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Manipulation of microparticles using surface


acoustic wave in microfluidic systems: A brief
review

Article in Korea-Australia rheology journal · December 2012


DOI: 10.1007/s13367-011-0031-5

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Korea-Australia Rheology Journal
Vol. 23, No. 4, December 2011 pp. 255-267
DOI: 10.1007/s13367-011-0031-5

Manipulation of microparticles using surface acoustic wave in


microfluidic systems : a brief review
Jeonghun Nam, Hyunjung Lim and Sehyun Shin*
School of Mechanical Engineering, Korea University, Seoul, Korea
(Received October 21, 2011)

Abstract
Manipulation of microparticles, which include engineering particles, droplets and cells, has gained attention
in various research fields that use microfluidic devices, such as biochemical analyses and clinical diagnosis.
Among the microparticle manipulation techniques, microparticle separation has become particularly critical
for continuous flow-based analysis, including biochemical assay and clinical diagnosis. Recently, micro-
particle manipulation techniques using single surface acoustic wave (SAW) or multiple SAWs, namely
standing surface acoustic waves (SSAWs) have gained attention in microfluidics because they are non-inva-
sive, label-free, and easy to integrate into microfluidic circuits. This review paper focuses foremost on the
most recent advances and application of SAW-driven microparticle separation in microfluidics, and presents
analytical models for acoustic separation in microparticle suspension. In addition, recent developments in
SAW-driven microparticle manipulation are categorized according to their applications and discussed.
Keywords : microfluidics, surface acoustic waves (SAW), manipulation, separation, sorting, particles

1. Introduction particles in complex fluids, which contain polymer beads,


ceramics, cells, nanoparticles, and droplets, has become a
Recently, micro total analysis system (micro TAS) and critical issue in various applications, including industrial
lab-on-a-chip (LOC) technologies have advanced rapidly. processing (Xia et al., 2002), environmental assessment
These techniques offer many advantages, including the (Doucet et al., 2004), biochemical analyses (Dittrich et al.,
reduction in sample and reagent use, high sensitivity, and 2006; Wu et al., 2008), and clinical diagnosis (Cheng et
short processing time, compared to conventional tech- al., 2007; Gascoyne et al., 2004).
niques. Among the many essential techniques such as sam- Therefore, the recent advancements of continuous flow-
ple preparation (filtration, washing, sorting, separation), based microparticle separation techniques are reviewed in
translation (pumping, valving), and sensing/detection, the this paper, and the fundamental theory describing the
manipulation technique of microparticles has become most acoustic forces involved in and the analytical models used
important for the micro TAS. for microparticle separation in suspension are described. In
Among the microparticle manipulation techniques, the addition, various applications of microparticle manipula-
separation of microparticles from complex fluids, also tion using single SAW or multiple SAWs are categorized
called colloids, has gained much attention in the area of and discussed.
continuous flow-based biological and chemical analyses
(Bhagat et al., 2010; Cheng et al., 2007; Dittrich et al., 2. Operating Principles and Methods
2006; Gascoyne et al., 2004; Gossett et al., 2010; Jones,
2002; Lenshof and Laurell, 2010; Wu et al., 2008). Blood, Microfluidic-based microparticle separation systems
for example, would be the most familar complex fluid, have been developed by various approaches. The
consisting of poly-dispersed blood cells in plasma. Plate- approaches can be classified as active- or passive- methods
lets, circulating tumor cells (CTCs), and nucleated red based on the separation priniciple. As listed in Table 1, pas-
blood cells (NRBCs) frequently need to be separated from sive methods are based on the hydrodynamic force effect
a blood sample. In addition to application to a blood sam- due to channel geometry (Choi et al., 2011; Tan et al.,
ple, the microfluidic-based separation technology is widely 2004; Tan et al., 2008; Yang et al., 2009) or flow profile
applied in various industrial applications. The separation of (Maenaka et al., 2008; Tan and Lee, 2005), whereas active
methods use external forces for separation of microparti-
*Corresponding author: lexerdshin@korea.ac.kr cles such as optical force (Hung et al., 2010), electokinetic/
© 2011 The Korean Society of Rheology and Springer dielectric forces (Braschler et al., 2008; Cui et al., 2009;

Korea-Australia Rheology Journal December 2011 Vol. 23, No. 4 255


Jeonghun Nam, Hyunjung Lim and Sehyun Shin

digitated transducers (IDTs) patterned on a piezoelectric


substrate as shown in Fig. 1(a), which contracts and
expands upon application of a RF (Radio Frequency) sig-
nal of AC voltages to the IDTs. Continuous deformations
of the piezoelectric substrate result in surface acoustic
wave (SAW) generation and propagation along the sub-
strate surface. The wavelength of the SAW is determined
by the IDT pitch design, λ = 2d , and the working fre-
quency f of the SAW is determined by the relation,
f = cs ⁄ λ , where cs is the wave propagation speed in the
piezo-electrical substrate ( cs : 3950~4000 m/s for LiNbO3
(lithum-niobate)) (Wong, 2002). When the SAW comes
into contact with a liquid, the acoustic energy diffracts into
the liquid due to the difference between the wave propa-
Fig. 1. Surface acoustic wave microfluidic device. (a) Single sur- gation speed in the piezoelectric substrate, cs , and that in
face acoustic wave (SAW) generated by patterned inter- the liquid, c l (~1485 m/s for water), launching the leaky
digitated transducers (IDTs) on a piezoelectric substrate. SAW with decaying amplitude. The refraction angle, which
The wavelength of SAW is determined by the IDT pitch is referred to as the Rayleigh angle, can be calculated by the
design, λ = 2d . (b) Multiple SAWs, which create the ratio of the sound velocity in the piezoelectric substrate to
standing surface acoustic wave (SSAW), are actuated by the sound velocity in the liquid, θR = sin –1(c1 ⁄ cs) .
a pair IDTs on the surface of a piezoelectric substrate. The Acoustic streaming resulting from the compressibility of
superposition of two opposing, identical SAWs results in
the bulk fluid at the high frequency used for SAW actu-
the standing surface acoustic wave (SSAW).
ation induces the bulk fluid to move. Acoustic streaming of
surface acoustic waves is typically used in microfluidic
Jellema et al., 2009; Kim et al., 2008; Piacentini., 2011), mixing (Sritharan et al., 2006; Tseng et al., 2006), pump-
magnetic force (Berger et al., 2001; Pamme et al., 2006; ing (Cecchini et al., 2008; Guttenberg et al., 2004), con-
Qu et al., 2008), pneumatic force (Lee et al., 2009; Wakui centration (Li et al., 2007; Li et al., 2008; Raghavan et al.,
et al., 2010), and bulk acoustic forces (Adams et al., 2010; 2010), microparticle patterning (Smorodin et al., 2005;
Evander et al., 2007; Laurell et al., 2007; Lenshof et al., Strobl et al., 2004), and microparticle directing (Franke et
2009; Nilsson et al., 2004; Petersson et al., 2005; Petersson al., 2009; Franke et al., 2010).
et al., 2007; Thevoz et al., 2010). Recently, a compre- On the other hand, multiple SAWs, which create a stand-
hensive review was done on the most recent developments ing surface acoustic wave (SSAW), can be formed by actu-
in microparticle separation technology in microfluidics ating a pair of interdigitated transducers (IDTs). When AC
(Bhagat et al., 2010; Gossett et al., 2010; Lenshof and Lau- signals are applied to a pair of IDTs, two series of surface
rell, 2010). acoustic waves from each IDT propagate in opposite direc-
Although microparticle separation systems in microflu- tions to the microchannel. The superposition of two oppos-
idics have advanced in various ways, they can be further ing, identical SAWs give rise to constructive and
improved to use the physical properties of microparticles, destructive interference, which results in a standing surface
such as size, density, or deformability. A novel micropar- acoustic wave (SSAW) with pressure nodes (minimum
ticle separation method based on the intrinsic physical pressure amplitude) and anti-pressure nodes (maximum
properties of microparticles, which is able to yield high- pressure amplitude), as shown in Fig. 1(b). These pressure
throughput, high-resolution and label-free, is needed espe- fluctuations result in lateral acoustic radiation forces that
cially for biological and chemical applications. act on the microparticles suspended in a medium, making
More recently, a method of microparticle manipulation them migrate to either the pressure nodes or the anti-pres-
using surface acoustic wave (SAW) has been proposed and sure nodes, depending on the relative density and com-
this method uses the physical properties of microparticles, pressibility between the microparticles and the medium, as
such as size, density, or compressibility. Unlike electrical shown in Fig. 2. Recently, several research groups intro-
(Piacentini, 2011), optical (Hung et al., 2010) or magnetic duced standing surface acoustic wave (SSAW)-based
methods (Qu et al., 2008), the SAW-based microparticle microparticle manipulation techniques in microfluidics,
manipulation method features non-invasiveness, low such as microparticle jetting (Tan et al., 2009), micropar-
power operation with high energy density, no contamina- ticle focusing (Shi et al., 2008b; Shi et al. 2011; Zeng et
tion, and easy integration into microfluidics by soft lithog- al., 2010), microparticle tweezing (Shi et al., 2008a; Shi et
raphy techniques. al., 2009a; Wood et al., 2008; Wood et al., 2009), and
SAW-based manipulation devices are made up of inter- microparticle separation (Nam et al. 2011a; Nam et al.

256 Korea-Australia Rheology Journal


Manipulation of microparticles using surface acoustic wave in microfluidic systems : a brief review

Fig. 2. Working principle of microparticle migration in SSAW-working area. Constructive and destructive interferences, which result
from the superposition of two opposing SAWs, generate SSAW with pressure nodes (minimum pressure amplitude) and anti-
pressure nodes (maximum pressure amplitude). These pressure fluctuations result in acoustic radiation forces on the micro-
particles in the medium, forcing them to migrate toward either the pressure nodes or the anti-pressure nodes, depending on the
relative density and compressibility between the microparticles and the medium.

Table 1. Methods for the separation of microparticles

Method Name Advantages Disadvantages References

Challenging when
Channel using high concen- Choi et al., 2011, Tan et al., 2004,
High resolution
geometry tration sample Multi- Tan et al., 2008, Yang et al., 2009
steps for high purity
Passive
High flow rate
Easy integration into massive Requiring dilution of Maenaka et al., 2008,
Flow profile
parallel system sample Tan and Lee, 2005
Wide range of flow rate

Few application in
continuous system
Optical High resolution Low efficiency Hung et al., 2010
High-cost laser
equipments required

Braschler et al., 2008, Cui et al.,


Electrokinetic/ Easy integration Difficult in
2009, Jellema et al., 2009, Kim et
dielectic Able to detect biological states fabrication
al., 2008, Piacentini., 2011

High-cost equip-
Pneumatic Non-invasive Lee at al., 2009, Wakui et al., 2010
ments required

Active Adams et al., 2010, Evander et al.,


Bulk Acoustic Non-invasive 2007, Laurell et al., 2007, Lenshof
Wave Non-labeling Expensive materials et al., 2009, Nilsson et al., 2004,
(BAW) Any particles available Petersson et al., 2005, Petersson et
al., 2007, Thevoz et al., 2010

Berger et al., 2001, Pamme et al.,


Magnetic Relatively high recovery ratio Low flow rate
2006, Qu et al., 2008

Non-invasive
Surface Acoustic
Non-labeling Franke et al., 2009, Franke et al.,
Wave Exsitance of force-
Any particles available Flexible func- 2010, Shi et al., 2009b, Nam et al.
(single or less effective area
tion by designing electrode 2011a, Nam et al. 2011b
multiple SAWs)
Easy to integrate with other techniques

Korea-Australia Rheology Journal December 2011 Vol. 23, No. 4 257


Jeonghun Nam, Hyunjung Lim and Sehyun Shin

2011b; Shi et al. 2009b). radiation forces. Each force has already been well devel-
The configuration of IDTs is also regarded as a critical fac- oped for analytical models in previous researches and their
tor affecting the performance of a single SAW or multiple detailed derivations can be found elsewhere (Bruus, 2008;
SAWs. The electrodes of interdigitated transducers (IDTs) Lee et al., 2006; Shi et al., 2009b).
can be formed in various configurations for specific pur- Firstly, it is necessary to estimate the width of the
poses: (1) parallel IDTs ,which are commonly used (Franke focused flow due to hydrodynamic focusing with sheath
et al. 2009; Nam et al. 2011a; Nam et al. 2011b; Shi et al., flows to predict the maximum displacement of a particle
2008a; Shi et al., 2008b; Shi et al., 2009a; Shi et al., 2009b, from the center of the microchannel. Without hydrody-
Shi et al., 2011; Wood et al., 2008; Wood et al., 2009; Zeng namic focusing, microparticles will be widely dispersed
et al., 2010), (2) tapered IDTs (Franke et al., 2010), and (3) along the width of the microchannel. Therefore, each
focused IDTs (Tan et al., 2009), which also can be patterned microparticle is affected by the external force field dif-
in a parallel or orthogonal (Shi et al., 2009a; Wood et al., ferently at different locations along the microchannel
2009) arrangement depending on their purpose. For exam- width. Prefocusing the microparticles with a narrow width
ple, orthogonally patterned IDTs are favorable for micro- before applying external forces may help mitigate this
particle tweezing. Therefore, SAW based techniques can be problem (Adams and Soh, 2010; Franke et al., 2010; Kim
a versatile tool for microparticle manipulation in biochem- et al., 2008; Lee et al., 2009; Nam et al., 2011a; Nam et al.,
ical analyses and clinical diagnosis. 2011b; Pamme et al., 2006; Petersson et al., 2007; Pia-
centini et al., 2011; Shi et al., 2009b; Theovoz et al.,
3. Theoretical Analysis 2010). The width of the focused flow (wf) can be estimated
by the volume flow rates of the inlet channel (Qi) and side
Prior to developing an analytical model for microparticle channels (Qs), and by the velocity ratio (γ), which is the
movement in a SSAW working area, it is necessary to ratio of the average velocities γ = vf ⁄ vo .
define the flow condition and corresponding assumptions
w w o Qi
as follows: (1) the microchannel flow is steady, laminar, dhydro = -----f = ----------------------------
- (1)
2 2γ ( Qi + 2Qs )
and fully developed; (2) the fluids are Newtonian fluid; (3)
the fluids and microparticles have the same density; (4) all Further, v is the average velocity, and the subscripts of
microchannels have the same height; (5) the viscosities of f, o, i, and s indicate the focused, outlet, inlet, and side
all the fluids (sample fluid and sheath fluid) are identical; channels, respectively. For flow in flat rectangular channels
and (6) the lateral acoustic radiation force is uniform of low aspect ratio, the velocity would be uniform in the
throughout the test section. In fact, since the typical sample lateral direction , described by a parabolic profile across
fluid consists of a very low concentration of microparticles the channel height, which means that the flow velocity
suspended in the same sheath fluid, the viscosity of micro- ratio ã would be about unity. (Stiles et al., 2005) Therefore,
particle suspension is almost the same as that of the sheath the width of the focused stream wf can be easily predicted
fluid. And, there is no need to consider the effect of vis- by Eqn. (1).
cosity on hydrodynamic focusing in multiple fluid flows. Secondly, diffusive force also causes the displacement of
In microchannels, pressure nodes form in a two-dimen- a particle, as described by Bruus earlier (Bruus, 2008).
sional plane along the axial flow, since the SSAW is per-
ddiffuse = Dtw (2)
pendicular to the axial flow direction. The two-dimensional
particle distribution would be dependent on the aspect ratio While the microparticles experience acoustic radiation
and the channel height of the microchannel, since the forces, they diffuse toward the side walls according to their
acoustic radiation force propagates from the surface to the diffusivities. Generally, small-sized microparticles diffuse
fluid. Therefore, rectangular channels with low aspect faster than larger particles (Weigl and Yager, 1999).
ratios would be more effective for applying SSAWs on Although diffusive force is dominant for small particles in
microparticles suspended in fluid. a microfluidic channel, its effect on the displacement of
The behavior of microparticles in a microfluidic channel microparticles was not considered in a previous analytical
in the SSAW working area can be predicted from various model (Shi et al., 2009b).
forces, including the acoustic radiant force, viscous drag Thirdly, under acoustic radiation pressure, a surface
force, diffusive force, gravity force, and buoyancy force. acoustic wave pushes microparticles in a perpendicular
The gravity force and the buoyancy force cancel each direction to the flow. The acoustic radiation force Fr and
other, because the densities of both particles and the sus- the acoustic contrast factor Φ can be described as follows
pending medium are almost balanced. To estimate the dis- (Yosioka and Kawasima, 1955):
placement of a particle from the hydrodynamically focused 2
πp0Vp βm⎞
center plane of the microchannel, it is necessary to con- Fr = –⎛ --------------------
- Φ( β, ρ ) sin ( 2kx ) (3)
⎝ 2λ ⎠
sider three primary forces: viscous, diffusion, and acoustic

258 Korea-Australia Rheology Journal


Manipulation of microparticles using surface acoustic wave in microfluidic systems : a brief review

and the diffusion of microparticles enables more accurate pre-


diction of microparticle displacement, regardless of the
5ρp – 2ρm βp
Φ = ---------------------
- – ------ (4) size and flow rates of the microparticles.
2ρp + ρm βm
The displacement of microparticles in the SSAW work-
where p0 , Vp , λ, k, x, ρ and β correspond to the pressure ing area can be can be predicted. Microparticles in the
amplitude, the particle volume, the wavelength, the wave SSAW working area are forced to migrate to either pres-
vector, the distance from a pressure node to an anti-pressure sure nodes or anti-pressure nodes depending on the nota-
node, the density, and the compressibility of particles and tion of the acoustic contrast factor, Φ, which is a function
medium, respectively. Also, subscripts p and m indicate the of the density and compressibility of the microparticle and
particles and suspension medium, respectively. On the other the medium, respectively, as described in Eq. (4). For pos-
hand, in addition to the acoustic radiation force, viscous itive Φ or negative Φ, acoustic contrast factor, the acoustic
drag force toward the opposite direction of the micropar- radiation force caused by the pressure fluctuations in the
ticles’ velocity relative to the flow also acts on the micro- microchannel moves the microparticles toward the pres-
particles, which can be described as follows (Shi et al., sure nodes or the anti-pressure nodes, respectively, as
2009b): shown in Fig. 2. For example, since the value of Φ is 0.32
for RBCs, 0.97 for WBC, and 0.67 for platelets, all blood
Fv = –6πηrv (5)
cells tends to migrate to pressure nodes (Dao et al., 2003;
where η, r, and v correspond to the medium viscosity, the Dong et al., 1999; Haga et al., 1998; Ku, 2006; Lam et al.,
particle radius, and the relative velocity, respectively. With 2011; Weiser and Apfel, 1982). Moreover, to manipulate
detailed consideration of the acoustic radiation force and microparticles effectively in the microchannel, the num-
the viscous drag force, the drifting time of a microparticle bers and the positions of the pressure nodes and anti-pres-
can be calculated as follows: sure nodes should be controlled by adjusting the acoustic
x wavelength and the width of the microchannel.
------------⎞ ln ⎛ -----------------⎞
⎛ 3ληr tan 2πx 2
⎝ π ⎠ ⎝ λ ⎠ x
-1
t = -----------------------------------------------------
2
(6) 4. Experimental Analysis of SAW
[ p 0 V p β m Φ ( ρ, β ) ]
where r is the particle radius. Further details can be found Using a single surface acoustic wave (SAW) and mul-
elsewhere (Shi et al., 2009b). From a given working time, tw, tiple SAWs, microparticles can be manipulated in a microf-
the displacement of a microparticle in the direction perpen- luidic environment. In this section, most recent studies on
dicular to the flow can be approximately predicted as follows: microparticle manipulation based on single SAW or SSAW
are categorized according to their working principles and
λ- tan –1( ec )
dacoustic = ----- , (7) their applications, and are then reviewed.

2 4.1. Microparticle switching/directing using SAW
p 0 V p β m Φ ( ρ, β ) 2πx
- + ln ⎛ tan ⎛ -----------1⎞ ⎞
where c = tw ----------------------------------- Unlike SSAW-based microfluidics which uses the acous-
3λ η
2 2 ⎝ ⎝ λ ⎠⎠
-------------- tic radiation force to manipulate the microparticles, SAW-
π based microfluidics is based on acoustic streaming induced
Here, the pressure amplitude, p0, is defined as (PZ/A)1/2, by a leaky SAW, as mentioned in an earlier chapter.
where P is the input power of the AC signal, A is the Recently, acoustic streaming has been used for various
SSAW working area, and Z is the product of density and applications, such as pumping (Schneider et al., 2008) and
SAW velocity of the substrate (Pierce, 1989). mixing (Sritharan et al., 2006) in open microfluidic sys-
Therefore, the displacement of a microparticle, with con- tems. Moreover, acoustic streaming enables a non-labeling
sideration of hydrodynamic focusing, diffusion, acoustic radi- and fast microparticle sorting in the microfluidic channel.
ation force and viscous drag force, can be described as follows: Franke et al. (2009) used surface acoustic waves (SAWs)
to direct water droplets and polyacrylamide particles of 20
dtatal = dhydro + ddiffuse + dacoustic
ìm in a microchannel. When the surface acoustic wave
(SAW) power is switched off, all droplets flow along the
w λ –1 c
= -----f + Dtw + ------ tan ( e ) (8) upper outlet channel, which has lower flow resistance than
2 2π
the lower outlet channel. On the other hand, When the
In fact, the previous standard model (Shi et al., 2009b) acoustic power is switched on, the acoustic streaming
considered only the two terms of the hydrodynamic focus- induced by the IDTs drives the droplets to the lower outlet
ing and the acoustic radiation force. However, it was found channel, as shown in Fig. 3. Recently, Franke et al. (2010)
that the diffusive term was not negligible (Bruus, 2008). demonstrated an advanced cell sorting device using SAWs
Thus, the proposed analytical model with consideration of actuated by tapered IDTs. The tapered IDTs with decreas-

Korea-Australia Rheology Journal December 2011 Vol. 23, No. 4 259


Jeonghun Nam, Hyunjung Lim and Sehyun Shin

the propagating SAW because the finger spacing satisfied


the acoustic resonance condition at one position. Various
types of cells, such as HaCaT cells (human keratinocytes),
fibroblasts from mice and MV3 melanoma cells, were
directed and sorted directly from bulk media at rates as fast
as several kHz without cell damage due to shear forces.

4.2. Microparticle focusing using SSAW


Conventional microparticle focusing can be achieved by
several methods, such as hydrodynamic focusing (Wong et
al., 2003), dielectrophoresis (Wang et al., 2007), and elec-
trokinetic focusing (Wang et al., 2005). Focusing of micro-
particles in microfluidic devices utilizing standing surface
acoustic waves has been newly reported by some groups.
Shi et al. (2008b) first suggested a SSAW-based focusing
technique for a microchannel. Two interdigitated trans-
ducers (IDTs) were patterned on a piezoelectric LiNbO3
substrate, and a PDMS microchannel was aligned and
bonded between the two identical IDTs. A dilute solution
of fluorescent microparticles of 1.9 µm in water was
injected into the microchannel at flow velocity of 6.7 cm/s.
Forced by the standing surface acoustic waves actuated by
application of RF signals at 38.2 MHz (resonance fre-
quency) to the two IDTs, the particles with positive acous-
tic contrast factors migrated toward the center of the
channel where the pressure nodes existed and were
focused, as shown in Fig. 4.
Enhanced microparticle focusing was reported by Zeng
et al. (2010). In fact, the propagation and the absorption
loss of standing surface acoustic waves (SSAWs) have crit-
ical effects on microparticle manipulation efficiency in a
microfluidic channel. Zeng et al. added patterned Bragg
Reflectors (BR) outside the IDTs enhance the formation of
the standing surface acoustic wave (SSAW) between the
two IDTs. Additionally, air cavities were introduced on
both sides of the PDMS microchannel, reducing the
microfluidic channel walls to 50 µm in the SSAW working
area. A solution of red fluorescent polystyrene particles of
2 µm was injected and an AC signal was stimulated by a
RF signal generator at 32.2 MHz (resonance frequency)
and 23 dBm (applied power) was applied to the IDTs to
generate standing surface acoustic waves. As a result,
microparticle focusing was enhanced by the standing sur-
face acoustic wave in combination with BR and the min-
Fig. 3. Schematic of the acoustic sorting devices (a) before and
(b) after SAW was generated. (c) When the SAW is
imized PDMS side wall in the SSAW working area.
switched off, all water droplets flow along the upper out- Recently, three-dimensional (3D) continuous micropar-
let channel due to its lower flow resistance. (d) When the ticle focusing was reported (Shi et al., 2011). 3D hydro-
SAW is switched on, the acoustic streaming drove the dynamic focusing was developed because of two-
water droplets in the lower channel of the branch. dimensional (2D) hydrodynamic focusing had several lim-
Reprinted from Franke et al. (2009) with permission from itations: difficulties in microparticle sorting and separation
The Royal Society of Chemistry. when the vertical direction varied, different chemical reac-
tion times across the depth of the channel, optical inter-
rogation, and so on. A few 3D hydrodynamic focusing
ing finger spacing provided a narrow wave path width for techniques in microfluidic devices have been suggested

260 Korea-Australia Rheology Journal


Manipulation of microparticles using surface acoustic wave in microfluidic systems : a brief review

Fig. 4. Schematic of the SSAW-induced miroparticle focusing


device, illustrating its working mechanism. The width of Fig. 5. SSAW-induced three-dimensional microparticle focusing
microchannel was designed to contain only one pressure device (a) Schematic of the experimental setup for mon-
node at the center of the channel such that microparticles itoring the microparticle behavior in the vertical direction
focused at that node when the SSAW was actuated. using a 45o prism adjacent to the channel. Distribution of
Reprinted from Shi et al. (2008b) with permission from fluorescent light from excited microparticles (b) before
The Royal Society of Chemistry. and (c) after SSAW was reflected through the prism into
the microscope to be recorded for analysis. Reprinted
from Shi et al. (2011) with permission from The Royal
Society of Chemistry.
(Chang et al., 2007; Mao et al., 2007; Sundararajan et al.,
2004; Terray and Hart, 2010; Yang et al., 2005). However,
most of the previous devices need an excessive sheath fluid ety of microparticle tweezing techniques has been devel-
and complicated structure of multi-layer channels. Stand- oped using optical tweezers (Ashikin et al., 1987; Grier,
ing surface acoustic waves allowed sheathless 3D hydro- 2003), magnetic tweezers (Ino et al., 2008; Lee et al.,
dynamic focusing of 1.9 µm fluorescent microparticles in a 2004; Lee et al., 2007), dielectrophoresis (Ho et al., 2006;
single-layer PDMS microfluidic channel of 50 µm width Mittal et al., 2007; Thomas et al, 2009; Wang et al., 2005),
and 100 µm height with high aspect ratio. Once the micro- acoustophoresis based on bulk acoustic wave (Manneberg
particles migrated toward the pressure nodes at the cen- et al., 2009; Nilsson et al., 2004; Petersson et al., 2007;
terline of the channel, the particles tended to concentrate at Wiklund et al., 2006), and so on. However, these previous
points of maximum kinetic energy in the vertical direction. methods have limitations: they are bulky, have complicated
Therefore, as shown in Fig. 5, the suspended micropar- setups, and require pre-labeling etc.
ticles were three-dimensionally focused in both horizontal A novel tweezing method using the standing surface
and vertical directions in the microfluidic channel. The acoustic wave (SSAW) was proposed by Wood et al.
standing surface acoustic wave-based microparticle focus- (2009), as shown in Fig. 6. Carboxylate functionalized flu-
ing device enables simpler, faster focusing compared to orescent latex particles of 0.5, 1, and 2 µm were attracted
previous focusing devices. toward the pressure nodes or anti-pressure nodes formed
by the standing surface acoustic wave (SSAW) in a microf-
5. Microparticle Tweezing using SSAW luidic channel or chamber. The number of one-dimen-
sionally patterned particle lines and the distance between
Microparticle tweezing has several applications in fields these lines could be manipulated by changing the working
such as micro-sensor array (Flaim et al., 2005; Wheeler et resonance frequencies. Moreover, two-dimensional (2D)
al., 2005), tissue engineering (Stevens et al., 2005), and particle patterning could be carried out in the microfluidic
regenerative medicine (Khetani and Bhatia, 2007). A vari- chamber by arranging the position of two pairs of IDTs.

Korea-Australia Rheology Journal December 2011 Vol. 23, No. 4 261


Jeonghun Nam, Hyunjung Lim and Sehyun Shin

6. Microparticle Separation using SSAW

Among the types of microparticle manipulation, the sep-


aration of microparticles from complex fluids has gained
much attention for continuous flow-based biological and
chemical analyses. In the standing surface acoustic wave
working area, larger particles experience higher acoustic
forces and migrate at a larger lateral displacement than
smaller particles. Therefore, by adjusting the channel
length, SAW power, flow velocity, etc., microparticles of
different sizes can be separated in the microchannel.
Shi et al. (2009b) reported a novel method of continuous
particle separation by using the standing surface acoustic
wave (SSAW) in a microfluidic channel. A mixture of par-
ticles of equal density but different sizes was injected
through two side inlets and a sheath flow of deionized
water was used to push the particles in the mixture solution
near the side walls. By generating one-dimensional stand-
ing surface acoustic waves (SSAWs) across the micro-
channel, fluorescent polystyrene beads of 0.87 µm and
4.17 µm in size experienced different amounts of acoustic
forces in the SSAW working area and migrated with dif-
ferent lateral displacements. Therefore, Shi et al. (2009b)
could separate a mixture of particles by their sizes within
360 ms. However, they needed two sheath flows, the cen-
Fig. 6. SSAW-induced microparticle tweezing device (a) Sche- tral sheath flow and the outer sheath flow. The central
matic of the four-port acoustic wave device showing sheath flow separated the two particle streams, and the sec-
acoustic tweezing of microparticles in a fluidic capillary
ond sheath flow from the outer inlet prevented micropar-
formed with a glass cover-slip, with (1) Signal generator,
ticles from becoming trapped and aggregating along the
(2) power amplifier, and (3) power splitter. Two pairs of
IDTs were patterned in orthogonal arrangement. Images
sidewall of the microchannel.
of microparticles confined within the fluidic channel were Recently, the Shin group reported size-dependent micro-
taken (b) prior to and (c) after activation of two orthog- particle separation using standing surface acoustic waves
onal SAWs. Reprinted from Wood et al. (2009) with per- (SSAWs) (2011a). Unlike the previous separation tech-
mission from America Institute of Physics. nique proposed by Shi et al. (2009b), a particle suspension
was focused hydrodynamically at the center of the micro-
channel as a focused stream of width ranging between 10
Shi et al. (2009a) reported similar results with only 2 IDTs and 14 µm. The advantages of this method were the min-
located in orthogonal directions. This technique enabled imization of the applied shear rate on microparticles during
tweezing not only 1.9 µm fluorescent (Dragon Green) separation, which would be critical for the separation of
polystyrene beads, but also 6 µm bRBCs and 800 nm E. shear-dependent biological cells, such as platelets, and the
coli cells dyed with green fluorescence proteins (GFP) placement of the microparticles in the SSAW-effective
encoded plasmids. The SSAW-based microparticle tweez- area. In fact, there is a SSAW-less effective area near the
ing techniques used comparatively lower power than other wall due to the propagation of SAWs with a Rayleigh angle
patterning methods and required only a few seconds to from the substrate surface to the bulk fluid (Alvarez et al.,
drive the particles to pressure nodes or anti-pressure 2008; Shilton et al., 2008). Microparticles placed near the
nodes. Also, the microparticles which reached the nodes side wall may be difficult to manipulate due to the Ray-
experienced almost no acoustic forces. Therefore, dam- leigh angle. Therefore, if it is inevitable that microparticles
ages due to acoustic radiation forces during the focusing are to be placed near the side walls, a second sheath fluid
were trivial. would be required to dislocate the microparticles from the
The microparticle tweezing technique based on standing SSAW-less effective area (Shi et al., 2009b). In this
surface acoustic wave (SSAW), so called “acoustic twee- research, to generate standing surface acoustic waves
zers”, can offer advantages of high speed, low power con- (SSAWs), the resonance working frequency were set at
sumption and easy integration with microfluidic devices. 19.5 MHz. Microparticles of different sizes (1, 5 and
10 µm) but with the same density showed different lateral

262 Korea-Australia Rheology Journal


Manipulation of microparticles using surface acoustic wave in microfluidic systems : a brief review

having three different sizes under lateral acoustic forces


can be separated, as shown in Fig. 7. Also, an analytical
model to predict the microparticles’ displacements in the
microchannel was developed.
Based on the previous results, Nam et al. (2011b)
recently reported a novel application of a standing surface
acoustic wave (SSAW)-based separation technique in
microfluidics for the direct separation of platelets from
whole blood, as shown in Fig. 8. To avoid high shear rate-
induced activation of platelets during the separation pro-
cess, the whole blood sample was hydrodynamically
focused at the center of the microchannel by injecting
sheath flows through the two side inlets. Also, the max-
imum shear rate observed at the interface near the hydro-
dynamic focusing area was 333.3 s-1, which was
significantly smaller than the threshold shear rate (2200 s-1)
to activate platelets (Shankaran et al., 2003) The pressure
nodes, where unwanted large blood cells would be forced
to migrate by acoustic forces, were designed to be located
at the side walls. Finally, platelets could be collected
Fig. 7. Separation of microparticles having three different sizes in through the center outlet. By means of cytometric analysis,
the acoustic device. The observation location was 5 mm the RBC clearance ratio from whole blood, which was
downstream from the onset of the SSAW field. Reprinted defined as the ratio of the number of RBCs found at the
from Nam et al. (2011) with permission from Springer.
side outlets to the total number of injected RBCs, was over
99% and the purity of the collected platelets at the center
outlet was close to 98%.

7. Conclusions and Future Perspectives

In this paper, we reviewed currently available micro-


particle manipulation techniques which utilize the single
surface acoustic wave (SAW) or the multiple SAW, namely
the standing surface acoustic wave (SSAW). Compared to
other microparticle manipulation methods, SAW/SSAW-
based methods are non-invasive, harmless to microparti-
cles, applicable to all types of microparticles regardless of
their properties, consume low power and, most impor-
tantly, are easy to integrate with microfluidic devices.
Standing surface acoustic wave (SSAW) based micropar-
ticle separation has become more important than other
microparticle manipulation techniques because it is critical
to various applications, such as industrial processing, envi-
Fig. 8. Selective platelet separation from whole blood in the acous- ronmental assessment, biochemical analyses, and clinical
tic device. Whole blood sample was injected and focused
diagnosis. SSAW-based separation techniques need to be
hydrodynamically by the sheath flow. Blood particles in the
investigated further.
SSAW working area were separated in a size-gradient man-
ner. Larger blood cells (RBCs and WBCs) were driven to
Future investigations can focus on three areas: 1) addi-
the side walls of the channel and flowed through the side tional developments and applications of the separation
outlets, while platelets were mainly sorted and collected in technique, 2) various other applications of SAW, and 3)
the center outlet. Reprinted from Nam et al. (2011b) with integration of the separation technique with other tech-
permission from The Royal Society of Chemistry. niques.
Microparticle separation in microfluidics using SAW can
be especially useful for the separation of bio-particles with
displacements toward the side walls where pressure nodes different physical properties such as size, density, and com-
were generated by the two IDTs. Therefore, microparticles pressibility. Also, separation based on physical properties

Korea-Australia Rheology Journal December 2011 Vol. 23, No. 4 263


Jeonghun Nam, Hyunjung Lim and Sehyun Shin

of particles enables rapid detection and analysis of bio- Acknowledgement


particles without the need for pre-treatment of the samples
such as labeling or biochemical treatment processes. Sep- This work was supported by the National Research
aration of nano-scale particles by their size has become Foundation of Korea (NRF) grant funded by the Korea
important in environmental and biological research fields, government (MEST) (No. 2011-0020090).
because it can be used in toxicity assessments by moni-
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