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Analyst's Preface
Research is being conducted on the concentration and separation of particles and fluids through various channel designs
using inertial microfluidics. In general, the inertial force is ignored in microfluidics, but in the middle range of Reynolds number
(Re) from 1 to 100, it has a theoretical background that inertial microfluidics occurs between the Stokes region and the turbulent
flow region. In this range, both the inertia and the fluid viscosity have finite values, so that the driving force of the inertial
microfluidics device, such as inertial movement and secondary flow, can be derived. Since the inertial force can be maximized
with high processing capacity, inertial microfluidic devices are simple and inexpensive devices, but inertial microfluidic devices
are very useful for sample processing. In this analysis, starting from the basic mechanics of particles, we introduce the recently
developed concept of inertial microfluidics and deal with its applications in depth. Finally, particle control using fluid inertia inside
Key words: Inertial microfluidics, Lift force, Drag Force, Inertial migration, Secondary flow, inertial microfluidics
Body mechanics, lift, drag, inertial movement, secondary flow
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A phenomenon in which particles move laterally in a straight Therefore, it can be divided into four areas [8].
channel and arrive at an equilibrium position from a
sufficiently large distance, observed more than 50 years (a) 10-4 < Re < 0.2
ago [5]. This phenomenon is caused by the shear gradient µv t
lift force ( FLS), which pushes particles from the center of
f drag = 12
a
the channel due to the curved velocity distribution, and the
wall-induced lift force (which pushes particles from the wall This region is the well-known Stokes drag
surface due to the interaction between the particles and the force. where vt is the relative velocity of the fluid to
wall). It is caused by the interaction between the wall lift the particle.
force ( FLW) . The equilibrium position of the two lift forces
is generally approximately 0.6 times the radius from the (b) 0.2 < Re < 500-1000
center of the channel in the case of a circular channel. ÿv t ) 0.678
f = 12 1+ 0.15
( Re drag
Secondary flow occurs when there is an obstruction in a a
curved or straight channel [6, 7]. Along the curvature of the
curved channel, inconsistency in the momentum of the fluid (c) 500-1000 < Re < 2×105
occurs at the center and near the wall, which induces a 2
0.22
drag
f=ÿv ft
pressure difference, resulting in secondary flow. The center
2. Basic Mechanics of Particle Behavior in Channels Brownian motion is a random motion that
occurs when particles suspended in a fluid collide
2.1. viscous resistance
with atoms or molecules of the fluid. According to
the Einstein-Smoluchowski theory, the mean square
Drag occurs when there is relative motion between
the fluid and the object. The drag force acting on a
distance that a particle spreads during the particle's
2 2r = 6 Dt
= ×fdragdrag =
FS f ÿa
drag /4
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ÿ ÿ
One 3 ÿÿ
= ÿ×
FLR ÿa ÿf (u f up ) ÿ
kT 8
D
= 3ÿÿa
The direction of Magnus is the relative and angular velocity vectors.
ÿ
k is the Boltzmann constant (1.3806488×10-23 is vertical, and rotates at an angular velocity of actual ÿS .
ÿ
J·K-1 ), and T is the absolute temperature [9]. If particles The relative speed ÿ of the sphere is:
and flow systems move in microchannels, the Péclet
ÿÿ
ÿ ÿS=0.5
ÿ ÿ×
u f
[10].
representative velocity of the fluid. A large Péclet number indicates that 2.4. Saffman force
the motion of the particles due to the flow is large, while a small Péclet number
The Péclet number indicates that the movement of particles The inertial movement of the particle is caused by
due to diffusion is large. Diffusion is generally negligible in the presence of walls as well as the particle's inertia in the
inertial fluid dynamics. parabolic velocity distribution. When there is no channel
wall, the velocity distribution is uniform and there is no
2.3. Magnus force velocity gradient, so inertial movement does not occur.
Thus, the existence of the wall generates velocity gradients
Assume that a fixed cylinder rotates at a constant and shear-induced particle rotation. And it induces
angular velocity (ÿ) under the condition of inviscid flow additional drag force by the wall on the particle. The lateral
with a uniform U velocity and no slip occurs on the surface force generated by this slip-shear motion is called the
of the cylinder. According to Bernoulli's law, the pressure Saffman force. The flow around the particle is disturbed
below the cylinder is greater than the pressure above it. by the wall, which has a different inertial effect from the
Therefore, the amount of cylinder lift per unit length is as particle in the infinite flow [11]. Using the matched
follows [11]. asymptotic expansion method, Saffman calculated the
lateral lift force of a particle under infinite flow conditions.
ÿ ÿÿ
=
2
× The magnitude of this force is
F ÿa
LRÿfU ÿ
2
The lift of a sphere rotating in a stationary state, = ÿÿÿ
FK/S 4Va
( One
) 1/2
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The velocity gradient caused by the existence of the wall Same as [13].
causes the Magnus force and the Saffman force to move the particle
in the transverse direction. In general, the impact of the wall retards 3 * *ÿ5/2
vZ =
ÿ
Re s v s(d 2 + 2.21901d +
...)
the horizontal and vertical movement of the particle and imposes a 16
transverse movement. When the particle is very small compared to
the size of the channel, the main role of the wall is to slow the particle This means that for a large d* , as d* goes to infinity, the
down and move it away from the wall. In addition, when the size of lateral speed gradually decreases and converges to zero.
the channel and the particle are similar, the movement of the particle
is severely inhibited [11]. First, when the size of the particle is very In addition, not only the lateral lift force, but also the effect of
small compared to the channel, the direction the wall increases the lift force. Therefore, when a/2lw<<1<<1/ Res,
of motion of the particle is parallel or perpendicular to the wall. the lift force by the wall is as follows [14].
follows [13].
µv t
f a = 16 f 3/2
a ÿ 3 a One ÿ
=3
F dÿÿav S 1+ Re S
ÿ
ÿÿ ..
ÿ
0.095 ÿ ÿ ÿÿ+ ÿ
n1
= ( 2 1 2 3)(+ nn
ÿ
If the size of the particle and the size of the channel have the
2sinh 2 1+n )ÿ + +2n1 sinh
) 2 ( ÿW
× W
2 2
ÿ)ÿ)ÿ same number of digits in the bounding flow, the surrounding particles
2
+
ÿ ÿ ÿ 4sinh ( [(
n0
. 5 (ÿ) ] (ÿÿ
2 n1 sinh
) (ÿ W
W move to the center of the channel. To prevent the channel from
where ÿW=cosh-1 (2/ a) is a function of the size of the particle channel to the diameter of the particle) must be less than 1.
and the distance from the wall, and lw is the distance from the center
of the particle to the channel wall. This shows that the force increases
acts to push the particle away from the wall. If d* <<1 (d* = ÿf lwÿs/ If the curvature of the undisturbed flow becomes zero, simple
ÿ), the transversal velocity is expressed as [12]. shear flow occurs. If the particle is slow compared to the flow, the
pressure is high on the wall side and moves the particle to the center
where VS is the settling velocity of the particles in the particle approaches the center.
stationary state. Transverse speed when the sphere is positioned near a wall
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This occurs and pushes the particles to the wall. viscosity [17].
2.7. net inertia lift deformability when the droplet or bubble is not very close to the
wall [18].
force due to slip shear, and the wall induced drag and velocity 16 ÿ
gradient due to flow disturbance. due to shear-induced drag. Of f ÿ( )d =
(ÿ d1 + )3
)ÿ
induced drag force tends to move the particle toward the wall, and 140 3 ÿ d2 +
ÿ ÿ
the wall-induced drag force tends to move it toward the center of
the channel. The particle is located where these two forces are in
Here, d is the distance of the droplet from the center of the
equilibrium.
channel, and when ÿd < 1 or ÿd > 10, the deformability-induced
Asmolov used the coherent asymptotic expansion method
drag acts on the center of the channel.
to obtain the net inertial drag for a spherical particle that is very
By Di Carlo, the inertial lift force expression was derived
small compared to the channel in a Poiseuille flow [15].
when the particle is close to the center of the channel and d/H<0.1
[16].
FL= f ÿLU
f
a /2H4 2
center
F L, inertial = ÿ10 Rp Ua(d/
µ H)
affected and healthy red blood cells or otherwise cancer cells [20,
Biological particles such as cells and vesicles undergo
21]. Figure 1 shows the inertial force acting on a particle.
deformation within the channel. This deformation induces an
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3
3. Recent inertial microfluidics H
×U
= 3ÿÿH
Lmin ÿ 3
2U L ÿ fUa
3.1. straight channel
Particles randomly distributed in a straight channel with a where UL is the lateral movement speed of the particle and
circular cross-section move laterally from the center of the channel As follows.
0.5), the particle is located in the center of the channel width, about
And the size of the particle and the size of the channel
0.2H away from the wall
[23]. The minimum length (Lmin) required to reach the The Reynolds number considered is additionally considered.
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When Rp<<1, the particle mainly receives the drag velocity in a secondary flow can be inferred as
Hur et al. isolated an enveloped progenitor from rat adrenal And approximately, the size of UD can be obtained as
digestive fluid in a channel with a high aspect ratio [24]. And follows [28].
inertial lift force separating the particles. The authors experiences both inertial lift and secondary flow drag. In most
demonstrated that it can remove 80% of bacteria. Afterwards, cases, since the particle density is similar to that of a fluid, it
Zhou et al. modified the shape of the channel to have a low is possible to ignore the effect of the particle centrifugal force.
aspect ratio in two steps to increase the separation efficiency When the sign of the channel curvature is the same, the
of the particles [26]. channel has a spiral structure and the direction of the
In general, using a straight channel has the advantage particle is related to its secondary flow drag. This drag force
that the channel shape is simple and can be operated easily. acts on all particles in the vortex rotating symmetrically. In
However, there is a problem in that the cross-sectional shape contrast, inertial lift tends to direct particles to a specific
of the channel is limited to provide sufficient lateral lift and location. Therefore, the ratio between the inertial lift force
increases flow resistance. and the Dean drag force (Rf=a3 R/ H4 ) determines the behavior of the particle.
3.2. spiral channel when Rf goes to ÿ, the inertial lift force dominates, so the
particles are located in the equilibrium position regardless of
When a fluid flows through a curved channel, a the secondary flow [4]. In most cases, the equilibrium position
secondary flow occurs due to the velocity difference between due to the inertial lift force is controlled by the secondary flow
the center and the wall of the channel. The center of the at a moderate Rf . The
channel has a large inertia, and due to the centrifugal effect, sorting and separation of particles in spiral channels
a pressure gradient is generated at the cross section of the has been intensively performed by various groups. Among
channel, resulting in a flow that flows out of the curve. Due them, passive separation or alignment of particles or cells
to the pressure gradient at the center of the channel, the using inertial lift and secondary flow is frequently used in
fluid around the wall, which was relatively still, circulates these spiral channels. Bhagat et al. perfectly separated 7.32
inside, eventually forming two symmetrical vortices [4]. The ÿm and 1.9 ÿm polystyrene particles [29], and
secondary flow in the curved channel is affected by the Dean Kuntaegowdanahalli et al. separated 10, 15, and 20 ÿm
number and the Reynolds number. When the hydraulic beads with 90% efficiency [30]. In addition, this separation
diameter of the square tube is H and the radius of curvature ability is helpful for studies related to cell properties and cell
1/2
Cancer cells, known as malignant tumors, have the
K = H/
( 2R) Re
potential to invade or proliferate in other tissues in our body.
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network is the cause [31]. During the process of It can be seen that they can be separated.
metastasis, cancer cells come out of the solid tumor Guan et al. introduced a novel spiral channel with
and enter the blood vessels to become circulating tumor a trapezoidal cross section and showed that this channel
cells (CTCs). Such CTC analysis is known to be very has higher separation efficiency than a simple rectangular
important for cancer treatment and diagnosis. Hou et al. channel [34]. They observed that the case of trapezoidal
proposed a spiral channel to isolate CTCs from blood cross section was more sensitive to the size and flow of
[32]. The CTC separation device showed the the particle, so that a distinct process of change
performance of separating CTCs without any abnormality according to the size of the particle in the measured
or deformation in a non-labeled and clogged method. flow rate appeared. [35] This device shed 7.5 ml of blood
Figure 2(a) shows the passive double spiral channel for 8 minutes and showed the efficiency of removing all
proposed by Sun et al. This device isolated cancer cells 10 CTCs contained in it.
(MCF-7 and HeLa cells) from diluted blood at an
efficiency of 3.33 × 107 cells per min [33]. Compared to
a single helix channel, it can transport particles with better efficiency.
Fig. 2 (a) Double spiral channel for separation of circulating tumor cells (CTC) from blood,
(b) spiral channel with trapezoidal cross-section for rapid separation of cancer cells [1].
3.3. Straight channels with columns and shrink-extension By using the Nin channel, it is possible not only to focus
arrangements particles but also to separate multiple particles. Figure
3(a) shows that polystyrene beads with diameters of 4
In addition to curved channels, convective ÿm and 10 ÿm are pipe-separated by generating a
secondary flow is also generated by installing secondary flow similar to a Dean vortex using this CEA
disturbance obstacles in straight channels. This study channel [37]. Particles of relatively large size are greatly
was initially proposed to increase the mixing efficiency. affected by this inertial lift force and move in the direction
Park et al. demonstrated that if a rectilinear channel of repeating expansion and contraction. On the other
repeatedly contracts and expands, particles can be hand, small-sized particles receive a lot of Dean drag
three-dimensionally focused into a single streamline and move in the opposite direction. Using this concept,
[36]. At the entrance of the constriction region, centrifugal it is possible to separate particles or cells of different
force acts and two symmetrical vortices are generated sizes.
at the cross section of the channel. This contraction-expansion array (CEA) is supported.
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Figure 3 (a) inertial separation channel using contraction-expansion array, (b) inertial focusing channel using symmetric contraction-expansion arrangement,
and (c) inertial separation channel using circular column[1].
Even if these CEAs are made symmetrically, In addition to raising, research is also conducted to
secondary flows can be generated. Park et al. used generate horizontal micro-vortices in the contraction-
this symmetrical CEA to focus the particles in three expansion chamber under high flow conditions. Shelby
dimensions and created an orifice at the end of the et al. demonstrated horizontal microvortices for the
channel to show that the particles were focused in two first time using diamond-shaped cavities [39]. The
dimensions (Fig. 3(b)) [38]. It was confirmed that the rotation speed of these micro vortices is very fast,
focusing position of particles in this device changes about 12 m sÿ1 , and the radial acceleration has a
according to the particle Reynolds number Rp . When magnitude of 106 g . This rapid acceleration is effective
Rp is in the range of 0.8 to 2.3, the particles are located in promoting biochemical reactions. An optical tweezer
on both sides. However, when Rp is in the range of 3.0 is also used to generate micro-vortices. Later, Di
to 3.5, it is located in the center of the channel. This Carlo's group introduced the concept of
focusing characteristic is caused by the inertial drag centrifuge-on-a chip using this vortex trap ping and
and inertial force caused by the mismatch between the inertial movement and used it to selectively separate
moving trajectories of the particles and the fluid in the target particles [40]. This chip has a straight channel
region where contraction and expansion occur. Such section and a symmetrical CEA, and creates a cavity
a device is called multiorifice flow fractionation (MOFF). expansion section to generate microvortices. Particles
Although this MOFF has many advantages, it has a focused in a straight channel circulate in a micro vortex
relatively low recovery yield. In order to improve these while transversely moving in an extended area. Here,
disadvantages, many researchers are conducting it is further developed to selectively trap particles and
studies to improve this and isolate cells associated apply it to blood and other biological samples to isolate
with CTC or other malignant cells.
diseases. When a secondary flow is generated in such a channel cross section
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to generate irreversible twisted flows. As shown in Fig. which equilibrium is reached becomes one position, and
3(c), the flow can be controlled in various ways by it becomes more complicated as the number of Dean
adjusting the position of the continuous columns inside increases. The forces acting on these are the inertial lift
the channel. Amini et al. efficiently separated particles force (FL) and the Dean drag force (FD), and the focusing
and flows using these complex shapes [41]. Nunes et al. position of the particles varies according to the
also fabricated non-circular particles using microchannels relationship between these forces. If FL<<FD, particle
with such pillars [42]. It has a great advantage because focusing does not occur. And in the case of FD<<FL ,
it can produce various shapes by controlling the flow. particle focusing similar to a straight channel is observed.
The relationship between the two forces is defined as FL/
FD=2R/H(a/H)3 Re n (n<0) as follows. It is proportional
3.4. meandering channel to the third power of the particle and channel size.
Therefore, even with the same Reynolds number, small
In a curved channel, the curvature is in one particles are not focused regardless of the channel
direction. Therefore, after a certain length, the secondary length, and large particles are focused quickly. Based
flow reaches a steady state. However, in the case of a on this concept, various channels and flow cytometry
serpentine channel, the situation becomes complicated systems for focusing particles have been proposed.
because the curvature is constantly changing. When the Figure 4 is a hybrid microfluidic device that uses both
curvature changes, the secondary flow does not reach inertial movement and magnetophoresis to separate
the steady state after each rotation. Accumulation of CTCs from blood. In this device, there is a circular
these abnormal states can lead to unpredictable particle column arrangement to separate the smallest red blood
behavior. cells first, then the meandering channel allows the white
Di Carlo et al studied the change in the inertial blood cells and CTC to flow and align them by inertial
movement of particles when the curvature changes [23]. movement, and then a strong magnetic field is applied to
The four equilibrium positions of the particles in the linear the final channel to remove them. For this purpose, the CTC is magnetically lab
channel changed to two symmetrical positions. threshold
Figure 4. Hybrid microfluidic system (inertial displacement, magnetophoresis) for the separation of CTCs from blood [1]
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not only have a mixing effect but also focus particles in the 10. R. Clift, JR Grace and ME Weber, Bubbles,
center of the channel, enabling various applications and drops, and particles, Courier Corporation, 2005.
high processing efficiency. 11. E. Michaelides, Particles, bubbles & drops: their motion,
heat and mass transfer, World Scientific, Singapore, 2006.
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