Flame synthesis of superparamagnetic Fe/Nb nanocomposites for biomedical applications

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1 Available online at Proceedings of the Combustion Institute 32 (2009) Proceedings of the Combustion Institute Flame synthesis of superparamagnetic Fe/Nb nanocomposites for biomedical applications J.A. Nuetzel a, C.J. Unrau a, R. Indeck b, R.L. Axelbaum a, * a Department of Energy, Environmental, and Chemical Engineering/Center for Materials Innovation, Washington University in Saint Louis, St. Louis, MO 63130, USA b Department of Electrical and Systems Engineering, Washington University in Saint Louis, St. Louis, MO 63130, USA Abstract Iron/niobium nanocomposite particles are produced using the sodium flame and encapsulation (SFE) process. Ferrocene is added to the vapor-phase metal halide/sodium reaction to produce metallic iron particles encapsulated in niobium. To accomplish this, the ferrocene is combined with niobium chloride vapor and this mixture is injected as a turbulent jet into a stream of sodium vapor. The ferrocene is expected to decompose upstream of the flame to form iron particles, which pass through the niobium chloride-sodium reaction zone wherein they are encapsulated in niobium. The salt byproduct then encapsulates these particles, preventing oxidation. The as-produced Fe/Nb particles were found to contain Fe particles that are less than 15 nm in diameter and are superparamagnetic with a coercivity of 50 Oe and a saturation magnetization of over 200 emu/g of Fe. In addition to possessing a strong magnetic response and small remnant magnetization, the iron/niobium composite particles are expected to be biocompatible and X-ray opaque. Consequently, these materials hold promise for magnetic navigation in biomedical applications. Ó 2009 The Combustion Institute. Published by Elsevier Inc. All rights reserved. Keywords: Sodium; Superparamagnetic; Composite nanoparticles; Iron; Niobium 1. Introduction * Corresponding author. address: rla@wustl.edu (R.L. Axelbaum). Magnetic nanomaterials are of interest for biomedical applications including magnetic targeted drug delivery, magnetic catheter guidance, and magnetically guided and activated hyperthermic catabolism of tumors. These applications employ magnetic transport and are similar in terms of their material requirements [1]. Specifically, particles used in these applications must possess a strong magnetic response but with minimal remnant magnetization or hysteresis. A strong magnetic response is desirable, as it minimizes the strength of the magnetic field that is required. Remnant magnetization must be avoided because it could lead to undesirable behavior of the magnetized particles. For example, while ferromagnetic particles have a strong magnetic response, their remnant magnetization causes them to flocculate after being exposed to a magnetic field. This could result in obstructions in the vasculature if introduced in the blood stream. Flocculation can be avoided by utilizing superparamagnetic materials, which have no remnant magnetization but still have a magnetic response on the order of typical ferromagnetic materials [1 3]. Similarly, since ferromagnetic particles possess hysteresis, the response of these particles to a magnetic field /$ - see front matter Ó 2009 The Combustion Institute. Published by Elsevier Inc. All rights reserved. doi: /j.proci

2 1872 J.A. Nuetzel et al. / Proceedings of the Combustion Institute 32 (2009) would depend on the magnetic history of the particles, making the particle response unpredictable. Superparamagnetic materials do not suffer from hysteresis. When the size of an iron particle is sufficiently small (<15 nm), the particle can contain only one magnetic domain. The single domain structure gives rise to superparamagnetic behavior in which the magnetic particle is free to align with an applied field and produce a strong magnetic moment. Yet when the field is removed, thermal agitation will cause the particle to revert to a zero net magnetization. While iron nanoparticles have the desirabled magnetic properties, elemental iron is toxic in the body [4]. Thus, a biocompatible material is needed to encapsulate the iron so that it can be employed in medical applications. Such iron nanocomposites have been produced by a variety of techniques. Yang et al. [5] synthesized iron nanoparticles encapsulated with nickel using an oxidation reduction process involving hydrazine. These particles were shown to be nearly uniform in size (6 nm) and possess superparamagnetic properties. Chastellain et al. [6] produced superparamagnetic composite nanoparticles by first forming iron nanoparticles through coprecipitation in water followed by encapsulation with polyvinyl alcohol. Wang et al. [7] formed iron mullite composite nanoparticles through reduction of an iron mullite solution produced from a sol-gel process. These particles were shown to be only partially superparamagnetic. Finally, Tartaj and Serna [8] employed microemulsions to synthesize superparamagnetic particles consisting of a core with Fe particles dispersed in a silica matrix and a shell consisting only of silica. In this study, superparamagnetic nanocomposite particles are produced with an iron core and a niobium shell. The nanocomposite particles are produced in a one-step process using the Sodium Flame and Encapsulation (SFE) process [9,10]. Iron nanoparticles are synthesized to a size of less than 15 nm in diameter to ensure that they are superparamagnetic. These particles are subsequently encapsulated with niobium metal, which serves as a biocompatible shield [11]. An additional benefit of niobium is that it has a large cross section for X-ray absorption and thus serves as an X-ray attenuator so that the particles can be observed in real time as they move through the body using small doses of radiation [12]. 2. The sodium flame and encapsulation process The SFE process is a controlled application of the reaction between vaporous sodium and metal halides. Many single component metals, including niobium, have been produced using the SFE process [9,10]. Niobium is produced via the reaction: NbCl 5 þ 5Na! Nb þ 5 ð1þ The halide is introduced into the heated reactor where it mixes with sodium and reacts to form a pure metal and a salt byproduct. When the gases cool, the salt condenses on the particles creating a protective encapsulate. The thermodynamics of Reaction 1 are such that the thermodynamic yield approaches 100% provided that the temperature is sufficiently low (<1400 K). In addition, Reaction 1 is hypergolic, eliminating the need for an ignition source and ensuring complete reaction even at very low temperatures. Sodium/halide reactions have been observed at temperatures as low as 600 K. The ability to have complete reaction over a wide range of temperatures allows flame temperature to be modified to control other aspects of the process, such as sintering rate or condensation of the salt byproduct. In this work, we demonstrate the SFE process for production of iron/niobium nanocomposite powders. The SFE process is used to produce niobium and an iron precursor is added to the halide stream to produce iron. Precursor selection is critical to ensure that the iron is formed in a region of the flame so that it can be of appropriate size and encapsulated by niobium. The resulting product must yield iron crystallites of less than 15 nm that are largely covered with niobium. In addition to the need to encapsulate the iron for biocompatibility, it is also necessary that the iron particles be encapsulated to protect them from post-flame oxidation. If iron nanoparticles of the required size were exposed to air, they would oxidize and lose their high saturation magnetization. An important benefit of the SFE process for making these nanocomposites is that it is a continuous one-step process, which is in contradistinction to the other processes discussed in the previous section. The oxidation sensitive iron component is encapsulated with biocompatible niobium particles in situ. In addition, post-flame oxidation is inhibited by the salt encapsulate that is also formed during the SFE process. The iron particle size of the nanopowders produced in the SFE reaction can be adjusted by reactant concentration and reactor temperature. No additional processing steps are necessary to ensure the fine grain size and magnetic characteristics that are appropriate for the desired biomedical applications. Finally, minimal post-processing of the produced particles is required and the salt byproduct can be removed down to less than 10 ppm, as has been demonstrated for both water washing and vacuum sublimation [13]. 3. Experiment In order to produce an iron/niobium nanocomposite, an iron precursor is added to the

3 J.A. Nuetzel et al. / Proceedings of the Combustion Institute 32 (2009) SFE process. To produce iron encapsulated in niobium, (as opposed to, for example, niobium encapsulated in iron) it is necessary to first form the iron particles and then to rapidly encapsulate them in niobium. In this way, the growth of the iron particles can be arrested due to the presence of niobium. Thus, if done appropriately, the niobium can serve two purposes: (1) to encapsulate the iron, making it both resistant to post-flame oxidation and biocompatible, and (2) to act as an inhibitor to aggregated growth of the iron nanoparticles in the flame by physically separating one iron particle from another through the presence of niobium. The latter is valuable as it allows the concentration of iron precursor to be high, thus maximizing production rate, while ensuring the iron particle size is sufficiently small that superparamagnetic behavior is attained. To accomplish this, ferrocene was chosen as the iron precursor because its decomposition temperature of 650 K [14], gives it the appropriate property necessary to form iron particles first. Ferrocene has the additional benefits in that it is stable and safe to use. As ferrocene approaches the flame front, it is expected to decompose, allowing iron particles to nucleate before the Na/NbCl 5 reaction zone (Fig. 1). Thus, the iron is encapsulated in niobium to form composite nanoparticles. These particles are then encapsulated by the condensing salt. For this study the reactants were maintained at dilute concentrations (Na = 0.1% and NbCl 5 = 0.7% by mole), allowing temperature to be controlled by the reactor temperature. The mass ratios of Fe to Nb as well as the reactor and burner head temperatures are shown for three experiments in Table 1. As shown in Fig. 1 the burner consists of three concentric tubes through which the gases issue. The inside diameter of the inner (jet) tube is 2 mm, the middle tube is 12 mm and the outer tube is 63 mm. The jet diameter and operating conditions are chosen to ensure a turbulent jet flame, which can be visually confirmed through a sight port. A schematic diagram of the reactor is shown in Fig. 2. Liquid sodium is delivered to a vaporizer via a heated syringe pump. The sodium is then vaporized and mixed with argon before entering the outer coflow (Fig. 1). Niobium chloride is gasified in a heated bubbler-type apparatus by sublimation of niobium chloride powder in a metered stream of argon. The bubbler was calibrated by drawing the gas mixture exiting the bubbler through a room-temperature glass tube filled with vermiculite. This caused the niobium chloride to condense within the tube and then the tube was weighed to obtain the mass gain in a prescribed amount of time. The ferrocene was delivered and calibrated in a manner similar to that of the niobium chloride. The chloride and argon were mixed and introduced through the central tube. An inner coflow of argon surrounds the central tube, acting as a sheath flow to avoid particle buildup on the central tube. The hypergolic nature of Reaction 1 results in spontaneous reaction on mixing and thus, the sheath flow acts to delay mixing between the chloride and sodium streams, which eliminates particle deposition on the burner tubes. Argon for critical flows is metered by mass flow controllers and for other flows it is metered with rotameters. The reactor, reservoirs, and lines are heated and insulated, and temperatures are controlled with programmable set-point controllers. Powders are collected on a porous stainless steel filter which can be rotated and scraped to continuously remove the collected powder. The resulting powder falls through a collection chute into a collection bottle. A number of analytical tools were used to determine the composition, size, morphology, and magnetic properties of the nanocomposite powders. Composition was determined with inductively coupled plasma mass spectroscopy (ICP-MS). Particle size and morphology were determined with a Hitachi S4500 field emission Fig. 1. Graphical representation of the SFE reaction showing desired ferrocene decomposition behavior.

4 1874 J.A. Nuetzel et al. / Proceedings of the Combustion Institute 32 (2009) Table 1 Results for experiments A C Run Fe/Nb mass ratio (from ICP) Saturation magnetization (emu/g) (emu/g-fe) Coercivity (Oe) Burner head temp. ( C) A 4.4: B 4.3: C 2.5: Reactor temp. ( C) scanning electron microscope (SEM). Additional information on elemental composition was obtained using energy dispersive spectroscopy (EDS). X-ray diffraction (XRD) was performed to identify crystalline phase and estimate crystalline size. The induced magnetic moment and coercivity of the nanoparticles were determined using an EG&G PARC model 4500 vibrating sample magnetometer (VSM). H M data of the resulting magnetic behavior was obtained and adjusted for sample weight. Coercivity and the saturation magnetization of the samples were obtained from the hysteresis curve. A Digital Instruments Nanoscope was used to perform magnetic force microscopy (MFM) on a sample to verify the superparamagnetic properties of the materials. With MFM, a visual contrast is apparent where ordered magnetic domains intersect. In a superparamagnetic material, we expect to see very little contrast at the micro scale, as there should be no overall magnetic order. The salt encapsulated powder was pressed against an optical flat with a vise in a room temperature die for 72 h to achieve the surface finish sufficient for the MFM analysis. 4. Results Prior to synthesis of composite nanopowders, the reactor operating conditions were optimized by running simulations of flow conditions using the FLUENT computational fluid dynamics package. Nanopowders were subsequently produced using three sets of run conditions. For runs A and B, reactant and ferrocene flow rates were held constant while reactor and burner head temperatures were varied. For run C, the ferrocene flow rate was reduced while maintaining the reactor and burner head temperatures used for run B. These quantities were varied in order to determine their effects on the coercivity and saturation magnetization of the particles. A typical SEM image of unwashed (salt encapsulated) powder is shown in Fig. 3a. The total particle size is in the range of nm. There is minimal evidence of fine un-encapsulated material on the surfaces of the salt particles, suggesting nearly complete encapsulation. Figure 3b shows a Fe/Nb sample after removal of the salt encapsulate by water washing. The composite particle size is in the range of nm in diameter. The mass fraction of iron and niobium of each sample was determined by ICP-MS and the results are shown in Table 1. Samples from runs A and B had similar Fe/Nb mass ratios as expected since the ferrocene and NbCl 5 flow rates were held constant for these experiments. Wide field EDS analysis conducted on each sample produced similar results and a typical result is shown in Fig. 4. Both niobium and iron are present and the mass ratio calculated from this spectrum is comparable with the results from ICP analysis. Although EDS and ICP analysis both indicate that iron and niobium are present in the particles, the peaks corresponding to these elements were not present in the spectrum generated by X-ray diffraction analysis (Fig. 5). The XRD spectrum shown in Fig. 5 was obtained from an unwashed sample and the only peaks observed correspond to (halite peaks are superimposed on the spectrum). The iron and niobium peaks do not appear in the XRD spectrum because the individual crystallite sizes of the particles are very small or the material is amorphous. XRD peaks corresponding to crystallite sizes smaller than circa 10 nm are broad and can be lost in the background. This gives some indication that the size of the iron core is small enough to yield superparamagnetic behavior. In order to determine if these particles behave superparamagnetically, samples from runs A and B were analyzed with a vibrating sample magnetometer (VSM). The VSM data for samples A and B are shown in Fig. 6 and numerical values for the saturation magnetization and coercivity are given in Table 1. The saturation magnetization is the maximum induced magnetic moment that can be obtained in a magnetic field; beyond this field no further increase in magnetization occurs. Coercivity is a measurement of the amount of magnetic field required to remove the remnant magnetization from a ferromagnetic material. Both samples had a saturation magnetization of about 220 emu/g-fe which was determined by dividing the saturation value of the magnetic moment in Fig. 6 by the appropriate iron mass fraction found from Table 1. This high saturation magnetization is desirable for the biomedical applications mentioned above as it reduces the strength of the magnetic field gradient that is required to move the particles. Furthermore, this suggests that the iron has not been oxidized as iron oxide at room temperature is not magnetic.

5 J.A. Nuetzel et al. / Proceedings of the Combustion Institute 32 (2009) Fig. 2. Reactor schematic and flow diagram. While metastable c-fe 2 O 3 which is used in the recording industry is magnetic, it is not produced during low temperature oxidation in air. Thus, the relatively high saturation magnetization attests to the effectiveness of the Nb encapsulation. Although samples from both runs had similar saturation magnetizations, the sample from run A had a higher coercivity than that of run B as illustrated by comparing the width of the hysteresis curves in Fig. 6a and b. Coercivity is given by the point where the hysteresis curve crosses the positive x-axis and thus, the coercivities of powders from runs A and B were 100 Oe and 50 Oe, respectively. A true superparamagnet would have a coercivity of zero and although neither sample demonstrated perfect superparamagnetic behavior, the low coercivity of the sample from run B indicates the presence of nanoscale iron at a mean particle size of less than 15 nm, which is the superparamagnetic transition size [1 3]. If a significant amount of iron particles in the powder were larger than 15 nm, the coercivity of the sample would be significantly larger since just above this size, coercivity reaches a maximum value [1]. Thus, the powder from run B can be considered to be superparamagnetic. The difference in coercivity between the powders from runs A and B indicates a change in the size distribution of iron particles, with run B containing smaller iron particles. The experimental conditions for runs A and B were similar except that the temperature of the reactor and the burner head was 50 C lower for run B. The decrease in temperature would cause the rate of ferrocene decomposition to decrease and thus, iron particles formed after ferrocene decomposition would be encapsulated by niobium at a smaller size than for the higher temperature case. In addition, the lower reactor temperature would decrease coalescing of the iron and thus reduce the crystallite size. These effects could account for the lower coercivity of the powders from run B. A lower coercivity than that obtained from run B would be desirable, however, temperatures could not be reduced further as lower temperatures would cause the sodium vapor to condense. Thus, for run C the powder was produced by reducing the ferrocene concentration while maintaining the same temperatures as those of run B. The ferrocene concentration was reduced enough so that the Fe/Nb mass ratio was smaller than that of run B by about a factor of 2. This gave a mass ratio of 2.5 to 1 for the powder of run C. VSM analysis and magnetic force microscopy (MFM) were performed on this powder to determine its magnetic properties. The coercivity of the powder, as determined by VSM analysis, was 50 Oe and thus, the coercivity was not reduced from that of run B. In fact, reducing the ferrocene concentration only reduced the saturation magnetization (Table 1), which is undesirable. This suggests that there may be a limitation to the SFE process in terms of the lowest value of coercivity that can be achieved, with further reduction in iron particle size only decreasing the saturation magnetization. For the MFM analysis, a 100 lm 2 area was studied and relatively smooth transitions in phase were observed, which is consistent with superparamagnetic behavior. If ferromagnetism were the dominant phenomenon, distinct large phase, high contrast grain boundaries would be present. The

6 1876 J.A. Nuetzel et al. / Proceedings of the Combustion Institute 32 (2009) Intensity Theta (deg) Fig. 5. XRD spectrum of an unwashed sample with halite peaks superimposed. The lack of iron or niobium peaks suggests that their crystallite size is below circa 10 nm. decomposition of ferrocene followed by nucleation of iron particles, encapsulation of these particles by niobium and further encapsulation of the Fe/Nb particles by the salt byproduct. The magnetic properties of these particles proved to be a function of the system temperature with a lower temperature leading to a smaller iron particle size and consequently, improved superparamagnetic properties. These superparamagnetic Fe/Nb nanoparticles Fig. 3. (a) SEM image of unwashed powder from run A showing nm particles. (b) SEM image of waterwashed powder showing nm iron/niobium composite particles. 30 Intensity Na Cl Fe C O Nb Cl Energy (kev) Moment (emu/g) Field (Oe) b 50 Fig. 4. Wide field EDS analysis of powder from run A. results of this study indicate that nanocomposite particles with superparamagnetic characteristics can be produced efficiently using the SFE process. Moment (emu/g) 0 5. Conclusions The Sodium Flame and Encapsulation process has been extended to production of Fe/Nb nanocomposite particles. These particles are formed by Field (Oe) Fig. 6. VSM data for powders from (a) run A and (b) run B.

7 J.A. Nuetzel et al. / Proceedings of the Combustion Institute 32 (2009) may be useful for biomedical applications such as magnetic targeted drug delivery, magnetic catheter guidance, and magnetically guided and activated hyperthermic catabolism of tumors. Acknowledgments This research was funded under the NSF-NIRT program. R.L.A. and Washington University may receive income based on a license of related technology by the University to Cabot Corporation. Cabot Corporation did not support this work. References [1] Q.A. Pankhurst, J. Connolly, S.K. Jones, J. Dobson, J. Phys. D Appl. Phys. 36 (13) (2003) R167 R181. [2] A.K. Giri, J. Appl. Phys. 81 (3) (1997) [3] E.F. Kneller, F.E. Luborsky, J. Appl. Phys. 34 (3) (1962) [4] M.E. Conrad. Available at: < [5] C. Yang, J. Xing, Y. Guan, J. Liu, H. Liu, J. Alloy Compd. 385 (1 2) (2004) [6] M. Chastellain, A. Petri, H. Hofmann, J. Coll. Interf. Sci. 278 (2) (2004) [7] H. Wang, T. Sekino, K. Niihara, Chem. Lett. 34 (3) (2005) [8] P. Tartaj, C.J. Serna, J. Am. Chem. Soc. 125 (51) (2003) [9] R.L. Axelbaum, Powder Metall. 43 (4) (2000) [10] D.P. Dufaux, R.L. Axelbaum, Combust. Flame 100 (3) (1995) [11] Adv. Mater. Process 161(9) (2003) [12] Z.H. Levine, S. Grantham, C. Tarrio, et al., J. Natl. Inst. Stan. 108 (1) (2003) 10. [13] J.L. Barr, R.L. Axelbaum, M.E. Macias, J. Nanopart. Res. 8 (1) (2006) [14] R.L. Vander Wal, L.J. Hall, Combust. Flame 130 (1 2) (2002)