富集, 通过双膜的设置构造并行的两个离子耗尽区, 进而使得电泳迁移率不同的带电粒子在强电场屏障下实现分离. 本文利用数值模拟来阐述所提出富集分离装置的基本机理, 阐明关键控制参数的影响, 进而为后续的分离粒子提取提供有利条件.

    图1所示, 双膜富集分离系统主要由主通道、离子交换膜和缓冲液通道组成, 主通道设置有两个入口, 一个出口, 为了方便起见, 定义为inlet 1, inlet 2和outlet, inlet 1注入KCl, DNA和BSA的混合溶液, inlet 2注入KCl溶液, outlet收集回收液, 在inlet 1和inlet 2通道内嵌有一个阳离子交换膜(cation exchange membrane, CEM), inlet 2和outlet通道之间也嵌有一个CEM. CEM连接主通道和缓冲液通道, 缓冲液为KCl溶液.

    图  1  系统示意图
    Figure  1.  System diagram

    微通道表面在电解液中通常会带有一定量的电荷, 吸引溶液中的反粒子而形成双电层, 由于在其他位置保持电中性, 这样就使得溶液中产生净电荷, 当外部施加电压时, 溶液便会形成定向流动即电渗流(electroosmotic flow, EOF). 在CEM附近, 垂直电场EN驱动阳离子穿过CEM进入缓冲液通道, 同时排斥阴离子远离CEM, 溶液中由于离子电中性条件, 要求阳离子浓度也要随之降低, 因此CEM一侧形成离子耗尽区, 在另一侧阳离子穿过膜, 进入缓冲液通道, 由于离子保持电中性, 使得在这一侧形成离子富集区, 在稳定状态下, 阴离子因浓度差产生的扩散通量完全抵消其在电场作用下的电迁移通量, 在CEM的一侧附近形成一个浓度相对于主体溶液线性降低的扩散边界层(diffusion boundary layer, DBL), 同时另一侧附近形成浓度逐步升高的DBL, 这一现象称为ICP [32]. 在扩散边界层由于其电导率低, 所以形成一个梯度电场.

    带电物质在微通道内主要受到流体曳力FD和电场力FE的作用

    $$ \qquad\qquad\qquad {{\boldsymbol{F}}_{{{\mathrm{D}}}}} = \frac{{RT{\boldsymbol{U}}}}{D} $$ (1)
    $$\qquad\qquad\qquad {{\boldsymbol{F}}_{{{\mathrm{E}}}}} = ZF{\boldsymbol{E}} $$ (2)

    式中, T是温度, U是流体速度, R是气体常数, D是扩散系数, Z是化合价, E是电场.

    当带电粒子所受FDFE相等时, 带电粒子可以富集, 当|FD| > |FE|, 带电粒子不能稳定富集. 如图2所示, ICP效应会在两个离子交换膜前产生两个强电场, 通过调控主通道内的流体速度, 带电物质所受的流体曳力相应增加, 如果DNA在第一个离子交换膜前|${\boldsymbol{F}}_{{{\mathrm{D}}}}^{{\mathrm{DNA}}} $| = |${\boldsymbol{F}}_{{{\mathrm{E}}}}^{{\mathrm{DNA}}} $|, 此时DNA富集; 而BSA在第一个离子交换膜前|${\boldsymbol{F}}_{{{\mathrm{E}}}}^{{\mathrm{BSA}}} $| < |${\boldsymbol{F}}_{{{\mathrm{D}}}}^{{\mathrm{BSA}}} $|, 在第二离子交换膜前|${\boldsymbol{F}}_{{{\mathrm{E}}}}^{{\mathrm{BSA}}} $| = |${\boldsymbol{F}}_{{{\mathrm{D}}}}^{{\mathrm{BSA}}} $|, 那么BSA在第二个电场富集, 此时就实现了带电物质在两个离子交换膜前分别富集.

    图  2  DNA和BSA在系统内的受力分析
    Figure  2.  Analysis of DNA and BSA under force in the system

    图3显示了双膜富集分离系统的模拟模型. 该模型的关键部分是一个长度为L, 宽度为H的主通道和长度为L3的支通道 , 主通道内嵌有两个长度Lm = 1 μm的阳离子交换膜, 为了方便起见, 将第一个阳离子交换膜定义为CEM1, 第二个阳离子交换膜定义为CEM2, 膜表面阳离子浓度设为Cm (这是由平衡CEM中固定电荷密度的要求所决定的). 微通道表面带负电荷, inlet 1注入KCl, DNA和BSA的混合溶液, inlet 2注入KCl溶液, outlet用来收集废液, 在inlet 1, inlet 2和outlet边界分别施加电压VL, VMVR, 诱发从左到右的电渗流(第一类电渗流), 同时在inlet 1施加压力P0, inlet 2施加压力P1, outlet施加压力P2, CEM1表面电压设置为Vm1, CEM2表面电压设置为Vm2, Vcm1 = (VL + VM)/2−Vm1, Vcm2 = (VM + VR)/2−Vm2, Vcm为跨膜电压, 用来表征没有ICP效应的外部电场确定的膜位置电压与施加在膜上的实际电压之间的差异, 也就是实际中微通道与膜连接处的电压降.

    图  3  仿真示意图
    Figure  3.  Simulation diagram

    不可压缩流体流动、离子运输和电势的控制方程为Navier-Stokes, Nernst-Plank和Possion方程描述

    $$ \rho \left[\frac{{\partial {\boldsymbol{U}}}}{{\partial t}} + \left( {{\boldsymbol{U}} \cdot \nabla } \right){\boldsymbol{U}}\right] = - \nabla P + \eta \nabla \cdot (\nabla {\boldsymbol{U}}) - {\rho _e}\nabla \varPhi $$ (3)
    $$ \nabla \cdot {\boldsymbol{U}} = 0 $$ (4)
    $$ \frac{{\partial {C_i}}}{{\partial t}} = - \nabla \cdot {{\boldsymbol{J}}_i} $$ (5)
    $$ {{\boldsymbol{J}}_i}{\text{ = }} - \left[{D_i}\nabla {C_i} + {Z_i}\left(\frac{{{D_i}F}}{{RT}}\right){C_i}\nabla \varPhi \right] + {\boldsymbol{U}}{C_i} $$ (6)
    $$ - \nabla \cdot (\varepsilon \nabla \varPhi ) = {\rho _e} $$ (7)
    $$ {\rho _e} = e\sum\limits_{i = 1}^n {{Z_i}{C_i}} $$ (8)

    式中, U是速度, P是压力, CiCi (x, y, t) 和 JiJi (x, y, t)分别表示物质i的浓度和通量. 为了方便起见, 我们用i = 1表示K + , i = 2表示Cl, i = 3表示DNA, i = 4表示BSA. ZiDi表示物质i的价态和扩散系数, Φ是电势, T是绝对温度. FR分别是法拉第常数和气体常数. ρe是自由空间电荷密度, 其中e是基本电荷. 参数ρ, ηε分别是溶液的质量密度、动态黏度和介电常数.

    在膜表面假定: (1)阴离子在膜上的通量为0; (2) CEM1和CEM2的K + 离子浓度为Cm; (3) CEM1表面的电动势为Vm1, CEM2表面的电动势为Vm2; (4)膜表面对流体不渗透, 无滑移

    $$ {{\boldsymbol{J}}_i} \cdot {\boldsymbol{n}} = 0\;\;(i = 2,3,4),{C_1} = {C_{\mathrm{m}}},{\varPhi _1} = {V_{{\mathrm{m}}1}},{\varPhi _2} = {V_{{\mathrm{m}}2}} $$ (9)

    其中n为流体计算域的外法向单位向量.

    微通道壁面边界条件为: (1)壁面带电密度为σ; (2)壁面无滑移; (3)阴阳离子均不可渗透, 即

    $$ \nabla \varPhi \cdot {\boldsymbol{n}} = {\sigma _ - }/\varepsilon ,{\boldsymbol{U}} = {\boldsymbol{0}},{{\boldsymbol{J}}_i} \cdot {\boldsymbol{n}} = 0\;\;(i = 1,2,3,4) $$ (10)

    在inlet 1边界: (1)所有离子浓度与初始浓度相同; (2)电势为VL; (3)压力为P0, 即

    $$ {C_i} = {C_{i,0}}\;(i = 1,2,3,4),\varPhi = {V_{\mathrm{L}}},P = {P_0} $$ (11)

    在inlet 2边界: (1) K + 和Cl浓度与初始浓度相同; (2)电势为VM; (3)压力为P1, 即

    $$ {C_i} = {C_{i,0}}\;(i = 1,2),\varPhi = {V_{\mathrm{M}}},P = {P_1} $$ (12)

    在outlet边界: (1)流体流动采用自由边界条件; (2)电势为VR, 即

    $$ \varPhi = {V_{\mathrm{R}}},\nabla {\boldsymbol{U}} \cdot {\boldsymbol{n}} = 0,P = {P_{\text{2}}},\nabla {C_i} \cdot {\boldsymbol{n}} = 0\;\;(i = 1,2,3,4) $$ (13)

    本文使用Comsol Multiphysics 5.6a求解耦合的Navier-Stokes方程、Nernst-Plank方程和Poisson方程, 获得稳态电势场、流场以及浓度场, 并分析其物理过程.

    在模型中, L = 200 μm, H = 0.5 μm, L3 = 20 μm, L1 = 60 μm, L2 = 40 μm和Lm = 1 μm, 膜表面阳离子浓度Cm = 2 mM, 微通道表面带负电荷, 壁面电荷密度σ = −1 mC/m2, inlet 1的离子浓度分别为C1,0 = 1 mM, C2,0 = 1 mM, C3,0 = 1.0 × 10−7 mM和C4,0 = 1.0 × 10−7 mM, inlet 2的离子浓度分别为C1,0 = 1 mM和C2,0 = 1 mM, 离子的扩散系数分别为D1 = 1.97 × 10−9 m2/s, D2 = 2.03 × 10−9 m2/s, D3 = 4.516 × 10−11 m2/s和D4 = 1.011 × 10−11 m2/s [33], 离子的价态分别为Z1 = 1, Z2 = −1, Z3 = −22和Z4 = −14, 在inlet 1, inlet 2和outlet边界分别施加电压VL = 20VT, VM = 10VT, VR = 0和VT = 25.8 mV代表热电压, 诱发从左到右的电渗流(第一类电渗流), inlet 1施加压力P0, inlet 2施加压力P1 = P0/2.4, outlet施加压力P2 = 0.

    Vcm1 = 5VT, Vcm2 = 10VTP0 = 400 Pa时, 微通道内DNA和BSA的浓度分布如图4(a)和图4(b)所示, 此时DNA富集在CEM1前, BSA富集在CEM2前.

    图  4  DNA和BSA在微通内的浓度分布
    Figure  4.  Distribution of DNA and BSA concentrations in microchannels

    图5(a)显示了微通道中心处的K + 和Cl浓度, 可以看到在系统中产生了两个耗尽区, CEM选择性地将K + 输送出主通道, 同时Cl在电力作用下会反向迁移, 这时在膜附近产生了一个低浓度的耗尽区, 在CEM1前K + 和Cl最低浓度为0.1 mM, CEM2前K + 和Cl的最低浓度为12 μM, 值得注意的是K + 和Cl浓度在通道内是存在差异的, 这是DNA和BSA取代Cl的结果, 在任何位置, 聚焦一种低迁移率的物种必须降低其他高迁移率的共带电物种的浓度, 这是因为它们的电中性条件的限制. 因此, 迁移率较高的离子部分被较低迁移率的离子所取代. 图5(b)展示了微通道中心处的DNA和BSA浓度分布, 此时DNA和BSA在两个膜前分别实现了富集且DNA在CEM1前的最高浓度为12 μM, BSA在CEM2前的最高浓度为6 μM.

    图  5  各离子在微通道内的浓度分布
    Figure  5.  Distribution of ion concentrations in microchannels

    图6(a)和图6(b)显示了CEM1和CEM2前的流场分布. 可以看出CEM2前的涡流更加明显, 这是由于跨膜电压的不同导致的. 在低电压下CEM附近的耗尽区相对稳定, 随着跨膜电压的逐渐升高, 在CEM附近的高电压或电流下, 产生电渗不稳定性波动. 这种不稳定性是由于形成了扩展空间电荷层(extended space chargr layer, ESC), 导致形成强烈的涡旋.

    图  6  CEM前的速度分布
    Figure  6.  Flow velocity distribution in front of CEM

    图7(a)和图7(b)显示了CEM1和CEM2附近的电场分布, 在CEM1和CEM2前离子的耗尽作用使得在膜前离子浓度变得极低, 低电导率的耗尽区产生了强电场, 在CEM1前负电荷电流主要由Cl携带, 在x = 37 μm处Cl浓度为0.5 mM, DNA浓度为12 μM, DNA浓度仅占Cl浓度2.3%, x = 134 μm处Cl浓度为3.2 μM, BSA浓度为6 μM, BSA的浓度约为Cl的2倍, 此时负电荷电流由BSA和Cl共同携带, 负电荷守恒要求被取代的位置的电场必须更高, 使得在CEM2前的电场呈现一个较高的平台. 如图7(a)所示, 为了比较在CEM1前DNA和BSA所受电场力和流体曳力的不同, 取x = 37 μm处, 即DNA在CEM1前富集的中心位置, 取平均电场2503.4 V/m和最高流体速度0.124 mm/s比较, 1 M DNA所在200 μm长, 0.5 μm宽, 100 μm高的通道内受电场力为0.05 N, 流体曳力为0.06 N, 相差不大. 而BSA所受电场力为0.03 N, 流体曳力为0.3 N, 流体曳力为电场力10倍, 此时BSA在CEM1前的流体曳力大于电场力, 使得其可以通过CEM1, 而在电场更高的CEM2富集.

    图  7  CEM前的电场分布
    Figure  7.  Electric field distribution in front of CEM

    施加外部压力P0会促进流体的流动. 保持Vcm1 = 5VT, Vcm2 = 10VT不变, 如图8(a)所示, 当P0 = 0时, 此时微通道内的流速以电渗流为主, 当P0 增加到600 Pa时, CEM1前的平均流速u1和CEM2前的平均流速u2几乎呈线性增加, 提升了近2倍. 速度的变化使得膜附近的离子的水平通量增加, 减小了离子耗尽的程度. 因此横向电场表现略微升高的现象. 更高的流速则会冲溃耗尽区, 造成电场强度的下降. 整体而言, 此时膜前的电场只有轻微的变化, E1的变化范围约为15%, E2的变化范围约为20%. 流速的增加使得DNA和BSA两种带电粒子所受的流体曳力相应增加, 对于BSA来说, 在CEM1前的流体曳力要远远高于其所受到的电场力, 促使其较容易通过CEM1.

    图  8  Vcm1 = 5VT,Vcm2 = 10VT, CEM1和CEM2前流速和电场随P0的变化
    Figure  8.  Vcm1 = 5VT, Vcm2 = 10VT, dependence of fluid flow velocity and electric field in front of CEM1 and CEM2 with P0

    为了分析不同参数对分析物的影响, 采用富集倍数r = Ci/Ci,0表征分析物的富集程度. 如图9(a)所示, 随着压力的增加, BSA的富集倍数逐渐降低, 当压力增加到600 Pa时, 在CEM1前, BSA的富集倍数仅为6倍, 对于DNA来说, 随着流体速度的增加, 水流曳力逐渐将DNA带进微通道内, 并将其带到电场更高的位置, 使得富集倍数逐渐升高, 当压力增加到600 Pa, DNA在CEM1前的富集倍数为2.1 × 105, 对于在CEM1前, 施加的压力越高流体流速也会越高, 使得DNA和BSA分离的更加彻底, 但这并不意味着流体流速越大越好, 过高的流速使得CEM1前DNA所受的流体曳力逐渐增大, 直至高于其所受的电场力, 当压力到600 Pa时, CEM2前DNA的富集倍数为3.21 × 104, 此时在CEM2前DNA和BSA的分离并不彻底, 除此之外, 过高的速度同样使得BSA所受的流体曳力增加, 造成CEM2前的富集倍数下降(图9(b)). 压力主要影响微通道内DNA和BSA的流体曳力, 过高的压力使得DNA在CEM1前所受的流体曳力大于所受的电场力, 并在CEM2前富集, 造成分离效果不佳.

    图  9  Vcm1 = 5VT,Vcm2 = 10VT, DNA和BSA的富集倍数随P0的变化
    Figure  9.  Vcm1 = 5VT, Vcm2 = 10VT, dependence of enrichment factor of DNA and BSA with P0

    跨膜电压是诱发ICP产生的重要条件, 在系统中起着至关重要的作用. 当压力P0 = 400 Pa, CEM2的跨膜电压Vcm2 = 10VT, Vcm1的逐渐升高驱动更多的K+通过CEM1离开通道, 从而逐渐产生离子耗尽并进一步增强, 这也会使得其CEM1前产生更高的电场. 如图10(b)所示, 当Vcm1 < 3VT, 离子耗尽效应并不明显, 电场缓慢增长. 随着Vcm1升高, 离子耗尽区充分形成, 电场快速增加, 同时, 随着Vcm1的增加, CEM1驱动K+更快地通过, 带动流体流速逐渐升高, 当Vcm1达到8VT时, CEM1前产生涡流, 使得微通道内的速度变得迟缓甚至有略微下降.

    图  10  P0 = 400 Pa,Vcm2 = 10VT, CEM1和CEM2前流速和电场随Vcm1的变化
    Figure  10.  P0 = 400 Pa,Vcm2 = 10VT, dependence of fluid flow velocity and electric field in front of CEM1 and CEM2 with Vcm1

    图11(a)和图11(b)显示了随Vcm1的升高在CEM1前和CEM2前DNA和BSA富集倍数的变化. 当Vcm1 < 3VT时, 微通道内的流体流速并不足以将DNA带进微通道, 此时DNA所受的电场力大于其所受的流场力, 因此并不富集, 对于BSA而言, 在CEM1前所受的流体曳力大于其所受的电场力, BSA仍然可以通过CEM1进入下游, 在CEM2前富集, 当Vcm1 > 6VT时, CEM1前的耗尽区充分形成, 过高的电场屏障使得BSA并不能充分泄漏到下游, 此时在CEM1前DNA和BSA共存, 分离并不彻底. CEM2前由于流体流速的增加, 而电场几乎没有变化(图5(b)), 使得BSA所受的流体曳力增加, 部分BSA仍然不可避免地泄漏到下游, 呈现出来是富集倍数的下降, 当Vcm1从0升高到10 VT时, BSA的富集倍数下降了约2/3. Vcm1影响微通道内流体流速和CEM1前的电场, 过高的Vcm1使得部分BSA在CEM1前所受的电场力大于其所受的流体曳力, 并在CEM1前富集, 造成分离的不充分.

    图  11  P0 = 400 Pa,Vcm2 = 10VT, DNA和BSA的富集倍数随Vcm1的变化
    Figure  11.  P0 = 400 Pa, Vcm2 = 10VT, dependence of enrichment factor of DNA and BSA with Vcm1

    压力P0 = 400 Pa, CEM1的跨膜电压Vcm1 = 5VT, Vcm2逐渐升高对于系统的影响如图12(a)和图12(b)所示. 随着 Vcm2的逐渐升高, 驱动更多的K+通过CEM2离开通道, 带动流体流动增加, 同时CEM2前的耗尽区逐渐形成而产生更高的电场. 表现在u1u2的增加, 对于电场强度而言, Vcm2的升高主要影响E2的升高, 同时在一定范围内不会影响CEM1前的耗尽作用, 这里的影响指的主要是流速的影响, 前面我们已经提到过, 在一定范围内的流速增加不会明显改变电场强度, 但是过高的流速会破化耗尽区造成电场的下降, 当Vcm2升高到40VT时, E1开始有较为明显的下降趋势, 升高到60VT时已经下降了约60%, 这对整个系统来说是不利的.

    图  12  P0 = 400 Pa,Vcm1 = 5VT, CEM1和CEM2前流速和电场随Vcm2的变化
    Figure  12.  P0 = 400 Pa,Vcm1 = 5VT, dependence of fluid flow velocity and electric field in front of CEM1 and CEM2 with Vcm2

    对于BSA来说, 流速和CEM2前电场的增加使得其更容易通过CEM1, 同时更容易在CEM2富集, 图13(a)和图13(b)显示了随着 Vcm2的逐渐升高, CEM1前和CEM2前DNA和BSA富集倍数的变化, Vcm2的逐升高带来流速的升高, DNA和BSA所受的流体曳力增大, 使得在CEM1前BSA几乎没有残留, DNA被带到电场更高的位置富集, 获得更高的富集倍数, 但当Vcm2过高时, 过高的流速使部分DNA在CEM1前所受的流体曳力大于其所受的电场力, 不可避免地来到CEM2前, 造成分离效果下降. 值得注意的是, 过高的跨膜电压同样容易引起不稳定涡流[34], 在实验中也得到了广泛验证, Vcm2的设置应在一个合理的范围内. Vcm2影响微通道内流体流速和CEM2前的电场, 过高的Vcm2使得部分DNA在CEM1前所受的流体曳力大于其所受的电场力, 并在CEM2前富集, 造成分离的并不充分.

    图  13  P0 = 400 Pa,Vcm1 = 5VT, DNA和BSA的富集倍数随Vcm2的变化
    Figure  13.  P0 = 400 Pa, Vcm1 = 5VT, dependence of enrichment factor of DNA and BSA with Vcm2

    本文建立了一种基于离子浓差极化效应的双膜系统用于多带电粒子的分离富集. 该系统通过设置两个离子交换膜, 通过压力调控系统流速, 改变带电粒子的受力状态, 使得不同淌度的两种粒子分别在不同膜前富集进而实现分离. 本文以DNA和BSA为例系统性地探究了入口处压力及双膜两端跨膜电压对DNA和BSA富集分离的影响规律. 结果证明, 当Vcm1 = 5VT, Vcm2 = 10VTP0 = 400 Pa时, 第一个耗尽区产生的高电场对两种粒子施加的电场力小于BSA所受流体曳力, 同时大于DNA所受流体曳力, DNA在CEM1前的富集倍数达1.2 × 105, BSA的富集倍数仅为41, 而BSA在CEM2前的富集倍数达6.0 × 104, 这表明该系统可实现DNA和BSA的高效富集及有效分离. 值得注意的是, 虽然本文建立的模型为二维, 但其富集及分选机理及结果可为三维实验环境提供理论依据. 同时, 本文提出的原理仍然可以扩展到其他多种带电粒子的富集和分离. 因此, 本文提出的双膜系统将为多粒子同时富集并分离及多级ICP级联系统设计提供新的思路和理论指导.

  • 图  1   系统示意图

    Figure  1.   System diagram

    图  2   DNA和BSA在系统内的受力分析

    Figure  2.   Analysis of DNA and BSA under force in the system

    图  3   仿真示意图

    Figure  3.   Simulation diagram

    图  4   DNA和BSA在微通内的浓度分布

    Figure  4.   Distribution of DNA and BSA concentrations in microchannels

    图  5   各离子在微通道内的浓度分布

    Figure  5.   Distribution of ion concentrations in microchannels

    图  6   CEM前的速度分布

    Figure  6.   Flow velocity distribution in front of CEM

    图  7   CEM前的电场分布

    Figure  7.   Electric field distribution in front of CEM

    图  8   Vcm1 = 5VT,Vcm2 = 10VT, CEM1和CEM2前流速和电场随P0的变化

    Figure  8.   Vcm1 = 5VT, Vcm2 = 10VT, dependence of fluid flow velocity and electric field in front of CEM1 and CEM2 with P0

    图  9   Vcm1 = 5VT,Vcm2 = 10VT, DNA和BSA的富集倍数随P0的变化

    Figure  9.   Vcm1 = 5VT, Vcm2 = 10VT, dependence of enrichment factor of DNA and BSA with P0

    图  10   P0 = 400 Pa,Vcm2 = 10VT, CEM1和CEM2前流速和电场随Vcm1的变化

    Figure  10.   P0 = 400 Pa,Vcm2 = 10VT, dependence of fluid flow velocity and electric field in front of CEM1 and CEM2 with Vcm1

    图  11   P0 = 400 Pa,Vcm2 = 10VT, DNA和BSA的富集倍数随Vcm1的变化

    Figure  11.   P0 = 400 Pa, Vcm2 = 10VT, dependence of enrichment factor of DNA and BSA with Vcm1

    图  12   P0 = 400 Pa,Vcm1 = 5VT, CEM1和CEM2前流速和电场随Vcm2的变化

    Figure  12.   P0 = 400 Pa,Vcm1 = 5VT, dependence of fluid flow velocity and electric field in front of CEM1 and CEM2 with Vcm2

    图  13   P0 = 400 Pa,Vcm1 = 5VT, DNA和BSA的富集倍数随Vcm2的变化

    Figure  13.   P0 = 400 Pa, Vcm1 = 5VT, dependence of enrichment factor of DNA and BSA with Vcm2

  • [1]

    Wang YC, Han J. Pre-binding dynamic range and sensitivity enhancement for immuno-sensors using nanofluidic preconcentrator. Lab on a Chip, 2008, 8(3): 392-394 doi: 10.1039/b717220f

    [2]

    Rzhevskiy AS, Kapitannikova AY, Vasilescu SA, et al. Isolation of circulating tumor cells from seminal fluid of patients with prostate cancer using inertial microfluidics. Cancers, 2022, 14(14): 3364 doi: 10.3390/cancers14143364

    [3]

    Huang L, Zhang X, Feng Y, et al. High content drug screening of primary cardiomyocytes based on microfluidics and real-time ultra-large-scale high-resolution imaging. Lab on a Chip, 2022, 22(6): 1206-1213 doi: 10.1039/D1LC00740H

    [4]

    Lim J, Kang B, Son HY, et al. Microfluidic device for one-step detection of breast cancer-derived exosomal mRNA in blood using signal-amplifiable 3D nanostructure. Biosensors and Bioelectronics, 2022, 197: 113753 doi: 10.1016/j.bios.2021.113753

    [5]

    Basova EY, Foret F. Droplet microfluidics in (bio) chemical analysis. Analyst, 2015, 140(1): 22-38 doi: 10.1039/C4AN01209G

    [6] 秦潇潇, 张忠, 孙晓琳等. 微流控纸芯片在食品安全快速检测中的应用. 食品安全质量检测学报, 2022, 13(23): 7715-7724 (Qin Xiaoxiao, Zhang Zhong, Sun Xiaolin, et al. Application of microfluidic paper-based chips in rapid food safety testing. Journal of Food Safety & Quality, 2022, 13(23): 7715-7724 (in Chinese) doi: 10.3969/j.issn.2095-0381.2022.23.spaqzljcjs202223029

    Qin Xiaoxiao, Zhang Zhong, Sun Xiaolin, et al. Application of microfluidic paper-based chips in rapid food safety testing. Journal of Food Safety & Quality, 2022, 13(23): 7715-7724 (in Chinese) doi: 10.3969/j.issn.2095-0381.2022.23.spaqzljcjs202223029

    [7] 成伟清, 陈思嘉, 李龙飞等. 一种基于电压控制与场放大样品堆积实现离子在线双富集的电泳微芯片研究. 分析试验室, 2020, 39(10): 1143-1147 (Cheng Weiqing, Chen Sijia, Li Longfei, et al. Research on ion online dual enrichment in electrophoretic microchips based on voltage control and field amplification sample stacking. Chinese Journal of Analysis Laboratory, 2020, 39(10): 1143-1147 (in Chinese)

    Cheng Weiqing, Chen Sijia, Li Longfei, et al. Research on ion online dual enrichment in electrophoretic microchips based on voltage control and field amplification sample stacking. Chinese Journal of Analysis Laboratory, 2020, 39(10): 1143-1147 (in Chinese)

    [8]

    Li N, He S, Li C, et al. Sensitive analysis of metoprolol tartrate and diltiazem hydrochloride in human serum by capillary zone electrophoresis combining on column field-amplified sample injection. Journal of Chromatographic Science, 2021, 59(5): 465-472 doi: 10.1093/chromsci/bmab025

    [9]

    Zha G, Xiao X, Tian Y, et al. An efficient isoelectric focusing of microcolumn array chip for screening of adult beta-thalassemia. Clinica Chimica Acta, 2023, 538: 124-130 doi: 10.1016/j.cca.2022.10.021

    [10]

    Kwok T, Chan SL, Zhou M, et al. High‐efficient characterization of complex protein drugs by imaged capillary isoelectric focusing with high‐resolution ampholytes. Separation Science Plus, 2023, 6(2): 2200142 doi: 10.1002/sscp.202200142

    [11]

    Peli Thanthri SH, Linz TH. Controlling the separation of native proteins with temperature in thermal gel transient isotachophoresis. Analytical and Bioanalytical Chemistry, 2023, 415(18): 4163-4172 doi: 10.1007/s00216-022-04331-w

    [12]

    Futai N, Fukazawa Y, Kashiwagi T, et al. A modular and reconfigurable open-channel gated device for the electrokinetic extraction of cell-free DNA assays. Analytica Chimica Acta, 2022, 1200: 339435 doi: 10.1016/j.aca.2022.339435

    [13] 姜金华, 从奥博, 王月坤等. 基于三叉型离子交换膜的带电粒子微流控富集芯片的研究. 分析化学, 2022, 50(4): 585-592 (Jiang Jinhua, Cong Aobo, Wang Yuekun, et al. Research on charged particle microfluidic enrichment chip based on trivalent ion exchange membrane. Analytical Chemistry, 2022, 50(4): 585-592 (in Chinese)

    Jiang Jinhua, Cong Aobo, Wang Yuekun, et al. Research on charged particle microfluidic enrichment chip based on trivalent ion exchange membrane. Analytical Chemistry, 2022, 50(4): 585-592 (in Chinese)

    [14]

    Park S, Sabbagh B, Abu-Rjal R, et al. Digital microfluidics-like manipulation of electrokinetically preconcentrated bioparticle plugs in continuous-flow. Lab on a Chip, 2022, 22(4): 814-825 doi: 10.1039/D1LC00864A

    [15]

    Lee JH, Song YA, Han J. Multiplexed proteomic sample preconcentration device using surface-patterned ion-selective membrane. Lab on a Chip, 2008, 8(4): 596-601 doi: 10.1039/b717900f

    [16]

    De Valença J, Jõgi M, Wagterveld RM, et al. Confined electroconvective vortices at structured ion exchange membranes. Langmuir, 2018, 34(7): 2455-2463 doi: 10.1021/acs.langmuir.7b04135

    [17]

    Wang YC, Stevens AL, Han J. Million-fold preconcentration of proteins and peptides by nanofluidic filter. Analytical Chemistry, 2005, 77(14): 4293-4299 doi: 10.1021/ac050321z

    [18]

    Jia M, Kim T. Multiphysics simulation of ion concentration polarization induced by a surface-patterned nanoporous membrane in single channel devices. Analytical Chemistry, 2014, 86(20): 10365-10372 doi: 10.1021/ac502726u

    [19]

    Kim M, Jia M, Kim T. Ion concentration polarization in a single and open microchannel induced by a surface-patterned perm-selective film. Analyst, 2013, 138(5): 1370-1378 doi: 10.1039/c2an36346a

    [20]

    Ngom SM, Flores-Galicia F, Delapierre FD, et al. Electropreconcentration diagrams to optimize molecular enrichment with low counter pressure in a nanofluidic device. Electrophoresis, 2020, 41(18-19): 1617-1626 doi: 10.1002/elps.202000117

    [21]

    Lee S, Park S, Kim W, et al. Nanoelectrokinetic bufferchannel-less radial preconcentrator and online extractor by tunable ion depletion layer. Biomicrofluidics, 2019, 13(3): 034113 doi: 10.1063/1.5092789

    [22]

    Wang J, Han L, Xu Z. Nano-electrokinetic ion concentration in the ion enrichment zone. Microsystem Technologies, 2019, 25: 711-717 doi: 10.1007/s00542-018-3999-7

    [23]

    Ouyang W, Han J. Universal amplification-free molecular diagnostics by billion-fold hierarchical nanofluidic concentration. Proceedings of the National Academy of Sciences, 2019, 116(33): 16240-16249 doi: 10.1073/pnas.1904513116

    [24]

    Kim D, Ihm S, Park S, et al. Concentric ion concentration polarization desalination for efficient En-bloc preconcentration and desalination. Desalination, 2021, 499: 114810 doi: 10.1016/j.desal.2020.114810

    [25] 刘伟, 龚玲艳, 朱育丹等. 嵌有离子选择性膜的微通道内增强电渗流及脱盐效应分析. 中国科学: 技术科学, 2018, 48: 17-24 (Liu Wei, Gong Lingyan, Zhu Yudan, et al. Analysis of enhanced electroosmotic flow and desalination effect in microchannels with ion-selective membranes. Science in China: Technological Sciences, 2018, 48: 17-24 (in Chinese)

    Liu Wei, Gong Lingyan, Zhu Yudan, et al. Analysis of enhanced electroosmotic flow and desalination effect in microchannels with ion-selective membranes. Science in China: Technological Sciences, 2018, 48: 17-24 (in Chinese)

    [26]

    Qian F, Yan H, Jiao K, et al. Pressure-driven electrokinetic energy conversion in conical nanochannels with ion concentration polarization. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2023, 675: 132002 doi: 10.1016/j.colsurfa.2023.132002

    [27]

    Kim J, Jeon J, Wang C, et al. Asymmetric nanochannel network-based bipolar ionic diode for enhanced heavy metal ion detection. ACS Nano, 2022, 16(5): 8253-8263 doi: 10.1021/acsnano.2c02016

    [28]

    Sabbagh B, Park S, Yossifon G. Microvalve-Based tunability of electrically driven Ion transport through a microfluidic system with an ion-exchange membrane. Analytical Chemistry, 2023, 95(16): 6514-6522 doi: 10.1021/acs.analchem.2c04600

    [29]

    Song H, Wang Y, Garson C, et al. Nafion-film-based micro–nanofluidic device for concurrent DNA preconcentration and separation in free solution. Microfluidics and Nanofluidics, 2014, 17: 693-699 doi: 10.1007/s10404-014-1357-3

    [30]

    Chiu PH, Weng CH, Yang RJ. Preconcentration and separation of mixed-species samples near a nano-junction in a convergent microchannel. Sensors, 2015, 15(12): 30704-30715 doi: 10.3390/s151229824

    [31]

    Choi J, Huh K, Moon DJ, et al. Selective preconcentration and online collection of charged molecules using ion concentration polarization. Rsc Advances, 2015, 5(81): 66178-66184 doi: 10.1039/C5RA12639H

    [32] 李子瑞. 离子浓差极化效应及其在微纳流控分子富集系统中的应用进展. 中国科学: 技术科学, 2018, 48(11): 1151-1166 (Li Zirui. Progress in ion concentration polarization effect and its application in micro/nano flow control molecular enrichment system. Science in China: Technological Sciences, 2018, 48(11): 1151-1166 (in Chinese)

    Li Zirui. Progress in ion concentration polarization effect and its application in micro/nano flow control molecular enrichment system. Science in China: Technological Sciences, 2018, 48(11): 1151-1166 (in Chinese)

    [33]

    Gong L, Ouyang W, Li Z, et al. Force fields of charged particles in micro-nanofluidic preconcentration systems. AIP Advances, 2017, 7(12): 125020 doi: 10.1063/1.5008365

    [34]

    Kumar P, Rubinstein SM, Rubinstein I, et al. Mechanisms of hydrodynamic instability in concentration polarization. Physical Review Research, 2020, 2(3): 033365 doi: 10.1103/PhysRevResearch.2.033365

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出版历程
  • 收稿日期:  2023-12-14
  • 录用日期:  2024-02-01
  • 网络出版日期:  2024-02-01
  • 发布日期:  2024-02-02
  • 刊出日期:  2024-05-17

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