Metastable  -FeNi Nanostructures with Tunable T C Kelsey J. Miller, M. Sofman, and M.E. McHenry Dept. of Mat. Sci. and Engr., Carnegie Mellon University, Pittsburgh, PA USA Motivation Materials - FeNi Design Results Research Objectives Synthesis [1] K. Okawa, et al. J. Appl. Phys., 99, 08H102, (2006). [2] Binary Alloy Phase Diagrams: Second Edition, Vol. 2. Editor: Thaddeus B. Massalski ( ). [3] Rosensweig, RE, J. Magn. Magn. Mater. 252, 370 (2002). [4] L.Y. Zhang,et al. J. Magn. Magn. Mat. 311, 228–33 (2007). Recently, Local Hyperthermia and Thermoablative therapies have gained acceptance as feasible techniques for cancer treatment with minimal side effects [1]. Due to reduced blood flow in tumors, cancer cell are more susceptible to high temperature and typically die in temperature ranges at which healthy cells can survive for prolonged times. Local Hyperthermia involves selectively elevating the temperature of the cancerous tissues to 2-9°C above the normal body temperature (37°C) and is usually used in conjunction with other forms of treatment like chemotherapy or radiotherapy. It helps enhance the cytotoxicity of the drug or radiation, reducing their dosage and minimizing the damage to the healthy tissue. Thermoablation refers to the process of raising the temperature of cancer cells up to 56°C or higher which results in carbonization, coagulation and cell necrosis. Magnetic Hyperthermia employs magnetic nanoparticles (MNPs) to generate heat under the application of a radio frequency (RF) AC magnetic field. Traditionally, iron oxide systems have been extensively studied for this purpose due to their excellent biocompatibility. However, metallic systems have much higher moments in comparison to oxides and hence can offer higher heating rates at much lower concentration. Iron-Nickel (Fe-Ni) nanoparticle systems present exciting possibilities for improving hyperthermia efficiency as they exhibit large magnetic moments, naturally form stable, protective ferrite shells aiding in functionalization and improving biocompatibility, and have a tunable Curie temperature (T C ) with composition allowing for the self-limiting heating of these nanoparticles at the Curie temperature. Dispersion & Functionalization FeNi ferrofluid produced by dispersing MNPs in Polyethylene glycol (PEG) surfactant The goal of this research is to synthesize Fe 1-X Ni x (x=10-30) nanoparticles with a Curie temperature (T C ) of 37-47°C appropriate for biomedical application. The ultimate aim is to stabilize the  -FeNi phase of appropriate composition and T C to correspond to biologically relevant temperatures. The nanoparticles contained within a fluid (ferrofluids) should exhibit self-limited heating properties at the Curie temperature, the point at which they become non-magnetic and stop heating. These self-limiting particles are targeted for biomedical applications in hyperthermia and thermoablative cancer therapy BCC FCC Components of system  FeNi nanoparticles  Jet-Casting was used to synthesize amorphous ribbon of Fe 1-X Ni X (x=10-30) alloys  Crushed into nano-size particles using high- energy mechanical mill  Annealed samples into  phase field (T>700 °C) followed by water quench   Ferrofluid  Coated MNPs with sodium oleate and polyethylene oxide (PEO) surfactants to stabilize in aqueous solution  RF heating study  Heating rates of ferrofluids were measured at biologically safe frequencies ( kHz) with field amplitudes of Oe RF Losses in Ferrofluids Experimental Design MNPs in a ferrofluid generate heat when exposed to an AC magnetic field. The heat generated (ΔT) is influenced by magnetization (M d ) and relaxation time (  R ). Two dominant paths of relaxation: the reorientation of the magnetic moment within each particle against a magnetic anisotropy barrier (Néel relaxation) and the reorientation of a particle itself against the viscous friction within the fluid (Brown relaxation) Stainless Steel Balls Nano-powder Ref. [3] Rosensweig, J. Magn. Magn. Mater., 252, (2002). Production of amorphous ribbons using jet-casting with controlled nanocrystalline size by melting transition metal elements with glass formers and cooling them at 1,000,000 °C/min RF Heating Application FeNi alloy free energy diagrams at 200°C and 500°C, respectively. The phase that has the lowest Gibbs free energy at a particular composition will spontaneously form at that given temperature. FeNi binary phase diagram [2] with compositional dependence of the Curie temperature (left) This Tc behavior for the  -FeNi phase can be extrapolated to metastable regions of the FeNi phase diagram [2] where desired Tc’s near 27°C are predicted to occur near the 27 % nickel composition (right) BCC FCC BCC FCC BCC FCC BCC (111) (110) (020) (200) (220) (211) (311) (222) (400) X-ray diffraction patterns labeled with hkl planes of the constituent phases revealed the crystal structure before annealing to be a mix of BCC  -Fe and FCC FeNi 3. A Scherer’s analysis of line broadening in XRD patterns revealed a mean particle size of ~20 nm. TEM was used to examine the morphology of the Fe 73 Ni 27 nanoparticles after 24 hrs of high-energy mechanical milling and selected area electron diffraction (SAED) was used to identify present crystalline phases. Mean particle size was determined to be 20 nm from a sampling of ~100 nanoparticles. The SAED pattern confirms the presence of the FCC-gamma phase, where the position and relative intensities of diffracted rings match well with theoretical values for FCC  -FeNi. This XRD pattern shows that after annealing and quenching the Fe 73 Ni 27 sample, the metastable mix of BCC  -Fe and FCC FeNi 3 was transformed into solely FCC phase region; indicated by the FCC peaks. This shows that a nearly exclusive  -FeNi phase was successfully achieved. The extra small peaks, when matched with known XRD patterns, are spinel ferrite oxidation (NiFe 2 O 4 ). Mechanical milling crushes ribbons into nano-sized particles by mechanical grinding and mixing actions Crushing Annealing The powder was then annealed to 700 °C, in the  -FeNi phase field, for 2 hrs followed by quenching in water to retain the metastable FCC  -FeNi phase Nanoparticle and Ferrofluid Synthesis RF Heating Study Fe 3 O 4 f = 55 kHz  Very substantial heating rates are shown for iron-oxide particles [4] (left), but the maximum increase in temperature never exceeds 50°C in a period of 10min. This value is very low due to the small magnetic dipole moment of oxides.  Fe 73 Ni 27 nanoparticles show improved heating rates from room temperature to 100°C, reaching a heating rate of 80°C in a period of 2min at 200 Oe applied field. The plot also shows a leveling off of the heating rate around the Curie temperature of the alloy, demonstrating the self-regulated heating ability of Curie-limited FeNi nanoparticles.  Using a much lower concentration and field, FeNi nanoparticles would still be able to reach temperatures necessary for thermotherapy in a reasonable time. Magnetic Properties Measurement Magnetization versus temperature, M vs. T, plots obtained for Fe 73 Ni 27 nanoparticles after a 2hr anneal at 700°C. The Curie temperature, T C, of each phase was estimated by squaring the reduced magnetization and extrapolating to m=M/Ms=0. A T C of 120°C for the FCC  -FeNi phase is observed upon heating of the alloy from room temperature to 200°C. This plot also shows the transformation of the metastable FCC  -FeNi phase back into the higher Curie temperature BCC  -Fe phase upon heating to 600°C. The BCC  -Fe phase is shown to have a T C around 550°C. We note the good agreement of the experimentally estimated values of T C with the values predicted from the Tc(  -Fe,Ni) dotted lines as shown earlier in the Fe-Ni phase diagram [2] for the Fe 73 Ni 27 composition.  Once in the γ-FeNi phase, the Fe:Ni composition can be varied to tune the Tc in these MNPs which can have important application in the radio frequency (rf) magnetic heating for cancer thermotherapies vol% 19nm Fe 3 O 4 Dextran coated vol% 20 nm Fe 73 Ni 27 PEG coated Applied Field: Conclusions  Synthesized FeNi nanoparticles from jet-casting amorphous ribbons followed by mechanical milling.  TEM images of annealed powders confirmed presence of FCC FeNi and allowed for particle size analysis.  Magnetic measurements clearly show a low Tc from γ-FeNi nanoparticles which can be tunable with Fe:Ni composition.  Demonstrated superior RF heating capabilities in FeNi MNPs suspended in PEG.  Demonstrated sharp heating rate transition in Curie-limited FeNi MNPs for self-regulated heating behavior.  Preliminary studies show uptake of FeNi MNPs into HeLa cells and a high percentage of living cells after exposure. References Biocompatibility Study Fe 73 Ni 27 uptake in HeLa cells (63x) Hoechst Live cells (20x) Propidium iodide (PI)- dead cells (20x) (Photos from Ryan Chehanske) Working in collaboration with Prof. Kris Dahl’s research group at Carnegie Mellon University to test cytotoxicity of the nanoparticles using fluorescence microscopy. Preliminary results show uptake of Fe 73 Ni 27 MNPs into HeLa cells and a high percentage of live cells (from Hoechst Blue DNA dye) after exposure.