Phan1,a 1 Department of Physics, University of South Florida, Tampa, Florida 33620, USA 2 Institute of Materials Science, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, C
Trang 1A 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: http://dx.doi.org/10.1063/1.4862395
View Table of Contents: http://scitation.aip.org/content/aip/journal/jap/115/17?ver=pdfcov
Published by the AIP Publishing
Articles you may be interested in
Methotrexate conjugated magnetic nanoparticle for targeted drug delivery and thermal therapy
J Appl Phys 115, 17B516 (2014); 10.1063/1.4866080
Size-dependent ferrohydrodynamic relaxometry of magnetic particle imaging tracers in different environments
Med Phys 40, 071904 (2013); 10.1118/1.4810962
Detection of low-concentration superparamagnetic nanoparticles using an integrated radio frequency magnetic
biosensor
J Appl Phys 113, 104701 (2013); 10.1063/1.4795134
Magnetoacoustic imaging of magnetic iron oxide nanoparticles embedded in biological tissues with microsecond
magnetic stimulation
Appl Phys Lett 100, 013704 (2012); 10.1063/1.3675457
Nanomechanics of magnetically driven cellular endocytosis
Appl Phys Lett 99, 183701 (2011); 10.1063/1.3656020
Trang 2A highly sensitive magnetic biosensor for detection and quantification
of anticancer drugs tagged to superparamagnetic nanoparticles
J Devkota,1J Wingo,1T T T Mai,2X P Nguyen,2N T Huong,3P Mukherjee,1
H Srikanth,1,a)and M H Phan1,a)
1
Department of Physics, University of South Florida, Tampa, Florida 33620, USA 2
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
(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
Fe3O4nanoparticles (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 Fe3O4nanoparticles to which
Curcumin was tagged A high capacity of the MX-based biosensor in quantitative analysis of
Curcumin-loaded Fe3O4nanoparticles 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
low-concentration magnetic biomarkers in biological systems.V C 2014 AIP Publishing LLC
[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.13 This method provides several
advan-tages over conventional optical and electrochemical
techni-ques.2 However, a precise detection of small amounts of
cancer cells that have taken up magnetic nanoparticles or
biomolecules/anticancer drugs attached to magnetic
nanopar-ticles in real biological systems is a challenging task and
requires magnetic sensors with improved sensitivity.3
Recently, particular attention has been paid to the
devel-opment 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.411
GMI sensors are also cost-effective, power-efficient, reliable,
quick-response, and portable.4 Basically, GMI is a large
change in the ac impedance (Z¼ 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
sys-tems by evaluating the change in GMI of a soft
ferromag-netic amorphous ribbon due to the fringe fields of the
nanoparticles located on the surface of the ribbon.9,11A large
body of work has been performed to prove the usefulness of this biosensing technique.411For instance, Yanget 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 8we have recently shown that by exploiting the real and imagi-nary 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.9The MX-based sensor shows the most sensitive detection of superparamagnetic nanopar-ticles (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 nano-holes onto the surface of a ribbon with the use of an appro-priate 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 chemi-cally stabilize the surface of Fe3O4 nanoparticles Since
Fe3O4nanoparticles 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
a) Authors to whom correspondence should be addressed Electronic
addresses: sharihar@usf.edu and phanm@usf.edu.
JOURNAL OF APPLIED PHYSICS 115, 17B503 (2014)
Trang 3Fe3O4 nanoparticles of 10 6 2.5 nm diameter were
chemically stabilized by coating with Alg (which is a
poly-saccharide extracted from brown algae), then functionalized
with Cur (which is a yellow compound isolated from
rhi-zome ofCurcuma longa L plant and is widely used as an
anticancer drug for applications in drug delivery and
hyper-thermia) 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
super-paramagnetic 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
nano-particles, a biosensor prototype was designed using a
com-mercial Co65Fe4Ni2Si15B14 amorphous ribbon (MatglasV R
2714A) of dimension 16 mm 2 mm 0.015 mm as a
mag-netic sensing element The sensing region of the ribbon
sur-face was treated with 5 ll of17 vol % HNO3, then rinsed
with DI water after 24 h with the water molecules on the
rib-bon 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
con-centrations on the ribbon surface were recorded over a
rib-bon 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 sensitivityðgÞ
for a given frequency were defined and calculated as
DX
X ¼X Hð Þ XðHmaxÞ
XðHmaxÞ 100%; (1) and
g¼ ½MXmax; MNP ½MXmax; PR; (2)
where½MXmax ¼ DX
X
h i max is the maximum value of the MX ratio given in Eq.(1) MNP and PR stand for magnetic
nano-particles and plain ribbon, respectively
Figure2(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 nano-particle solution and after removing the solution completely For all the samples the MX curves show a double-peak fea-ture (see, inset of Fig.2(a)), due to the presence of transverse magnetic anisotropy in a Co-based amorphous ribbon.911 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 nanopar-ticles) does also not alter the DX/X ratio of the plain ribbon, indicating a negligible corrosion effect of water on the pres-ently 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 nano-particles 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
FIG 1 Magnetic hysteresis loop of the Fe 3 O 4 -Alg-Cur nanoparticles The
inset shows a typical SEM image of the Fe 3 O 4 -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
Fe 3 O 4 -Alg-Cur nanoparticle solution, and after removing the solution The inset shows an enlarged view of the DX/X profiles; (b) Frequency depend-ence 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)
Trang 4Fe3O4-Alg-Cur nanoparticle solution over a frequency range
of 0.2–2.5 MHz Figure 2(b) shows the frequency
depend-ence of maximum MX ratio (i.e., [DX/X]max) for these
sam-ples [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]maxare obtained
for the plain ribbon with and without water, the presence of
Fe3O4-Alg-Cur nanoparticles results in significantly larger
values of [DX/X]maxin 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
nanopar-ticles 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.411 For this reason, a frequency of 0.2 MHz was
chosen for studies of detection of Fe3O4-Alg-Cur nanopar-ticles 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 (from3.5% for 10 ng/ml
to30% 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 Fe3O4nanoparticles.9
In summary, we have demonstrated the possibility of using the magneto-reactance effect of a soft ferromagnetic amor-phous ribbon with a nanohole-patterned surface to develop a highly sensitive magnetic biosensor for detection and quantifi-cation of anticancer drugs tagged to superparamagnetic nanoparticles
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)
1
D R Baselt, G U Lee, M Natesan, S W Metzger, P E Sheehan, and R.
J Colton, Biosens Bioelectron 13, 731 (1998).
2 S X Wang and G X Li, IEEE Trans Magn 44, 1687 (2008).
3
J Llandro, J J Palfreyman, A Ionescu, and C H W Barnes, Med Bio Engin Comp 48, 977 (2010).
4 G V Kurlyandskaya, J Magn Magn Mater 321, 659 (2009).
5 A Kumar, S Mohapatra, V Fal-Miyar, A Cerdeira, J A Garcia, H Srikanth, J Gass, and G V Kurlyandskaya, Appl Phys Lett 91, 143902 (2007).
6 H Yang, L Chen, C Lei, J Zhang, D Li, Z.-M Zhou, C.-C Bao, H.-Y.
Hu, X Chen, F Cui, S.-X Zhang, Y Zhou, and D.-X Cui, Appl Phys Lett 97, 043702 (2010).
7
L Chen, C C Bao, H Yang, D Li, C Lei, T Wang, H Y Hu, M He, Y Zhou, and D X Cui, Biosens Bioelectron 26, 3246 (2011).
8 T Wang, Y Zhou, C Lei, J Lei, and Z Yang, Sens Actuators B 186, 727 (2013).
9
J Devkota, C Wang, A Ruiz, S Mohapatra, P Mukherjee, H Srikanth, and M H Phan, J Appl Phys 113, 104701 (2013).
10 J Devkota, A Ruiz, P Mukherjee, H Srikanth, and M H Phan, IEEE Trans Magn 49, 4060 (2013).
11
J Devkota, T T T Mai, K Stojak, P T Ha, H N Pham, X P Nguyen,
P Mukherjee, H Srikanth, and M H Phan, Sens Actuators B 190, 715 (2014).
FIG 3 (a) Magnetic field dependence of the MX ratio (DX/X) at 0.2 MHz
for various concentrations of Fe 3 O 4 -Alg-Cur; (b) Particle concentration
de-pendence of the sensor’s detection sensitivity.