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Progress in Chemistry 2021, Vol. 33 Issue (10): 1780-1796 DOI: 10.7536/PC200871 Previous Articles   Next Articles

• Review •

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: Revised: Online: Published:
  • 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)
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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

Key words: particle focusing, passive focusing, microfluidic device, inertial focusing, elasto-inertial focusing
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
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
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
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]
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]
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]
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
Fig.7 (a)~(d) Elasto-inertial focusing mechanism in square microchannel; (e)multi-trains focusing in low AR straight rectangular microchannel[140]
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]
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
Table 3 Summary of biological particle sorting methods based on passive focusing technology
Application Sample Channel type Optimum performance ref
Cancer cell speparation from blood Blood without diluted,
hematocrit ~45%		 Contraction-expansion array Recovery: ~99.7%
Throughput: 1.1×108cells/min		 155
CTCs speparation from blood Blood, 2~2.5× diluted spiral Recovery: ~80%
Throughput: 3mL/h		 33
Cancer cell speparation from blood Blood, 50× diluted Spiral Recovery:~73.75%
Throughput: 2 mL/min		 156
Extraction of plasma from blood Blood, 20× diluted Serpentine Recovery:~99.75%
Throughput: 350 μL/min		 157
Separation of microalgae from
bacteria		 Chlorella and Bacillus Subtilis mixtures Straight contraction-
expansion array		 efficiency: 100%
Throughput: 1μL/min		 160
Exosome sorting MCF-7 cell medium Wavy Serpentine Recovery: ~81%
Throughput: 25μL/min		 34
Bacteria separation from blood Whole blood Straight rectangular Recovery: ~81%
Throughput: 60μL/h		 161
Exosome sorting Cell culture media Straight rectangular Recovery: ~80%
Throughput: 200μL/h		 30
Rare tumer cell separation from blood Untreated whole blood Straight rectangular Efficiency: ~95%
Throughput: 9mL/h		 164
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