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A highly sensitive magnetic biosensor for detection and quantification of anticancer
drugs tagged to superparamagnetic nanoparticles
J. Devkota, J. Wingo, T. T. T. Mai, X. P. Nguyen, N. T. Huong, P. Mukherjee, H. Srikanth, and M. H. Phan
Citation: Journal of Applied Physics 115, 17B503 (2014); doi: 10.1063/1.4862395
View online: />View Table of Contents: />Published by the AIP Publishing
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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
[ />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)

Authors to whom correspondence should be addressed. Electronic
addresses: and

0021-8979/2014/115(17)/17B503/3/$30.00

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.

115, 17B503-1

C 2014 AIP Publishing LLC
V

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17B503-2

Devkota et al.

J. Appl. Phys. 115, 17B503 (2014)

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 À XðHmax Þ
 100%;
¼
X
XðHmax Þ

(1)

g ¼ ½MXŠmax; MNP À ½MXŠmax; 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 ½MXŠmax 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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Devkota et al.

J. Appl. Phys. 115, 17B503 (2014)

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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