NANO LETTERS
Modifying the Surface Properties of Superparamagnetic Iron Oxide Nanoparticles through A Sol−Gel Approach
2002 Vol. 2, No. 3 183-186
Yu Lu, Yadong Yin, Brian T. Mayers, and Younan Xia* Department of Materials Science and Engineering, Department of Chemistry, UniVersity of Washington, Seattle, Washington 98195 Received November 28, 2001; Revised Manuscript Received December 20, 2001
ABSTRACT This paper describes a sol−gel approach for the coating of superparamagnetic iron oxide nanoparticles with uniform shells of amorphous silica. The coating process has been successfully applied to particles contained in a commercial ferrofluid (e.g., the EMG 304 of Ferrofluidics) and those synthesized through a wet chemical process. The thickness of silica coating could be conveniently controlled in the range of 2−100 nm by changing the concentration of the sol−gel solution. Fluorescent dyes, for example, 7-(dimethylamino)-4-methylcoumarin-3-isothiocyanate (DACITC) and tetramethylrhodamine-5-isothiocyanate (5-TRITC), have also been incorporated into the silica shells by covalently coupling these organic compounds with the sol−gel precursor. These multifunctional nanoparticles are potentially useful in a number of areas because they can be simultaneously manipulated with an externally applied magnetic field and characterized in situ using conventional fluorescence microscopy.
This paper describes a sol-gel method based on the hydrolysis of tetraethyl orthosilicate (TEOS) for coating iron oxide nanoparticles with conformal, uniform shells. The thickness of these silica shells could be tuned from ∼2 up to ∼100 nm simply by varying the concentration of the solgel precursor. Fluorescent dyes could also be incorporated into these silica shells through a covalent coupling between these organic dyes and the sol-gel precursor. Magnetic nanoparticles of iron oxides have been extensively exploited as the materials of choice for ferrofluids,1 high-density information storage,2 magnetic resonance imaging (MRI),3 tissue-specific releasing of therapeutic agents,4 labeling and sorting of cells,5 and separation of biochemical products.6 Most of these applications require the nanoparticles to be chemically stable, uniform in size, and welldispersed in liquid media. As a result of anisotropic dipolar attraction, pristine nanoparticles of iron oxides tend to aggregate into large clusters and thus lose the specific properties associated with single-domain, magnetic nanostructures. Surfactants with relatively high concentrations are often required to prevent such a aggregation. The presence of large amounts of surfactants in these systems may severely interfere with the medical and biological applications. In addition, the reactivity of iron oxide particles has been shown to greatly increase as their dimensions are reduced, and * To whom correspondence chem.washington.edu 10.1021/nl015681q CCC: $22.00 Published on Web 01/11/2002
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particles relatively small in size may undergo rapid biodegradation when they are directly exposed to biological environments. It has been demonstrated that the formation of a passive coating of inert materials such as silica on the surfaces of iron oxide nanoparticles could help prevent their aggregation in liquid and improve their chemical stability.7 Another advantage for the silica coating is that this surface is often terminated by a silanol group that can react with various coupling agents to covalently attach specific ligands to the surfaces of these magnetic nanoparticles.8 Such a capability will open the door to the design and synthesis of magnetic carriers that can be used to deliver specific ligands to target organs via the antibody-antigen recognition. Two different approaches have been explored to generate silica coatings on the surfaces of iron oxide particles. The first method relied on the well-known Sto¨ber process,9 in which silica was formed in situ through the hydrolysis and condensation of a sol-gel precursor. This method was originally applied to ferromagnetic rod-like nanoparticles,10 then to micrometer-sized hematite colloids by Matijevic and co-workers,11 and later extended to other iron oxide nanoparticles by a number of research groups.12 Recently, this method was further explored by several groups to form silica shells on nanoparticles of metals such as gold and silver.13 The other method was based on microemulsion synthesis,14 in which micelles or inverse micelles were used to confine and control the coating of silica on core nanoparticles. This
Figure 2. (A-C) TEM images of iron oxide nanoparticles whose surfaces have been coated with silica shells of various thicknesses. In this case, the thickness of silica coating could be adjusted by controlling the amount of precursor added to the solution: (A) 10, (B) 60, and (C) 1000 mg of TEOS to 20 mL of 2-propanol. (D) A HRTEM image of the iron oxide nanoparticle whose surface has been uniformly coated with 6 nm of amorphous silica shell.
Figure 1. (A) A TEM image of the superparamagnetic iron oxide nanoparticles contained in the ferrofluid EMG 304. (B) A HRTEM image of the nanoparticle whose infringe spacings match those of maghemite (γ-Fe2O3). The lattice spacings for the (113) and (220) planes are 0.48 and 0.29 nm, respectively. (C) A HRTEM image of the nanoparticle that could be assigned as magnetite (Fe3O4). The indicated (220) planes are separated from each other by 0.29 nm.
method might require much effort to separate the core-shell nanoparticles from the large amount of surfactants associated with the microemulsion system. Our initial effort was focused on the coating of superparamagnetic nanoparticles contained in commercial ferrofluids, for example, EMG 304 of Ferrofluids (Nashua, NH), a water-based dispersion of iron oxide particles with dimensions in the range of 5-15 nm. These particles were stabilized by adding surfactants (such as oleic acid) to the dispersion medium. Figure 1A shows the TEM image of some particles that were extracted from EMG 304 by solvent evaporation. High-resolution TEM (HRTEM) studies indicate that there are probably two types of iron oxide particles in this dispersion: maghemite (γ-Fe2O3, Figure 1B) and magnetite (Fe3O4, Figure 1C).15 The coexistence of maghemite and magnetite could be attributed to the oxidation of Fe3O4 to γ-Fe2O3 during the synthesis.16 Both nanoparticles are single crystalline in structure, and each of them is made of one single magnetic domain. As a result, they exhibit the superparamagnetic behavior and only possess a magnetic moment in the presence of an external magnetic field.17 When the magnetic field is removed, these nanoparticles will return to their nonmagnetic states immediately. These magnetic nanoparticles could be directly coated with amorphous silica, produced via the hydrolysis of a sol-gel precursor. Because the iron oxide surface has a strong affinity 184
toward silica, no primer was required to promote the deposition and adhesion of silica. In a typical procedure, 0.3 mL water-based ferrofluid (EMG 340) was diluted with 4 mL deionized (DI) water and 20 mL 2-propanol. Under continuous mechanical stirring, 0.5 mL ammonia solution (30wt %, Aldrich) and various amounts of TEOS (Aldrich, used as-received) were consecutively added to the reaction mixture. The reaction was allowed to proceed at room temperature for ∼3 h under continuous stirring. The growth of silica shells on iron oxide nanoparticles involved the basecatalyzed hydrolysis of TEOS and subsequent condensation of silica onto the surfaces of iron oxide cores. The coreshell nanoparticles could be separated from the reaction medium by centrifuging at ∼4000 rpm and then redispersed into DI water. Due to the presence of negative charges on the surfaces of silica shells, these magnetic nanoparticles having a core-shell structure could form very stable dispersions in water without adding other surfactants. The ratio between the concentrations of iron oxide nanoparticles and TEOS had been optimized to avoid the homogeneous nucleation of silica and thus the formation of core-free silica spheres. Although several parameters (such as the growth time and the concentration of ammonia catalyst or water10) could be employed to control the thickness of silica shell, we found it most convenient and reproducible to adjust the shell thickness by changing the concentration of TEOS precursor. Figure 2A-C shows the TEM images of iron oxide nanoparticles whose surfaces had been coated with silica shells using different TEOS concentrations. Note that the silica shell was homogeneous on each individual iron oxide particle, regardless of its original morphology. As a result, the shape of each iron oxide nanoparticle was essentially retained during silica coating, especially when the shell was relatively thin (Figure 2A). In this case, the polydispersity of the Nano Lett., Vol. 2, No. 3, 2002
original nanoparticles was also maintained. When the thickness of silica coating was increased, the core-shell nanoparticles became more monodispersed because of a reduction in the relative size distribution. Figure 2D shows the HRTEM image of a silica-coated iron oxide nanoparticle. This image clearly indicates the single crystallinity of the iron oxide core and the amorphous nature of the silica shell. An examination on the interface between iron oxide and silica suggests the formation of a conformal coating of silica on the nanoparticle core. Due to the presence of a homogeneous structure on the core surface and a strong chemical affinity between iron oxide and silicate, it was possible to generate such a coreshell nanoparticle (of any specific size) with the iron oxide nanoparticle encapsulated in the center. Aggregation between iron oxide nanoparticles prior to or during the coating process sometimes led to the trapping of multiple nuclei in a single silica shell. Typical distributions for nuclei per shell were on the order of 70% monomers, 19% dimers, 7% trimers, and 5% greater than trimers. An increased ratio of monomers may be favored through decreased iron oxide concentration and good mixing by sonication to ensure that the core particles are well separated before coating begins. Fluorescent iron oxide-silica nanoparticles have also been synthesized by incorporating organic dyes into the silica shells using a modified sol-gel procedure.18 In this case, the dyes had a thioisocyanate functional group that could be coupled to the amine group of 3-aminopropyl-triethoxysilane (APS, Aldrich) through an addition reaction. The covalent bond formed in this reaction could stabilize the fluorescent dye and make it possible to chemically incorporate this dye into the silica shell by cohydrolyzing with TEOS. Two fluorescent dyes were selected as examples to demonstrate the concept: 7-(dimethylamino)-4-methylcoumarin-3-isothiocyanate (DACITC) and tetramethylrhodamine5-isothiocyanate (5-TRITC) (Molecular Probes, Eugene, OR). In a typical procedure, 0.2 × 10-3 g of DACITC (or 5-TRITC) was added to a mixture of 0.5 mL APS coupling agent and 5 mL 2-propanol after this mixture had been degassed for 10 min. The reaction was allowed to proceed at room temperature for 24 h in the dark under the protection of nitrogen gas. The as-synthesized APS-DACITC compound was mixed with TEOS precursor (1:4, v/v) and then injected into the ferrofluid solution to form core-shell nanoparticles. DACITC has its excitation and emission maxima at 400 and 476 nm. 5-TRITC has its excitation and emission maxima at 543 and 571 nm. Figure 3A and B shows the fluorescence optical microscopy images of DACITC- and 5-TRITC-labeled core-shell samples taken with a Leica inverted optical microscope (DMIRBE). These two samples were prepared by evaporating 10 µL of as-synthesized nanoparticle dispersions on silicon substrates in the presence of a 27 megagauss magnetic field (Polysciences, Warrington, PA). These magnetic nanoparticles had been lined up to form chain-like structures (with their longitudinal directions oriented along the magnetic field) due to the attractive interaction between the magnetic moments. The insets are TEM images of the corresponding nanoparticles (deposited Nano Lett., Vol. 2, No. 3, 2002
Figure 3. Fluorescent microscopy images of chain-like structures formed by silica-coated iron oxide nanoparticles in the presence of an external magnetic field. The silica coatings of these nanoparticles had been derivatized with fluorescent organic dyes by coupling (A) DACITC, and (B) 5-TRITC with the APS precursor. The insets show TEM images of these core-shell nanoparticles that were deposited on TEM grids under no magnetic field.
on TEM grids under no magnetic filed), showing the coreshell structure for these two samples. In summary, we have demonstrated a convenient method for coating superparamagnetic nanoparticles of iron oxide with uniform shells of amorphous silica. The thickness of this silica coating could be easily controlled in the range of 2-100 nm by changing the concentration of the TEOS precursor. In addition to the iron oxide nanoparticles contained in commercial ferrofluids, this procedure has also been successfully extended to magnetite nanoparticles synthesized using a wet chemical method.19 In this case, superparamagnetic core-shell nanoparticles with a similar control over the structure and uniformity were obtained.20 The silica shells could also be labeled with fluorescent organic dyes to generate multifunctional nanoparticles that exhibit a unique combination of magnetic and optical properties. We believe that the sol-gel process described 185
here can also be extended to other metal oxide systems to fabricate core-shell nanoparticles with various properties for different applications.21 In addition to their uses as dispersions in liquid media, those magnetic particles with relatively thick shells could also serve as building blocks to construct photonic crystals whose band gap properties could be manipulated using an external magnetic field.21 Acknowledgment. This work has been supported in part by a DARPA-DURINT subcontract from Harvard University, a Fellowship from the David and Lucile Packard Foundation, and a Career Award from the National Science Foundation (DMR-9983893). Y.X. is a Research Fellow of the Alfred P. Sloan Foundation (2000-2002). Y.Y. and B.T.M. thank the Center for Nanotechnology at the UW for a Graduate Student Fellowship and an IGERT Fellowship (supported by the NSF, DGE-9987620), respectively. References (1) Rosensweig, R. Ferrohydrodynamics; Cambridge University Press: Cambridge, 1985. (2) Ozaki, M. MRS Bull. 1989, December, 35. (3) Babes, L.; Denizot, B.; Tanguy, G.; Jacques, J.; Jeune, L.; Jallet, P. J. Colloid Interface Sci. 1999, 212, 474. (4) (a) Gupta, P. K.; Hung, C. T. Life Sci. 1989, 44, 175. (b) Fukushima, T.; Sekizaqa, K.; Jin, Y.; Yamaya, M.; Sasaki, H.; Takishima, T. Am. J. Physiol. 1993, 265, L67. (5) Chemla, Y. R.; Crossman, H. L.; Poon, Y.; McDermott, R.; Stevens, R.; Alper, M. D.; Clarke, J. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 14268. (6) (a) Whitesides, G. M.; Kazlauskas, R.; Josephson, L. TIBTEH 1983, 114. (b) Ugelstad, J.; Berge, A.; Ellingsen, T.; Schmid, R.; Nilsen, T.-N.; Mork, P. C.; Stenstad, P.; Hornes, E.; Olsvik, O. Prog. Polym. Sci. 1992, 17, 87. (7) See, for example, (a) Butterworth, M. D.; Illum, L.; Davis, S. S. Colloids Surf. A 2001, 179, 93. (b) Szabo, D. V.; Vollath, D. AdV. Mater. 1999, 11, 1313. (c) Donselaar, L. N.; Philipse, A. P.; Suurmond, J. Langmuir 1997, 13, 6018. (d) Liu, Q.; Xu, Z.; Finch,
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J. A.; Egerton, R. Chem. Mater. 1998, 10, 3936. (e) Correa-Duarte, M. A.; Giersig, M.; Kotov, N. A.; Liz-Marza´n, L. M. Langmuir 1998, 14, 6430. See, for example, Ulman, A. Chem. ReV. 1996, 96, 1533. Sto¨ber, W.; Fink, A.; Bohn, E. J. Colloid Interface Sci. 1968, 26, 62. (a) Homola, A. M.; Rice, S. L. U.S. Patent 4,280,918, 1981. (b) Bruce, C. A.; Homola, A. M.; Lorenz, M. R. U.S. Patent 4,333,961, 1982 (c) James, R. O.; Bertucci, S. J.; Oltean, G. L. U.S. Patent 5,217,804, 1993. Ohmori, M.; Matijevic, E. J. Colloid Interface Sci. 1992, 150, 594. (a) Klotz, M.; Ayral, A.; Guizard, C.; Menager, C.; Cabuil, V. J. Colloid Interface Sci. 1999, 220, 357. (b) Philipse, A. P.; van Bruggen, M. P. B.; Pathmamanoharan Langmuir 1994, 10, 92. (a) Wang, G.; Harrison, A. J. Colloid Interface Sci. 1999, 217, 203. (b) Liz-Marza´n, L. M.; Giersig, M.; Mulvaney, P. Chem. Commun. 1996, 731. (c) Liz-Marza´n, L. M.; Giersig, M.; Mulvaney, P. Langmuir 1996, 12, 4329. (a) Santra, S.; Tapec, R.; Theodoropoulou, N.; Dobson, J.; Hebard, A.; Tan, W. Langmuir 2001, 17, 2900. (b) Chang, S.-Y.; Liu, L.; Asher, S. A. J. Am. Chem. Soc. 1994, 116, 6745. Iakovenko, S. A.; Trifonov, A. S.; Giersig, M.; Manedov, A.; Nagesha, D. K.; Hanin, V. V.; Soldatov, E. C.; Kotov, N. A. AdV. Mater. 1999, 11, 388. (a) Vandenberghe, R. E.; Vandenberghe, R.; De Grave, E.; Robbrecht, G. J. Magn. Magn. Mater. 1980, 15, 1117. (b) Sato, T.; Iijima, T.; Seki, M.; Inagaki, J. J. Magn. Magn. Mater. 1987, 65, 252. (c) Tronc, E.; Belleville, P.; Jolivet, J. P.; Livage, J. Langmuir 1992, 8, 313. See, for example, Thiaville, Miltat, J. Science 1999, 284, 1939. (a) Verhaegh, N. A. M.; van Blaaderen, A. Langmuir 1994, 10, 1427. (b) van Blaadern, A.; Vrij, A. Langmuir 1992, 8, 2921. Cornell, R. M.; Schwertmann, U. The Iron Oxides: Structure, Properties, Reactions, Occurrence and Uses, VCH: Weinheim, 1996, p 493. Note: Chemically synthesized magnetite nanoparticles were stabilized by oleic acid to obtain surface properties similar to those of commercial ferrofluid EMG 304. Sharrock, M. P. MRS Bull. 1990, March, 53. (a) Wen, W.; Wang, N.; Ma, H.; Lin, Z.; Tam, W. Y.; Chan, C. T.; Sheng, P. Phys. ReV. Lett. 1999, 82, 4248. (b) Xu, X.; Friedman, G.; Humfeld, K. D.; Majetich, S. A.; Asher, S. A. AdV. Mater. 2001, 13, 1681.
NL015681Q
Nano Lett., Vol. 2, No. 3, 2002
