Nanotechnology

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Enhanced magnetic anisotropy and heating efficiency in multi-functional

manganese ferrite/graphene oxide nanostructures
To cite this article: Anh-Tuan Le et al 2016 Nanotechnology 27 155707

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Page 1 of 29 CONFIDENTIAL - AUTHOR SUBMITTED MANUSCRIPT NANO-108590.R1

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Enhanced magnetic anisotropy and heating
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9 efficiency in multi-functional manganese
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13 ferrite/graphene oxide nanostructures
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Anh-Tuan Le1*, Chu Duy Giang1, Ta Quoc Tuan1, Vu Ngoc Phan1, Javier Alonso2,3*, Jagannath
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20 Devkota2, Eneko Garaio4, José Ángel García3,5, R. Martín-Rodríguez4, M.L. Fdez-Gubieda4,5,
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22 Hariharan Srikanth2, and Manh-Huong Phan2*
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26 Department of Nanoscience and Nanotechnology-DoNST, Advanced Institute for Science and
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28 Technology (AIST), Hanoi University of Science and Technology (HUST), 01 Dai Co Viet
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30 Street, Hai Ba Trung District, Hanoi 10000, Vietnam
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34 Department of Physics, University of South Florida, Tampa, FL 33620, USA
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37 BCMaterials Edificio Nº. 500, Parque Tecnológico de Vizcaya, Derio 48160, Spain
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40 Department of Electricity and Electronics, University of Basque Country (UPV/EHU), Leioa
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42 48940, Spain
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46 Department of Applied Physics II, University of Basque Country (UPV/EHU), Leioa 48940,
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48 Spain
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KEYWORDS: Magnetic nanoparticles; Graphene oxide; Magnetic hyperthermia, Biodetection
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A promising nanocomposite material composed of MnFe2O4 (MFO) nanoparticles of ~17 nm
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6 diameter deposited onto graphene oxide (GO) nanosheets was successfully synthesized using a
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8 modified co-precipitation method. X-ray diffraction (XRD), transmission electron microscopy
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(TEM), and selected area electron diffraction (SAED) confirmed the quality of the synthesized
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13 samples. Fourier Transform Infrared (FTIR) measurements and analysis evidenced that the MFO
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15 nanoparticles were attached to the GO surface. Magnetic measurements and analysis using the
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18 modified Langevin model evidenced the superparamagnetic characteristic of both the bare MFO
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20 nanoparticles and the MFO-GO nanocomposite at room temperature, and an appreciable increase
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22 of the effective anisotropy for the MFO-GO sample. Magnetic hyperthermia experiments
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25 performed by both calorimetric and AC magnetometry methods indicated that relative to the bare
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27 MFO nanoparticles, the heating efficiency of the MFO-GO nanocomposite was similar at low ac
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fields (0-300 Oe) but became progressively larger with increasing ac fields (> 300 Oe). This has
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32 been related to the higher effective anisotropy of the MFO-GO nanocomposite. In comparison
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34 with the bare MFO nanoparticles, a smaller reduction in the heating efficiency was observed in
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37 the MFO-GO composites when MFO-GO were embedded in agar or when their concentration
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39 was increased, indicating that the GO helped minimize the physical rotation and aggregation of
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41 the MFO nanoparticles. These findings can be of practical importance in exploiting this type of
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44 nanocomposite for advanced hyperthermia. Magnetoimpedance-based biodetection studies also
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46 indicated that the MFO-GO nanocomposite could be used as a promising magnetic biomarker in
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48 biosensing applications.
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1. Introduction
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7 There have been a growing number of studies on magnetic nanoparticles (MNPs), due to their
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9 potential applications in nanomedicine, including targeted drug delivery, hyperthermia, magnetic
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12 resonance imaging (MRI), and biodetection1-3. In most of the applications, MNPs are required to
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14 possess non-toxicity, biocompatibility, mono-dispersity, stability in colloidal media, high
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16 magnetic moment, and freedom from remanent field. Due to their excellent biocompatible
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19 properties, superparamagnetic iron-oxide nanoparticles have long been exploited for biomedical
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21 applications1,4-6. However, the net magnetic moments of the nanoparticles are drastically reduced
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23 when particles approach sizes below ~10 nm, making them hardly usable for some applications4.
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26 Therefore, continuing efforts have been devoted to the synthesis of new MNPs with improved
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28 magnetic properties7-11. Interestingly, Doaga et al.9 have reported that relative to Fe3O4
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nanoparticles, manganese-doped iron oxide nanoparticles of MnxFe1-xFe2O4 (0 ≤ x ≤ 1) show the
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33 enhanced saturation magnetization (Ms) and hence the enhanced specific absorption rate (SAR),
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35 which is a measure of heating efficiency.
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39 On the other hand, graphene oxide (GO) is a two-dimensional material with potentially important
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41 applications in spintronic devices12. Its large specific surface area is also ideal for the
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43 immobilization of a large number of substances, including biomolecules, drugs, and
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46 nanoparticles13. It has been found that the sheets of graphene oxide are apparently biocompatible
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48 without obvious toxicity, and very promising for applications in targeted drug delivery14. This
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has led to an increasing interest in the realization of hybrid GO-MNPs composed of magnetic
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53 nanoparticles attached to the surface of GO nanosheets15,16. Bai et al.15 reported the good SAR of
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55 Fe3O4 nanoparticles deposited onto GO sheets for prospective applications in magnetic
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hyperthermia. In addition, Peng et al.16 nicely showed that manganese ferrite (MnFe2O4 or MFO)
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decorated GO nanocomposites could work both as heating agents and magnetic resonance
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6 imaging (MRI) contrast agents. However, the results obtained for the MFO-GO nanocomposites
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8 were not directly compared to those of the bare nanoparticles, which left an important and
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unanswered question about the effects of the GO nanosheet on the magnetic behavior and
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13 therefore, on the SAR. Such knowledge is essential in manipulating the heating efficiency of this
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15 type of hybrid nanostructure for advanced hyperthermia.
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19 The aforementioned studies have motivated us to synthesize a nanocomposite material composed
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21 of ~17 nm MnFe2O4 nanoparticles deposited onto graphene oxide nanosheets, as well as to
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23 perform a systematic study of their magnetic, inductive heating, and biosensing properties. Our
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26 study indicates that relative to the bare MFO nanoparticles, the MFO-GO nanocomposite
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28 possesses an enhanced magnetic anisotropy and hence the enhanced SAR for AC fields > 300
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Oe. The GO also promotes disaggregation of the nanoparticles, thus improving the heating
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33 capacity of the MFO-GO composite. These observations pinpoint the important effects of GO on
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35 the magnetic and inductive heating responses of the MFO-GO nanosystem. In addition, we have
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38 demonstrated the possibility of detecting small amounts of MFO-GO using a
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40 magnetoimpedance-based biosensor. Overall, the MFO-GO nanocomposite is a very promising
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42 candidate material for a wide variety of biomedical applications, including magnetic
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45 hyperthermia, targeted drug delivery, and biomolecular detection.
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2. Experimental Methods
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55 2.1 Materials
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Analytical-grade manganese chloride tetrahydrate (MnCl2.4H2O, ≥99%), ferric chloride
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6 hexahydrate hydrogen (FeCl3.6H2O ≥ 99%), sodium hydroxide (NaOH), ammonium hydroxide
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8 (NH3, 25%), potassium permanganate (KMnO4, 99.9%), hydrogen peroxide (H2O2, 30%),
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sulfuric acid (H2SO4, 98 %), hydrochloric acid (HCl, 37%), and nitric acid (HNO3, 63%) used in
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13 this study were purchased from Shanghai Chemical Reagent Co. Ltd
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20 2.2 Synthesis of graphene oxide (GO) nanosheets
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23 Graphite (coal powder) was fabricated from coal, by milling method, in Vietnam. GO nanosheets
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were synthesized from the coal powder by the modified Hummer method as described
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28 previously17. Briefly, graphite powder was mixed with HNO3, KMnO4, then the mixture was
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30 converted to exploited graphite (EG) under microwave 800 W for 1 minute. In a typical process,
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1 g of coal powder was mixed with HNO3 and KMnO4 at a volume ratio of 1:2:1.5, respectively.
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35 The EG was oxidized to graphene oxide (GO) with H2SO4, KMnO4, and H2O2. Graphene oxide
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37 was washed with HCl(5%) and ionized water with repeated centrifugation for purifying. In this
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40 reaction, the mixture of 2 g of EG, 8 g of KMnO4, and 1 g of NaNO3 was added slowly to 160
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42 mL of 98% H2SO4 at 5 °C in ice-water bath and then stirred for 30 min. Ice-water bath was
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44 removed, and then temperature was increased slowly to 45°C and continuously stirred for 2 h.
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47 Deionized water was added slowly to the mixture which was stirred until purple fumes were
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49 inhibited. By increasing reaction temperature to 95°C and stirring the mixture for 1 h, the
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resulting product of the GO nanosheets was obtained with yellow-brown color. The GO
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54 nanosheets were then treated by H2O2 30% and HCl 10% solution to eliminate KMnO4, MnO2,
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56 and other metal ions that remained in the GO solution. The final GO products were purified by
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filtering, washing several times by ultrasonic vibration, centrifugation with deionized water, and
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6 removal of ultrafine carbon powder that was not oxidized.
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13 2.3 Synthesis of MnFe2O4 (MFO) nanoparticles
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16 First, MnFe2O4 NPs were synthesized by a co-precipitation method. Briefly, 2.7 g (0.02 mol)
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18 FeCl3•6H2O and 0.99 g (0.01 mol) MnCl2•4H2O were dissolved in 100 mL of deionized the
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21 water and stirred under air in 10 min so that the molar ratio of Mn:Fe in the solution is 1:2. Then
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23 0.5 M NaOH solution was slowly added into the mixture. The color of the solution changed
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immediately from orange to dark brown. After that, the mixture was stirred in water bath at 80°C
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28 for a period of time. The precipitate was collected by magnet and washed several times by
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30 deionized water before being dried at 80°C for 1h. The main advantages of this method are short
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synthesis time, high crystallinity and low cost.
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39 2.4 Synthesis of MnFe2O4-GO (MFO-GO) nanocomposites
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43 In a same way, the MnFe2O4-GO nanocomposites were synthesized by a modified co-
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45 precipitation method. The FeCl3•6H2O and MnCl2•4H2O were dissolved in deionized water with
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molar ratio of Mn:Fe in the solution is 1:2. The resulting mixture was mixed with the GO
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50 nanosheets suspension (0.6 mg/mL) while stirring for 30 min. The solution was then constantly
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52 stirred and heated to 80ºC. Next, 20 mL of 0.5 M NaOH solution was added slowly to the
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55 solution of complex. The color of solution changed immediately from orange to dark brown after
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57 addition of NaOH indicating the formation of MnFe2O4 nanoparticles. The precipitation reaction
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was then kept at temperature about 80ºC for 1 hour. The product of MnFe2O4-GO nanocomposite
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6 was separated from solution by external magnetic field and washed several times by deionized
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8 water and acetone
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15 2.5 Characterization methods
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18 High-resolution transmission electron microscopy (HRTEM, FEI Tecnai, 200 kV) was
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21 conducted to determine the morphology and distribution of the MFO nanoparticles on the GO
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23 nanosheets. The samples for HRTEM characterization were prepared by placing a drop of
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colloidal solution on a carbon-coated copper grid that was dried at room temperature. The
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28 composition of the MFO-GO nanocomposite was characterized by energy-dispersive X-ray
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30 analysis (5410 LV JEOL). The crystalline structure of the as-prepared MFO-GO nanocomposite
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was analyzed by X-ray diffraction (XRD, Bruker D5005) using Cu-Kα radiation (λ = 0.154 nm)
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35 at room temperature. The background was subtracted using linear interpolation method. The
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37 chemical groups were analyzed using FTIR measurements, samples were collected with one
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40 layer coating in potassium bromide and compressed into pellets, and spectra in the range of 400
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42 cm−1 to 4000 cm−1 were recorded with Nicolet 6700 FT-IR instrument. The magnetic
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44 measurements were performed using a physical property measurement system (PPMS) by
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47 Quantum Design, with a vibrating sample magnetometer (VSM) option. The M-H loops were
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49 measured at room and low temperatures in magnetic fields up to 30 kOe. Magnetic hyperthermia
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measurements were accomplished using both calorimetric and AC magnetometry methods. The
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54 calorimetric hyperthermia was carried out with a 4.2 kW Ambrell Easyheat LI 3542 system. A
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measurements and the magnetic field was tuned from 200 to 800 Oe. AC magnetometry was
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6 done using a home-made set-up18 on a suspension of 1.5 mg/ml of nanoparticles in water. The
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8 magnetic field amplitude was tuned between 0-380 Oe. The frequency was kept around 300 kHz
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in both cases.
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14 For biodetection measurements, a magnetoimpedance-based sensor using an amorphous ribbon
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16 of the composition Co65Fe4Ni2Si15B14 (METGLAS® 2714A) and dimension 10 mm × 2 mm ×
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19 15 μm was fabricated. The impedance (Z) across the sensor head was measured for drop-casted
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21 samples of MFO nanoparticles and MFO-GO nanocomposites (10 μl, 4 mg/ml) by a four point
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23 measurement technique using an HP4192A impedance analyzer in the presence of axial dc
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26 magnetic field H ranging in between ±120 Oe. A detailed description of the magnetoimpedance
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28 (MI) measurement system can be found in Devkota et al.19.
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35 3. Results and Discussion
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38 3.1 Structural Characterization
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42 A two-step process was employed for synthesis of the MnFe2O4-GO magnetic nanocomposites.
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44 The first step was to create the GO nanosheets with oxygen-containing functional groups by
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using a modified Hummer method. These functionalized groups ensure the good dispersibility
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49 and stability of the GO product in aqueous medium. In addition, the functionalized groups
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51 introduce more binding sites for anchoring the precursors of metal ions for MnFe2O4 NPs. In a
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second step, the MnFe2O4 NPs was formed on the surface of GO sheets via co-precipitation
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56 reaction of Fe+3 and Mn+2 ions in the GO solution to produce water-dispersible GO-MnFe2O4
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composite materials. The formation of MnFe2O4 NPs on the surface of GO nanosheets was
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6 confirmed using TEM and XRD measurements.
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9 Bright TEM images (see Fig. 1(a) and (b)) indicate that we obtained polyhedral nanoparticles of
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12 MnFe2O4, with an elongated shape and an average size of 17±5 nm, deposited onto GO sheets of
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14 a few μm length and about 3-5 layers thickness. In all the obtained TEM images, the MFO
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16 nanoparticles were always observed on the surface of the GO sheets, indicating a successful
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19 anchoring of the nanoparticles. The cubic spinel ferrite structure of the nanoparticles was clearly
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21 reflected in the selected-area electron diffraction (SAED) patterns taken using TEM (inset to Fig.
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23 1(a)), and the high resolution TEM (HRTEM) images showed the well-resolved lattice fringes
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26 (Fig 1(c)). The lattice spacings were measured to be ~ 0.25 and ~0.3 nm which correspond to the
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28 (311) and (220) lattice planes. As can also be seen in Fig 1(c), after the precipitation reaction, the
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MFO nanoparticles were anchored to the surface of the GO nanosheets.
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34 The XRD analysis was also employed to confirm the crystalline nature of MnFe2O4 NPs as
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36 shown in Fig. 1(d). The XRD pattern exhibits eight characteristic peaks at 2θ = 18.9 o, 29.7,
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39 34.98, 36.5o, 42.52, 52.63, 56.19 and 61.96, indexed as (111), (220), (311), (222), (400),
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41 (422), (511) and (440), respectively. These peaks are similar to those from JCPDS 10-0319 for a
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44 cubic spinel ferrite structure of MnFe2O4. The XRD pattern of the GO nanosheets exhibited a
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46 broad peak at 10.9º (not shown here) corresponding to the (002) interlayer spacing of 0.81 nm 17.
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48 The XRD pattern of the MFO-GO sample shows only a few small peaks (~45º, 65º…) that could
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51 be related to the presence of impurities in GO. These results reveal that MnFe2O4 NPs coated on
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4 a) b)
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44 Figure 1. (a,b) Bright field TEM images of the MFO nanoparticles deposited onto the graphene
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oxide nanosheets. In the inset to (a) the size distribution of the MFO nanoparticles is presented,
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49 while in the inset to (b), the SAED image of the MFO nanoparticles showing the corresponding
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51 diffraction rings is shown; (c) HRTEM image showing the lattice fringes of the MFO
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To elucidate the interaction of MnFe2O4 NPs with the functional groups on the surface of
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6 GO sheets, Fourier Transform Infrared (FTIR) spectra were recorded and analyzed. FTIR is a
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8 useful technique to confirm that the nanoparticles are anchored to GO surface, as has been shown
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by several groups15,16 including ours17. Fig. 2 shows the FTIR spectra of the GO sheets, MFO
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13 NPs and MFO-GO nanocomposite samples. It can be seen that a broad adsorption band at 3450
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15 cm-1 for all the samples corresponds to the normal polymeric O–H stretching vibration of H2O.
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18 The band at 1630 cm−1 is associated with stretching of the C=O bond of carboxylic groups, while
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20 the absorption peaks at 1268 cm−1 and 1051 cm−1 correspond to the stretching of epoxide groups,
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22 respectively20. The absorption peak around 584-593 cm−1, which is only present in the FTIR
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25 spectra of MFO NPs and MFO-GO nanocomposites, is a characteristic peak corresponding to the
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27 stretching vibration of Fe–O21.
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A noticeable change in intensity of the adsorption bands of the oxygenated functional groups was
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6 found in the FTIR spectrum of the MFO-GO nanocomposite. This is the result of the presence of
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8 the MFO NPs attached to the surface of the GO nanosheets and the reduction of graphene oxide
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to graphene ratio during the synthesis process. The variation of stretch adsorption intensity in the
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13 case of MFO-GO nanocomposite demonstrates that strong interactions exist between MFO NPs
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15 and the remaining functional groups on both basal planes (hydroxyl group OH) and edges
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18 (carboxyl group C–OH) of the GO sheets through the formation of a coordination bond or
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20 through simple electrostatic attraction. In addition, the slight shift of the peak corresponding to
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22 the stretching vibration of Fe-O bond in the MFO-GO hybrids relative to the bare MFO NPs also
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25 suggests that the MFO NPs are bound to the GO surface.
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3.2 Magnetic Characterization
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35 The room temperature M-H loops were measured for the MFO nanoparticles without and with
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37 GO nanosheets. The results are plotted in Fig. 3. For both samples, the recorded magnetization
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40 was normalized to the total mass of the sample (including the masses of graphene oxide and
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42 MFO NPs). Nearly zero coercivity and remanence magnetization are observed in the
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44 measurements at 300 K, suggesting that the MFO nanoparticles exhibit a superparamagnetic
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47 behavior at room temperature. To confirm this, we have fitted our M-H data to a standard
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49 Langevin expression with an added paramagnetic contribution:
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52 ∞
𝜇𝐻
53 𝑀(𝐻) = 𝑀𝑆 ∫ 𝐿 ( ) 𝑓(𝐷)𝑑𝐷 + 𝜒𝐻
54 0 𝑘𝐵 𝑇
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where D is the diameter of the nanoparticles, f(D) corresponds with a Log-Normal size
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6 distribution, and L(x) = cotanh(x)-1/x. χ corresponds with the susceptibility of the paramagnetic
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8 contribution. As seen in Fig. 3, the fitting results for both the MFO and MFO-GO samples at 300
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K are very good, demonstrating the superparamagnetic nature of the synthesized samples. Such a
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13 behavior indicates that at room temperature dipolar interactions between MFO nanoparticles are
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15 relatively weak in the MFO-GO composites, which is beneficial for preventing the magnetic
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18 aggregation of the MFO-GO composites.
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40 8
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M (emu/g)

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M (emu/g)

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30 MFO
31 20 fit 4 MFO-GO
32 fit
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34 10 2
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36 5 1
300 K 300 K
37 0 0
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39 H (kOe) H (kOe)
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42 1.2 60
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1 50
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M (emu/g)

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M/Ms

MFO
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10 K
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0 0
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Figure 3. M-H loops measured at room temperature for (a) the MFO nanoparticles and (b) the
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8 MFO-GO nanocomposite, and (c) measured at 10 K for MFO and MFO-GO. In (d) we present
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10 the M-H loops measured at room temperature together with their fittings to the law of approach
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13 to saturation.
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16 In addition, we have found a noticeable increase of the high field slope due to the additional
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18 paramagnetic contribution (~10%) for the MFO-GO nanocomposite. This may suggest that the
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21 effective anisotropy field (Hk) is larger for this sample as compared to the MFO NPs, and/or
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23 there could be an additional magnetic contribution from impurities in the GO as revealed from
24
25
the XRD pattern. To get more information about this, we have carried out low temperature (10
26
27
28 K) M-H loop measurements. As can be seen in Fig. 3 (c), the MFO-GO nanocomposite exhibits
29
30 again a high field slope, and the coercivity of the MFO-GO composites (~725 Oe) is appreciably
31
32
33
higher than that of the MFO nanoparticles (~200 Oe), which again suggests an increase in the
34
35 anisotropy of the MFO-GO system. In order to estimate the effective anisotropy, Keff, we have
36
37 fitted the experimental data using the law of approach to saturation22. The high field
38
39
40 magnetization curves can be analyzed in terms of the following expression:
41
42
43 𝑀 = 𝑀𝑆 (1 – 𝑏/𝐻 2 ) + 𝜒𝐻
44
45
46
47
where MS is the saturation magnetization and b is correlated with the effect of the anisotropy, Keff
48
49 = μ0MS(15b/4)1/2. χ corresponds again with the susceptibility of the paramagnetic contribution.
50
51 The good fittings have been obtained for both samples, as indicated in Fig. 3 (d). The anisotropy
52
53
54 values obtained for the MFO and MFO-GO samples are 6.4 105 and 1.4 106 erg/cm3,
55
56 respectively. This indicates that when the MFO NPs are deposited onto the GO nanosheets using
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our synthesis method, the effective anisotropy field of the system is enhanced. The increase in
4
5
6 Keff will expectedly affect the SAR of the MFO-GO nanocomposite.
7
8
9
10
11
12
13 3.3 Magnetic Hyperthermia
14
15
16
17
18
19 60
20 60 MFO-GO
MFO 800 Oe (water)
21 55 (water)
55
22 50 50
23 600 Oe
45 45
24 T (ºC)
T (ºC)

25 40 40
400 Oe
26
35 35
27
28 30 1 mg/ml 30
200 Oe
29 25 25
30
31 20 20
0 500 1000 1500 2000 2500 3000 0 500 1000 1500 2000 2500 3000
32 time (s) time (s)
33
34
35
60 60
36 MFO-GO
MFO 55
37 55 (agar)
(agar)

38 50
50
39
40 45 45
T (ºC)
T (ºC)

41 40 40
42
35 35
43
44 30 30
45 25 25
46
47 20 20
0 500 1000 1500 2000 2500 3000 0 500 1000 1500 2000 2500 3000
48 time (s) time (s)
49
50 Figure 4. Heating curves of the MFO nanoparticles and the MFO-GO nanocomposite
51
52
53 (suspended in water and in agar) at different AC fields 200 < H < 800 Oe and f = 310 kHz.
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To elucidate this, we have performed hyperthermia experiments on these two samples with the
4
5
6 same concentration of MFO nanoparticles (1 mg/ml). The mass concentration of MFO
7
8 nanoparticles (~20%) in the MFO-GO sample was evaluated using the saturation magnetization
9
10
11
values obtained from the previous magnetic fittings (Fig. 3). As can be seen in this figure, by
12
13 changing the intensity of the applied field, the final reached temperature can be controlled, and
14
15 the desired 40-44ºC range, where the cancer cells are more susceptible to heat than healthy
16
17
18 ones23, can be easily reached just after a few minutes. It must be noted that the hyperthermia
19
20 measurement at an ac field of 800 Oe for the MFO-GO sample was stopped when reaching 60 ºC
21
22 because our temperature probe calibration is no longer valid above 60 ºC. It can also be seen that
23
24
25 the heating rate at this field for the MFO-GO sample increases appreciably. This becomes more
26
27 obvious by comparing the SAR values for both the MFO and MFO-GO samples in Fig. 5. Here,
28
29
the SAR values have been derived from the following formula:
30
31
32
33 Δ𝑇
𝑆𝐴𝑅 = 𝐶 𝜙
34 Δt 𝑝
35
36
37 where Φ corresponds to the concentration of magnetic material, Cp is the heat capacity of water,
38
39
40 and ΔT/Δt is the initial slope of the heating curves. We corrected both the heat losses to the
41
42 environment and the heat transfer from the coil following the procedure described by Simeonidis
43
44
45
et al.24.
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4 350
5
6 300 MFO 1mg/ml
7 MFO 1mg/ml + 2%agar
8 MFO-GO 1mg/ml
9
SAR (W/g) 250 MFO-GO 1mg/ml + 2% agar
10
11 200
12
13
14 150
15
16
17
100
18
19 50
20
21
22
0
200 300 400 500 600 700 800
23
24 H (Oe)
25
26 Figure 5. SAR vs. magnetic field plots for the MFO nanoparticles and the MFO-GO
27
28
29 nanocomposites, both in 1 ml of water and in 1ml of water+2% agar.
30
31
32
33
34 The obtained SAR values are comparable with those reported for similar nanoparticles9,25. As
35
36
observed, the SAR vs. H behavior tends to saturate in the case of the MFO sample, while it keeps
37
38
39 increasing for the MFO-GO sample. As compared to the bare MFO nanoparticles, the SAR of
40
41 the MFO-GO nanocomposite is similar at low AC fields (0-300 Oe) but for higher fields, it
42
43
44 progressively becomes larger.
45
46
47 In order to gain more insight into this behavior, we have also performed magnetic hyperthermia
48
49 measurements using an AC magnetometry setup18. AC magnetometry is based on estimating the
50
51
52 SAR of the nanoparticles directly from the AC M-H loops’ area. We recall that the SAR is
53
54 directly related to the area of the M-H loops via the following formula: SAR = Area ×
55
56
frequency23. Contrary to the previous method, AC magnetometry allows us to directly observe
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how the M-H loop area changes with increasing AC field, for both samples, and therefore gives
4
5
6 us a direct depiction of the differences in the magnetic response of the MFO nanoparticles when
7
8 they are free or attached to the GO nanosheet surface.
9
10
11
12
13
14
100
15 a) b) c)
20 20
16 MFO MFO-GO MFO
80 MFO-GO
17 10 10

SAR (W/g)
M (emu/g)

M (emu/g)

18 60
19 0 0

20 40
-10 -10
21
20
22 -20 -20 300 kHz
23 0
-400 -300 -200 -100 0 100 200 300 400 -400 -300 -200 -100 0 100 200 300 400 0 50 100 150 200 250 300 350 400
24
H (Oe) H (Oe) H (Oe)
25
26
27
28 Figure 6. (a-b) AC M-H loops taken at room temperature for the MFO and MFO-GO samples
29
30 (c) SAR vs field evolution curves as obtained from the previous AC M-H loop areas.
31
32
33
34
35
36 In Figure 6 we have plotted the AC loops of the MFO and MFO-GO samples and the
37
38 corresponding SAR vs size evolution. Due to measurement limit, the maximum field that we
39
40 could apply at 310 kHz was 400 Oe instead of 800 Oe obtained with previous measurements, but
41
42
43 this is still enough to see the differences in the response of both samples. As can be seen, the AC
44
45 M-H loops of the MFO-GO sample are appreciably wider than those of the MFO samples,
46
47
48
especially at high fields. As a result, a larger AC area and hence the larger heating efficiency
49
50 were obtained for the MFO-GO sample, as depicted in Figure 6 (c). Above ~250 Oe, the SAR
51
52 values of the MFO-GO sample become bigger than those of the MFO nanoparticles, and the
53
54
55 evolution of SAR vs field tends to slightly saturate for the MFO nanoparticles while it increases
56
57 linearly for the MFO-GO sample. The obtained values are in qualitatively good agreement with
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what was measured by calorimetric methods. A slight discrepancy in SAR values determined
4
5
6 from these two methods could be related to inaccuracies derived from calorimetric methods,
7
8 which arise mainly from the lack of matching between thermal models, experimental setups and
9
10
11
measuring conditions as suggested by Andreu et al.26
12
13
14 This increase in the coercivity and the AC M-H loop area for the MFO nanoparticles when
15
16 attached to the GO nanosheets is directly related to their enhanced effective anisotropy (as was
17
18
19 shown before) and the geometric effect of the GO sheets. When the applied field is high enough
20
21 (~250 Oe) maximum heat power is transferred to the MFO-GO nanocomposite and the area of
22
23 the M-H loops appreciably increases.
24
25
26
27 Concerning the effect of anisotropy in magnetic hyperthermia, it has been reported that by using
28
29 magnetic nanoparticles with an exchange-coupled core/shell structure, the effective anisotropy of
30
31
32
the nanoparticles can be tuned to a level which results in an enhancement of the SAR27.
33
34 Martínez-Boubeta et al.28 have experimentally demonstrated that highly anisotropic long chains
35
36 of magnetic nanoparticles give rise to the increased SAR. Very recently, we have achieved
37
38
39 higher values of the SAR for the cubic FeO/γ-Fe2O3 nanoparticles as compared to their spherical
40
41 counterpart (200 vs. 135 W/g at 600 Oe)29. These observations point to the important fact that the
42
43 saturation magnetization is not a sole factor in determining the SAR, and that the heating
44
45
46 efficiency of the magnetic nanoparticles can be improved by tuning their effective anisotropy.
47
48 Therefore, in the present study, the increase in the high-field SAR for the MFO-GO sample as
49
50
compared to the MFO sample can be attributed to the increased effective anisotropy of this
51
52
53 sample (Fig. 3(c)).
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In addition, we have studied the effect of the medium viscosity on the hyperthermia response of
4
5
6 the MFO and MFO-GO samples. A 2% agar solution, known to mimic the higher viscosity of
7
8 cancer cells24, was used to embed the nanoparticles. This also restricts the movement of the
9
10
11
nanoparticles and allows us to analyze the contribution of the physical rotation to their heating
12
13 efficiency. Ideally, this contribution should be as small as possible, since when inserted in cancer
14
15 cells, particles cannot rotate as easily as in water. As depicted in Fig. 5, for the MFO
16
17
18 nanoparticles the SAR greatly decreases when inside the agar solution, indicating that an
19
20 important part of the heating stems from the physical rotation of the nanoparticles. However, the
21
22 SAR values only slightly decrease for the MFO-GO nanocomposite, making it more desirable for
23
24
25 hyperthermia application. The fact that the SAR values do not vary appreciably for the MFO-GO
26
27 composites when embedded in agar can be understood given that when the nanoparticles are
28
29
attached to the GO surface, they already have their movement constrained, and therefore, the
30
31
32 main contribution to the heating in this system must arise due to the magnetic hysteresis losses.
33
34
35
36
37
38
200 300
39
40 MFO 1mg/ml MFO-GO 1mg/ml
MFO 3mg/ml 250 MFO-GO 3mg/ml
41
150
42
200
SAR (W/g)

SAR (W/g)

43
44 100 150
45
46 100
47 50
48 50
49
50 0 0
51 200 300 400 500 600 700 800 200 300 400 500 600 700 800
52 H (Oe) H (Oe)
53
54 Figure 7. SAR vs. magnetic field plots at two different concentrations: 1 and 3 mg/ml, for the
55
56 MFO nanoparticles and the MFO-GO nanocomposite.
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We have also studied how the heating efficiency is affected by the concentration of MFO
4
5
6 nanoparticles, by comparing the SAR values for MFO and MFO-GO samples with two
7
8 concentrations of nanoparticles, 1 and 3 mg/ml (see Fig. 7). As observed, by increasing the
9
10
11
concentration from 1 to 3 mg/ml, the SAR decreases. This can be related to the effect of stronger
12
13 interactions between the nanoparticles when aggregated30, which can hinder their heating
14
15 capability. However, a clear difference is observed between both samples: the reduction of the
16
17
18 SAR value is appreciably higher for the MFO nanoparticles (~50%) than for the MFO-GO
19
20 nanocomposites (~30%). This can be understood by taking into account that in the case of the
21
22 MFO-GO nanocomposites, the GO sheets helped reduce the aggregation of MFO particles even
23
24
25 when we increased their concentration. This clearly reveals that MFO-GO nanocomposites
26
27 provide a way to diminish the problem of the particle aggregation in biomedical applications.
28
29
30
31 Plain Ribbon
32 30
MFO 1.5 (b) MFO
33 25 MFO-GO MFO-GO
34
20 (a)
Z/Z (%)

35 1.0
 (%)

36 15 -2 0 2
37
38 10 0.5
39 5
40
41 0 0.0
42 -100 -50 0 50 100 0 1 2 3 4 5
43 H (Oe) f (MHz)
44
45
46
47 Figure 8. a) Magnetic field dependence of the MI ratio for the plain ribbon, the ribbon with the
48
49
50 MFO nanoparticles, and the ribbon with the MFO-GO nanocomposite. b) figure of merit
51
52 (described in text) as a function of frequency for the ribbon with the MFO nanoparticles, and the
53
54 ribbon with the MFO-GO nanocomposite.
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Finally, to test the possible uses of the MFO nanoparticles and the MFO-GO nanocomposite as
4
5
6 magnetic markers for magnetically labeled molecular biodetection we have performed
7
8 magnetoimpedance (MI) experiments on the sensor probe with and without these magnetic
9
10
11
markers. The MI ratio and detection sensitivity of the sensor were evaluated as
12
13
14 Δ𝑍 𝑍(𝐻) − 𝑍(𝐻𝑚𝑎𝑥 )
15 = × 100
𝑍 𝑍(𝐻𝑚𝑎𝑥 )
16
17
18
19 and
20
21
22 Δ𝑍 Δ𝑍
23 𝜂=[ ] −[ ]
24
𝑍 max 𝑡𝑒𝑠𝑡 𝑠𝑎𝑚𝑝𝑙𝑒 𝑍 max 𝑝𝑙𝑎𝑖𝑛 𝑟𝑖𝑏𝑏𝑜𝑛
25
26
27 where Hmax = 120 Oe is the maximum dc magnetic field to saturate the impedance of a test
28
29
sample and [ΔZ/Z]max is the maximum value of the MI ratio.
30
31
32
33 Fig. 8(a) shows the magnetic field dependence of MI ratio for the plain ribbon, the ribbon with
34
35 the MFO nanoparticles, and the ribbon with the MFO-GO nanocomposite measured at f = 0.6
36
37
38
MHz. The inset of Fig. 8(a) shows an enlarged portion of the low-field MI curves. As observed,
39
40 the MI ratio for the plain ribbon had the smallest value and increased for the drop-casted test
41
42 samples. The maximum values of the MI ratio are 26.4%, 27.2%, and 27.9% for the plain ribbon,
43
44
45 the ribbon with the MFO nanoparticles, and the ribbon with the MFO-GO nanocomposite,
46
47 respectively. In the present study, we have considered the important figure-of-merit (η), which is
48
49 a relative change in the MI ratio due to the presence of the MFO nanoparticles or the MFO-GO
50
51
52 nanocomposite. Values of η calculated using the previous equation are plotted over a wide
53
54 frequency range, as shown in Fig. 8(b). It can be seen in this figure that in the investigated
55
56
57
frequency range the values of η are higher for the MFO-GO nanocomposite than for the MFO
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nanoparticles. This finding is of practical importance, as the MFO-GO nanocomposite can be
4
5
6 better used as a magnetic biomarker for applications in medical diagnosis. The increase in the MI
7
8 ratio due to the presence of the MFO nanoparticles or the MFO-GO nanocomposite can be
9
10
11
explained by considering the disturbance of the applied dc longitudinal and ac transverse fields
12
13 due to the presence of the fringe fields of the MFO nanoparticles on the surface of the ribbon5.
14
15 The higher values of MI ratio and η obtained for the MFO-GO nanocomposite can be attributed
16
17
18 to the suppressed physical motion of the MFO nanoparticles on the graphene sheet, as well as the
19
20 enhanced effective anisotropy of the sample.
21
22
23
4. Conclusions
24
25
26
27 We have successfully synthesized and characterized the properties of a nanocomposite composed
28
29 of superparamagnetic MFO nanoparticles deposited onto GO nanosheets. Relative to the bare
30
31
32
MFO nanoparticles, the MFO-GO nanocomposite shows an enhanced high-field SAR due to the
33
34 increased effective anisotropy and the reduced aggregation of the MFO nanoparticles on the GO.
35
36 This finding can be of practical importance in exploiting this type of nanocomposite for
37
38
39 advanced hyperthermia. The successful use of a magnetoimpedance-based biosensor to detect a
40
41 small amount of MFO-GO indicates that the MFO-GO nanocomposite can be used as a
42
43 promising magnetic biomarker in biosensing applications.
44
45
46
47 Acknowledgements
48
49 Research at USF was supported by Grant USAMRMC W81XWH-10-2-0101. Javier Alonso
50
51
52
acknowledges the financial support provided through a postdoctoral fellowship from Basque
53
54 Government. The work at HUST was supported by Vietnam’s National Foundation for Science
55
56 and Technology Development (NAFOSTED) through a fundamental research project (code:
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103.04-2012.60). One of authors (A.T. Le) would like to acknowledge the Center for Electron
4
5
6 Nanoscopy, Technical University of Denmark (DTU CEN) for HRTEM works. Ta Quoc Tuan
7
8 also acknowledges the financial support from NAFOSTED through basic research project code
9
10
11
103.02-2011.47.
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