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化学进展 2021, Vol. 33 Issue (10): 1780-1796 DOI: 10.7536/PC200871 前一篇   后一篇

• 综述 •

微流控芯片上的颗粒被动聚焦技术

蒋炳炎1,2, 彭涛1,2, 袁帅1,2, 周明勇1,2,*()   

  1. 1 中南大学高性能复杂制造国家重点实验室 长沙 410083
    2 中南大学机电工程学院 长沙 410083
  • 收稿日期:2020-08-27 修回日期:2020-12-03 出版日期:2021-10-20 发布日期:2020-12-28
  • 通讯作者: 周明勇
  • 基金资助:
    国家自然科学基金重点国际(地区)合作研究项目(51920105008); 湖南省重点领域研发计划项目(2019SK2221); 湖南省研究生科研创新项目(CX20210210)

Passive Focusing Techniques of Particles in Microfluidic Device

Bingyan Jiang1,2, Tao Peng1,2, Shuai Yuan1,2, Mingyong Zhou1,2()   

  1. 1 State Key Laboratory of High Performance Complex Manufacturing, Central South University,Changsha 410083, China
    2 College of Mechanical and Electrical Engineering, Central South University,Changsha 410083, China
  • Received:2020-08-27 Revised:2020-12-03 Online:2021-10-20 Published:2020-12-28
  • Contact: Mingyong Zhou
  • Supported by:
    National Natural Science Foundation of China (Key International (Regional) Joint Research Program)(51920105008); Key Research and Development Program of Hunan Province(2019SK2221); Hunan Provincial Innovation Foundation for Postgraduate(CX20210210)

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。

Particle focusing in microfluidic device is a rapidly growing research field due to its wide applications in biology, chemistry, engineering, and medicine. Precise and high-throughput focusing can be a pivotal pretreatment step for counting, detection and separation application. Generally, focusing technologies can be divided into active, passive and sheath-assisted methods. The active and sheath-assisted methods rely on external energy field or sheath flow, which can accurately control the position of particles in microchannel, but require integrating other complex functional elements. Passive focusing uses fluid inertia, viscoelasticity, and other characteristics to control the equilibrium position of particles in the microchannel,and it has been proven to be a powerful tool due to the simplicity, label-free, biocompatible, contact-free, low-cost, and high throughout nature. A large amount of experimental and numerical work has been carried out on the passive focusing technology from the aspects of chip structure, microfluidic characteristics, and particle characteristics. In this review, the fundamental hydrodynamic forces and the basic principles related to the focusing mechanism were firstly briefly introduced and discussed. Then the state of the art of detailed passive focusing methods was presented. At last, the focusing methods were summarized and future development in this field was predicted.

Contents

1 Introduction

2 Hydrodynamic forces and basic principles

2.1 Hydrodynamic forces

2.2 Basic principles for particle passive focusing

3 Inertial focusing techniques

3.1 Inertial focusing in straight microchannels

3.2 Inertial focusing in curved microchannels

3.3 Inertial focusing in multi-staged microchannels

3.4 Micro-vortex induced focusing

4 Elasto-inertial focusing

4.1 Elasto-inertial focusing in straight microchannels

4.2 Elasto-inertial focusing in curved microchannels

5 Application of passive focusing technology in biological particle separation

6 Conclusion and prospects

()
图1 微流道中颗粒受到的水动力载荷。(a)直流道中的惯性力;(b)方形流道中的弹性力;(c)曲流道中产生的迪恩涡流
Fig. 1 Schematic of hydrodynamic forces in microfluidics. (a) Inertial forces in a straight microchannel; (b) elastic force distribution in a square cross-section microchannel; (c)Dean secondary flow
图2 颗粒在直流道中的惯性聚焦平衡。(a)圆形截面;(b)方形截面(AR=1,虚线为最初平衡位置,实线为雷诺数增大后的平衡位置);(c)矩形截面(AR<1);(d)聚焦机理的二阶模型[35];(e)半圆形和三角形截面流道[79]
Fig. 2 Inertial equilibrium positions in the straight microchannel. (a) Circular cross-section; (b) square cross-section (AR=1, dotted line represents initial focus position, solid line represents equilibrium position after Reynolds number increases); (c) rectangular cross-section (AR<1); (d) two-stage migration model[35]; (e) semicircular and triangular cross-section[79], copyright 2016, Published by The Royal Society of Chemistry
图3 颗粒在蛇形流道中的惯性聚焦。(a)对称直角过渡[88];(b)非对称曲率蛇形流道[31];(c)对称曲率蛇形流道[92]
Fig. 3 Inertial focusing in serpentine channel. (a)Symmetric right angle transition[88]; (b) asymmetric curvature serpentine microchannel[31], Copyright (2007) National Academy of Sciences, USA;(c) symmetric curvature serpentine microchannel [92],Copyright (2019), American Chemical Society
图4 曲流道中的惯性聚焦。(a)螺旋流道中的聚焦机理[70];(b)不同深宽比下螺旋流道中的流速分布[103];(c)随流速变化的颗粒聚焦五阶模型[107];(d)随曲率、粒径约束比和流速变化的颗粒迁移机理[113]
Fig. 4 Particle focusing in spiral microchannel. (a) Focusing mechanism in spiral microchannel[70]; (b) velocity distribution of spiral channel with different aspect ratios[103]; (c) a fifth-stage model to illustrate the correlation betweenequilibrium position and flow rate[107]; (d) migration mechanism of particles in channels with variable curvature, confinement ratio, and flow rate[113]
图5 多阶流道中的惯性聚焦。(a)直流道和非对称蛇形组合流道[17];(b)不同AR矩形截面流道组合流道[114]
Fig. 5 Particle focusing in multi-staged microchannel. (a)Staged microfluidics consists of straight rectangular and asymmetric serpentine microchannel[17];(b) staged microfluidics consists of rectangular cross-section with different AR[114]
图6 微涡流诱导下的颗粒惯性聚焦。(a)直流道布置微柱后的颗粒聚焦[119];(b)扩缩直流道[39]
Fig. 6 Micro-vortex induced particle focusing. (a) Particle focusing in microchannel with cylindrical obstacles[119]; (b) particle focusing in straight microchannel with contraction and expansion cavity[39]
表1 各种颗粒惯性聚焦方法的概括
Table 1 Summary of various particle inertial focusing methods in microfluidic device
Channel
structure
Channel dimension(μm) Particle(a in μm) Length fraction Flow rate Dimensionless number ref
Straight rectangular (100,120,140,160)×25 PS (9.9) 0.06~0.93%v/v 0.003~0.096 mL/min Rp (0.4~1.6) 74
Straight Trapezoid (100~200)×(50~70) PS (10,20,45) 0.1%v/v 0.05~5 mL/min Rc (20~800) 78
Straight rectangular (25~35)×47 PS (3,6) 0.08%w/v 20~110 μL/min Rc (13~72) 81
Straight triangle 100×50 μm, 120° PS (7,10,15,18) ~(1~2)×105/mL 0.003~0.65 mL/min Rc (8.4~190) 80
Symmetric serpentine
Right-angled bend
200×40 PS (8,9.9,13) 0.025~0.1%w/w 0.59~1 mL/min Rc (118~200) 88
Symmetric serpentine (200~300)×(50~110)
δ (250~375)
PS (5,10,13,15,20) 0.05~0.1%w/v 0.1~2 mL/min De (5~110) 92
Asymmetric serpentine+
straight rectangle
I: 100×5 (min.)
II: 30×50
PS (10.2) 0.1% w/v 0.0033~0.1 mL/min Rp (0.2~6.0) 17
isosceles triangle;
Semicircle
w(50,80) h (40)
Dia (50) h (40)
PS (7,9.9) 0.05~0.1% w/w - Rp (0.008~3.2) 79
Straight + straight I: 50×25 II: 50×10 PS (10,15,20) 0.1%v/v 0.15~0.21 mL/min Rc (2.6~78) 114
Symmetric serpentine 350×91 δ: 800 PS (10,15,20) 0.01 wt% 0.4~2.7 mL/min Rc (30~205) 93
Asymmetric serpentine 20×10(min.) PS (0.92,2) 0.01~1%v/v 0.01~1.4 mL/min Rc (11.1~1550) 99
Spiral rectangular 250×50(min.)
δ: 1440 (min.)
PS (2,7,10) 0.1% w/v 2~3.5 mL/min De (0~30) 102
Spiral rectangular 150×50 PS (5,10) 0.5 wt% - De (0.86~15.53) 107
Spiral rectangular 500×130 PS (10,15,20) 0.1~0.3% v/v 0.92~3 mL/min De (4.4~14.6) 67
Spiral trapezoidal 600×80, 600×140 PS(5.8,9.8,15.5,26.3) - 0.5~8 mL/min - 82
Spiral rectangular 150×50 PS (0.2~20) - 0.1~0.7 mL/min De (1.73-12.08) 109
Spiral rectangular 160×50 PS (2.1,4.8) ~0.015%v/v - De (0.31-4.58) 108
Spiral :micro-obstacles 900×100 PS (7.3,9.9,15.5) - 1.5~5.25 mL/min Rc (0-666.7) 112
Semi-circular and serpentine curve 100×50 PS (2.2,4.8,9.9) 0.1%w/w 0.05 mL/min
0.005 mL/min·s-1
Rc (10-470) 36
Curve and spiral 100×50 PS (4.4,9.9,15) 0.021-0.23%v/v - Rc (0-400) 113
Straight+semicircular 69×92 PS (5,7.3,10.4,
15.5,20.3)
~105/mL 0.2~1.5 mL/min - 37
Reverse wavy curved 125×40 PS (1,3,5,7,10,15) 6×106/mL 0.049~0.198 mL/min Rc (10-40) 100
Straight rectangular:
Obstacle Arrays
h: 39 PS (6,10,15) - 0.001~0.004 mL/min - 118
Stepped Straight 81×41.5,21×81 PS (7.9,9.9,13) 0.1%w/w - Rc~ 83.33 120
Straight Square+ rectangular(pillars) 100×100,
320×100,50×100
PS (9.9,15,19) 0.05~0.5%w/w 0~0.8 mL/min Rc~ 66.7 119
Straight rectangular expansion 40×50,200×50 PS (7) 0.25%v/v 0.010~0.2 mL/min Rp (0.8-3.5) 39
Straight with triangular
expansion
50×70 PS(3.2,4.8,9.9) ~105/mL 0.05~0.7 mL/min Rc(20.82-329.12) 124
Stepped straight 200×40 PS(9.9,13,24) (0.5~2)×105/mL 0.2~1.5 mL/min Rc (29.2-218.7) 122
Spiral rectangular 100×30,24×10,10×1.4 PS(10,3,1,0.44) 107~105/mL 0.05~0.2 mL/min - 104
图7 (a)~(d)方流道中的弹-惯性聚焦机理;(e)矩形截面流道中多平衡位置聚焦[140]
Fig.7 (a)~(d) Elasto-inertial focusing mechanism in square microchannel; (e)multi-trains focusing in low AR straight rectangular microchannel[140]
图8 曲流道中的弹-惯性聚焦。(a)螺旋流道中的弹-惯性聚焦[68];(b)螺旋流道中随流速变化下的弹-惯性聚焦机理[147]
Fig. 8 Elasto-inertial focusing in curved microchannel. (a) Dean flow coupled elasto-inertial focusing in spiral microchannel[68] ; (b) focusing mechanism with different flow rates[147]
表2 微流控芯片上的颗粒弹-惯性聚焦技术概括
Table 2 Summary of elasto-inertial focusing in microfluidic deice
Channel structure Channel
dimension
Viscoelastic
medium
Particle (a in μm) Flow rate Dimensionless number ref
Straight square 50×50 500 ppm PEO PS(5.9) 40~200 μL/h El (3.21~21.5) Wi (1.61~8.04) 126
Spiral rectangular 100×25 500~5000 ppm PEO PS(1.5,5,10) 50~750 μL/h De(2.4~18) 68
Spiral rectangular 215×50
AR(1/4~1/2)
6.8 wt% PVP
500 ppm PEO
PS(10) 1~240 μL/min Rc (0.04~9.66) Wi (0.17~47.80)
De (0.06~1.407)
147
Straight with square
expansion
50×50+150×50 6.8 wt% PVP PS(6) 0.12~1 mL/h Wi (0~5.8) 141
Straight circular φ50~φ181 0.05 wt% PEO, 8 wt% PVP PS(5,10) 1~120 μL/min Wi(0.1~2.6) Rc(0.002~0.087) 136
Straight square 80×80 0.1% w/v HA PS(1,3,6,8) 0.6~50 mL/min Wi (2.6~566) 32
Straight with triangular expansion 100×50 500 ppm PEO PS(3.2,4.8,13) 10~240 μL/min Wi (22.74~181.92) Rc (2.31~18.48) 142
Straight rectangular h=50
AR(1/3~1)
0.05 wt% PEO
8 wt % PVP
PS(2,5,10) 1~180 μL/min Rc(0~31.71)Wi (0~97.07) 134
Straight square 5×5 +5×50 500 ppm PEO PS(0.1,0.2,0.5,1,2.4) 5~15 μL/h Wi (178~533)Rc (0.11~0.33) 69
Straight rectangular h=25,AR(1/4-1/1) 500~4000 ppm PEO PS(6.4,10,15) 0.05~0.6 mL/h Rc (0.35~30.07)
Wi (1.668~57.715)
140
Spiral rectangular 140×50 2.0~8.0 wt% PVP PS(10) 10~60 μL/h Rc (0.012~0.076)Wi (0.74~4.44) 149
Multi-curvature serpentine 125×40 0.001~0.1wt%PEO PS(0.3,2,3,5,7,10,15) 49.41~197.60 μL/min Rc(6.52~39.84)
Wi(0.74~2.96)
148
Straight square 50×50 0.01~1 wt% PEO PS(4.8) 40~320 μL/h Wi (0.09~25.6)Rc(0.1~0.8) 131
Straight square and trapezoid 75×75 2000 ppm PEO PS(3,5,10) 1~250 μL/min - 135
Straight square 50×50 6.6 wt% PVP PS(6) 0.02~0.16 mL/h Wi (0.20)Rc (0.0007) 146
Straight square 50×50 2.5~50 ppm λ-DNA PS(6,10,15) 0.04~3 mL/h Wi (99.4~1491)Rc (0.71~10.6) 138
Straight rectangular 80×12 1% w/v PEO PS(0.02,0.04
0.1,0.2,0.5)
- Wi (1.3~3.25)Rc(0.00017~0.65) 145
double spiral 30×4 0.2~0.6 wt% PEO PS(0.05,0.075,0.1,0.2,0.5,1,2) 0.32~2.45 μL/h Wi (0.09~0.67) 150
表3 基于被动聚焦技术的生物颗粒分选方法的概括
Table 3 Summary of biological particle sorting methods based on passive focusing technology
[1]
Whitesides G M. Nature, 2006, 442(7101): 368.
[2]
Sackmann E K, Fulton A L, Beebe D J. Nature, 2014, 507(7491): 181.

doi: 10.1038/nature13118     URL    
[3]
Yeo L Y, Chang H C, Chan P P Y, Friend J R. Small, 2011, 7(1): 12.

doi: 10.1002/smll.v7.1     URL    
[4]
Nagrath S, Sequist L V, Maheswaran S, Bell D W, Irimia D, Ulkus L, Smith M R, Kwak E L, Digumarthy S, Muzikansky A, Ryan P, Balis U J, Tompkins R G, Haber D A, Toner M. Nature, 2007, 450(7173): 1235.

doi: 10.1038/nature06385     URL    
[5]
Xuan X C, Zhu J J, Church C. Microfluid.Nanofluidics, 2010, 9(1): 1.
[6]
Lenshof A, Laurell T. Chem.Soc.Rev., 2010, 39(3): 1203.
[7]
Gossett D R, Weaver W M, Mach A J, Hur S C, Tse H T K, Lee W, Amini H, DiCarlo D. Anal.Bioanal.Chem., 2010, 397(8): 3249.
[8]
Lee C Y, Chang C L, Wang Y N, Fu L M. Int.J.Mol.Sci., 2011, 12(5): 3263.
[9]
Gossett D R, Tse H T K, Lee S A, Ying Y, Lindgren A G, Yang O O, Rao J, Clark A T, diCarlo D. PNAS, 2012, 109(20): 7630.

doi: 10.1073/pnas.1200107109     pmid: 22547795
[10]
Benítez J J, Topolancik J, Tian H C, Wallin C B, Latulippe D R, Szeto K, Murphy P J, Cipriany B R, Levy S L, Soloway P D, Craighead H G. Lab Chip, 2012, 12(22): 4848.

doi: 10.1039/c2lc40955k     pmid: 23018789
[11]
Nilsson J, Evander M, Hammarström B, Laurell T. Anal.Chimica Acta, 2009, 649(2): 141.
[12]
Livak-Dahl E, Sinn I, Burns M. Annu.Rev.Chem.Biomol.Eng., 2011, 2(1): 325.
[13]
Salieb-Beugelaar G B, Simone G, Arora A, Philippi A, Manz A. Anal.Chem., 2010, 82(12): 4848.
[14]
Pamme N. Lab a Chip, 2007, 7(12): 1644.

doi: 10.1039/b712784g     URL    
[15]
Lin Y, Gritsenko D, Feng S L, Teh Y C, Lu X N, Xu J. Biosens.Bioelectron., 2016, 83: 256.
[16]
CrevillÉn A G, Ávila M, Pumera M, González M C, Escarpa A. Anal.Chem., 2007, 79(19): 7408.
[17]
Oakey J, Applegate R W Jr, Arellano E, Carlo D D, Graves S W, Toner M. Anal.Chem., 2010, 82(9): 3862.
[18]
Shi J J, Mao X L, Ahmed D, Colletti A, Huang T J. Lab Chip, 2008, 8(2): 221.

doi: 10.1039/B716321E     URL    
[19]
Demierre N, Braschler T, Muller R, Renaud P. Sens. Actuat.B:Chem., 2008, 132(2): 388.
[20]
Liang L T, Xuan X C. Microfluid.Nanofluidics, 2012, 13(4): 637.
[21]
MacDonald M P, Spalding G C, Dholakia K. Nature, 2003, 426(6965): 421.

doi: 10.1038/nature02144     URL    
[22]
Ross D, Locascio L E. Anal.Chem., 2002, 74(11): 2556.
[23]
Mao X L, Waldeisen J R, Huang T J. Lab a Chip, 2007, 7(10): 1260.

doi: 10.1039/b711155j     URL    
[24]
DiCarlo D. Lab Chip, 2009, 9(21): 3038.

doi: 10.1039/b912547g     pmid: 19823716
[25]
Zhang J, Yan S, Yuan D, Alici G, Nguyen N T, Ebrahimi Warkiani M, Li W H. Lab Chip, 2016, 16(1): 10.

doi: 10.1039/c5lc01159k     pmid: 26584257
[26]
Lu X Y, Liu C, Hu G Q, Xuan X C. J.Colloid Interface Sci., 2017, 500: 182.
[27]
Urbansky A, Olm F, Scheding S, Laurell T, Lenshof A. Lab Chip, 2019, 19(8): 1406.

doi: 10.1039/c9lc00181f     pmid: 30869100
[28]
Chiu Y J, Cho S H, Mei Z, Lien V, Wu T F, Lo Y H. Lab Chip, 2013, 13(9): 1803.

doi: 10.1039/c3lc41202d     URL    
[29]
Wu M X, Ouyang Y, Wang Z Y, Zhang R, Huang P H, Chen C Y, Li H, Li P, Quinn D, Dao M, Suresh S, Sadovsky Y, Huang T J. PNAS, 2017, 114(40): 10584.

doi: 10.1073/pnas.1709210114     URL    
[30]
Liu C, Guo J Y, Tian F, Yang N, Yan F S, Ding Y P, Wei J Y, Hu G Q, Nie G J, Sun J S. ACS Nano, 2017, 11(7): 6968.

doi: 10.1021/acsnano.7b02277     URL    
[31]
Di Carlo D, Irimia D, Tompkins R G, Toner M. PNAS, 2007, 104: 18892.

pmid: 18025477
[32]
Lim E J, Ober T J, Edd J F, Desai S P, Neal D, Bong K W, Doyle P S, McKinley G H, Toner M. Nat.Commun., 2014, 5(1):4120.
[33]
Hou H W, Warkiani M E, Khoo B L, Li Z R, Soo R A, Tan D S, Lim W T, Han J, Bhagat A A S, Lim C T. Sci. Rep., 2013, 3: 1259.

doi: 10.1038/srep01259     pmid: 23405273
[34]
Zhou Y N, Ma Z C, Tayebi M, Ai Y. Anal.Chem., 2019, 91(7): 4577.
[35]
Zhou J, Papautsky I. Lab Chip, 2013, 13(6): 1121.

doi: 10.1039/c2lc41248a     URL    
[36]
Gossett D R, Carlo D D. Anal.Chem., 2009, 81(20): 8459.
[37]
Zhang Y, Zhang J, Tang F, Li W H, Wang X H. Anal.Chem., 2018, 90(3): 1786.
[38]
Hsu C H, DiCarlo D, Chen C, Irimia D, Toner M. Lab a Chip, 2008, 8(12): 2128.

doi: 10.1039/b813434k     URL    
[39]
Park J S, Song S H, Jung H I. Lab Chip, 2009, 9(7): 939.

doi: 10.1039/B813952K     URL    
[40]
Amini H, Lee W, diCarlo D. Lab a Chip, 2014, 14(15): 2739.

doi: 10.1039/c4lc00128a     URL    
[41]
Xiang N, Zhu X L, Ni Z H. Prog. Chem., 2011, 23: 1945.
项楠, 朱晓璐, 倪中华. 化学进展, 2011, 23: 1945.).
[42]
Yuan D, Zhao Q B, Yan S, Tang S Y, Alici G, Zhang J, Li W H. Lab Chip, 2018, 18(4): 551.

doi: 10.1039/c7lc01076a     pmid: 29340388
[43]
Ni C, Jiang D, Xu Y L, Tang W L. Prog. Chem., 2020, 32: 519.
( 倪陈, 姜迪, 徐幼林, 唐文来. 化学进展, 2020, 32: 519.).

doi: 10.7536/PC190907    
[44]
Stoecklein D diCarlo D. Anal.Chem., 2019, 91(1): 296.
[45]
Lu M Q, Ozcelik A, Grigsby C L, Zhao Y H, Guo F, Leong K W, Huang T J. Nano Today, 2016, 11(6): 778.

doi: 10.1016/j.nantod.2016.10.006     URL    
[46]
Zhang T L, Hong Z Y, Tang S Y, Li W H, Inglis D W, Hosokawa Y, Yalikun Y, Li M. Lab a Chip, 2020, 20(1): 35.

doi: 10.1039/C9LC00785G     URL    
[47]
Bayareh M. Chem.Eng.Process.Process.Intensif., 2020, 153: 107984.
[48]
Rubinow S I, Keller J B. J.Fluid Mech., 1961, 11(3): 447.
[49]
Saffman P G. J.Fluid Mech., 1965, 22(2): 385.
[50]
Zeng L Y, Balachandar S, Fischer P. J.Fluid Mech., 2005, 536: 1.
[51]
Matas J, Morris J, Guazzelli E. Oil Gas Sci.Technol. Rev.IFP, 2004, 59(1): 59.
[52]
Asmolov E S. J.Fluid Mech., 1999, 381: 63.
[53]
Matas J P, Morris J F, Guazzelli É. J.Fluid Mech., 2004, 515: 171.
[54]
Chan P C H, Leal L G. J.Fluid Mech., 1979, 92(1): 131.
[55]
Stan C A, Ellerbee A K, Guglielmini L, Stone H A, Whitesides G M. Lab Chip, 2013, 13(3): 365.

doi: 10.1039/C2LC41035D     URL    
[56]
Hur S C, Henderson-Maclennan N K, McCabe E R B, DiCarlo D. Lab a Chip, 2011, 11(5): 912.

doi: 10.1039/c0lc00595a     URL    
[57]
Pathak J A, Ross D, Migler K B. Phys.Fluids, 2004, 16(11): 4028.
[58]
Magda J J, Lou J, Baek S G, DeVries K L. Polymer, 1991, 32(11): 2000.

doi: 10.1016/0032-3861(91)90165-F     URL    
[59]
Feng H D, Magda J J, Gale B K. Appl.Phys.Lett., 2019, 115(26): 263702.
[60]
Leshansky A M, Bransky A, Korin N, Dinnar U. Phys.Rev.Lett., 2007, 98(23): 234501.
[61]
Rodd L E, Scott T P, Boger D V, Cooper-White J J, McKinley G H. J.Non Newton.Fluid Mech., 2005, 129(1): 1.
[62]
Rodd L E, Cooper-White J J, Boger D V, McKinley G H. J.Non Newton.Fluid Mech., 2007, 143(2/3): 170.
[63]
Nam J, Lim H, Kim D, Jung H, Shin S. Lab Chip, 2012, 12(7): 1347.

doi: 10.1039/c2lc21304d     URL    
[64]
Berger S A, Talbot L, Yao L S. Annu.Rev.Fluid Mech., 1983, 15(1): 461.
[65]
Ookawara S, Higashi R, Street D, Ogawa K. Chem.Eng.J., 2004, 101(1/3): 171.
[66]
Bhagat A A S, Kuntaegowdanahalli S S, Papautsky I. Microfluid.Nanofluidics, 2009, 7(2): 217.
[67]
Kuntaegowdanahalli S S, Bhagat A A S, Kumar G, Papautsky I. Lab Chip, 2009, 9(20): 2973.

doi: 10.1039/b908271a     pmid: 19789752
[68]
Lee D J, Brenner H, Youn J R, Song Y S. Sci.Rep., 2013, 3(1): 3258.
[69]
Young K J, Won A S, Sik L S, Min K J. Lab Chip., 2012, 12: 2807.

doi: 10.1039/c2lc40147a     pmid: 22776909
[70]
Bhagat A A S, Kuntaegowdanahalli S S, Papautsky I. Lab a Chip, 2008, 8(11): 1906.

doi: 10.1039/b807107a     URL    
[71]
Leal L G. Annu.Rev.Fluid Mech., 1980, 12(1): 435.
[72]
Seo K W, Kang Y J, Lee S J. Phys.Fluids, 2014, 26(6): 063301.
[73]
Humphry K J, Kulkarni P M, Weitz D A, Morris J F, Stone H A. Phys.Fluids, 2010, 22(8): 081703.
[74]
Reece A E, Oakey J. Phys.Fluids, 2016, 28(4): 043303.
[75]
SegrÉ G, Silberberg A. Nature, 1961, 189(4760): 209.

doi: 10.1038/189209a0     URL    
[76]
Ciftlik A T, Ettori M, Gijs M A M. Small, 2013, 9(16): 2764.

doi: 10.1002/smll.201201770     pmid: 23420756
[77]
Mashhadian A, Shamloo A. Anal.Chimica Acta, 2019, 1083: 137.
[78]
Moloudi R, Oh S, Yang C, Ebrahimi Warkiani M, Naing M W. Microfluid.Nanofluidics, 2018, 22(3): 1.
[79]
Kim J, Lee J, Wu C, Nam S, DiCarlo D, Lee W. Lab Chip, 2016, 16(6): 992.

doi: 10.1039/c5lc01100k     pmid: 26853995
[80]
Mukherjee P, Wang X, Zhou J, Papautsky I. Lab Chip, 2019, 19(1): 147.

doi: 10.1039/C8LC00973B     URL    
[81]
Masaeli M, Sollier E, Amini H, Mao W B, Camacho K, Doshi N, Mitragotri S, Alexeev A, DiCarlo D. Phys.Rev.X, 2012, 2(3): 031017.
[82]
Guan G F, Wu L D, Bhagat A A, Li Z R, Chen P C Y, Chao S Z, Ong C J, Han J. Sci.Rep., 2013, 3(1): 1475.
[83]
Wyss H M, Blair D L, Morris J F, Stone H A, Weitz D A. Phys.Rev.E, 2006, 74(6): 061402.
[84]
Mutlu B R, Edd J F, Toner M. PNAS, 2018, 115: 7682.

doi: 10.1073/pnas.1721420115     URL    
[85]
Stone H A. Nat.Phys., 2009, 5(3): 178.
[86]
Lee M G, Choi S, Park J K. Appl.Phys.Lett., 2009, 95(5): 051902.
[87]
Yoon D H, Ha J B, Bahk Y K, Arakawa T, Shoji S, Go J S. Lab Chip, 2009, 9(1): 87.

doi: 10.1039/B809123D     URL    
[88]
Zhang J, Li W H, Li M, Alici G, Nguyen N T. Microfluid.Nanofluidics, 2014, 17(2): 305.
[89]
Shamloo A, Mashhadian A. Phys.Fluids, 2018, 30(1): 012002.
[90]
Jiang D, Tang W L, Xiang N, Ni Z H. RSC Adv., 2016, 6(62): 57647.

doi: 10.1039/C6RA08374A     URL    
[91]
Yin P J, Zhao L, Chen Z Z, Jiao Z Q, Shi H Y, Hu B, Yuan S F, Tian J. Soft Matter, 2020, 16(12): 3096.

doi: 10.1039/D0SM00084A     URL    
[92]
Zhang J, Yuan D, Zhao Q B, Teo A J T, Yan S, Ooi C H, Li W H, Nguyen N T. Anal.Chem., 2019, 91(6): 4077.
[93]
Özbey A, Karimzadehkhouei M, Akgönül S, Gozuacik D, Ko塂ar A. Sci.Rep., 2016, 6(1): 1.
[94]
Sun S F, Wang C, Chen Y, Cheng Z D, Cai X Y, Bu E Q. J. Eng. Thermophys., 2017, 38: 1758.
( 孙思帆, 王超, 陈颖, 成正东, 蔡小燕, 卜恩奇. 工程热物理学报, 2017, 38: 1758.).
[95]
Tang W L, Xiang N, Zhang X J, Huang D, Ni Z H. Acta Phys.Sin., 2015, 64(18): 184703.
唐文来, 项楠, 张鑫杰, 黄笛, 倪中华. 物理学报, 2015, 64(18): 184703.)
[96]
Di Carlo D, Edd J F, Irimia D, Tompkins R G, Toner M. Anal.Chem., 2008, 80(6): 2204.
[97]
Wang C, Sun S F, Chen Y, Cheng Z D, Li Y X, Jia L S, Lin P C, Yang Z, Shu R Y. Microfluid.Nanofluidics, 2018, 22(3): 25.
[98]
Sollier E, Murray C, Maoddi P, diCarlo D. Lab Chip, 2011, 11(22): 3752.

doi: 10.1039/c1lc20514e     pmid: 21979377
[99]
Wang L, Dandy D S. Adv.Sci., 2017, 4(10): 1700153.
[100]
Zhou Y N, Ma Z C, Ai Y. Microsyst.Nanoeng., 2018, 4(1): 5.
[101]
Bhagat A A S, Kuntaegowdanahalli S S, Kaval N, Seliskar C J, Papautsky I. Biomed.Microdevices, 2010, 12(2): 187.
[102]
Russom A, Gupta A K, Nagrath S, Carlo D D, Edd J F, Toner M. New J.Phys., 2009, 11(7): 075025.
[103]
Martel J M, Toner M. Phys.Fluids, 2012, 24(3): 032001.
[104]
Cruz J, Hooshmand Zadeh S, Graells T, Andersson M, Malmström J, Wu Z G, Hjort K. J.Micromech.Microeng., 2017, 27(8): 084001.
[105]
Cruz J, Graells T, WalldÉn M, Hjort K. Lab Chip, 2019, 19(7): 1257.
[106]
Paiè P, Bragheri F, DiCarlo D, Osellame R. Microsyst.Nanoeng., 2017, 3(1): 1.
[107]
Xiang N, Yi H, Chen K, Sun D K, Jiang D, Dai Q, Ni Z H. Biomicrofluidics, 2013, 7(4): 044116.

doi: 10.1063/1.4818445     URL    
[108]
Xiang N, Chen K, Sun D K, Wang S F, Yi H, Ni Z H. Microfluid.Nanofluidics, 2013, 14(1/2): 89.
[109]
Xiang N, Shi Z G, Tang W L, Huang D, Zhang X J, Ni Z H. RSC Adv., 2015, 5(94): 77264.

doi: 10.1039/C5RA13292D     URL    
[110]
Chen Z Z, Zhao L, Wei L J, Huang Z Y, Yin P J, Huang X W, Shi H Y, Hu B, Tian J. Sens. Actuat.B:Chem., 2019, 301: 127125.
[111]
Al-Halhouli A, Albagdady A, Al-Faqheri W, Kottmeier J, Meinen S, Frey L J, Krull R, Dietzel A. RSC Adv., 2019, 9(33): 19197.

doi: 10.1039/c9ra03587g    
[112]
Shen S F, Tian C, Li T B, Xu J, Chen S W, Tu Q, Yuan M S, Liu W M, Wang J Y. Lab Chip, 2017, 17(21): 3578.

doi: 10.1039/C7LC00691H     URL    
[113]
Martel J M, Toner M. Sci.Rep., 2013, 3(1): 3340.
[114]
Wang X, Zandi M, Ho C C, Kaval N, Papautsky I. Lab Chip, 2015, 15(8): 1812.
[115]
Zhou J, Giridhar P V, Kasper S, Papautsky I. Lab Chip, 2013, 13(10): 1919.

doi: 10.1039/c3lc50101a     URL    
[116]
Kim J A, Lee J R, Je T J, Jeon E C, Lee W. Anal.Chem., 2018, 90(3): 1827.
[117]
Choi S, Park J K. Lab Chip, 2007, 7(7): 890.

doi: 10.1039/b701227f     URL    
[118]
Choi S, Park J K. Anal.Chem., 2008, 80(8): 3035.
[119]
Chung A J, Pulido D, Oka J C, Amini H, Masaeli M, diCarlo D. Lab Chip, 2013, 13(15): 2942.

doi: 10.1039/c3lc41227j     pmid: 23665981
[120]
Chung A J, Gossett D R, DiCarlo D. Small, 2013, 9(5): 685.

doi: 10.1002/smll.201202413     pmid: 23143944
[121]
Song S, Choi S. J.Chromatogr.A, 2013, 1302: 191.
[122]
Zhao Q B, Zhang J, Yan S, Yuan D, Du H P, Alici G, Li W H. Sci.Rep., 2017, 7(1): 41153.
[123]
Lee M G, Choi S, Kim H J, Lim H K, Kim J H, Huh N, Park J K. Appl.Phys.Lett., 2011, 98(25): 253702.
[124]
Zhang J, Li M, Li W H, Alici G. J.Micromech.Microeng., 2013, 23(8): 085023.
[125]
Caserta S, D'Avino G, Greco F, Guido S, Maffettone P L. Soft Matter, 2011, 7(3): 1100.

doi: 10.1039/C0SM00640H     URL    
[126]
Yang S, Kim J Y, Lee S J, Lee S S, Kim J M. Lab Chip, 2011, 11(2): 266.

doi: 10.1039/C0LC00102C     URL    
[127]
Groisman A, Steinberg V. Nature, 2000, 405(6782): 53.

doi: 10.1038/35011019     URL    
[128]
Groisman A, Steinberg V. Nature, 2001, 410(6831): 905.

doi: 10.1038/35073524     URL    
[129]
Seo K W, Byeon H J, Huh H K, Lee S J. RSC Adv., 2014, 4(7): 3512.

doi: 10.1039/C3RA43522A     URL    
[130]
Dai Q, Xiang N, Cheng J, Ni Z H, Acta Phys. Sin., 2015, 64: 1.
( 戴卿, 项楠, 程洁, 倪中华. 物理学报, 2015, 64: 1.).
[131]
Song H Y, Lee S H, Salehiyan R, Hyun K. Rheol.Acta, 2016, 55(11/12): 889.
[132]
Liu C, Xue C D, Chen X D, Shan L, Tian Y, Hu G Q. Anal.Chem., 2015, 87(12): 6041.
[133]
del Giudice F, Romeo G, D'Avino G, Greco F, Netti P A, Maffettone P L. Lab a Chip, 2013, 13(21): 4263.

doi: 10.1039/c3lc50679g     URL    
[134]
Xiang N, Dai Q, Ni Z H. Appl.Phys.Lett., 2016, 109(13): 134101.
[135]
Raoufi M A, Mashhadian A, Niazmand H, Asadnia M, Razmjou A, Warkiani M E. Biomicrofluidics, 2019, 13(3): 034103.

doi: 10.1063/1.5093345     URL    
[136]
Xiang N, Dai Q, Han Y, Ni Z H. Microfluid.Nanofluidics, 2019, 23(2): 16.
[137]
Tang W L, Fan N, Yang J Q, Li Z, Zhu L Y, Jiang D, Shi J P, Xiang N. Microfluid.Nanofluidics, 2019, 23(3): 42.
[138]
Kim B, Kim J M. Biomicrofluidics, 2016, 10(2): 024111.

doi: 10.1063/1.4944628     URL    
[139]
Won S K, Ran H Y, Joon L S. Appl. Phys. Lett., 2014, 104: 213702.

doi: 10.1063/1.4880615     URL    
[140]
Yang S H, Lee D J, Youn J R, Song Y S. Anal.Chem., 2017, 89(6): 3639.
[141]
Cha S, Kang K, You J B, Im S G, Kim Y, Kim J M. Rheol.Acta, 2014, 53(12): 927.
[142]
Yuan D, Zhang J, Yan S, Pan C, Alici G, Nguyen N T, Li W H. Biomicrofluidics, 2015, 9(4): 044108.

doi: 10.1063/1.4927494     URL    
[143]
Yuan D, Tan S H, Zhao Q B, Yan S, Sluyter R, Nguyen N T, Zhang J, Li W H. RSC Adv., 2017, 7(6): 3461.

doi: 10.1039/C6RA25328H     URL    
[144]
Fan L L, Wu X, Zhang H, Zhao Z, Zhe J, Zhao L. Microfluid.Nanofluidics, 2019, 23(10): 117.
[145]
Asghari M, Cao X B, Mateescu B, van Leeuwen D, Aslan M K, Stavrakis S, de Mello A J. ACS Nano, 2020, 14(1): 422.

doi: 10.1021/acsnano.9b06123     URL    
[146]
Yang S, Lee S S, Ahn S W, Kang K, Shim W, Lee G, Hyun K, Kim J M. Soft Matter, 2012, 8(18): 5011.

doi: 10.1039/c2sm07469a     URL    
[147]
Xiang N, Zhang X J, Dai Q, Cheng J, Chen K, Ni Z H. Lab a Chip, 2016, 16(14): 2626.
[148]
Zhou Y N, Ma Z C, Ai Y. Lab Chip, 2020, 20(3): 568.

doi: 10.1039/C9LC01071H     URL    
[149]
Xiang N, Ni Z H, Yi H. Electrophoresis, 2018, 39(2): 417.

doi: 10.1002/elps.201700150     pmid: 28990196
[150]
Liu C, Ding B Q, Xue C D, Tian Y, Hu G Q, Sun J S. Anal.Chem., 2016, 88(24): 12547.
[151]
Yuan D, Sluyter R, Zhao Q B, Tang S Y, Yan S, Yun G L, Li M, Zhang J, Li W H. Microfluid.Nanofluidics, 2019, 23(3): 41.
[152]
BankÓ P, Lee S Y, Nagygyörgy V, Zrínyi M, Chae C H, Cho D H, Telekes A. J. Hematol. Oncol., 2019, 12(1): 48.
[153]
Reece A, Xia B Z, Jiang Z L, Noren B, McBride R, Oakey J. Curr. Opin. Biotechnol., 2016, 40: 90.

doi: 10.1016/j.copbio.2016.02.015     URL    
[154]
Dalili A, Samiei E, Hoorfar M. Anal., 2019, 144(1): 87.
[155]
Lee M G, Shin J H, Bae C Y, Choi S, Park J K. Anal. Chem., 2013, 85(13): 6213.

doi: 10.1021/ac4006149     URL    
[156]
Abdulla A, Liu W J, Gholamipour-Shirazi A, Sun J H, Ding X T. Anal. Chem., 2018, 90(7): 4397.

doi: 10.1021/acs.analchem.7b04210     pmid: 29537252
[157]
Zhang J, Yan S, Li W H, Alici G, Nguyen N T. RSC Adv., 2014, 4(63): 33149.

doi: 10.1039/C4RA06513A     URL    
[158]
Zhang J, Yuan D, Sluyter R, Yan S, Zhao Q B, Xia H M, Tan S H, Nguyen N T, Li W H. IEEE Trans. Biomed. Circuits Syst., 2017, 11(6): 1422.

doi: 10.1109/TBCAS.4156126     URL    
[159]
Yuan D, Zhao Q B, Yan S, Tang S Y, Zhang Y X, Yun G L, Nguyen N T, Zhang J, Li M, Li W H. Lab Chip, 2019, 19(17): 2811.

doi: 10.1039/c9lc00482c     pmid: 31312819
[160]
Yuan D, Zhang J, Sluyter R, Zhao Q B, Yan S, Alici G, Li W H. Lab Chip, 2016, 16(20): 3919.

pmid: 27714019
[161]
Faridi M A, Ramachandraiah H, Banerjee I, Ardabili S, Zelenin S, Russom A. J. Nanobiotechnology, 2017, 15(1): 1.
[162]
Tian F, Zhang W, Cai L L, Li S S, Hu G Q, Cong Y L, Liu C, Li T J, Sun J S. Lab Chip, 2017, 17(18): 3078.

doi: 10.1039/c7lc00671c     pmid: 28805872
[163]
Yuan D, Zhang J, Yan S, Peng G R, Zhao Q B, Alici G, Du H J, Li W H. Electrophoresis, 2016, 37(15/16): 2147.
[164]
Tian F, Cai L L, Chang J Q, Li S S, Liu C, Li T J, Sun J S. Lab Chip, 2018, 18(22): 3436.

doi: 10.1039/c8lc00700d     pmid: 30328446
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