A Review of Microreactors for Process Intensification ^†

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.

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 microfluidics 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 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 devices 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 additive 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 microchannels 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 technology, 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 preserves the 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 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.

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 microreactors, 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 commonly 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 methods 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 spectrometry, 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 thermal and 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 it easier to create and produce a modular ceramic microreactor featuring inner dimensions 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 significantly reducing the dimensions of equipment, this approach can yield considerable economic advantages, enhance inherent safety, and diminish the overall environmental footprint.

3.1. Mixing and Chemical Modification of Polymer Solutions

Microreactors have also been used in the mixing and chemical modification of different 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).

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 microreactor with a dual-pipe axle configuration, where two immiscible liquids flow through the inner and outer tubes, with this microreactor demonstrating remarkable efficiency.

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 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 nanomaterials. 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.

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 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 underscore 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 microreactors 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 investment 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 materials, manufacturing methods, and incorporating automation and sensors. Such progress is essential for successfully creating, improving, and marketing catalytic systems. Integrating 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 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 sensors and automation could revolutionize reaction development and production processes, leading to faster process lead times. Microfluidics has advanced to include various applications such as high-throughput screening, biological analysis, the use of portable energy devices, and reaction kinetics studies. Microreactor systems are employed in the pharmaceutical 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.