Microreatores para Intensificação de Processos

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Citation: Bugay, C.A.; Caballas, M.C.;
Mercado, S.B.; Rubio, J.F.; Serote, P.K.;
Villarte, P.N.; Rubi, R.V.C. A Review of
Microreactors for Process Intensification.
Eng. Proc. 2024, 67, 21. https://
doi.org/10.3390/engproc2024067021
Academic Editors: Blaž Likozar and
Juan Francisco García Martín
Published: 28 August 2024
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Proceeding Paper
A Review of Microreactors for Process Intensification †
Crizha Ann Bugay 1, Mae Czarella Caballas 1, Steven Brian Mercado 1 , Jason Franco Rubio 1, Patricia Kayla Serote 1,
Patrick Norman Villarte 1 and Rugi Vicente C. Rubi 2,*
1 Chemical Engineering Department, College of Engineering, Pamantasan ng Lungsod ng Maynila,
General Luna, Corner Muralla St., Intramuros, Manila 1002, Philippines; cabbugay2021@plm.edu.ph (C.A.B.);
mcccaballas2021@plm.edu.ph (M.C.C.); sbsmercado2021@plm.edu.ph (S.B.M.);
jfrrubio2021@plm.edu.ph (J.F.R.); pkdserote2020@plm.edu.ph (P.K.S.); pncvillarte2021@plm.edu.ph (P.N.V.)
2 Chemical Engineering Department, College of Engineering, Adamson University, Ermita,
Manila 1000, Philippines
* Correspondence: rugi.vicente.rubi@adamson.edu.ph
† Presented at the 3rd International Electronic Conference on Processes—Green and Sustainable Process
Engineering and Process Systems Engineering (ECP 2024), 29–31 May 2024; Available online:
https://sciforum.net/event/ECP2024.
Abstract: Microreactors for process intensification transform chemical synthesis, providing precise
control over reactions in compact devices and enhancing efficiency. This review article explores their
application in chemical synthesis, emphasizing advantages in mixing, temperature control, and heat
transfer. It delves into fundamental aspects, addressing challenges in design, operation, material
selection, and scaling. Fundamental microreactor design principles involve scaling strategies such as
internal and external numbering up, geometric similarity, and continuous pressure drop procedures.
Materials like silicon, steel, and polymers, particularly polydimethylsiloxane (PDMS), play a crucial
role in microreactor construction. Fabrication techniques, including microfabrication, are essential for
creating complex designs and ensuring reliability. This review addresses challenges and research
gaps while showcasing the versatility of microreactors. Challenges include automation, integration,
finding optimal configurations, process optimization, and cost analyses. Overcoming these challenges
is crucial for widespread adoption in industries like pharmaceuticals and petrochemicals. The future
for microreactors will revolve around recent advancements, collaboration between academia and
industry, and the integration of automation and sensors. This positions microreactors as key players
in revolutionizing chemical production, with potential applications in fuel cells, mini-chemical plants,
and next-generation catalysts. Therefore, it is of the utmost importance to address the current
challenges and advance research related to this study in order to solidify their role in shaping the
future of chemical engineering.
Keywords: microreactors; process intensification; catalytic biomass conversion; green chemistry;
fabrication techniques; heat transfer; automation; scaling strategies; sustainability
1. Introduction
The integration of eco-friendly and sustainable practices has become increasingly
essential in chemical synthesis, prompting a significant shift towards process intensification
(PI) to enhance efficiency. This transformative approach, which has gained wide acceptance
in both academic research and industrial development, is exemplified by the innovative
application of microreactor technology. According to Rial et al. [1], the field of microflu-
idics represents a highly intelligent solution that has emerged from the intensification
design approach.
Microreactors are microfluidic devices with dimensions typically falling within the
10–1000 µm range. They are distinguishable from conventional reactors and are commonly
produced using diverse methods, often involving silicon or glass materials. Additionally,
microreactor technology involves scaling down chemical reactors to dimensions between
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Eng. Proc. 2024, 67, 21 2 of 9
sub-micron- and sub-millimeter-levels (about 50 µm to 2 mm), leading to improvements
in the physical and chemical aspects of reaction engineering. Microreactors offer several
advantages over macroreactor systems, such as a high surface-to-volume ratio; enhanced
heat and mass transfer rates; increased operational safety; reduced costs for operation,
maintenance, and construction; shorter residence timesl and improved energy and material
efficiency [2].
Microreactor technology aligns seamlessly with PI principles, particularly in processes
that require careful mixing, precise temperature control, or effective interfacial heat/mass
transfer [3]. This review article delves into the utilization of microreactors for green PI in
catalytic biomass conversion, with a specific emphasis on synthesizing chemicals and fuels
with added value from biomass sources. From furanic platform chemicals to assisting in
the oxidation and hydrogenation of derivatives from lignocellulosic biomass in a liquid
phase and biodiesel synthesis, microreactors have shown versatility in enhancing reaction
performance [4].
2. Microreactor Design and Operation
Fundamental ideas underpin the design and functioning of microreactors, setting
them apart from conventional chemical reactors. Scaling is essential because these small de-
vices have lower operating volumes but higher surface-to-volume ratios. This scale-down
improves the overall effectiveness of both mass and heat transfer processes and allows for
exact control over reaction conditions. Given the difficulties presented by the small-scale
environment, careful study of materials and production methods is required. Important
considerations affecting the choice of material are resistance to corrosion, thermal stability,
and suitability with specific chemicals. Furthermore, fabrication techniques like addi-
tive manufacturing and microfabrication are essential to producing complex designs and
guaranteeing the dependability of microreactors. Because of their enhanced surface area
and smaller dimensions, these systems accelerate transfer processes, including both heat
transfer and mass transfer, which improves the processes’ rate of reaction. Microreactor
performance is greatly influenced by flow patterns and mixing methods, which can have
an impact on product quality and response uniformity. Since fluid flow in microchan-
nels is dynamic, optimizing response outcomes requires a thorough understanding of
flow patterns.
2.1. Fundamental Principles of Microreactor Design and Operation
Dong et al. [5] present specific strategies associated with scaling microreactor tech-
nology, focusing on the basic ideas and useful techniques. The strategies they studied
include extending reactor length, internal and external scaling, maintaining geometric
similarity, and maintaining continuous pressure drop procedures. It was observed that
internal numbering up preservesthe beneficial hydrodynamics and transfer properties of
individual microreactors, requiring advanced flow distribution management. However,
because individual channel connections are becoming increasingly expensive, external
numbering up faces scalability challenges. Solutions to problems with fluid distribution
can be found in scaling up techniques such as channel elongation. However, as channel
diameters grow, axial dispersion, mixing, and heat transfer must be carefully managed.
Although each scaling technique has advantages, combining several methodologies is a
practical way to satisfy the demanding scale-up requirements of the pharmaceutical and
fine chemical industries.
Cole et al. [6] reported that in scaling prexasertib monolactate monohydrate synthesis,
a variety of strategies are needed for developing microreactors for the pharmaceutical
and fine chemical industries (scale factors 100–1000). The overall scale-up factor considers
the channel number (or SN), length (or SL), and diameter (or SD). Internal and external
numbering up with certain factors (e.g., SN = 40) can produce a scale-up factor with a
numerical value of 800 for highly exothermic processes stressing heat control. If mass
transfer or mixing is a crucial factor, choosing a larger SD with static mixing components is
Eng. Proc. 2024, 67, 21 3 of 9
preferable. However, it is important to keep in mind that the maximum SL is restricted by
the pressure drop.
Moreover, heat transfer is also an integral principle in a microreactor. In a report by
Rebrov et al. [7], it is stated that, in order to ensure isothermal operation and prevent the
emergence of axial temperature profiles, the design of micro-structured reactors with single-
phase distribution in fluid flow, as shown in Figure 1, is required. Maintaining a consistent
temperature of the coolant is the key to achieving good heat transfer in microreactors. The
specific heat flow is influenced by two main factors: the channel wall surface area and the
coefficient of total heat transfer. The total heat transfer coefficient considers the resistance
of the cooling fluid, channel wall, and the reacting fluid within the channel wall. These
factors highlight how crucial it is for microreactors to have excellent heat transfer efficiency
to regulate temperatures ranges.
Eng. Proc. 2024, 6, x FOR PEER REVIEW 3 of 9 
 
 
numbering up with certain factors (e.g., SN = 40) can produce a scale-up factor with a 
numerical value of 800 for highly exothermic processes stressing heat control. If mass 
transfer or mixing is a crucial factor, choosing a larger SD with static mixing components 
is preferable. However, it is important to keep in mind that the maximum SL is restricted 
by the pressure drop. 
Moreover, heat transfer is also an integral principle in a microreactor. In a report by 
Rebrov et al. [7], it is stated that, in order to ensure isothermal operation and prevent the 
emergence of axial temperature profiles, the design of micro-structured reactors with sin-
gle-phase distribution in fluid flow, as shown in Figure 1, is required. Maintaining a con-
sistent temperature of the coolant is the key to achieving good heat transfer in microreac-
tors. The specific heat flow is influenced by two main factors: the channel wall surface area 
and the coefficient of total heat transfer. The total heat transfer coefficient considers the 
resistance of the cooling fluid, channel wall, and the reacting fluid within the channel wall. 
These factors highlight how crucial it is for microreactors to have excellent heat transfer 
efficiency to regulate temperatures ranges. 
(a) (b) 
Figure 1. (a) Fluid and heat flow in a single-phase microreactor. (b) Single-phase microreactor struc-
ture. 
2.2. Materials and Fabrication Techniques in Microreactor Operations 
According to Bojang et al. [8], building small-scale microreactors requires the creation 
of mechanisms that allow liquids to flow through them and disperse organic and bio-
organic materials. These reactors, which are sometimes called analytical systems, have 
particular uses in a variety of industries. Materials, including silicon and steel, are used in 
their construction; silicon is a commonly used option since it is readily available, reason-
ably priced, and compatible with the advancement of microreactor technology. Due to its 
laminar flow dynamic system, silicon may be used as a hypergolic fuel in the chemical 
industry, even under difficult surface conditions. 
Moreover, it was emphasized by Halldorsson et al. [9] that the molding procedure, 
which uses polydimethylsiloxane (PDMS), makes building microreactors simple. Poly-
mers that are flexible and easy to produce, such as PDMS, are essential to building micro-
reactors. Exothermic gas-phase reactions are particularly well managed by small-scale sil-
icon microreactors, which are renowned for their adaptability in handling reaction condi-
tions and for preserving steady heat flow even at extremely elevated temperatures. 
In line with the fabrication techniques, methods such as microfabrication are com-
monly utilized. According to Medina et al. [10], a wide range of materials and substrates 
have been reported to be engraved and modeled using a variety of microfabrication meth-
ods since the emergence of the early instruments based on microelectromechanical sys-
tems. Several methods have been explored and shown to be practical in this context for 
fully integrating chromatographic media, injectors, ionization sources, interfaces for mass 
spectrometry, solvent delivery systems, and mass on-chip analyzers. Also, Knitter et al. 
[11] discussed microfabrication and its application to ceramic microreactors. In their pa-
per, they state that the fabrication of ceramic microreactors is a fundamental component 
Figure 1. (a) Fluid and heat flow in a single-phase microreactor. (b) Single-phase microreactor structure.
2.2. Materials and Fabrication Techniques in Microreactor Operations
According to Bojang et al. [8], building small-scale microreactors requires the creation
of mechanisms that allow liquids to flow through them and disperse organic and bio-
organic materials. These reactors, which are sometimes called analytical systems, have
particular uses in a variety of industries. Materials, including silicon and steel, are used in
their construction; silicon is a commonly used option since it is readily available, reasonably
priced, and compatible with the advancement of microreactor technology. Due to its
laminar flow dynamic system, silicon may be used as a hypergolic fuel in the chemical
industry, even under difficult surface conditions.
Moreover, it was emphasized by Halldorsson et al. [9] that the molding procedure,
which uses polydimethylsiloxane (PDMS), makes building microreactors simple. Polymers
that are flexible and easy to produce, such as PDMS, are essential to building microreactors.
Exothermic gas-phase reactions are particularly well managed by small-scale silicon mi-
croreactors, which are renowned for their adaptability in handling reaction conditions and
for preserving steady heat flow even at extremely elevated temperatures.
In line with the fabrication techniques, methods such as microfabrication are com-
monly utilized. According to Medina et al. [10], a wide range of materials and substrates
have been reported to be engraved and modeled using a variety of microfabrication meth-
ods since the emergence of the early instruments based on microelectromechanical systems.
Several methods have been explored and shown to be practical in this context for fully
integrating chromatographic media, injectors, ionization sources, interfaces for mass spec-
trometry, solvent delivery systems, and mass on-chip analyzers. Also, Knitter et al. [11]
discussed microfabrication and its application to ceramic microreactors. In their paper,
they state that the fabrication of ceramic microreactors is a fundamental component in
applications requiring both higher thermaland chemical resistance. However, it faces
challenges due to the intricate patterning details required in the micrometer range. In
order to overcome this hurdle, a rapid prototype process chain that combines low-pressure
ceramic injection molding and stereolithography can be considered. This approach makes
Eng. Proc. 2024, 67, 21 4 of 9
it easier to create and produce a modular ceramic microreactor featuring inner dimen-
sions of less than one millimeter, demonstrating the effectiveness of the rapid prototyping
process chain.
In applications related to chemical processes, it has been emphasized that there is
experimental evidence for the potential of microreactors to drastically reduce reaction times.
Burns and Ramshaw [12] studied immiscible liquid–liquid flow, demonstrating that narrow
channel reactors can achieve stable parallel flow, a condition optimal for rapid mass transfer.
This is crucial for reactions like the nitration of benzene, where efficient mass transfer is key
to minimizing by-products. Remarkably, their experiments using capillary reactors with
relatively modest bore sizes achieved industrially competitive reaction rates, highlighting
the efficiency and scalability of microreactor technology for accelerating chemical processes.
Consequently, Olivieri et al. [13] highlight the conventional approach to soybean oil
epoxidation, which typically involves batch or fed-batch reactors and lengthy reaction
times ranging from 8 to 12 h. By drastically reducing the reaction volume into minuscule
channels, these reactors facilitate high heat and mass transfer, crucial factors for accelerating
reaction rates. The large surface-to-volume ratio in microreactors ensures efficient contact
between reactants, leading to significantly shorter reaction times compared to conventional
methods. This was evidenced by He et al. [14], who demonstrated a reduction in reaction
time to approximately 7 min while maintaining comparable reaction conditions. This
improvement in efficiency highlights the potential of microreactors to revolutionize the
soybean oil epoxidation industry by significantly increasing productivity and reducing
production costs.
2.3. Flow Patterns and Control in Microreactor Operations
Su et al. [15] discussed the importance of flow pattern and control in the context of
polymer synthesis. Precise manipulation of molecular weights and product shapes can be
achieved using microreactor flow control. The unique characteristics of polymerization
provide difficulties because of large fluctuations in fluid properties, even if microreactors
improve transport qualities over traditional batch reactors. The processes of homogeneous,
heterogeneous, and photopolymerization are all covered by it.
Furthermore, the importance of flow control was further emphasized by Bratsun et al. [16],
as they proposed a design for a microreactor using continuous flow with the cell narrowed
and the incorporation of an adjustable gap. This design allows for the adjustment of both
the reaction rate and the yield of the product by varying the gap width in both space and
time. The Darcy equation with permeability variations is the simplified version of the fluid
flow equation. This paper shows how spatially distributed relief on reactor walls may
control reagent flows, with mixing intensity exhibiting flexibility in operation. This flexible
microreactor design satisfies the pharmaceutical industry’s demand for concise, accurate
management of reaction outputs and flow patterns.
In addition to the above, how microreactors are being applied in both small- and large-
scale production to reduce or control reaction times must also be emphasized. Yoshida [17]
defines reaction time in a flow microreactor as the duration between the introduction
of a reagent and either the addition of a quenching agent to halt the reaction or the
subsequent introduction of another reagent. Notably, their study emphasizes the direct
correlation between reaction time and the length of the reactor channel. By manipulating
the channel length, researchers can significantly decrease the reaction time within the
microreactor system.
3. Applications of Microreactors
Process intensification through the use of microdevices aims to minimize capital and
energy expenditures and environmental effects by downsizing chemical plants. By signifi-
cantly reducing the dimensions of equipment, this approach can yield considerable economic
advantages, enhance inherent safety, and diminish the overall environmental footprint.
Eng. Proc. 2024, 67, 21 5 of 9
3.1. Mixing and Chemical Modification of Polymer Solutions
Microreactors have also been used in the mixing and chemical modification of dif-
ferent substances. For instance, Zha et al. [18] used microreactors to mix and chemically
modify polymer solutions through a gas–liquid two-phase flow process. It was shown
that this system can generate a side-by-side bubble flow, facilitating a faster reaction. The
inclusion of gas has been recognized as a beneficial factor in promoting the blending of
polymer solutions in capillary microreactors. In addition, simple mathematical models
have been developed to assess the micro mixing efficiency of gas slug and annular flow
in microreactors and evaluate the impact of shear and internal circulation. These models
were created by analyzing the velocity profiles of the gas and liquid phases. Furthermore,
it was discovered that the gas introduction method impacts the initial arrangement of
reactant concentrations in the microreactor [19]. Finally, the implementation of the gas
introduction approach significantly enhances the sulfonation process of polystyrene in
capillary microreactors.
3.2. Synthesis of Ionic Liquids
Microreactors are also used for the synthesis of ionic liquids as shown in Figure 2.
Large-scale ionic liquid production is limited by batch processes that are not efficient for
the alkylation stage [20]. In a study by Waterkamp et al. [21], a continuously operating
microreactor was used to produce 1-butyl-3-methylimidazolium bromide ([BMIM]Br).
Eng. Proc. 2024, 6, x FOR PEER REVIEW 5 of 9 
 
 
3. Applications of Microreactors 
Process intensification through the use of microdevices aims to minimize capital and 
energy expenditures and environmental effects by downsizing chemical plants. By signif-
icantly reducing the dimensions of equipment, this approach can yield considerable eco-
nomic advantages, enhance inherent safety, and diminish the overall environmental foot-
print. 
3.1. Mixing and Chemical Modification of Polymer Solutions 
Microreactors have also been used in the mixing and chemical modification of differ-
ent substances. For instance, Zha et al. [18] used microreactors to mix and chemically mod-
ify polymer solutions through a gas–liquid two-phase flow process. It was shown that this 
system can generate a side-by-side bubble flow, facilitating a faster reaction. The inclusion 
of gas has been recognized as a beneficial factor in promoting the blending of polymer 
solutions in capillary microreactors. In addition, simple mathematical models have been 
developed to assess the micro mixing efficiency of gas slug and annular flow in microre-
actors and evaluate the impact of shear and internal circulation. These models were cre-
ated by analyzing the velocity profiles of the gas and liquid phases. Furthermore, it was 
discovered that the gas introduction method impacts the initial arrangement of reactant 
concentrations in the microreactor [19]. Finally, the implementation of the gas introduc-
tion approach significantly enhances the sulfonation process of polystyrene in capillary 
microreactors. 
3.2. Synthesis of Ionic Liquids 
Microreactors are also used for the synthesis of ionic liquids as shown in Figure 2. 
Large-scale ionic liquid production is limited by batch processes that are not efficient for 
the alkylation stage [20]. In a study by Waterkamp et al. [21], a continuously operating 
microreactor was used to produce 1-butyl-3-methylimidazoliumbromide ([BMIM]Br). 
 
Figure 2. (a) Vortex-type microreactor (top view). (b) Microreactor working principle. 
A microreactor with a micro-structured mixer with a channel width of 450 µm and 
reaction tubes with an inner diameter ranging from 2 to 6 mm produces 9.3 kg/day of 
([BMIM]Br). Waterkamp et al.’s experiment pointed out that Imidazolium-based ionic liq-
uids can be produced effectively and continuously in microreactors, removing the require-
ment for extra solvents to regulate reactions. Their study emphasizes how crucial the high 
specific surface area of the reaction system is for effectively dispersing heat from highly 
exothermic processes. By optimizing microreactors and adjusting the surface-to-volume 
ratio based on the desired reaction temperature, it is possible to achieve a 100-fold increase 
in Space Time Yield (STY). Even at the highest temperature tested, very few contaminants 
were found in the product, which had a purity of over 99%. Further tests investigating 
temperatures beyond 100 °C and gauge pressures above 2 bar may show relationships 
between temperature, residence duration, and contaminants. 
Figure 2. (a) Vortex-type microreactor (top view). (b) Microreactor working principle.
A microreactor with a micro-structured mixer with a channel width of 450 µm and
reaction tubes with an inner diameter ranging from 2 to 6 mm produces 9.3 kg/day of
([BMIM]Br). Waterkamp et al.’s experiment pointed out that Imidazolium-based ionic
liquids can be produced effectively and continuously in microreactors, removing the
requirement for extra solvents to regulate reactions. Their study emphasizes how crucial
the high specific surface area of the reaction system is for effectively dispersing heat from
highly exothermic processes. By optimizing microreactors and adjusting the surface-to-
volume ratio based on the desired reaction temperature, it is possible to achieve a 100-fold
increase in Space Time Yield (STY). Even at the highest temperature tested, very few
contaminants were found in the product, which had a purity of over 99%. Further tests
investigating temperatures beyond 100 ◦C and gauge pressures above 2 bar may show
relationships between temperature, residence duration, and contaminants.
3.3. Synthesis of Inorganic Particles
Microreactors as shown in Figure 3, can also be applied in the synthesis of inorganic
particles such as fine particles [22]. In another study, Nagasawa and Mae [23] designed a mi-
croreactor with a dual-pipe axle configuration, where two immiscible liquids flow through
the inner and outer tubes, with this microreactor demonstrating remarkable efficiency.
Eng. Proc. 2024, 67, 21 6 of 9
Eng. Proc. 2024, 6, x FOR PEER REVIEW 6 of 9 
 
 
3.3. Synthesis of Inorganic Particles 
Microreactors as shown in Figure 3, can also be applied in the synthesis of inorganic 
particles such as fine particles [22]. In another study, Nagasawa and Mae [23] designed a 
microreactor with a dual-pipe axle configuration, where two immiscible liquids flow 
through the inner and outer tubes, with this microreactor demonstrating remarkable effi-
ciency. 
 
Figure 3. Schematic of the flow in the microreactor. 
By maintaining a laminar and annular flow, the system creates a micro space along 
the fluid wall’s outer edge. By varying the inner tube diameter, the reactor’s connected 
nucleation and particle growth sections produce mono-modal spherical titania particles 
with precise size control, ranging from 45 nm to 121 nm. Moreover, nucleus generation 
and particle growth occur at the fluid interface of this axle dual pipe microreactor, which 
guarantees successful particle creation without wall precipitation [24]. Of particular im-
portance for industrial applications, the technology reduces the possibility of microchan-
nel blockage related to particle synthesis conditions, guaranteeing steady, uninterrupted 
production at a high throughput. In a related experiment by Yu et al. [20], the continuous 
one-step synthesis of zeolite within a microreactor further highlighted its efficiency. This 
method lowers the cost of large-scale zeolite synthesis and prevents batch-to-batch prod-
uct differences. 
3.4. Synthesis of Organic Nanomaterials 
Microreactors as presented in Figure 4, can also be used to synthesize organic nano-
materials. Biopolymer nanoparticles find extensive applications thanks to their notewor-
thy properties, including their commendable rheological characteristics, water dispersi-
bility, texture, appearance, and various other attributes [19]. Zhang et al. [24] addressed 
the challenge of poor solubility in medicinal components by producing nano-sized itra-
conazole (ITZ) particles with a continuous flow droplet-based microreactor. 
 
 
Figure 4. Schematic of the microreactor system. (a) Droplet-based microreactor system (metal cross 
junction channel). (b) Metal t-shaped microreactor system. 
Figure 3. Schematic of the flow in the microreactor.
By maintaining a laminar and annular flow, the system creates a micro space along
the fluid wall’s outer edge. By varying the inner tube diameter, the reactor’s connected
nucleation and particle growth sections produce mono-modal spherical titania particles
with precise size control, ranging from 45 nm to 121 nm. Moreover, nucleus generation and
particle growth occur at the fluid interface of this axle dual pipe microreactor, which guar-
antees successful particle creation without wall precipitation [24]. Of particular importance
for industrial applications, the technology reduces the possibility of microchannel blockage
related to particle synthesis conditions, guaranteeing steady, uninterrupted production at a
high throughput. In a related experiment by Yu et al. [20], the continuous one-step synthesis
of zeolite within a microreactor further highlighted its efficiency. This method lowers the
cost of large-scale zeolite synthesis and prevents batch-to-batch product differences.
3.4. Synthesis of Organic Nanomaterials
Microreactors as presented in Figure 4, can also be used to synthesize organic nanoma-
terials. Biopolymer nanoparticles find extensive applications thanks to their noteworthy
properties, including their commendable rheological characteristics, water dispersibility,
texture, appearance, and various other attributes [19]. Zhang et al. [24] addressed the
challenge of poor solubility in medicinal components by producing nano-sized itraconazole
(ITZ) particles with a continuous flow droplet-based microreactor.
Eng. Proc. 2024, 6, x FOR PEER REVIEW 6 of 9 
 
 
3.3. Synthesis of Inorganic Particles 
Microreactors as shown in Figure 3, can also be applied in the synthesis of inorganic 
particles such as fine particles [22]. In another study, Nagasawa and Mae [23] designed a 
microreactor with a dual-pipe axle configuration, where two immiscible liquids flow 
through the inner and outer tubes, with this microreactor demonstrating remarkable effi-
ciency. 
 
Figure 3. Schematic of the flow in the microreactor. 
By maintaining a laminar and annular flow, the system creates a micro space along 
the fluid wall’s outer edge. By varying the inner tube diameter, the reactor’s connected 
nucleation and particle growth sections produce mono-modal spherical titania particles 
with precise size control, ranging from 45 nm to 121 nm. Moreover, nucleus generation 
and particle growth occur at the fluid interface of this axle dual pipe microreactor, which 
guarantees successful particle creation without wall precipitation [24]. Of particular im-
portance for industrial applications, the technology reduces the possibility of microchan-
nel blockage related to particle synthesis conditions, guaranteeing steady, uninterrupted 
production at a high throughput. In a related experiment by Yu et al. [20], the continuous 
one-step synthesis of zeolite within a microreactor further highlighted its efficiency. This 
method lowers the cost of large-scale zeolite synthesis and prevents batch-to-batch prod-
uct differences.3.4. Synthesis of Organic Nanomaterials 
Microreactors as presented in Figure 4, can also be used to synthesize organic nano-
materials. Biopolymer nanoparticles find extensive applications thanks to their notewor-
thy properties, including their commendable rheological characteristics, water dispersi-
bility, texture, appearance, and various other attributes [19]. Zhang et al. [24] addressed 
the challenge of poor solubility in medicinal components by producing nano-sized itra-
conazole (ITZ) particles with a continuous flow droplet-based microreactor. 
 
 
Figure 4. Schematic of the microreactor system. (a) Droplet-based microreactor system (metal cross 
junction channel). (b) Metal t-shaped microreactor system. 
Figure 4. Schematic of the microreactor system. (a) Droplet-based microreactor system (metal cross
junction channel). (b) Metal t-shaped microreactor system.
The study of Zhang et al. examined the effects of stabilizers, drug concentration,
residence period, flow rate ratio, and other variables on the formation of nanoparticles.
When the droplet system was compared to traditional laminar flow, the study showed
better results. ITZ nanoparticles were created in droplets that were smaller and more
uniformly dispersed, indicating that the use of amphiphilic stabilizers, extended residence
times, or higher initial concentrations can all regulate particle agglomeration and growth.
Lastly, Jose et al. [25] created a scalable, accurate method for the continuous synthesis
of two-dimensional metal-organic frameworks. The kinetics of precipitation in the fluid
passing through the microchannel was examined. They created the basis for an ongoing
process for synthesizing nanoparticles based on organic materials. They also noted that
Eng. Proc. 2024, 67, 21 7 of 9
during the process, the conversion rate was five orders of magnitude greater than that
achieved in a batch reactor.
4. Challenges and Research Gaps
Microreactors and other microdevices have demonstrated remarkable efficacy in
enhancing chemical production through process intensification, due to its exceptional
capabilities in heat and mass transfer, minimal change in temperature, rapid and effective
combination, and reduced duration. Nevertheless, the adoption of this technology depends
on addressing several key challenges, including delving into areas like automation and
integration, synthesizing optimal configurations for microprocess units, refining process
optimization strategies, and conducting thorough cost analyses. It is imperative to under-
score that overcoming these challenges holds the key to unlocking the full potential of
microreactors in revolutionizing chemical production [26].
According to a study by Suryawanshi et al. [27], the utilization of small-scale microre-
actors in chemical engineering is rapidly advancing, especially in the synthesis of organic
compounds, pharmaceuticals, and fine chemicals. Also, microreactors have been applied
in biofuel production, specifically in the production of biodiesel from vegetable oils [28].
While there have been successful practical applications of microreactors, the adoption
of microprocesses in the industry is not yet widespread. Scaling up production poses a
challenge due to the absence of a universally credited procedure for transitioning from
laboratory-scale environments to pilot-scale environments and larger production facilities.
The pharmaceutical industry faces challenges in achieving goals due to its traditional
manufacturing methods. Adopting continuous manufacturing, especially with the use of
microreactors, could streamline the process by accelerating chemical reactions. However,
the primary challenge in microreactors pertains to the compatibility of reaction mixtures,
specifically heterogeneous mixtures. Reactions with half-lives between 1 s and 10 min are
optimal for micro-scale devices, but exceeding this range hinders bridging the gap between
lab scale and industrial scale [29].
Furthermore, the petrochemical industry has not yet pursued the commercial-scale
implementation of microreactors. The hurdles for innovation include (1) the increased
likelihood of failure due to a mix of new components or factors; (2) inadequate familiarity
with scaling up processes; (3) the reliability of the equipment is either unknown or subpar;
and (4) the increased probability of safety, health, or environmental concerns. Additionally,
for large-scale petrochemical applications, the linear cost-scaling rule makes the capital in-
vestment required for microreactors considerably more expensive than standard equipment,
presenting a significant challenge [30].
Some more gaps related to microreactors for process intensification implementation
are operating issues, safety concerns, and their integration with existing processes. Based on
evidence from the study of Klais et al. [31], if the temperature control system malfunctions,
it can trigger uncontrollable reactions in the microreactor, connecting the pipe and annular-
channel reactor. Thus, it is crucial to consider these deviations while assessing the risks
involved. Therefore, the general validity of the inherently safe reactor design concept using
microreactors is questionable. Lastly, the limitations of small dimensions, including the risk
of clogging and high pressure drops, make micro-structured reactor technology unsuitable
for industrial-scale applications. While studies suggest benefits for about 44% of synthesis
processes in smaller-scale production, challenges such as handling solids and clogging
issues need to be addressed for practical implementation [32].
5. Future Outlooks
In microreactor technology (MRT), recent advancements have centered on new materi-
als, manufacturing methods, and incorporating automation and sensors. Such progress
is essential for successfully creating, improving, and marketing catalytic systems. Inte-
grating automation and sensors could lead to promising commercial applications such as
efficient fuel cells and mini-chemical plants [33]. MRT initially emerged as a technological
Eng. Proc. 2024, 67, 21 8 of 9
push instead of a market pull. Still, current trends show a shift towards developing
MRT systems for various commercial applications via collaborations between universities
and companies [34]. The emergence of MRT provides a potential new platform for next-
generation catalysts and multiphase catalytic process technologies. Incorporating sensors
and automation is essential in developing extremely efficient fuel cells and mini-chemical
plants requiring less supervision and maintenance from operators.
Microreactors have a promising future in process intensification. The integration of sen-
sors and automation could revolutionize reaction development and production processes,
leading to faster process lead times. Microfluidics has advanced to include various appli-
cations such as high-throughput screening, biological analysis, the use of portable energy
devices, and reaction kinetics studies. Microreactor systems are employed in the pharma-
ceutical and fine chemical sectors for laboratory research and manufacturing applications
because of their documented economic advantages and enhanced safety measures [35].
Innovative microfabrication processes and reactor interfaces are now being developed to
expand the range of uses for microreactors. Micromixers use several techniques to enhance
rates of heat and mass transfer and facilitate continuous-flow operations.
Author Contributions: Conceptualization, R.V.C.R.; writing—original draft preparation, C.A.B.,
M.C.C., S.B.M., J.F.R., P.K.S. and P.N.V.; writing—review and editing, R.V.C.R.; supervision, R.V.C.R.;
project administration, R.V.C.R. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
Data Availability Statement: The original contributions presented in the study are included in the
article, further inquiries can be directed to the correspondingauthor.
Conflicts of Interest: The authors declare no conflicts of interest.
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	Introduction 
	Microreactor Design and Operation 
	Fundamental Principles of Microreactor Design and Operation 
	Materials and Fabrication Techniques in Microreactor Operations 
	Flow Patterns and Control in Microreactor Operations 
	Applications of Microreactors 
	Mixing and Chemical Modification of Polymer Solutions 
	Synthesis of Ionic Liquids 
	Synthesis of Inorganic Particles 
	Synthesis of Organic Nanomaterials 
	Challenges and Research Gaps 
	Future Outlooks 
	References