Scalable synthesis of heterostructure of Fe2O3–Au nanomaterials for application in biological detection

In terms of developing high-performing, multifunctional hetero-nanostructures, an exact control of the growth dynamics at the interface of metal nanoparticles (NPs) and metal oxides is of great significance. Having this in mind, we reported a facile and efficient approach to anchor and control the growth process of Au NPs on the surface of iron oxide, and to synthesis α–Fe2O3–Au heterogeneous structure. The nanocomposite exhibits its outstanding multifunctional performance, the energy absorption rate and energy transfer efficiency of α–Fe2O3–Au heterogeneous structure is obviously more than that of α–Fe2O3 materials. FDTD simulation results also show that α–Fe2O3–Au heterogeneous structure have excellent absorption light property and surface Raman effect compared to the single materials, and exhibit enhanced analysis enhancement factor (to 5 × 104) with R6G molecule probe in SERS measurement. Furthermore, for the electrocatalytic activity of H2O2, the sensitivity and detection limit is 42.265 μA mM−1 cm−2 and 1.166 μM, respectively. This work provides an innovative synthetic route for new heterogeneously structured nanocomposites.


Introduction
During the past few decades, heterogeneously structured nanocomposites have attracted significant attention because of its multifunctional properties, which can be applied in SERS [1,2], magnetic sensors [3,4], and medical equipment [5]. For metal/metal oxide hetero-nanostructures, which show excellent photocatalytic and electrocatalytic performances, leading to well-defined morphologies are required, which provide reasonable contact areas and strong material synergies [6]. However, the synthesis of heterojunction materials and to tailor their properties is one of the research hotspot and important subjects in the field of nanocomposites, and how to solve the lattice mismatches between metal and metal oxide materials is not only a challenges for developing modern synthetic methodology, but also important for extending their potential applications.
At present, a number of imaging modalities has been applied in disease diagnosis and treatment, such as near-infrared fluorescence (NIRF), magnetic resonance imaging (MRI), photoacoustic imaging (PA), computed tomography (CT), and so on [7,8]. Nanocomposites integrating multifunction can effectively improve the imaging sensitivity and space resolution to accurately identify the localization and size of the tumor tissue. Surface-enhanced Raman spectroscopy (SERS) as a sensitive non-invasive 'molecular fingerprint' technology be able to offer an ideal method for medical diagnoses and therapy [9]. Up to now, various precious metals including Au, Ag and other materials have been employed as SERS-active substrate to obtained the reliable signal from the probe molecules [10,11]. However, considering the cost and the complicated synthesis process of the precious metals, the main synthetic strategy is focusing on the combination of low cost materials and the precious metals to constructed multifunctional heterojunction materials, which possess electrocatalysis and SERS properties etc, to minimizes the amount of precious metal used and extends the performance from single material. Hematite is one of the suitable candidate to meet the above-mentioned requirements and exhibits great potential for wide applications in medical treatment, photocatalyst, magnetic sensors and information storage [12,13]. Ferromagnetic nanoparticles (Fe 3 O 4 ) is used in a lot of the magnetic separation, imaging and catalytic fields [5,14]. However, weak magnetic α-Fe 2 O 3 nanocomposites has rarely reported, particularly in the research for the structure and morphology of α-Fe 2 O 3 -Au nanocomposites. Simultaneously, how to exact control the dynamics factor of the growth process and anchoring Au NPs on the surface of iron oxide substrate, it is still a great challenge to develop new facile synthetic strategies to building multifunctional heterojunction materials.
Hence, in the current work, we reported a facile and efficient approach to achieve morphology control of heterogeneously structured α-Fe 2 O 3 -Au NPs, and obtained the uniform growth of Au NPs on the surface of iron oxide by wet-chemical synthetic strategies. The structure and performance of heterogeneously structured α-Fe 2 O 3 -Au NPs are discussed in detail. We measured the photothermal, SRES and electrochemical catalysis properties of α-Fe 2 O 3 -Au NPs, which is obviously improved compared with that of the single materials. As well as it has excellent electrochemical catalysis for H 2  were obtained from Sinopharm Chemical Reagent Co., Ltd. The deionized water used in all of the experiments was 18.25 MΩ·cm, and the chemical regents used in the preparation were analytical grade and without any further purification.

Synthesis of α-Fe 2 O 3 -Au
NPs with smell ring-like, large ring-like, and cannular-like morphologies The small ring-like, large ring-like and cannular-like of α-Fe 2 O 3 NPs was carried out following a modified hydrothermal procedure [15]. 1.3 ml FeCl 3 solution (0.3 M) was added into 38 ml deionized water, and 0.4 ml K 2 HPO 4 (18 mM), 0.4 ml Na 2 SO 4 (55 mM) was added in order under vigorous stirring. After 10 min, the mixed solution was transferred into a Teflon-lined stainless steel autoclave and heat at 220°C for 48 h. After the synthesis, the autoclave was cooled to room temperature, the precipitate was separated by centrifugation, and washed with distilled water and absolute ethanol. Next, the final product was dispersed and stored in deionized water for further use. Noted that, for large ring-like α-Fe 2 O 3 NPs, the amount of FeCl 3 solution (0.3 M) was 2 ml based on other parameters being hold, for cannular -like of α-Fe 2 O 3 NPs, the amount of FeCl 3 solution (0.3 M) and K 2 HPO 4 (18 mM) solution was 2 ml and 0.89 ml respectively, while other parameters remain unchanged. The α-Fe 2 O 3 -Au heterogeneous structure nanocomposite was produced by seed growth method. In a typical synthesis process of α-Fe 2 O 3 -Au NPs, 2 ml of a colloidal solution of α-Fe 2 O 3 NPs (1 mg ml −1 ) was mixed with 13 ml deionized water in a 25 ml glass vial under vigorous stirring at a speed of 500 rpm and the room temperature. Then, 0.6 ml lysine solution (10 mM) was added dropwise, after continue stirring for 24 h, Then 2.17 ml HAuCl 4 solution (1 mM), the value of pH was adjusted to 10.7 by 50 μl KOH solution (2 M), was quickly added into α-Fe 2 O 3 /lysine suspension solution. Next, 13 μl sodium citrate solution (0.1 mM) was added under dark condition and stirring for 24 h. The mixed solution was transferred into a new glass vial and 0.3 ml L-AA solution (0.1 M) was added dropwise. After 30 min, the product was separated by centrifugation, washed with deionized water and anhydrous ethanol, respectively. The final product was dispersed into deionized water.

Characterization
The morphology of the samples was characterized by field emission scanning electron microscope (FESEM, FEI Quanta 250) at an acceleration voltage of 20 kV and transmission electron microscopy (TEM, JEOL-2100) operated at an acceleration voltage of 200 kV. The structural characterization was further investigated by x-ray diffraction (XRD), which was performed on a Bruker-AXS D8 Advance diffractometer operated at 40 kV voltage and 30 mA current using Cu Kα radiation (λ=1.5418 Å) in the range of 15°to 90°. The UV-vis spectrum of the samples was recorded on a Hitachi UV-vis spectroscope (UV-4100). The surface structure of the samples was investigated through the x-ray photoelectron spectroscopy (XPS, Kratos Axis UL equipped with monochromatic Al Ka radiation, 150 W, 5 kV at 1486.6 eV) by referencing the spectra use the C 1s peak at a binding energy of 284.8 eV.

Performance measurements
We also investigate the photothermal properties, SERS properties, and Finite Difference Time Domain (FDTD) simulation, as well as electrochemical catalysis properties of H 2 O 2 . The details as shown in the supporting information.

Microstructures and characterization
The morphology of α-Fe 2 O 3 NPs was well-controlled in the presence of PO 4 3− /SO 4 2− ion. Observed in detail, panels a, d and g of figure 1 show the SEM images of the α-Fe 2 O 3 NPs. Panels b, e and h of figure 1 show the TEM images of the α-Fe 2 O 3 -Au NPs, and the hollow structure and size distribution has been marked by the corresponding geometrical models. The average radius (r) of small ring-like α-Fe 2 O 3 -Au NPs (Fe 2 O 3 -Au-r1) is around 38.3 nm, and the average ring thickness (d) and the height (L) is about 19.6 nm and 56.8 nm (figure S1 is available online at stacks.iop.org/MRX/6/1250b5/mmedia), respectively. It is worthwhile to note that the Au NPs is covered and anchored onto the surface of α-Fe 2 O 3 NPs, thus the stability of Au NPs is largely enhanced, so as to improve the catalysis stability of the α-Fe 2 O 3 -Au NPs [16]. When the concentration of Fe 3+ ion was increasing, as shown in figures 1(d) and (e), the value of average radius, ring thickness and the height was increased to 47.   [17,18]. The UV/Vis spectra of the as synthesis NPs revealed their ultraviolet absorption difference under 600 nm wavelength ( figure 2(b)). There is obvious  [19,20]. Simultaneously, the red shift of the absorption peak of α-Fe 2 O 3 NPs indicates the present of α-Fe 2 O 3 -Au heterojunction structure, which is consistent with the TEM result.
Further evidence for the composition and purity of these products was also performed by XPS spectra, to investigate the atom valence state and the synergistic effect between Au NPs and α-Fe 2 O 3 NPs. All spectra have corrected by C 1s (284.8 eV). As shown in figure 3(a), compared with the XPS spectra obtained from the pure α-Fe 2 O 3 NPs, a new peak of Au 4f and Au 4d can be observed from the sample after anchoring Au NPs, and Au 4f 7/2 (83.8 eV) and Au 4f 5/2 (87.5 eV) diffraction peak can be used to prove Au 0 state [21][22][23]. The representative high-resolution spectra of the Au 4f regions are shown in figures 3(b)-(d), the diffraction peak in 85.0 eV (Au + ) and 86.0 eV (Au 3+ ) is cannot find demonstrate that the Au atom valence state is Au 0 in α-Fe 2 O 3 -Au NPs rather than oxidation state Au ion. The binding energy of Au 4f 7/2 is shift to the left (the direction of the negative axis, figure S4), which shows that there are the strong interaction between Au NPs and α-Fe 2 O 3 substrate [18,24,25].

Photothermal properties measurements of α-Fe 2 O 3 -Au NPs
Light absorption in nanoparticles is readily dissipated as heat. In this study, we used 808 nm wavelength laser irradiation 10 min (energy density 0.4 W cm −2 ). For all solutions containing nanoparticles, a significant temperature rise in the bulk solution is observed after the laser is turned on at time, t=150 s. As shown in figure 4(a), the α-Fe 2 O 3 -Au NPs heat the surrounding bulk aqueous solution to maximum temperatures, T max ≈42°C, while the pure α-Fe 2 O 3 NPs, T max ≈37.2°C, the DI water used as controls show very small temperature increase. The Fe 2 O 3 -Au-r1 heat the bulk solution to slightly higher temperatures than that of the large rings-like and cannular-like NPs ( figure 4(b)). The rise of temperature of α-Fe 2 O 3 NPs is about 8°C at a irradiation cycle and it is about 15°C for the α-Fe 2 O 3 -Au NPs at the same condition, while the temperature change of H 2 O solution is very slow, which will be a prospect applied to actual photothermal therapy [26]. The energy absorption rate and heat dissipation rate of the nanocomposites is shown in figure 4(c). The energy absorption rate and the energy transfer efficiency of heterogeneously structured α-Fe 2 O 3 -Au NPs is obviously more than that of α-Fe 2 O 3 hollow structure (figure 4(d)), which prove that the loaded Au NPs improve the absorption efficiency of light and photoelectron energy absorption rate of the heterogeneously structured α-Fe 2 O 3 -Au NPs. This consequence is consistent with the UV-vis result. Furthermore, the heat dissipation rate of each kind material is relatively low indicates the absorption photon energy is mainly used to rise the system temperature [27]. This suggest that heterogeneously structured α-Fe 2 O 3 -Au NPs can be used for optics catalysis and light degradation process.

FDTD simulation testing of α-Fe 2 O 3 -Au NPs
In order to explain the photothermal property and find the diversity between α-Fe 2 O 3 -Au and α-Fe 2 O 3 NPs, we used FDTD simulation to display the difference of the α-Fe 2 O 3 -Au and α-Fe 2 O 3 NPs under irradiation. FDTD simulation with 400-1000 nm wavelength transverse-electric light source and vertical irradiation on the surface of nanoparticle ( figure 5(a)). The small amplitude of the local electric field in the polarization direction of Au and α-Fe 2 O 3 NPs, which indicates that the effect of surface plasma enhancement is weak (figures 5(b)-(e)). The amplitude of the local electric field of Au NPs is more than that of the α-Fe 2 O 3 NPs, and the effect of the surface plasma enhancement is obviously improved when loaded Au NPs to form heterogeneously structured α-Fe 2 O 3 -Au NPs (figures 5(f)-(h)) [28]. As the dimensional changed, the amplitude of the local electric field of α-Fe 2 O 3 -Au NPs is rise from 2.2 to 7.3. Simultaneously, the contacting area between Au NPs and substrate (α-Fe 2 O 3 NPs) is an important factor for the heterogeneous structure which have excellent absorption light property and surface Raman effect than single materials [6].

SERS measurements of α-Fe 2 O 3 -Au NPs
In order to further prove the synergistic effect between Au NPs and substrate (α-Fe 2 O 3 NPs) and expand the application field of α-Fe 2 O 3 -Au heterogeneous structure, we used R6G (10 −6 M) as probe molecular to test the SERS property of α-Fe 2 O 3 -Au NPs ( figure 6). The α-Fe 2 O 3 NPs made no response to R6G molecular and the vibration peak was not shown in the SERS process. However, the vibration peak of α-Fe 2 O 3 -Au NPs is obviously enhanced and show SERS enhancement effect for R6G molecular. We have choice Raman peak in 614 cm −1 as the research object, the obtained AEF of Au NPs, α-Fe 2 O 3 -Au-r1, α-Fe 2 O 3 -Au-r2 and

Electrochemistry measurements of H 2 O 2 :
We have used α-Fe 2 O 3 -Au NPs as electrode materials to test the electrochemical catalytic ability of H 2 O 2 in physiology system (PBS, pH=7.4). Cyclic voltammetry (CV) curve is shown in figure 7(a), The current response of α-Fe 2 O 3 -Au heterogeneous structure was obvious higher than that of Au NPs and α-Fe 2 O 3 NPs when system containing 200 μM H 2 O 2 at a scan rate of 50 mV s −1 . The α-Fe 2 O 3 -Au electrode presents the most significant enhancement in cathode peak current among the as-used electrodes, indicating a quite sensitive nature of the α-Fe 2 O 3 -Au electrode toward H 2 O 2 [29][30][31][32]. The best response from α-Fe 2 O 3 -Au-c NPs due to Au NPs is uniform loaded on the surface of NPs, and the smaller thickness bring the higher size effect and large contact area. Figure 7

Conclusions
In conclusion, we reported a facile and efficient approach to achieve morphology control of heterogeneously structured α-Fe 2 O 3 -Au NPs. SEM, TEM, XRD, UV-vis, and XPS characterization was used to prove the existence of heterogeneous structure. The lattice mismatches between metal and metal oxide materials is well solved, and the anchoring Au nanoparticles on the small ring, large-ring, and cannulars-like α-Fe 2 O 3 NPs are all similar morphologically. In addition, we extend the research to investigate the photothermal property, FDTD simulation, SERS and electrochemistry measurements for H 2 O 2 of heterogeneously structured α-Fe 2 O 3 -Au NPs. The heterogeneous structure obviously improves the energy absorption rate and efficient energy transfer of the photothermal property. As the SERS-active substrate, the AEF is 5×10 4 . The heterogeneously structured α-Fe 2 O 3 -Au NPs display excellent response capacity due to the improved electronic transmission ability from Au NPs is uniform loaded on the surface of α-Fe 2 O 3 NPs and the large contact area. The synthetic route in this article shows the innovative in the preparation technique of new heterogeneous structures. In general, the α-Fe 2 O 3 -Au heterogeneous structure are multifunctional, and these multifunctional properties have been exploited to create structures that are more economical and active than pure Au nanoparticle catalysts and will also find real world applications.