JOURNAL OF APPLIED PHYSICS 115, 17B503 (2014)
A highly sensitive magnetic biosensor for detection and quantification of anticancer drugs tagged to superparamagnetic nanoparticles J. Devkota,1 J. Wingo,1 T. T. T. Mai,2 X. P. Nguyen,2 N. T. Huong,3 P. Mukherjee,1 H. Srikanth,1,a) and M. H. Phan1,a) 1
Department of Physics, University of South Florida, Tampa, Florida 33620, USA Institute of Materials Science, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam 3 Department of Physics, Hanoi National University, 334 Nguyen Trai, Hanoi, Vietnam 2
(Presented 7 November 2013; received 23 September 2013; accepted 21 October 2013; published online 17 January 2014) We report on a highly sensitive magnetic biosensor based on the magneto-reactance (MX) effect of a Co65Fe4Ni2Si15B14 amorphous ribbon with a nanohole-patterned surface for detection and quantification of anticancer drugs (Curcumin) tagged to superparamagnetic (Fe3O4) nanoparticles. Fe3O4 nanoparticles (mean size, 10 nm) were first coated with Alginate, and Curcumin was then tagged to the nanoparticles. The detection and quantification of Curcumin were assessed by the change in MX of the ribbon subject to varying concentrations of the Fe3O4 nanoparticles to which Curcumin was tagged. A high capacity of the MX-based biosensor in quantitative analysis of Curcumin-loaded Fe3O4 nanoparticles was achieved in the range of 0–50 ng/ml, beyond which the detection sensitivity of the sensor remained unchanged. The detection sensitivity of the biosensor reached an extremely high value of 30%, which is about 4–5 times higher than that of a magneto-impedance (MI) based biosensor. This biosensor is well suited for detection of C 2014 AIP Publishing LLC. low-concentration magnetic biomarkers in biological systems. V [http://dx.doi.org/10.1063/1.4862395] A combination of magnetic sensors with functionalized magnetic nanoparticles offers a promising approach for a highly sensitive, simple, and quick detection of cancer cells and biomolecules.1–3 This method provides several advantages over conventional optical and electrochemical techniques.2 However, a precise detection of small amounts of cancer cells that have taken up magnetic nanoparticles or biomolecules/anticancer drugs attached to magnetic nanoparticles in real biological systems is a challenging task and requires magnetic sensors with improved sensitivity.3 Recently, particular attention has been paid to the development of a new class of magnetic biosensor based on the giant magneto-impedance (GMI) effect, because of its high detection sensitivity achieved at ambient temperature.4–11 GMI sensors are also cost-effective, power-efficient, reliable, quick-response, and portable.4 Basically, GMI is a large change in the ac impedance (Z ¼ R þ jX, where R and X are ac resistance and reactance, respectively; j is imaginary unit) of a ferromagnetic conductor subject to a dc magnetic field.9 Since GMI often occurs at high frequencies (f > 1 MHz), where the skin effect is significant enough to confine the ac current to a sheath close to the surface of the conductor, it is very sensitive to change in near-surface magnetic signals. Therefore, it is possible to detect various concentrations of magnetic nanoparticle-based biomarkers in biological systems by evaluating the change in GMI of a soft ferromagnetic amorphous ribbon due to the fringe fields of the nanoparticles located on the surface of the ribbon.9,11 A large a)
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body of work has been performed to prove the usefulness of this biosensing technique.4–11 For instance, Yang et al. have successfully developed a GMI-based microchannel system for quick and parallel genotyping of human papilloma virus type 16/18 and for targeted detection of gastric cancer cells.6,7 While previous efforts were devoted mainly to developing magnetic biosensors based on the GMI effect which have limited detection sensitivities (5–10%),4–8 we have recently shown that by exploiting the real and imaginary components of GMI, namely, the ac magneto-resistance (MR) and magneto-reactance (MX) effects, it is possible to improve the detection sensitivity of the biosensor by up to 50% and 100%, respectively.9 The MX-based sensor shows the most sensitive detection of superparamagnetic nanoparticles (mean size, 10 nm) at low concentrations. In effort to further improve the detection sensitivity of this biosensor, we have recently developed a method of patterning nanoholes onto the surface of a ribbon with the use of an appropriate concentration of HNO3 acid.10 We have shown that the presence of nanoholes on the surface of the ribbon improves the detection sensitivity of the sensor significantly. In this work, we show the high capacity of using a MX biosensor for detection and quantification of anticancer drug Curcumin (Cur) tagged to superparamagnetic (Fe3O4) nanoparticles via bio-functionalized nanoconjugates (Fe3O4-Alg-Cur), where Alginate (Alg) was used to chemically stabilize the surface of Fe3O4 nanoparticles. Since Fe3O4 nanoparticles are widely used as magnetic resonance imaging (MRI) contrast agents, our biosensing technique can also be used as a new, low-cost, fast and easy pre-detection method before MRI.
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Fe3O4 nanoparticles of 10 6 2.5 nm diameter were chemically stabilized by coating with Alg (which is a polysaccharide extracted from brown algae), then functionalized with Cur (which is a yellow compound isolated from rhizome of Curcuma longa L. plant and is widely used as an anticancer drug for applications in drug delivery and hyperthermia) to obtain the Fe3O4-Alg-Cur nanoparticles of 120 6 15 nm diameter. The detail of the synthesis of these functionalized nanoparticles has been reported elsewhere.11 The inset of Fig. 1 shows a typical SEM image of the Fe3O4-Alg-Cur nanoparticles. The room-temperature superparamagnetic nature of the Fe3O4-Alg-Cur nanoparticles is evident with the absence of the coercivity (HC 0) in the magnetic hysteresis M(H) loop taken at 300 K and the best fit of the M(H) data to the Langevin function.11 To perform experiments to detect Fe3O4-Alg-Cur nanoparticles, a biosensor prototype was designed using a commercial Co65Fe4Ni2Si15B14 amorphous ribbon (MatglasV 2714A) of dimension 16 mm 2 mm 0.015 mm as a magnetic sensing element. The sensing region of the ribbon surface was treated with 5 ll of 17 vol. % HNO3, then rinsed with DI water after 24 h with the water molecules on the ribbon surface to be allowed to evaporate naturally at room temperature. Changes in MX of the ribbon before and after drop-casting Fe3O4-Alg-Cur nanoparticles with various concentrations on the ribbon surface were recorded over a ribbon length of 10 mm using an HP4192A impedance analyzer at a fixed ac current of 5 mA and in axial dc magnetic fields of up to 6120 Oe. The MX ratio and detection sensitivity ðgÞ for a given frequency were defined and calculated as R
DX XðH Þ XðHmax Þ 100%; ¼ X XðHmax Þ
(1)
g ¼ ½MXmax; MNP ½MXmax; PR ;
(2)
Figure 2(a) shows the magnetic field dependence of the MX ratio (DX/X) taken at 0.5 MHz for a plain ribbon, with 10 ll of DI water, 10 ll of a 250 ng/ml Fe3O4-Alg-Cur nanoparticle solution and after removing the solution completely. For all the samples the MX curves show a double-peak feature (see, inset of Fig. 2(a)), due to the presence of transverse magnetic anisotropy in a Co-based amorphous ribbon.9–11 The presence of water and Fe3O4-Alg-Cur nanoparticles on the surface of the ribbon has negligible influence on the double-peak structure of the DX/X profile. The presence of water (with and without dispersed Fe3O4-Alg-Cur nanoparticles) does also not alter the DX/X ratio of the plain ribbon, indicating a negligible corrosion effect of water on the presently used ribbon. It is worth noting here that the presence of Fe3O4-Alg-Cur nanoparticles on the surface of the ribbon results in an increase in the DX/X ratio by 18%. This increase in the MX ratio can be explained by considering the effect of the fringe fields of Fe3O4-Alg-Cur nanoparticles on the superposition of the applied axial dc magnetic field and the induced transverse ac field (due to an ac current flowing along the axis of the ribbon).9,11 To probe the effects of water and Fe3O4-Alg-Cur nanoparticles on the MX response of the ribbon at different frequencies, we have measured the MX of the plain ribbon, with water (10 ll), and with 10 ll of a 250 ng/ml
and
where ½MXmax ¼
h i
DX X max
is the maximum value of the MX
ratio given in Eq. (1). MNP and PR stand for magnetic nanoparticles and plain ribbon, respectively.
FIG. 1. Magnetic hysteresis loop of the Fe3O4-Alg-Cur nanoparticles. The inset shows a typical SEM image of the Fe3O4-Alg-Cur nanoparticles.
FIG. 2. (a) Magnetic field dependence of the MX ratio (DX/X) at 0.5 MHz for the plain ribbon, with water (10 ll), with 10 ll of a 250 ng/ml Fe3O4-Alg-Cur nanoparticle solution, and after removing the solution. The inset shows an enlarged view of the DX/X profiles; (b) Frequency dependence of the maximum MX ratio ([DX/X]max) for these samples. The inset shows the frequency dependence of the sensor detection sensitivity (g) as calculated using Eq. (2).
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chosen for studies of detection of Fe3O4-Alg-Cur nanoparticles of varying concentrations. Figure 3(a) displays the magnetic field dependence of the MX ratio at 0.2 MHz for the ribbon with Fe3O4-Alg-Cur nanoparticles at various concentrations. Using Eq. (2), the detection sensitivity (g) has been calculated for all particle concentrations, and its variation with particle concentration is depicted in Fig. 3(b). It can be seen that g first increases sharply in the range of 0–50 ng/ml (from 3.5% for 10 ng/ml to 30% for 50 ng/ml) and then remains almost unchanged for higher concentrations (50 ng/ml–250 ng/ml). A similar trend has recently been reported and explained in detail by us for the case of non-functionalized Fe3O4 nanoparticles.9 In summary, we have demonstrated the possibility of using the magneto-reactance effect of a soft ferromagnetic amorphous ribbon with a nanohole-patterned surface to develop a highly sensitive magnetic biosensor for detection and quantification of anticancer drugs tagged to superparamagnetic nanoparticles.
FIG. 3. (a) Magnetic field dependence of the MX ratio (DX/X) at 0.2 MHz for various concentrations of Fe3O4-Alg-Cur; (b) Particle concentration dependence of the sensor’s detection sensitivity.
Fe3O4-Alg-Cur nanoparticle solution over a frequency range of 0.2–2.5 MHz. Figure 2(b) shows the frequency dependence of maximum MX ratio (i.e., [DX/X]max) for these samples. [DX/X]max is largest at 0.2 MHz and decreases sharply with increasing frequency in the range of 0.2–2.5 MHz. From a biosensing perspective, it is interesting to highlight that while almost identical values of [DX/X]max are obtained for the plain ribbon with and without water, the presence of Fe3O4-Alg-Cur nanoparticles results in significantly larger values of [DX/X]max in the frequency range of 0.2–2.5 MHz. We have defined the detection sensitivity of the sensor (g), using Eq. (2), as the difference in [DX/X]max between the plain ribbon and the ribbon with Fe3O4-Alg-Cur nanoparticles. The variation in g with frequency is plotted in inset of Fig. 2(b). As one can see in this figure, g has a maximum value of 30% at 0.2 MHz and decreases sharply with increase in the frequency. This value of g is about 4–5 times higher than that of a GMI-based biosensor reported in the literature.4–11 For this reason, a frequency of 0.2 MHz was
The research at USF was supported by the Florida Cluster for Advanced Smart Sensor Technologies and by USAMRMC through Grant Nos. W81XWH-07-1-0708 and W81XWH1020101/3349. The research at IMS-VAST was supported by the National Foundation for Science and Technology Development of Vietnam through Grant No. 103.02-2011.31 (NXP). The research at HUS was supported by the National Foundation for Science and Technology Development of Vietnam through Grant No. 103.02-2012.69 (NTH).
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