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a r t i c l e i n f o Even as gigahertz (GHz) acoustic streaming has developed into a multi-functional platform technology for biochemical applications, including ultrafast microfluidic mixing, microparticle operations, and cellar or vesicle surgery , its theoretical principles have yet to be established. This is because few studies have been conducted on the use of such high frequency acoustics in microscale fluids. Another difficulty is the lack of velocimetry methods for microscale and nanoscale fluidic streaming. In this work, we focus on the basic aspects of GHz acoustic streaming, including its micro-vortex generation principles, theoretical model, and experimental characterization technologies. We present details of a weak-coupled finite simulation that represents our current understanding of the GHz-acoustic-streaming phenomenon. Both our simulation and experimental results show that the GHz-acoustic-induced interfacial body force plays a determinative role in vortex generation. We carefully studied changes in the formation of GHz acoustic streaming at different acoustic powers and flow rates. In particular, we developed a microfluidic-particle-image velocimetry method that enables the quantification of streaming at the microscale and even nanoscale. This work provides a full map of GHz acoustofluidics and highlights the way to further theoretical study of this topic.
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Theoretical and experimental characterizations of gigahertz acoustic streaming in
microscale uids
Weiwei Cui, Wei Pang, Yang Yang, Tiechuan Li, Xuexin Duan
State Key Laboratory of Precision Measuring Technology & Instruments, College of Precision
Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin 300072, China
abstractarticle info
Even as gigahertz (GHz) acoustic streaming has developed into a multi-functional platform technology for bio-
chemical applications, including ultrafast microuidic mixing, microparticle operations, and cellar or vesicle sur-
gery, its theoretical principles haveyet to be established. Thisis because few studies have been conducted on the
use of such high frequency acoustics in microscale uids. Another difculty is the lack of velocimetry methodsfor
microscale and nanoscaleuidic streaming.In this work,we focus on the basicaspects of GHz acoustic streaming,
including its micro-vortex generation principles, theoretical model, and experimental characterization technolo-
gies. We present details of a weak-coupled nite simulation that represents our current understanding of the
GHz-acoustic-streaming phenomenon. Both our simulation and experimental results show that the GHz-
acoustic-induced interfacial body force plays a determinative role in vortex generation. We carefully studied
changes in the formation of GHz acoustic streaming at different acoustic powers and ow rates. In particular,
we developed a microuidic-particle-image velocimetry method that enables the quantication of streaming
at the microscale and even nanoscale. This work provides a full map of GHz acoustouidics and highlights the
way to further theoretical study of this topic.
Copyright © 2019 Tianjin University. Publishing Service by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
This is an open access article under the CC BY-NC-ND license (
Acoustic streaming
Body force
Microuidic PIV
1. Introduction
The term acoustouidics refers to a new eld that combines acous-
tics with microuidics by conning acoustic waves or energy within a
microuidic system to stimulate the micro/nanoscale motions of uids
and particles, and interactions between them.
In recent decades, re-
searchers have developed different kinds of acoustouidic strategies.
From the acoustic wave form perspective, there are two basic wave
types, i.e., standing waves and travelling waves. Generally, acoustic
waves with frequencies ranging from kHz to several MHz are generated
by a PZT plate, which is placed on the substrate of a microchannel
Standing waves form in the microuidic channel because the
acoustic wavelengths at such frequencies are similar to the
microchannel scale, i.e., from several hundred to tens of micrometers.
The spatial patterns of acoustic antinodes or nodes provide a gradient
physical eld for particle trapping and operations.
Acoustic waves
travelling on the substrate surface (typically a surface acoustic wave
(SAW)) can push the particle or uids away much like shooting pool.
The above strategies utilize the acoustic radiation force. It is very easy
perform microscale manipulations or even to manipulate millimeter-
scale particles. For example, both standing waves and SAW-based
travelling waves have been widely investigated for use in cell
The basic idea of these applications is to push the bigger
cells from the main ow. From the frequency perspective, the most
commonly used frequencies range from kilohertz to tens of megahertz.
The acoustic frequency is determined by the resonators used. For exam-
ple, for PZT, the thickness vibration is related to the plane thickness.
The frequency of a SAW is determined by the interdigital (IDT) periodic
In other words, the reason that ultrahigh frequency (gener-
ally above 300 MHz) acoustouidics has rarely been explored is due to
the lack of high frequency resonators. GHz SAWs are fabricated for com-
munication purposes, but IDT distances are too small tofabricate by the
conventional fabrication process available to university researchers. On
the other hand, GHz SAWs cannot withstand high power, which also
limits their use in liquids.
Acousticstreaming is a simple yet practical means of effectively trig-
gering uid motion by directly introducing acoustic energy to a specic
region. Microscale vortex streaming induced by acoustic-driven
and sharp edges
have served as convenient
acoustouidic tools for microuidic mixing and particle manipulations.
Construction and operation of these inserted components, however, re-
main a professional task, as does the difculty of maintaining long-term
stability. SAW-driven microuidics has become a very useful uid actu-
ation method due to its ability to transfer a large amount of momentum
into uids. Using this approach, complex uidic and particle operations
Nanotechnology and Precision Engineering 2 (2019) 1522
Corresponding author.
E-mail address: (X. Duan).
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have been realized in microuidic systems.
The typical amplitudes of
SAWs are on the order of nanometers or less, however, owing to the
high frequencies used (10100 MHz), the accelerations induced by
these waves are enormous (over 10
In addition, the attenuation
length of high frequency SAWs is comparable with the scale of
microuidic systems, which enables the coupling of most SAW energies
with uids. Shilton et al. experimentally demonstrated the ability of
SAWs with operating frequencies of up to 1.1 GHz with respect to re-
ned nanoscale manipulation, thereby revealing the signicance of
the use of ultrahigh frequencies to effectively generate acoustouidic
streaming in microscale uids.
As well, Ye Ai et al. used focused ultra-
high frequency SAWs (193636 MHz) to generate a micro-vortex, and
then developed this technique as a versatile tool for performing contin-
uous micro/nanoparticle manipulation.
Recently, we demonstrated the use of a GHz-acoustic-wave resona-
tor to generate a localized micro-vortex, which we applied to some ex-
citing applications including microuidic mixing,
and cellar surgery.
However, at present, almost all of
the developed high frequency acoustouidic techniques are at their
very earliest developmental stages, and their theoretical principles
have yet to be established. In this work, we investigate and reveal the
properties of GHz-acoustic-induced vortex streaming, including GHz
acoustic device, streaming generation, and microscale streaming char-
acterizations, and present a full picture of GHz acoustic streaming and
its microuidic applications. We develop an analysis model to quantita-
tively characterizevortex streaming, and offer a simple method for trac-
ing and characterizing microuidic streaming motion to replace the use
of particle image velocimetry (PIV).
2. Theoretical description of GHz-acoustic-uid interaction
2.1. GHz acoustic device
The solid mounted piezoelectric acoustic resonator (SMR) is a typi-
cal lm bulk acoustic wave resonator. As shown in Fig. 1(a), the core
structure of an SMR is essentially a multi-layer sandwich, with a piezo-
electric lm in the center sandwiched by two electrodes. When an elec-
trical signal is applied to the electrodes, the electric elds trigger a
mechanical vibration within the piezoelectric lm by the piezoelectric
effect. Behind the sandwich structure is a Bragg reector, which blocks
any leakage of acoustic energy into the substrate and connes the
acoustic waves to within the piezoelectric layer. Fig. 1(b) shows the vi-
bration mode of an SMR. The SMR works in the thickness extensional
mode, which is excited in a vertically grown piezoelectric material
lm by coupling the vertical electric eld through the d
coefcient. Both the wave velocity and resonant frequency of the TE
mode are much higher than those of any other possible modes for a
given piezoelectric lm, and offers the highest energy transduction.
The frequency of an SMR can be estimated by the following
where dis the thickness of the piezoelectric lm, and c,ρare, respec-
tively, the stiffness coefcient and density of the piezoelectric lm ma-
terial, i.e., alumina nitride here. We note that the thickness of the
piezoelectric layer of an SMR can be precisely controlled to within
from several nanometers to several micrometers during the lm depo-
sition process, which enables the accurate fabrication of acoustic de-
vices witha frequency from hundreds of megahertz to tens of gigahertz.
The SMR is fabricated using a standard complementary metal
oxidesemiconductor (CMOS) process, as presented in our previous
This process is illustrated in Fig. 2 and can be described as fol-
lows. SMR devices are fabricated on 100-mmundoped Si wafers, begin-
ning with the deposition of the Bragg reector. AlN and SiO
layers are
alternatively deposited through physical and chemical vapor deposition
(PVD and CVD), respectively. Then, a sandwiched structure comprising
a bottom electrode (BE), piezoelectric layer (AlN), and top electrode
(TE) is deposited andpatterned layer by layer: The BE of the acoustic de-
vice consists of 600-nm thick Mo deposited via PVD on top of the Bragg
reector, and the lm is then patterned by photolithography and
plasma etching into a pentagon. PVD is used again to deposit the piezo-
electric layera 1000-nm thick AlN lmon top of the BE,with a crystal
orientation along the c-axis. In the nal step, the SMR is capped with a
gold TE lm, which is deposited using E-beam evaporation followed
by a wet etch. The thicknesses of the Au electrodes and underlying Cr
adhesive layer are 300 nm and 50 nm, respectively. We congured the
electrode area to be 20,000 μm
such that the SMR had a characteristic
impedance of 50 Ωto match the impedance of the external circuits.
We then used a PDMS microchannel prepared with soft lithography to
ensure microscale connement of the liquid samples and acoustic
waves. Fig. 2(b) shows a schematic of the prepared GHz acoustouidic
chip consisting of an SMR and a microchannel.
Fig. 3(a) shows a scanning electron microscope (SEM) image of a
fabricated SMR device. The sandwich structure is pentagon-shaped
and connes the resonating region of the SMR. We measured the per-
formance of the SMR in air and water, respectively, with a network an-
alyzer (Agilent, E5071C). As Fig. 3(b) shows, the quality value (Q-value)
is dramatically decreased when the device is submerged in water,
which is considered to be mainly caused by acoustic leakage into the liq-
uid. Generally, the serial resonant frequency is used as the working fre-
quency of the acoustouidic chip, which is about 1560 MHz here.
2.2. Some key parameters
As shown in Fig. 2(b), the SMR vibrates at a resonant frequency in
the GHz range. The vibrating displacement (A) of the SMR surface can
be described simply as follows: A=ξsin(ωt). The acceleration can be
obtained by
. With an assumed magnitude of about 10 nm, the
acceleration is greater than 10
, which is faster than any other
known technique except that of particle accelerators. For this reason,
it is possible to obtain extraordinary inertial behavior from uids and
particles down to the nanoscale. However, many other factors must be
considered that can affect the nal performances. When submerged in
water, it would be interesting to explore what would occur. Prior to de-
scribing our acoustouidic experiment, we introduce and discuss some
critical concepts and parameters, including the Stokes boundary layer,
acoustic decay length, and body force.
2.2.1. Stokes boundary layer
According to the classical RayleighSchlichting streaming model,
the acoustic triggered uid bulk can be divided into two parts, as
shown in Fig. 4, in which the light blue region supports a horizontal
Fig. 1. (a) Schematic structure of the SMR, and (b) thickness-extensional vibration of the
SMR working at resonant frequency.
Table 1
Values of parameters used in model calculation.
(m/s) μ(Pa·s) μξ
(nm) F(MHz)
1500 1.0087 × 10
1.0100 × 10
10 1560
16 W. Cui et al. / Nanotechnology and Precision Engineering 2 (2019) 1522
sinusoidal pressure wave (magenta line) of wavelength λin the hori-
zontal direction parallel to the wall. The dark blue region is the viscous
boundary layer of sub-micrometre thickness δ, wherein large shear
stress appears to generate the boundary layer (Schlichting) streaming
rolls (yellow arrow line), which then drive the bulk (Rayleigh) stream-
ing rolls (red). In traditional standing wave systems at ordinary acoustic
frequency, the streaming pattern is periodic in the horizontal direction
with periodicity λ/2, and thus only the top and bottom walls are subject
to the no-slip boundary condition. The energy within these two regions
is attributed to acoustic dissipation. The expression for the viscous
boundary layer thickness can be written as follows
where μ,ρ
are, respectively, the viscosity and density of the liquid, and
ωis the acoustic frequency. In viscous acoustics, the length is about 0.01
2.2.2. Acoustic decay length
When the acoustic wave transfers into the liquid, it is subject to an
acoustic damping effect and the acoustic energy is radiated into the liq-
uid with an attenuation coefcient of β
where ρ
and c
are the density and sound speed in the liquid, respec-
tively; μand μrepresent the dynamic and bulk viscosities of the
ows, respectively; and the attenuation length of the TE-mode acoustic
waves is dened as βl
1, which is proportional to ω
. This high fre-
quency will induce a short decay length, and enable rapid energy dissi-
pation within a rather short propagation distance near the SMRliquid
interface. As shown in Fig. 5, we calculated the decay length of 1560-
MHz acoustic waves in water to be 7.5 μm, which is much shorter
than the channel height, thereby avoiding the formation of standing
The analysis of the decay length of GHz acoustic waves reveals that
most of the acoustic energy is dissipated within or near the thin viscous
boundary layer. Considering that the thickness of the GHz acoustic trig-
gered boundary layer is on the order of ~10 nm, the energy is ultra-
conned and would generate a great stress force in the liquid.
2.2.3. Body force
The attenuation of SMR-generated acoustic waves into liquid intro-
duces a body force at the SMRliquid interface, which is expressed as
where ξis the maximum amplitude of the acoustic waves at the SMR
liquid interface. Eq. (4) indicates that the body force scales with ω
which reveals the signicance of applying ultrahigh frequency to gener-
ate greater momentum to actuate the microuids. Fig. 5 shows the
body-force distribution generated by the SMR with an initial value on
the order of 10
. Another critical issue is the localization or
Fig. 2. (a) Fabrication of SMR and SMR-based acoustouidic chip,including Bragg reector deposition (1), BE deposition andpattern (2), piezoelectric layerdeposition and pattern (3), TE
deposition and wet etch (4). (b) Cross-sectional illustration of the multilayered device structure of GHz acoustouidic chip. From bottom to top are the high-resistivity silicon substrate,
Bragg reector (containing three pairs of AlN and SiO
layers to attenuate acoustic waves leaking into the Si substrate (inset)), bottom electrode (BE, Moly), piezoelectric layer, top
electrode (TE, Au), and PDMS channel.
Fig. 3. (a) SEM image of a fabricated SMR. (b) Measured performance of the SMR both in air and liquid.
17W. Cui et al. / Nanotechnology and Precision Engineering 2 (2019) 1522
focus of the bodyforce region. Because the resonantregion of the SMR is
dened by the pentagon-shaped sandwiched structure, the body force
is naturally focused within the locally conned region.
3. Weak-coupled nite-element simulations
To evaluate the microuidic streaming triggered by GHz acoustic
waves, we used COMSOL software to perform a nite-element simula-
tion of the uid motion in a spatially conned area with a height of 50
μm (as shown in Fig. 6(a)). Considering the fact that the interaction be-
tweensuchhighfrequencyacousticsanduids is as yet not clearly un-
derstood, we conducted a weak-coupled simulation and neglected the
nonlinear effects. Investigations of GHz acoustic streaming in micro/
nanoscale uids are ongoing. The acoustic streaming response of the
uid is characterized using a second-order system of equations, which
in turn is driven by rst-order equations. The uid response is governed
by the standard NavierStokes equation for a linear, viscous compress-
ible uid. As discussed above, we introduced the GHz-acoustic-wave-
induced body force into the NavierStokes equation by presetting a
boundary condition, as follows:
where Vis the velocity vector, Pis the pressure, and ρ,μdenote the den-
sity and viscosity of uid, respectively.
We considered the SMR to be the ideal device with a perfect match
layer on the substrate, despite the fact that the fabricated device con-
tains aws that can provide various pathways for acoustic energy leak-
age into the substrate. Another factor is the heating effect caused by the
acoustic energy dissipation. The heating ability of the SMR has been
characterized within the microuidic system.
Localized heat has
been demonstrated to generate vortex streaming in various optouidic
systems at velocities on the order of μm/s.
Here, we studied the heat-
streaming effect using a two-dimensional nite-element simulation,
and we used parameters from the experimental data described in our
previous paper.
The preset conditions of the heat-streaming simulation are shown in
Fig. 6(b). The heat-streaming effect is expressed in the following:
∇∙ −kTþρCTvðÞ¼Q;ð6Þ
where Qis the input heat ux, and Cand kdenote the heat capacity and
thermal conductivity of the uid, respectively. The input heat source is
assumed to be at the liquidsolid interface. The prole of the heat ux
is assumed to be Gaussian and focused in the center of the source. The
Fig. 4. Schematic of the RayleighSchlichting streaming model.
Reproduced with permission.
Copyright 2012 The Royal Society of Chemistry
Fig. 5. Body-force distribution above the SMR surface. The decay length is labelled at the
point where the body force decreases to 1/e of the initial value. The inserted SEM image
shows the SMR devic e, in which the pentagon-shape is the resonant region. A two-
dimensional nite-element simulation of the acoustic eld across the red line on the
resonator generates a distribution of body force on the surface. An ultra-large body force
generates a strea ming beam into the liquid to drive away the liquid abo ve the SMR.
According to the mass continuous equation, the liquid from the surrounding area would
ow to the surface of the SMR and ultimately form a closed rotating vortex. The value of
the parameters in Eqs. (3) and (4) are listed in Table 1.
Fig. 6. Two-dimensional nite-element simulation of UHF acoustic eld and acoustic-
heater-induced streaming within microchannels. (a)(b) Preset boundary conditions for
acoustic-streaming and heat-streaming simulations, respectively. Body force and heat
source are resp ectively applied at the boundary with a w idth of 100 μm, and other
parameters are the same as those in the acoustic streaming simulation.
18 W. Cui et al. / Nanotechnology and Precision Engineering 2 (2019) 1522
uid motion obeys the Navier-Stokes equation, and we set the external
force term to be proportional to the temperature gradient.
4. Two experimental characterization methods
4.1. Setup of the experimental characterization system
The SMR is excited by a radio frequency (RF) signal generator (MXG
Analog Signal Generator, Agilent, N5181A 100 kHz3GHz)andapower
amplier (Mini-Circuits, with 35 dBm enhancement of the original RF
source power). Prior to the microuidic mixing experiments, we
cleaned the channels by ushing them with ultrapure (UP) water at a
ow rate of 20 μL/min. We then introduced the UP water with and with-
out uorescent dye (FITC, 20 μg/mL) into the chip via two inlets using a
syringe pump (New Era Pump Systems, Inc.). We maintained equal ow
rates for both streaming experiments, and set their total ow rates Qto
5μL/min, 10 μL/min, 20 μL/min, 40 μL/min, 60 μL/min, and 80 μL/min.
We measured the operating frequency of the SMR by frequency sweep-
ing and used the serial resonant value as the working frequency. All ex-
periments were recorded using a orescent microscope (Olympus,
BX53) integrated with a CCD camera (DP73), with the images captured
at 25 frames per second.
4.2. Microuidic mixing
As localized micro-streaming can generate laminar ows within
microuidic systems, different laminar ows can be mixed to reect
and characterize the strength of the acoustic streaming. We described
the mixing effect of a GHz acoustouidic chip in our previous paper,
as well as detailing the characterization method. Briey, the mixing per-
formance is determined by examining a cross-sectional area of the
microuidic mixer perpendicular to the ow direction in terms of a
mixing index (MI). In theexperiment, we used an FITC solution and ac-
quired the uorescence intensity value of i-th pixel (I
interest (ROI) to characterize the concentrations,
as follows:
MI ¼1
where Nis the number of pixels along the line of the ROI, I
and Iare the
intensity values of the i-th pixel and the average value of Npixels in the
mixed region, respectively, and Irepresents the intensity value in the
unmixed region.
4.3. Microuidic particle image velocimetry(μ-PIV)
To better understand the vortex mixing principles, we developed a
dynamic model by analyzing the molecule transfer process at the inter-
face of the vortex and owing uids. Fig. 7(a) shows the mass transfer of
two laminar ows at the vortex edge, wherein the vortex velocity, V,
equals the ow velocity, and V
,denes the mixing length from the un-
mixed to the mixed region. The vortex area is conned by the edges of
= 1, and the inuence of the ow rate on the vortex area is deter-
mined by normalizing the vortex velocity eld with the ow velocity.
Fig. 7(b) shows the values of V/V
on the labelled line on the simulated
vortex velocity eld. The inner edge of the vortex is closer to the center
of the device (x= 300 μm), and the vortex area is primarily tuned by
adjusting its outside edges according to the experimental results.
5. Results and discussion
5.1. Generation of acoustic streaming
Fig. 8(a) shows the maximum velocity of the vortex as a function of
the applied power, which reveals alinear relationship between velocity
and power. The insert in Fig. 8(a) shows the results of the experimental
vortex generation in microows, which demonstrate the formation of
vortex streaming, and which t well with the simulation results. Fig. 8
(b) shows the heat-streaming effect simulated by a 2-D model, with
the conditions preset as in Fig. 6(b). The results show that acoustic-
dissipation-generated heat can induce a pair of vortices similar to the
acoustic-streaming effect. We plotted and tted the relationship be-
tween maximum velocity and temperature. Compared with the vortex
induced by the acoustic elds, for which the velocity is on the order of
m/s, the streaming generated by heat is much weaker, on the order of
μm/s. Thus, the streaming induced by the acoustic-heating effect can
be neglected, as the vortex is mainly induced by the acoustic-
streaming effect.
5.2. Mixing index characterizations
As shown in Fig. 8(a), vortex streaming is effectively generated in
the microuids. We can clearly see that there are multiple vortices
(those in the downstream are hidden by the well-mixed orescence
ow) around the resonator device, which agrees well with the simula-
tion results. The vortex can efciently mix the laminar ows, thereby
Fig. 7. The relative balance of the vortex streaming and ow velocities determines the
vortex shape and area. (a) The location of V/V
=1denes the vortex edges, as well as
the mixing region wherein the ow of UP water enters the mixed region with ow
velocity, V
distributions for different ow rates. The simulated water vortex
streaming represents the velocity eld inside static microuids, and the plotted V/V
distributions are obtained by dividing the static-case velocity value on the labelled red
dash line by the ow velocity.
19W. Cui et al. / Nanotechnology and Precision Engineering 2 (2019) 1522
Fig. 8. (a) Simulated velocity eld of acoustic streaming (insert)and tted relationship between simulated maximum velocity and applied power. (b) Simulated heat-streamingvelocity
eld and tted relationship between temperature and maximum velocity. The insert in (a) is the experimental result of the micro-vortex within the microchannels, and the insert in
(b) shows the heat transfer inside uids when heated by the resonator at a power of 500 mW.
Fig. 9. (a) The ow rate is maintained at 5 μL/min,and the applied powerwas set at 100 mW, 300 mW,and 500 mW from left to right, respectively. Thecurves represent the uorescence
intensity on the labelled line in the mixed region (downstream). (b) The applied power is maintained at500 mW, and the ow rate was varied from 10 μL/min, 40 μL/min, to 80 μL/min,
respectively. (c)(d) Mixing index in response to applied power and ow rate, respectively. The red dashed line in (c) represents the saturated mixing index value.
20 W. Cui et al. / Nanotechnology and Precision Engineering 2 (2019) 1522
enabling a homogenous mixed ow in the downstream (i.e., mixed re-
gion). Fig. 9(a) and (b) show the streaming elds of the vortices for dif-
ferent power and ow-rate conditions. In the upstream, two vortices
can be clearly observed by the border lines of the uorescent dye.
First, we evaluated the power effects on the formation of the micro-
vortex. The simulation result shows that the power input of the device
has a strong effect on the rotation speed of the micro-vortex, which is
directly related to the uid mixing efciency in the microchannel. Ex-
perimentally, we studied this issue by analyzing the shape of the vortex
formed at different input powers. Fig. 9(a) shows the streaming eld in-
duced by the SMR with applied power values of 100 mW, 300 mW, and
500 mW, respectively, at the same ow rate (5 μL/min). At a lower input
power (100 mW),the vortex remains approximately symmetrical along
the ow direction and the streaming area does not cover the full
microchannel, which results in poor mixing. When the power is in-
creased to 500 mW, the behavior of the vortex array becomes much
more intense, and disturbs the uids in a larger area until it is conned
by the boundaries of the microchannel, thereby improving the mixing
efciency. This result conrms the simulation results, which indicated
that a higher power input will induce faster vortex formation, and
thus improve the uid mixing efciency. Next, we experimentally in-
vestigated the effect of the ow velocity (V
) in the microchannel. We
obtained the ow velocity by dQ
dA, where Qis the ow rate and Ais the
cross-section area of the microchannel. Here, we use the average veloc-
ity (Vf) to represent the ow velocity eld. While keeping the same
input power (500 mW), we varied the ow rate (Q)at10μL/min, 40
μL/min, and 80 μL/min. As shown in Fig. 9(b), a higher ow rate reduces
the vortex area and connes the shape, which is a similar result to the
lower power case in Fig. 9(a), and therefore weakens the mixing effect.
We can conclude that both the input power and the ow conditions
conne the vortex, and the uid mixing efciency can be nely tuned
by these parameters. To further quantify the inuence of different
input power and ow conditions, we carefully characterized the mixing
efciency using the mixing index presented in Eq. (7).AsshowninFig. 9
(c), for a given ow rate, the mixing efciency increases with increased
power. In the low-power range, the mixing index has an approximately
linear relationship to the applied power. Combined with the simulation
results, this reveals that the mixing efciency is proportional to the ve-
locity of the vortex. The power applied to the SMR can be varied from
several milliwatts to several watts to tune the mixing efciency over a
rather large range. Fig. 9(d) shows that for a given applied power, the
mixing efciency increases with decreases in the ow rate in most
cases. In particular, in the low-power case, the mixing efciency is
greatly inuenced by the ow rate. This is due to the fact that the vortex
is conned by the ow, which limits the disturbance range inside the
microchannel. The inuence of the ow rate is less apparent in the
high-power case, since when high power is applied, the SMR induces
a much stronger vortex to offset the inuence of the owing uids.
5.3. Microuidic-particle-image velocimetry (μ-PIV)
Based on the denition of the vortex edge, the vortex area can be ob-
tained in both simulations and experiments by acquiringthe curve ratio
of the vortex area. The curves in Fig. 10(a) show the vortex edges at dif-
ferent ow rates, with the corresponding radii obtained shown in Fig. 10
(b). As the vortex velocity on the edges is approximately equal to the
ow velocity, the vortex velocity triggered by different power levels
and the velocity distribution within the vortex can be directly measured
using the ow tuning method. The above analysis highlights a new ap-
proach for measuring the streaming velocity eld that can replace PIV
methods. Fig. 10(c) shows the radius values obtained from Fig. 7(b),
which show a similar functional relationship as those obtained in the
6. Conclusions
In conclusion, both our simulation and experimental results demon-
strated the determinative role of GHz acoustics in streaming generation.
To understand the GHz-acoustic-induced microscale vortex streaming,
we introduced the classical RayleighSchlichting model to explore the
particular case of such high frequencies. Even though the theoretical
principles can be illustrated rather reasonably, there remain many as-
pects of the acoustic-uid interaction process that are unclear. In addi-
tion to a mixing index, we developed a micro-PIV method in which
the vortex edges are dened, which enables a determination of the pre-
cise velocimetry within microscale and even nanoscale uids. For the
rst time, in this work, we introduced a whole map of GHz
acoustouidics from its theoretical principles to experimental charac-
terizations, which contribute to broadening the understanding of GHz-
acoustic-uid interactions.
The authors gratefully acknowledge nancial support from the Na-
tional Natural Science Foundation of China (Grant Nos. 91743110,
61674114, 21861132001), National Key R&D Program of China (Grant
No. 2017YFF0204600), Tianjin Applied Basic Research and Advanced
Technology (Grant No. 17JCJQJC43600), the Foundation for Talent Sci-
entists of Nanchang Institute for Microtechnology of Tianjin University,
and the 111 Project (Grant No. B07014). We also thank Prof. Mark Reed
at Yale University for useful discussions.
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... When in acoustic environment, the surface displacement is positively correlated to the power level and body force strength. Longer displacement suggests stronger body force, and stronger body force then generates vortex (around the resonator) with faster velocity [37]. Through the figure, even though non-excited resonators would also be interfered to generate vortices due to mechanical couplings, strength of vortex around the excited resonator will be much more significant and make other vortices omittable. ...
... A GHz BAW array chip is fabricated considering above crosstalk suppression methods for test purpose. The 2 GHz signal operated array is fabricated using a standard complementary metal-oxide-semiconductor (CMOS) process [37]. Detailly, on a silicon substrate, the Braggard Reflecting Structure, which is a stack structure of silicon oxide (SiO 2 ) and AlN, are deposited first to be the reflector of BAW. ...
Addressable trapping and manipulations of micro/nano-scale bioparticles is often necessary and critically important in microfluidic devices for biological and medical applications. While GHz bulk-acoustic-wave (BAW) resonators have shown their excellent performance in trapping, rotating, and focusing particles down to nanometers, arraying them for addressable manipulation is a great challenge due to the crosstalk among resonators. This paper presents the electrical and mechanical crosstalk analysis to GHz BAW array with proposed circuit-level models. Crosstalk mechanisms are thoroughly revealed, which contribute to clarify the design rules of GHz BAW array with low crosstalk. A 4 x 4 BAW array chip is designed and experimental results show the chip can achieve addressable control with negligible crosstalk, demonstrating the rationality of the analysis. The crosstalk analysis, as well as the derived design rules, will lead to the design of a high-performance GHz BAW array with great potential for applications that require massive, addressable, and precise particle manipulation. [2021-0236]
... Here, we qualitatively discuss the influence of the boundary conditions and the force status of the trapped particles by simulation. Once the device was fixed, the strength and distribution of the acoustic streaming were mainly determined by the geometry of the microchannel 59,63,64 . We then calculated the distribution of the acoustic field in 2D models under different geometric confinements, as shown in Supplementary Fig. S3. ...
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At the single-cell level, cellular parameters, gene expression and cellular function are assayed on an individual but not population-average basis. Essential to observing and analyzing the heterogeneity and behavior of these cells/clusters is the ability to prepare and manipulate individuals. Here, we demonstrate a versatile microsystem, a stereo acoustic streaming tunnel, which is triggered by ultrahigh-frequency bulk acoustic waves and highly confined by a microchannel. We thoroughly analyze the generation and features of stereo acoustic streaming to develop a virtual tunnel for observation, pretreatment and analysis of cells for different single-cell applications. 3D reconstruction, dissociation of clusters, selective trapping/release, in situ analysis and pairing of single cells with barcode gel beads were demonstrated. To further verify the reliability and robustness of this technology in complex biosamples, the separation of circulating tumor cells from undiluted blood based on properties of both physics and immunity was achieved. With the rich selection of handling modes, the platform has the potential to be a full-process microsystem, from pretreatment to analysis, and used in numerous fields, such as in vitro diagnosis, high-throughput single-cell sequencing and drug development.
... There are reports of 2.13 MHz bulk streaming in well trays used to agglomerate cells via streaming for tissue engineering and cancer trials, with methods to avoid adversely affecting the cell integrity 166 . A gigahertz-order bulk wave device was devised to drive acoustic streaming responsible for particle collection, alongside a method for particle image velocimetry of the streaming to even the nanoscale 156 . We also expect to see a growing number of applications for acoustic streaming-based particle manipulation in biomedical applications beyond the traditional trapping and transport concepts, such as work in which oocytes are denuded without contact 167 . ...
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Acoustofluidic technologies utilize acoustic waves to manipulate fluids and particles within fluids, all in a contact-free and biocompatible manner. Over the past decade, acoustofluidic technologies have enabled new capabilities in biomedical applications ranging from the precise patterning of heterogeneous cells for tissue engineering to the automated isolation of extracellular vesicles from biofluids for rapid, point-of-care diagnostics. In this Primer, we explain the underlying physical principles governing the design and operation of acoustofluidic technologies and describe the various implementations that have been developed for biomedical applications. We aim to demystify the rapidly growing field of acoustofluidics and provide a unified perspective that will allow end users to choose the acoustofluidic technology that is best suited for their research needs. The experimental set-ups for each type of acoustofluidic device are discussed along with their advantages and limitations. In addition, we review typical types of data that are obtained from acoustofluidic experiments and describe how to model different forces acting on particles within an acoustofluidic device. We also discuss data reproducibility and the need to establish standards for the deposition of data sets within the field. Finally, we provide our perspective on how to optimize device performance and discuss areas of future development. Acoustofluidic techniques use acoustic waves for contact-free manipulation of fluids and particles within fluids, enabling their use in a wide range of biomedical applications. In this Primer, Rufo et al. outline the design and operation of acoustofluidic systems and describe their implementation.
The hydrodynamic method mimics the in vivo environment of the mechanical effect on cell stimulation, which not only modulates cell physiology but also shows excellent intracellular delivery ability. Herein, a hydrodynamic intracellular delivery system based on the gigahertz acoustic streaming (AS) effect is proposed, which presents powerful targeted delivery capabilities with high efficiency and universality. Results indicate that the range of cells with AuNR introduction is related to that of AS, enabling a tunable delivery range due to the adjustability of the AS radius. Moreover, with the assistance of AS, the organelle localization delivery of AuNRs with different modifications is enhanced. AuNRs@RGD is inclined to accumulate in the nucleus, while AuNRs@BSA tend to enter the mitochondria and AuNRs@PEGnK tend to accumulate in the lysosome. Finally, the photothermal effect is proved based on the large quantities of AuNRs introduced via AS. The abundant introduction of AuNRs under the action of AS can achieve rapid cell heating with the irradiation of a 785 nm laser, which has great potential in shortening the treatment cycle of photothermal therapy (PTT). Thereby, an efficient hydrodynamic technology in AuNR introduction based on AS has been demonstrated. The outstanding location delivery and organelle targeting of this method provides a new idea for precise medical treatment.
Previous studies on ultrasound-propelled nano- and microparticles have considered only systems in which the particle orientation is perpendicular to the direction of propagation of the ultrasound. However, in future applications of these particles, they will typically be able to attain other orientations. Therefore, using direct acoustofluidic simulations, here we study how the propulsion of triangular nano- and microparticles, which are known to have a particularly efficient acoustic propulsion and are therefore promising candidates for future applications, depends on their orientation relative to the propagation direction of a traveling ultrasound wave. Our results reveal that the propulsion of the particles depends strongly on their orientation relative to the direction of wave propagation and that the particles tend to orient perpendicularly to the wave direction. We also address the orientation-averaged translational and angular velocities of the particles, which correspond to the particles' effective propulsion for an isotropic exposure to ultrasound. Our results allow assessment of how free ultrasound-propelled colloidal particles move in three spatial dimensions and thus constitute an important step toward the realization of envisaged future applications of such particles.
A surge of research in intracellular delivery technologies is underway with the increased innovations in cell‐based therapies and cell reprogramming. Particularly, physical cell membrane permeabilization techniques are highlighted as the leading technologies because of their unique features, including versatility, independence of cargo properties, and high‐throughput delivery that is critical for providing the desired cell quantity for cell‐based therapies. Amongst the physical permeabilization methods, sonoporation holds great promise and demonstrates to deliver a variety of functional cargos, such as biomolecular drugs, proteins, and plasmids, to various cells including cancer, immune, and stem cells. However, traditional bubble‐based sonoporation methods usually require special contrast agents. Bubble‐based sonoporation methods also have high chances of inducing irreversible damage to critical cell components, lowering the cell viability, and reducing the effectiveness of delivered cargos. To overcome these limitations, several novel non‐bubble‐based sonoporation mechanisms are under development. This review will cover both the bubble‐based and non‐bubble‐based sonoporation mechanisms being employed for intracellular delivery, the technologies being investigated to overcome the limitations of traditional platforms, as well as perspectives on the future sonoporation mechanisms, technologies, and applications. This review presents a comprehensive evaluation of the current state of sonoporation research and its advantages and limitations. Particularly, this review covers the current bubble‐based sonoporation mechanisms and the novel upcoming non‐bubble‐based sonoporation mechanisms and their respective technologies that are utilized to enhance intracellular delivery. This review concludes with a perspective on how the field of sonoporation can advance.
We for the first time propose and validate an electromechanical impedance spectroscopy (EMIS) technique to determine the resonance frequency (fr) of micromixers for effective cavitation microstreaming. Theoretical fr predictions of the oscillating bubble have been inaccurate because it was assumed that the bubble had a spherical shape even though bubbles are commonly trapped in low-profile air pockets, and thus their shapes are not spherical. Additionally, an empirical excitation-frequency search can be time-consuming and may overlook the exact value of fr. Strong electromechanical coupling between a piezoelectric transducer and a microfluidic chip (i.e., a mechanical structure) allows straightforward, rapid fr determination (∼4.5 min) using EMIS. To validate the EMIS method, we compare microstreaming patterns generated by bubbles excited at four different values of resonance frequencies using a high-speed imaging setup: 1) fr,B, the theoretical fr assuming a spherical bubble, 2) fr,Beq, the theoretical fr based on the concept of an “equivalent spherical bubble” having a surface area equal to the vibrating air-water interface area, 3) fr,Pf, the EMIS-based fr of a piezoelectric transducer, and 4) fr,Cf, the EMIS-based fr of the microfluidic chip bonded with the transducer. After confirming that fr,Cf yields the strongest cavitation microstreaming, the air-pocket shape is designed with consideration of the bubble stability and mixing effectiveness. A micromixer chip with the designed air pockets is excited at fr,Cf and exhibits rapid homogenization (37.2 s) of diluted ink and deionized water in the mixing chamber (61.9 μL). Additionally, an experimentally validated, adhesive-tape-supported laser microfabrication technique allows rapid prototyping (∼10 min) of polymethyl methacrylate microfluidic chips with an excellent dimensional accuracy, machining resolution, and surface smoothness. We expect the proposed EMIS-based technique for resonance-frequency determination and the simple, rapid laser microfabrication method to be widely employed for bio-/chemical microfluidic applications in the near future.
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Hydrodynamic force loading platforms for controllable cell mechanical deformation play an essential role in modern cell technologies. Current systems require assistance from specific microstructures thus limiting the controllability and flexibility in cell shape modulation, and studies on real‐time 3D cell morphology analysis are still absent. This article presents a novel platform based on acoustic streaming generated from a gigahertz device for cell shape control and real‐time cell deformation analysis. Details in cell deformation and the restoration process are thoroughly studied on the platform, and cell behavior control at the microscale is successfully achieved by tuning the treating time, intensity, and wave form of the streaming. The application of this platform in cell membrane permeability modulation and analysis is also exploited. Based on the membrane reorganization during cell deformation, the effects of deformation extent and deformation patterns on membrane permeability to micro‐ and macromolecules are revealed. This technology has shown its unique superiorities in cell mechanical manipulation such as high flexibility, high accuracy, and pure fluid force operation, indicating its promising prospect as a reliable tool for cell property study and drug therapy development.
Here, we present a high performance uncooled near-infrared (NIR) detector comprising of a giga hertz (GHz) solidly mounted resonator (SMR) and gold nanorods (GNRs) arrays. By coupling the localized surface plasmon resonances of GNRs, the resonator system exhibits optimized optical response to vis-NIR region. Both simulation and experiments demonstrate the hybrid GNRs-SMR exhibit significantly enhanced optical responsive sensitivity of NIR, the tunable aspect ratios (AR) of GNRs enable resonator respond sensitively to selected light. Specially, taking advantage of the acoustofluidic effect of SMR, the GNRs can be controllably and precisely modified on the microchip surface in an ultra-short time, which addresses one of the most fundamental challenges in the localized functionalization of micro/nano scale surface. The presented work opens new directions in development of novel miniaturized, tunable NIR detector.
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Developing microrobots for precisely manipulating micro/nanoscale objects has triggered tremendous research interest for various applications in biology, chemistry, physics, and engineering. Here, a novel hypersonic‐induced hydrodynamic tweezers (HSHTs), which use gigahertz nano‐electromechanical resonator to create localized 3D vortex streaming array for the capture and manipulation of micro‐ and nanoparticles in three orientations: transportation in a plane and self‐rotation in place, are presented. 3D vortex streaming can effectively pick up particles from the flow, whereas the high‐speed rotating vortices are used to drive self‐rotation simultaneously. By tuning flow rate, the captured particles can be delivered, queued, and selectively sorted through the 3D HSHTs. Through numerical simulations and theoretical analysis, the generation of the 3D vortex and the mechanism of the particles manipulation by ultrahigh frequency acoustic wave are demonstrated. Benefitting from the advantages of the acoustic and hydrodynamic method, the developed HSHTs work in a precise, noninvasive, label‐free, and contact‐free manner, enabling wide applications in micro/nanoscale manipulations and biomedical research.
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Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro- and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contact-free, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine.
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We present an acoustic microfluidic mixing approach via acousto-mechanically induced micro-vortices sustained by localized ultrahigh frequency (UHF) acoustic fields. A micro-fabricated solid-mounted thin-film piezoelectric resonator (SMR) with a frequency of 1.54 GHz has been integrated into microfluidic systems. Experimental and simulation results show that UHF-SMR triggers strong acoustic field gradients to produce efficient and highly localized acoustic streaming vortices, providing a powerful source for microfluidic mixing. Homogeneous mixing with 87% mixing efficiency at a Peclet number of 35520 within 1 ms has been achieved. The proposed strategy shows a great potential for microfluidic mixing and enhanced molecule transportation in minimized analytical systems.
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Despite increasing demand in the manipulation of nanoscale objects for next generation biological and industrial processes, there is a lack of methods for reliable separation, concentration and purification of nanoscale objects. Acoustic methods have proven their utility in contactless manipulation of microscale objects mainly relying on the acoustic radiation effect, though the influence of acoustic streaming has typically prevented manipulation at smaller length scales. In this work, however, we explicitly take advantage of the strong acoustic streaming in the vicinity of a highly focused, high frequency surface acoustic wave (SAW) beam emanating from a series of focused 6 μm substrate wavelength interdigital transducers patterned on a piezoelectric lithium niobate substrate and actuated with a 633 MHz sinusoidal signal. This streaming field serves to focus fluid streamlines such that incoming particles interact with the acoustic field similarly regardless of their initial starting positions, and results in particle displacements that would not be possible with a travelling acoustic wave force alone. This streaming-induced manipulation of nanoscale particles is maximized with the formation of micro-vortices that extend the width of the microfluidic channel even with the imposition of a lateral flow, occurring when the streaming-induced flow velocities are an order of magnitude larger than the lateral one. We make use of this acoustic streaming to demonstrate the continuous and differential focusing of 100 nm, 300 nm and 500 nm particles.
Acoustic actuation of fluids at small scales may finally enable a comprehensive lab-on-a-chip revolution in microfluidics, overcoming long-standing difficulties in fluid and particle manipulation on-chip. In this comprehensive review, we examine the fundamentals of piezoelectricity, piezoelectric materials, and transducers; revisit the basics of acoustofluidics; and give the reader a detailed look at recent technological advances and current scientific discussions in the discipline. Recent achievements are placed in the context of classic reports for the actuation of fluid and particles via acoustic waves, both within sessile drops and closed channels. Other aspects of micro/nano acoustofluidics are examined: atomization, translation, mixing, jetting, and particle manipulation in the context of sessile drops and fluid mixing and pumping, particle manipulation, and formation of droplets in the context of closed channels, plus the most recent results at the nanoscale. These achievements will enable applications across the disciplines of chemistry, biology, medicine, energy, manufacturing, and we suspect a number of others yet unimagined. Basic design concepts and illustrative applications are highlighted in each section, with an emphasis on lab-on-a-chip applications.
A method based on standing surface acoustic waves (SSAWs) is proposed to pattern and manipulate microparticles into a three-dimensional (3D) matrix inside a microchamber. An optical prism is used to observe the 3D alignment and patterning of the microparticles in the vertical and horizontal planes simultaneously. The acoustic radiation force effectively patterns the microparticles into lines of 3D space or crystal-lattice-like matrix patterns. A microparticle can be positioned precisely at a specified vertical location by balancing the forces of acoustic radiation, drag, buoyancy, and gravity acting on the microparticle. Experiments and finite-element numerical simulations both show that the acoustic radiation force increases gradually from the bottom of the chamber to the top, and microparticles can be moved up or down simply by adjusting the applied SSAW power. Our method has great potential for acoustofluidic applications, building the large-scale structures associated with biological objects and artificial neuron networks.
On-chip integrating several functional components for developing integrated lab-on-a-chip microsystem remains as a challenge. In this work, by employing multiple microelectromechanical resonators both as actuators and sensors, on-chip heating, mixing and chemical reaction monitoring are successfully demonstrated. Mechanism studies using COMSOL simulations indicate that the local heating and mixing are induced by the acoustic wave attenuation during its transmission in liquid. On-line chemical reaction monitoring is realized by viscosity sensing using the same resonator through impedance analysis. Classic Diels-Alder reaction in a single droplet was performed to verify the feasibility of using such microsystem for mixing, heating and online reaction monitoring at microscale.
Efficient delivery of genes and therapeutic agents to the interior of the cell is critical for modern biotechnology. Herein, a new type of chemical-free cell poration method— hypersonic poration—is developed to improve the cellular uptake, especially the nucleus uptake. The hypersound (≈GHz) is generated by a designed piezoelectric nano-electromechanical resonator, which directly induces normal/shear stress and “molecular bombardment” effects on the bilayer membranes, and creates reversible temporal nanopores improving the membrane permeability. Both theory analysis and cellular uptake experiments of exogenous compounds prove the high delivery efficiency of hypersonic poration. Since target molecules in cells are accumulated with the treatment, the delivered amount can be controlled by tuning the treatment time. Furthermore, owing to the intrinsic miniature of the resonator, localized drug delivery at a confined spatial location and tunable arrays of the resonators that are compatible with multiwell plate can be achieved. The hypersonic poration method shows great delivery efficacy combined with advantage of scalability, tunable throughput, and simplification in operation and provides a potentially powerful strategy in the field of molecule delivery, cell transfection, and gene therapy.
Cell and particle trapping experience a rising interest in a microfluidic context. Trapping of cells in suspension at distinct locations in a microfluidic domain is relevant for cell biological lab-on-a-chip systems, where a trap provides a well-definable microenvironment for cell response studies. This paper reports a novel acoustophoretic cell trapping effect on oscillating sharp edge structures which protrude into a microfluidic channel. These edge structures (125–250 $$\upmu \hbox {m}$$μm length, 10–80 $$\upmu \hbox {m}$$μm width in the experiments) were found to attract cells and particles strongly and reliably upon simple piezoelectric excitation around 1 MHz. The method is contact- and label-free, robust, and biocompatible. The physical trapping effect is experimentally characterized, and a numerical model is proposed, based on the theory of acoustic radiation forces.