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Review

Towards Sustainable Scaling-Up of Nanomaterials Fabrication: Current Situation, Challenges, and Future Perspectives

1
Laboratory of Mechanic Process Energy and Environment, National School of Applied Sciences, Ibn Zohr University, P.O. Box 1136/S, Agadir 80000, Morocco
2
Laboratory of Industrial Chemistry and Reaction Engineering (TKR), Åbo Akademi University, 20500 Åbo/Turku, Finland
3
Laboratory of Chemical Engineering and Valorization of Resources, LGCVR-UAE/U14FST, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University, P.O. Box 416, Tangier 93000, Morocco
4
Laboratory LSIA, ENSAH, Abdelmalek Essaadi University, Tetouan 93000, Morocco
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Eng 2025, 6(7), 149; https://doi.org/10.3390/eng6070149
Submission received: 13 May 2025 / Revised: 19 June 2025 / Accepted: 24 June 2025 / Published: 1 July 2025
(This article belongs to the Section Materials Engineering)

Abstract

Nanomaterials are present everywhere today and represent the new industrial revolution. Depending on the application, there are many ways to synthesize nanomaterials with different properties. The industrial production of nanomaterials faces various challenges at different stages, going from conception and design to implementation and scaling-up of the production process, which can limit the growth of practical application at a large-scale scope, such as due to the lack of reproducibility, safety, and environmental impact. Here, we discuss current advances achieved for nanomaterial production at a large scale, encompassing a range of synthetic strategies and post-treatment modifications used to enhance the nanomaterials’ performance. A particular interest is devoted to highlighting the progress of MoS2 nanomaterials’ application. Thus, overcoming those discussed challenges becomes a new prospect for the future perspectives of industrial nanomaterials and nanotechnologies.

1. Introduction

The nanomaterials field deals with the design, synthesis, characterization, and application of extremely small objects (i.e., materials with at least one dimension ranging between 1 and 100 nm) [1]. Such functional materials can be found in nature, like clays, oxides, and/or hydroxides of Fe, Al, Si, etc., and magnetite in magnetostatic bacteria, etc. [2]. The concept of nanomaterials was first proposed in 1959 at the conference held by Nobel prize winner Richard Feynman [3], where he proposed the development of “Molecular machines” [4]. Then, Norio Taniguchi first used this term in a publication published in 1974, in which he examined the semiconductor process at the nanoscale [5]. In the following years, the field of nanotechnology was boosted by the discovery of fullerenes in 1985 [6] and the discovery of carbon nanotubes in 1991 [7]. The development of microscopy characterization tools, such as scanning tunnel microscopy (STM), transmission electron microscopy (TEM), atomic force microscopy (AFM), and so on, is taking nanotechnology to new frontiers and allowing the investigation and study of materials as small as 0.2 nm as shown in Figure 1 [8]. At this level, materials have unique properties that cannot be described with classical models and theories, for example, in the case of semiconductors: the quantum effects (tunnel effect, discrete energy levels, etc.) occur when the thickness of an active layer is less than 10 nm [9]. Since then, nanotechnology has become an important pillar of the modern chemical and materials industry, in the so-called next industrial revolution [10].
The nanotechnology market is one of the fastest-growing markets in chemicals and materials, with revenue that stood at $7.27 billion in 2017, and an expected compound annual growth rate (CAGR) for the years from 2018 to 2023 has been estimated to be 17% [13]. This latter is owing primarily to the continuous development of technologies for nanomaterials production in response to the increased demand from the growth of the nanotechnology market related to various end-use industry applications such as electronics, textiles, pharmaceuticals [14], energy [15,16], aerospace [17], biotechnology and food [18]. A particular interest is related to a significant rise in demand for efficient and cost-effective healthcare treatment and diagnostics, which propels the adoption of nanomaterials in the drug delivery and medical devices sectors.
The interest in nanomaterials is mainly due to the large surface-to-volume ratio (or specific surface area), allowing appropriate physicochemical properties, making them more reactive [19].
As an example, Table 1 shows an illustration of various research topics relevant to significant nanomaterial applications. For example, metal-organic frameworks (MOFs), known for their large surface areas and internal volumes, have found several useful applications in catalysis, separations, and gas storage [20]. In the electronic field [21], the Bi-based nanomaterials have been used in various applications such as thermoelectric devices [22], optical devices [23], giant magnetoresistance (GMR), and superconductivity devices [24,25]. In medicine, nanomaterials are used in various ways: to repair and regenerate bones [26], control drugs, deliver vaccines, diagnose cell-based diseases, and make progress in a new generation of the medicinal field [27,28]. Moreover, note that the fastest-growing application of nanomaterials is mainly related to catalytic reactions such as polymerization, combustion additives, and conversion of biomass to bioenergy [29]. Nowadays, another emerging application is related to the lubrication-making domain involving the use of nanomaterials such as MoS2 and WS2 [30,31] as additives to base oil or other lubricants to enhance their tribological properties.
Even though lab-scale research in the field of nanomaterials design and development is well established, only a few processes are scalable to industrial scale. The present review is devoted to a discussion of current advances achieved for nanomaterials production at a large scale, alongside current challenges and future perspectives.

2. Scalable Synthesis Routes of Nanomaterials

To date, the developed synthesis techniques for nanomaterials, including those that have been successfully transferred to an industrial scale, can be grouped into three major approaches: Top-down, Bottom-up, and hybrid. As a general rule, Table 2 shows an overview of the main existing synthesis methods of nanoparticles and their classification.
The pros and cons of each approach, alongside the enumeration of main methods, will be discussed in this section.

2.1. Top-Down Methods

Those techniques of nanomaterials production consist of reducing the size of bulk material until reaching the nanoscale [91]. Although the top-down approach is relatively easy to manipulate, the application of top-down technologies for large-scale production [92] might result in significant environmental impact associated with waste generation [93,94] in addition to the lack of control over the shape and structure of the particles [95].
Over the past decades, there has been a wide variety of top-down manufacturing techniques that have been implemented using different media that span from chemical and electrochemical means to photofabrication, laser machining, electron-and ion-beam milling (IBM), plasma etching, and powder blasting [96].

2.1.1. Mechanical/Mechanochemical Milling

Milling processes are the simplest top-down manufacturing technique through mechanical milling and generally without chemical reaction [97]. This process was developed in the 70 s to provide new alloys with nanostructured powder [95]. The exerted power is obtained following the milling process (ball or attrition miller; e.g., tungsten carbide ball), carried out usually under appropriate solution (e.g., toluene), speed (revolutions per minute), and the time of milling. In addition to its simplicity and ability to prepare different nanomaterials, this technique can work at low temperatures, so the growth step is slow [94]. The mechanical method allows a reduction of the average grain size from 50–100 µm up to 2–20 nm.
On the other hand, mechanochemical reactions can be carried out by involving chemical reactions using precursor materials such as metals, alloys, or mixtures of powders to generate the desired composition of the nanomaterial, surface-modifying agents, and process control solutions. The final products usually have heterogeneous size distributions and variable morphologies, which contain impurities and defects, and thus are mostly used for nano-grained bulk material or nanocomposites, but not for precision applications [98].
The reduction of the process cost and the industrialization of products can be achieved by using a variety of precursors, like oxides, carbonates, sulfates, chlorides, fluorides, and others. Different ball mills have been developed for mechanical attrition, such as tumbler mills, attrition mills, shaker mills, vibratory mills, planetary mills, etc. [99]. The method includes shaking or violent agitation. The material powder is placed in a sealed container with coated balls of hardened steel or tungsten carbide. The mass ratio for the ball to the powder shall be 5:10, with a typical particle diameter of 50 µm for the powder. The kinetic energy of balls is a function of their mass and velocity; as a consequence, high-density materials like steel and tungsten are preferable as means of milling [95,100].

2.1.2. Solid-State Segregation

Solid-state segregation is usually used to synthesize quantum dots of metals and semiconductors [101]. This method is based on the mixing of precursors in a liquid glass melt at high temperature, followed by cooling down to the phase transition temperature. The supersaturation of precursors will convert to metals, and nanoparticles are formed through nucleation of the supersaturated metals, followed by growth through the diffusion of the nanoparticles through the solid. This process is used in the formation of nanocrystalline cobalt aluminate (CoAl2O4) nanoparticles, which can be used as an inorganic ceramic blue pigment for applications in paint, glass, porcelain enamels, and fiber. Its optical properties can also be used in manufacturing color filters for automotive lamps or luminescent materials in optical devices [102].

2.2. Bottom-Up Techniques

In opposition to the top-down approach, the bottom-up techniques are based on the chemical reduction of molecular precursors leading to the formation of metal atoms through a self-assembly process, of atoms and molecules precisely where they are needed [91]. Here, the molecules or atomic building blocks fit together to produce nanoparticles, as shown in Figure 2. The Bottom-up techniques are more favorable and popular in the synthesis of nanoparticles since they allow the production of high-quality nanomaterials with controlled intrinsic properties such as size, morphology, and crystal structure, and they involve a variety of techniques, yet they can be classified into two main categories: vapor phase and liquid phase techniques.

2.2.1. Liquid Phase Techniques

Liquid phase (or wet chemical) techniques are, as the name suggests, the ones working in the liquid phase, depending on the nature of the liquid used (organic solvent, supercritical fluid, etc.). Various techniques are existing in the literature to synthesize and produce nanomaterials, however, all previous methods share a similar methodology: starting with the mixing of precursor materials in suitable solvents with appropriate reactants (reductant, precipitant, stabilizer, etc.) to generate a supersaturated solution and initial nucleation, followed by growth of the initial nucleus into nanoparticles via precipitation. The nanomaterials are collected via filtration, centrifugation, or as a coating on a specific substrate, followed by cycles of washing and drying to remove impurities, and then calcination to generate nanomaterials of the desired morphology and crystalline structure. In this work, we will focus on the techniques that offer large-scale manufacturing possibilities.
Supercritical Fluids
Supercritical fluids (SCF) are fluids that are beyond their critical point, where they show unique properties such as density, viscosity, and diffusivity different from those of liquid and gas phases [103]. These unique properties push toward their utilization in the production of nanomaterials since they offer the possibility to avoid organic solvents, using mild conditions of temperature and generation of well-dispersed nanomaterials [104,105,106], which makes the SCF technology one of the promising techniques in nanomaterials production.
Preparation methods for metallic nanomaterials using SCF have been widely reviewed [107]. In a conventional SFC process, the metal precursors are first dissolved in a supercritical fluid (like scH2O or scCO2), followed by deposition onto a support, then a chemical reduction allows return to a metallic state. The choice of supercritical fluid is based on its availability and dielectric constant; usually, H2O and CO2 are the most used.
In practice, there are several SCF setups used to synthesize nanomaterials, from which we can mention:
  • static supercritical fluid (SSF) process;
  • rapid expansion of supercritical solutions (RESS);
  • particles from gas-saturated solutions (PGSS);
  • precipitation from compressed antisolvent (PCA);
  • aerosol solvent extraction system (ASES);
  • supercritical antisolvent process (SAS);
  • solution enhanced dispersion by supercritical fluids (SEDS);
  • supercritical antisolvent process with enhanced mass transfer (SAS-EM);
  • hydrothermal synthesis under supercritical conditions via flow reactor (HTSSF);
  • hydrothermal synthesis under supercritical conditions via batch reactor (HTSSB);
  • supercritical fluids drying (SCFD);
  • supercritical fluid extraction emulsions (SFEE).
Among the different nanomaterials obtained using SCF techniques, oxide nanomaterials are of interest since some of them, such as Ge oxide nanomaterials that are relatively challenging to synthesize, have been obtained by the SCF methods. Noteworthy is that the SCF allows both batch and flow regime production of nanomaterials while reproducing similar nanomaterials on the laboratory scale. The Zn-Ce oxide nanomaterials were synthesized at a large scale, using continuous supercritical water, by mixing aqueous solutions of the metal salts at room temperature with a flow of supercritical water in a confined jet mixer, resulting in ion results almost identical to laboratory scale [108,109,110,111].
Another example is the continuous tuning of silver nanomaterials’ size over a large range, which was achieved using the CO2 microemulsion-templating method [112]. Using a surfactant concentration of 20 mM, a precursor-to-stabilizer concentration ratio of M = 6, and a temperature of 40 °C, synthesized silver nanomaterials were continuously tuned from 3 to 8 nm by reducing the pressure.
Solvothermal and Hydrothermal
The solvothermal and hydrothermal processes consist of dissolving precursors in a solvent (solvothermal) or water (hydrothermal), heated at a very high temperature and under high pressure in a closed vessel (autoclave) for several hours (usually 6–48 h), leading to nucleation and growth of nanoparticles [113]. The main advantage of this technique is the production of nanoparticles with a crystalline structure that is relatively uncontaminated and thus does not require purification or post-treatment annealing [93]. In addition to that, those techniques allow for precise control over the size and shape distribution of the nanoparticles. These characteristics can be modified by changing some parameters, such as reaction temperature, reaction time, solvent type, surfactant type [114], electrolyte [30], and precursor type [115].
Currently, the solvothermal synthesis of nanomaterials is hard to apply on a large scale, due to its harsh reaction conditions for most of the existing industrial reactors. However, there are some examples of possible scalable processes to do it. One is represented by the highly crystalline hydrophilic and hydrophobic magnetic 20 nm Fe3O4 nanoparticles exhibiting a room temperature magnetization as high as 84 electromagnetic-unit/g [115]. According to this report, a single reaction could give 86% (1.4 g) or 68% (0.9 g) yields of hydrophilic and hydrophobic magnetite nanocrystals, respectively. Another one is the synthesis of Bi2S3 and Sb2S3 nanorods from single-source precursors under air at relatively low reaction temperatures [116]; however, neither the yield of the reaction in the laboratory nor at a large scale was mentioned. One more example in the literature is the relatively large-scale synthesis of fluorescent carbon nanoparticles by solvothermal, which only produces 7 g [117,118]. This is due mainly to the small volume of autoclaves able to work under solvothermal conditions. Still, these yields are low and quite immature to go to industrial production.
On the other hand, the use of hydrothermal synthesis has proven to be useful in the synthesis of customized nanomaterials with precise control over the particle size, morphology, and composition [119,120,121] Some hydrothermal techniques have successfully transitioned to industrial scale through the use of continuous hydrothermal processes, which employ continuous-flow reactors instead of traditional batch autoclaves. An example of the successful large-scale manufacturing of nanomaterials is the SHYMAN project, which uses hydrothermal continuous synthesis to produce nanomaterials by mixing superheated or supercritical water with an aqueous flow containing a dissolved metal salt. Figure 3 shows a scheme of the system flow used in the SHYMAN plant. This method shows high scalability from laboratory scale (g/h) to industrial scale (Tonnes/year) with costs below 10 euros/kg for some nanomaterials [32], in addition to the production of various nanomaterials such as metal perovskite Ba1−xSrxTiO3 [122], MoS2 [123], TiO2 [40], Bi2CuO4 [124] Cu2−xTe, VO2 and ZrO2, [119,120,121].
Sonochemical
The sonochemical process involves the application of ultrasound radiation in the frequency range of 0.020–10 MHz. Typically, an ultrasonic system consists of a power source, a piezoelectric system including electrodes, a horn with a stainless-steel collar, a reaction vessel, and a bath container [103,126]. This method has been used to produce nanomaterials with unusual properties since the unique conditions (very high temperatures (5000 K), pressures (>20 MPa), and cooling rates (>109 K/s)) facilitate the formation of smaller particles (goes down to 2 nm) and different shapes of products compared to other methods [95,127]. In addition to the possibility of producing large quantities of nanomaterials for industrial purposes [128,129]. Some of the applications of sonochemistry in nanomaterial generation are: HgTe-PVK [130], Fe3O4-FeP [131], MnO2 [132], and core/shell Pt/Ru [133].
Sol-Gel
Sol-gel is considered to be one of the simplest and most commonly used methods for the synthesis of nanoparticles. It is composed of a few straightforward steps, as shown in Figure 4. The sol-gel technique is used to prepare 35% of nanomaterials worldwide, which makes it one of the most used techniques to prepare nanomaterials. It is a chemical method that comprises a solution working as a precursor for an assimilated system of distinct particles [134], which offers the potential control of the whole reaction during synthesis [135]. It was first used to prepare monolithic glass, ceramics, and aerogel materials at an industrial scale at a relatively low temperature. It is just in the last few years that it has been developed for the production of advanced nanomaterials and coatings [136,137,138]. The sol is a colloidal solution made of suspended solids in a liquid phase, and the gel can be considered a solid macromolecule dispersed in a solvent. This technique consists of the transformation of the sol into a gel state with a post-treatment and transition into solid oxide material.
This technique shows many advantages, such as working in low temperatures, flexibility, high purity, and uniform structure; however, it suffers from one significant disadvantage, which is the difficulty in synthesizing precursors. In fact, hydrolysable organometallic precursors are not easy to synthesize, which increases the overall cost of production. A wide range of nanomaterials synthesized by sol-gel techniques is reported in the literature such as CdTe [133], g-Fe2O3 [140], K(WO4)2 [141], LiMn2-xCrxO4 [142], Co0,9Sm0.05Fe2.05O5 [143].

2.3. Vapor Phase Technique

The manufacturing processes of nanomaterials, labeled as vapor phase, consist of the evaporation of precursors in the reactor, followed by rapid cooling. Sometimes, it is followed by an application of a coating or functionalization before the collection of products. Vapor phase techniques are classified as bottom-up techniques characterized by the source of energy to evaporate precursors (flame, thermal, plasma, etc.), the mechanisms of nucleation and growth, the nature of precursor (metals, organometallics, halides, etc.), and state allow these distinctions between different processes in the same group [93,144].

2.3.1. Chemical Vapor Deposition (CVD)

The CVD method is a vacuum method based on the reaction between the substrate and gaseous phase precursors to obtain high-quality-performance solid materials, as indicated in Figure 5 below. It was used mainly at an industrial scale to produce thin film materials for semiconductor industries before being extended to the production of nanomaterials. The activation of the CVD reaction can be due to a temperature increase (thermal CVD) or enhanced by plasma assist (plasma-enhanced CVD) [145,146].
The high yield, low setup cost, and ability to allow large-scale and continuous processes of CVD have made it attractive to industries. A typical industrial CVD installation is usually composed of a gas delivery system, substrate transport, reaction chamber (or reactor), energy source, control system of pressure, and exhaust gas treatment system before by-products are released [147]. The gases are delivered first into the reaction chamber, which is operated at a high temperature (up to 1200 °C). The gas composition also includes inert gases, such as argon and nitrogen, that are usually used as a carrier. The gases pass through the reactor to encounter the heated substrate, where their reaction forms a solid layer that is deposited onto the substrate’s surface. The critical operation parameters of this are the process temperature and pressure of the system.
Some applications of this technique are:
  • Preparation of monodispersed gold nanoparticles on different organic and inorganic supports [148,149].
  • Development of a rapid method for the growth of metal nanoparticles on nanowires using the plasma-enhanced CVD technique [150].
  • Preparation of Ni nanoparticles with sizes varying from 2 to 6 nm (depending on the nanowire substrate temperature).
  • Fabrication of crystalline WO3 nanoparticles by the Hot-wire method [103,151].

2.3.2. Arc Discharge Technique

This technique is based on vaporizing metal using an electric arc as an energy source. It consists of charging two electrodes of the metal to be vaporized in the presence of inert gas, and then a large current is applied until the reach of breakdown voltage, finally, the arc created across the two electrodes leads to the vaporization of a small amount of metal of one electrode to another [152]. This method produces a small number of nanomaterials, but it is characterized by its reproducibility and flexibility (different compounds such as metal oxides can be produced using oxygen or other reactive gases) [144] However the control of the concentration is extremely important, indeed, high concentration of vaporized metal can leads to the production of larger particles [153].
A European research project, BUONAPART-E (Better Up-scaling and Optimization of Nanoparticle and Nanostructure Production by Means of using Electrical Discharges), led to the generation of nanomaterials by using the arc discharge technique. The process is simple, flexible, and reliable, and the production rate ranges between 0.1 and 10 g/h per optimized single unit. The utilization of multiple electrode pairs in parallel optimizes both rates of production and particle size. The project led to several pilot plant facilities, having production rates between 1 and 10 kg/day, mainly depending on the type of metal. For Cu, the measured production rate is 67 g/h (1.6 kg/day); for Ag, this would be 14 g/h (0.35 kg/day); for Zn, 356 g/h (8.5 kg/day) [154].

2.3.3. Plasma Process

Particle synthesis is usually connected to dusty plasma (plasma containing particles). The plasma processes are divided into two main categories: plasma spray synthesis and microwave plasma process. The first is conducted using fluid (gas, solid) or solid media and it involves four stages [155]: first, the solid precursors enters into the plasma reactor by a gas carrier, then heating, melting, and dissociation into gas species of precursors, followed by reaction of the gas species to form new seed cluster and finally growth and nucleation to form nanomaterials. The advantages of this method are its simplicity, the low cost, and the ability to achieve mass production; however, requirements for safety and efficient particle collection limit the application of this method [94].
The microwave plasma process is based on electric charges carried by particles originating in the plasma zone, which leads to the reduction of agglomeration and coagulation thanks to the benefits of the charged particles. Lower temperature can be achieved due to the dissociation and ionization of the reactants compared to CVD, but the electrical charges of the particles remain. The main advantages of this technique are: the ability to produce un-agglomerated particles, high production rates, and narrow particle size distribution [156,157,158]. Some of the synthesized nanoparticles using the plasma process are: TiO2 [159], Silicon [160], Fe3Al [161], amorphous carbon, and iron [162].

2.4. Hybrid Techniques

Those techniques can be considered as top-down and bottom-up techniques at the same time. They are based on patterning a surface through exposure to light, laser, or ions, followed by etching and/or formation of the desired structure by deposition of the material. The main advantage of these techniques is that relatively large quantities of 1D nanostructures can be synthesized, using a variety of available materials [163]. There are many different variants of lithography depending on the source of energy and the surface, such as photolithography, electron beam lithography, X-ray lithography, focused ion beam lithography, and neutral atomic beam lithography.

2.4.1. Photolithography

Figure 6 shows a schema of the photolithography technique, which is used in producing computer chips and nanomaterials. It is based on using a beam of UV light to reduce pattern size, which is projected onto a wafer, which will cause a photochemical reaction when it strikes the resist. The exposed part of this latter is dissolved, forming a replica of the mask pattern, followed by dissolving in acidic solutions to finally have the nanomaterial. Despite the simplicity of the concept of photolithography, its implementation is complex and expensive because the masks need to be aligned perfectly with the pattern on the wafer, and this latter has to be a single crystal [129].

2.4.2. Scanning Probe Microscopy

The scanning probe microscopy (SPM) is a technique based on the creation of patterns on the substrate at the nanometer scale, and high-resolution surface characterization at the nanometer scale. In recent years, it has evolved into a powerful tool for nanoscale patterning and controlled material synthesis. Beyond imaging, SPM now enables the precise manipulation of atoms and molecules, opening new pathways for the fabrication of functional nanomaterials, including metals, semiconductors, and organic structures.
While traditionally limited to small-scale applications, recent advancements have enabled its use in large-scale nanomaterial synthesis. For instance, researchers have developed an autonomous SPM-based platform called AutoOSS, which uses deep learning and reinforcement learning to control chemical reactions on surfaces. This system was successfully applied to synthesize hundreds of porphyrin-based nanostructures on gold substrates by selectively removing bromine atoms from precursor molecules [164].
SPM-based techniques have been used to generate both metallic and semiconductive nanomaterials by patterning these materials and transferring the patterns onto underlying substrates. A key advantage of SPM is its dual functionality: the same instrument can be used for both writing the pattern and imaging the result. This capability has enabled the fabrication of complex 2D and 3D nanostructures, contributing significantly to the development of advanced materials for electronics, photonics, and energy applications [165,166].

2.4.3. Template Fabrication

The template fabrication is seen by many as one of the most effective ways to create various nanostructures; it is based on using a nanometer-sized template, before growing into the desired structure [167]. The methodology is simple: First of all, templates of ordered nanopores have to be made. Secondly, the pores should be filled with the chosen materials using the previous methods. Examples of this technique include the assembly of nanoparticles [168,169], carbon nanotubes [170], and nanowires [171,172]. Lithographic templates can also be used to create hierarchical order [173]: the nanostructures can themselves have internal features with dimensions significantly smaller than those of the original template [174] and can serve as scaffolds for the assembly of still smaller components [175].

3. Emerging Technologies for Scalable Nanomaterial Synthesis

3.1. Computer-Aided Tools

Computer-aided tools have become essential in scaling nanomaterials (NMs) production from laboratory to industrial levels, enabling precise control over synthesis conditions, reactor design, and product quality. By integrating process simulation platforms like Aspen Plus® and DWSim, among others, with experimental findings and kinetic models [176,177,178,179], researchers can model nanoparticle formation dynamics and optimize continuous manufacturing processes. These tools also facilitate sustainability assessments through life cycle analysis [180,181,182,183] and are increasingly enhanced by machine learning to accelerate process optimization and reduce experimental overhead [184,185].
Several simulation studies have been conducted to analyze large-scale nanomaterial (NM) production, categorized by the type of material produced. For metal-based NMs, studies on copper and gold nanoparticles focus on chemical reduction methods and their economic feasibility. For instance, an analysis of a large-scale process for producing copper nanoparticles using chemical reduction concluded that the process is economically viable with a payback period of two years [186]. Similarly, designed and modeled a large-scale process to produce magnetite nanoparticles, highlighting the economic feasibility and technical challenges, compared two large-scale processes (CoMoCat and HiPCO) for producing carbon nanotubes, identifying the first process as more cost-effective [187,188].
In the realm of organic-based NMs, Larbi et al. simulated a process for producing chitin nanofibers and nanocrystals from raw chitin, emphasizing the importance of process optimization [178]. Hachhach et al. used simulation software to model the production of molybdenum disulfide nanoparticles at a large scale, demonstrating the process’s economic feasibility [189]. Additionally, an exergy analysis of a large-scale process is conducted for producing TiO2/chitosan microbeads, highlighting the potential for energy savings. These studies underscore the importance of process optimization, integration, and environmental impact assessment in the CAD of large-scale NM synthesis processes. Hence, such digital approaches support the development of efficient, reproducible, and environmentally responsible large-scale NM production systems [190,191].
The use of artificial intelligence (AI) and machine learning (ML)has gained momentum recently in the field of nanomaterials production, allowing predictive modeling, real-time optimization, and autonomous experimentation, significantly accelerating the discovery and production of advanced materials. For instance, Google DeepMind’s A-Lab combines AI with robotics to autonomously design, synthesize, and analyze new materials, offering a scalable solution for clean energy and electronic applications [192]. Similarly, explainable ML models have been developed to map complex synthesis–property relationships, such as in the case of MoS2 and VO2, where ML was used to control the synthesis [119,184,193].

3.2. Additive Manufacturing and 3D Printing Approaches

3D printing offers a transformative approach to scaling up nanomaterial production by enabling precise, high-throughput fabrication of nanostructured materials with tailored properties. Unlike previously mentioned methods, 3D printing enables bottom-up assembly of NMs into macroscale structures with controlled architectures. Techniques such as direct ink writing (DIW), fused deposition modeling (FDM), and two-photon polymerization (2PP) have been adapted to deposit nanocrystal-based inks in layered or patterned configurations, facilitating large-area production while maintaining nanoscale precision. For example, extrusion-based 3D printing can continuously deposit colloidal nanocrystal inks to form conductive films, energy storage electrodes, or catalytic scaffolds at industrial scales [194,195]. The Figure 7 shows a simple schematic of the hybrid 3D printing process.
A key advantage of 3D printing is its ability to create hierarchical structures that combine nanoscale features with macroscale geometries, enhancing mechanical, electrical, or optical performance. Printed aerogels and porous nanocomposites can achieve controlled porosity for lightweight yet strong materials, while aligned nanowire arrays can be fabricated for anisotropic conductivity or sensing applications. Additionally, multi-material 3D printing enables the integration of various nanomaterials, including drugs, metals, ceramics, and polymers [196]-into hybrid architectures, expanding applications in flexible electronics, photovoltaics, and biomedical devices. Recent developments in high-speed sintering and laser-assisted printing have further accelerated throughput, positioning 3D printing as a viable strategy for industrial-scale nanomaterial production.
Nevertheless, challenges remain regarding ink formulation, process speed, and post-processing requirements. Ensuring the stability and viscosity of nanocrystal dispersions is essential for continuous printing, while advances in automated deposition and roll-to-roll printing are expected to improve productivity. Future work should focus on integrating AI-driven process control and sustainable formulation strategies to minimize waste and energy demands. As the technology matures, 3D printing is poised to play a pivotal role in bridging laboratory-scale NM synthesis and full-scale manufacturing.
Figure 7. Schematic illustration of the hybrid 3D printing process: (a) creation of the designed cylindrical structures using FDM, (a1) visual representation of the 3D printed cylindrical formations, (b) ink deposition of Pf-127/AuNPs mixture into the cylinders enclosed with the SEM of AuNPs, (c) laser setup of the nanoscale assembly AuNPs within the confines, and (c1) the 3D simulation spectrum of light-induced heat generation [197].
Figure 7. Schematic illustration of the hybrid 3D printing process: (a) creation of the designed cylindrical structures using FDM, (a1) visual representation of the 3D printed cylindrical formations, (b) ink deposition of Pf-127/AuNPs mixture into the cylinders enclosed with the SEM of AuNPs, (c) laser setup of the nanoscale assembly AuNPs within the confines, and (c1) the 3D simulation spectrum of light-induced heat generation [197].
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3.3. Ionic Liquids

Ionic liquids (ILs) are liquids consisting entirely of ions and can be further defined as molten salts having melting points lower than 100 °C [198]. They have emerged as a versatile medium for the synthesis and modification of nanomaterials, offering unique properties that facilitate large-scale production. These low-melting organic salts, composed of cations and anions, provide a highly structured environment that influences the morphology and size of the nanoparticles formed. The low surface tension of many ILs leads to high nucleation rates, resulting in smaller particles. Additionally, ILs can act as electronic and steric stabilizers, preventing particle growth and aggregation. This makes them particularly useful in producing nanomaterials with consistent and desirable properties [199].
One of the significant advantages of using ionic liquids in nanomaterial synthesis is their ability to create hybrid structures. For instance, ILs embedded with nanoparticles can be introduced into other materials, forming films or dispersions in polymers [200]. This versatility extends to various types of nanomaterials, including carbon nanomaterials, silicon and germanium nanoparticles, metallic nanoparticles, and oxide-based nanostructures. The electrochemical synthesis of these nanomaterials in ILs has shown promising results, with applications ranging from energy storage devices to catalysis [201,202,203]. The tunable nature of ILs allows for the customization of nanomaterial properties, enhancing their performance in specific applications.
Examples of successful nanomaterial production using ionic liquids include the synthesis of metal nanoparticles and conductive polymer films [201]. These materials have been utilized in various fields, such as electronics, medicine, and environmental science. For instance, ILs have been used to produce gold nanoparticles with controlled size and shape, which are essential for biomedical applications [200]. Similarly, carbon nanomaterials synthesized in ILs have shown improved electrochemical properties, making them suitable for use in supercapacitors and batteries [201]. The ability to produce high-quality nanomaterials on a large scale using ionic liquids highlights their potential in advancing nanotechnology and addressing global challenges.

4. Challenges Facing the Development of Nanomaterial Production and Future Perspectives

Despite significant progress in nanotechnology and the rise of many commercialized products involving nanomaterials. This technology faces a substantial obstacle when translating scientific results from academic journals into applications for industrial technologies because of the following challenges:
  • Safety challenges: Various studies showed the effects of exposure to the nanomaterials on human health, and it is easy to penetrate the body [204]. Inhaled nanomaterials can cause tissue damage and subsequent systemic effects, in addition to impairing the ability of macrophages to phagocytose and clear particles, and this may contribute to inflammatory reactions [205,206]. Another risk is the ability of the particles to move through the blood to vital organs, which can cause cardiovascular and other extrapulmonary effects [207,208]. As we are going toward large-scale production of nanomaterials in many industries, it is just a matter of time before gradual as well as accidental releases of nanomaterials will occur, hence the challenge of inventing safer processes [209].
  • Environmental Impact: The effect of the environmental impact is a matter of concern in the design of production methods of nanomaterials; the principles of green chemistry present a framework for that design. It is believed that the top-down techniques generate more waste than bottom-up [210]. On the other hand, various bottom-up techniques use and/or generate toxins, while others require high energy consumption [211].
  • Reproducibility: nanomaterials applications required the conservation of the same properties as in the laboratory, for example in nano-lubrication, the MoS2 and WS2 shapes, size, and other properties are crucial in this application [212], or the carbon nanotubes which only have a significant impact if they are produced with uniform properties [213,214]. However, a slight variation of a parameter in the synthesis will result in a change in the product’s properties. This cannot be done with the majority of top-down techniques that are unable to control surface structure.
  • The physical stability of nanomaterials can be affected both during and after production. Therefore, it is essential to characterize both the processes and the nanomaterials themselves. To reduce physical alterations, it is crucial to identify and analyze key manufacturing parameters during the development phase [215].
To overcome the current challenges and unlock the full potential of nanomaterials, we propose the following future directions:
  • Stronger Academia-Industry Collaboration: Bridging the gap between research and application requires closer partnerships between academic institutions and industrial stakeholders. Such collaborations can align research objectives with real-world needs, accelerate technology transfer, and foster innovation in scalable production methods.
  • Development of Scalable, Green Manufacturing Technologies: Future research should prioritize environmentally friendly and energy-efficient synthesis techniques. Projects like SHYMAN, which combines academic and industrial expertise to scale up hydrothermal processes while reducing CO2 emissions and costs, exemplify this direction [153].
  • Integration of Machine Learning and Artificial Intelligence: AI and ML are emerging as transformative tools in nanomaterial research. These technologies can optimize synthesis parameters, predict material properties, and accelerate the discovery of novel nanostructures. For instance, ML algorithms can analyze vast datasets from experimental and simulation studies to identify patterns and correlations that would be difficult to detect manually. AI-driven platforms can also enable autonomous laboratories, where robotic systems guided by ML models conduct experiments, analyze results, and refine synthesis protocols in real time. Incorporating these tools into nanomaterial development pipelines can significantly enhance reproducibility, efficiency, and innovation.
  • Standardization and Regulatory Frameworks: Establishing standardized protocols for nanomaterial characterization, safety assessment, and environmental impact evaluation will enhance reproducibility and facilitate regulatory approval. This is crucial for building public trust and ensuring safe integration into consumer products.
  • Investment in Pilot-Scale Demonstrations: Initiatives such as ADDNANO, SHYMAN, and other projects have shown that pilot-scale demonstrations are vital for validating laboratory findings under industrial conditions. Continued investment in such initiatives will be key to overcoming scale-up barriers and optimizing performance [32,153,216].
  • Focus on Societal Impact: Nanomaterials hold immense potential to address global challenges, from reducing carbon emissions to enabling sustainable technologies. Future research should emphasize applications that contribute to societal well-being, aligning technological advancement with environmental and ethical considerations [217].

5. Conclusions

To date, research at the laboratory scale in the design and development of nanomaterials continues to expand; however, unfortunately, only a few processes are transferable to the industrial scale. The difficulties in this transition are mainly related to the adoption of different production processes depending on the desired properties and quantity, as well as the cost, either on economic, safety, or environmental levels. The development of such a process is a very challenging task, and it can be considered a long-term goal. Nevertheless, to continue feeding the market in a short time, the scale-up of the synthesis method showing industrial potential can be a solution. In this framework, various routes of nanoparticle synthesis from top-down to bottom-up are presented and discussed with respect to their scaling-up and transition to real industrial manufacturing. However, although bottom-up techniques are easier to handle and allow the elaboration of high-quality nanomaterials, in addition to their low yields, the lack of control over intrinsic properties such as size, morphology, and crystalline defects is a major drawback, which limits their use on a large scale. In contrast, top-down strategies are well-populated and more applicable since they allow obtaining nanoparticles with desired properties and controlled characteristics. Yet, more efforts can be made to further improve innovative strategies, allowing the transition from laboratory to industrial scale, while respecting the issues and challenges already mentioned. The SHYMAN, BUONAPART-E, and ADDNANO projects could be taken as success stories of the development of new synthesis methods overcoming those challenges. The big market of nanomaterials pushes towards the adoption of different production processes depending on the desired properties and quantity, in addition to the cost, both economic and environmental. The development of such a process is a very challenging task, and it can be considered a long-term goal. However, to continue feeding the market in a short time, the scale-up of the synthesis method showing industrial potential can be a solution; some success stories of this transition can be mentioned here, such as ADDNANO, BUONAPART-E, and SHYMAN, among others.

Funding

This work was financially supported by the Research Institute for Solar Energy and New Energies, IRESEN, Morocco, under the project Innowind13 Nanolubricant.

Data Availability Statement

The underlying data can be provided upon reasonable request by email to the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. (A) Typical AFM scan of CH4 grown nanotubes (900 °C with 0.2 nm thick Ta-oxide on SiO2). (B) TEM image of a CH4 grown SWNT (900 °C with 0.2 nm Ta-oxide grown on SiO2 TEM membrane). (a) HR-TEM images of Mn3O4 viewed at 50 nm scale and (b) 2 nm scale. (c) HR-TEM images of CuMn2O4 at the 50 nm scale and (d) 2 nm scale. (e) HR-TEM images of CuMn2O4/MWCNTs at the 50 nm scale and (f) 2 nm scale [11,12].
Figure 1. (A) Typical AFM scan of CH4 grown nanotubes (900 °C with 0.2 nm thick Ta-oxide on SiO2). (B) TEM image of a CH4 grown SWNT (900 °C with 0.2 nm Ta-oxide grown on SiO2 TEM membrane). (a) HR-TEM images of Mn3O4 viewed at 50 nm scale and (b) 2 nm scale. (c) HR-TEM images of CuMn2O4 at the 50 nm scale and (d) 2 nm scale. (e) HR-TEM images of CuMn2O4/MWCNTs at the 50 nm scale and (f) 2 nm scale [11,12].
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Figure 2. Schematic of Bottom-up and Top-down Techniques [102].
Figure 2. Schematic of Bottom-up and Top-down Techniques [102].
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Figure 3. Schematic diagram of the continuous hydrothermal flow synthesis (CHFS) process used in the direct synthesis of VO2 (M) nanoparticles [125].
Figure 3. Schematic diagram of the continuous hydrothermal flow synthesis (CHFS) process used in the direct synthesis of VO2 (M) nanoparticles [125].
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Figure 4. Main steps of the sol-gel technique [139].
Figure 4. Main steps of the sol-gel technique [139].
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Figure 5. Scheme of a CVD system [95].
Figure 5. Scheme of a CVD system [95].
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Figure 6. Simple scheme of photolithography [70]: In step (a), an oxidized silicon wafer is coated with a 1 µm thick photoresist layer. A beam of UV light is directed through a patterned mask and focused by lenses to reduce the image size, initiating a photochemical reaction in the exposed resist areas. In step (b), the wafer undergoes development, during which the exposed photoresist is dissolved, revealing a replica of the mask pattern. Step (c) involves immersing the wafer in an acidic solution that selectively etches away the exposed silica layer, leaving the resist and silicon intact. In step (d), the remaining photoresist is removed using a different acidic solution, exposing the underlying silicon. Finally, in step (e), further etching removes silicon from the exposed regions, forming nanoscale channels that define the chip’s structure.
Figure 6. Simple scheme of photolithography [70]: In step (a), an oxidized silicon wafer is coated with a 1 µm thick photoresist layer. A beam of UV light is directed through a patterned mask and focused by lenses to reduce the image size, initiating a photochemical reaction in the exposed resist areas. In step (b), the wafer undergoes development, during which the exposed photoresist is dissolved, revealing a replica of the mask pattern. Step (c) involves immersing the wafer in an acidic solution that selectively etches away the exposed silica layer, leaving the resist and silicon intact. In step (d), the remaining photoresist is removed using a different acidic solution, exposing the underlying silicon. Finally, in step (e), further etching removes silicon from the exposed regions, forming nanoscale channels that define the chip’s structure.
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Table 1. Table showing the scope and reach of nanomaterials in various market sectors [32].
Table 1. Table showing the scope and reach of nanomaterials in various market sectors [32].
Application AreaMaterials/CompoundsUses/Functions
PharmaceuticalIM/PVP, HA/PVP [33]Implant strengtheners, Formulated insolubles [34,35]
ElectronicsSt-Fe/SnO2, Ag/Cu/ITO, YAG/ZrO2-Ce [36,37]Conductors/magnets, Printable inks (e.g., RFID), Laser lenses [38,39]
HealthcareAg, TiO2/ZnO, Fe2O3/Fe3O4 [40,41,42]Antimicrobial [43], Sunscreens [44], Pigments [35]
MedicalYAG/ZrO2-Ce, Fe2O3/Fe3O4, HA/CaPO4 [45,46,47]Cell signaling, MRI contrast agents, Artificial bone agents [48,49,50]
CatalystsFe2O3/Mo-Fe, Cu/CuO, CeO, Ag/Pd/Pt [51,52,53,54]CNTs synthesis, Polymerization enhancers, Combustion additives, Generic metals [55,56]
MaterialsSiO2, YAG/ZrO2, ZnO/Cd2SnO4 [57,58,59]Scratch resistance, Strength enhancers, Smart material coatings [60,61,62]
Table 2. An overview of the synthesis processes of nanomaterials and their classification.
Table 2. An overview of the synthesis processes of nanomaterials and their classification.
Bottom UpTop DownOther Methods
Vapor/Aerosol Phase SynthesisLiquid Phase Synthesis (Wet Method)Solid Phase Synthesis (Mechanical)
Chemical vapor deposition [63]
-Thermally-activated (TA)
-Plasma-enhanced (PE)
-Flame-assisted (FA)
-Electrochemical (EC)
-Laser-assisted (LA)
-Metal-organic (MO)
-Metal-catalyzed (MC)
-Aerosol-assisted (AA)
-Direct-liquid (DL)
-Atom layer (AL)
-Template-assisted (TA)
Physical vapor deposition [64,65]
-Evaporation/MBE
-Sputtering
Spray pyrolysis
-Tubular reactor
-Vapor flame reactor
-Emulsion combustion
Flame [66,67]
-Flame aerosol
-Flame spray
-Flame pyrolysis
Other [68,69,70,71]
-Arc discharge
-Submerged arc discharge
-Solid-Vapor synhesis
Chemical pro-precipitation [72]
-Microwave assisted
-Metalorganic
-Solvothermal/hydrothermal
-Sonication assisted
-Polyol
-Template
Sol-Gel [73,74,75,76]
-Pchimi method
-Reverse micelle
Microemulsion [77,78]
-Micelle
-Reverse micelle
Electrochemical deposition [79]
-Cathodic deposition
-Anodization
Other [80,81,82]
-Electrospraying
-Sonochemical
-Precipitation, Freeze drying
-Plasma, Microwave, Radiation, Electric field
Mechanical milling/solid-state phase segregation [83,84,85]Biologically assisted [64,86,87]
-Intercellular
-Extracellular
Hybrid or product-specific methods
-HIPOC
-CaNaCAT
Nano-fabrication (patterning/manipulation)
-Lithography/etching [88,89]
-Self-assembly/template assisted [90]
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Hachhach, M.; Bayou, S.; El Kasmi, A.; Saidi, M.Z.; Akram, H.; Hanafi, M.; Achak, O.; El Moujahid, C.; Chafik, T. Towards Sustainable Scaling-Up of Nanomaterials Fabrication: Current Situation, Challenges, and Future Perspectives. Eng 2025, 6, 149. https://doi.org/10.3390/eng6070149

AMA Style

Hachhach M, Bayou S, El Kasmi A, Saidi MZ, Akram H, Hanafi M, Achak O, El Moujahid C, Chafik T. Towards Sustainable Scaling-Up of Nanomaterials Fabrication: Current Situation, Challenges, and Future Perspectives. Eng. 2025; 6(7):149. https://doi.org/10.3390/eng6070149

Chicago/Turabian Style

Hachhach, Mouad, Sanae Bayou, Achraf El Kasmi, Mohamed Zoubair Saidi, Hanane Akram, Mounir Hanafi, Ouafae Achak, Chaouki El Moujahid, and Tarik Chafik. 2025. "Towards Sustainable Scaling-Up of Nanomaterials Fabrication: Current Situation, Challenges, and Future Perspectives" Eng 6, no. 7: 149. https://doi.org/10.3390/eng6070149

APA Style

Hachhach, M., Bayou, S., El Kasmi, A., Saidi, M. Z., Akram, H., Hanafi, M., Achak, O., El Moujahid, C., & Chafik, T. (2025). Towards Sustainable Scaling-Up of Nanomaterials Fabrication: Current Situation, Challenges, and Future Perspectives. Eng, 6(7), 149. https://doi.org/10.3390/eng6070149

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