Redefining Quantum Dot Synthesis with Additive-Manufactured Microfluidics—A Review

Abstract

Quantum dots with sizes between 1 and 100 nm possess unique optical and electronic properties, making them valuable in energy, bioimaging, and optoelectronics fields. While traditional synthesis methods offer control over QD properties, they face challenges in scalability and reproducibility. Integrating microfluidics addresses these issues, providing precise control and high-throughput capabilities. This review highlights the transition from PDMS-based devices to additive-manufactured microfluidics, emphasizing their ability to overcome limitations in traditional methods. These advancements smooth the way for scalable, cost-effective, and sustainable QD production with enhanced application potential.

1. Introduction

The term quantum dots can seem confusing at first sight, as it is not a term that is heard in everyday life. It refers to a tiny particle (nanoscale) considered a semiconductor. These particles have a unique optical and electronic property caused by a phenomenon called quantum confinement [1]. This phenomenon occurs due to the tiny dimensions of quantum dots (1 nm to 100 nm [2]), which limits the movement of electrons within the dots. As a result of this limitation, the energy levels and behavior of the electrons change, leading to variations in the optical and electronic properties depending on the size of the quantum dot. Thus, we can understand that the key to controlling and manipulating these properties is controlling the size of quantum dots.

The discovery of quantum dots dates back to 1980, when Alexey Ekimov and Valerii Kudryavtsev were among the first to observe that the optical properties of nanocrystals depend on their size [3]. Since then, the presence of this material has been expanding in various fields, as researchers and scientists have continued conducting experiments and discovering more about its properties [4,5,6]. Quantum dots can be made from various semiconductor materials such as cadmium sulfide (CdS), cadmium selenide (CdSe), lead sulfide (PbS), and indium phosphide (InP) [7]. To date, quantum dots are still attracting scientists from different fields, especially in nanotechnology research, due to their wide range of applications, including sensors, bio-imaging, drug delivery, and theranostics [8].

Going back in time, in 1981, the Russian physicist Alexey Ekimov noticed the quantum size effects in glass matrices doped with semiconductor nanocrystals [9]. Later, Louis E. Brus at Bell Labs in the United States discovered similar size-dependent optical properties in colloidal solutions of nanocrystals. These studies set a solid base for later research in the quantum dots field, highlighting the outstanding potential of the nanoparticles in the progress of different scientific and technological fields. As time passes, nanotechnology and material science advancements have greatly improved the synthesis approaches and control of the quantum dots’ characteristics. Researchers have developed various techniques and methods to produce quantum dots while having the ability to control the size, shape, surface, and overall properties of the quantum dots. As a result of having this ability, quantum dots have been involved in different applications, especially in optoelectronics and biomedical imaging [10], as well as energy-related fields such as solar energy harvesting [11].

To simplify this idea, Figure 1 illustrates how the size of the quantum dots affects the color of the light they produce when exposed to blue light (450 nm wavelength). The color of light produced differs depending on the size of the dot. Smaller quantum dots (around 2 nm) produce green light, while larger ones (around 6 nm) produce red light. Quantum dots with sizes in between produce lights going from green, yellow, orange, and finally red as the size of the dot increases. This is due to the relationship between the size of the quantum dot and the band gap. In smaller quantum dots, the band gap is more prominent, resulting in the emission of higher energy (shorter wavelength) light, such as green. As the size increases, the band gap decreases, leading to the emission of lower energy (longer wavelength) light, such as red.

In Figure 2, you can see the specific emission spectra of the quantum dots after being exposed to blue light. So, when light with energy matching the band gap is absorbed, it moves an electron from the valence band to the conduction band. The electron then falls back to the valence band and releases a photon, which causes the emission [13]. We can see that the emissions of quantum dots are narrower than those of other fluorophores or organic dye molecules. Each color produced depends on the size of the quantum dot.

Now, to fully understand what quantum dots are and how they work, it is essential to know the properties of quantum dots, which can be broadly categorized into three types: optical, electronic, and structural. These properties are not independent; instead, they are determined by a combination of several factors, including the size, shape, surface structure, composition, and crystallinity of the quantum dots. One of the most critical aspects influencing these properties is the bandgap, which can be tuned by changing the size of the quantum dots. Another approach to modifying the bandgap is through core alloying—by incorporating different elements into the core material, it is possible to tailor the electronic structure and achieve desired optical characteristics [15,16].

This means introducing or mixing different materials in the central part of the quantum dots to change their properties. These properties are what differentiate quantum dots from other materials, and therefore, they become useful in different applications such as sensing [17], medical treatments and diagnostics [18,19], and biotechnology [20], as well as materials science [21].

Starting with the optical properties, one of the most significant features of quantum dots is their behavior and how they interact with light. The particle size can affect the optical properties, which can also be affected by different things, including the synthesis method and materials [22]. One of the optical properties of quantum dots is that they can absorb light and then release it back, called photoluminescence. As mentioned, the particle size can affect the photoluminescence, which means that the emission color will differ depending on the particle size. Another optical property of the quantum dots is the absorption with various excitonic peaks. These peaks show the specific wavelengths of light that the quantum dots can absorb effectively. Thus, quantum dots can be engineered to absorb a particular wavelength of light, reducing lost energy [11]. In addition to that, the fluorescence emission of quantum dots is narrow and symmetric, with a broad absorption range and a narrow emission spectrum. This leads to high color purity and brightness, handy for display technologies and fluorescent imaging in biological applications [5,23].

Quantum dots also possess unique electronic properties due to the quantum confinement of electrons. Similarly, their optical properties are influenced by the synthesis method and materials used to produce the quantum dots. The energy levels in quantum dots are fixed at a certain level, creating distinct energy gaps between them. As the quantum dots become smaller, the space between them grows, which impacts the electronic properties of the quantum dot [7]. Moreover, when an electron is confined in a tiny space, its interaction with the holes increases. This increases exciton binding energy and changes electronic transitions, making quantum dots sensitive to size changes. However, to achieve quantum confinement, it is essential to consider the Bohr condition, which states that the size of the nanoparticle must be smaller than the exciton Bohr radius [24]. Another electronic property is the ability to generate multiple excitons. Now, in a standard semiconductor, a single photon excites one electron, forming an electron–hole pair, known as an exciton [25]. However, quantum dots can generate multiple excitons when the wavelength of the photon absorbed is greater than the size of the quantum dot, allowing for multiple charge carriers to be created from a single photon. This creation of multiple charge carriers is more efficient in terms of energy transfer [11].

Moving to the structural properties of quantum dots, the crystalline composition, surface structure, and the presence of defects influence them. These properties are essential for understanding the stability, reactivity, and interaction of quantum dots with other materials. Quantum dots typically comprise semiconductor materials like CdS, CdSe, PbS, and InP. They are usually synthesized to have highly crystalline structures, which is crucial for their optical and electronic performance. These spherical crystals are often smaller than 6 nm, with size-dependent photoluminescence properties and a long lifespan [8]. The crystallinity of quantum dots significantly impacts their quantum efficiency and photostability. Moreover, they can be produced in various shapes, including rod-shaped quantum dots [7]. Another thing that affects the properties of quantum dots is the surface structure, which plays an essential role in their chemical reactivity and stability. For example, surface defects can obstruct the charge carriers and reduce the photoluminescence efficiency as a result [7]. However, passivation with organic or inorganic ligands can improve stability and enhance optical properties [26].

2. Applications

Due to their properties, quantum dots have become an interesting material for various applications and have been used across different fields. For example, in energy production, they are integrated into solar panels; in the medical field, they are used for bioimaging; and they also appear in other areas such as display technologies and nanofillers [27,28,29,30,31]. These and most other quantum dot-based applications mainly benefit from their unique optical properties [32]. Figure 3 shows the key fields where quantum dots are applied. Starting with LEDs, quantum dots (QDs) have been extensively used in LED technology, particularly in III–V heterostructures, where they are integrated into multilayer structures on semiconductor substrates, such as InAs/GaAs QDs. Although there are challenges with interface control and post-processing analysis, advancements like InxGa1–xAs capping layers and chemically etched nanomembranes have improved performance [33,34]. Colloidal InP QDs are especially notable for their tunable and bright photoluminescence (PL), which is further enhanced with ZnSe/ZnS multishells, making them ideal for display applications [35,36,37]. Other materials, such as silicene QDs and halide-exchanged CsPb(Br/I)3 QDs, are also being explored for specific emission ranges [38,39]. QDs are employed in various LED types, including those based on CsPbX3, CuInS2/ZnS, and CdSe nanoplatelets [40,41,42,43].

Quantum dots (QDs) have also been integrated into photovoltaic devices to enhance energy conversion efficiency. This includes the use of CdS, CdSe, and PbS QDs, with ongoing improvements in capping and passivation techniques [44,45,46,47]. Ligand and solvent engineering are crucial for enhancing QD film performance, along with developments in homogeneous QD dispersion in polymers and theoretical models designed to improve QD-based energy applications [48,49,50,51]. Moreover, QDs are widely used in photodetectors and sensing technologies, including photoconductors and broadband detectors. In the IR region, PbS and Ag2Se QDs are used for high responsivity and mid-wavelength detection [52,53,54]. Printing techniques have made it possible to develop broadband photodetector arrays [55,56]. Additionally, QDs like WS2 and CsPbBr3 are applied in UV photodetectors and phototransistors, enhancing both sensitivity and balanced photodetection [57,58]. On the biomedical side, QDs’ high luminescence and biocompatibility make them suitable for bioimaging, diagnostics, and biosensing. They are used as fluorescent labels for imaging [59,60], in biosensors, and cell imaging applications, often synthesized using novel methods like microfluidic processes [61]. Environmentally, QDs serve as selective probes for metal ion sensing in water and wastewater, and also act as adsorbents for organic pollutants [62,63,64]. Beyond that, QDs are used in semiconductor photocatalysis to convert light into chemical energy, improving reaction efficiency and introducing new catalytic pathways. Carbon-based QDs, for example, have been shown to enhance hydrogen evolution and oxygen reduction reactions [65,66,67,68]. Lastly, QDs are also used in industrial applications such as magnetic particle inspection, product authentication, and encapsulation, showcasing their versatility [69,70,71].

3. Synthesis Approaches

There are many ways to produce or synthesize quantum dots, but they can generally be categorized into two main groups of techniques, as shown in Figure 4. It is important to note that the methods shown in the figure are just selected examples; each approach includes a wide variety of techniques developed over the years. The first one is the top-down technique. Its name gives a clue about how it works. Imagine starting with a large block of material and breaking it down into tiny particles. That is basically how this approach functions. It begins with a bulk semiconducting material, which is then physically or chemically broken down into nano-sized particles to produce quantum dots [72]. Although this technique can be used to synthesize quantum dots, it is usually not preferred for large-scale production [73]. That is mainly due to lower yields, higher costs, and the harsh conditions often required to achieve a usable product [74]. On the other hand, we have the bottom-up technique, which works in the opposite direction. Instead of breaking something down, this method builds particles up from atoms or molecules. The process involves assembling basic building blocks that nucleate and grow into nanoparticles, eventually forming monodispersed colloids through self-assembly [75].

4. Hot Injection (HI)

The hot injection method is one of the widely used methods when it comes to synthesizing different variants of quantum dots [76]. Multiple researchers reported the use of the HI method to synthesize quantum dots and nanocrystals [77,78,79,80,81,82,83,84,85]. In the HI method, the quantum dots are formed by injecting reactants at high temperatures to obtain the final product. These reactants can be anything, depending on the type of quantum dots desired. As shown in Figure 5, reactant one is typically placed in a flask with solvent, octadecene, and a stabilizing agent, such as oleic acid. This mixture is heated until it reaches a temperature of around 120 °C for a while, typically 1 h. This is performed to ensure that all the moisture is removed. After that, the mixture is heated more until it reaches 150 °C under nitrogen gas; the temperature is lowered to 100 °C. This makes reactant one ready. At the same time, reactant two is placed in another flask with the same solvent, octadecene, and oleic acid. The mixture is heated to 120 °C under vacuum to dry it out. After reaching that stage, more oleic acid is added to the flask at the same temperature as nitrogen gas. Then, the temperature is increased to a level between 140 and 200 °C. When the temperature is high enough, a small amount of reactant is injected into the flask that contains reactant two. This initiates the reaction immediately, taking a few seconds. After that, the mixture is cooled in an ice bath.

In the HI method, the first stage, nucleation, begins immediately after injection. The growth stage then commences, which helps control the size of the particles. The high temperature used in this process allows for better control over the shape and quality of the QDs, and the ice bath is used to terminate the growth. It is essential to note that the reaction environment significantly impacts the final product of quantum dots. For example, changing the injection temperature and/or the number of stabilizing agents can improve the brightness and size uniformity of the QDs produced [78,79]. Overall, the hot injection method is useful due to its ability to control the size and optical properties of the quantum dots produced. However, it might be challenging due to the need for rapid injection, as well as the requirement of a no-oxygen environment to prevent the QDs from damage [86].

Figure 5. Fabrication process using the HI method [87].

Figure 5. Fabrication process using the HI method [87].

5. Ultrasonication-Assisted Method

Multiple researchers have reported the synthesis of quantum dots by a scalable and straightforward ultrasonication-assisted method without the need for inert gas protection [88,89]. They reported that this method is much more efficient than the HI method, as it requires a high temperature and is complicated. The Ultrasonication-Assisted Ambient-Air Synthesis Method. In this method, as shown in Figure 6, two reactants are prepared. Reactant 1 should dissolve in a solvent at 100 °C, continually stirring. On the other hand, Reactant 2 is similarly dissolved in another solvent at the same temperature. The concept here is simple: the synthesis begins by injecting 150 µL of Reactant 1 into 1.5 mL of Reactant 2 while strong and nonstop stirring. This will result in the formation of nanoplatelets (NPLs) within approximately 3 s. After about 5 s, 2 mL of an antisolvent is introduced to initiate nucleation and growth of the NPLs, keeping the stirring on for about 1 min. Now, to obtain the quantum dots, 200 µL of acid is added to the solution, which is then subjected to ultrasonication at 100 W for 3 min. This process effectively reduces the NPLs to uniformly sized QDs. Now, the advantage of this method is that it does not need an isolated environment to synthesize the QDs. Also, the final product seems to have excellent monodispersion with a high-photoluminescence quantum yield. However, a possible downside of this method is that the reliance on ultrasonication could lead to variations in results if not carefully controlled.

6. Wet and Dry Milling

Now, most methods used to synthesize QDs are, at some point, complicated or risky, such as those involving high temperatures, gases, and solvents, which can limit their practical application. In this case, milling comes in handy as it simplifies the process by grinding or milling essential components together, avoiding issues related to solubility. This concept seems promising, especially since many researchers have tried to synthesize quantum dots using it and even tried to improve it [90,91,92,93,94,95,96]. This approach is promising and straightforward as it reduces many risks associated with the other method, making the production process much easier and more cost-effective. However, this method is not free of challenges. Although it is simpler and much easier to apply, it often results in QDs with lower photoluminescent quantum yields than those synthesized through the previously mentioned solution-based methods. Besides that, the surface defects caused during the milling process can decrease the quality of the final product of QDs. After all, this method is still a promising one. Still, further innovations and research are needed to overcome these challenges and increase the efficiency of the final product to compete with other solvent-based QD products.

7. Continuous Flow Synthesis

The previously mentioned approaches and methods have been beneficial for a long time. However, it always had a downside. Whether on the impact on the final product, isolated reaction environment, or the high temperatures it demands [97,98]. Therefore, researchers have been trying to develop noble methods using conventional methods. Unfortunately, it turned out to be as complicated as the conventional ones [99,100,101]. Researchers have found another promising alternative: flow reactors for producing quantum dots. Here, the flow synthesis methods became interesting due to their outstanding mixing abilities, providing a controlled reaction environment and the ability to change the reaction environment as needed [102]. Also, these reactors are advantageous when it comes to mass and heat transfer, reproducibility, and better yield compared to the conventional method in synthesis methods [103,104]. These flow reactors have been successfully used to synthesize different types of nanomaterials, such as metal nanoparticles, metal oxides, and colloidal semiconductors [105,106,107,108].

The method works simply. As shown in Figure 7, both reactants, 1 and 2, are prepared in separate syringes and then injected into a PTFE tube using a syringe pump. They are mixed, and flow to a location where the tube is immersed in a water bath maintained at 30 °C to ensure consistent reaction conditions. This initiates the formation of the nanocrystals within seconds. The reaction product is later collected in a container immersed in an ice bath to stop the reaction and prepare the product for further treatment and processing. One of the crucial characteristics of this method is that it eliminates the need for a reassessed reaction environment. Researchers stated that they conducted the experiment at room temperature and used the chemicals as received. Moreover, this method eliminates the need for high temperatures during the synthesis process, which simplifies the whole process [109].

Table 1. Comparing the QD synthesis methods.

Method	Process Description	Advantages	Disadvantages	Reaction Environment	Time Efficiency
Hot Injection (HI)	High-temperature injection of reactants in a controlled environment enables the production of quantum dots with precise size and shape control.	Allows for precise control over size and optical properties; high-quality quantum dots.	It requires high temperatures and rapid injection, which is challenging without an oxygen-free environment.	Requires an inert atmosphere, typically nitrogen gas, and high temperatures.	Rapid nucleation and growth occur within seconds, but require preparation time.
Ultrasonication-Assisted	A scalable method involving ultrasonication in ambient air enables the rapid formation of nanoparticles without the need for inert gas protection.	No need for an isolated environment; produces monodispersed quantum dots with high photoluminescence yield.	Results can vary depending on ultrasonication conditions and are less consistent than those of other methods.	Operates in ambient air; no exceptional environment required.	Swift process (within minutes) with immediate nucleation.
Wet and Dry Milling	Simple grinding or milling components to produce quantum dots can avoid solubility issues, but often results in lower-quality products.	A cost-effective and straightforward process with fewer risks, thereby avoiding solubility issues.	Lower photoluminescence quantum yield; surface defects can reduce final product quality.	No specific environmental requirements, simple grinding/milling.	Relatively slow, depending on milling time and desired particle size.
Continuous Flow	Reactants are mixed in a continuous flow reactor at controlled temperatures, providing consistent and reproducible quantum dot synthesis.	Enhanced reproducibility and yield; no need for high temperatures or specialized environments.	Complex setup; not as straightforward as batch processes.	Controlled environment within a flow reactor; usually does not require inert gases.	Efficient for continuous production; reaction times are short, but setup can be time-consuming.

shows that each synthesis method for quantum dots offers unique strengths and challenges tailored to specific requirements. The hot injection (HI) method stands out for its ability to produce high-quality quantum dots with precise control over size and optical properties, albeit at the cost of requiring high temperatures, an inert environment, and a technically demanding setup. By contrast, the ultrasonication-assisted method is more accessible, enabling rapid synthesis in ambient air while achieving excellent photoluminescence. However, its results may vary due to the sensitivity of ultrasonication parameters. Meanwhile, wet and dry milling methods simplify the synthesis process by eliminating the need for solvents and inert gases, providing a cost-effective alternative, though often at the expense of product quality due to surface defects and lower quantum yields. The continuous flow approach offers enhanced reproducibility and scalability, precisely controlling reaction parameters, reducing waste, and improving safety, making it highly efficient for high-throughput production.

Overall, the choice of synthesis method highly depends on the requirements of the application, including the desired properties of the quantum dots, scalability, and available resources, such as financial ones. As previously mentioned, some methods excel in terms of control and precision, while others offer simplicity and ease of scaling. This highlights the need for careful consideration when selecting the most appropriate technique for quantum dot production.

8. Advancing Quantum Dot Synthesis with Additive-Manufactured Microfluidics

8.1. Introduction to Microfluidics in QD Synthesis

Microfluidics, manipulating fluids within micrometer-scale channels, offers unparalleled control over fluid dynamics, reaction kinetics, and microenvironmental conditions. Operating on tiny volumes, typically ranging from 10⁻⁹ to 10⁻¹⁸ L, microfluidics significantly reduces reagent consumption and enhances reaction precision [109,110]. These attributes make it particularly advantageous for nanoparticle synthesis, where precise control over size, shape, and composition is critical [11]. In microfluidic systems, laminar flow dominates, enabling controlled diffusion-based mixing and enhanced heat and mass transfer. These properties are essential for the rapid and homogeneous synthesis of quantum dots (QDs), ensuring high uniformity and narrow size distributions [104,111]. Furthermore, microfluidic systems are adaptable to real-time parameter adjustments, such as flow rate and reagent concentration, enabling the synthesis of QDs with tunable optical and structural properties, which are crucial for applications in optoelectronics and biomedicine [112]. Figure 8, presented here, provides a schematic representation of a basic microfluidic system, illustrating its utility in chemical synthesis.

Now, the synthesis of QDs using traditional batch methods faces well-documented challenges, such as variability in size distribution, limited scalability, and inconsistent reproducibility. Microfluidic systems solve these issues by enabling enhanced control over reaction conditions. The ability to precisely manipulate reagent concentrations, flow dynamics, and reaction temperatures allows for monodisperse QDs with consistent optical and physical properties [114]. Improved uniformity is achieved through droplet-based microfluidics, where individual reactions are confined to discrete droplets, reducing cross-contamination and ensuring consistent particle size across batches [111]. Regarding scalability, microfluidic systems excel by employing parallelized channel operations, which allow for high-throughput production while maintaining uniform quality, a feat challenging to achieve in traditional batch synthesis [111,114]. These features collectively position microfluidics as a transformative platform for QD synthesis, offering significant advancements over conventional methodologies.

Over time, microfluidics has evolved significantly, transitioning from basic fluid handling systems to sophisticated platforms for nanomaterial synthesis. Early microfluidic devices were primarily employed for chemical synthesis and molecular assays, but their application in quantum dot (QD) synthesis has expanded through technological innovations. The integration of additive manufacturing into microfluidic fabrication has enabled the rapid prototyping of multilayered and complex device designs. Such advancements have been leveraged for the ultrafast synthesis of nanoparticles, including silver nanoparticles and QDs, demonstrating industrial scalability and efficiency [7,112]. Additionally, the advent of continuous-flow microfluidic systems has facilitated real-time optimization and monitoring of reaction parameters, resulting in superior control over the size and composition of QDs. This continuous synthesis approach reduces energy and material consumption, providing a sustainable and scalable alternative to traditional batch methods [115].

Microfluidic systems offer significant advantages over traditional batch synthesis methods, particularly in terms of size control, cost efficiency, scalability, and reproducibility. Due to uncontrolled reaction conditions, traditional batch processes often produce QDs with broad size distributions and variable quality. In contrast, microfluidic reactors achieve size distributions with less than 10% standard deviation, a marked improvement in uniformity [115,116].

Table 2. Advantages of microfluidic systems compared to traditional synthesis techniques.

Metric	Traditional Synthesis Methods	Microfluidic Methods	References
Size Control	Wide particle size distribution due to uncontrollable reaction conditions.	Produces nanoparticles with <10% standard deviation in size distribution through precise reaction control.	[114]
Cost Efficiency	High material and energy consumption; expensive fabrication processes.	Reduces material and energy usage; microreactors are inexpensive and rapidly fabricated (e.g., CO2-laser).	[104,112]
Scalability	Struggles to maintain consistent quality when scaled up; batch processes can be inefficient.	Designed for continuous flow production, allowing scalable and consistent QD synthesis.	[115,117]
Reproducibility	Variable conditions often lead to inconsistent quality between batches.	Ensures thermal and chemical homogeneity, resulting in consistent reaction conditions and reproducible QDs.	[116]
Reaction Efficiency	Slower reaction rates and limited separation of nucleation and growth processes.	Facilitates rapid heat and mass transfer, enabling faster reactions and better control of growth processes.	[102]
Environmental Impact	High waste generation and energy demands.	Minimizes waste through precise control and efficient material use.	[111]

, presented in this section, comprehensively compares microfluidic systems and traditional synthesis methods, highlighting key metrics such as size control, cost, scalability, and reproducibility.

Cost efficiency is another advantage, as microfluidic systems reduce reagent and energy consumption over time despite potentially higher initial setup costs. Scalability, a standard limitation of batch methods, is effectively addressed through the continuous flow nature of microfluidic reactors, allowing for seamless scale-up without compromising product quality [115]. Furthermore, microfluidics ensures high reproducibility, as controlled reaction environments maintain consistent properties across QD batches. Integrating real-time monitoring and automation further enhances this reproducibility, enabling the rapid optimization of synthesis conditions [115]. Collectively, these advantages establish microfluidics as a superior methodology for QD synthesis, streamlining production processes and encouraging the exploration of novel quantum dot compositions and functionalities that were previously unattainable.

8.2. Key Achievements of Microfluidics in QD Synthesis

Microfluidic technology has revolutionized the synthesis of quantum dots (QDs) by providing unparalleled control over reaction conditions, leading to significant advancements in their structural and optical properties. One of the most notable achievements is the production of QDs with a narrow size distribution, which is critical for applications requiring consistent optical characteristics, such as bioimaging and optoelectronics. This precise size control is achieved by regulating reaction parameters within microfluidic systems, including temperature, flow rates, and precursor concentrations. These parameters are notoriously difficult to stabilize in conventional batch processes, making microfluidics a superior alternative [117].

For example, segmented flow microreactors, a subset of microfluidic systems, have been shown to enhance mixing efficiency and minimize residence time distribution. These attributes ensure the synthesis of QDs with uniform size and improved optical properties [116]. Additionally, the continuous and scalable nature of microfluidic synthesis makes it particularly appealing for industrial applications, where reproducibility and efficiency are crucial. The integration of real-time monitoring tools, such as in situ photoluminescence and absorbance detection modules, further optimizes the synthesis process by providing immediate feedback on reaction dynamics and QD quality [102].

Microfluidic platforms also enable the synthesis of complex QD structures, such as core–shell and multi-shell configurations, which exhibit enhanced stability and photoluminescence due to improved surface passivation and reduced defect states. These advanced structures have expanded the applicability of QDs in fields such as photovoltaics, where stability and quantum efficiency are critical [102]. Moreover, the ability to fine-tune synthesis parameters within microfluidic systems has facilitated the creation of QDs with tailored emission spectra, allowing their use in particular applications requiring precise wavelength emissions.

The success of microfluidic synthesis in quantum dot (QD) production is underpinned by the materials and reactor designs employed in these systems. Polydimethylsiloxane (PDMS) is one of the most commonly used materials for fabricating microfluidic chips due to its biocompatibility, optical transparency, and affordability. However, its hydrophobic nature necessitates surface modifications for specific reactions [118].

Microfluidic reactors can be categorized into three main types: continuous laminar flow, segmented flow, and droplet-based designs. Continuous laminar flow reactors are valued for their simplicity and ability to manage single-phase liquid flows. In contrast, segmented flow microreactors, which incorporate gas or liquid segments, are designed to enhance mixing and minimize residence time distribution, resulting in more uniform QD size and properties [116]. Droplet-based microreactors take this precision a step further by encapsulating reaction mixtures within droplets, mitigating clogging risks and enabling highly controlled reaction conditions [102].

Additional materials, such as polytetrafluoroethylene (PTFE) and glass, are frequently used in microreactors due to their chemical resistance and thermal stability. These properties are particularly advantageous for handling the high temperatures and corrosive precursors often required in QD synthesis [117]. The integration of online detection systems, including fluorescence and absorbance modules, into these reactors enables researchers to monitor reaction progress and QD properties in real-time, further enhancing the reproducibility and quality of the synthesis process [116].

Microfluidic synthesis has been instrumental in advancing the properties of several types of quantum dots (QDs), particularly CdSe, InP, and perovskite QDs. Each type has benefited uniquely from the precision and scalability microfluidic platforms offer. CdSe QDs, among the first to be synthesized using microfluidics, demonstrate the technology’s ability to produce high-quality, monodisperse nanoparticles with narrow emission spectra and enhanced photoluminescence quantum yields. These improvements are achieved through meticulous control of flow rates and reaction temperatures within microchannels [116]. InP QDs, known for their lower toxicity than cadmium-based QDs, have also seen significant advancements. Microfluidic synthesis has enabled the formation of core–shell structures, such as InP/ZnS, which are critical for enhancing the stability and optical performance of these QDs [117]. Perovskite QDs, particularly CsPbX3, have benefited immensely from microfluidic platforms that allow rapid nucleation and growth, leading to QDs with tunable emission spectra and high quantum yields. These properties make them ideal candidates for optoelectronic applications [117].

Table 3. Overview of quantum dot types and their synthesis parameters in microfluidic systems [118].

QD Type	Synthesis Parameters	Achieved Properties	Application
Ag2S	Liquid droplet micro-reactor using soybean oil and glycol as the medium	Water solubility is crucial for biological applications	Not specified
ZnO	Combined ultrasonic and microfluidic technology	Quantum yield of 64.7; increased with ultrasonic temperature	Not specified
Carbon QDs (CQDs)	Polytetrafluoroethylene microtubes with thermal decomposition	Not specified	Not specified
CQDs	Multilayer structure chip system with ascorbic acid and dimethyl sulfoxide	Diameter: 3.3 nm; quantum yield of 2.6 (moderate photoluminescence)	Precise control of the reaction process for consistent QD production
CsPbX3 Perovskite	Droplet-based microfluidic platform with online absorbance and fluorescence detection	Enabled real-time characterization, crucial for optimizing synthesis	Not specified

here summarizes key studies on microfluidic QD synthesis, highlighting the synthesis parameters, achieved properties, and potential applications.

8.3. Challenges and Limitations of Current PDMS-Based Microfluidic Systems

Microfluidic platforms face several material limitations that impact their performance and application scope. One of the most significant issues is the permeability of polydimethylsiloxane (PDMS), a commonly used material in microfluidic chip fabrication. PDMS is known for its gas permeability, which, while beneficial for specific applications like long-term cell culture, also leads to the absorption of hydrophobic small molecules. This absorption can significantly affect the accuracy of experiments, particularly in toxicity testing of environmental pollutants, as even minor absorption can alter cellular responses [119]. Additionally, PDMS’s high elasticity can lead to the deformation of microchannels, complicating fluid handling and impacting reproducibility [120]. Furthermore, its incompatibility with organic solvents can result in material leaching and absorption of hydrophobic molecules, compromising biochemical assay integrity [120]. Alternatives like polymethylmethacrylate (PMMA) and polycarbonate (PC) are used but have challenges, such as a lower fabrication resolution than PDMS and difficulties with multilayer structures due to alignment issues [121]. Thermal bonding for glass microchips is time-intensive and irreproducible, presenting further challenges for large-scale production [120]. Exploring materials like cycloolefin copolymer (COC) and polystyrene (PS) offers potential solutions to these limitations [119].

Scaling up microfluidics for quantum dot (QD) synthesis involves several design constraints. Maintaining uniform flow distribution across multiple units is critical for consistent QD quality. This is achieved by designing trunk–branch structures with larger trunk diameters to reduce flow resistance differences [122]. Narrow channels in microfluidic chips, while advantageous for specific reactions, increase fluid viscosity and hinder mixing. Transitioning to three-dimensional channel designs can improve mixing and flow rates, requiring advanced fabrication methods like femtosecond laser direct writing. Clogging, especially in solid–liquid reactions, is another issue. Specific channel geometries can facilitate solid–liquid mixture passage, addressing this challenge. Furthermore, scaling up requires precise control over reaction conditions, such as temperature and flow rates, which are challenging to maintain uniformly in larger systems. Integrating automated control systems and real-time monitoring can enhance scalability [116]. The flexibility of additive manufacturing in fabricating complex structures offers a promising pathway, although material properties must be carefully managed [122].

The costs of traditional microfluidic devices significantly impact their adoption in large-scale production. Conventional fabrication methods, such as casting PDMS or PMMA onto master molds, are labor-intensive and require skilled personnel, hindering mass production [112]. Additionally, these methods are limited in creating nonplanar structures, further complicating scaling efforts [112]. High investment costs for clean-room facilities and skilled staff exacerbate economic barriers. Moreover, the lack of a “killer application” that drives market demand further limits large-scale adoption [123]. Advancements in additive manufacturing, such as 3D printing, offer cost-efficient solutions and enable rapid prototyping, making mass production more feasible [112].

As shown in

Table 4. Challenges of current microfluidic platforms.

Challenge Type	Impact on QD Synthesis	Proposed Solutions	References
Material Limitations	Alteration of reaction conditions due to absorption, solvent incompatibility, and structural instability	Exploration of alternative materials (e.g., COC, PS) and surface modifications	[119,120,121]
Design Constraints for Scaling Up	Inconsistent QD quality, clogging, and difficulty in maintaining uniform reaction conditions	Use of trunk–branch structures, three-dimensional channel designs, and automated control systems	[116,122]
Cost Constraints	High costs of traditional methods and cleanroom facilities	Use of 3D printing to reduce costs and enable complex designs	[112,123]

, current microfluidic platforms face various challenges that hinder their effectiveness in quantum dot (QD) synthesis and broader applications. These challenges are categorized into material limitations, design constraints for scaling up, and cost constraints. Each challenge is accompanied by specific impacts on QD synthesis, such as altered reaction conditions, inconsistent product quality, or economic barriers to commercialization. Proposed solutions, including exploring alternative materials, advanced design strategies, and using cost-efficient fabrication techniques like 3D printing, are detailed alongside relevant studies addressing these issues. This comprehensive overview highlights the critical areas for innovation and improvement in microfluidic technology.

8.4. Additive-Manufactured Microfluidics

In the context of additive-manufactured microfluidics for quantum dot (QD) synthesis, several materials have been identified as particularly suitable for fabricating microfluidic devices. Due to their distinct properties, epoxy (EP) resin and acrylic–butadiene–styrene (ABS) resin are the most commonly used epoxy (EP) resins. EP resin is widely employed to create devices with precise structural features, such as inner and outer channel diameters, which are crucial for fluid control in QD synthesis. Conversely, ABS resin exhibits a larger water contact angle, making it more hydrophobic, a property beneficial for applications like fluid encapsulation [122]. Additionally, stereolithography apparatus (SLA) 3D printing technology enables the production of monolithic, multilayered microfluidic chips. This method creates complex, nonplanar structures, improving the rapid and efficient synthesis of nanoparticles, such as silver nanoparticles, that are relevant to QD synthesis [112]. These materials and methods enhance the scalability and functionality of devices used in QD synthesis, enabling precise reaction control and high-quality output.

Also, additive-manufactured microfluidics significantly improve flow dynamics and reaction control by leveraging additive manufacturing techniques. For instance, fine-tuning surface roughness in microchannels reduces flow resistance, optimizing fluid behavior. By achieving surface roughness below 200 nm, devices minimize flow rate inconsistencies [124]. Advanced fabrication methods, such as femtosecond laser micromachining, create three-dimensional structures that enhance mixing efficiency and accelerate reaction rates, addressing traditional challenges like clogging in solid–liquid systems. The integration of conductive materials, such as carbon nanofibers, enables additional functionalities like embedded electrical wiring, which is essential for complex applications [125]. These advancements allow for more efficient and scalable chemical processes.

Moreover, the transition to additive-manufactured systems offers substantial cost and environmental advantages over traditional methods, such as soft lithography. Unlike photolithography, additive manufacturing automates device fabrication, reducing production time and labor costs while enabling rapid prototyping [126]. Furthermore, additive manufacturing minimizes material waste by building structures layer by layer, contributing to sustainability. The use of thermoplastics compatible with recycling enhances environmental benefits, while cost-effective consumer-grade printers lower economic barriers [126]. The flexibility to combine materials in a single build also supports multifunctionality, reducing environmental impact.

The resolution and precision of additive manufacturing are critical in determining the quality and performance of microfluidic devices. High-resolution methods, such as stereolithography (SLA) and two-photon polymerization (2PP), produce intricate structures with fine features essential for precise fluid control [126]. However, post-curing and support removal processes in SLA can influence device quality [124]. Smooth surfaces achieved through optimized printing parameters enhance fluid dynamics, while multi-layered, high-precision designs enable complex integrations for applications such as quantum dot (QD) synthesis and diagnostics [112]. Continued advancements in materials and printing techniques push the boundaries of application-specific device fabrication.

It is now clear that the evolution of microfluidic technology has shifted from traditional fabrication techniques, such as soft lithography with PDMS, to innovative approaches like additive manufacturing. PDMS-based devices have been widely used for their flexibility, transparency, and ease of prototyping, making them a go-to choice in early microfluidic applications. However, they have notable limitations, such as difficulties creating complex three-dimensional geometries and compatibility issues with certain chemicals. In contrast, additive-manufactured microfluidic devices provide a significant advantage by enabling the fabrication of intricate three-dimensional structures directly from digital designs, offering new opportunities for advanced applications. This transition marks a significant step forward in microfluidics, redefining the balance between precision, scalability, and material versatility to meet diverse experimental and industrial needs.

Building on this progress, additively manufactured microfluidic devices have gained significant attention as an alternative to PDMS-based systems. One of the key benefits of this approach is its ability to produce three-dimensional structures that are challenging or nearly impossible to create with conventional fabrication methods, such as soft lithography. These traditional techniques are typically limited to two-dimensional structures, whereas additive manufacturing enables the construction of complex microfluidic devices from computer-assisted design (CAD) models. This capability broadens the range of applications for microfluidics by supporting more intricate device designs and advancing fluid control for various experimental setups [123,127,128].

Table 5. Comparison of additive-manufacturing methods of microfluidics.

Technique	Fundamentals	Capabilities	Strengths	Weaknesses	Source
Inkjet 3D Printing (i3DP)	i3DP uses inkjet technology to deposit material layer by layer, operating in continuous or drop-on-demand modes, with drop-on-demand preferred for better droplet control.	Capable of creating complex devices but faces challenges in removing support material from enclosed channels; decent resolution but limited by surface roughness and material availability.	Suitable for rapid prototyping; decent resolution.	Difficult to remove support material, higher costs, and surface roughness.	[129,130,131,132,133]
Stereolithography (SLA)	SLA involves the spatially controlled photopolymerization of liquid resin, using either a laser or DLP; objects are built layer by layer, with both free surface and constrained surface configurations.	Known for good resolution and ability to create transparent, biocompatible devices; limited by available resins and challenges in removing uncured resin from small channels.	Better resolution, material variety, and biocompatibility.	Limited by resin options, challenging post-processing for enclosed structures.	[134,135,136,137,138]
Two-Photon Polymerization (2PP)	2PP uses a femtosecond laser for high-resolution polymerization, enabling the creation of intricate three-dimensional microstructures within devices and achieving sub-micron precision.	It provides the highest resolution, ideal for nanoscale features; however, it is prolonged and costly, limiting its practicality for routine or large-scale fabrication.	Superior resolution; ideal for nanoscale features.	Very slow; extremely costly; requires specialized equipment; not suitable for large-scale production.	[139,140,141,142]
Extrusion Printing (FDM)	FDM extrudes thermoplastic filament through a heated nozzle layer by layer, making it widely used due to its simplicity and material versatility.	Cost-effective and compatible with mass production, but lower resolution and rough surface finishes make it less suitable for fine microfluidic work.	Cost-effective, compatible with mass production, and versatile material options.	Lower resolution, rough surfaces, limited minimum channel size, and slower than other techniques.	[143,144,145,146,147]

provides an overview of the different additive manufacturing methods, including inkjet 3D printing (i3DP), stereolithography (SLA), two-photon polymerization (2PP), and extrusion printing (FDM), comparing their strengths and limitations.

Table 5 shows that additive manufacturing techniques offer diverse capabilities for fabricating microfluidic devices, each with distinct strengths and limitations tailored to specific needs. Inkjet 3D printing (i3DP) utilizes inkjet technology to deposit material layer by layer, operating in continuous or drop-on-demand modes, with the latter providing better control over droplet placement. This method is particularly suited for rapid prototyping, allowing the efficient creation of complex designs. However, its resolution is decent rather than exceptional, and challenges arise with surface roughness and the removal of support materials, particularly in enclosed channels. Additionally, material availability can limit its use, and higher costs may be a consideration for some applications. Stereolithography (SLA) is known for its precision and the ability to produce transparent, biocompatible devices. It employs spatially controlled photopolymerization to build objects layer by layer, offering excellent resolution and compatibility with various materials. SLA is preferred for applications demanding fine structural details and optical clarity. However, the method is constrained by the limited availability of resin options and the challenges in removing uncured resin from intricate or enclosed features, which can complicate post-processing and reduce efficiency for highly complex designs. Two-photon polymerization (2PP) represents the most advanced technique in terms of resolution, achieving sub-micron precision through femtosecond laser-driven polymerization. This method enables the fabrication of intricate three-dimensional microstructures, making it ideal for nanoscale detail applications. Despite its unparalleled precision, 2PP is limited by its slow processing speed, extremely high costs, and reliance on specialized equipment. These factors make routine use or large-scale production impractical, confining its applications to specialized research or niche fields. Extrusion printing (FDM), on the other hand, stands out for its simplicity, cost-effectiveness, and versatility. By extruding thermoplastic filaments through a heated nozzle, FDM is well-suited for mass production and accommodates a wide range of materials. However, its resolution is relatively low, and the resulting rough surface finishes make it less suitable for applications demanding fine microfluidic features. Additionally, the method is limited by slower production speeds and constraints on minimum achievable channel sizes, which can impact its utility in producing highly detailed or complex microfluidic devices.

However, for high precision and nanoscale features, 2PP is unmatched, while SLA offers a balance of resolution and material variety for biomedical and optical applications. i3DP provides a flexible and rapid prototyping option, but may struggle with support material removal and surface quality. FDM is the most cost-effective and accessible, ideal for straightforward designs and large-scale production, but less capable of resolution and surface detail. These trade-offs emphasize the importance of aligning the manufacturing method with project goals, balancing cost, scalability, resolution, and material properties.

On paper, additive-manufactured microfluidics can be a good alternative to PDMS-based ones. However, is it formable? In particular, its applicability is limited in part by the technical inability to reliably print microfluidic channels with dimensions less than several hundred microns in a reasonable-sized device [148]. Are there any models in the market that can be used to form and print such a complex geometry?

Table 6. Comparison of additive-manufacturing technologies and models for microfluidic device fabrication.

Manufacturing Technology	Model/Manufacturer	Material	Resolution (x, y, z) μm	Advantages Reported	Disadvantages Reported	Application	Source
Inkjet 3D Printing (i3DP)	ProJet 3500 HD	Acrylonitrile	39 × 39 × 29	Vertically printed channels have dimensional stability and smooth surfaces.	Features along the Y-axis have rough surfaces and low dimensional accuracy.	Study of printing performance for microfluidic features.	[149]
Inkjet 3D Printing (i3DP)	ProJet 3000 HD	VisiJet M3 Polymer	38 × 38 × 32	Modular assembly and integrated microfluidic circuits.	Residual flow observed through closed interactions; limited optical properties, biocompatibility.	Fabrication of fluidic circuit components like capacitors, diodes, and transistors.	[150]
Stereolithography (SLA)	Miicraft (Taiwan)	Acrylate-based resin	56 × 56 × 50	Transparent, low-cost microfluidic chips.	It requires improvement in resin properties and hardware; coatings are needed for templates.	Gradient generation, droplet extraction, and glucose sensing.	[136,137]
Stereolithography (SLA)	Asiga PicoPlus 27	PlasCLEAR	27 × 27 × 0.25	Biocompatible microfluidic chips with <100 μm channels can be printed.	Not reported.	Fabrication of microfluidic chips for cell culturing and sensor integration.	[151]
Two-Photon Polymerization (2PP)	Ti laser (Kapteyn-Murnane)	SU-8-negative photoresist	Not reported	High-resolution and small-scale structures were fabricated.	Time-consuming for complex structures.	Fabrication of microchannels and trapping yeast cells.	[141]
Fused Deposition Modeling (FDM)	Dimension SST 768	ABS-P400	254 × 254 × 254	Variable widths are achievable in single devices at low cost.	Surface roughness affects laminar flow; there is a limited choice of polymers.	Capillary valves in centrifugal microfluidic devices.	[152]

shows various additive manufacturing technologies and the specific models used by different manufacturers for fabricating microfluidic devices. Each printer has unique advantages and limitations based on its material, resolution, and application.

For example, ProJet 3500 HD and ProJet 3000 HD, both from 3D Systems, are inkjet-based printers. The 3500 HD uses Acrylonitrile and is known for producing vertically printed microfluidic channels with good dimensional stability and smooth surfaces. However, it struggles with roughness and low dimensional accuracy along the Y-axis. It is ideal for studies focusing on printing microfluidic features. The 3000 HD, on the other hand, uses the VisiJet M3 polymer, sourced from 3D Systems, based in Rock Hill, South Carolina, United States, allowing for modular assembly and integration of microfluidic circuits. However, it faces issues like residual flow and limited optical properties, restricting its use in more precise or biocompatible applications. Miicraft (Taiwan) and Asiga PicoPlus 27 are SLA-based printers. Miicraft uses acrylate-based resin to produce transparent, low-cost microfluidic chips, but requires resin properties and hardware improvement. This printer is suited for applications like gradient generation and glucose sensing. The Asiga PicoPlus 27, using PlasCLEAR, manufactured by Asiga, located in Sydney, Australia, offers excellent biocompatibility and can print microfluidic chips with channels smaller than 100 μm, which is helpful in cell culturing and sensor integration. No disadvantages are reported for this model, making it a reliable choice for bio-related applications. Kapteyn–Murnane’s Ti laser, a two-photon polymerization system, uses SU-8-negative photoresist by Kayaku Advanced Materials, located in Westborough, Massachusetts, United States, to achieve high-resolution and fine-scale structures. While time-consuming for complex designs, it excels at fabricating microchannels and trapping cells in microfluidic devices, making it suitable for biological assays. Dimension SST 768 by Stratasys, an FDM printer, uses ABS-P400 material and was also produced by Stratasys in Eden Prairie, Minnesota, United States, and offers the flexibility of achieving variable widths at low cost. However, the surface roughness of FDM prints affects laminar flow, limiting its use in specific microfluidic applications. Despite this, it is a popular choice for fabricating capillary valves in centrifugal microfluidic devices, especially in diagnostic applications. Thus, the choice of printer largely depends on the application. For high-resolution, biocompatible microfluidic devices, models like the Asiga PicoPlus 27, sourced from Asiga, headquartered in Sydney, Australia, or Kapteyn–Murnane Ti laser manufactured by KMLabs (Kapteyn-Murnane Laboratories), located in Boulder, Colorado, United States, are preferable. ProJet and Dimension SST 768 printers offer practicality for more cost-effective and versatile solutions, though they have certain limitations in accuracy and surface quality.

The resolution capabilities of the chosen fabrication technique primarily determine the minimum achievable channel dimensions in additive-manufactured microfluidics. Two-photon polymerization (2PP) stands out for its exceptional precision, enabling the creation of sub-micron features, including channels smaller than 10 µm. However, 2PP’s application is often limited by its low throughput and higher operational costs. Stereolithography (SLA), a more accessible method, typically produces channels in the 50–100 µm range, contingent on printer specifications and resin properties. In contrast, extrusion-based techniques, such as fused deposition modeling (FDM), are generally constrained to channel sizes no smaller than several hundred microns, due to nozzle diameter limitations and material extrusion behavior. These dimensional constraints directly influence flow dynamics, mixing efficiency, and the reaction environment within microfluidic devices. Consequently, selecting an appropriate fabrication method necessitates a balance between desired resolution, throughput, and cost considerations [148].

The thermal performance of additive-manufactured microfluidic devices is intrinsically linked to the materials and fabrication techniques employed. Devices fabricated using photopolymer-based methods, such as stereolithography (SLA), typically exhibit thermal stability up to approximately 120 °C, constrained by the thermal properties of the resins used. In contrast, thermoplastics like polydimethylsiloxane (PDMS) and cyclic olefin copolymer (COC), when processed through techniques like hot embossing or injection molding, can withstand temperatures up to 200 °C, making them more suitable for applications requiring elevated temperatures. Notably, specific quantum dot (QD) synthesis processes, such as the production of CdTe quantum dots, have been successfully conducted at temperatures ranging from 70 °C to 90 °C, which are well within the operational limits of these materials. However, for high-temperature QD syntheses, such as those requiring conditions above 300 °C, alternative fabrication approaches involving high-temperature-resistant materials like glass or ceramics may be necessary. Therefore, the selection of fabrication materials and methods must be carefully aligned with the thermal requirements of the intended QD synthesis process to ensure device integrity and performance [153].

The cost-effectiveness and production capacity of additive-manufactured microfluidic systems are critical factors for their application in quantum dot (QD) synthesis. One of the key benefits of using additive manufacturing is its low fabrication cost; depending on the printer type and material, a single microfluidic device can cost anywhere from a few tens to a couple of hundred US dollars. This makes it easier to prototype and test different designs quickly, which is helpful when optimizing the synthesis process for specific QD characteristics. However, while these systems offer excellent control over reaction parameters, their small channel dimensions naturally limit the flow rate. As a result, the total output is relatively low compared to conventional batch processes. In most reported cases, QD production rates are in the range of a few milligrams per hour, which is suitable for experimental or small-scale applications but not yet ideal for industrial production. To overcome this, some researchers are exploring continuous-flow synthesis and parallelizing multiple channels within the same device to improve throughput without compromising the quality or uniformity of the quantum dots produced [116,154].

Overall, one of the core benefits of additive-manufactured microfluidic devices is the shift from labor-intensive PDMS molding to a more automated, CAD-based workflow. This enables modular design, simulation of fluid dynamics, and remote collaboration, streamlining the iterative development and testing process [138,155]. The design of additive-manufactured devices can also be tailored for specific applications, integrating advanced features such as custom valves, fluidic connectors, and interlocking components directly into the structure. This reduces assembly requirements and opens new possibilities for incorporating autonomous and embedded control mechanisms [156]. Additionally, the “additive” nature of 3D printing, where structures are formed by successive layering rather than material removal or etching, presents an eco-friendly and cost-effective option that minimizes waste and enables rapid prototyping [157]. One of the key limitations still being addressed is the resolution of these systems. For example, stereolithography (SLA) can achieve channel sizes down to around 50–100 µm, while more advanced techniques like two-photon polymerization (2PP) can create sub-micron channels. On the other hand, fused deposition modeling (FDM) is typically limited to several hundred microns due to nozzle diameter and material properties [148]. These physical constraints influence the internal flow behavior and mixing characteristics inside the device, resolving an important consideration when designing specific synthesis conditions.

Another important point is the thermal performance. While PDMS-based systems typically cap at around 120 °C, some additive-manufactured devices using thermoplastics like cyclic olefin copolymer (COC) can withstand higher temperatures, up to around 200 °C. This makes them suitable for many QD synthesis processes, especially those conducted in the 70–150 °C range. However, for reactions requiring temperatures above 300 °C, such as some hot-injection methods, high-temperature materials like glass or ceramics may still be needed [158,159]. The cost-effectiveness and production capacity of these systems are also worth mentioning. Depending on the printer and material, a single device can range from a few tens to a couple of hundred US dollars. This low cost makes rapid prototyping and iterative testing more accessible. However, the actual production yield of quantum dots is typically low, on the order of milligrams per hour, due to the limited flow rates in microchannels. This is sufficient for research and small-batch synthesis, but presents a challenge for industrial scaling. To address this, researchers are experimenting with parallelized microchannels and continuous flow systems to improve throughput while keeping the quality and uniformity of the quantum dots [159].

While promising, additive-manufactured devices still face material-related challenges, particularly in terms of biocompatibility, optical transparency, and chemical resistance. Unlike PDMS, which remains a gold standard in biological applications due to its flexibility and transparency, many printable resins still fall short in these aspects. Nevertheless, improvements in resin chemistry and the development of new formulations are actively bridging these gaps [158]. As material science advances and modular digital designs become more accepted, additive-manufactured microfluidic platforms will likely continue to gain ground, especially in academic, research, and low-volume production settings. Aligning these platforms with user-friendly interfaces and commercial standards may also enhance adoption and make advanced microfluidics more accessible to broader scientific and industrial communities [138,160].

8.5. Current Challenges and Opportunities in Additive-Manufactured Microfluidics and Quantum Dot Synthesis

Recent research shows that current additive-manufactured microfluidics face several limitations that hinder their broader application and development. A key challenge lies in the resolution of printed features. For example, the limited laser beam size in stereolithography (SLA) can restrict the production of fine details, making traditional methods, such as soft lithography, more competitive for specific high-precision applications. Additionally, the high cost of advanced 3D printers, ranging from USD 2000 to USD 10,000, limits the accessibility of experimenting with alternative materials. Using nonproprietary resins often voids warranties, further discouraging innovation [126]. Material compatibility also presents a challenge. Many photopolymers require optimization for biological applications, and some have shown toxicity in long-term studies, necessitating further research into sterilization techniques and material alternatives. The inability to print multiple materials simultaneously constrains the functionality of microfluidic devices despite progress in creating interconnects with multiple materials using commercial printers. Additionally, fabrication speed is a limitation, especially with high-resolution techniques like two-photon polymerization, which have slow build times despite their accuracy [159].

Integrating complex three-dimensional structures also remains challenging due to the technical limitations of current additive manufacturing technologies. Achieving the desired resolutions often requires combining different machines, which increases time and cost. Finally, traditional materials like polydimethylsiloxane (PDMS) are not directly printable, restricting the replication of established designs based on these materials [126]. Addressing these challenges requires advancements in resolution, material compatibility, and cost-effectiveness to unlock the full potential of additive-manufactured microfluidics in diverse applications.

Despite these challenges, additive-manufactured microfluidics have shown transformative potential in quantum dot (QD) synthesis, offering enhanced precision and scalability. Integrating additive manufacturing and microfluidic technology allows for the rapid and precise synthesis of nanoparticles, including silver nanoparticles, in under a second. This demonstrates the high-throughput potential of these systems [112]. This is particularly advantageous for QD synthesis, where uniformity in size and shape is critical for optical properties [102].

Additive-manufactured microfluidics also address the issues of uncontrolled reactions and reproducibility in traditional batch synthesis. By providing a controlled environment, they enhance reaction rates and allow precise modulation of parameters, ensuring consistent QD quality [116]. Furthermore, incorporating conductive materials, like carbon nanofibers, into printed microchannels opens applications in electronic devices and biofuel cells, where embedded wiring is essential [125]. The potential for automation and rapid prototyping in additive-manufactured systems significantly reduces production costs and time, making them attractive for large-scale applications. Additionally, advancements in real-time monitoring and control within microfluidic platforms enhance the quality and consistency of QD production, which is crucial for high-performance devices [117].

Quantum dot technology itself holds transformative potential in energy and medicine. In the energy sector, QDs are pivotal in developing solar cells with tunable band gaps, optimizing light absorption across broader spectra, and enhancing efficiency. They are also being explored to enhance charge and discharge rates in lithium-ion batteries [11]. In medicine, QDs are revolutionizing imaging and diagnostics due to their size-dependent fluorescence and high sensitivity, enabling precise detection of biological targets [161]. Moreover, their integration into lab-on-a-chip (LOC) devices could streamline synthesis and accelerate clinical translation, enabling personalized healthcare solutions [102]. Biocompatible coatings and non-toxic materials like carbon and silicon address cytotoxicity concerns, broadening QD applications in diagnostics and treatments [161].

9. Discussion and Conclusions

Quantum dots (QDs) synthesis has advanced significantly, with various methods developed to refine their unique optical and electronic properties. Each synthesis approach has specific advantages and limitations that affect the potential applications of QDs across different fields. By examining these methods closely, we can identify the technical challenges each approach presents and the broader implications for future research and industrial applications.

The hot injection (HI) method has become a foundational technique in QD synthesis due to its capacity to produce high-quality quantum dots with excellent control over size. This method’s efficacy is mainly due to the rapid nucleation process initiated by the swift injection of precursors at elevated temperatures, which results in highly uniform particle sizes and shapes. However, the HI method has notable limitations. The necessity for an inert atmosphere, typically maintained with nitrogen or argon gas, adds complexity. At the same time, the high temperatures involved increasing both energy costs and safety risks, especially when scaled up. Additionally, the rapid and precise injection timing demands sophisticated equipment and skilled operation, presenting challenges for scalability and reproducibility. Environmental concerns are also relevant, as solvents like octadecene and stabilizing agents, such as oleic acid, generate hazardous waste, requiring careful disposal protocols and strict safety standards to minimize occupational risks. In contrast, the ultrasonication-assisted method provides a more accessible alternative by removing the need for inert gas protection and high temperatures. Through ultrasonication, rapid nucleation and growth of QDs occur at lower temperatures and ambient conditions, making this synthesis approach more straightforward and cost-effective. Nonetheless, ultrasonication introduces its own set of challenges. Localized heating and cavitation effects can result in inconsistencies in particle size and distribution, and parameters such as power, frequency, and duration require meticulous optimization for reproducibility. Additionally, extended ultrasonication may induce surface defects in the QDs, impacting optical properties and lowering photoluminescence yield. Mechanical milling methods, both wet and dry, offer a straightforward and economical option for QD synthesis involving the physical breakdown of bulk materials into nanoscale particles. Wet milling uses a liquid medium to help control particle size and reduce aggregation, whereas dry milling offers simplicity by eliminating solvents. However, this simplicity comes at a cost, as milling often introduces defects and impurities that negatively affect the QDs’ optical and electronic properties. Broad size distributions are common in milled QDs, which limits their performance in applications that require precise uniformity. Additionally, contamination from milling equipment can compromise purity, an essential factor in bioimaging and optoelectronics.

The shift from batch processing to continuous flow synthesis marks a substantial improvement in QD production. Flask-based continuous flow systems enhance reproducibility and scalability by creating controlled reaction environments with consistent mixing, enabling better regulation of nucleation and growth. However, these systems demand more complex setup and operational requirements than traditional batch reactors, as they need precise control over the flow rates, temperatures, and reactant concentrations. The significant initial investment and advanced monitoring systems required for continuous flow reactors can hinder widespread adoption, particularly in settings with limited resources.

Microfluidic technology for QD synthesis, mainly through lab-on-chip (LoC) devices, represents a significant leap toward miniaturization and precision. LoC devices offer unparalleled control over reaction parameters due to their small volumes and high surface-area-to-volume ratios, promoting uniform particle formation via rapid mixing and efficient heat transfer within microchannels. Despite these advantages, LoC synthesis faces challenges with device fabrication and compatibility. Producing microfluidic devices often relies on soft lithography, which is time-consuming and requires specialized cleanroom facilities. Some materials, such as PDMS, may also be incompatible with certain solvents or reactants, potentially affecting QD stability and synthesis efficiency. Furthermore, scaling up LoC synthesis to an industrial level remains challenging due to the inherently small scale of these systems. The emergence of additive manufacturing technologies like stereolithography (SLA) and two-photon polymerization (2PP) has opened new pathways for creating intricate microfluidic devices with complex three-dimensional structures. These advanced manufacturing techniques enable precise channel designs that improve mixing, reaction control, and quality of QDs. However, high costs, material limitations, and slower fabrication speeds restrict their broader adoption. Balancing high-resolution features with cost-effectiveness is a critical challenge, and ensuring material compatibility with the chemical environments needed for QD synthesis is essential to prevent contamination or degradation.

A key challenge across all QD synthesis methods is balancing the need for precise control over QD properties with scalability, cost-efficiency, and environmental sustainability. Many synthesis techniques rely on toxic elements such as cadmium and lead, raising concerns over their environmental and health impacts. The handling and disposing of hazardous materials and chemical waste underscore the urgency of developing greener synthesis methods. Research should prioritize environmentally friendly approaches, including non-toxic, earth-abundant materials and solvents, lower energy consumption, and reduced waste. Carbon-based QDs and bio-based solvents offer promising alternatives to hazardous materials, contributing to a more sustainable approach. Bridging the gap between lab-scale synthesis and industrial production also requires addressing issues related to reaction kinetics, heat transfer, and mixing efficiency at larger scales. Continuous flow reactors and automated microfluidic systems hold potential for industrial QD production, yet they need further optimization and cost reduction. Innovations in materials, such as indium phosphide (InP) as a less toxic alternative to cadmium-based QDs and advancements in perovskite QDs with exceptional optical properties, illustrate the potential for material innovation to improve performance while reducing toxicity. Efforts to improve QD stability and functionality through surface modification are critical, with effective passivation strategies reducing surface defects, enhancing quantum yield, and enabling bioconjugation for biomedical applications. As QD synthesis converges with advanced manufacturing techniques like additive manufacturing, we may see new possibilities for large-scale, cost-effective fabrication of QD-based devices, particularly in fields such as optoelectronics and photovoltaics. Regulatory frameworks and safety standards are essential to guide the transition of QDs from research settings to commercial applications, ensuring safe and sustainable production practices.

After all, advancements in QD synthesis will depend on cross-disciplinary collaboration among chemists, materials scientists, engineers, and environmental scientists. Such multidisciplinary efforts are vital to accelerate the development of innovative synthesis methods and the discovery of new applications, pushing the boundaries of what can be achieved with quantum dots in scientific and industrial fields.

In conclusion, the properties of quantum dots are affected but their size, which is determined during their synthesis. Over the past years, various methods have been developed to produce efficient quantum dots for the intended application. Each of these methods has its pros and cons. For example, processes like hot injection and ultrasonication-assisted synthesis allow for precise control over the size and quality of quantum dots, while approaches such as wet and dry milling offer more straightforward and more cost-effective alternatives but sacrifice an amount of the product quality.

The integration of lab-on-chip and microfluidic devices shows a huge advancement in the quantum dot synthesis field. These methods allow for rapid, consistent, controlled synthesis. At the same time, it minimizes waste and effort. Its most advantageous point is control over the synthesis process. As a result, they are highly promising for large-scale production where precision and efficiency are critical. Quantum dots are already causing a revolutionary and significant impact in different applications and fields, such as improving the performance of solar panels, LEDs, and display systems, supporting imaging techniques in the medical field. Their ability to emit different light colors based on size is particularly valuable in display technologies and bioimaging. Moreover, quantum dots have also been studied for their potential applications in environmental sensing, as they can detect pollutants with high precision and efficiency.

As more studies are conducted, this field will continue to evolve, revealing much more potential for these materials than expected. However, there are challenges that still need to be overcome, such as making synthesis methods more scalable, cost-effective, and straightforward, while also reducing any negative environmental impact. Therefore, continued research, experiments, and developments in this field are important to reveal the full potential of quantum dots and drive future technological breakthroughs.