A State-Of-The-Art Review of Mixing in Microfluidic Mixers
A State-Of-The-Art Review of Mixing in Microfluidic Mixers
A State-Of-The-Art Review of Mixing in Microfluidic Mixers
REVIEWS
The State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University,
Beijing 100084, China
Abstract Microreaction technology is one of the most innovative and rapid developing fields in chemical engineering, synthesis and process technology. Many expectations toward enhanced product selectivity, yield and purity,
improved safety, and access to new products and processes are directed to the microreaction technology. Microfluidic mixer is the most important component in microfluidic devices. Based on various principles, active and passive
micromixers have been designed and investigated. This review is focused on the recent developments in microfluidic mixers. An overview of the flow phenomena and mixing characteristics in active and passive micromixers is
presented, including the types of physical phenomena and their utilization in micromixers. Due to the simple fabrication technology and the easy implementation in a complex microfluidic system, T-micromixer is highlighted as an
example to illustrate the effect of design and operating parameters on mixing efficiency and fluid flow inside microfluidic mixers.
Keywords micromixing, microfluidics, T-shaped micromixer, microfabrication techniques, microreaction technologies, microelectromechanical systems
INTRODUCTION
CLASSIFICATION OF MICROMIXERS
Micromixers can be classified into active and
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passive mixers (Fig. 1). The active mixer requires external forces such as pneumatic or mechanical vibration to enhance mixing efficiency. Also, it requires
complex fabrication processes, more complex to
package and control, and is difficult to integrate with
other fluidic components [8], whereas passive mixers
generally have longer mixing length than active mixers, require no external agitation, easy to fabricate and
incorporate with other fluidic components [912].
Figure 2 Electrokinetic instability micromixer [17]
(Points 1 and 2 are the inlet ports for fluid A and fluid B,
whereas point 5 is the outlet port for mixing fluids. Side channel ports 3 and 4, connected to either side of the mixing chamber, allow for ac excitation)
2.1
Active micromixers
Active mixers use external perturbation to introduce vorticity into laminar flow [1321]. Ultrasonics
[13], pressure field disturbance [14], thermal [15],
magnetically [16] and electrokinetics [17] driven mixers are a few examples having been demonstrated to
date. Electrokinetics is a branch of electrohydrodynamics (EHD) that describes the coupling of ion
transport, fluid flow and electric fields and is distinguished from EHD by the relevance of interfacial
charge at solid-liquid interfaces. The fluid flow in this
class of devices is often stable and strongly damped
by viscous forces (with Re being 1 or smaller). However, heterogeneous ionic conductivity fields in the
presence of applied electric fields can, under certain
conditions, generate an unstable flow field owing to
electrokinetic instabilities (EKI) by which the action
of fluctuating electric fields causes the two fluids to
stretch and fold rapidly and promote mixing [17, 18].
Oddy et al. [17] used fluorescent experiment to observe
the performance rapid stretching and folding of a homogeneous fluorescence tracer in EKI mixer (Fig. 2). A
mixing time of 2.5 s for a mixing volume of 0.1 l
was achieved. Recently, Posner and Santiago [18] presented a parametric experimental study of convective
EKI in an isotropically etched cross-shaped microchannel with three inlets and one-outlet (Fig. 3).
Active mixing can also be achieved by using ultrasonic vibrations generated from piezoelectric materials to introduce turbulence in the fluid flow to enhance mixing. An ultrasonic micromixer was realized
and tested by a dilution experiment, and employing
the dye uranine [19]. In the presence of ultrasonic
Figure 4
Passive micromixers
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(a)
(b)
(c)
Figure 5 Passive mixers: (a) SuperFocus mixer [12]; (b) Triangular interdigital micromixer [37]; (c) Hydrodynamic
focusing mixer [12]
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Figure 6
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FABRICATION MATERIALS
As sequence of a unique characteristics and applications of microfluidic devices, properties of materials are critical for both fabrication and successful
application of these devices. Different materials have
different electric potential introduced by the wall and
also quite different effects on the flow medium and on
the characteristics of the mixing. Two approaches to
flow manipulation are prevalent in passive micromixers: the first relying on channel geometry to generate
chaotic advection and increased circulation, and the
second on channel surface properties. Micromixer
wall with electrically charged surface heterogeneities
may increase mixing efficiencies by creating localized
regions of flow circulation. Surface charge heterogeneities have been suggested as a mechanism for enhanced mixing in electroosmotic flows [5456]. Electroosmotic flow is generated by the surface charge on
the microchannel walls in combination with an electric field along the microchannel. For example, polymer materials exhibit a wide range of charge and
charge densities, electroosmotic flow in microchannels made from different polymer materials is highly
variable. Electroosmotic flow has been measured in
various polymer microchannels fabricated by laser
ablation [57], and imprinting [58], and in poly- (methylmethacrylate) (PMMA) channels fabricated by
LIGA (X-ray lithography, electroforming and moulding techniques) methods [59]. These fabrication methods, as well as the material itself, can affect the surface charge density and therefore have profound effect
on the electroosmotic flow. On the other hand, in
some applications such as mixing of electrokinetic
flows, silicon cannot be used because of its electrically conducting properties [60]. Typically, silicon oxide (or glass) surfaces are negatively charged at neutral pH due to deprotonated silanol groups ( Si O ).
When these surfaces come in contact with a solution
containing ions, positive ions will be attracted to the
(a)
(b)
Figure 8 Slit-type (a) interdigital micromixer made in
stainless steel [7], and Microfluidic Lab Chip (b) manufactured by plastic thin film lamination [61]
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Figure 10 Temperature gradient as a function of the hydraulic diameter and aspect ratio () for square and rectangular microchannels [75] (Re300)
Judy et al. [76];0.1;1
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(a)
(b)
Figure 11 Criteria for distinction between (a) diffusioncontrolled process, and (b) activation-controlled process [100]
(t: residence time)
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Figure 13 Tracer profiles on the cross section of the mixing channel 300
m behind its
entrance for
mean velocities
1
1
1
of (a) 0.9 ms
,
(b)
1.05
ms
,
(c)
1.1
ms
,
(d) 1.15 ms1,
(e) 1.2 ms1 and (f) 1.4 ms1 [106]
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(a)
(a)
(b)
Figure 15 The effect of the presence of addition parts on
mixing efficiency [110]
(b)
Figure 14 The effect of pulsing in mixing quality: (a) No
pulsing nor ribs; (b) There is pulsing and ribs along the
floor of the main channel [90]
6.2
is 60 m. Many arrangements of obstacles were investigated. This work found that obstacles in a microchannel at low Re cannot generate eddies or recirculation.
However, the results demonstrated that obstacles
could improve mixing performance at high Re. Under
this condition, the asymmetric arrangement of obstacles could alter the flow directions and forces fluids to
merge and create transversal mass transport. Recently,
Lin et al. [112] studied the effect of J-shaped baffles on
mixing efficiency. The simulated and experimental
results showed that the T-mixer with J-shaped baffles
exhibited better mixing performance, and the percentage of mixing was about 1.2 to 2.2 times higher than
those without baffles (Fig. 16). These results revealed
that the J-shaped baffles could result in lateral convection
in the main channel, resulting in improved mixing.
(a)
(b)
Figure 16
Mixing percentage in the tee channel
with/without J-shaped baffles calculated from (a) simulated
results, and (b) experimental results [112]
with baffles;without baffles
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(a)
(b)
(c)
(d)
Figure 17 Comparison of the concentration plot of the black fluid for the
four geometries [109]
(The data is for the case of 5 Hz pulsing at the same mean velocity of 1 mms 1 from each inlet, all of the channels are
200 m wide by 120 m deep)
6.3
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(a)
(b)
(c)
(d)
Figure 20 The effect of applied electrical field on performance of T-micromixer: (a) initial condition; (b) after
the application of an electric field of intensity E4105
Vm 1; (c) same as (b) with an electric field intensity of E
6105 Vm 1 and (d) variation of the mixing index with the
intensity of the DC electric field [124]
For the proposed active-double-T-shaped micromixer, the mixing ratio can be as high as 95%
within a mixing length of 1000 mm downstream from
FUTURE TOPICS
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21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
Stroock, A.D., Dertinger, S.K.W., Ajdari, A., Mezic, I., Stone, H.A.,
Whitesides, G.M., Chaotic mixer for microchannels, Science, 295,
647651 (2002).
Liu, R.H., Stremler, M.A., Sharp, K.V., Olsen, M.G., Santiago, J.G.,
Adrian, R., Aref, H., Beebe, D.J., Passive mixing in a
three-dimensional serpentine microchannel, J. Microelectromech.
Syst., 9, 190197 (2000).
Lee, Y.K., Deval, J., Tabeling, P., Ho, C.M., Chaotic mixing in
electrokinetically and pressure driven micro flows, In: Proc. 14
IEEE Workshop MEMS, Interlaken, Switzerland, 483486 (2001).
Dodge, A., Jullien, M.C., Lee, Y.K., Niu, X., Oskkels, F., Tabeling, P.,
An example of a chaotic micromixer: The cross-channel micromixer, C. R. Phys., 5, 557563 (2004).
Hessel, V., Zimmerman, W.B., Investigation of the convective motion through a staggered herringbone micromixer at low Reynolds
number flow, Chem. Eng. Sci., 61, 29772985 (2006).
Stroock, A.D., Weck, M., Chiu, D.T., Huck, W.T.S., Kenis, P.J.A.,
Patterning electro-osmotic flow with patterned surface charge,
Phys. Rev. Lett., 84, 33143317 (2000).
Barker, S.L.R., Ross, D., Tarlov, M.J., Gaitan, M., Locascio, Locascio, L.E., Control of flow direction in microfluidic devices with
polyelectrolyte multilayers, Anal. Chem., 72, 59255929 (2000).
Hau, W.L.W., Trau, D.W., Sucher, N.J., Wong, M., Zohar, Y., Surface-chemistry technology for microfluidics, J. Micromech. Microeng., 13, 272278 (2003).
Roberts, M.A., Rossier, J.S., Bercier, P., Girault, H., UV laser machined polymer substrates for the development of microdiagnostic
systems, Anal. Chem., 69, 20352042 (1997).
Locascio, L.E., Perso, C.E., Lee, C.S., Measurement of electroosmotic flow in plastic imprinted microfluid devices and the effect of
protein adsorption on flow rate, J. Chromatogr., A 857, 275284
(1999).
Henry, A.C., Tutt, T.J., Galloway, M., Davidson, Y.Y., Mcwhorter,
C.S., Soper, S.A., McCarley, R.L., Surface modification of
poly(methyl methacrylate) used in the fabrication of microanalytical
devices, Anal. Chem., 72, 53315337 (2000).
Nguyen, N.T., Wu, Z., MicromixersA review, J. Micromech.
Microeng., 15, R1R16 (2005).
Schulte, T.H., Bardell, R.L., Weigl, B.H., Microf luidic technologies in clinical diagnostics, Clin. Chim. Acta, 321, 110 (2002).
Lima, C.T., Zhang, Y., Bead-based microfluidic immunoassays: The
next generation, Biosensors and Bioelectronics, 22, 11971204
(2007).
Hawkes, J.J., Coakley, W.T., Force field particle filter, combining
ultrasound standing waves and laminar flow, Sens. Actuators B
Chem., 75, 213222 (2001).
Hawkes, J.J., Coakley, W.T., Groschl, M., Benes, E., Armstrong, S.,
Tasker, P.J., Nowotny, H., Single half-wavelength ultrasonic particle filter: predictions of the transfer matrix multilayer resonator
model and experimental filtration results, J. Acoustic. Soc. Am., 111,
12591266 (2002).
Becker, H., Locascio, L., Polymer microfluidic devices, Talanta,
56, 267287 (2002).
Murakami, Y., Endo, T., Yamamura, S., Nagatani, N., Takamura, Y.,
Tamiya, E., On-chip micro-flow polystyrene bead-based immunoassay for quantitative detection of tacrolimus, Anal. Biochem., 334
(1), 111116 (2004).
Luo, C., Fu, Q., Li, H., Xu, L., Sun, M., Ouyang, Q., Chen, Y., Ji, H.,
PDMS microfludic device for optical detection of protein immunoassay using gold nanoparticles, Lab. Chip, 7, 726729 (2005).
Matsubara, Y., Murakami, Y., Kobayashi, M., Morita, Y., Tamiya, E.,
Application of on-chip cell cultures for the detection of allergic response, Biosens. Bioelectron., 19 (7), 741747 (2004).
Peterson, S.L., McDonald, A., Gourley, P.L., Sasaki, D.Y.,
Poly(dimethylsiloxane) thin films as biocompatible coatings for
microfluidic devices: Cell culture and flow studies with glial cells,
J. Biomed. Materi. Res. A, 72A (1), 1018 (2005).
Gourley, P.L., Copeland, R.G., Cox, J.D., Hendricks, J.K., McDonald,
A.E., Peterson, S.L.G., Biocompatible semiconductor optoelectronics, J. Biomed. Opt., 7 (4), 546554 (2002).
Engler, M., Kockmann, N., Kiefer, T., Woias, P., Convective mixing
and its application to microreactors, In: 2th Int. Conf. Microchannels Minichannels, New York, USA, 2412, 781787 (2004).
Xu, B., Ooi, K.T., Mavriplis, C., Zaghloul, M.E., Viscous dissipation effects for liquid flow in microchannels, Model. Simulat. Microsyst., 100103 (2002)
Xu, B., Ooi, K.T., Mavriplis, C., Zaghloul, M.E., Evaluation of
viscous dissipation in liquid flow in microchannels, J. Micromech.
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
515
516
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125