Chemical Engineering Journal 374 (2019) 68–78

Contents lists available at ScienceDirect

Chemical Engineering Journal

journal homepage: www.elsevier.com/locate/cej

Acoustic cavitation and ultrasound-assisted nitration process in ultrasonic T

microreactors: The effects of channel dimension, solvent properties and
temperature
⁎
Shuainan Zhaoa,b, Chaoqun Yaoa, Qiang Zhanga,b, Guangwen Chena, , Quan Yuana
a
Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
b
University of Chinese Academy of Sciences, Beijing 100049, China

H I GH L IG H T S

• Acoustic cavitation behavior in microchannel was systematically investigated.

• The critical microchannel size to eliminate confinement effect was obtained.
• Acoustic cavitation was promoted in liquid with low viscosity and tension.
• An operation guideline for ultrasound-assisted nitration process was established.

A R T I C LE I N FO A B S T R A C T

Dedicated to the 70th anniversary of Dalian Experimental studies on acoustic cavitation and ultrasound-assisted nitration reaction were systematically in-
Institute of Chemical Physics, CAS. vestigated in two laboratory-built ultrasonic microreactors by tuning the microchannel dimension, solvent
properties and temperature. Under ultrasound irradiation, acoustic cavitation microbubbles were generated and
Keywords: underwent violent oscillation in microchannel. With the decrease of channel size, acoustic cavitation was largely
Acoustic cavitation confined, and channel size 1 × 1 mm2 was recognized as the critical size to eliminate the confinement effect.
Meso-scale Acoustic cavitation was also highly dependent on the properties of sonicated liquids. The onset of surface wave
Confinement effect
oscillation on gas bubble was obviously promoted with decreasing solvent viscosity and surface tension.
Nitration reaction
Ultrasonic microreactors
Additionally, ultrasound-assisted nitration process of toluene was studied in a temperature-controlled ultrasonic
microreactor. The effects of channel size as well as liquid properties on ultrasound intensification agreed well
with the finding in cavitation research. Under ultrasound power 50 W, toluene conversion was enhanced by
9.9%–36.3% utilizing 50 vol.% ethylene glycol aqueous solution as ultrasound propagation medium, exhibiting
ultrasound applicability on intensifying fast reaction processes in microreactors.

1. Introduction difficult to control in conventional reactors (e.g., nitration reaction,

Microreactors, as one of the most promising method of process in-
tensification, has attracted considerable attention during the last two
decades [1–3]. The characteristic dimension of microreactor is typically
on the order of sub-millimeters to millimeters, which offers a significant
augmentation of mass/heat transfer rate over conventional equipment
[4–6]. In addition, precise control of reaction conditions (e.g., tem-
perature, pressure), improved safety, and ease of scale up are also well-
known advantages of microreaction technology [7,8]. Microreactors
have been widely used for studying and optimizing chemical reactions,
especially for highly exothermic and explosive reactions that are
H2O2 oxidation, halogenation reaction) [9–13]. Chambers et al. [14]
performed the continuous fluorination of 4-nitrotoluene in a three-
channel microreactors with the conversion reaching up to 78%, which
was significantly higher than that obtained in conventional batch op-
eration. Despite the advantages of microreaction technology, there still
exist significant problems retarding its widespread application. As flow
of common liquids in microchannels are characterized by low values of
Reynolds number, the flows are always laminar with mixing of fluids
being dominated by purely diffusion processes [15,16]. The time scale
to eliminate mass transfer limitations is relatively long when con-
sidering fast reactions that go to completion in a matter of seconds [17].

⁎
Corresponding author.
E-mail address: gwchen@dicp.ac.cn (G. Chen).

https://doi.org/10.1016/j.cej.2019.05.157
Received 15 April 2019; Received in revised form 21 May 2019; Accepted 23 May 2019
Available online 24 May 2019
1385-8947/ © 2019 Elsevier B.V. All rights reserved.
S. Zhao, et al.
Nomenclature
f frequency, Hz
M molar mass of the product, kg/mol
n molar ratio
Ph hydrostatic pressure, Pa
ΔP pressure drop, Pa
QL water flow rate, mL/min
Qtot total reactant flow rate, mL/min
Rr linear resonance size
T temperature, °C
X conversion of toulene
XA ultrasound-assisted toluene conversion
Z measured impedance
Ultrasound has recently been utilized to overcome such limitations
in microreactors [18–20]. When ultrasound of sufficient intensity is
transmitted through a liquid medium, micron-sized bubbles are gen-
erated and oscillate violently in response to acoustic pressure fluctua-
tion, i.e., acoustic cavitation [21,22]. A variety of mechanical effects
are induced (e.g., microstreaming, shock wave) and in turn accelerate
the mixing process greatly [19,23]. The applicability of ultrasonic mi-
croreactor has been demonstrated in various fields, including mixing,
extraction and reaction [18,24–27]. John et al. [28] investigated the
hydrolysis process of p-nitrophenyl acetate in a laboratory-built ultra-
sonic microreactor. After exposure to ultrasound, intense emulsification
of reactants was initiated, resulting in a 2.5 times improvement in yield.
In our previous work, we have also investigated the ultrasound-assisted
extraction processes of both water-octanol system and water-toluene
system using the same experimental set-up [25,29,30]. Under identical
ultrasound energy input, the mass transfer rates for the two systems
were enhanced by 1.3–1.7 and 1.5–2.3 times, respectively, indicating
that ultrasound enhancement was closely related to solvent properties
[30]. Additionally, ultrasound enhancement was also highly dependent
on channel dimension. Hubner et al. [18] compared the yield en-
hancement of hydrolysis reaction in an ultrasonicated capillary with its
diameter increasing from 300 to 1600 μm, finding that ultrasound en-
hancement increase with the increase of channel size. A similar trend
was also observed by Dong et al. [24] when investigating the homo-
geneous mixing process of uranine solution and water. In microchannel
1 × 1 mm2, mixing time was greatly reduced with ultrasound by one or
two orders of magnitude from 24–32 s to 0.2–1.0 s. However, the
Fig. 1. (a) Structure of the directly coupling ultrasonic microreactor, (b) Schematic diagram of the microchannel structure on the microreactor plate.
69
Chemical Engineering Journal 374 (2019) 68–78
ρ density, kg/m3
κ adiabatic exponent
λ wavelength, m
σ interfacial tension, N/m
ω mass function
Acronyms
ER enhancement ratio, calculated as (XA − X)/X
EG ethylene glycol
FEP fluorinated ethylene propylene
MR microchannel
USMR 1 directly coupling ultrasonic microreactor
USMR 2 temperature-controlled ultrasonic microreactor
ultrasonic mixing performance dropped sharply with the decrease of
channel size, even showing no obvious enhancement at the micro-
channel with dimension of 500 × 250 μm2. The weaker ultrasound
enhancement in smaller channel was attributed to its confined cavita-
tional activity (termed as confinement effect) [24,31], while the de-
tailed mechanism how channel dimension influence cavitation behavior
as well as the critical channel size to eliminate confinement effect still
remains elusive. Therefore, implementing such studies is of vital im-
portance to the optimization and further application of ultrasonic mi-
croreactor.
In this work, the effects of dissolved gas, channel dimension, solvent
properties and temperature on acoustic cavitation behavior were sys-
tematically investigated. To justify the cavitation research, ultrasound-
assisted toluene nitration process was then studied in a temperature-
controlled ultrasonic microreactor. Finally, an operational guidance
was proposed for the optimized application of ultrasonic microreactor
to chemical processes, including proper channel dimension and ultra-
sound transmission medium.
2. Materials and methods
2.1. Materials
Toluene (99.5 wt% purity), sulfuric acid (98 wt%), nitric acid (98 wt
%) and sodium bicarbonate (NaHCO3, 99.5 wt% purity) were pur-
chased from Tianjin Kemiou Chemical Reagent Co., Ltd. Anhydrous
ethanol (99.7 wt% purity) and ethylene glycol (99.0 wt% purity) were
S. Zhao, et al.
procured from Tianjin Damao Chemical Co., Ltd. and Sinopharm
Chemical Reagent Co., Ltd., respectively. All chemicals were used as
received without further treatment.
2.2. Apparatus
2.2.1. Directly coupling ultrasonic microreactor (USMR 1)
The acoustic cavitation behavior in microchannel was investigated
utilizing a directly coupling ultrasonic microreactor (abbreviated as
USMR 1). As shown in Fig. 1(a), a 3 mm thick microreactor plate (Ti-
tanium) was directly coupled with a Langevin-type ultrasonic trans-
ducer (ZFHN-100-21.5, Baoding Zhengjie Electric, china) using ultra-
sonic transmission gel (THD 383, Taiheda, China). Sealing of the
microreactor was realized by bonding a transparent polycarbonate film
(0.2 mm in thickness) to the microreactor plate, through which optical
observation of microbubble cavitation behavior was also attained.
Fig. 1(b) illustrates the schematic diagram of the microchannel struc-
ture. The microchannel consisted of a T-junction with two 500 μm wide
branches merging into a 500 μm main channel. In order to investigate
the effect of channel dimension on acoustic cavitation, the width of the
square-shaped channel was gradually enlarged from 0.5 to 2.5 mm
(abbreviated as MR0.5, MR1.0, MR1.5, MR2.0 and MR2.5, respec-
tively). During the experiments, acoustic cavitation process in micro-
channel was monitored by a high speed camera (Phantom M310, Vision
Research) at a frame rate of 40,000 fps. The whole ultrasonic micro-
reactor was illuminated by a metal halide light source (MME-250,
MORITEX SCHOTT). To enable better visualization of the cavitation
Fig. 2. Configuration of the temperature-controlled ultrasonic microreactor (USMR 2).
70
Chemical Engineering Journal 374 (2019) 68–78
details, the microchannel was magnified by 6-fold with a zooming lens
(1-50487, Navitar).
2.2.2. Temperature-controlled ultrasonic microreactor (USMR 2)
In order to realize temperature control during nitration process, a
temperature-controlled ultrasonic microreactor was then fabricated by
integrating a square-shaped container (Aluminum alloy LY12,
93 × 93 × 12.5 mm3) with ultrasonic transducer (Fig. 2(a)). As shown
in Fig. 2(b), the container was hollowed out in the center
(61 × 61 × 9 mm3) and then sandwiched by an upper cover plate and
lower insulation plate (made of Polyarylsulfone). Five through-holes
were processed on the walls of the hollowed container (Fig. 2(c)),
through which reactants as well as circulating fluid were introduced. A
capillary microreactor was installed in the container by two brackets
(Fig. 2(d)). In this way, ultrasonic oscillation can be directly transferred
into the capillary from the brackets. The temperature of the capillary
microreactor was tuned by a thermostat (F12-ME refrigerated/heating
circulator, Julabo, Germany) pumping circulating fluid into and out of
the container. The real-time temperature of the circulating fluid was
monitored by a thermocouple from through-hole 5. During the ex-
periments, ultrasonic oscillation was both directly (by brackets) and
indirectly (through circulating fluid) transmitted into the capillary
microreactor.
The resonant frequencies of the two laboratory-built ultrasonic
microreactors were measured using an impedance analyzer (PV70A,
Beijing Band Era, China), being 19.76 (USMR 1) and 21.21 kHz (USMR
2), respectively (see details in the Supporting Information). During the
S. Zhao, et al. Chemical Engineering Journal 374 (2019) 68–78

experiments, both ultrasonic microreactors were excited at their re-
sonance frequencies using a signal generator (AFG2112, GW InSTEK),
whose signal was amplified by a RF power amplifier (AG 1016, T&C
Power Conversion). Additionally, an impedance matcher (TIK LF-7-
070114, T&C Power Conversion) was utilized to match the impedance
difference between ultrasonic microreactors and power amplifier.
During the experiments, the net power applied to the ultrasonic mi-
croreactor (referred as ultrasound power in the following section) was
tuned in the range of 5–50 W. After exposure to ultrasound, an obvious
increase of temperature was observed in USMR 1. In comparison, the
temperature in USMR 2 was controlled precisely, with its maximum
deviation from the setting temperature being less than 0.5 °C. The
temperature fluctuation of two ultrasonic microreactors after exposure
to ultrasound was covered in the Supporting Information.
2.3. Products analysis
The nitration of toluene was carried out in the temperature-con-
trolled ultrasonic microreactor (USMR 2) with mixed acid (68.11 wt%
H2SO4, 21.89 wt% HNO3, 10 wt% H2O) being used as the nitrating
agent. The molar ratio of nitric acid to toluene was fixed at 1.05. In the
experiment, the nitration product from USMR 2 was first collected in a
small beaker, which contained excessive amounts of ice-water to ter-
minate the reaction. The obtained sample was then separated via a
separatory funnel, after which the organic phase was retained and
washed three times with saturated NaHCO3 solution and deionized
water to remove the dissolved trace acid and inorganic substances,
respectively. Finally, the composition of the organic phase was ana-
lyzed utilizing a gas chromatograph (Agilent 7890B, Column: DB1701,
30 m × 0.32 mm × 0.25 μm). The gas chromatograph was equipped
with a flame ionization detector with nitrogen serving as the carrier
gas. The conversion of toluene (X) was calculated as follows:
ωi / M
ni = n
∑i = 1 (ωi / Mi ) (1)
n The effect of channel dimension on acoustic cavitation behavior was
⎛ ⎞
X = 1 − ⎜nt / ∑ ni⎟
⎝ i = 1 ⎠ (2)
where Mi is the molar mass of the product i. ωi, ni represent the mass
function and molar ratio of product i in the organic phase (e.g., toluene,
o-nitrotoluene, m-nitrotoluene, p-nitrotoluene, 2,4-dinitrotoluene, 2,6-
dinitrotoluene), respectively. nt denotes the molar ratio of toluene in
the organic phase.
extremely hard, with no microbubble being observed. Considering this,
the liquid medium was all used without degassing in this experiment.
3.1.1. Effect of bubble size on microscopic cavitation behavior
Once generated, microbubble will oscillate intensely in response to
acoustic pressure fluctuation. According to Minnaert [36,37], under
given ultrasound frequency, there exists a linear resonance size of mi-
crobubble, where the bubble resonates with the driving wave. The re-
sonance size Rr is obtained as:
1 3κPh
Rr =
2πf ρ (3)
where κ, Ph, ρ represent the adiabatic exponent of the gas inside the
bubble, hydrostatic pressure and density of the working liquid, re-
spectively. f denotes the driving frequency of ultrasonic wave, i.e.,
20 kHz in this work. For an air bubble (κ = 1.4) in water (998 kg/m3)
under atmospheric pressure (Ph = 101 kPa), the resonance size was
calculated to be 165 μm. Microbubbles with size nearing the resonance
size oscillated more violently in response to sound wave. As shown in
Fig. 4, under ultrasound power 10 W in MR1.0, typical changes in the
oscillation behavior of microbubbles were observed with increasing
bubble size. For small bubble with radius being around 50 μm, micro-
bubble oscillated radially with symmetrical pulsation of the bubble
volume (termed as volume oscillation). The frequency of volume os-
cillation was observed to be 20 kHz, which agreed well with the driving
ultrasound frequency. With the increase of bubble radius to 120 μm,
surface distortion of the originally spherical bubble set in and bubble
oscillation developed into shape mode. When the bubble radius ap-
proached the resonance size 165 μm, bubble oscillation became un-
stable and underwent rapid explosive growth, followed by a violent
collapse (transient cavitation). With the further increase of bubble ra-
dius to 240 μm, bubble size was far away from the resonance size, re-
sulting in bubble oscillation going back again to shape mode.
3.1.2. Effect of channel dimension on cavitational activity
investigated in USMR 1 with microchannel dimension increasing from
0.5 to 2.5 mm (MR0.5 to MR2.5). During the experiments, the flow rate
of water (QL) was fixed at 3.0 mL/min. The pressure drop along mi-
crochannel was measured to be 21.5 kPa utilizing a differential pressure

3. Results and discussion

3.1. Cavitational activity

As acoustic cavitation is the dominant mechanism responsible for

the intensification of ultrasound-assisted processes [19,30,32], a thor-
ough understanding on cavitation behavior and its relation with ex-
perimental parameters (e.g., dissolved gas, channel dimension, solvent
properties, and temperature) is highly needed. To elucidate it, cavita-
tion behavior of both acoustic cavitation microbubble and introduced
gas slug under varying experimental parameters were then in-
vestigated.
Acoustic cavitation is defined as the formation, growth, oscillation,
and collapse of dynamic bubbles in a liquid after exposure to acoustic
pressure waves [33]. In reality, the required energy for the formation of
cavitation bubbles from liquid nuclei is extremely high in confined
microchannel [34], bubbles therefore often originate from either the
direct injection or prior trapped/dissolved gas in liquid [35]. As shown
in Fig. 3, under ultrasound power 10 and 30 W in MR2.5, microbubbles
were generated and oscillated intensely in pure water (undegassed). In Fig. 3. Acoustic cavitation behavior in pure water and degassed water in
comparison, the initiation of acoustic cavitation in degassed water was MR2.5, scale bar 500 μm.

71
S. Zhao, et al. Chemical Engineering Journal 374 (2019) 68–78

Fig. 4. Microscopic cavitation behavior of microbubbles in MR1.0 with different size. Ultrasound power 10 W, QL 3.0 mL/min, scale bar 500 μm.

sensor (0–100 kPa, 692.930107101, Huba control), i.e., water hydro- size to eliminate confinement effect, the oscillation behavior transition
static pressure in MR0.5 was 21.5 kPa higher than that in MR2.5. As of microbubble in the enlargement region was further analyzed. Fig. 7
acoustic cavitation will be suppressed with increasing hydrostatic illustrates the oscillation mode transition of microbubble when passing
pressure, the influence of that pressure difference on acoustic cavitation through the enlargement zone connecting MR0.5 to MR1.0, MR1.0 to
behavior should be studied first [37]. Therefore, the cavitation beha- MR1.5, MR1.5 to MR2.0 and MR2.0 to MR2.5 respectively (abbreviated
vior in MR0.5 with different water hydrostatic pressure were compared. as MR 0.5–1.0, MR 1.0–1.5, MR 1.5–2.0 and MR 2.0–2.5). It should be
When water flow from MR0.5 to MR2.5 along the microchannel, MR0.5 noted that only obvious mode change was identified as transition, e.g.,
serve as the inlet of main channel with water hydrostatic pressure being bubble oscillation transits from volume mode to shape mode through
122.8 kPa. Otherwise, MR0.5 serve as the outlet of the main channel the enlargement zone. As transition of microbubble oscillation was
and the water hydrostatic pressure in MR0.5 equals the atmospheric observed in MR 0.5–1.0, it indicated that bubble oscillation was ori-
pressure 101.3 kPa. Fig. 5 illustrates the oscillation modes of micro- ginally confined in MR0.5. The confined behavior of microbubble in
bubbles with varying size (10–200 μm) and ultrasound power (5–30 W)
under these two circumstances. The open and solid symbol in Fig. 5
represent the respective microbubble cavitation behavior under Ph
101.3 and 122.8 kPa. The critical size R1 for microbubble volume-shape
oscillation transition was found to decrease with the increase of ultra-
sound power, which was due to that higher acoustic pressure promote
violent bubble oscillation. Additionally, no significant difference was
observed between the critical size R1 for Ph 101.3 and 122.8 kPa, i.e.,
the influence of hydrostatic pressure fluctuation along microchannel on
acoustic cavitation behavior can be excluded in this work.
As the influence of pressure drop along microchannel was excluded,
the acoustic cavitation behaviors in microchannel with increasing di-
mension from 0.5 to 2.5 mm were then investigated. Fig. 6 gives an
intuitive insight into the cavitation transition of microbubble when
enlarging channel size. When microbubble flowed from MR0.5 to
MR1.0, the original volume pulsation of microbubble was transited to
erratic shape deformation. The phenomenon that acoustic cavitation
being constrained in the narrower channel was also defined as con-
finement effect [24,31,38]. When channel size increased from 2.0 to
2.5 mm, the amplitude of the periodic surface distortion of microbubble
remained constant, indicating that confinement effect was eliminated Fig. 5. Comparison of microbubble cavitation behavior in MR0.5 with hydro-
with the increase of channel size. To characterize the critical channel static pressure 101.3 and 122.8 kPa.

72
S. Zhao, et al.
Fig. 6. Transition behavior of bubble oscillation with the increase of channel size.
Fig. 7. Effect of channel size on confinement effect.
smaller channel is possibly attributed to the high viscosity gradient near
its channel wall [22,31]. With the increase of channel dimension to MR
1.0–1.5, MR 1.5–2.0 and MR 2.0–2.5, the effect of viscosity gradient on
bubble oscillation weakens and no transition was observed.
In addition to the enlargement zone, cavitation behavior in in-
dividual channel was also systematically studied. Fig. 8 illustrates the
cavitation distribution of microbubble with varying ultrasound power
(P) and bubble size (R) in MR0.5, MR1.0 and MR1.5, respectively. In
comparison to MR1.0 and MR1.5, no transient cavitation was observed
in MR0.5, even when ultrasound power shoot over 30 W. In MR1.0 and
MR1.5, with the increase of ultrasound power, bubble oscillation was
found to transit from volume to shape mode, and finally transient ca-
vitation. When further increased bubble size, microbubble deviated
from the resonance size (165 μm) and its oscillation returned back to
shape mode. The obtained results agreed well with the conclusion in
Section 3.1.1.
To further figure out the critical channel size that exert confinement
on microbubble cavitation behavior, the critical bubble size R1 for vo-
lume-shape transition in MR0.5, 1.0, 1.5 were then compared (as shown
in Fig. 9(a)). The transition line between volume and shape mode in
MR1.0 was found to deviate far from that in MR0.5, but agree well with
that in MR1.5, indicating that acoustic cavitation was confined in
MR0.5 compared to MR1.0 and 1.5 [24]. The critical bubble size R2, R3
73
Chemical Engineering Journal 374 (2019) 68–78
for shape-transient and transient-shape transition in MR1.0 and 1.5
were also compared to determine whether the confinement effect exists
therein. As illustrated in Fig. 9(b), the two transition line coincided with
each other, indicating that no confinement exists when microchannel
size shoot over 1.0 mm.
3.1.3. Effect of liquid properties on cavitational activity
In our previous work, liquid properties (e.g., viscosity, surface
tension) were found to exert significant influence on acoustic cavitation
behavior [25]. In order to figure out the respective effects of viscosity
and surface tension, a series of aqueous solutions were prepared by
adding a moderate amount of ethylene glycol (EG) and surfactant so-
dium dodecyl sulfate (SDS). Table 1 illustrates the properties of ethy-
lene glycol and SDS aqueous solutions at different bulk concentrations.
With the addition of EG (50 vol%), the viscosity of water was increased
by 3 times, while its surface tension was barely reduced by 20%. Si-
milarly, the surface tension of water was obviously reduced from 74.18
to 31.64 mN/m by dissolving 0.2 wt% SDS. As the size of cavitation
nuclei is uncontrollable with the addition of SDS, nitrogen gas was
therefore introduced and uniformly dispersed in the microreactor,
through which ultrasound induced oscillation of gas bubble can be
characterized.
Fig. 10 illustrates the surface wave oscillation of gas bubble in the
prepared solutions. For water-N2 system, surface wave was first in-
itiated at the bubble tip when ultrasound power reached 19 W, and then
expanded to bubble body with increasing ultrasound power. The
threshold power (PT) to first initiate surface wave was increased by
adding ethylene glycol in water. As the general effect of viscosity is to
produce friction and loss of mechanical energy during ultrasonic os-
cillation [22,39], surface wave was therefore harder to be initiated in
highly viscous liquid, resulting in a maximum PT of 30 W in 50 vol%
ethylene glycol aqueous solution (viscosity 3.81 cP). In contrast to
ethylene glycol, PT was found to decrease sharply by the addition of
SDS. As shown in Fig. 11(a), PT was obviously reduced to 11 W at 0.2 wt
% SDS aqueous solution (surface tension 31.64 mN/m). The restraining
effect of surface tension on the initiation of surface wave lies in its
tendency to maintain the bubble to a spherical shape [22,39–41]. The
wavelength λ and frequency f of the initiated surface wave were also
measured. As illustrated in Fig. 11(b), the measured wavelengths were
in good agreement with the predicted ones obtained by the dispersion
relation of capillary wave, i.e., λ = (2πσ/f2ρ)1/3 [42]. This indicates
that the initiated surface wave is also capillary wave with whose dy-
namics being dominated by surface tension.
S. Zhao, et al. Chemical Engineering Journal 374 (2019) 68–78

Fig. 9. Effect of channel dimension on microbubble oscillation transition from

volume mode to shape mode (a) and from shape mode to transient cavitation
(b).
The cavitation distribution in MR0.5, 1.0, and 1.5 were indicated by diamond,
square and triangle symbol, respectively. The open and solid symbol represent
volume-shape transition and shape-transient transition in Fig. 9(a) and (b),
respectively.

Fig. 12(a), no obvious response to ultrasound was observed at bubble-

water interface under temperature 5 °C. When increasing the water
temperature to 45 °C, surface wave oscillation was initiated, indicating
that higher temperature promoted acoustic cavitation process. The
reason lies in that both liquid viscosity and surface tension decrease
sharply with increasing temperature (see details in the Supporting
Information), resulting in easier initiation of surface wave. Fig. 12(b)
and (c) compares the cavitation behavior in water and 50 vol% ethylene
glycol aqueous solution, finding that surface wave was harder to be
initiated in bubble-ethylene glycol aqueous solution system due to its
obviously higher viscosity.
Fig. 8. Cavitation distribution of microbubble with varying ultrasound power
and bubble size in MR0.5 (a), MR1.0 (b) and MR1.5 (c), respectively.
3.2. Nitration reaction
3.1.4. Temperature
As acoustic cavitation is closely related to ultrasound intensifica-
The effect of temperature (5, 25, 45 °C) on acoustic cavitation be-
tion, nitration of toluene was then conducted in the temperature-con-
havior was investigated using water and 50 vol% ethylene glycol aqu-
trolled ultrasonic microreactor to justify the cavitation research. The
eous solution as sonicated liquid. Experiments were conducted in the
conversion of toluene (X) was measured to investigate the effects of
temperature-controlled ultrasonic microreactor (USMR 2) with a gas
reaction temperature, flow rate, channel dimension, and physico-
bubble being pre-trapped in the hollow container. As shown in
chemical properties of the circulating fluid on ultrasound

74
S. Zhao, et al.
Table 1
Fluid properties of ethylene glycol and SDS aqueous solutions at different bulk concentrations.
EG content (vol%)
0 12.5 25 37.5
ρ [kg/m ]3
1.00 1.02 1.05 1.06
μ [cP] 1.06 1.42 1.91 2.67
σ [mN/m] 74.18 68.44 64.94 62.15
intensification.
3.2.1. Effect of ultrasound on toluene conversion
As toluene nitration is highly exothermic with reaction heat being
approximately −125 kJ/mol, it therefore proposes a severe challenge
for micro-capillaries to realize rapid heat removal during reaction
process [43,44]. The heat transfer behaviors of fluorinated ethylene
propylene capillary (FEP, ID 1.0 mm) as well as stainless capillary (316,
ID 1.0 mm) were compared in advance [45,46], finding that stainless
capillary was capable of removing reaction heat rapidly (see details in
the Supporting Information). Fig. 13 illustrates the conversion of to-
luene X under varying reaction temperatures (5–45 °C), reactant flow
rates (Qtot 1.5–4.5 mL/min) and ultrasound power (50 W) in a stainless
capillary (ID 1.0 mm). Under silent condition, X increased with the
increase of reaction temperature, which greatly accelerated the reaction
rates. Additionally, due to the fact that elevated Qtot corresponds to
reduced residence time, X decreased with the increase of Qtot. Under
Qtot 1.5 mL/min, X was measured to be in the range of 27.5%–64.4%.
When Qtot was increased to 4.5 mL/min, X was sharply decreased to the
range of 11.9%–55.3%. After exposure to ultrasound, toluene conver-
sion was obviously improved. At reaction temperature 25 °C, X was
increased by 6.2% when Qtot equaled 1.5 mL/min. Further increasing
the reaction temperature to 45 °C, the increment of X decreased to 4.5%
due to the more intense cavitational activity in circulating fluid, which
caused an excessive energy loss during ultrasonic transmission. In ad-
dition to reaction temperature, the promotion effect of ultrasound also
decreased with the increase of reactant flow rate, being barely 1.9% at
Qtot of 4.5 mL/min. The respective enhancement ratio of ultrasound (ER
is obtained as (XA-X)/X, where XA represents the ultrasound-assisted
toluene conversion) at Qtot 1.5 mL/min and 4.5 mL/min were calcu-
lated, being 7.1%–14.0% and 0.9%–8.0%, respectively. The decreasing
ultrasound intensification effect with increasing Qtot can be explained
Fig. 10. Surface wave oscillation of gas bubble under varying ultrasound power and liquid. QL 3 mL/min, QG 1 mL/min, scale bar 500 μm.
75
Chemical Engineering Journal 374 (2019) 68–78
SDS content (wt%)
50 0.05 0.10 0.15 0.20
1.08 1.00 1.00 1.00 1.00
3.81 1.06 1.06 1.06 1.06
58.60 50.98 40.55 34.77 31.64
as follows: Smaller Qtot corresponds to longer ultrasound processing
time and more ultrasound power input per unit volume of reactants.
Consequently, the mixing between reactants became more sufficient to
provide a higher X.
3.2.2. Channel dimension
As acoustic cavitation was confined in microchannel with dimen-
sion less than 1.0 mm, the ultrasound-assisted nitration process was
therefore carried out in capillary 0.6 to justify the cavitation research.
Fig. 14 illustrates the measured toluene conversion in capillary with an
inner diameter of 0.6 mm and 1.0 mm, respectively. The reactant flow
rate in capillary 0.6 was set to be 0.54 mL/min to keep identical su-
perficial velocity with capillary 1.0. Under silent condition, the toluene
conversion in capillary 0.6 was measured to be in the range of
41.4%–69.3%, much higher than that in capillary 1.0. The obviously
higher conversion was attributed to the larger available mass transfer
interfacial area obtained in capillary 0.6 [47]. After exposure to ultra-
sound, X was increased in both capillary 0.6 and 1.0. As shown in
Fig. 14(b), ultrasound enhancement ratio (ER) first increase with the
increase of temperature from 5 to 15 °C, which is due to the more in-
tense cavitational activity in microchannel. Further increasing tem-
perature, ER was found to display a decreasing trend instead of the
expected increase. The reason lies in that ultrasound transmission ef-
ficiency of the circulating fluid decrease with increasing temperature.
Overall, the conversion of toluene were enhanced by 5.8%–9.1% and
7.1%–14.0% in capillary 0.6 and 1.0, individually. The much lower
enhancement ratio obtained in capillary 0.6 agreed well with the ca-
vitation research, indicating that ultrasound intensification was indeed
confined in smaller microchannel.
3.2.3. Ultrasound transmission medium
As discussed in Section 3.1.3, the physicochemical properties of
S. Zhao, et al. Chemical Engineering Journal 374 (2019) 68–78

Fig. 11. (a) The effects of viscosity and surface tension on threshold power to initiate surface wave oscillation on gas-liquid interface, (b) Comparison of the measured
wavelengths of generated surface wave with predicted ones obtained from capillary wave theory. QL 3.0 mL/min, QG 1.0 mL/min, scale bar 500 μm.

sonicated liquid play an important role on acoustic cavitation behavior. mechanical vibration of microbubble and dissipated into heat. In view
With the increase of liquid viscosity, the onset of acoustic cavitation of this, 50 vol% ethylene glycol aqueous solution (viscosity 3.81 cP)
become more difficult, i.e., ultrasound power can be transmitted was used as the temperature-controlled circulating fluid to take the
through liquid more efficiently instead of being transformed into place of water (viscosity 1.06 cP). In order to verify it, experiments

Fig. 12. (a). Effect of temperature on the initiation of surface wave in water and 50 vol% ethylene glycol aqueous solution, ultrasound power 10 W, (b) Initiation of
surface wave with increasing temperature and ultrasound power in water, (c) Initiation of surface wave with increasing temperature and ultrasound power in 50 vol
% ethylene glycol aqueous solution.

76
S. Zhao, et al. Chemical Engineering Journal 374 (2019) 68–78

were conducted with liquid flow rate being fixed at 1.5 mL/min. As
shown in Fig. 15, under ultrasound irradiation, X was enhanced by
7.1%–14.0% and 9.9%–36.3% with water and 50 vol% ethylene glycol
aqueous solution being the circulating fluid, respectively. The obviously
higher enhancement ratio indicated that highly viscous liquid can work
as better ultrasound transmission medium, and promoted the ultra-
sound-assisted reaction process carried out in microreactors.

4. Conclusion

The effects of channel dimension, solvent properties as well as

Fig. 13. Effects of reaction temperatures, reactant flow rates and ultrasound on
conversion of toluene.
temperature on acoustic cavitation and ultrasound-assisted nitration
reaction process were investigated in two laboratory-built ultrasonic
microreactors, respectively. Acoustic cavitation in microchannel with
dimension 0.5 mm, 1.0 mm and 1.5 mm were compared, finding that
microbubble oscillation was confined in smaller channels due to the
much higher viscosity gradient near the channel wall. With the increase
of channel dimension to 1.0 mm, the confinement effect of channel wall
was eliminated and cavitation distribution of microbubble resembled
that with channel dimension 1.5 mm. In addition to channel dimension,
acoustic cavitation was also closely related to solvent properties. The
threshold power to initiate surface wave at gas slug increased from
19 W to 30 W with the increase of solvent viscosity from 1.06 to 3.81
cP, while decreased from 19 W to 11 W with the decrease of solvent
surface tension from 74.18 to 31.64 mN/m. It indicated that ultrasound
intensification effect can be maximized for liquid with lower viscosity
and surface tension, and in turn higher viscous liquid can function as
efficient ultrasound propagation medium. As solvent viscosity and
surface tension decreased with increasing temperature, it also had an
influence on acoustic cavitation.
Nitration of toluene was conducted in a temperature-controlled ul-
trasonic microreactor to verify the cavitation research. With the in-
crease of capillary diameter from 0.6 to 1.0 mm, ultrasound enhance-
ment on toluene conversion was found to increase from 5.8%–9.1% to
7.1%–14.0% due to the less confined acoustic cavitation in larger mi-
crochannel. The result that wider microchannel correspond to higher
enhancement agrees well with the finding on acoustic cavitation.
Furthermore, by replacing water with 50 vol% ethylene glycol aqueous
solution as ultrasound propagation medium, toluene conversion was
further enhanced by 9.9%–36.3%, indicating that viscous liquid can be
more effectively on transporting ultrasound energy. The study in this
work help better understand the influence of operational parameter on
ultrasound intensification effect, which will surely provide guidance for
further optimization and application of ultrasonic microreactor on fast
reaction processes.

Fig. 14. (a) Effect of channel dimension on conversion of toluene. (b)

Comparison of ultrasound enhancement ratio with varying dimension of mi-
crochannel.

Fig. 15. Effect of circulating fluid on conversion of toluene.

77
S. Zhao, et al.
Acknowledgements
We greatly acknowledge the financial support for this project from
the National Natural Science Foundation of China (Nos. 91634204,
U1608221), Dalian Science & Technology Innovation Fund (No.
2018J11CY019), DICP (DICP ZZBS 201706), the Youth Innovation
Promotion Association CAS-China (No. 2017229). Authors also would
like to thank Jiansheng Chu, Fengjun Jiao and Hengqiang Li from our
group for their help in manufacturing the microreactor and setting up
the experimental platform.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.cej.2019.05.157.
References
[1] V. Hessel, D. Kralisch, N. Kockmann, T. Noel, Q. Wang, Novel process windows for
enabling, accelerating, and uplifting flow chemistry, ChemSusChem 6 (2013)
746–789.
[2] M.N. Kashid, L. Kiwi-Minsker, Microstructured reactors for multiphase reactions:
state of the art, Ind. Eng. Chem. Res. 48 (2009) 6465–6485.
[3] C. Yao, Z. Dong, Y. Zhao, G. Chen, Gas-liquid flow and mass transfer in a micro-
channel under elevated pressures, Chem. Eng. Sci. 123 (2015) 137–145.
[4] C. Zhu, C. Li, X. Gao, Y. Ma, D. Liu, Taylor flow and mass transfer of CO2 chemical
absorption into MEA aqueous solutions in a T-junction microchannel, Int. J. Heat
Mass Transfer 73 (2014) 492–499.
[5] Y. Song, J. Song, M. Shang, W. Xu, S. Liu, B. Wang, Q. Lu, Y. Su, Hydrodynamics
and mass transfer performance during the chemical oxidative polymerization of
aniline in microreactors, Chem. Eng. J. 353 (2018) 769–780.
[6] J. Yue, G. Chen, Q. Yuan, L. Luo, Y. Gonthier, Hydrodynamics and mass transfer
characteristics in gas-liquid flow through a rectangular microchannel, Chem. Eng.
Sci. 62 (2007) 2096–2108.
[7] M.N. Kashid, A. Gupta, A. Renken, L. Kiwi-Minsker, Numbering-up and mass
transfer studies of liquid–liquid two-phase microstructured reactors, Chem. Eng. J.
158 (2010) 233–240.
[8] P. Plouffe, M. Bittel, J. Sieber, D.M. Roberge, A. Macchi, On the scale-up of micro-
reactors for liquid–liquid reactions, Chem. Eng. Sci. 143 (2016) 216–225.
[9] J. Yoshida, A. Nagaki, T. Yamada, Flash chemistry: fast chemical synthesis by using
microreactors, Chem.-A Eur. J. 14 (2008) 7450–7459.
[10] Z. Wen, F. Jiao, M. Yang, S. Zhao, F. Zhou, G. Chen, Process development and scale-
up of the continuous flow nitration of trifluoromethoxybenzene, Org. Process Res.
Dev. 21 (2017) 1843–1850.
[11] M. Shang, T. Noël, Q. Wang, V. Hessel, Packed-bed microreactor for continuous-
flow adipic acid synthesis from cyclohexene and hydrogen peroxide, Chem. Eng.
Technol. 36 (2013) 1001–1009.
[12] J. Shen, Y. Zhao, G. Chen, Q. Yuan, Investigation of nitration processes of iso-oc-
tanol with mixed acid in a microreactor, Chin. J. Chem. Eng. 17 (2009) 412–418.
[13] L. Li, C. Yao, F. Jiao, M. Han, G. Chen, Experimental and kinetic study of the ni-
tration of 2-ethylhexanol in capillary microreactors, Chem. Eng. Process.: Process
Intensif. 117 (2017) 179–185.
[14] R.D. Chambers, D. Holling, R.C.H. Spink, G. Sandford, Elemental fluorine - Part 13.
Gas-liquid thin film microreactors for selective direct fluorination, Lab Chip 1
(2001) 132–137.
[15] K.F. Jensen, Microreaction engineering - is small better? Chem. Eng. Sci. 56 (2001)
293–303.
[16] A.D. Stroock, S.K. Dertinger, A. Ajdari, I. Mezić, H.A. Stone, G.M. Whitesides,
Chaotic mixer for microchannels, Science 295 (2002) 647–651.
[17] R.L. Hartman, J.P. McMullen, K.F. Jensen, Deciding whether to go with the flow:
evaluating the merits of flow reactors for synthesis, Angew. Chem.-Int. Ed. 50
(2011) 7502–7519.
[18] S. Hubner, S. Kressirer, D. Kralisch, C. Bludszuweit-Philipp, K. Lukow, I. Jaenich,
A. Schilling, H. Hieronymus, C. Liebner, K. Jaehnisch, Ultrasound and micro-
structures-a promising combination? Chemsuschem 5 (2012) 279–288.
[19] D.F. Rivas, P. Cintas, H.J.G.E. Gardeniers, Merging microfluidics and
78
Chemical Engineering Journal 374 (2019) 68–78
sonochemistry: towards greener and more efficient micro-sono-reactors, Chem.
Commun. 48 (2012) 10935–10947.
[20] S. Kuhn, T. Noel, L. Gu, P.L. Heider, K.F. Jensen, A Teflon microreactor with in-
tegrated piezoelectric actuator to handle solid forming reactions, Lab Chip 11
(2011) 2488–2492.
[21] S.Y. Tang, S. Manickam, T.K. Wei, B. Nashiru, Formulation development and op-
timization of a novel Cremophore EL-based nanoemulsion using ultrasound cavi-
tation, Ultrason. Sonochem. 19 (2012) 330–345.
[22] T.G. Leighton, R.E. Apfel, The acoustic bubble, J. Fluid Mech. 96 (1994)
2616–2617.
[23] A. Brotchie, F. Grieser, M. Ashokkumar, Effect of power and frequency on bubble-
size distributions in acoustic cavitation, Phys. Rev. Lett. 102 (2009).
[24] Z. Dong, S. Zhao, Y. Zhang, C. Yao, Q. Yuan, G. Chen, Mixing and residence time
distribution in ultrasonic microreactors, AlChE J. 62 (2017) 1404–1418.
[25] S. Zhao, Z. Dong, C. Yao, Z. Wen, G. Chen, Q. Yuan, Liquid-liquid two-phase flow in
ultrasonic microreactors: cavitation, emulsification, and mass transfer enhance-
ment, AlChE J. 64 (2018) 1412–1423.
[26] J.J. John, S. Kuhn, L. Braeken, T. Van Gerven, Temperature controlled interval
contact design for ultrasound assisted liquid-liquid extraction, Chem. Eng. Res. Des.
125 (2017) 146–155.
[27] S. Aljbour, T. Tagawa, H. Yamada, Ultrasound-assisted capillary microreactor for
aqueous-organic multiphase reactions, J. Ind. Eng. Chem. 15 (2009) 829–834.
[28] J.J. John, S. Kuhn, L. Braeken, T. Van Gerven, Ultrasound assisted liquid–liquid
extraction with a novel interval-contact reactor, Chem. Eng. Process.: Process
Intensif. 113 (2017) 35–41.
[29] S. Zhao, C. Yao, Z. Dong, Y. Liu, G. Chen, Q. Yuan, Intensification of liquid-liquid
two-phase mass transfer by oscillating bubbles in ultrasonic microreactor, Chem.
Eng. Sci. 186 (2018) 122–134.
[30] S. Zhao, C. Yao, Z. Dong, G. Chen, Q. Yuan, Role of ultrasonic oscillation in che-
mical processes in microreactors: a mesoscale issue, Particuology (2019), https://
doi.org/10.1016/j.partic.2018.08.009.
[31] Y. Iida, T. Tuziuti, K. Yasul, A. Towata, T. Kozuka, Bubble motions confined in a
microspace observed with stroboscopic technique, Ultrason. Sonochem. 14 (2007)
621–626.
[32] M. Sivakumar, S.Y. Tang, K.W. Tan, Cavitation technology–a greener processing
technique for the generation of pharmaceutical nanoemulsions, Ultrason.
Sonochem. 21 (2014) 2069–2083.
[33] L.W.M. van der Sluis, M. Versluis, M.K. Wu, P.R. Wesselink, Passive ultrasonic ir-
rigation of the root canal: a review of the literature, Int. Endodontic J. 40 (2007)
415–426.
[34] M. Ashokkumar, T.J. Mason, Sonochemistry, Kirk‐Othmer Encyclopedia of
Chemical Technology (2000).
[35] M. Ashokkumar, F. Cavalieri, F. Chemat, K. Okitsu, A. Sambandam, K. Yasui,
B. Zisu, Handbook of Ultrasonics and Sonochemistry, Springer, 2016.
[36] M. Minnaert, On musical air bubbles and the sounds of running water, PMag 16
(1933) 235–248.
[37] W. Lauterborn, T. Kurz, Physics of bubble oscillations, Rep. Prog. Phys. 73 (2010).
[38] Y. Iida, K. Yasui, T. Tuziuti, M. Sivakumar, Y. Endo, Ultrasonic cavitation in mi-
crospace, Chem. Commun. 20 (2004) 2280–2281.
[39] D.M. Hosny, D. Hudgens, T. Cox, Cavitation Correlation to Fluid Media Properties,
SAE Technical Paper, 1996.
[40] S. Hara, W. Schowalter, Dynamics of nonspherical bubbles surrounded by viscoe-
lastic fluid, J. Non-Newtonian Fluid Mech. 14 (1984) 249–264.
[41] T. Jagannathan, R. Nagarajan, Investigation of acoustic cavitation energy in ul-
trasonic tanks, J. Pure Appl. Ultrason. 32 (2010) 95–100.
[42] Z. Dong, C. Yao, Y. Zhang, G. Chen, Q. Yuan, J. Xu, Hydrodynamics and mass
transfer of oscillating gas-liquid flow in ultrasonic microreactors, AlChE J. 62
(2016) 1294–1307.
[43] C.Y. Chen, C.W. Wu, Thermal hazard assessment and macrokinetics analysis of
toluene mononitration in a batch reactor, J. Loss Prev. Process Ind. 9 (1996)
309–316.
[44] Z. Wen, M. Yang, S. Zhao, F. Zhou, G. Chen, Kinetics study of heterogeneous con-
tinuous-flow nitration of trifluoromethoxybenzene, React. Chem. Eng. 3 (2018)
379–387.
[45] E. Sahlin, S.G. Weber, Capillary zone electrophoresis in laboratory-made fluori-
nated ethylene propylene capillaries, J. Chromatogr. A 972 (2002) 283–287.
[46] P. Klemens, R. Williams, Thermal conductivity of metals and alloys, IMeRv 31
(1986) 197–215.
[47] D. Tsaoulidis, P. Angeli, Effect of channel size on mass transfer during liquid-liquid
plug flow in small scale extractors, Chem. Eng. J. 262 (2015) 785–793.