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Strategies of Large Scale Synthesis of Monodisperse Nanoparticles

Hongtao Cui1,*, Yongmei Feng2, Wanzhong Ren1, Tao Zeng1, Hongying Lv1 and Yanfei Pan1
College of Chemistry and Biology, Yantai University, Yantai 264005, China, 2College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China
Received: August 21, 2008; Accepted: October 7, 2008; Revised: October 8, 2008
1

Abstract: Intensive research focuses on the development of nanoparticles, not only for their fundamental scientific interest, but also for a variety of technological applications. Monodisperse nanoparticles with a size variation of less than 5% exceptionally have been received much attention, due to their novel and high performance induced by the strong dependence of properties upon the dimension of the nanoparticles. Their unique properties result in a great of potential applications in the area of ultra-high density magnetic storage media, electronics, biomedical usage, medical diagnosis, catalyst, etc. This is stimulating a high level of interest in the development of large scale synthesis techniques of monodisperse nanoparticles. In this article, the recent advance about the relevant aspects of large scale synthesis approaches for various monodisperse nanoparticles was summarized.

Keywords: Monodisperse, nanoparticle, large scale synthesis. INTRODUCTION According to the acquired knowledge, novel properties and high performances of nanoparticles are presented not only due to their small size, but also their uniform size distribution. Monodisperse nanoparticles with a size variation of less than 5% show unique properties and higher performances as compared with the corresponding polydisperse nanoparticles. The noted applications of monodisperse nanoparticles include quantum dots in the areas of optics, biology and computation, magnetic materials in the areas of high-density magnetic recording, medical diagnostics, magnetic resonance imaging and drug delivery etc [1-8]. However, to use their excellent properties for human benefit, their large scale production processes with high product quality are highly required to be developed. Chemical preparation of monodispersed nanoparticles involves the process of precipitation of a solid phase from solution, which includes the nucleation and growth of particles in the solution. Control of nucleation and the following growth are the key factors for the synthesis of monodisperse nanoparticles. Uniformity of the particle size distribution is only achieved through a short nucleation period that produces all the particles obtained at the end of reaction. In this article, recent advance is briefly summarized for the large scale production approaches of different monodisperse nanoparticles, which include metals, metal alloys, metal oxides, multi-metallic oxides quantum dots and other non-oxide compounds. CHEMICAL STRATEGIES OF PREPARATION (1) High Temperature Decomposition and Reduction Routes of Organometallic Compounds and Metal Complexes Since the decomposition approach of organometallic compounds was first introduced in the early 1990s to
Address correspondence to this author at the College of Chemistry and Biology, Yantai University, Yantai 264005, China; E-mail: htcui@ytu.edu.cn 1872-2105/09 $100.00+.00

produce monodisperse quantum dots [9] as shown in TEM image of Fig. (1), it has been a common way to obtain monodisperse nanoparticles. Organometallic compounds are complexes which feature direct metal-carbon bonds between metal and organic ligand. Other complexes without containing M-C bonds such as iron pentacarbonyl and tetrakis(trifluorophosphine) nickel are still categorized in this class, because their properties and reactivity patterns are typical of organometallic compounds. Due to the unique

Fig. (1). 5.1 nm CdSe monodisperse nanoparticles prepared by decomposition of organometallic compound [9].
2009 Bentham Science Publishers Ltd.

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properties, they gained an advantage on the preparation of monodisperse nanoparticles. The general scheme of the organometallic route can be described as two representative synthetic procedures. The first is that pyrolysis of organometallic reagents is initiated by their rapid injection into a hot high boiling point solvent, providing temporally discrete homogeneous nucleation and permitting controlled growth of particles. The second is that reagents including organometallic compounds are mixed at low temperature and the resulting solution is slowly heated in controlled manner to generate nuclei. The particle growth occurs by the further addition of resultants, or particle size is increased by aging at high temperature by Oswalt ripening. The growth of particles can be stopped by the rapid decrease of reaction temperature. Through the careful control of reaction conditions such as time, temperature and the concentration of reagents and stabilizing surfactants, uniformity of the particle size distribution can be achieved. A typical example of the first synthetic procedure is the preparation of CdSe [9]. Dimethylcadmium and bis(trimethylsily)selenium dissolved in trioctylphosphine were rapidly injected to a 300C solvent of tri-n-octylphosphine oxide to allow the decom-position of organometallic compounds. The final nano-particles were obtained after reaction at 230-260C for a few hours. In this category of preparation, it was found that the size distribution of semiconductor particles can be focused through the concentration control of reactants. At the same time, their shape was controlled through the manipulation of growth kinetics such as anisotropic growth [1,10]. For the second synthetic approach, the synthesis of monodisperse iron nanoparticles [11,12] is exampled. Under inert atmosphere, iron pentacarbonyl was added to a solution at a temperature of higher than 100C which contained dehydrated octyl ether as high boiling point solvent and oleic acid as surfactant, forming metal surfactant complex. Then, the obtained complex was heated to reflux temperature and was aged at this temperature for 1 hour to allow the complete decomposition of metal complex. The resulting mixture solution was cooled and centrifuged to separate the iron nanoparticles. Usually, high decomposition temperature results in the formation of metal oxide on the surface of metal nanoparticles. The problem can be resolved by the lowering of temperature. For example, during the preparation of iron nanoparticles through the decomposition of pentacarbonyl iron, the iron precursor solution was injected to kerosene(solvent) instead of octyl ether at a moderate temperature of 180C, producing 2g iron monodisperse nanoparticles without the formation of iron oxide on the particle surface [13]. The group of Chaudret [14] described another low temperature decomposition approach of organometallic compounds to produce metal and alloy monodisperse nanoparticles. Its process can be generalized as following: carboxylic acid (preferably oleic acid) and amine (preferably oleylamine) were dissolved in a solvent (preferably ether). The obtained solution was then mixed with organometallic metal to form a reactant solution. The solution was heated at 150C under pressure of 3 Bars of H2 to allow the decomposition of metal precursor for 48 hours to obtain shape controlled nanoparticles.

Most of transition metal naoparticles can be prepared by the simple decomposition of metal complexes or organometallic precursors, including cobalt, nickel, ironcobalt alloy and so on [11,15]. Metal oxides [16,17] can be synthesized through the oxidation of metal nanoparticles produced from the decomposition of metal complex or organometallic precursors. For instance, iron nanoparticles [16] were formed first at a refluxing temperature by the decomposition of iron complex which was synthesized at 100C in octyl ether with oleic acid as surfactant. The resulting iron particle containing solution was cooled to room temperature, following by the addition of dehydrated trimethylamine-N-oxide as oxidizing agent, and then the oxidation of iron to iron oxide nanoparticles was carried out at 130C (Fig. 2). The oxidation process does not always follow the mode of metal formation and its oxidation. The organometallic compounds or the intermediates can be oxidized directly to metal oxides by any oxidizing agents such as air, water vapor, the organic oxidizing agents and the other non-organic oxidizing agents [18].

Fig. (2). Low resolution and high resolution TEM image of 13 nm -Fe2O3 nanoparticles prepared by the oxidation of iron nanparticles obtained from the decomposition of iron complex [16].

It is quite difficult for using decomposition of organometallic compounds to prepare some metal alloys. One important reason is the unavailability of some organometallic precursors due to their complicated and harsh preparation procedures. Therefore, metal salts are considered to be used for the preparation of alloys. In a successful production of monodispersed FePt nanoparticles, an organometallic iron (iron pentacarbonyl) was used as iron source precursor. At the same time, a platinum salt (platinum acetylacetonate) was used as platinum precursor. Iron pentacarbonyl was added to a 100 C solution containing the platinum acetylacetonate and the reducing agent. The synthesis of FePt nanoparticles was realized by the simultaneous thermal decomposition of iron pentacarbonyl and reduction of Pt salt in the present of surfactant [19,20]. However, the stoichiometry of FePt is difficult to control due to the fact that reaction temperature is higher than boiling point of iron pentacarbonyl which is evaporated before its incorporation into the alloy. Therefore, iron salts such as iron acetylacetonate instead of organometallic iron are used as the

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iron precursors [1]. Other disadvantages of organometallic precursors, such as iron pentacarbonyl, are their highly toxic and flammable characteristics, which are quite unsuitable for the industrial production. Therefore, in the recent progress, organometallic compounds were replaced by metal salts to produce the metal oxides [21] by the decomposition of metal salts, or metal by the decomposition and reduction of metal salts [5,22,23] in the hot solvent. TEM image [23] in Fig. (3 ) shows the 7 nm Pd monodisperse nanparticles synthesized by decomposition and reduction of Pd surfactant-complex. At first, Pd-surfactant complex was prepared by reacting Pd(acac)2 and trioctylphosphine in an argon atmosphere. Pd particles were then formed by the decomposition of the complex in a solvent of trioctylphosphine at 300C and reduction by CO molecules generated in situ from the thermal decomposition of acetylacetonate.

synthesized by the decomposition and the reduction by glycol after aging at this temperature for 50 min. A modified polyol process [29] was proposed using a polymer (polyvinylpyrrolidone) to control the size and the dispersity of the silver nanoparticles (Fig. 4). In a typical experiment, ethylene glycol solution of silver nitrate and polyvinylpyrrolidone was heated to 120C and maintained at this temperature for several hours. After cooling and dilution with water, the reaction mixture afforded silver particles having a mean particle size of 21 nm. However, when this process is scaled up, the size and shape of the particles became non-uniform and the formation of large chunks, needle-like particles and the like was observed. To resolve this problem, an improved procedure was proposed to avoid the local concentration gradients and inhomogeneous reaction conditions, through the rapid combination of preheated solutions of polymer and silver precursor [30].

Fig. (4). TEM images of silver nanoparticles whose dispersity and size were controlled by the concentration of silver precursor and polymer [29].

Fig. (3). 7 nm Pd monodisperse nanoparticles synthesized by decomposition and reduction of Pd surfactant-complex [23].

Some reductants used for the reducing of metal salt, such as superhydride (LiB(Et)3H) [24], are flammable and corrosive. As substitution, polyol is widely used to reduce the metal salts to metal particles, which is named polyol process. Polyol process, in which polyol (1,2-propanediol, 1,2-docecanediol, 1,2-hexanedecanediol, 1,2-octanediol etc.) act as a mild reducing agent, is a popular route for the synthesize metals and metal alloy monodisperse nanoparticles [25-27]. It allows an accurate and reproducible control of the particles in a broad size range from a few nanometers to a few micrometers. At the same time, high boiling point of polyols can also be used as solvent as well as reducing agents. In a case of this type of polyol process [28], platinum acetylacetonate and iron (III) acetylacetonate were dissolved in tetraethylene glycol, following by the heating to 300C under irradiation of microwaves and nitrogen gas bubbling. FePt monodisperse nanoparticles were then

Recently, the decomposition approach of metal salts is extended to the preparation of metal oxides and multimetallic oxides, where they are obtained by the thermal decomposition of metal complex salts in hot solvent with high boiling point. In a typical synthesis of magnetite nanoparticles [31,32], iron(III) acetylacetonate, 1,2-hexadecanediol, oleic acid, oleyl amine were dissolved in dioctyl ether and heated to reflux for 30 minutes to allow the formation of magnetite nanoparticles. The particles in the obtained mixture solution were precipitated and separated by centrifugation. In a similar way, by changing the cobalt salt to other metal salts, various MFe2O4 nanoparticles can be made, in which M=Zn, Cu, Ni, Co, Mn, Cr, V, Ti, Mg, or Ba. The particle size can be controlled by changing the stabilizer/iron salt ratio or the reaction temperature. Another strategy, developed by Hyeons group, exhibits potential future in industrial application. This could be specialized with the preparation of iron oxide of high quality as shown by a typical TEM image in Fig. (5). These monodisperse nanoparticles [7] were prepared as large as 40g in a

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economical and low toxic characteristics [33-35]. For the preparation of rare earth oxide monodisperse nanoparticles, the transformation of rare earth oleate to oxide can not be completely finished until 500C. However, by the catalysis of the base of oleylamine, the decomposition temperature of rare earth complex can be lowered to 310C [6]. (2) Solvothermal and Hydrothermal Routes Solvothermal and hydrothermal approaches utilize solvent under elevated pressures and temperature above or below its critical point to increase the solubility of a solid and to speed up reaction between precursors. Under supercritical conditions, solvent exhibit characteristics of both a liquid and a gas, where the interfaces of solids and solvent lack surface tension, yet the solvent shows high viscosities and easily dissolves chemical compounds that would otherwise exhibit very low solubility under ambient conditions. Some processes of solvothermal and hydrothermal approaches simply take advantage of the increased solubility and reactivity of metal salts and complexes at elevated temperatures and pressures without bringing the solvent to its critical point [36].
Fig. (5). 12 nm magnetite monodisperse nanoparticles. Inset is a photograph showing a Petri dish containing 40 g of the monodisperse magnetite nanoparticles [7].

batch by decomposition of iron-oleate salt precursors, which is described in an overall preparation scheme Fig. (6). The solution containing iron chloride and sodium oleate was heated to 70C and kept at the same temperature for 4 hours to obtain an iron-oleate complex. The obtained complex was added into a dehydrated octadecene solution with oleic acid as surfactant under inert atmosphere at room temperature. The resultant mixture was heated to 320C for the decomposition of the complex to metal oxide. The obtained solution containing the nanoparticles was cooled to the room temperature, and then separated by centrifuging. The particle size can be controlled by using various solvents with different boiling points. This approach is extended readily to the preparation of other transitional metal oxides and multimetallic oxides by using different metal salts. The corresponding metal nanoparticles can be prepared by the self reduction of the resultants at higher reaction temperature. This route is evaluated as a general process for the industrial production of metals, metal oxides and multi-metallic oxides without further size-selection step due to its facile,

Solvothermal and hydrothermal approaches feature high temperature and pressure in a sealed reaction vessel. Usually, their systems consist of three components: precursors, surfactants and solvents, and the precursors include organometallic compounds, metal complexes or inorganic species. Solvothermal and hydrothermal processes have recently been extensively applied in the fundamental researches for the synthesis of monodisperse nanoparticles with new structures and properties. This is due to the well control of growth dynamics and agglomeration of the nanoparticles [37-40]. No matter what well quality control of the route induced by harsh reaction conditions of solvothermal and hydrothermal approaches, it is quite difficult for them to be applied in industrial synthesis application due to their elevated pressure and temperature during reaction, which is the reason of a few related documents in patents. However, the description for them in patents maybe provides a way of comprehension for the well synthetic control preparation of monodisperse nanoparticles in large scale. The simplest solvothermal procedure, exampled with ZnO nanoparticle preparation [41], uses the high pressure reaction of methylzinc isopropoxide in hexadecane at 200 C for 10 hours, yielding 1.2g ZnO particles of less than 10 nm. For the further improvement of nanoparticle size uniformity, an

Fig. (6). The overall preparation scheme of monodisperse nanoparticles by decomposition of metal oleate precursors [7].

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invert micelle solvothermal approach was adopted in the synthesis of Ge particles [42]. Invert micelle solution was formed by mixing of GeCl4, phenyl-GeCl3, hexane (invert micelle solvent) and pentaethylene glycol ether (capping agent and shape controlling agent). The micelle solution was heated in a Parr reactor to 280 C for 72 hours, reduced by Na, producing quite monodispersed Ge nanoparticles. The particle size and dispersity was controlled by the formed invert micelles. Solvothermal approach has been found that it is quite unique for the synthesis of nitrides nanoparticles. Some nitrides, such as GaN of rocksalt-phase, were traditionally prepared at high pressure and temperature. Qians group [43] adopted a thermal reaction of Li3N and GaCl3 in which benzene was used as the solvent under pressure of 5 Mpa at 280 C, yielding 30 nm mainly hexagonal-phase GaN with a small fraction of rocksalt-phase GaN. Hydrothermal process using water as reaction medium follows the similar chemistry of solvothermal approach to prepare monodisperse nanoparticles. Synthesis of metal oxides by this route usually uses pre-prepared hydroxide as precursors before the hydrothermal treatment [44-46]. In a typical synthesis of cerium-titanium composite oxide nanoparticles [44], a suspension of pre-prepared (Ce,Ti) (OH)4 was acidized by nitric acid. Then, the mixture was placed in a closed vessel for a hydrothermal treatment at 300 C. The obtained oxide slurry was cooled to room temperature and excess water was decanted, following the pH adjustment to 4 by NH4OH. The final oxide particles were collected by the repeated washing and the following filtration.

surrounding aqueous solution. Reverse micelles are formed by the directing of hydrophilic head groups toward the aqueous micelles core with outward hydrophobic groups to organic medium [47]. Since cetyltrimethylammonium bromide (CTAB) was used as surfactant to prepare the first micelles by Hoar and Schulman [48] in 1943, CTAB [49] was investigated thoroughly for the synthesis of micelle. Besides the CTAB, sodium bis(2-ethylhexyl)sulfosuccinate (Aerosol OT or AOT) [50] is the most notably anion surfactant during the recent years. Other less commonly used surfactants are nonionic, most based on polyethylene ethers such as pentaethylene glycol dodecyl ether [51], CH3(CH2)11-O-(CH2-CH2-O-)5-H [52] or Triton-X [53]. Micelles, which are thermodynamically stable, acts as a nano-reactor to limit occurrence of reactions inside the water or oil pools, where the size and dispersity of particle are controlled by the droplet size and the surfactants[54]. The formation of reverse micelles is through the mixing of surfactant, cosurfactant, organic solvent and water. The pre-parations of nanoparticles through this way are categorized into two approaches. The first one is to mix two different reverse micelles, and reaction occurs by the coalescence and materials exchange between the micelles. The second is by the coalescence and reaction between one reactant in oil phase and another reactant in the water pool of reverse micelles. Monodisperse metal nanoparticles as shown in Fig. (8) can be prepared by reducing of metal salts in the reverse micelles. For example, FePt nanoparticles were synthesized by mixing of two micelles of metal precursor and reducing agents [55]. The metal precursor micelle was obtained by dispersing of triammonium iron trioxalate, potassium chloroplatinate aqueous solution in surfactant containing decane. The reducing agent (NaBH4) containing micelle was obtained in the same way. The FePt monodisperse nanoparticles were formed by the mixing of the two reverse micelles and the heat treatment at 50 C for 1 hour. The final

Fig. (7). 13 nm PbSe monodisperse nanoparticles prepared by solvothermal route [40].

(3) Micelle Routes When concentration of surfactant exceeds the critical micelle concentration in water, micelles are formed as aggregates of surfactant molecules. Normal micelles are formed by the orientation of hydrophobic hydrocarbon chains of surfactants toward the interior of the micelle, and the contact of hydrophilic groups of the surfactants with the

Fig. (8). TEM image of Ag2Se nanoparticles prepared by hydrothermal process [46].

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Normal micelles are oil droplets in water, where the length of the surfactant akyl chain controls the size of the droplets. For example, SiO2 nanoparticles were prepared through this approach [58], where normal micelles were first produced by the mixing of AOT and n-butanol in large amount of water, following with the second step of triethoxyvinylsilane dissolving into oily micelles. The hydrolysis and condensation of Si precursor was initiated by aqueous ammonia which was added into the water phase. A two phase procedure developed by Brust [59] represents a modified micelle route, which focuses on the preparation of Au and other metal monodispersed nanoparticles. This route is involved in reduction of metal salts in the interface of oil and water in the micelles under vigorous stirring as exampled in the preparation of Au monodisperse nanoparticles [60]. Starting from an aqueous solution of AuCl4-, the tetrachloroaurate ions were transferred to an organic phase by vigorously mixing the aqueous solution with a toluene solution of tetraoctylammonium bromide (TOAB) (TOAB is a well known phase-transfer catalyst). After adding C10H21SH to the organic phase, an aqueous solution of NaBH4 was subsequently introduced into the mixture to form micelles under rapid stirring. Colloidal gold was formed in the interface of micelles and was subsequently isolated by vacuum evaporation and following precipitation with methanol. (4) Sol-Gel Routes Sol-gel process is a widely used wet chemistry synthesis technique for the preparation of various oxide materials. Traditionally, it refers to the hydrolysis and condensation of alkoxide-based precursors. Recently, its meaning has been extended to any kinds of condensation procedures occurring between precursors to form M-O-M bridges. The precursors include the conventional alkoxides, metal complexes and metal salts. The conventional sol-gel processes for the preparation of metal oxides are divided to synthesis step where an amorphous phase of the desired oxide is formed and an annealing step where the obtained precursor is heated to a high temperature to crystallize the solid. This usually causes the aggregation of the produced nanoparticles and does not allow the formation of uniform-sized particles. Therefore, it is very difficult to obtain monodisperse nanoparticles through hydrolytic sol-gel route. However, monodispersed nanoparticles can still be prepared by a modified hydrolytic sol-gel route, where the hydrolysis, condensation, and crystallization occur in a high boiling point solvent under the protection of surfactants [61-63]. In a typical synthesis of TixSn(1-x)O2 [61], titanium and tin alkoxides were mixed with oleic acid under a nitrogen gas atmosphere to form a reaction solution. Trimethylamine oxide as reaction initiator was dissolved in water to form a catalyst solution. The two solution was mixed together and heated to 100 C to initiate reaction of hydrolysis, condensation and crystallization to produce TixSn(1-x)O2 nanoparticles. The particle size can be controlled by appropriate selection of the type of alkoxy group in the alkoxides. Since a non-hydrolytic sol-gel approach [64] for the preparation of metal oxides and multi-metallic oxides was established in the early 1990s, it recently became a new route

Fig. (9). TEM image of Cu nanoparticles synthesized by reverse micelle approach [54].

product was collected through destroying of particle containing reverse micelles, repeated washing and particle settling. During the reaction, the dispersity of the particles was controlled by the ratio of water and surfactant.

Fig. (10). Preparation scheme of FePt monodisperse nanoparticles by reverse micelle route [55].

Metal oxides, metal carbonate, metal sulfide and other non-metal nanoparticles were synthesized inside the reverse micelles by hydrolysis and precipitation procedures. In an example of metal oxide nanoparticle preparation, maghemite [56] was produced through hydrolysis of FeCl3.6H2O in water pool. Reverse micelles were formed by the mixing of metal salt solution and dibenzylether using oleic acid as surfactant. The hydrolysis of FeCl3 and the following condensation to form iron hydroxide were initiated and promoted by propylene oxide (proton scavenger) which was dissolved in oil phase. Yielding of maghemite nanoparticles was realized by the refluxing of the obtained hydroxide in tetralin solvent at above 200 C. By adjusting molar ratio of distilled water and metal salt, or molar ratio of water and surfactant, the particle size can be tuned. Non-metal oxides are usually synthesized through precipitation occurring inside micelles. In a typical synthesis of ZnCO3 monodisperse nanoparticles [57], two 8 nm reverse micelles were prepared by using zinc nitrate and ammonium carbonate as precursors respectively, n-Octane as solvent, cetyl trimethylammonium bromide and n-butanol as surfactant and cosurfactant. The two micelles were mixed together, allowing the exchange of the solutes which resulted in the precipitation of ZnCO3.

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generation of monodisperse nanoparticles. Its essential controlling factors include styles of precipitation reaction, pH, concentration, temperature, surfactants etc. All these factors must focus on the nucleation with only one burst formation of nuclei during the whole precipitation reactions. The preparation of metal oxides by precipitation can generally be classified into two categories: one is that the precursors obtained by precipitation reaction are required to be heat treated at high temperature for the crystallization; another is the direct formation of metal oxide during reaction. During the preparation of oxides, the products of precipitation, particularly those performed at or near room temperature, are usually amorphous. In those cases where hydroxides or carbonates of mixed metals are precipitated from solution and subjected to a calcination or postannealing process, some aggregation is unavoidable due to the heat treatment at high temperature. Therefore, there is little chance of the particles being monodispersed, which can be exampled by the synthesis of ZnO [67] through precipitation reaction. The zinc hydroxide was prepared with the reaction between zinc ions and KOH in methanol solution, followed by the drying of obtained hydroxide gel to form the crystallized ZnO. The obtained ZnO shows a wide particle size distribution induced by aggregation. The kind of aggregation can be decreased by using of aggregation inhibitor during the heat treatment. In a synthesis of yttriumstabilized zirconia (YSZ) nanoparticles [68], hydrous YSZ precursor was prepared by the precipitation reaction of metal salts with NH4OH. The obtained YSZ precursor was mixed with SrCO3 nanoparticles, and then followed by the calcination of the mixture at 600 C. The nearly monodispersed YSZ nanoparticles were obtained by avoiding the aggregation between YSZ particles through the physical isolation of SrCO3 nanoparticles. The SrCO3 as impurity was dissolved by the washing with 10% HNO3.

Fig. (11). Preparation scheme of TixSn(1-x)O2 by a sol-gel route [61].

for the uniform-sized nanoparticles. In conventional hydrolytic sol-gel processes, sol and gel are formed due to the formation of M-O-M bridges through hydrolysis and condensation reactions. However, in the non-hydrolytic solgel route, M-O-M bridges formation results from the nonhydrolytic condensation of metal precursors. Non-hydrolytic sol-gel processes are classified into two categories: nonhydrolytic hydroxylation reaction and aprotic condensation reactions [65]. The latter is the frequently used reaction for the synthesis of nanoparticles. In this process, M-O-M bridges are formed by the condensation reaction between two metal centers with functional groups through removing a small organic molecule through ether elimination, ester elimination and alky halide elimination. Through the nonhydrolytic sol-gel approach, monodispersed or nearly monodispersed nanoparticles can be produced [62,66].

Fig. (12). TEM image of zirconia monodisperse nanoparticles prepared by non-hydrolytic sol-gel route [66].

(5) Chemical Precipitation Routes Chemical precipitation is a widely used approach for the preparation of nanoparticles. During the process of precipitation, nucleation is a key step of the precipitation process and a large number of small particles are generated. In the following, secondary process such as Ostwald ripening and aggregation dramatically affect the size of the particles. Due to its simultaneous occurrence of nucleation, growth, coarsening and agglomeration processes, careful control of the reaction conditions is required for the

Fig. (13). TEM image of nearly monodispered YSZ nanoparticles prepared by precipitation route with a post calcination step [68].

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On the other hand, direct formation of metal oxide during reaction gains better chance for the goal of monodisperse state than the first approach through careful control of nucleation and avoiding of the heat-treatment induced aggregation. A typical illustration is the preparation of anatase TiO2 [69]. The precipitation and crystallization of TiO2 were initiated by the dropewise addition of aqueous acidic solution of hydrazine to an acidic solution of titanium tetrachloride. The nearly monodispersed nanoparticles of the product were collected through the filtration, washing and drying step. For the example of mixed metal oxides such as (CoxMn1x)3O4 [70], its crystalline phase was formed by the autoxidation of Mn(OH)2. In the synthesis, aqueous solution of Co(NO3)2 and Mn(NO3)3 was added dropwise to a LiOH solution, where LiOH was used as precipitating agent. The nearly monodisperse (Cox Mn1x)3O4 nanoparticles were produced by the in situ autoxidation of Mn(OH)2 in the solution. LiOH was applied as precipitating agent in stead of the widely utilized NH4OH due to the ammonium ions retardation on the autoxidation of Mn(OH)2.

technique, so that only semiconductor nanoparticles of a specific particle size can be isolated and extracted to achieve monodispersion. There exists a conventional and subtle size selection technique for metal chalcogenide quantum dots, namely the size-selective photoetching method [71-73]. This method utilizes the fact that the energy gap increases due to the quantum size effect as the particle size of the semiconductor nanoparticles decreases, and that the metal chalcogenide semiconductor undergoes oxidizing melting as it is irradiated with light in the presence of dissolved oxygen. Specifically, semiconductor nanoparticles with a wide particle size distribution are irradiated with monochromatic light of a wavelength shorter than the wavelength of the absorption edge of the particles, so that semiconductor nanoparticles with larger particle sizes are selectively optically excited and dissolved, thereby obtaining smaller semiconductor nanoparticles with uniform particle size. In a typical process of size selection of metal chalcogenide, the size selective photoetching was described as following [71]. First, bubbling is performed using nitrogen gas in polydispersed semiconductor nanoparticles containing solution which are stabilized by hexametaphosphate. Another bubbling is conducted using oxygen for 10 min. Then, methylviologen is added to the solution and irradiation of monochromatic light is conducted to optically dissolve the semiconductor nanoparticles while stirring. When the semiconductor nanoparticles with a size deviation of more than 15% are irradiated with light with wavelength 476.5 nm, the resulted particles exhibit a very narrow particle size distribution with a standard deviation of 6%. The sizeselective photoetching procedure is not only used in sizeselective photoetching of semiconductor nanoparticles but also in that of other nanoparticles to which size-selective photoetching can be applied. Examples of the other nanoparticles are those of Ag, Au, other metals, and singlecrystal carbon [72]. Other size selection procedures, such as electrophoretic separation method [74] that takes advantage of the variation of surface charge of the nanoparticle depending on particle size, the exclusion chromatography [75] that takes advantage of the difference in retention time, are quite unsuitable for large scale size selection due to their high operation cost. Size selective precipitation [76-79] is a frequently used technique for the narrowing of the particle size distribution. This procedure takes advantage of the difference in dispersibility into an organic solvent depending on particle size. The dispersibility of particles with different size can be manipulated by solvent composition of the nanocrystallite suspension. A typical size selective precipitation may be illustrated by an example of CdSe [76]. The CdSe nanocrystallites are stabilized in solution by the formation of a lyophilic coating of alkyl groups on the crystallite outer surface. The alkyl groups are provided by the coordinating solvent (butanol) which is used during the growth period. The interparticle repulsive force introduced by the lyophilic coating prevents aggregation of the particles in solution. The effectiveness of the stabilization is strongly dependent upon the interaction of the alkyl groups with the solvent. Gradual addition of non-solvent (methanol) will lead to the sizedependent flocculation of the nanocrystallites, resulting in first flocculating of the largest particles.

Fig. (14). TEM image of nearly monodispersed (CoxMn1x)3O4 nanoparticles synthesized by precipitation at room temperature [70].

(6) Size Selection for Monodisperse Nanoparticles The definition of monodisperse nanoparticle is strictly referred to the specified particles with a size variation of less than 5%. Although careful control of nucleation and particle growth, avoiding occurrence of secondary nucleation during the particle growth, can lead to the formation of monodisperse nanoparticles, sometimes, it is inevitable to exceed this standard size deviation of particles induced by the reaction conditions and preparation methods. In this case, size selection is necessary for the synthesis of monodisperse nanoparticles, especially for the large scale production. The physicochemical properties of semiconductor nanoparticles appear in dependence on particle size due to the quantum size effect. Accordingly, it is necessary to accurately conduct a particle-size selection from the semiconductor nanoparticles immediately after preparation that have a wide particle size distribution, using a chemical

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Cui et al. [2] Liu C, Wu X, Klemmer T, et al. Polyol process synthesis of monodispersed FePt nanoparticles. J Phys Chem B 2004; 108: 6121-6123. Xie J, Peng S, Brower N, Pourmand N, Wang S, Sun S. One-pot synthesis of monodisperse iron oxide nanoparticles for potential biomedical applications. Pure Appl Chem 2006; 78: 1003-1014. Zhao F, Yuan M, Zhang W, Gao S. Monodisperse lanthanide oxysulfide nanocrystals. J Am Chem Soc 2006; 128:11758-11759. Lee Y, Lee G, Shim J, et al. Monodisperse PtRu nanoalloy on carbon as a high-performance DMFC catalyst. Chem Mater 2006; 18: 4209-4211. Si R, Zhang Y, Zhou H, Sun L, Yan C. Controlled-synthesis, self assembly behavior, and surface dependent optical properties of high quality rare earth oxide nanocrystals. Chem Mater 2007; 19, 18-27. Park J, An K, Hwang Y, et al. Ultra-large-scale syntheses of monodisperse nanocrystals. Nat Mater 2004; 3: 891-895. Lee Y, Lee J, Bae C, et al. Large scale synthesis of uniform and crystalline magnetite nanoparticles using reverse micelles as nanoreactors under reflux conditions. Adv Funct Mater 2005; 15:503-509 Murray CB, Norris DJ, Bawendi MG. Synthesis and characterization of nearly monodisperse CdE (E=S, Se, Te) semiconductor nanocrystallites. J Am Chem Soc 1993; 115: 8706-8715. Kudera S, Carbone L, Casula MF, et al. Selective growth of pbse on one or both tips of colloidal semiconductor nanorods. NanoLett 2005; 5:445-449. Hyeon T.: US20040247503 (2004). Grancharov, S., O'Brien, S., Held, G., Murray, C.B.: US20060140868 (2006). Yang H, Ito F, Hasegawa D, Ogawa T, Takahashi M. Facile large scale synthesis of monodispersed Fe nanoparticles by modest temperature decomposition of iron carbonyl. J Appl Phy 2007; 101:09J112. Renaud, P., Dumestre, F., Chaudret, B., Fromen, M. C., Casanove, M.J., Zurcher, P., Stumpf, R., Amiens, C.: WO03071561 (2003). Bonitatebus, P.J., Acar, H.Y.: US20040022937 (2004). Hyeon T, Lee S, Park J, Chung Y, Na H. Synthesis of highly crystalline and monodisperse maghemite nanocrystallites without a size-selection process. J Am Chem Soc 2001; 123:12798-12801. Hultman, K., Willis, A., O'Brien, S., Brown, T.R., Harris, P., Turro, N.J., Grzenda, A.L.: US20070059775 (2007) Kahn, M., Monge, M., Maisonna, A., Chaudret, B.: US20060245998 (2007). Sun S, Murray CB, Weller D, Folks L, Moser A. Monodisperse FePt nanoparticles and ferromagnetic FePt nanocrystal superlattices. Science 2000; 287: 1989-1992. Murray, C.B., Sun, S., Weller, D.K.: US20016302940 (2001). O'brien, S., Yin, M.: US20070140951 (2007). Kim, J., Moon, J., Jeong, S., Kim, D., Park, B.: US20070180954 (2007). Kim S, Park J, Jang Y, et al. Synthesis of monodisperse palladium nanoparticles. Nano Lett 2003; 3; 1289-1291. Murray, C.B., Sun, S.: US20016262129 (2001). Mizuno, M., Sasaki, Y., Inoue, M.: US20060068217 (2006). Belcher, A., Reiss, B., Mao, C., Solis, D.J.: US20087374893 (2008). Sun, S.: US20046676729 (2004). Hirai, H., Waki, K.: US20050204865 (2005). Silvert PY, Herrera-Urbinab R, Tekaia-Elhsissena K. Preparation of colloidal silver dispersions by the polyol process Part 2. Mechanism of particle formation. J Mater Chem 1997; 7: 293-299. Vanheusden, K., Kunze, K., Kim, H., Stump, A.D. Schult, A.B., Hampden-smith, M.J. Edwards, C., James, A.R., Caruso, J., Kodas, T.T., Haubrich, S.T., Kowalski, M.H.: US20070034052 (2007). Sun, S.: US20056962685 (2005). Sun S, Zeng H, Robinson DB, et al. Monodisperse MFe2O4 (M =Fe, Co, Mn) Nanoparticles. J Am Chem Soc 2004; 126: 273-279. Hyeon, T., Park, J.: US2006133990 (2006). Hyeon, T., Park, J.: WO06057467 (2006). Hyeon, T., Park, J.: WO06057533 (2006). Cushing BL, Kolesnichenko VL, OConnor CJ. Recent advances in the liquid-phase syntheses of inorganic nanoparticles. Chem Rev 2004; 104: 3893-3946.

In a process described by group of Roberts [80], sizeselective precipitation of semiconductor nanoparticles is achieved by finely tuning the solvent strength of the CO2/hexane medium by simply adjusting the applied CO 2 pressure. These subtle changes affect the balance between osmotic repulsive and van der Waals attractive forces, thereby allowing fractionation of the nanocrystals into multiple narrow size populations. In another process [81], through the size dependent interfacial interaction between the nanoparticles, the particle-particle separation distance was modified by selecting a suitable surfactant type and/or conditions. Smaller particles were stabilized against agglomeration and larger particles were agglomerated and settled. CURRENT & FUTURE DEVELOPMENTS With the great development of nanotechnology, monodisperse nanoparticles are showing their promising application in different areas. Among all the available approaches for their synthesis, some of them are quite capable for the control of particles size and size distribution, providing high quality products. For example, micelle route can be used to synthesize various monodisperse nano-particles including metal, metal oxides and quantum dots. However, micelle route can not be applied in the large scale industrial production due to its inherent disadvantages such as low concentration of reactant, large mount of surfactant, repeated washing for removal of surfactant, impurities etc. High temperature decomposition of metal complexes is a widely used route, not only owing to its well control of nucleation and particle growth, but also its typical charac-teristics for the large scale synthesis. Hereinto, the route developed by Hyeon group [7, 33-35] is the most promising general approach. It can produce monodisperse nanoparticles of metals, metal alloys, metal oxides and multi-metallic oxides with very high quality in large scale. The most important point is the use of low cost precursors and mild reaction condition. The trend for large scale production of monodisperse nanoparticles is the use of low cost precursors, simple process, low consumption of energy, environment friendly and no further process of size selection. The existing approaches do not fully follow this trend in every aspect. A much simpler route is still highly required. Recently, an epoxide assisted sol-gel route was developed, showing potential future in large scale synthesis of monodisperse metal oxide nanoparticles. The particles can be obtained by one step reaction which is performed by the simply boiling of ethanol solution of metal salts after the addition of epoxide. The epoxide acts as an acid scavenger that consumes protons from the metal aquo complexes [M(H2O)x]n+, which promotes the hydrolysis and condensation of the complexes resulting in the formation of sol and gel. This route has the typical characteristics of the developing trend for the large scale preparation of uniform-sized nanoparticles. Although the work is still under the way, it has been proven a general route for the synthesis of iron based spinel type monodisperse nanoparticles [82]. REFERENCES
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