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Facile large-scale synthesis of mesoporous silica nanoparticles at room temperature in a monophasic system with fine size control
Microporous and Mesoporous Materials 288 (2019) 109595
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Microporous and Mesoporous Materials journal homepage: www.elsevier.com/locate/micromeso
Facile large-scale synthesis of mesoporous silica nanoparticles at room temperature in a monophasic system with fine size control
T
Chansong Kima,1, Seokyoung Yoonb,1, Jung Heon Leea,b,c,* a
School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon-si, Gyeonggi-do, 16419, Republic of Korea SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University (SKKU), Suwon-si, Gyeonggi-do, 16419, Republic of Korea c Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon-si, Gyeonggi-do, 16419, Republic of Korea b
A R T I C LE I N FO
A B S T R A C T
Keywords: Large-scale synthesis Nanoscale tunability Mesoporous silica nanoparticle Stöber method Continuous-injection-based monophasic liquid (CIMPL) process
Mesoporous silica nanoparticles (MSNs) are generally synthesized using a biphasic system at high temperature. However, this method requires a time-consuming washing process and hinders large-scale synthesis because of difficulty in controlling the thermal homogeneity. We demonstrate a strategy to synthesize MSNs in a facile manner through a continuous-injection-based monophasic liquid process, modified from the Stöber method, by using a constant silica source injection system in a monophasic environment without heating. We could not only increase the amount of synthesized particles up to gram-scale by simply increasing the volume of the reaction but also obtain MSNs that had intact spherical structures, were controllable in size, and were well dispersed in an aqueous solution with a narrow size distribution. Using this synthesis method, we also prove the influence of various factors affecting the size, structure, and discreteness of the MSNs. As our study presents a straightforward and highly reproducible method for large-scale synthesis of MSNs and, more importantly, demonstrates its detailed mechanism, we expect that this work will provide guidance for highly efficient large-scale synthesis of various porous nanomaterials with high monodispersity, which is critical for the practical use of nanomaterials in diverse areas.
1. Introduction Mesoporous materials are a class of materials containing pores with diameters between 2 and 50 nm. Due to the large quantities of internal pores, the surface area of mesoporous materials is significantly larger than that of dense materials; these unique characteristics offer opportunities to develop interesting applications in new directions [1–4]. In particular, mesoporous silica nanoparticles (MSNs) possess not only general characteristics of mesoporous structures but also have the advantages of high biocompatibility, feasibility of surface modification, and capability to load drugs, genes, and diverse chemicals, [5–7]; therefore, they have been widely used in versatile applications such as biological adhesives [8], catalysts [9–11], drug delivery systems [12,13], separation systems [14,15], cosmetics [16], and imaging agents [17]. It is well known that small MSNs (less than 100 nm in size) have advantages over larger MSNs for biological uses, as the small MSNs are taken up easily by cells through an endocytosis pathway [18,19].
Furthermore, when small MSNs are injected into a human body, they demonstrate longer blood circulation time. Thus, small MSNs are more likely to be concentrated in tumor tissues through an enhanced permeability and retention effect [20]. Therefore, it is important to synthesize small MSNs with high monodispersity and narrow size distribution. Tetraethyl orthosilicate (TEOS) is generally used as a silica source to prepare MSNs based on the Stöber method [21]. However, TEOS not only has low solubility in aqueous solutions but also alters the pH as it generates silicic acid after hydrolysis. As the pH affects the rates of hydrolysis and condensation of the silica source, it is one of the most important factors determining the size and shape of MSNs synthesized through the sol-gel method [22]. Thus, MSNs are generally synthesized using a biphasic system by mixing TEOS with an organic (usually nonpolar) solvent, where the silica source can be dissolved into the organic solvent and diffused into the aqueous phase constantly with minimal pH variation (Fig. S1) [23–25]. However, these organic solvents can increase the cost of industrial production of MSNs because they are
*
Corresponding author. School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon-si, Gyeonggi-do, 16419, Republic of Korea. E-mail address: [email protected] (J.H. Lee). 1 These authors contributed equally to this work. https://doi.org/10.1016/j.micromeso.2019.109595 Received 5 June 2019; Received in revised form 2 July 2019; Accepted 5 July 2019 Available online 06 July 2019 1387-1811/ © 2019 Elsevier Inc. All rights reserved.
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for the synthesis of MSNs with different is summarized in Table S1. To remove CTAB from lyophilized MSN pores through the thermal method, the lyophilized particles were calcined for 3 h at 600 °C after heating with 10 °C/min increment followed by cooling down to room temperature naturally.
expensive and require rigorous washing to remove organic chemicals after the reaction; moreover, these solvents may adversely affect the environment owing to their virulent nature [26,27]. To produce large quantities of MSNs, it is necessary to increase the reaction volume. Furthermore, to accelerate the kinetics of diffusion of the silica source to the aqueous phase, it is essential to synthesize MSNs in high-temperature environments. However, MSNs synthesized via a heating process often have a broad size distribution and large amounts of impurities because of the difficulty in controlling the thermal homogeneity of the entire reaction solution [28]. Thus, many previous studies reporting the synthesis of nanoparticles through heating could not avoid these critical issues; consequently, the scale of the reaction volume, the production yield, and the quality of the synthesized nanoparticles were limited [29,30]. To address these problems, some studies proposed the synthesis of MSNs at room temperature. However, in most cases, the resulting nanoparticles have the limitations of a relatively large size [31,32], wide size distributions, and incomplete structures [33]. Herein, we propose a novel method for the large-scale synthesis of monodisperse small MSNs with a fine size distribution at room temperature (27 °C). This simple method is based on an aqueous process, requiring only a surfactant for the formation of micellar templates, a silica source, and a basic catalyst. To add TEOS into the reaction solution constantly, we employed a syringe pump in a monophasic system, rather than applying external heat in a biphasic system. The synthesized MSNs were produced in gram-scale, had intact spherical structures, were controllable in size, and were well dispersed in the aqueous solution with a narrow size distribution.
2.3. Calculation of synthetic yield of MSNs To compute the synthetic yield, the dried MSNs were calcined and weighed. To calculate the synthetic yield much more precisely, we also weighed the mass of MSNs in 1 mL of the solution after washing the resultant MSNs five times with ethanol to completely remove CTAB from inside the particles and evaporated the solvent. Based on the mass of MSNs in 1 mL of the solutions, the mass and synthetic yield of the resultant MSNs in total solution were calculated by multiplying the volume of the reaction solution. 2.4. Characterization
2. Experimental
To confirm surface morphologies of the MSNs, field emission scanning electron microscopy (FE-SEM; JEOL JSM-7600F) was used. TEM images were obtained using the JEM-2100F instrument (JEOL) operating at 200 kV. A Nano ZS90 system (Malvern) was utilized for the zeta potential and hydrodynamic size measurements. The Brunauer–Emmett–Teller (BET) and Barrett–Joyner–Halenda (BJH) analyses were carried out to measure the surface area and pore diameter of MSNs using TriStar Ⅱ 3020 (Micromeritics), respectively. BET and BJH measurements were carried out by inserting N2 gas through the vacuum port and monitoring the gas adsorbed on the nanoparticles’ surface with 10.0 mg of MSNs after drying for 12 h at 300 °C.
2.1. Materials and reagents
3. Results and discussion
Cetyltrimethylammonium bromide (CTAB) (98%, Sigma-Aldrich), sodium hydroxide (NaOH) (98%, Samchun), methanol (99.8%, Samchun), and TEOS (99%, Sigma-Aldrich) were used for the synthesis of MSNs. Deionized water (18.2 MΩ cm) was prepared using a Sartorius Arium®Pro Ultrapure water system and was used for experiments. All the reagents were used without further purification. Every glassware was cleaned using NaOH solution and aqua regia before use. Special care must be taken when researchers handle high concentration of NaOH solution and aqua regia.
Scheme 1 shows the CIMPL process used to synthesize MSNs at room temperature. CTAB was used to form micelles, which work as templates for the formation of a mesoporous structures in an aqueous solution, and NaOH was used to induce a basic reaction condition [30,34]. We injected TEOS solution as a silica source into the reaction system at a constant rate using a syringe pump system to avoid using an organic solvent and to synthesize MSNs without heating. After the optimization of the experimental conditions, we obtained MSNs in various sizes ranging from 15 to 56 nm with high monodispersity by regulating the experimental conditions. We denoted MSNs of sizes 56.0 ± 2.4, 45.4 ± 2.3, 37.4 ± 3.3, 22.9 ± 1.9, and 15.5 ± 1.4 nm as MSN50, MSN40, MSN30, MSN20, and MSN10, respectively (Fig. 1a–c and S2). The effect of each component affecting the size, structure, and discreteness of the resultant nanoparticles is described in the latter part of this paper. The synthesized MSNs have mesoporous structures with pores exposed toward the external surface. This shows that the pores of MSNs have access to the external environment. In addition, the pores of MSNs were slightly disordered because of the use of alcohol as a co-solvent for TEOS injection
2.2. Synthesis of MSNs The MSNs were synthesized through a continuous-injection-based monophasic liquid (CIMPL) process, modified from the Stöber method, by using a constant silica source injection system through a syringe pump system. For example, to synthesize 37.4 ± 3.3 nm of MSNs (MSN30), 5.0 mM CTAB, 100 mM NaOH aqueous solutions, and 20% (v/ v) TEOS in methanol solution were used. To describe the steps in detail, 10 mL of CTAB solution was vigorously stirred for 30 min after introducing 170 μL of NaOH stock solution to induce a basic reaction condition. Then, a syringe pump system was used to inject TEOS into the reaction solution continuously at constant rates. A total of 1.0 mL of TEOS solution was injected through a microbore tubing connected to the reaction chamber using the syringe pump at a 20 μL/h rate. Few hours later, the color of the solution turned to white and became turbid, indicating the successful formation of MSNs. After the TEOS solution was introduced into the reaction system, further reaction was proceeded for 24 h with stirring. Finally, the reaction solution was centrifuged at 18,000 rcf for 20 min, washed with ethanol two times, and lyophilized overnight to collect MSNs. To increase the mass of resultant particles to gram-scale, both the volume of all chemicals for synthesis and TEOS injection rate were simply increased three hundredfold under constant concentration of reagent conditions. The reaction requirement
Scheme 1. Schematic of CIMPL process for the synthesis of MSNs at room temperature. 2
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Fig. 1. Images of MSNs synthesized through the CIMPL process. Transmission electron microscopy (TEM) images of (a) MSNs synthesized under different conditions (scale bar: 100 nm), and (b) enlarged them (scale bar: 10 nm). (c) Average diameter of each MSNs, and (d) picture of MSN30 synthesized in small-scale after CTAB extraction. (e) TEM image of MSNs synthesized in large-scale (scale bar: 100 nm).
micellar templates (Fig. 2b and c) [37]. Furthermore, this value of surface area is much larger than that of non-porous silica nanoparticles and is similar to those of MSNs synthesized through other methods reported in previous works [8,29,30,34]. The zeta potential of MSNs shows a positive surface charge, because the negative charge of the silanol group was not sufficiently strong to compensate the positive charge of CTAB (38.1 mV) [38]. Subsequently, we investigated the role of three major factors affecting the size, structure, and discreteness of MSNs: TEOS injection rate, concentration of CTAB, and the volume of the injected NaOH stock solution (pH of the reaction system) into the reaction system (Fig. 3 and S3). We also verified the effect of the concentration of TEOS using a TEOS solution diluted in different ratios and suggested that the concentration of TEOS also affects the final structure of the MSNs. Therefore, the concentration of TEOS solution was fixed after optimization. The effect of TEOS injection rate on the size and distribution of MSNs was explained through the modified LaMer diagram (Fig. 4) [39,40]. As the TEOS injection rate was increased, MSNs became smaller because the fast injection of TEOS significantly increased the concentration of hydrolyzed TEOS beyond homogeneous nucleation level (Chom) and produced a large number of initial nuclei required to form MSNs (Fig. 4a). When the silica source was fully injected in a very short time (one-shot injection), polydisperse MSNs were synthesized (Fig. 3a one-shot). As the amount of hydrolyzed TEOS is extremely high
(Fig. 1b). The short-chain alcohol tends to disrupt the structural order of the mesoporous phase under a low surfactant concentration condition [30,35]. We could obtain 44.4 mg of MSNs through a single synthesis process after drying (Fig. 1d). Furthermore, by simply increasing the reaction volume three hundredfold, monodisperse and discrete MSNs were successfully obtained in gram-scale (16.4 g), which was three hundredfold mass compared to that of MSNs synthesized in small-scale (Fig. 1e and S3). We also calculated the synthetic yield of MSNs obtained through both in small and large-scale syntheses (See Supplementary Information for calculation method), and we concluded that if this CIMPL process is used for MSN synthesis, we can increase the mass of resultant MSNs with constant yield (~29%) (Tables S2 and S3). To precisely analyze the porosity of MSNs prepared by large-scale synthesis, the organic components physically adsorbed on the surface of MSNs were removed through calcination. The mass composition of MSNs was evaluated using thermogravimetric analysis (TGA) under air condition. The weight decrease up to 100 °C indicates water evaporation, whereas the subsequent decrease beyond 200 °C indicates the removal of CTAB (Fig. 2a) [36]. After complete removal of the adsorbed organic components, the specific surface area and pore size distribution of the MSNs were measured using the BET and BJH methods, respectively. The particles had a large surface area (~550 m2/g) with pores of size 3.6 nm, which corresponds to the size of a CTAB micelle. This indicates that the mesoporous structure of MSNs was formed on the CTAB
Fig. 2. TGA and BET measurements of MSNs synthesized via the CIMPL process. (a) TGA curve of MSNs synthesized in large-scale, (b) nitrogen adsorption-desorption isotherms, and (c) the corresponding pore size distribution of MSNs. 3
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Fig. 3. TEM images of MSNs prepared under different (a) TEOS injection rates, (b) CTAB concentrations, and (c) NaOH volume conditions. Scale bar: 100 nm.
pH of the solution was extremely high (Fig. 3c NaOH 340 μL and S6), we found the chain-like structures resulted from the depletion of CTAB by measuring the zeta potential of MSNs (Table S4). The depletion of CTAB was attributed to the fast reaction rate and large amount of nucleus, which resulted in the lack of CTAB share per MSN. Finally, when TEOS was fully introduced into the reaction solution instantly (Fig. 3a one-shot) or the volume of the injected NaOH stock solution was very low (Fig. 3c NaOH 5 μL), hollow shell structures were commonly observed. As this synthetic reaction of MSNs was performed under a dynamic and complicated condition, where the parameters affecting the synthesis of MSNs, such as the pH and concentrations of CTAB, TEOS, and alcohol were varied continuously, the detailed formation mechanism of the mesoporous hollow shells is unclear. The concentrations of free CTAB and hydrolyzed TEOS decreased as the reaction proceeded because they were consumed for the generation of MSNs. In the case of one-shot injection, a large amount of TEOS was abruptly hydrolyzed, resulting in the sudden generation of a large amount of silicic acid and a decrease in pH [41]. As the structure of a CTAB micelle depends on the reaction condition [42,43], similar large micellar templates can be formed in the presence of methanol under both one-shot TEOS injection and NaOH deficient conditions [44]. These large CTAB structures eventually result in the formation of hollow mesoporous silica shells (Fig. S5). Besides, when the TEOS solution was introduced into the reaction system, emulsions were formed in the aqueous reaction solution because of the non-polar properties of TEOS molecules. Once the amount of the NaOH became too low to
under this condition, the concentration of hydrolyzed TEOS remains significantly higher than Chom for a certain duration, which induces multiple nucleation (Fig. 4b). The concentration of CTAB exerted an influence on the morphology and discreteness of MSNs. As the surfactant works not only as a soft template but also as an MSN stabilizer, the MSNs containing sufficient amount of CTAB will have enough electrostatic repulsion applied between them, resulting in discrete MSNs. Therefore, under the surfactant deficient conditions, the surface charge of MSNs will be decreased (Table S4). If the concentration of CTAB decreases, the electrostatic repulsive force between the initial nuclei will not be sufficiently strong for good dispersion in the reaction solution, resulting in chain-like silica structures. The silica chain became thicker and longer as the concentration of CTAB decreased (Fig. 3b CTAB 0.1–2.5 mM). When the surfactant concentration in the solution was extremely low (Fig. 3b CTAB 0.1–0.5 mM), very small (~15 nm) and non-porous (dense) silica nanoparticles were also formed. This might have been due to the consumption of most of the free surfactants to build chain-like structures, resulting in the formation of small and dense silica nanoparticles owing to the lack of CTAB micellar templates. Moreover, the volume of the injected NaOH stock solution affects the structures of MSNs. The hydrolysis and condensation rates of the silica source are highly dependent on the pH, which, consequently, significantly affects the final shape of the nanoparticles [22]. In this study, the synthesized MSNs had rough surfaces at low pH and became smooth and spherical as the pH increased (Fig. 3c). However, when the
Fig. 4. Schematic of the kinetics of the synthesis of MSNs for (a) TEOS injection rate (continuous injection) and (b) injection types. Csol and Chom represent the solubility and homogeneous nucleation concentration, respectively. 4
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effectively proceed the sol-gel reaction (Fig. 3c NaOH 5 μL), the silica formation reaction could occur only on the surface of the emulsions, leading to hollow silica structures [38,45]. These results show that this CIMPL method allows us to tune the reaction kinetics by injecting a silica source into the reaction system slowly in a controlled manner and have much more freedom and control in MSN synthesis in comparison to previously reported methods.
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4. Conclusions We successfully synthesized discrete and monodisperse MSNs at a large scale using the CIMPL process at room temperature and demonstrated the role of each major factor that affects the size, shape, and discreteness of MSNs. We observed that the TEOS injection rate and the pH of the synthesis solution determine the size and structure of the MSNs, respectively, because they lead to different amounts of hydrolyzed TEOS and free surfactant along with varied reaction rates. In addition, the variation in the concentration of CTAB resulted in different repulsive forces between individual nuclei, affecting the size and discreteness of the MSNs. Finally, we successfully controlled the size of MSNs on the scale of 10 nm by systematically modulating the CTAB concentration, pH of the reaction solution, TEOS injection rate, and TEOS concentration and prepared highly monodisperse and discrete MSNs in gram-scale by simply increasing the reaction volume. As demonstrated, understanding the role of these individual factors is important as these results can be adapted for the synthesis of other mesoporous particles with complex shapes. Finally, as the CIMPL process is straightforward and highly reproducible for the synthesis of MSNs in large quantities, we expect that this method will provide a new guidance for highly efficient large-scale synthesis of various porous nanoparticles with high monodispersity. Considering the importance of large-scale synthesis of mesoporous nanomaterials with high monodispersity in industries, this method can bring a significant impact in many fields including cosmetic, biomedical, sensing, and catalytic areas. Notes The authors declare no competing financial interests. Acknowledgements This research was supported by the grant of National Research Foundation of Korea funded by the Ministry of Science and ICT for Bioinspired Innovation Technology Development Project (NRF2018M3C1B7021997) and the grant supported by Korea Electric Power Corporation (Grant number: R18XA02). Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.micromeso.2019.109595. References [1] B.P. Bastakoti, S. Ishihara, S.-Y. Leo, K. Ariga, K.C.W. Wu, Y. Yamauchi, Langmuir
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Contents lists available at ScienceDirect
Microporous and Mesoporous Materials journal homepage: www.elsevier.com/locate/micromeso
Facile large-scale synthesis of mesoporous silica nanoparticles at room temperature in a monophasic system with fine size control
T
Chansong Kima,1, Seokyoung Yoonb,1, Jung Heon Leea,b,c,* a
School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon-si, Gyeonggi-do, 16419, Republic of Korea SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University (SKKU), Suwon-si, Gyeonggi-do, 16419, Republic of Korea c Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon-si, Gyeonggi-do, 16419, Republic of Korea b
A R T I C LE I N FO
A B S T R A C T
Keywords: Large-scale synthesis Nanoscale tunability Mesoporous silica nanoparticle Stöber method Continuous-injection-based monophasic liquid (CIMPL) process
Mesoporous silica nanoparticles (MSNs) are generally synthesized using a biphasic system at high temperature. However, this method requires a time-consuming washing process and hinders large-scale synthesis because of difficulty in controlling the thermal homogeneity. We demonstrate a strategy to synthesize MSNs in a facile manner through a continuous-injection-based monophasic liquid process, modified from the Stöber method, by using a constant silica source injection system in a monophasic environment without heating. We could not only increase the amount of synthesized particles up to gram-scale by simply increasing the volume of the reaction but also obtain MSNs that had intact spherical structures, were controllable in size, and were well dispersed in an aqueous solution with a narrow size distribution. Using this synthesis method, we also prove the influence of various factors affecting the size, structure, and discreteness of the MSNs. As our study presents a straightforward and highly reproducible method for large-scale synthesis of MSNs and, more importantly, demonstrates its detailed mechanism, we expect that this work will provide guidance for highly efficient large-scale synthesis of various porous nanomaterials with high monodispersity, which is critical for the practical use of nanomaterials in diverse areas.
1. Introduction Mesoporous materials are a class of materials containing pores with diameters between 2 and 50 nm. Due to the large quantities of internal pores, the surface area of mesoporous materials is significantly larger than that of dense materials; these unique characteristics offer opportunities to develop interesting applications in new directions [1–4]. In particular, mesoporous silica nanoparticles (MSNs) possess not only general characteristics of mesoporous structures but also have the advantages of high biocompatibility, feasibility of surface modification, and capability to load drugs, genes, and diverse chemicals, [5–7]; therefore, they have been widely used in versatile applications such as biological adhesives [8], catalysts [9–11], drug delivery systems [12,13], separation systems [14,15], cosmetics [16], and imaging agents [17]. It is well known that small MSNs (less than 100 nm in size) have advantages over larger MSNs for biological uses, as the small MSNs are taken up easily by cells through an endocytosis pathway [18,19].
Furthermore, when small MSNs are injected into a human body, they demonstrate longer blood circulation time. Thus, small MSNs are more likely to be concentrated in tumor tissues through an enhanced permeability and retention effect [20]. Therefore, it is important to synthesize small MSNs with high monodispersity and narrow size distribution. Tetraethyl orthosilicate (TEOS) is generally used as a silica source to prepare MSNs based on the Stöber method [21]. However, TEOS not only has low solubility in aqueous solutions but also alters the pH as it generates silicic acid after hydrolysis. As the pH affects the rates of hydrolysis and condensation of the silica source, it is one of the most important factors determining the size and shape of MSNs synthesized through the sol-gel method [22]. Thus, MSNs are generally synthesized using a biphasic system by mixing TEOS with an organic (usually nonpolar) solvent, where the silica source can be dissolved into the organic solvent and diffused into the aqueous phase constantly with minimal pH variation (Fig. S1) [23–25]. However, these organic solvents can increase the cost of industrial production of MSNs because they are
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Corresponding author. School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon-si, Gyeonggi-do, 16419, Republic of Korea. E-mail address: [email protected] (J.H. Lee). 1 These authors contributed equally to this work. https://doi.org/10.1016/j.micromeso.2019.109595 Received 5 June 2019; Received in revised form 2 July 2019; Accepted 5 July 2019 Available online 06 July 2019 1387-1811/ © 2019 Elsevier Inc. All rights reserved.
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for the synthesis of MSNs with different is summarized in Table S1. To remove CTAB from lyophilized MSN pores through the thermal method, the lyophilized particles were calcined for 3 h at 600 °C after heating with 10 °C/min increment followed by cooling down to room temperature naturally.
expensive and require rigorous washing to remove organic chemicals after the reaction; moreover, these solvents may adversely affect the environment owing to their virulent nature [26,27]. To produce large quantities of MSNs, it is necessary to increase the reaction volume. Furthermore, to accelerate the kinetics of diffusion of the silica source to the aqueous phase, it is essential to synthesize MSNs in high-temperature environments. However, MSNs synthesized via a heating process often have a broad size distribution and large amounts of impurities because of the difficulty in controlling the thermal homogeneity of the entire reaction solution [28]. Thus, many previous studies reporting the synthesis of nanoparticles through heating could not avoid these critical issues; consequently, the scale of the reaction volume, the production yield, and the quality of the synthesized nanoparticles were limited [29,30]. To address these problems, some studies proposed the synthesis of MSNs at room temperature. However, in most cases, the resulting nanoparticles have the limitations of a relatively large size [31,32], wide size distributions, and incomplete structures [33]. Herein, we propose a novel method for the large-scale synthesis of monodisperse small MSNs with a fine size distribution at room temperature (27 °C). This simple method is based on an aqueous process, requiring only a surfactant for the formation of micellar templates, a silica source, and a basic catalyst. To add TEOS into the reaction solution constantly, we employed a syringe pump in a monophasic system, rather than applying external heat in a biphasic system. The synthesized MSNs were produced in gram-scale, had intact spherical structures, were controllable in size, and were well dispersed in the aqueous solution with a narrow size distribution.
2.3. Calculation of synthetic yield of MSNs To compute the synthetic yield, the dried MSNs were calcined and weighed. To calculate the synthetic yield much more precisely, we also weighed the mass of MSNs in 1 mL of the solution after washing the resultant MSNs five times with ethanol to completely remove CTAB from inside the particles and evaporated the solvent. Based on the mass of MSNs in 1 mL of the solutions, the mass and synthetic yield of the resultant MSNs in total solution were calculated by multiplying the volume of the reaction solution. 2.4. Characterization
2. Experimental
To confirm surface morphologies of the MSNs, field emission scanning electron microscopy (FE-SEM; JEOL JSM-7600F) was used. TEM images were obtained using the JEM-2100F instrument (JEOL) operating at 200 kV. A Nano ZS90 system (Malvern) was utilized for the zeta potential and hydrodynamic size measurements. The Brunauer–Emmett–Teller (BET) and Barrett–Joyner–Halenda (BJH) analyses were carried out to measure the surface area and pore diameter of MSNs using TriStar Ⅱ 3020 (Micromeritics), respectively. BET and BJH measurements were carried out by inserting N2 gas through the vacuum port and monitoring the gas adsorbed on the nanoparticles’ surface with 10.0 mg of MSNs after drying for 12 h at 300 °C.
2.1. Materials and reagents
3. Results and discussion
Cetyltrimethylammonium bromide (CTAB) (98%, Sigma-Aldrich), sodium hydroxide (NaOH) (98%, Samchun), methanol (99.8%, Samchun), and TEOS (99%, Sigma-Aldrich) were used for the synthesis of MSNs. Deionized water (18.2 MΩ cm) was prepared using a Sartorius Arium®Pro Ultrapure water system and was used for experiments. All the reagents were used without further purification. Every glassware was cleaned using NaOH solution and aqua regia before use. Special care must be taken when researchers handle high concentration of NaOH solution and aqua regia.
Scheme 1 shows the CIMPL process used to synthesize MSNs at room temperature. CTAB was used to form micelles, which work as templates for the formation of a mesoporous structures in an aqueous solution, and NaOH was used to induce a basic reaction condition [30,34]. We injected TEOS solution as a silica source into the reaction system at a constant rate using a syringe pump system to avoid using an organic solvent and to synthesize MSNs without heating. After the optimization of the experimental conditions, we obtained MSNs in various sizes ranging from 15 to 56 nm with high monodispersity by regulating the experimental conditions. We denoted MSNs of sizes 56.0 ± 2.4, 45.4 ± 2.3, 37.4 ± 3.3, 22.9 ± 1.9, and 15.5 ± 1.4 nm as MSN50, MSN40, MSN30, MSN20, and MSN10, respectively (Fig. 1a–c and S2). The effect of each component affecting the size, structure, and discreteness of the resultant nanoparticles is described in the latter part of this paper. The synthesized MSNs have mesoporous structures with pores exposed toward the external surface. This shows that the pores of MSNs have access to the external environment. In addition, the pores of MSNs were slightly disordered because of the use of alcohol as a co-solvent for TEOS injection
2.2. Synthesis of MSNs The MSNs were synthesized through a continuous-injection-based monophasic liquid (CIMPL) process, modified from the Stöber method, by using a constant silica source injection system through a syringe pump system. For example, to synthesize 37.4 ± 3.3 nm of MSNs (MSN30), 5.0 mM CTAB, 100 mM NaOH aqueous solutions, and 20% (v/ v) TEOS in methanol solution were used. To describe the steps in detail, 10 mL of CTAB solution was vigorously stirred for 30 min after introducing 170 μL of NaOH stock solution to induce a basic reaction condition. Then, a syringe pump system was used to inject TEOS into the reaction solution continuously at constant rates. A total of 1.0 mL of TEOS solution was injected through a microbore tubing connected to the reaction chamber using the syringe pump at a 20 μL/h rate. Few hours later, the color of the solution turned to white and became turbid, indicating the successful formation of MSNs. After the TEOS solution was introduced into the reaction system, further reaction was proceeded for 24 h with stirring. Finally, the reaction solution was centrifuged at 18,000 rcf for 20 min, washed with ethanol two times, and lyophilized overnight to collect MSNs. To increase the mass of resultant particles to gram-scale, both the volume of all chemicals for synthesis and TEOS injection rate were simply increased three hundredfold under constant concentration of reagent conditions. The reaction requirement
Scheme 1. Schematic of CIMPL process for the synthesis of MSNs at room temperature. 2
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Fig. 1. Images of MSNs synthesized through the CIMPL process. Transmission electron microscopy (TEM) images of (a) MSNs synthesized under different conditions (scale bar: 100 nm), and (b) enlarged them (scale bar: 10 nm). (c) Average diameter of each MSNs, and (d) picture of MSN30 synthesized in small-scale after CTAB extraction. (e) TEM image of MSNs synthesized in large-scale (scale bar: 100 nm).
micellar templates (Fig. 2b and c) [37]. Furthermore, this value of surface area is much larger than that of non-porous silica nanoparticles and is similar to those of MSNs synthesized through other methods reported in previous works [8,29,30,34]. The zeta potential of MSNs shows a positive surface charge, because the negative charge of the silanol group was not sufficiently strong to compensate the positive charge of CTAB (38.1 mV) [38]. Subsequently, we investigated the role of three major factors affecting the size, structure, and discreteness of MSNs: TEOS injection rate, concentration of CTAB, and the volume of the injected NaOH stock solution (pH of the reaction system) into the reaction system (Fig. 3 and S3). We also verified the effect of the concentration of TEOS using a TEOS solution diluted in different ratios and suggested that the concentration of TEOS also affects the final structure of the MSNs. Therefore, the concentration of TEOS solution was fixed after optimization. The effect of TEOS injection rate on the size and distribution of MSNs was explained through the modified LaMer diagram (Fig. 4) [39,40]. As the TEOS injection rate was increased, MSNs became smaller because the fast injection of TEOS significantly increased the concentration of hydrolyzed TEOS beyond homogeneous nucleation level (Chom) and produced a large number of initial nuclei required to form MSNs (Fig. 4a). When the silica source was fully injected in a very short time (one-shot injection), polydisperse MSNs were synthesized (Fig. 3a one-shot). As the amount of hydrolyzed TEOS is extremely high
(Fig. 1b). The short-chain alcohol tends to disrupt the structural order of the mesoporous phase under a low surfactant concentration condition [30,35]. We could obtain 44.4 mg of MSNs through a single synthesis process after drying (Fig. 1d). Furthermore, by simply increasing the reaction volume three hundredfold, monodisperse and discrete MSNs were successfully obtained in gram-scale (16.4 g), which was three hundredfold mass compared to that of MSNs synthesized in small-scale (Fig. 1e and S3). We also calculated the synthetic yield of MSNs obtained through both in small and large-scale syntheses (See Supplementary Information for calculation method), and we concluded that if this CIMPL process is used for MSN synthesis, we can increase the mass of resultant MSNs with constant yield (~29%) (Tables S2 and S3). To precisely analyze the porosity of MSNs prepared by large-scale synthesis, the organic components physically adsorbed on the surface of MSNs were removed through calcination. The mass composition of MSNs was evaluated using thermogravimetric analysis (TGA) under air condition. The weight decrease up to 100 °C indicates water evaporation, whereas the subsequent decrease beyond 200 °C indicates the removal of CTAB (Fig. 2a) [36]. After complete removal of the adsorbed organic components, the specific surface area and pore size distribution of the MSNs were measured using the BET and BJH methods, respectively. The particles had a large surface area (~550 m2/g) with pores of size 3.6 nm, which corresponds to the size of a CTAB micelle. This indicates that the mesoporous structure of MSNs was formed on the CTAB
Fig. 2. TGA and BET measurements of MSNs synthesized via the CIMPL process. (a) TGA curve of MSNs synthesized in large-scale, (b) nitrogen adsorption-desorption isotherms, and (c) the corresponding pore size distribution of MSNs. 3
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Fig. 3. TEM images of MSNs prepared under different (a) TEOS injection rates, (b) CTAB concentrations, and (c) NaOH volume conditions. Scale bar: 100 nm.
pH of the solution was extremely high (Fig. 3c NaOH 340 μL and S6), we found the chain-like structures resulted from the depletion of CTAB by measuring the zeta potential of MSNs (Table S4). The depletion of CTAB was attributed to the fast reaction rate and large amount of nucleus, which resulted in the lack of CTAB share per MSN. Finally, when TEOS was fully introduced into the reaction solution instantly (Fig. 3a one-shot) or the volume of the injected NaOH stock solution was very low (Fig. 3c NaOH 5 μL), hollow shell structures were commonly observed. As this synthetic reaction of MSNs was performed under a dynamic and complicated condition, where the parameters affecting the synthesis of MSNs, such as the pH and concentrations of CTAB, TEOS, and alcohol were varied continuously, the detailed formation mechanism of the mesoporous hollow shells is unclear. The concentrations of free CTAB and hydrolyzed TEOS decreased as the reaction proceeded because they were consumed for the generation of MSNs. In the case of one-shot injection, a large amount of TEOS was abruptly hydrolyzed, resulting in the sudden generation of a large amount of silicic acid and a decrease in pH [41]. As the structure of a CTAB micelle depends on the reaction condition [42,43], similar large micellar templates can be formed in the presence of methanol under both one-shot TEOS injection and NaOH deficient conditions [44]. These large CTAB structures eventually result in the formation of hollow mesoporous silica shells (Fig. S5). Besides, when the TEOS solution was introduced into the reaction system, emulsions were formed in the aqueous reaction solution because of the non-polar properties of TEOS molecules. Once the amount of the NaOH became too low to
under this condition, the concentration of hydrolyzed TEOS remains significantly higher than Chom for a certain duration, which induces multiple nucleation (Fig. 4b). The concentration of CTAB exerted an influence on the morphology and discreteness of MSNs. As the surfactant works not only as a soft template but also as an MSN stabilizer, the MSNs containing sufficient amount of CTAB will have enough electrostatic repulsion applied between them, resulting in discrete MSNs. Therefore, under the surfactant deficient conditions, the surface charge of MSNs will be decreased (Table S4). If the concentration of CTAB decreases, the electrostatic repulsive force between the initial nuclei will not be sufficiently strong for good dispersion in the reaction solution, resulting in chain-like silica structures. The silica chain became thicker and longer as the concentration of CTAB decreased (Fig. 3b CTAB 0.1–2.5 mM). When the surfactant concentration in the solution was extremely low (Fig. 3b CTAB 0.1–0.5 mM), very small (~15 nm) and non-porous (dense) silica nanoparticles were also formed. This might have been due to the consumption of most of the free surfactants to build chain-like structures, resulting in the formation of small and dense silica nanoparticles owing to the lack of CTAB micellar templates. Moreover, the volume of the injected NaOH stock solution affects the structures of MSNs. The hydrolysis and condensation rates of the silica source are highly dependent on the pH, which, consequently, significantly affects the final shape of the nanoparticles [22]. In this study, the synthesized MSNs had rough surfaces at low pH and became smooth and spherical as the pH increased (Fig. 3c). However, when the
Fig. 4. Schematic of the kinetics of the synthesis of MSNs for (a) TEOS injection rate (continuous injection) and (b) injection types. Csol and Chom represent the solubility and homogeneous nucleation concentration, respectively. 4
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effectively proceed the sol-gel reaction (Fig. 3c NaOH 5 μL), the silica formation reaction could occur only on the surface of the emulsions, leading to hollow silica structures [38,45]. These results show that this CIMPL method allows us to tune the reaction kinetics by injecting a silica source into the reaction system slowly in a controlled manner and have much more freedom and control in MSN synthesis in comparison to previously reported methods.
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4. Conclusions We successfully synthesized discrete and monodisperse MSNs at a large scale using the CIMPL process at room temperature and demonstrated the role of each major factor that affects the size, shape, and discreteness of MSNs. We observed that the TEOS injection rate and the pH of the synthesis solution determine the size and structure of the MSNs, respectively, because they lead to different amounts of hydrolyzed TEOS and free surfactant along with varied reaction rates. In addition, the variation in the concentration of CTAB resulted in different repulsive forces between individual nuclei, affecting the size and discreteness of the MSNs. Finally, we successfully controlled the size of MSNs on the scale of 10 nm by systematically modulating the CTAB concentration, pH of the reaction solution, TEOS injection rate, and TEOS concentration and prepared highly monodisperse and discrete MSNs in gram-scale by simply increasing the reaction volume. As demonstrated, understanding the role of these individual factors is important as these results can be adapted for the synthesis of other mesoporous particles with complex shapes. Finally, as the CIMPL process is straightforward and highly reproducible for the synthesis of MSNs in large quantities, we expect that this method will provide a new guidance for highly efficient large-scale synthesis of various porous nanoparticles with high monodispersity. Considering the importance of large-scale synthesis of mesoporous nanomaterials with high monodispersity in industries, this method can bring a significant impact in many fields including cosmetic, biomedical, sensing, and catalytic areas. Notes The authors declare no competing financial interests. Acknowledgements This research was supported by the grant of National Research Foundation of Korea funded by the Ministry of Science and ICT for Bioinspired Innovation Technology Development Project (NRF2018M3C1B7021997) and the grant supported by Korea Electric Power Corporation (Grant number: R18XA02). Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.micromeso.2019.109595. References [1] B.P. Bastakoti, S. Ishihara, S.-Y. Leo, K. Ariga, K.C.W. Wu, Y. Yamauchi, Langmuir
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