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Fabrication of a non-enzymatic glucose sensor

field-effect transistor based on vertically-
oriented ZnO nanorods...

Article in Electrochemistry Communications March 2017

DOI: 10.1016/j.elecom.2017.03.006

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 Electrochemistry Communications 77 (2017) 107111

Contents lists available at ScienceDirect

Electrochemistry Communications

journal homepage: www.elsevier.com/locate/elecom

Fabrication of a non-enzymatic glucose sensor eld-effect transistor

based on vertically-oriented ZnO nanorods modied with Fe2O3
Raq Ahmad, Min-Sang Ahn, Yoon-Bong Hahn
School of Semiconductor and Chemical Engineering, Nanomaterials Processing Research Center, Chonbuk National University, 567 Baekjedaero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Republic
of Korea

a r t i c l e i n f o a b s t r a c t

Article history: Herein, we report a non-enzymatic glucose sensor eld-effect transistor (FET) based on vertically-oriented zinc
Received 25 January 2017 oxide nanorods modied with iron oxide (Fe2O3-ZNRs). Compared with ZnO-based non-enzymatic glucose sen-
Received in revised form 3 March 2017 sors, which show poor sensing performances, modication of ZnO with Fe2O3 dramatically enhances the sensing
Accepted 3 March 2017
behavior of the fabricated non-enzymatic FET glucose sensor due to the excellent electrocatalytic nature of Fe2O3.
Available online 06 March 2017
The fabricated non-enzymatic FET sensor showed excellent catalytic activity for glucose detection under opti-
Keywords:
mized conditions with a linear range up to 18 mM, detection limits down to ~ 12 M, excellent selectivity,
Field-effect transistor good reproducibility and long-term stability. Moreover, the fabricated FET sensor detected glucose in freshly
Non-enzymatic drawn mouse whole blood and serum samples. The developed FET sensor has practical applications in real sam-
Glucose sensor ples and the solution-based synthesis process is cost effective.
ZnO nanorod 2017 Elsevier B.V. All rights reserved.
Iron oxide

1. Introduction have recently been used to fabricate high-performance non-enzymatic

Glucose monitoring using sensors is a very active research area be-
cause glucose imbalance in the blood causes diabetes mellitus, a major
world-wide public health problem. Studies have shown that blood glu-
cose levels can rise due to changes in eating habits and increasing obe-
sity [1,2]. High blood glucose can cause damage to nerves, blood vessels
and organs [3]. Therefore, a reliable high-performance glucose sensor is
needed for the diagnosis and management of diabetic patients. Many ef-
forts in this direction have been made since the rst biosensor described
by Clark and Lyons in 1962 [4]; nanostructured materials in particular
have played a major part in the development of new biosensors [59].
This is because engineered nanostructured materials possess a high spe-
cic surface area for enzyme immobilization and electrochemical activ-
ity [1012].
A range of different nanostructured materials, including metals,
metal oxides and carbon-based nanomaterials, have been synthesized
and used to fabricate various electrochemistry-based glucose sensors
[57]. Most of the sensors are enzyme based, i.e. they rely on an enzyme
to catalyze the electrochemical reactions [13]. However, enzyme-based
electrodes are unstable, expensive, and easily lose activity during reuse
because of washing and drying steps. Non-enzymatic sensors have
therefore been developed to overcome these shortcomings, as they
offer the advantages of low cost and large-scale production [14]. Nano-
structured transition-metal oxides (e.g. CuO, TiO2, NiO, Co3O4, NiWO4)
Corresponding author.
E-mail address: ybhahn@chonbuk.ac.kr (Y.-B. Hahn).
glucose sensors, which exhibit better catalytic activity in alkaline medi-
um [1518].
Most electrochemical non-enzymatic sensors have been produced
using the conventional fabrication method, in which nanostructures
are synthesized separately and then attached to the conductive elec-
trode with the help of binders [1517]. Such an electrode suffers from
reduced electrocatalytic activity, low stability and poor reproducibility
[18]. To improve the contact between the nanostructures and the elec-
trode surface further, electrospinning, electrochemical anodization
and inkjet-printing methods have been used to deposit the
electrocatalyst on the electrode surface [19]. A solution-based synthesis
method has advantages compared to these methods, due to its low cost
and low temperature. However, most transition-metal oxides cannot be
grown directly on the electrode surface at low temperatures using a so-
lution method. Importantly, ZnO is the best candidate for low tempera-
ture growth on seeded substrates [20,21]. Furthermore, it is reported
that vertically-oriented ZnO nanostructures grown directly on electrode
surfaces are not only good for enzyme immobilization in enzyme-based
sensors, but also improve stability [21]. However, ZnO nanostructures
alone are not good candidates for a non-enzymatic glucose sensor it
is necessary to modify their surface with a potential catalyst.
In this research, we rst grew ZNRs on seeded substrates between
source-drain electrodes and then modied the vertically-oriented
ZNRs with Fe2O3 to fabricate a non-enzymatic FET glucose sensor. To
the best of our knowledge, this is the rst report on the fabrication of
a non-enzymatic FET sensor based on Fe2O3-ZNRs for glucose detection.
Overall, the results showed good sensitivity, a wide linear range, a low

http://dx.doi.org/10.1016/j.elecom.2017.03.006
1388-2481/ 2017 Elsevier B.V. All rights reserved.
108 R. Ahmad et al. / Electrochemistry Communications 77 (2017) 107111

detection limit, excellent reproducibility, selectivity, and long-term sta-
bility. The fabricated FET sensors were then utilized to detect glucose in
freshly drawn mouse whole blood and serum samples.
2. Experimental
2.1. Reagents
Zinc nitrate hexahydrate (Zn(NO3)26H2O, 99%), hexamethylenetet-
ramine (HMTA, 99%), iron(III) nitrate nonahydrate (Fe(NO3)39H2O,
98%), Naon, glucose (d-(+)-99.5%), cholesterol, ascorbic acid (AA),
dopamine (DA), L-cysteine (L-cys), uric acid (UA), glutamate (GA), D-
lactose, D-mannose, D-maltose, fructose, sucrose, and phosphate-buff-
ered saline (PBS, pH 7.4) were purchased from Sigma-Aldrich and
used without further purication.
2.2. Electrode preparation and characterizations
The fabrication of the non-enzymatic FET-based glucose sensor is
shown schematically in Fig. 1(a). First, Ag source-drain electrodes and
a ZnO seed layer were deposited by RF sputtering on a cleaned Si/SiO2
substrate (i). ZNRs were then grown using 40 mM of each
Zn(NO3)26H2O and HMTA in 50 mL DIW, transferred into a Pyrex
glass bottle, followed by heating at 80 C for 6 h after suspending the
seeded substrates upside down (ii). When the reaction was completed,
the electrodes were taken out, rinsed with DIW and dried. In the next
step, the ZNRs were modied with Fe2O3 by dip-coating using the pre-
cursor solution of 0.06 g Fe(NO3)39H2O in 20 mL DIW. The electrodes
were dipped for 2 min in the above solution, followed by drying at
room temperature and nally annealed at 400 C for 2 h (iii). The
source-drain electrodes were passivated with PDMS and the sensing
area was covered with 0.5 wt% Naon to prevent possible interference
from other species during glucose detection (iv).
The structures of the ZNRs and Fe2O3-ZNRs were investigated by
eld emission scanning electron microscopy (FESEM, Hitachi S4700)
equipped with energy dispersive X-ray spectroscopy (EDX), transmis-
sion electron microscopy (TEM) and high-resolution TEM (HRTEM;
JEOL-JEM-2010). All electrochemical experiments were conducted at
room temperature under ambient air conditions with a semiconductor
parameter analyzer (HP 4155A). The drain current was measured

Fig. 1. (a) Schematic illustration of the fabrication of the Fe2O3-ZNRs FET-based non-enzymatic glucose sensor; (b) surface FESEM, (c) cross-sectional FESEM image, and (d) EDX results of
as-grown ZNRs; low- (e) and high-magnication (f) FESEM images and EDX results (g) of the Fe2O3-ZNRs; (h) XRD patterns and TEM images of a ZNR (i) and of the Fe2O3-ZNRs (j). The
inset in (j) shows the HRTEM image of the Fe2O3-ZNRs.
 R. Ahmad et al. / Electrochemistry Communications 77 (2017) 107111
with a xed drain-source voltage of 0.1 V while the gate potential was
increased in the range 02.5 V. This was applied via an Ag/AgCl refer-
ence gate voltage immersed in a buffer solution containing the analyte.
3. Results and discussion
3.1. Structural characterization
Fig. 1(bd) shows the FESEM images of the as-synthesized ZNRs. It
can be seen that the ZNRs are dense, vertically-oriented, and uniformly
cover the seeded substrate. From the cross-sectional image (Fig. 1(c)),
the average length of the ZNRs is ~2.15 nm and their thickness is around
8090 nm. EDX analysis conrms the presence of the anticipated ele-
ments, including oxygen and zinc in 18.2 and 72.9 wt% concentrations,
respectively (Fig. 1(d)). The presence of silicon is due to the substrate.
After modication of the ZNRs with Fe2O3, the morphology of the
ZNRs became rough due to the Fe2O3 coating (Fig. 1(eg)). The low-
and high-magnication FESEM images depict the surface morphology
of the Fe2O3-ZNRs. EDX analysis of the Fe2O3-ZNRs show an additional
element peak of iron (Fe) with a concentration of ~13 wt% (Fig. 1(g)),
which demonstrates the successful modication of the ZNRs with Fe2O3.
The crystallinity of the as-synthesized ZNRs and Fe2O3-ZNRs was ev-
idenced by the XRD prole (Fig. 1h). The diffraction peaks of the as-syn-
thesized ZNRs are perfectly indexed to the hexagonal ZnO. The strong
intensity peak assigned to the (002) plane indicates that the ZNRs are
growing along the direction of the c-axis. However, the Fe2O3-ZNRs
showed additional peaks of Fe2O3 that are assigned to the single-
phase -Fe2O3; no peaks of other phases or impurities were detected.
All the diffraction peaks of the as-synthesized ZNRs and Fe2O3-ZNRs
were well-dened, conrming the good crystalline nature of these
two samples. Fig. 1(ij) shows the TEM analysis of the as-synthesized
ZNRs and Fe2O3-ZNRs. The images of the ZNRs clearly show the smooth
surface, and their length and diameter are consistent with FESEM
Fig. 2. (a) IV response of the non-enzymatic FET-based glucose sensor in 0.1 mM PBS solution (pH = 7.4) without glucose and with 1 mM glucose, (b) non-enzymatic IV response of
Fe2O3-ZNRs FET 0.1 mM PBS solution (pH = 7.4) with different concentrations of glucose, (c) calibrated linear curve, and (d) selectivity test. The inset in (b) shows the overall calibrated
curve with linear and nonlinear response.
109
observations. However, the surface of the Fe2O3-ZNRs was rough, as
the surface contains particles of Fe2O3 (Fig. 1(j)).
3.2. Sensing performance of the fabricated non-enzymatic FET sensor
To evaluate the sensing performance of the fabricated non-enzymat-
ic FET sensor, we measured the IV response of the sensor in 0.1 mM
PBS solution (pH = 7.4) before and after adding 1 mM glucose (Fig.
2(a)). In the absence of glucose, the FET sensor showed a negligible re-
sponse. A poor response was noticed with the FET with unmodied
ZNRs in the presence of glucose, which limits the use of plain ZNRs in
non-enzymatic glucose sensors. However, an excellent response was
observed with the Fe2O3-ZNRs based FET in the presence of glucose.
This can be attributed to the excellent electrocatalytic nature of Fe2O3,
which mediates the heterogeneous chemical oxidation or reduction of
the glucose, while the converted iron oxides can be continuously and si-
multaneously recovered by electrochemical oxidation or reduction due
to their high surface to volume ratio [22]. Additionally, in our sensor ma-
trix, the ZNRs work as a supporting material for Fe2O3, rapidly
transporting electrons during the electrochemical reaction due to their
good conductive property. Also, the less dense morphology of the
ZNRs provides better permeability of the sensing matrix to the solution.
The possible electrochemical reactions involved in glucose oxidation
through the Fe(III)/Fe(II) centers of Fe2O3 are given below [22]:
2FeIII Glucose2FeII Gluconolactone H2 O 1
Gluconolactone H2 O2H Gluconate 2
2FeII2FeIII 2e 3
In order to investigate the sensing parameters further, the IV re-
sponse of non-enzymatic glucose FET sensor was measured with
110 R. Ahmad et al. / Electrochemistry Communications 77 (2017) 107111
different concentrations (0.0522 mM) of glucose (Fig. 2(b)). The no-
ticeable current increased with increasing glucose concentrations in
the potential range 1.25 to 2.5 V. The average current in the above po-
tential range was used to produce a calibration plot, i.e. average current
versus glucose concentration (inset of Fig. 2(b)). At higher concentra-
tions (above 18 mM), the sensor's response was saturated, which may
be due to saturation of the active site of the catalyst. To calculate the
sensitivity, the linear range of the calibrated plot was drawn (Fig.
2(c)), which showed linearity up to 18 mM with a correlation coef-
cient (R2) of 0.9993. From the obtained slope, the sensitivity of the sen-
sor was calculated to be 105.75 A/mMcm2 in a wide linear range (0.05
18 mM), which is better than other non-enzymatic-based glucose sen-
sors using cyclic voltammetry and amperometric detection methods
[1517,19]. It is important to note that the overall measurement time
is only 10s, which permits rapid glucose detection. Furthermore, the
limit of detection (~12 M) was calculated based on a signal to noise
ratio of 3. It should be noted that only 10 L of analyte solution is needed
to measure the glucose concentration. The same applies to analysis of
the whole blood sample, avoiding the need to draw a lot of blood.
3.3. Anti-interference ability, reproducibility and stability
To check its selectivity, the response of the non-enzymatic FET sen-
sor was measured rstly in 4 mM glucose without interfering species,
then with 0.2 mM of each possible interfering species (i.e. cholesterol,
AA, DA, L-cys, UA, and GA), and nally in the presence of 0.2 mM of
each competing sugar (i.e. D-lactose, D-mannose, D-maltose, fructose,
and sucrose). As shown in Fig. 2(d), a very similar response was ob-
served in the presence of interfering species and other competing
sugars, which demonstrates that the glucose can be detected even in a
complex analyte solution such as a serum sample. This can be attributed
to the Naon covering, which eliminates the effect of negatively charged
interfering species (i.e. AA and UA). To check the reproducibility, six FET
sensors were fabricated and their response was measured. The results
showed a relative standard deviation (RSD) of 2.56%. In addition, the
Fig. 3. IV response curves of the FET sensor measured in the presence of 4 mM glucose (a); calibrated response curve (b); mouse whole blood samples (c); and ltered serum samples (d).
long-term storage stability of the FET sensor was tested intermittently
for 10 weeks in the presence of 4 mM glucose (Fig. 3(a)). As shown in
Fig. 3(b), 97.5% of the initial sensor response was retained after
10 week of use, demonstrating good stability. The results therefore
show excellent selectivity, reproducibility, and long-term stability, sug-
gesting that the developed non-enzymatic FET sensor is reliable for glu-
cose detection in real samples.
3.4. Real sample analysis
To check the applicability and reliability of our fabricated non-enzy-
matic FET sensor, we measured the glucose concentrations in four sam-
ples of mouse blood and ltered mouse serum. The IV responses are
shown in Fig. 3(c) and (d); optical images are included in the insets.
The glucose concentration in the whole blood and serum samples was
calibrated using the standard calibration curve for known glucose con-
centrations and compared with the results obtained using a chemistry
analyzer VetScan VS2 (Abaxis, Inc., Union City, CA 94587). The glucose
concentrations measured in the serum samples were similar to those
obtained using the blood chemistry analyzer. However, the glucose con-
centrations in the whole blood samples were slightly less (~35%) than
in the serum samples; this decrease in sensor response may be due to
the presence of different types of molecules in the whole blood sample.
Overall, the results obtained indicate the potential of this non-enzymat-
ic FET sensor for analysis of real samples.
4. Conclusion
In summary, we successfully fabricated a non-enzymatic FET glucose
sensor by using vertically-oriented ZNRs between source-drain elec-
trodes on a seeded substrate followed by modication with Fe2O3. The
sensor was used for glucose detection for the rst time. The vertically-
oriented ZNRs provided an excellent matrix for loading of Fe2O3,
which catalyzes the electro-oxidation of glucose during glucose detec-
tion. As a result, the non-enzymatic FET sensor showed excellent
 R. Ahmad et al. / Electrochemistry Communications 77 (2017) 107111
sensing performance with high sensitivity in a wide linear range, a low
detection limit, excellent selectivity, good reproducibility, and long-
term stability. In addition, the fabricated FET sensors have practical ap-
plications in real sample analysis. Thus, this cost-effective non-enzy-
matic FET sensor holds great potential for detection of glucose in
human blood samples.
Acknowledgements
This work was supported by the National Leading Research Labora-
tory program through the National Research Foundation (NRF) (NRF-
2016R1A2B2016665) of Korea funded by the Ministry of Science, ICT
& Future Planning. The authors also thank KBSI, Jeonju branch for SEM
analysis and Mr. Jong-Gyun Kang, Center for University Research Facility
(CURF) for taking good quality TEM images.
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