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Active and passive micromixers: A comprehensive review

Morteza Bayareh, Mohsen Nazemi Ashani, Azam Usefian

PII: S0255-2701(19)30873-6
DOI: https://doi.org/10.1016/j.cep.2019.107771
Reference: CEP 107771

To appear in: Chemical Engineering and Processing - Process Intensification

Received Date: 18 July 2019

Revised Date: 24 November 2019
Accepted Date: 1 December 2019

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Active and passive micromixers: a comprehensive review

Morteza Bayareh*, Mohsen Nazemi Ashani, Azam Usefian

Department of Mechanical Engineering, Shahrekord University, Shahrekord, Iran
*m.bayareh@sku.ac.ir

Highlights

 The present review (with 205 refs.) addresses the need for microdevices and presents the
basic microfluidic equations.

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 The review describes the relevant numerical and experimental approaches.
 Various types and designs of passive and active micromixers are discussed.

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Abstract
The present review (with 205 refs.) addresses the need for microdevices, presents the basic

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microfluidic equations and describes the relevant numerical and experimental approaches.
Various types and designs of passive and active micromixers are presented. In addition, the
relevant effective dimensionless or dimensional parameters and the fabrication technology for
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different micromixer types are introduced. Different general configurations of lamination,
obstacle, convergence-divergence and curved-channel are discussed for passive micromixers.
The active micromixers are categorized and described as pressure field driven, acoustic field
driven, magnetic field driven, electric field driven and thermal field driven.
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Keywords: Lab-on-a-Chip, Microfluidics, Passive micromixer, Active micromixer, Mixing

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efficiency

Nomenclature
c Species concentration (mol/lit) q Heat-flux vector (W/m2)
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Cs Sound velocity (m/s) R Mean radius of the channel curvature (m)

D Diffusion coefficient (m2/s) Re Reynolds number
De Dean number t Time (s)
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Dh Hydraulic diameter (m) T Temperature (K)

e Energy (J) U Mean velocity (m/s)
f Disturbance frequency (Hz) V Velocity vector (m/s)
f Body force vector (N) Greek symbols
Fo Fourier number κ The ratio of specific heats
k Thermal conductivity (W/m.K) λ Mean free space (m)
Kn Knudsen number μ Dynamic viscosity (Pa.s)
L Characteristic length (m) ρ Density (kg/m3)
MI Mixing index
p Pressure (Pa) σT Tangential temperature coefficient
Pe Peclet number σv Tangential momentum coefficient
Pr Prandtl number τ Shear stress tensor (Pa)

1. Introduction
Lab-on-a-Chip (LOC) or microfluidic chips have been of great interest over the past two
decades. Microfluidic has many applications in the fields of engineering, biotechnology and
medicine. The history of microfluidics dates back to the 1950s, which was specifically used in
the production of inkjet printers [1]. The mechanism of these printers was based on microfluidic
devices, because they include very small tubes that carry ink for printing. In the 1970s, with the
advancement of silicon technology, this technology was developed into small mechanical
machines [2]. In the 1980s, with the advent of micro-valves and micro-pumps, the use of small-
scale technology was increased [1, 2]. In these years, several analytical systems were proposed

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based on micron methods. All of these samples showed the precision and control of microfluidic
devices when the volume of fluid was reduced [1]. Microfluidics has reached advanced stages
and many achievements. In principle, microfluidics can be used in many engineering, bio and

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medical sciences especially in Micro-Electro-Mechanical Systems (MEMS). MEMS are
combinations of mechanical components, sensors, mechanical arms, and electronic components
that are located on a layer of strategic material, such as silicon. Nguyen and Wereley [2] have

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presented the Fig. 1 for a better understanding of the size of microfluidic devices and the volume
of the fluid.
Microfluidic technology has specific characteristics such as small-scale particle control, low cost
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and rapid response time [3]. The development of microfluidic devices has led to a lot of interest
in using these devices in medical science and experimental chips [4]. The advantages of these
devices include reduction of the consumption of samples (reactants), high controllability and the
ability to manipulate samples during the process as well as high surface to volume ratio [4].
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The analysis time in microfluidic devices is much shorter than that in milli-scale ones. On the
other hand, high surface-to-volume ratio is an ideal property for microfluidic systems [5].
Therefore, application of these devices with laboratory equipment reduces the time required for
analysis as well as the required space [6-7].
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Fig. 1. Dimensions and sizes of microfluidic devices [2].

In the field of engineering, mixing and separation are of particular importance. These processes
(especially particle separation) can be used inside the human body, for example, the drug
delivery. Different methods are used for mixing of fluids. There are several reviews on
micromixers [8-14].
Since new structures have been proposed to improve the mixing quality, these reviews should be
updated. In addition, the mentioned reviews considered the types of micromixers and did not
perform a comprehensive review on fabrication of micromixers. In the present work, different
mixing techniques, various fabrication methods, different numerical schemes and different
design variants are reviewed comprehensively. In addition, the present article addresses recent
operating principles and techniques that have not been covered in the other review manuscripts.

2. Basic microfluidic equations

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2.1. Fluid flow and heat transfer equations
In general, the governing equations for the simulation of mixing process of Newtonian and non-
Newtonian fluids are continuity, momentum, and energy equations. These equations in
conservative form are presented as follows, respectively [15]:

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𝜕𝜌 (1)
+ ∇. 𝜌𝑽 = 0
𝜕𝑡

𝜕𝜌𝑽
𝜕𝑡
= −∇. (𝜌𝑽𝑽) + 𝜌𝐟 + ∇. 𝛕
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𝜕𝜌𝑒 (3)
= ∇. (𝜌𝑒𝐕 − 𝛕𝑽 + 𝐪)
𝜕𝑡
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where 𝐕 is velocity vector, 𝜌 is the density, 𝐟 is the body forces, 𝛕 is shear stress tensor, e is the
energy, p is the pressure, and q is the heat-flux vector. The shear stress tensor can be expressed
for Newtonian and non-Newtonian fluids.
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2.2. Convection-diffusion equation

The concentration distribution is determined using convection-diffusion transport equation [13]:

𝜕𝐜 (4)
+ 𝐕. ∇𝐜 = 𝐃∇2 𝐜
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𝜕𝑡

where c and D are the species concentration and diffusion coefficient, respectively.
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2.3. Governing dimensionless parameters

Dimensionless parameters that are used to describe the mixing process include Reynolds number
(the ratio of inertia to viscous forces), the Peclet number (the ratio of mass transport due to
convection to that of diffusion), the Fourier number (the ratio of diffusion to inertia force),
Knudsen number, and Dean number. These dimensionless parameters are defined as follows,
respectively [8, 9]:
 𝜌𝑈𝐷ℎ (5)
𝑅𝑒 =
𝜇

𝑈𝐿 (6)
𝑃𝑒 =
𝐷

𝑓𝐷ℎ (7)
𝑆𝑡 =
𝑈

𝐿𝐷 (8)
𝐹𝑜 = 2
𝐷ℎ 𝑈

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𝜅𝜋 𝑈 (9)
𝐾𝑛 = √
2 𝐶𝑠 𝐿

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(10)
𝐷ℎ
𝐷𝑒 = 𝑅𝑒√
𝑅

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where 𝐷ℎ is hydraulic diameter, L is characteristic length scale, f is disturbance frequency, U is
average velocity, 𝐶𝑠 is the sound velocity, R is the mean radius of the channel curvature, and 𝜅 is
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the ratio of specific heats.
The Reynolds number determines the flow patterns. In channel flow, critical Reynolds number is
about 1500. The fluid flow regime in microchannels is typically laminar due to small dimensions
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of channels and low fluid flow velocity. Micromixers may reach high mixing index at low, high
or optimal Reynolds number depends on their geometries, types of fluids, boundary conditions,
and external actuators. Peclet number is employed when there is a competition between
convection and diffusion. For the mixing process with a constant diffusion coefficient, the Peclet
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number indicates the flow rate through the channel. For laminar flow, the Peclet number is
proportional to the mixing length [9]. The Strouhal number is used to characterize the operation
conditions of active micromixers according to the disturbance frequency. The Fourier number is
defined as the ratio of tr to tm, where tr is the residence time and tm is the mixing time [16]. If Fo <
1, tr is sufficient for occurrence of mixing. Hence, when Fo is greater than one, the complete
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mixing can be achieved by decreasing the flow rate, reducing the characteristic length scale, or
increasing the channel length. Knudsen number is used to determine the regimes of fluid
rarefaction. As a result, no-slip or slip boundary conditions are employed based on the values of
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Knudsen number. In gas flow problems, no-slip boundary condition is imposed on the channel
walls for Kn < 10-3. When 10-3 < Kn < 10-1, slip boundary condition is employed. The values of
10-1 < Kn < 101 indicate transitional flow regime [17]. Finally, the Dean number is considered
for the micromixers with curved channels (for more details, see Sec. 5.1.4).

3. Numerical approaches
Numerical simulations of mixing process have been performed using commercial softwares such
as ANSYS/CFX, FLUENT and COMSOL Multiphysics or written codes, for instance, lattice
Boltzmann technique. Finite volume method (FVM) [18] and finite element method (FEM) [19]
have been used to solve the velocity field. The Semi-Implicit Method for Pressure Linked
Equations (SIMPLE) [20] and Semi-Implicit Method for Pressure Linked Equations-Consistent
(SIMPLEC) [18] algorithms have been employed for pressure-velocity coupling. To discretize
the velocity fields, upwind Quadratic Upstream Interpolation for Convective Kinematics
(QUICK) [18] and second order [21] schemes have been used. QUICK method is usually
employed for structured grids along the channel and upwind second order is commonly used for
complex flow paths (see Sec. 3.2 for more details). Slip [22] and no-slip [18] boundary
conditions have been imposed on the walls of microchannel for hydrophobic and hydrophilic
surfaces, respectively. Since most of experimental devices are made of hydrophilic materials, no-
slip boundary condition is more common in numerical simulations compared to the slip one. No-
slip/no-jump boundary conditions are valid for most microscopic fluids. In other words, the
velocity and temperature of the fluid are equal to the velocity and temperature of the wall (uwall =
uliquid|wall and Twall = Tliquid|wall) [1, 2].

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The above governing equations are also valid for gas flows, but their boundary conditions are
different. For the case of gases, the slip boundary condition is applied for temperature and
velocity depends on the Knudsen number. The velocity slip condition was determined by

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Maxwell [23]:

2 − 𝜎𝑣 𝜕𝑢 3 𝜇 𝜕𝑇 (11)

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𝑢𝑔𝑎𝑠 − 𝑢𝑤𝑎𝑙𝑙 = 𝜆 | + |
𝜎𝑣 𝜕𝑦 𝑤𝑎𝑙𝑙 4 𝜌𝑇𝑔𝑎𝑠 𝜕𝑥 𝑤𝑎𝑙𝑙

Also, temperature jump condition is defined as follows [24]:

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2 − 𝜎𝑇 2𝑘 𝜆 𝜕𝑇 (12)
𝑇𝑔𝑎𝑠 − 𝑇𝑤𝑎𝑙𝑙 = |
𝜎𝑇 𝑘 + 1 𝑃𝑟 𝜕𝑦 𝑤𝑎𝑙𝑙
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where 𝜎𝑣 and 𝜎𝑇 are the tangential momentum and temperature accommodation coefficients,
respectively. 𝜆 is the mean free space, k is the thermal conductivity, and Pr is the Prandtl
number. Slip flow regime using the above boundary conditions have been investigated by some
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researchers [25-27]. For example, Reyhanian et al. [27] analyzed the micromixing of two gases
for 10-2 < Kn < 0.5 using direct simulation Monte Carlo.

3.1. COMSOL Multiphysics software

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As mentioned before, commercial softwares are employed to simulate the microfluidic process.
Since COMSOL Multiphysics software is widely used in the study of passive and active
micromixers, some details are provided on the procedure of numerical simulations using this
software. To simulate the mixing process in passive and active micromixers (see Sec. 5), two
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main modules are “Fluid Flow_ Laminar Flow” and “Chemical Species Transport_ Transport of
Diluted”. Simple geometries can be sketched using COMSOL software and complex ones should
be created using other softwares such as AutoCAD and SolidWorks and then exported the ECAD
or DXF files to COMSOL. For non-Newtonian fluids, the models (Power Law, Carreau Model,
and User Defined) are chosen as follows: Laminar Flow_Fluid Properties_Dynamic Viscosity:
non-Newtonian. For active micromixers, external actuator is selected as Electric Current,
Magnetic Fields, etc. in AC_DC module. As mentioned before, several numerical simulations
have been conducted to evaluate the mixing process using COMSOL Multiphysics software.
References [28-34, 93, 103, 105, 107, 127, and 185] are some articles used this software
published between 2017 and 2019.

3.2. Numerical diffusion

Numerical diffusion in the numerical solution of mixing at the microscale is one of the critical
issues [35-38]. The estimation of mixing index in micromixers is affected by numerical diffusion
errors due to the occurrence of oscillations on the interface between the fluids especially when
Pe >> 1. Okuducu and Aral [35] investigated three-dimensional swirl-induced micromixers with
two and four fluid injections using FVM to evaluate the numerical diffusion effects. They
demonstrated that at Re = 240, grid resolution has a significant effect on the estimation of
numerical diffusion errors. It was reported that two-inlet configuration leads to higher numerical
diffusion than four-inlet one. They concluded that numerical diffusion generated in swirling
micromixers depends on the Peclet value and the flow pattern. Also, Okuducu and Aral [36]

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analyzed the mixing performance of a T-shaped micromixer using FVM and FEM and different
types of mesh. They found that at Re = 0.1, similar amount of numerical diffusion is produced
for different types of mesh (hexahedral, prism, and tetrahedral). They revealed that FEM can

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produce higher numerical diffusion error than FVM. The average false diffusivity was computed
for connective-diffusive mixing by Liu [37]. The author proposed a method for different
numerical schemes and various types of mesh. It was demonstrated that first order upwind

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scheme produces higher false diffusion than QUICK one. However, the accuracy of second order
upwind, QUICK, and Monotone Upstream Scheme for Conservation Laws (MUSCL) schemes in
terms of false diffusion is about the same. In addition, it was revealed that tetrahedral cells lead
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to higher numerical diffusion than hexahedral ones.

4. Fabrication techniques
In recent years, microtechnology has been developed rapidly. Now, microchannels are integrated
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with accessories such as sensors, actuators and other electronic devices, and used in laboratories
for biological applications [39]. Nano- and micro-scale devices have been studied for many
years, however the devices that are now available are much more accurate than previous ones
[40]. The application of microdevices depends on their materials. These materials are non-
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organic, such as silicon, Plexiglas and glass, or organic such as polydimethylciloxane (PDMS)
and polymethyl methacrylate (PMMA) that are rapidly developing with different fluids [41]. The
polymers such as PDMS, PMMA, etc. are used for micro and nanodevices due to their low cost
and environmental compatibility [39]. One of the main features to fabricate the microfluidic
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devices is their geometry. Another important factor is the particle size of the materials. Recently,
Chaurasia et al. [42] presented a unified microfluidic technique using oil-encapsulated calcium
alginate microfibers. They demonstrated that the encapsulate shape can be tuned for different
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geometries include spherical, ellipsoidal, etc.

Nowadays, a variety of techniques have been developed by microfluidic engineers to fabricate
microfluidic devices. These approaches can be classified as laminates, polymer molding, three-
dimensional printing, and nanofabrication. Most of micromixers can be fabricated using polymer
laminates [43]. In this approach, two or more layers are bonded together to create the
microchannel. Common materials in laminate device fabrication include polycarbonate, PMMA,
Cyclic Olefin Copolymer (COC), and glass. Laser cutter (usually CO2 laser) or knife plotter are
used to cut each layer [44]. Adhesive and thermal bonding methods are employed for bonding
the layers [45]. Second category is polymer molding include soft lithography, injection molding,
and hot embossing. Soft lithography uses photolithography such as SU-8 to pour and cure the
polymer like PDMS [46]. The cured PDMS is bonded with a glass side to form the
microchannel. Micro injection molding uses thermoplastics to form microfluidic devices
commercially. In this method, the melted thermoplastic is injected into a mold cavity and then
cooled [47]. In hot embossing technique, thermoplastics or polymers such as polycarbonate,
PMMA, COC, and polyethylen teraphthalate are shaped as microfluidic devices using a mold,
pressure and heat [48]. Third fabrication category is 3D printing, in which three-dimensional
model is created by the printer. Acrylonitrile butadiene styrene (ABS), polycarbonate,
polyamide, polystyrene, and PDMS are usually employed to create microfluidic devices using
different 3D printing techniques [49]. The last method to fabricate microdevices is
nanofabrication includes top-down [50] and bottom-up [51] methods. Electron beam lithography
and extreme ultraviolet lithography are currently used to fabricate microdevices. Their cost and
serial processing are two limitations of these methods.

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5. Micromixers
Microfluidic devices based on their stimulus can be divided into two categories: passive and

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active devices. Passive microfluidic devices do not use any external actuator to drive the fluids,
guide the particles in the fluid, separate them, etc. Active microfluidic devices use external
energy sources for mixing, separation, etc.

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There are some equations used by the researchers to quantify the mixing quality. Table 1
summarizes these relations, where 𝐶𝑖 , 𝐶𝑜 , 𝐶̅ , 𝐶𝑜̅ and 𝐶∞ indicate the point concentration, the point
concentration in the non-mixing cross section, the average concentration, the average
concentration in the non-mixing cross section and the concentration of completed mixing,
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respectively. Also, N and 𝛿 denote the number of nodes in the considered section and the section
width, respectively. Eq. (13) computes the mixing index using intensities of pixels across a
cross-section of channel. At the inlet MI = 0.5 and when the fluids are mixed completely, MI =
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0. Eq. (14) is an improved definition for mixing index. In this equation, mixing index is non-
dimensionalized by comparing the standard deviation to the average intensity. Some researchers
called the ratio as the Absolute Mixing Index (AMI) [52]. The values of 1 and 0 indicate
unmixed and fully mixed states, respectively. When the mixing index is non-dimensionalized by
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comparing the standard deviation to the intensity in non-mixing cross section, Eq. (15) can be
used. The difference between Eq. (15) and Eq. (16) is that the last one is expressed based on the
integral of the point concentration and intensities of pixels.
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Table 1. The equations used by the researchers for calculating the mixing index.
Equation Reference Equation number
𝑁 (𝐶 − 𝐶̅ )2 1/2
𝑖 [53] (13)
𝑀𝐼 = [∑ ]
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𝑖=1 𝑁
(𝐶𝑖 − 𝐶̅ )2
1/2
[54] (14)
[∑𝑁 ]
𝑖=1 𝑁
𝑀𝐼 = 1 −
𝐶̅
1
(𝐶𝑖 − 𝐶̅ )2 2
[∑𝑁 ] [55] (15)
𝑖=1 𝑁
𝑀𝐼 = 1 − 1
(𝐶𝑜 − ̅̅̅
𝐶𝑜 )2 2
[∑𝑁 ]
𝑖=1 𝑁
 𝛿
∫0 |𝐶𝑖 − 𝐶∞ |𝑑𝑦 [56] (16)
𝑀𝐼 = 1 − 𝛿
∫0 |𝐶𝑜 − 𝐶∞ |𝑑𝑦

There are many researchers who studied the mixing process in active or passive micromixers.
Suh and Kang [57] evaluated the advantages and disadvantages of passive micromixers.

5.1. Passive micromixers

The use of external energy sources leads to an increase in the costs. On the other hand, an
enhancement of molecular diffusion and chaotic advection of fluids results in an increase in the
mixing quality of passive (static) micromixers. The molecular diffusion and chaotic advection of
fluids can be increased by an enhancement in the contact surface between the fluids and a
reduction in the mixing path [8]. Passive micromixers are initially divided into two- and three-

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dimensional ones based on their structural dimensions. It should be pointed out that fabrication
of two-dimensional passive micromixers using lithography is simpler than three-dimensional
ones. Many special structures have been proposed for passive micromixers. Parallel lamination,

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multi lamination, obstacle (or baffle) based, curved-channel, convergence-divergence based, and
unsymmetrical are some features that have been considered in numerical and experimental
investigations.

5.1.1. Lamination based patterns

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In parallel lamination micromixers, the inlet flows are divided into two (T-type and Y-type
mixers) or more sub-streams (multi lamination patterns) [8]. T-type and Y-type micromixers are
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well known structures in which two streams are injected into two separate channels. The fluid
flows are then combined in a straight channel. Since the molecular diffusion causes the fluids to
mix in these types of micromixers, two long straight microchannels are required to achieve high
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mixing efficiency at low Reynolds numbers. Hessel et al. [9] reported that the mixing length Lm
= Pe × w for laminar flow, where w is the channel width. To provide fast mixing in this type of
micromixers, the researchers generate secondary flow, swirling flow and vortices at high-
Reynolds-number problems. For example, Wong et al. [58] used a diamond step close to the
main straight channel of a T-type micromixer fabricated from silicone/glass to disturb the fluid
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flow for the Reynolds number range of 400-500 (Fig. 2a). Even though the straight microchannel
was not roughened, the diamond step caused the flow to be asymmetry due to flow circulation.
Gobby et al. [59] evaluated the effect of orientation of two inlets of micro Y-mixers on mixing
characteristics and found that the shortest mixing length can be achieved by placing a throttle
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section in the beginning of the straight channels (Fig. 2b).

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 (a) (b)

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Fig. 2. (a) Schematic of T-type micromixer fabricated from glass/silicon [58] and (b) methanol
mass fraction contours in a venturi-type Y-mixer used for the mixing of oxygen and methanol
[59].

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In multi lamination patterns, the fluids enter the mixer with different arrangements compared to
Y-type pattern. They include multiple flows [60], hydrodynamic focusing [9, 61], interdigitated
mixing [62, 63] and cyclone arrangements [64]. These feed patterns result in a reduction in the

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mixing distance, leading to an excellent mixing in the millisecond range [8, 9]. Most of multi-
laminating patterns have three dimensions [65-73], i.e. the streams are joined horizontally and
vertically in subsequent stages. Hong et al. [74] introduced a two-dimensional modified Tesla
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configuration (Fig. 3a) fabricated from cyclic olefin copolymer (COC) using thermal bonding.
The increase in the mixing quality of this micromixer is due to chaotic advection due to Coanda
effect. Hossain et al. [75] optimized the modified Tesla pattern by considering the ratio of the
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diffuser gap to the channel width and also the ratio of the curved gap to the channel width for
0.05 < Re < 40. Yang et al. [76] proposed a three-dimensional Tesla structure for realization of
the cancer cells (Fig. 3b). Hong et al. [74] and Yang et al. [76] reported that two- and three-
dimensional Tesla structures work well for Re > 5 and 0.1 < Re < 100, respectively. Other three-
dimensional designs that have been proposed for multi lamination micromixers include C-shape
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[77] (Fig. 4a), H-C-shape [78] (Fig. 4b), H-shape [79] (Fig. 4c), L-shape [80] (Fig. 4d) etc. Table
2 compares the lamination based micromixers.
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(a) (b)
Fig. 3. (a) Schematic of two-dimensional modified Tesla structure [74] and (b) three-dimensional
Tesla structure [76].

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(a) (b)

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(c) (d)
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Fig. 4. Schematic of three-dimensional multi lamination micromixers: (a) C-shape [77], (b)
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Table 2. Lamination based micromixers.
Characteristic/ Re Pe Mixing Materials Year Reference
mixing species efficiency
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Optimized zigzag 0.1-100 n/r 100% Numerical 2017 [28]

microchannel / n/r simulation
T-shape: simple and 1-80 n/r 91% PDMS 2018 [29]
serpentine / distilled
water and Rhodamine
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B
Hybrid / n/r 0.001-45 n/r 100% PDMS 2018 [30]
T-shape / blue dye 500 7×105 83% Silicon/Pyrex 2004 [58]
and a colorless liquid glass
Y-shape / oxygen and
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0.1 150 n/r n/r 2001 [59]

methanol
Interdigital 0.07 60 95% Glass 1999 [60]
Interdigital / acetyl n/a n/r n/r Glass 2004 [61]
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chloride and n-butyl

amine
Interdigital / water 2-341 6.41×103- n/r Glass 2003 [62]
blue and pure water 1.07×106
Star / dye liquid 108 n/r n/r Numerical 2003 [63]
simulation
Focusing / blue dye 0.15 200 n/r PDMS-Glass 2004 [65]
and pure water
Split-join / M chloric 18 n/r n/r Silicon 1996 [66]
acid + methyl orange
dissolved in water -
oil + air - water + air
Split-join / dyed n/r n/r n/r Silicon/glass 1999 [67]
water
Split-join / 0.05 50 97% Myler 2004 [68]
fluorescein dissolved
into two different
buffers
Multi-stream / dyed 0.1 14 n/r Silicon/ PDMS 2004 [69]
water
Split-join / phenol- 0.03-0.66 15-330 n/r Silicon/glass 1996 [70]
red and an acid
Four-layer / D2O and n/r n/a 90% Silicon 2011 [71]
H2O
Three-layer / red < 5.5 n/a 85% Numerical 2013 [72]
and green colored simulation

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water
Crossing manifold / n/r n/r 90% Numerical 2011 [73]
DI water and ethanol simulation

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Modified 2D Tesla n/r n/r n/r Cyclic Olefin 2004 [74]
/ dyed DI water Copolymer
(COC)
Modified 2D Tesla / 0.05-40 n/r 70.2% Numerical 2010 [75]

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dyed DI water simulation
3D Tesla / DI water 0.1-100 n/r 94% PDMS 2015 [76]
and DI water
solution containing
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fluorescent dye
C-shape / water and n/r n/r 90% Numerical 2000 [77]
ethyl alcohol simulation
H-C-shape / Blue- 1-100 n/r 93% Polycarbonate 2016 [78]
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and yellow-colored
food-grade water
H-shape / colored 0.08-4.16 n/r 98% Plexiglas 2012 [79]
water solutions
L-shape / deionized 1-20 2×103-4×104 n/r PDMS 2003 [80]
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water, HCl, and H2O2

Serpentine / dyed 1-120 1×104- n/r Numerical 2018 [81]
water and pure water 1.2×106 simulation
Serpentine / blue ink 0.1-100 n/r > 95% PMMA 2016 [82]
and yellow ink
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T-shape / deionized 100-500 n/r ~ 65% PMMA 2019 [83]

water
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5.1.2. Obstacle (baffle) based patterns

Generation of vortices and chaotic advection by inserting obstacles in the microchannel results in
a reduction in the mixing length especially in simple designs such as T- and Y-mixers. Many
numerical and experimental investigations have used different configurations of obstacles to
evaluate the mixing process. Obstacle on the walls and obstacle in the microchannel are two
main classifications. It should be pointed out that these patterns are combined with other
configurations such as convergence-divergence and spiral that will be described in sections 5.1.3
and 5.1.4, respectively.
First, the micromixers with obstacles in channel are considered. Different layouts for obstacle
array were investigated by Wang et al. [84] for a Y-type micromixer (Fig. 5a). They
demonstrated that the obstacles can disturb the liquid flows and generate turbulence only for high
Reynolds numbers. It was also showed that the most efficient arrangement corresponds to the
asymmetric one. Alam et al. [85] used cylindrical obstructions in a curved-channel micromixer
for 0.1 < Re < 60 to investigate the mixing index between water and ethanol (Fig. 5b). They
compared different shapes of obstruction and demonstrated that mixers with circular and
hexagonal cross-section obstacles exhibit the same mixing quality. Lin et al. [86] also used
cylindrical obstacles in a microchannel to improve the mixing performance for working at high
Reynolds numbers, 200 < Re < 2000. Razavi Bazaz et al. [87] optimized the arrangement of four
rectangular obstacles in a T-type micromixer for 0.1 < Re < 60. They used Taguchi method to
evaluate the sensitivity of obstacle geometry and revealed that their height is more effective than
their width. Bhagat et al. [88] investigated the sensitivity of height and shape of circular,

of
triangular, diamond (smooth) and diamond (stepped) in the mixing process and demonstrated
that as the height of obstructions increases, the mixing quality increases. They found that the use
of circular obstacles leads to higher mixing efficiency compared to other ones. The obstacle

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configurations include chevron, check mark, arc, and straight [89], leakage side-channels [90],
triangle [91] and staggered grooves [92-96] have been proposed by researchers to obtain short
mixing length and high mixing index for various ranges of Reynolds numbers. Sadeghcheri et al.

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[89] employed round corner rectangular (RCR) and hexagonal (H) chambers and investigated the
mixing efficiency using four different obstacles (Fig. 5c) numerically and experimentally. They
concluded that the mixing performance of RCR chamber with straight obstacles is higher than
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that of other geometries. Different staggered grooves have been also evaluated to get higher
mixing of fluids in shorter microchannel length. Recently, Hama et al. [93] investigated reverse-
staggered herringbone micromixer (Fig. 5d) numerically and experimentally for 1 < Re < 100.
They demonstrated that mixing efficiency does not depend on the Reynolds number and
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diffusion coefficient for this range of Reynolds number.

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(a) (b)
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Jo

(c) (d)
Fig. 5. Schematic of obstacle based micromixers in which they are placed in the channel: (a)
cylindrical array [84], (b) cylindrical obstacles in a curved-channel mixer [85], (c) round corner
rectangular (RCR) and hexagonal (H) chambers with chevron (CH), check mark (CM), arc (A),
and straight (S) obstructions [89] and (d) reverse-staggered herringbone [93].
It should be mentioned that some of lamination based, obstacle based and divergence-
convergence based micromixers are known as spilt-and-recombine (SAR) or split-joint
micromixers [74-76, 89, 97-98]. He et al. [97] experimentally and numerically showed that a D-
shaped obstacles lead to the generation of extended vortex and Dean vortices, resulting in the
maximum mixing efficiency of 95% for Re = 80. Baheri Islami and Ahmadi [98] combined
passive (using rectangular obstacles) and active mixers (using oscillatory inlet velocity) to
achieve maximum mixing index of 98% at Re = 0.156.
The second category of obstacle based micromixers is those with the obstacles embedded on the
walls [17, 99-102]. Karthikeyan et al. [100] used micromixers with triangular and rectangular
obstacles on the walls to analyze and optimize the mixing quality of fluids having very low
diffusivity (O ~ 10-12 m2/s) (Fig. 6a) using ANOVA approach. Four parameters of height, pitch,
width and shape of obstacles were evaluated to find optimum layout for mixing of water and

of
blood. Tsai et al. [101] proposed a planar micromixer with radial obstacles on its wall (Fig. 6b)
and demonstrated that Dean vortices, expansion vortices after the obstructions and converging-
diverging flow in the gap between obstacles and mixer wall force the fluids to merge. Milotin et

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al. [102] analyzed the mixing efficiency of micromixers with bare microtube and quarter and half
cross-section obstacles as the orifice for 0.2 < Re < 91 (Fig. 6c). They revealed that the mixing
efficiency could reach 100% for the case of quarter cross-section at Re = 91. Recently, the Koch

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fractal snowflake has been used in obstacle-based micromixers to improve their mixing
performance [103-15]. Zhang et al. [103] used staggered Koch fractal-based micromixer to
enhance the mixing efficiency (Fig. 6d). The baffles were placed at the top and bottom of a T-
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mixer, leading to the mixing efficiency of 95% for Re = 0.05 and Re = 100. Chen et al. [105]
proposed a Koch fractal mixer with rounding corner pattern (Fig. 6e) and demonstrated that the
pressure drop in the micromixer with rounding corners is lower than that with secondary fractal
one.
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Table 3 compares some configurations of obstacles embedded through the channels or on the
walls of micromixers.
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(a) (b)
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(c)
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(d) (e)
Fig. 6. Schematic of obstacle based micromixers in which they are embedded on the wall: (a)
rectangular obstacles [100], (b) radial obstacles on curved wall [101], (c) bare microtube and half

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and quarter cross-section obstacles [102], (d) staggered Koch fractal [103] and (e) Koch fractal
mixer with rounding corner pattern [105].

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Table 3. Obstacle based micromixers.
Characteristic Re Pe Mixing Materials Year Reference
efficiency
Circular obstacle 0.13-1333 100-106 55% Numerical 2002 [84]
re
array in channel simulation
Circular and 0.1-60 n/r 88% Numerical 2014 [85]
hexagonal obstacles simulation
in curved channel
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Cylindrical obstacle 0.2 200 n/r Silicon/glass 2003 [86]

in channel
Rectangular obstacle 0.1-60 n/r 74.5% Numerical 2016 [87]
in channel simulation
Circular, triangular, 0.02-10 n/r 30% PDMS 2007 [88]
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diamond (smooth)
and diamond
(stepped) obstacles in
channel
Chevron, check 0.1-40 n/r 99% PDMS 2013 [89]
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mark, arc, and

straight obstacles in
channel
Reverse-staggered 0.01-100 34.4-34400 n/r PDMS 2018 [93]
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herringbone in
channel
Triangular and n/a n/r 68% Numerical 2017 [100]
rectangular obstacles simulation
on the wall
Radial obstacles on 0.01-100 n/r 93% PDMS 2011 [101]
curved wall
Half and quarter 0.2-91 n/r 100% Numerical 2016 [102]
cross-section of simulation
circular obstacles on
the wall
Koch fractal baffles 0.05-100 n/r 95% Numerical 2019 [103]
on the wall simulation
Rounded Koch 0.1-100 n/r 90% Numerical 2019 [105]
fractal baffles on the simulation
wall

5.1.3. Convergence-divergence patterns

These configurations are designed based on the generation of expansion vortices when the cross-
sectional area increases abruptly. These vortices are created in the horizontal plane, leading to an
enhancement in the contact region between the fluids [106-107]. Thus, mixing quality increases.
As mentioned in the previous section, convergence-divergence configurations are usually
combined with other patterns such as obstacle based, SAR and curved-channel based ones [97,
108-113]. Khosravi Parsa and Hormozi [106] investigated the generation of Dean and expansion

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vortices in convergent-divergent based micromixers for 0.2 < Re < 75. The convergent-divergent
cross section was created by changing the phase shift between the side walls. The maximum
mixing efficiency of 90% was obtained for the phase shifts between π/2 and 3π/4. Recently,
Mondal et al. [107] compared the mixing performance of micromixers with two configurations,

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called raccoon and serpentine (Fig. 7a). Their results revealed that the mixing index increases
with the wavelength for two types of micromixer, however, the mixing performance of raccoon
one is more appropriate than the serpentine one for given Reynolds number and wavelength.

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Afzal and Kim [108-109] investigated different combinations of SAR and convergence-
divergence patterns for 10 < Re < 70 and showed that mixing index is strongly dependent on the
ratio of throat-width to the diameter of circular wall of the micromixer (Fig. 7b). Tran-Minh et
re
al. [111] designed a micromixer in which ellipse-like micropillars caused the fluid to converge
and diverge and reached the efficiency of 90% for laminar blood mixing (Fig. 7c). Chen and Li
[112] employed a topological micromixer to improve the mixing performance by increasing
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chaotic advection. The mixing efficiency was 95% and 85% for the ranges of (Re < 0.1 and Re >
10) and (0.1 < Re < 10), respectively.
Asymmetric structures of the microchannel are another category of divergence-convergence
micromixers. Rhombic micromixers proposed by Chung and Shih [113] and Hossain and Kim
[114] are two examples of asymmetric passive micromixers. Chung and Shih [113] revealed that
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combination effects of focusing/diverging, recirculation and Dean vortices lead to very high
mixing efficiency. It was observed that Dean vortices and recirculation are strongly depend on
the size of the gap between the baffle and channel wall. Their micromixer was modified by
Hossain and Kim [114]. They proposed two-split and three-split rhombic configurations and
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reached the mixing efficiency of 86% for three-split one at Re = 60. Recently, Raza and Kim
[115] investigated the mixing performance in unbalanced SAR micromixers for 0.1 < Re < 120
(Fig. 7d). They reported that the mixing efficiency reaches 86% and 95% for Re > 20 and Re >
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50, respectively. Table 4 compares some convergence-divergence based micromixers.

(a) (b)
 (c) (d)
Fig. 7. Schematic of convergence-divergence based micromixers: (a) serpentine [103], (b) SAR
and convergence-divergence [109], (c) ellipse-like micropillars [111], and (d) unbalanced SAR
[115].

Table 4. Convergence-divergence based micromixers.

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Characteristic Re Pe Mixing Materials Year Reference
efficiency
Sinusoidal side walls 0.2-75 n/r 90% Plexiglas 2014 [106]
Raccoon and 0.1-100 n/r ~ 100% Numerical 2019 [107]

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serpentine simulation
SAR and 10-70 n/r 95% Numerical 2012 [108]
convergence- simulation
divergence

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SAR and 10-70 n/r 95% Numerical 2014 [109]
convergence- simulation
divergence
Ellipse-like 0.238-2.38 238-2381 90% Numerical 2014 [111]
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micropillars simulation
Re < 0.1 n/r 85%
and Re > Numerical
Topological 10 simulation 2016 [112]
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0.1-10 95%
Rhombic > 20 n/r 84% PDMS 2007 [113]
Unbalanced SAR Re > 20 n/r 86% PDMS 2019 [115]
Re > 50 95%
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5.1.4. Curved-channel patterns

The main characteristic of curved micromixers is that they perform well at high Reynolds
numbers. The Dean number is a dimensionless parameter that describes the fluid flow in this
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type of micromixer [9]. It was revealed that for De > 150 and De < 150, the secondary flow
consists of two and four vortices, respectively [116]. It is obvious that several loops are required
to get high mixing efficiency. Hence, creative designs have been proposed to enhance the mixing
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performance of curved-channel mixers using few numbers of loops. In addition, as pointed out
before, this pattern is combined with other configurations such as obstacle-based and
convergence-divergence ones [109, 115]. Schönfeld and Hardt [117] proposed a three-
dimensional micromixer build up from two curved square channel relying on various types of
Dean vortices. Jiang et al. [118] found that the mixing process depends on the value of Dean
number that is larger or smaller than 140. They proposed a planer meander mixer and stated that
chaotic mixing is induced without multistep or three-dimensional structure (Fig. 8a). Spiral
microchannels with several mixing sections that are joined by a central S-section were proposed
by Sudarsan and Ugaz [119] (Fig. 8b). They considered five spiral configurations for 0.02 < Re <
18.6 and reported that transverse Dean flows lead to the mixing efficiency > 90%. Santana et al.
[120] used this design to mix Jatropha curcas oil and ethanol and showed that the mixing
performance of spiral micromixer is much higher than that of T-type one. Mehrdel et al. [121]
modified this design using expansion and contraction parts (Fig. 8c) and reached the mixing
efficiency of 85% and 98.5% for one and three loops with 10% expansion, respectively, at Re =
1. Inspired by spiral configurations, several designs have been proposed to investigate the effect
of Dean vortices on mixing performance of micromixers [122-130]. Scherr et al. [123] proposed
a logarithmic-spiral based micromixer experimentally using PDMS (Fig. 8d). They achieved
mixing efficiency of 86% for Re = 67 and demonstrated that logarithmic curvature leads to the
generation of three-dimensional Dean vortices due to variable cross-sectional area. A micromixer
composed of staggered three-quarter ring-shaped channels and a semi-circular channel was
designed by Sheu et al. [124] (Fig. 8e). The authors concluded that the secondary flows are
negligible for Re < 5 and are considerable at Re = 50. Double layers of spiral channel were used

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by Yang et al. [125] (Fig. 8f), Rafiei et al. [126] (Fig. 8g) and Clark et al. [127] (Fig. 8h) to
design three-dimensional micromixers. Yang et al. [125] demonstrated that mixing index
increases with the height of channel and using cylindrical geometry instead of cubical one. Rafiei

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et al. [126] developed a fine-threaded lemniscated-shaped mixer for 1 < Re < 1000 and reached
the mixing efficiency of > 90%. Non-rectangular cross-sections were employed by Clark et al.
[127] to investigate their effects on the Dean flows in a spiral micromixer. They showed that full

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mixing is obtained at Re = 20 in their proposed mixers, while it can be achieved at Re = 100 in
rectangular cross-section mixer. Table 5 compares curved-channel micromixers.
re
lP

(a) (b) (c)

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(d) (e)
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(f) (g) (h)

Fig. 8. Schematic of curved-channel micromixers: (a) planer meander mixer [118], (b) double
spiral [119], (c) double spiral with expansion and contraction [121], (d) logarithmic spiral [123],
(e) tapered curved [124], (f) two layers of spiral channels overlapped together [125], (g) fine-
threaded lemniscated-shaped [126], and (h) non-rectangular cross-section [127].

Table 5. Curved-channel micromixers.

Characteristic Re Pe Mixing Materials Year Reference
efficiency
3D curved square 2-2012 1-900 n/r Numerical 2004 [117]
channel simulation
planer curved > 313 n/r n/r PMMA 2004 [118]
channel < 313
Double spiral 0.02-18.6 n/r > 90% SEBS 2006 [119]
Double spiral with [121]
expansion and 0.1-10 439-1836 98.5% PDMS 2018
contraction

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Spiral and concentric 0.6 n/r ~ 40% Aluminum 2012 [122]
circular
Logarithmic spiral 1-70 n/r 86% PDMS 2012 [123]
Tapered curved 1-100 n/r 88% PDMS 2012 [124]

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Two layers of spiral
channels overlapped 8-40 n/r 90% Glass 2012 [125]
together
Fine-threaded 1-1000 n/r > 90% PDMS 2017 [126]

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lemniscated-shaped
Non-rectangular 1-100 n/r ~ 100% Numerical 2018 [127]
cross-section simulation
Spiral, interlocking- 0.01-50 n/r ~ 100% PDMS 2015 [128]
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semicircle, Ω channel
Double helical 0.003-30 n/r 99% Numerical 2015 [129]
channel simulation
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Square, semi-circle,
trapezoid cross 20-277 n/r > 90% PDMS 2017 [130]
sections

5.2. Active micromixers

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External energy sources are used to enhance the mixing quality by increasing the contact area
between the fluids, disturbing them or inducing the chaotic advection. Pressure filed [131-138],
acoustic filed [139-152], magnetic field [153-171], electric field [172-192], thermal field [193-
205], etc. are types of external energy sources.
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5.2.1. Pressure-driven micromixers

The earliest pressure-driven micromixer proposed by Deshmukh et al. [131] was a T-type
micromixer. They used an integrated planar micropump to induce alternative fluid perturbation
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by driving and stopping the flow in the channel. In other words, the step function was used to
generate pulsatile flow; hence many pulses were required to mix the fluids. Velocity pulsing has
been also used to disturb the fluids and increase their contact area [132-135]. Niu and Lee [132]
designed a pressure-driven micromixer according to fluid stretching and folding concepts (Fig.
9a). They used Lyapunov exponent to describe the chaotic behavior and optimize their proposed
micromixer. Wu et al. [136] investigated the effect of oscillatory/pulsatile flow on the mixing
performance of a micromixer (Fig. 9b). They demonstrated that stretching and folding of the
fluids increase due to oscillatory flow and the mixing index reaches 97% after four mixing units
for total flow rate of 44 ml/min and fluid viscosity of 8 mPa s. Li and Kim [137] used constant
input of water head pressure to create pulsatile pressure in the mixer unit (Fig. 9c). Their
proposed micromixer exhibited the mixing efficiency of about 90% for a range of flow rates up
to 20 μl/min and the frequency range of 14-20 Hz. Recently, Zhang et al. [138] investigated the
time pulsed mixing for Newtonian and viscoelastic fluids in a T-mixer (Fig. 9d). They
demonstrated that as the time pulsing increases, the mixing index of Newtonian fluids decreases
and increases for 0.002 < Re < 0.01 and 0.1 < Re < 0.2, respectively. They also revealed that the
mixing of viscoelastic fluids is independent of the time pulsing for Weissenberg numbers Wi <
20, however, it reaches a high value for Wi = 50. Table 6 compares some pressure-driven
micromixers.

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(a) (b)

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(c) (d)
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Fig. 9. Schematic of pressure-driven micromixers: (a) one pair of side channels [132], (b)
oscillatory/pulsatile flow in a micromixer [136], (c) Oscillator unit in a mixer [137], and (d)
time-pulsed flow in a micromixer [138].

Table 6. Pressure-driven micromixers.

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Characteristic Re Mixing Materials Year Reference

efficiency
Pulsatile flow 2.4 n/r SOI and quartz 2000 [131]
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wafers
Multiple side n/r n/r Modelling 2003 [132]
channels
Electric circuit 0.17 n/r Analytical 2012 [133]
methods solution
Planar mixing 83-250 90% n/r 2013 [135]
channel
Pulsatile n/r 90% PDMS 2017 [136]
micromixer
Oscillator and n/r 97% PMMA 2018 [137]
divergent chambers
 Newtonian:
Time-pulsed flow 0.002-0.1 ~ 53% PDMS 2019 [138]
Viscoelastic:
82%

5.2.2. Acoustic field driven micromixers

Acoustically-induced microstreams have been used in micromixers as the air bubbles in a liquid
are energized due to an acoustic field [139]. Moroney et al. [140] described the application of an
acoustic actuator to stir liquids in a flexible-plate-wave (FPW) system. Liu et al. [139] used a
piezoelectric disk to energize the bubbles at a frequency of 5 kHz. The use of higher frequencies
(> 50 Hz) leads to an increase in the temperature of fluids that is harmful for biological samples
[8, 141]. In bubble-based acoustic micromixers, single [139] or many bubbles [142] can be
generated due to different causes. Ahmed et al. [142] generated an air bubble in a horse-shoe
pattern in a micromixer using acoustic waves (Fig. 10a). The excited trapped air bubble disturbs

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the laminar flows in the channel, resulting in their excellent and so fast mixing. They
characterized the mixing time as t = dmix/vavg, where dmix and vavg are the distance between
unmixed and full mixed regions and the average fluid velocity, respectively. It was concluded

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that as the number of air bubbles increases, the mixing time decreases considerably [139]. Wang
et al. [143] investigated the influence of applied frequency (0.5-10 kHz) on mixing performance
of a micromixer (Fig. 10b) and concluded that low (0.5 kHz) and high frequencies (10 kHz) do

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not affect the mixing index. However, the mixing efficiency is strongly dependent on applied
frequencies between 1.0 to 5.0 kHz. This frequency range resulted in the generation of single or
multiple bubbles, leading to disturbance in the local flow field. They demonstrated that the
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mixing efficiency increases significantly by generation of bubbles in the frequency range of 1.0
to 5.0 kHz. Bubbles were not occurred in the microchannel outside this range of actuation
frequency. Orbay et al. [144] introduced a bubble-based acoustic micromixer with three inlets in
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which nitrogen injected into the center inlet to form bubbles in the mixer. Their proposed
micromixer worked well for high viscous liquids at low Reynolds numbers.
The other types of acoustic micromixers involve ultrasonic transducers [145-146], thin film
piezoelectric devices [147-148] and surface acoustic wave ones [149-150]. Yang et al. [146]
introduced a micromixer made up of glass to achieve a homogeneous mixture using ultrasonic
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vibration (Fig. 10c). The ultrasonic vibration was generated by a piezoelectric lead-zirconate-
titanate (PZT) ceramic. Luong et al. [151] proposed a surface-acoustic-wave-driven micromixer
using parallel and focusing interdigitated electrodes (Fig. 10d). It was showed that the mixing
performance depends on applied voltage. It was reported that the focusing type leads to higher
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mixing index compared to parallel one. Unlike many investigators who used planar piezoelectric
transducers with flat surfaces, Lim et al. [152] proposed concave and convex surface structures.
They revealed that convex geometry leads to higher mixing quality than flat and concave ones.
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Table 7 compares the characteristics of some acoustic field driven micromixers.

 (a) (b)

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(c) (d)
Fig. 10. Schematic of acoustic filed driven micromixers: (a) bubble-based acoustic micromixer
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[142], (b) bubble-based acoustic micromixer [143], (c) ultrasonic transducers [146], and (d)
parallel interdigitated electrodes design [151].

Table 7. Acoustic field driven micromixers.

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Characteristic Re Frequency Mixing Materials Year Reference

(kHz) efficiency
Bubble vibration n/r 5 91% PZT 2002 [139]
Single-bubbled based n/r 70-100 n/r PDMS 2009 [142]
Multi-bubbled based n/r 1-5 n/r PMMA 2012 [143]
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Multi-bubbled based ~ 0.01 1-5 93% PDMS 2016 [144]

Ultrasonic vibration 60 0-100 n/r Glass 2001 [146]
Surface-acoustic- 3.1-15.4 1300 88% PDMS 2010 [151]
wave-driven
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Piezoelectric
transducer with << 1 220-260 45% n/r 2019 [152]
curved surface

5.2.3. Magnetic-field driven micromixers

Micromixers are magnetically actuated by permanent magnet [153-158], electromagnet [159-
164], microstirrer [165-168] and integrated electrodes [169-170]. Chen and Zhang [171] gave a
review on magnetic field driven micromixers. As a part of present review article, we considered
the magnetically driven micromixers include articles published in recent years. Ballard et al.
[153] used a permanent magnet rotating over a micromixer with magnetic microbeads orbiting
around NiFe discs placed on the floor (Fig. 11a). Nouri et al. [155] used permanent magnet to
investigate the mixing process of deionized water and Fe3O4 ferrofluid in a rectangular cross-
sectional Y-mixer (Fig. 11b). Hejazian and Nguyen [156] employed a permanent magnet induced
non-uniform magnetic field in a straight microchannel to evaluate the mixing of diluted
ferrofluid and a non-magnetic flow (Fig. 11c). Kumar et al. [158] developed a numerical model
to simulate mass transfer enhancement due to a non-uniform magnetic field. They demonstrated
that mass transfer increases with magnetic field strength and size of magnetic particles.
Fu et al. [159] studied the mixing of ferrofluid and DI water in a micromixer which used an
electromagnet driven by a DC electric field (Fig. 11d) numerically and experimentally. The
permanent magnet was placed parallel to the microchannel. Ergin et al. [160] used microPIV
technique to analyze transient flow fields during the mixing process. A new magnetic
micromixer based on a flexible artificial cilium made up of Fe doped PDMS was presented by
Liu et al. [161]. The mixing efficiency of 80% was obtained using the cilia micromixer under a

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magnetic strength of 200 G. Four electromagnet placed opposite to each other were used in a
micromixer to mix Rhodamine dye and DI water by Soraj et al. [162] (Fig. 11e). They
determined a critical actuation frequency, where the mixing degree decreases with the actuation

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frequency for the frequencies greater than critical one. Boroun and Larachi [163] investigated the
mixing performance of a T-mixer under static, oscillating and rotating magnetic fields for 10 <
Re < 200. It was concluded that the mixing index increases with the magnetic field intensity.

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They reported that rotating magnetic field leads to better mixing performance compared to static
and oscillatory ones.
Kang et al. [165] used magnetic particles as magnetic chains to induce the chaotic mixing under
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a rotating magnetic field. Their results were presented based on Mason number that is the ratio of
magnetic to viscous forces. Symmetric and asymmetric motion of artificial cilia was investigated
by Chen et al. [166] for enhancing fluid mixing. They demonstrated that the mixing due to the
asymmetric motion is 1.34 times faster than that due to the symmetric one. Veldurthi et al. [167]
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placed a microrotor in a chamber to obtain maximum mixing quality. The magnetic actuator was
made of magnetic nanoparticles dispersed PDMS and the micromixer was fabricated with PDMS
(Fig. 11f). They achieved the mixing efficiency of 90%. Owen et al. [168] used a regular array of
magnetic microbeads to increase the fluid mixing in a channel. They reported that longer array of
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beads leads to higher mixing efficiency.

Kang and Choi [169] designed and fabricated a micropump for mixing at low Reynolds numbers.
They revealed that different lengths of electrodes lead to better mixing performance than the
electrodes with the same lengths. The micromixer worked based on the Lorentz force and the
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moving force applied on charged particles. Jeon et al. [170] evaluated the shape and arrangement
of electrodes and the applied voltage on the mixing of a reagent and phosphate buffered solution
(PBS).
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Table 8 compares some magnetic field driven micromixers.

 (a) (b)

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(c) (d)

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re
lP
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(e) (f)
Fig. 11. Schematic of magnetic field driven micromixers: (a) rotating permanent magnet [153],
(b) Permanent parallel magnet [155], (c) permanent parallel magnet [156], (d) electromagnet
driven by a DC electric field [159], (e) four electromagnet placed opposite to each other [162],
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(f) cylindrical chamber with microrotor [166].

Table 8. Magnetic field driven micromixers.

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Characteristic Re Magnetic Mixing Materials Year Reference

field strength efficiency
(G)
Permanent magnet
rotating over a << 1 n/r 70% PDMS 2016 [153]
micromixer with
magnetic microbeads
Permanent parallel n/r 1280-3000 90% Plexiglas 2017 [155]
magnet
Permanent parallel n/r 1750-2500 88% PDMS 2017 [156]
magnet
 Electromagnet 0.004 200 > 95% n/r 2010 [159]
and 0.02
Electromagnet n/r 2200 80% Fe doped 2016 [161]
PDMS
Electromagnet n/r 4200 and n/r Polystyrene 2016 [162]
6000
Static, oscillating and
rotating 10-200 0-90 kA/m ~ 53% Glass 2017 [163]
electromagnet
Electromagnet 5-50 n/r 96% Numerical 2019 [164]
simulation
Asymmetric 4.64×10-3 n/r 100% PDMS 2014 [166]
actuation of artificial
cilia
Cylindrical chamber 0-40 n/r 90% PDMS 2015 [167]

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with microrotor
Array of rotating n/r n/r ~ 72% NiFe 2016 [168]
magnetic microbeads
Integrated electrodes n/r n/r 27.8% PDMS 2011 [169]

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Integrated electrodes n/r n/r 100% Numerical 2017 [170]
simulation

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5.2.4. Electric-field driven micromixers
Electrohydrodynamic (EHD) disturbance [132, 172-174] and electrokinetic (EKI) instability
[175-192] are used in electrical field driven micromixers. Alternating current (AC) and direct
current (DC) electric fields are used to charge the fluids in EHD instability-based micromixers.
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The charged fluids disturb the interface, leading to an enhancement in the mixing performance of
micromixers. EI Moctar et al. [172] proposed a T-type micromixer in which an electric field that
was perpendicular to the interface was applied to the fluids, leading to the creation of a
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secondary flow. They used AC and DC electric fields at Re = 0.0174 and observed that a
reasonable mixing can be achieved in less than 0.1 s. A Y-mixer with an array of inclined
electrodes on the bottom of the main channel was considered by Huang et al. [173] (Fig. 12a).
The authors observed that four vortices are generated above each electrode pair so that two
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strong vortices remain for a long time and two weak ones cancelled out.
EKI instability occurs when a liquid or particles move towards a charged surface. EKI mixing
methods include electroosmosis [175-186], electrophoresis [187-189] and dielectrophoresis
[190-192]. Zhang et al. [175] numerically and analytically studied mixing of electroosmosis flow
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in microchannles with heterogeneous zeta potential. They demonstrated that symmetrical

secondary flows and asymmetrical rolls are generated due to heterogeneous zeta potential,
resulting in an improvement in the mixing rate of fluids. Ebrahimi et al. [176] considered a T-
type microchannel to evaluate the effect of non-uniform DC electric field on mixing and heat
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transfer characteristics for four ribbed channel configurations. They gave interesting results
about the mixing rate of fluids: if the Schmidt number is less than a critical one, the mixing index
decreases by applying the electric field. Vertical flow enhancement was also observed by
Bhattacharyya and Bera [177] for an electroosmosis-pressure driven microchannel with a
rectangular block due to the difference between the surface potential of block and the channel
wall. Ahmadian Yazdi et al. [179] investigated the effect of ionic size on diffusion in a Y-
micromixer at high zeta potentials. They revealed that the mixing length is a decreasing function
of ionic concentration for high zeta potentials. The mechanism of chaotic mixing was studied by
Shamloo et al. [180] using a charged electrode array with AC electric field. Different
configurations of one-ring, two-ring and diamond types were considered and it was reported that
the diamond type has maximum index of 99.8% in comparison one-ring and two-ring ones.
Matsubara and Narumi [181] proposed an electroosmotic micromixer with a staggered array of
electrodes with AC signal for 0.005 < Re < 1.0. They showed that a core vortex is generated
between the electrode pairs and two vortices are formed before and after them for the case of
oscillating electroosmotic flow. Kazemi et al. [182] studied the mixing performance of an
electroosmotic micromixer by placing an electrical conductive flap at the entrance of the main
channel. Asymmetrical planar floating-electrodes were mounted in a T-mixer by Zhang et al.
[185] to induce asymmetrical vortices. They obtained the mixing quality of 94.7% for a
frequency of 400 Hz with the mixing length of 3.2 mm. Recently, Usefian and Bayareh [186]
proposed a novel electroosmotic micromixer (Fig. 12b) in the presence of AC and DC electric
fields. Their results revealed that the generated vortices due to DC electric field are stronger than
those formed by AC one. It was showed that the mixing index increases with the applied voltage

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of AC and DC electric fields.
Electrophoresis is defined as the motion of conductive or non-conductive particles due to an
external electric field that is applied to a solution of an electrolyte. It should be pointed out that

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the use of conductive particles leads to higher mixing index due to convection. Daghighi and Li
[187] proposed a new electrophoresis micromixer including a cylindrical chamber connected to
straight channels. A circular conductive particle was placed in the chamber (Fig. 12c). They

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observed that the external electric field induces vortices around the particle, leading to an
enhancement in the mixing rate of the solution. The optimum angle of 45° was found for
applying the external electric field relative to the channel direction. Daghighi et al. [188]
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experimentally observed the vortices generated around conductive and non-conductive particles
due to the applied electric field. The generation of vortices and flow circulations around a
conductive particle was studied by Kazemi et al. [189] during mixing process in a micromixer
which consisted of a rectangular chamber connected to microchannels. They demonstrated that at
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a specific zeta potential, as the electric field increases, the outlet mass flow rate increases,
leading to a reduction in the mixing quality.
Dielectrophoresis is defined as the motion of neutrally particles due to AC electric field. It leads
to the formation of asymmetric polarization of the particles. A dipole moment is formed on the
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particles, resulting in a force causes the particles to move away or towards the electrodes. The
stretching and folding phenomena occur due to the accumulation of particles in a quasi no-
velocity region, leading to chaotic motion and an increase in the mixing index. Deval et al. [191]
presented a dielectrophoretic micromixer to induce the chaotic motion of particles and showed
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that the mixing time decreases dramatically. Similar to electrophoretic micromixers, conductive
particles can be used in dielectrophoretic ones to improve their mixing performance due to the
convection. Kim et al. [192] proposed a new micro/nano mixer based on dielectrophoresis
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technique (Fig. 12d). It was demonstrated that as the channel depth decreases, the mixing quality
increases. However, the channel depth must be greater than about 20 micrometers.
Table 9 summarizes the characteristics of some electric-field driven micromixers.
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(c) (d)

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Fig. 12. Schematic of electric-field driven micromixers: (a) EHD based micromixer with an array
of inclined electrodes [173], (b) an electroosmotic micromixer with two electrodes [186], (c)
electrophoretic micromixer with a conductive particle [187], and (d) dielectrophoretic
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micro/nano mixer [192].

Table 9. Electric-field driven micromixers.

Characteristic Re Frequency Mixing Materials Year Reference
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(Hz) efficiency
EHD (perpendicular 0.0174 0.5-100 ~ 81% Lexan 2003 [172]
electrode array)
EHD (inclined n/r 1000 94% n/r 2011 [173]
electrode array)
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Electroosmosis- 10 n/r 71% Numerical 2014 [178]

pressure driven simulation
Electroosmosis n/r n/r 99.5% Numerical 2015 [179]
mixing at high zeta simulation
potentials
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Electroosmosis n/r 2-16 99.8% Numerical 2016 [180]

mixing in a diamond simulation
type mixer
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Electroosmotic 0.2-2
micromixer with a 0.005-1.0 (dimensionless ~ 98% Numerical 2016 [181]
staggered array of frequency) simulation
electrodes
Electroosmotic Numerical
micromixer with a n/r n/r 51.5% simulation 2017 [182]
throat
Electroosmotic
micromixer with n/r n/r ~ 98% Numerical 2019 [183]
rotating inner simulation
obstacle
 Turbulent-like <1 1-10000 n/r Transparent 2017 [184]
electroosmotic mixer acrylic
Planar floating-
electrodes in a T- n/r 400 94.7% Glass 2018 [185]
mixer
Electroosmotic
micromixer with two n/r 0.5-4 ~ 96% PDMS 2019 [186]
electrodes in a
chamber
Electrophoretic n/r n/r 100% Numerical 2013 [187]
micromixer with simulation
cylindrical chamber
Electrophoretic
micromixer with n/r n/r 99.5% Numerical 2017 [189]
rectangular chamber simulation

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Dielectrophoretic 0.02 n/r n/r Si-SU8-glass 2002 [191]
micromixer
Dielectrophoretic n/r n/r n/r Silicon 2008 [192]
micromixer

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5.2.5. Thermal-field driven micromixers
Thermal energy can be used to improve mixing performance of micromixers by increasing the

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diffusion coefficient [193], utilizing thermal bubbles [194-196] or using electrothermal effects
[197-202]. Huang and Tsou [195] used microvalve and micropump to implement a thermal
bubble based micromixer (Fig. 13a). It was revealed that larger thermal bubbles lead to higher
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mixing capacity. Tan [196] simulated the mixing of a dye solution and pure water in a Y-mixer
with an embedded microheater (Fig. 13b). Thermal bubbles play the role of a micropump and
drive the streams. The author revealed that if the microheater embedded asymmetrically,
asymmetric vortex and secondary flow are generated, leading to an enhancement in the mixing
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rate. Maximum mixing index of 95.6% was obtained when the microheater was placed in the
channel inlet. Zhang et al. [199] employed AC electrothermal flow to increase the mixing of two
laminar streams. Two asymmetric planar electrodes were mounted along the microchannel and a
thin film resistive placed below the electrodes. They showed that the temperature gradient
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created by external heating leads to stretching and folding of fluid flow, resulting in higher
mixing quality. Electrothermal actuated micromixers were also investigated by Kunti et al. [200-
201]. Kunti et al. [200] used the characteristics of passive micromixers by using grooved floor
and the advantages of electrothermal micromixers by mounting pairs of asymmetric electrodes
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on the walls. They achieved the mixing efficiency of 97.25% for the flow rate of 29.9 μl/s. Meng
et al. [202] used AC electrothermal advantages to design a micromixer for biomicrofluidic
applications. The micromixer consisted of two straight channels and a cylindrical chamber. The
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streams were actuated in the chamber due to four arc electrodes (Fig. 13c), leading to the mixing
index of 100%.
Table 10 summarizes the characteristics of some thermal-field driven micromixers.
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(c)
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Fig. 13. Schematic of thermal-field driven micromixers: (a) thermal-bubble actuated micromixer
[195], (b) Y-mixer with an embedded microheater [197], and (c) AC electrothermal micromixer
with four arc electrodes [202].
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Table 10. Thermal-field driven micromixers.

Characteristic Flow rate Mixing Materials Year Reference
(μl/s) efficiency
Thermal-bubble 4.5 n/r SOI 2014 [195]
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actuated micromixer
Electrothermal 0.214 95.6% Numerical 2019 [196]
micromixer simulation
Electrothermal n/r 83.6% Numerical 2016 [199]
micromixer simulation
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Electrothermal 29.9 97.25% Numerical 2017 [200]

micromixer simulation
Electrothermal Inlet
micromixer velocity ~ 100% PDMS 2018 [202]
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40 μm/s

6. Discussion
Characteristic nondimensional numbers such as Reynolds number, Peclet number, Strouhal
number, Fourier number and Knudsen number determine the operation conditions of passive and
active micromixers. Since viscous effects are dominant in microscale, mixing occurs due to
molecular-diffusion mechanism. Hence, passive micromixers need long channel length or
complex geometry, leading to high pressure drop along the mixer. Thus, the ratio of mixing
index to pressure drop (MI/∆p) should be calculated. It is obvious that a fast flow (high-
Reynolds-number flow) has a short residence time (tr), hence higher disturbance frequency (for
active micromixers) or longer channel length (or shorter characteristic length) (for passive
micromixers) are required. As a result, Strouhal number and Fourier number characterize the
mixing process in active and passive micromixers, respectively. Mixing of viscoelastic fluids in
microchannels is affected by viscous and elastic effects. It was revealed that sharper and smaller
geometries can be used to increase the chaotic flow instability, leading to higher mixing quality
[203]. The dimensionless Deborah number that is defined as the ratio of elastic and viscous
forces is employed to characterize the mixing of viscoelastic fluid streams. As the Deborah
number increases, the flow instability at the interface is suppressed by the elastic force.
Therefore, the geometry and external actuators play a crucial role to improve the mixing
efficiency of viscoelastic fluids. The constitutive models such as Oldroyd-B, Phan-Thien-Tanner
(PTT), Giesekus, etc. can be used to describe the flow of viscoelastic fluids [204].
In numerical simulations, the quantification of the mixing index is strongly depends on the

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numerical diffusion error. Types of grid and discretization method have significant influences on
the generation of false diffusion in the numerical simulations. The presentation of reports about
the numerical diffusion error is required to obtain valid mixing index especially for three-

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dimensional micromixers. Time-dependent approach is another important issue in the numerical
study of micromixers. Most of numerical simulations have not considered time-dependent
scheme to evaluate the mixing performance of the micromixers. Since the mixing time is an

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essential characteristic parameter of micromixers, it is required to perform time-dependent
simulations especially for the case of validation with the experimental results.
Many fabrication techniques with different materials have been used to make micromixers.
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Nowadays, soft lithography using PDMS is widely used in academic microfluidic labs to
evaluate the mixing process or particle separation for biomedical devices. The PDMS can be
combined with carbon nanotubes or solid nanoparticles to exhibit different thermal and electrical
conductivities. In addition, hydrophobic-hydrophilic properties can be controlled by dispersing
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nanoparticles in the PDMS during the molding process. 3D printing technique is inexpensive for
fabricating micromixers in comparison with the molding method. Since the fabrication process is
controlled by machine, this technology is cheaper and faster than lithography, thus it can be
commercialized. However, the resolutions of PDMS products are higher than those of 3D
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printing ones [205]. In addition, the fabrication of multi-material chips is still a challenge for 3D
printing technology.
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7. Conclusions
Passive and active micromixers have been attracted many researchers in recent years due to their
applications in many situations such as chemical, medical and biochemical ones. Passive
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micromixers have been widely used due to their simple fabrication. To enhance their mixing
performance, three-dimensional complex designs have been proposed. The researchers combined
different configurations of passive micromixers to improve their mixing performance. The use of
active micromixers leads to higher mixing index for wider range of Reynolds numbers.
Experimentally, electric-field driven and thermal-field driven micromixers have not been
considered in comparison with the micromixers use pressure, magnetic and acoustic fields.

Conflict of Interest
The authors confirm that: This manuscript has not been submitted to, nor is under review at, another
journal or other publishing venue. The authors have no affiliation with any organization with a direct or
indirect financial interest in the subject matter discussed in the manuscript

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