Highly selective non-enzymatic electrochemical sensor based on a titanium dioxide nanowire-poly(3-aminophenyl boronic acid)-gold nanoparticle ternary nanocomposite

Article abstract of DOI:10.1039/c7ra09097h

A novel three component (titanium dioxide nanowire (TiO₂ NW), poly(3-aminophenyl boronic acid) (PAPBA) and gold nanoparticles (Au NPs)) based ternary nanocomposite (TNC) (designated as TiO₂ NW/PAPBA-Au TNC) was prepared by a simple two-stage synthetic approach and utilized for the fabrication of a non-enzymatic (enzyme-free) glucose (NEG) sensor. In stage 2, the PAPBA-Au NC was formed by oxidative polymerization of 3-APBA using HAuCl₄ as oxidant on the surface of pre-synthesized TiO₂ NW via electrospinning (stage 1). The formation of PAPBA-Au NC as the shell on the surface of the TiO₂ NW (core) was confirmed by field emission scanning electron microscopy (FE-SEM). Notably, we obtained a good peak to peak separation, and a high peak current for the redox Fe(CN)₆^3-/4- process indicating excellent electron transfer capability at the glassy carbon electrode (GCE)/TiO₂ NW/PAPBA-Au TNC interface. Also, the fabricated TiO₂ NW/PAPBA-Au TNC provides excellent electrocatalytic activity towards glucose detection in neutral (pH = 7.0) phosphate buffer solution. The detection of glucose was monitored using differential pulse voltammetry. The obtained sensitivity and detection limits are superior to many of the TiO₂ based enzymatic and non-enzymatic glucose sensors reported in the literature. Furthermore, the TiO₂ NW/PAPBA-Au TNC sensor is preferred because of its high selectivity to glucose in the presence of co-existing interfering substances and practical application for monitoring glucose in human blood serum samples.

Full text of DOI:10.1039/c7ra09097h

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Highly selective non-enzymatic electrochemical
sensor based on a titanium dioxide nanowire–
poly(3-aminophenyl boronic acid)–gold
nanoparticle ternary nanocomposite
Cite this: RSC Adv., 2018, 8, 2138
N. Muthuchamy,† A. Gopalan† and Kwang-Pill Lee *ab
a
ab
A novel three component (titanium dioxide nanowire (TiO
2
NW), poly(3-aminophenyl boronic acid) (PAPBA)
NW/PAPBA–Au
and gold nanoparticles (Au NPs)) based ternary nanocomposite (TNC) (designated as TiO
2
TNC) was prepared by a simple two-stage synthetic approach and utilized for the fabrication of a non-
enzymatic (enzyme-free) glucose (NEG) sensor. In stage 2, the PAPBA–Au NC was formed by oxidative
polymerization of 3-APBA using HAuCl
4
as oxidant on the surface of pre-synthesized TiO
2
NW via
NW
core) was confirmed by field emission scanning electron microscopy (FE-SEM). Notably, we obtained
electrospinning (stage 1). The formation of PAPBA–Au NC as the shell on the surface of the TiO
2
(
3
ꢀ/4ꢀ
a good peak to peak separation, and a high peak current for the redox Fe(CN)
6
process indicating
NW/PAPBA–Au TNC
NW/PAPBA–Au TNC provides excellent electrocatalytic activity
excellent electron transfer capability at the glassy carbon electrode (GCE)/TiO
interface. Also, the fabricated TiO
2
2
towards glucose detection in neutral (pH ¼ 7.0) phosphate buffer solution. The detection of glucose was
monitored using differential pulse voltammetry. The obtained sensitivity and detection limits are superior
Received 17th August 2017
Accepted 19th December 2017
to many of the TiO
2
based enzymatic and non-enzymatic glucose sensors reported in the literature.
Furthermore, the TiO
2
NW/PAPBA–Au TNC sensor is preferred because of its high selectivity to glucose
DOI: 10.1039/c7ra09097h
in the presence of co-existing interfering substances and practical application for monitoring glucose in
human blood serum samples.
rsc.li/rsc-advances
surface fouling by the absorption/passivation of the products.
The surface fouling inevitably limits the selectivity and sensi-
Diabetes, a global health problem affecting over 200 million tivity towards glucose oxidation over time. As a result, devel-
1
. Introduction
4,5
people, can cause disorders of the kidney, heart, neural system opment of non-enzymatic glucose (NEG) sensors is becoming
1
6
and retina. Hence, the monitoring of blood glucose levels is essential.
essential to prevent diabetic complications such as diabetes
Various nanostructured metals (e.g., Au, Pt, Pd, metal
from becoming more prevalent in modern society. Conven- oxides (e.g., NiO, Co
7
8
9
10
11
12
3
O
4
,
CuO ), their composites (e.g., CuO–
13
tional glucose sensors use glucose oxidase immobilized on SWCNT)), and nanocomposites (Cu based multicomponent
14
15
16
a solid electrode, to catalyze the oxidation of glucose in the nanobead), BiOCl–G nanohybrid sheets, CuO–MWCNT had
presence of oxygen to produce hydrogen peroxide and selec- been used to fabricate NEG sensors. A comprehensive review
2
tively monitor the glucose levels. Although such enzymatic has been published on the fabrication of NEG sensors using
17
glucose sensors are available commercially, they suffer from various nanomaterials. Among the metal oxide nanostructures
some limitations such as complex enzyme immobilization based sensors, TiO nanostructures have attracted much
2
procedures, instability due to the intrinsic nature of enzymes, interest due to their combinational properties such as high
sensitivity to the chemical environment (e.g. pH), and temper- surface area, electrocatalysis, non-toxicity, biocompatibility,
3
ature. Besides, long-term monitoring of the blood glucose and oxygen storage capacity. However, pristine TiO
electrodes
2
levels using an enzyme-based electrode is typically hampered by usually have poor electrochemical activity because of the low
18,19
conductivity of TiO2.
Nanocomposites of TiO , such as TiO2
2
modied with metal nanoparticles, are thus promising in NEG
2
0
a
sensors. Several binary composites based on TiO
such as
Research Institute of Advanced Energy Technology, Kyungpook National University,
2
21
22
23
24
Daegu, South Korea. E-mail: kplee@knu.ac.kr
b
TiO
–G, NiO–TiO
,
TiO
/CuO and TiO
2
/Pd, TiO /Co
3 4
O
2
2
2
2
Department of Nanoscience and Nanotechnology, Kyungpook National University, (ref. 25 and 26) were used for the fabrication of NEG sensors.
Daegu, South Korea
2
One dimensional (1D) nanostructures of TiO , specically
†
Authors contributed equally to this work.
2138 | RSC Adv., 2018, 8, 2138–2147
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
Scheme 1 Schematic diagram of the preparation of TiO
2
NW/PAPBA–Au TNC and electrochemical performance towards glucose detection.
nanowires (NW), possess essentially the common physical spectroscopy (EIS) and cyclic voltammetry (CV). The fabricated
characteristics as that of 2D and 3D nanostructures of TiO , but NEG sensor based on GCE/TiO NW/PAPBA–Au TNC electrode
geometrically offer the additional advantages like good trans- exhibited excellent performances towards electrochemical
2
2
27
2
port of electrons and mechanical stability. 1D TiO NWs, could glucose detection (Scheme 1), including high sensitivity and
also be integrated with other materials or nanomaterials to good selectivity in the presence of common interfering species
improve the surface area and electron transport properties. Our as compared to the pristine components, PAPBA and TiO NW,
2
recent research studies demonstrated that TiO2 based nano- as well over the glucose sensing performances based on other
composite can serve as the highly sensitive electrode for the TiO
2
based materials reported in literature (Table 1). Moreover,
However, the capability of utilizing GCE/TiO NW/PAPBA–Au TNC elec-
NW in combination with a glucose trode for determination of glucose levels in human serum is
selective polymer towards NEG sensor has not been reported so demonstrated, suggesting the potential of the fabricated NEG
far. sensor for practical diabetes diagnosis.
Boronic acid is well known to interact with 1,2- or 1,3-diols,
at physiological pHs or above, and form reversible covalent
28,29
determination of cholesterol and nitrate ions.
studies on the use of TiO
2
2
30
bonds to generate ve or six-membered cyclic complexes. The
chemical interactions between boronic acid and diols have been Table
between GCE/TiO
fabricated in this work and other glucose sensors
1
Comparison of glucose sensor analytical performances
NW/PAPBA–Au TNC, PAPBA–Au NC electrodes
2
utilized for the detection of diol-containing biomolecules, such
31–33
as sugars, dopamine, glycoproteins, and bacteria.
Boronic
acid groups containing polymers such as poly(3-aminophenyl
boronic acid) (PAPBA) have exhibited good operational Glucose sensor
stability and selectivity towards detection of glucose levels as
Sensitivity
[mA cm mM
Linear
range [mM]
ꢀ
2
ꢀ1
]
Reference
GOx/PANI-NF/GCE
—
0.01–1.0
0.01–3.2
0.01–5.5
0.02–6.0
0.006–1.5
Up to 3.0
0.010–1.42
3.0–9.0
0.1–4.0
0.1–8.0
0.40–8.0
0–8.0
0.006–0.14
0.2–1.0
44
45
46
47
48
49
50
51
52
53
54
21
55
56
57
58
compared to glucose oxidase and hence utilized for the fabri-
Cyt c/AuNPs/PANI-NS
63.1
4.62
6.31
0.24
11.3 ꢁ 1.3
5.32
14.56
0.39
0.94
—
6.20
—
9.9
32.6
5.01
34–37
cation of NEG sensors.
and catalytic properties, gold nanoparticles (Au NPs) have been
utilized widely in electrochemical applications.
Due to their fascinating electrical
PANI-NT/GOx
GOx/n-TiO /PANI/GCE
Au NPs in Pt/CNTs/TiO NTAs
2
38–40
2
41
combination with G (carbon 98, 90 (2016)); calix arene/boronic GOx/TiO
2
/CNTs
–SWCNT NWS
O/TiO
GOx/Ag/TiO
GOx/Pt/Gr/TiO
42
TiO
Cu
2
acids were used to improve the performance of NEG sensors.
In this background, we have constructed the NEG sensor
based on a new ternary nanocomposite (TNC) comprised of
2
2
2
NTAs
NTAs
2
TiO NW, Au NPs and PAPBA (designated as TiO NW/PAPBA– AuNPs–TiO NT
2
2
2
Au TNC) (Scheme 1). Firstly, 1D TiO NWs were synthesized by TiO
2
–GR
2
43
Chitosan–AuNPs
GOD/1DH S–TiO
electrospinning and hydrothermal processes. Followed by the
synthesis of TiO NWs, Au NPs distributed PAPBA NC was
formed on the surface of TiO NW by a one-step polymerization
of 3-APBA using auric chloride (HAuCl
The morphology and electrochemical properties of TiO
2
2
GOD/HNF–TiO
Naon-silica/
) as the oxidizing agent. MWCNTs-g-PANI/GOx
NW/ GCE/PAPBA–Au NC
GCE/TiO NW/
PAPBA–Au TNC
2
/GC
0.002–3.17
1–10
2
4
34.6
66.8
0.5–11.0
0.5–11.0
This work
This work
2
2
PAPBA–Au TNC were investigated by eld emission scanning
electron microscopy (FE-SEM) electrochemical impedance
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 2138–2147 | 2139

View Article Online
RSC Advances
Paper
dispersing 2 mg of the respective electrode modifying the
material in 0.1 mL of isopropyl alcohol and Naon (3 : 2 v/v)
solution. The mixture was sonicated for 10 min to obtain an
2
. Experimental details
2.1. Chemicals
HAuCl
4
, p-toluenesulfonic acid (p-TSA), 3-APBA, Ti(IV) isoprop- ink. About, 6 mL of the ink was dropped on the surface of pol-
2
oxide, polyvinylpyrrolidone (PVP, molecular weight < 40 000, ished glassy carbon electrode (GCE, area ¼ 0.07065 cm ) and
Fluka) acetic acid, glucose and human serum (from human male dried at room temperature.
AB plasma, USA origin, sterile-ltered) were purchased from
Sigma-Aldrich, South Korea and used as received. Ammonium
2
.4. Morphological characterization
peroxydisulfate (APS) was obtained from Samchum Chemicals,
South Korea. Phosphate buffer solution (PBS, pH ¼ 7) and
ethanol were obtained from OCI Company Ltd., South Korea.
Field emission scanning electron microscopy (FE-SEM) coupled
with energy dispersive X-ray (EDX) (Hitachi S-4300, Japan)
analysis was used to study morphology and elemental compo-
sition. The crystal structure of the prepared materials was
investigated by X-ray diffraction (XRD, Quantera SXM, ULVAC-
2
.2. Formation of TiO
The formation stages of TiO
preparation of TiO -NWs and (ii) simultaneous formation of
PAPBA and Au NPs on TiO NW.
.2.1. Preparation of TiO
preparation of pristine TiO NW are similar to that reported in
2
NW/PAPBA–Au TNC
2
NW/PAPBA–Au TNC include: (i)
ꢀ
PHI, Japan) using Cu Ka radiation (l ¼ 1.5406 A) in the 2q
2
ꢂ
range of 20–85 .
2
2
2
NW. The details of the
2
.5. Electrochemical properties and NEG sensing
2
43
our previous publication. In a typical procedure for the prepa- Electrochemical measurements were performed using Ivium-
ration of TiO NW, rstly, the composite titanate nanobers were Stat (Netherland) electrochemical interface with PC-controlled
2
obtained by electrospinning a sol–gel-transformed electro- analyzer workstation.
A conventional three-electrode cell
spinning dope. The electrospinning dope was prepared using assembly was used. The modied electrode was used as the
PVP, TiIP, acetic acid, and ethanol as follows. TiIP (2 mL) and PVP working electrode. Ag/AgCl and platinum wire were used as
(4 g) were added to an acetic acid : ethanol (3 : 7 v/v) 18 mL reference and counter electrodes, respectively. The electro-
solution and stirred for 2 h. The resulting electrospinning dope activity of the modied electrodes was evaluated using cyclic
was transferred into a plastic syringe equipped with a needle voltammetry in 0.1 M PBS (pH 7). The glucose detection
(
0.25 mm diameter) and subjected to electrospinning by applying experiments were carried out using differential pulse voltam-
ꢀ
1
a DC voltage of 25 kV using a programmable syringe pump at metry measurements at a scan rate of 0.05 V s with a pulse
ꢀ1
a ow rate of 0.7 mL h . The composite titanate nanobers were amplitude of 0.05 V, pulse rate of 0.5 s and pulse width of 50 ms
collected on a grounded rotating drum covered with an for various glucose concentrations in an electrochemical cell
aluminum foil placed at a distance of 15 cm from the spinneret. containing a magnetically stirred PBS electrolyte.
The composite titanate nanobers were sintered by calcination in
ꢂ
air at 500 C for 3 h. The calcined materials, TiO
2
-NWs, was
3
. Result and discussion
collected and washed with ethanol to remove impurities.
.2.2. Formation of PAPBA–Au NC on TiO NW. A solution
2
2
3.1. Morphology and structural characterization
containing 3-APBA (50 mM) and 10 mg of TiO -NWs was
prepared in 0.1 M p-TSA and stirred for 1 h. About 10 mL of
2
The morphologies of the as-prepared TiO NW/PAPBA–Au TNC,
2
PAPBA–Au NC, TiO NW/PAPBA NC and pristine PAPBA were
2
aqueous HAuCl
4
(5 mM) was added dropwise to the above
characterized by FE-SEM analysis. As shown in the FE-SEM
solution. The reaction was allowed to proceed for 24 h under
image of TiO
surface of TiO
2
NW/PAPBA–Au TNC (Fig. 1a), the smooth
NW (Fig. 1a, inset) was transformed into an
stirring. The dark green precipitate, (TiO
2
NW/PAPBA–Au TNC)
ꢂ
2
was washed several times with distilled water and dried at 60 C
in an air oven. For the comparison purposes, PAPBA–Au NC was
prepared by performing the polymerization of APBA using
HAuCl4 in the absence of TiO2 NW. Pristine PAPBA was
prepared as follows; a solution of 3-APBA (40 mL) was prepared
in 0.1 M p-TSA. And, about 10 mL of 0.25 M of APS solution was
uneven and bumpy surface, suggested that the surface of TiO
NW was completely covered with PAPBA–Au NC. On close
perusal of the surface of TiO NW/PAPBA–Au TNC (Fig. 1a), one
2
2
can identify two kinds of materials, spherical bright dots (Au
NPs) and the dark puffy mass (PAPBA). It is clear that Au NPs
were distributed within PAPBA matrix and existed on the
ꢂ
added dropwise into 3-APBA solution maintained at ꢃ5 C and
surface of TiO
TNC informed that nearly 17.63 wt% of elemental Au is pre-
sented in (Fig. 2). Thus, the treatment of HAuCl with 3-APBA in
the presence of TiO NW modied the TiO NW surface with
a PAPBA–Au shell layer. FESEM image of TiO NW/PAPBA NC
Fig. 1b) also reveals the modication of the surface of TiO NW.
2 2
NW. EDAX analysis of the TiO NW/PAPBA–Au
the mixture was stirred for 24 h. The precipitate (PAPBA) was
ꢂ
washed with water and dried at 60 C in an air oven. TiO
2
NW/
4
PAPBA–Au TNC was prepared by carrying out the polymeriza-
2
2
tion of 3-APBA in the presence of TiO NW using APS as the
2
2
oxidant.
(
2
In this case, a much increased (about 150 nm thick) shell layer
2
.3. Fabrication of modied electrodes for NEG sensing
TiO NW/PAPBA–Au TNC, PAPBA–Au NC, TiO
and pristine PAPBA modied electrodes were prepared by spherical Au NPs (diameters in the range 130–200 nm) on the
of PAPBA was formed on TiO NW surface. Fig. 1c displays the
2
2
2
NW/PAPBA NC image of PAPBA–Au NC with the distribution of larger sized
2140 | RSC Adv., 2018, 8, 2138–2147
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
Fig. 1 FE-SEM images of (a) TiO
2
NW/PAPBA–Au TNC, (inset: image of TiO
2
NW) (b) PAPBA–Au NC, (c) TiO
2
NW/PAPBA NC, (d) pristine PAPBA.
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
amorphous host matrix of PAPBA with minimum aggregations. 27.48 , 36.18 , 38.24 , 54.46 , 56.68 , 62.96 , 69.08 and 69.86
The pristine PAPBA had a granular morphology (Fig. 1d). that correspond to (110), (103), (004), (211), (220), (204), (116)
Fig. 3 shows the XRD patterns of the TiO NW/PAPBA–Au and (112) reections of anatase TiO , peaks corresponding to
2
2
ꢂ
ꢂ
TNC (Fig. 3a), PAPBA–Au NC (Fig. 3b). The XRD pattern of TiO2 the atomic planes of Au [2q ¼ 44.56 (200), 64.82 (220), and
NW/PAPBA–Au TNC (Fig. 3a) exhibits peaks centered at 2q ¼
2
Fig. 2 EDX spectrum of the TiO NW/PAPBA–Au TNC, PAPBA–Au NC,
TiO NW/PAPBA NC, pristine PAPBA.
2
Fig. 3 XRD pattern of the TiO
2
NW/PAPBA–Au TNC, PAPBA–Au NC.
RSC Adv., 2018, 8, 2138–2147 | 2141
This journal is © The Royal Society of Chemistry 2018

View Article Online
RSC Advances
Paper
ꢂ
ꢂ
7
7.68 (311)] and a broad band around 10–25 . The XRD pattern (Ipa)/cathodic peak currents (Ipc). The DE
p
of the GCE/TiO
2
of PAPBA–Au NC (Fig. 3b) comprises of an intense broadband NW/PAPBA–Au TNC, GCE/PAPBA–Au NC, GCE/TiO2 NW/
ꢂ
around 2q ¼ 10–25 (PAPBA) that is attributed to the periodi- PAPBA NC and GCE/pristine PAPBA electrodes were deter-
cally parallel chain of amorphous polymers of PAPBA and mined to be 0.04 V, 0.09 V, 0.27 V and 0.26, respectively, at
ꢂ
ꢂ
ꢀ1
a sharp peak Bragg reection peak at 2q ¼ 44.56 (Au (200)). The a scan rate 20 mV s . And, the GCE/TiO
2
NW/PAPBA–Au TNC
Au reection peaks at 38.24 (100) and 64.8 (220) are less electrode (Ipa ¼ 3.124 mA) exhibited nearly 1.8, 1.44 and 1.66
intense as compared to XRD pattern of the TiO NW/PAPBA–Au times higher Ipa as compared to GCE/PAPBA–Au NC, GCE/TiO
TNC (Fig. 3a). Thus, XRD pattern of TiO NW/PAPBA–Au TNC NW/PAPBA NC, and GCE/pristine PAPBA electrode, respec-
Fig. 3a) corroborates with the coexistence of crystalline TiO tively. The Ipa/Ipc linearly increased with the scan rate in the
Au atomic planes, and amorphous PAPBA.
ꢂ
2
2
2
(
2
,
ꢀ
1
range of 0.02 to 0.2 V s (Fig. 4, insets) and accompanied with
a positive shi in the anodic peak and the negative shi in the
3
ꢀ/4ꢀ
cathodic peak of the Fe(CN)6
redox process at modied
3
.2. Electrochemical properties
electrodes. Furthermore, with the increase in scan rate (0.02–
3.2.1. Electroactivity. The electroactivity, in terms of effi-
ꢀ1
0
.2 V s ), the DE
p
increased steadily with nearly a constant Ipa
/
ciency of the electron transport across the electrode/modifying
material interface, was monitored for the fabricated modied
electrodes using the bench mark redox couple Fe(CN)6
recording cyclic voltammograms (CVs) in the potential range from
I
pc ratio. These results suggested the quasi-reversible one-
3ꢀ/4ꢀ
electron behavior for the Fe(CN)
6
redox process at the
3
ꢀ/4ꢀ
, by
modied electrodes. The electrochemically accessible surface
area is an important empirical parameter to understand the
relationship between the specic electrode activity and the
structure/composition of the catalytic materials. The effective
electroactive surface area (A) of the modied electrodes was
ꢀ
1
ꢀ
0.20 V to 0.60 V, over the scan rates ranging from 0.02 V s
ꢀ
1
to 0.2 V s at the GCE/TiO
PAPBA–Au NC (Fig. 4b), GCE/TiO
GCE/pristine PAPBA (Fig. 4d) electrodes. The CV of the bare
2
NW/PAPBA–Au TNC (Fig. 4a), GCE/
2
NW/PAPBA NC (Fig. 4c) and
29
calculated by using the Randles–Sevcik equation. The A value
3
ꢀ/4ꢀ
GCE (Fig. 4a (inset)) in the presence of 5 mM of Fe(CN)6
for the GCE/TiO
2
NW/PAPBA–Au TNC, GCE/PAPBA–Au NC,
(
0.1 M KCl) is also presented for a comparative purpose.
GCE/TiO NW/PAPBA NC, GCE/pristine PAPBA was calculated
2
3
ꢀ/4ꢀ
Typically, the modied electrodes exhibited the Fe(CN)6
2
2
2
2
to be 8.22 cm , 5.40 cm , 5.06 cm and 4.67 cm , respectively.
redox transition peaks (Fig. 4a–d) as similar to the redox
transitions noticed at the bare GCE (Fig. 4a (inset)). However,
there are distinct differences between the anode peak to
The A value of GCE/TiO NW/PAPBA–Au TNC is 1.55, 1.62 and
2
1
.76 times higher than that of GCE/PAPBA–Au NC, GCE/TiO2
NW/PAPBA NC, GCE/pristine PAPBA. Based on the results on
p
cathode peak separation (DE ) and the anodic peak current
3
ꢀ/4ꢀ
ꢀ1
ꢀ1
Fig. 4 CV curves for 5 mM of Fe(CN)
6
(0.1 M KCl) at different scan rate from 0.02 V s to 0.20 V s at the modified electrodes GCE/TiO
NW/PAPBA NC (c), GCE/pristine PAPBA (d) and bare GCE (a, inset).
2
NW/PAPBA–Au TNC (a), GCE/PAPBA–Au NC (b), GCE/TiO
2
2142 | RSC Adv., 2018, 8, 2138–2147
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
3.2.2. Interfacial properties. Electrochemical impedance
spectroscopy (EIS) is an important electrochemical tool, which
can be useful to understand the charge transfer resistance at the
electrode and electrolyte interface of the modied electrodes.
The diameter of the semicircle in a Nyquist plot is a direct
measure of charge transfer resistance (R ). Fig. 6 presents of
ct
Nyquist plots of GCE/TiO NW/PAPBA–Au TNC (Fig. 6a), GCE/
2
PAPBA–Au NC (Fig. 6b), GCE/TiO NW/PAPBA NC (Fig. 6c) and
2
GCE/pristine PAPBA (Fig. 6d) electrodes recorded in 5 mM of
3
ꢀ/4ꢀ
Fe(CN)
TiO NW/PAPBA–Au TNC electrode has the lowest Rct (31.8 kU)
among the other electrodes; GCE/PAPBA–Au NC (41 kU, Fig. 6b),
GCE/TiO NW/PAPBA NC (46 kU, Fig. 6c) and GCE/pristine
6
(0.1 M KCl). Fig. 5 clearly informs that the GCE/
2
2
PAPBA (97 kU, Fig. 6d), suggesting that the TiO NW/PAPBA–
2
Au TNC lm signicantly improves the conductivity and elec-
tron transfer process. Therefore, the GCE/TiO NW/PAPBA–Au
TNC electrode was selected as the most suited modied elec-
trode for electrochemical detection of glucose.
2
2
Fig. 5 CV curves of GCE/TiO NW/PAPBA–Au TNC (a), GCE/PAPBA–
2
Au NC (b), GCE/TiO NW/PAPBA NC (c), GCE/pristine PAPBA (d) and
bare GCE (e) electrodes recorded in 0.1 M PBS (pH 7) solution. Scan
ꢀ1
rate: 50 mV s
.
3.3. NEG sensor performances
3
.3.1. Electrocatalytic oxidation of glucose. As compared to
electroactivity of modied electrodes, it can be concluded that
GCE/TiO NW/PAPBA–Au TNC electrode has the larger surface
area, lower DE and higher Ipa/Ipc, suggesting a faster electron
transfer kinetics at the GCE/TiO NW/PAPBA–Au TNC elec-
trode. And, the electrode properties of GCE/TiO NW/PAPBA–
cyclic voltammetry, the other electrochemical technique,
differential pulse voltammetry, is less likely to get affected by
the capacitive current. Differential pulse voltammetry measures
only the difference between the current at the beginning and
end of each pulse. We employed differential pulse voltammetry
to monitor the faradaic current response of modied electrodes
in the presence and absence of glucose (Fig. 7) at the optimized
differential pulse voltammetric conditions. Fig. 7 depicts the
differential pulse voltammograms (DPVs) obtained at the GCE
2
p
2
2
Au TNC (Fig. 5a), GCE/PAPBA–Au NC (Fig. 5b), GCE/TiO NW/
2
PAPBA (Fig. 5c), GCE/pristine PAPBA (Fig. 5d) and bare GCE
(
Fig. 5e) were evaluated in 0.1 M PBS (pH ¼ 7) solution. Typi-
cally, the anodic peak current at the modied electrodes was
compared with the bare GCE electrode. The anodic peak
ꢀ
1
modied with TiO
NW/PAPBA NC, and pristine PAPBA in the presence of 1 mM
glucose (Fig. 7a –d curves) and absence of glucose (Fig. 7a–e
2 2
NW/PAPBA–Au TNC, PAPBA–Au NC, TiO
current (at +0.50 V, the scan rate of +0.05 V s ) showed the
trend: GCE/pristine PAPBA < GCE/TiO NW/PAPBA NC < GCE/
PAPBA–Au NC < GCE/TiO NW/PAPBA–Au TNC. To specically
2
0
0
2
note, the anodic current at GCE/TiO NW/PAPBA–Au TNC is
2
the largest among the modied electrodes.
2
Fig. 7 DPV of glucose oxidation of GCE/TiO NW/PAPBA–Au TNC (a
0
0
0
and a ), GCE/PAPBA–Au NC (b and b ), GCE/TiO
2
NW/PAPBA NC (c
0
00
Fig. 6 Nyquist plots (Z versus Z ) of GCE/TiO
a), GCE/PAPBA–Au NC (b), GCE/TiO
2
NW/PAPBA–Au TNC and c ), GCE/pristine PAPBA (d and d') and bare GCE (e) in 1 mM
0
0
(
2
NW/PAPBA NC (c) and GCE/ glucose + 0.1 M PBS solution (solid lines; a –d ) and absence of
3
6
ꢀ/4ꢀ
ꢀ1
pristine PAPBA (d) electrodes recorded in 5 mM of Fe(CN)
KCl).
(0.1 M glucose (dashed lines; a–e). Scan rate: 0.05 V s , pulse amplitude:
0.05 V, pulse width: 50 ms.
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 2138–2147 | 2143

View Article Online
RSC Advances
Paper
Fig. 8 DPV for various glucose concentration (0.5 to 11 mM) at (a) GCE/TiO
2
NW/PAPBA–Au TNC and (b) GCE/PAPBA–Au NC modified
ꢀ1
electrodes in phosphate buffer (pH 7). Scan rate: 50 mV s , pulse amplitude: 50 mV, pulse width: 50 ms. (c) The plot of peak current I (mA) versus
concentration glucose at (i) GCE/TiO NW/PAPBA–Au TNC and (ii) GCE/PAPBA–Au NC modified electrodes.
2
curves) in 0.1 M PBS PBS solution (pH 7.0) at scan rate within ꢁ0.83% for glucose concentrations < 5.6 mM. The ISO
ꢀ
1
0
.05 V s . The modied electrodes GCE/TiO
TNC, GCE/PAPBA–Au NC, GCE/TiO NW/PAPBA NC, and GCE/ concentration levels below 5.6 mM. The lowest detection limit
pristine PAPBA show much higher peak currents (beyond the for glucose at the GCE/TiO NW/PAPBA–Au TNC is 9.3 mM,
potential of +0.25 V) as compared to the current responses in which satises the 15197:2013 requirement for a strip glucose
2
NW/PAPBA–Au 15197:2013 xes a limit of detection as 166 mM for glucose
2
2
the absence of glucose. Especially, the as-prepared GCE/TiO
2
2
sensor. The sensitivity of GCE/TiO NW/PAPBA–Au TNC (66.8 mA
0
ꢀ2
ꢀ1
NW/PAPBA–Au TNC (Fig. 7a ) modied electrode exhibited an cm mM ; Fig. 8c(i)) electrode was ꢃ2 times higher than the
ꢀ
2
ꢀ1
extraordinarily higher current response towards glucose oxida- sensitivity at PAPBA–Au NC (34.6 mA cm mM ; Fig. 8c(ii))
0
tion than noticed at GCE/PAPBA–Au NC (Fig. 7b ), GCE/TiO
2
2
electrode. The sensitivity, and linear range of the GCE/TiO NW/
0
0
NW/PAPBA NC (Fig. 7c ) and GCE/pristine PAPBA (Fig. 7d ) PAPBA–Au TNC based glucose sensor are much superior to that
modied electrodes. Typically, two distinct oxidation peaks of other reported glucose sensors based on TiO , Au NP, PANI
were observed at around 0.20 V and 0.47 V for the GCE/TiO and enzyme and its composites (Table 1).
NW/PAPBA–Au TNC electrode that corresponds to the oxidation Our results reveal that TiO NW/PAPBA–Au TNC exhibits
2
2
2
of glucose to gluconolactone and oxidation of gluconolactone to superior electroactivity, higher electrochemical surface area,
the product, respectively. The DPV of the bare GCE (Fig. 7e) in faster electron transfer kinetics, and interfacial characteristics
the presence of glucose was featureless and informed that the as compared to the pristine components. Also, it exhibits the
bare GCE was completely electro inactive towards glucose highest glucose sensing performances as compared to the TiO
2
oxidation in the potential range of interest. DPVs of the based materials reported in the literature (Table 1). We attribute
different concentrations of glucose, prepared by the proper
dilution of stock glucose solution, were evaluated at GCE/TiO
2
NW/PAPBA–Au TNC (Fig. 8a) and GCE/PAPBA–Au NC (Fig. 8b).
The size of the wave around 0.30 V to 0.50 V progressively
increased and became sharper as the concentration of glucose
increased for both modied electrodes (Fig. 8a and b). The
height of peak current at +0.47 V was taken as the measure of
quantifying the concentration of glucose. The exact current
values at the GCE/TiO NW/PAPBA–Au TNC (+0.47 V) were
2
generated from the potentiostat. A good correlation was found
between the concentrations of glucose and peak currents
(Fig. 8c). Typically, the glucose oxidation peak current showed
a linear increase with glucose concentration for the range
between 0.5 and 11 mM at GCE/TiO2 NW/PAPBA–Au TNC
(
Fig. 8c(i)) and GCE/PAPBA–Au NC (Fig. 8c(ii)) with correlation
2
coefficients (R ) as 0.9923 and 0.9917, respectively. The lowest
detection limits for glucose as estimated based on three times
of standard deviation from the blank were 9.3 mM and 23.4 mM
2
for the GCE/TiO NW/PAPBA–Au TNC (Fig. 8c(i)) and GCE/
PAPBA–Au NC (Fig. 8c(ii)) electrodes, respectively. The new ISO Fig. 9 DPV current responses at the GCE/TiO NW/PAPBA–Au TNC
2
electrode for 0.1 M PBS (pH 7.0) containing 1.0 mM glucose in the
presence of 1.0 mM each ascorbic acid (AA), uric acid (UA) dopamine
1
5197:2013 standard (as applicable from May 2016 onwards)
suggests the accuracy of blood glucose test strips within ꢁ20%
(
DA), fructose (Fru), lactose (Lac), sucrose (Suc) and mannose (Mon).
of laboratory results for glucose concentrations > 5.6 mM and
ꢀ1
Scan rate: 50 mV s , pulse amplitude: 50 mV, pulse width: 50 ms.
2144 | RSC Adv., 2018, 8, 2138–2147
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
2
Table 2 Recovery of glucose in human serum samples at the GCE/TiO NW/PAPBA–Au TNC electrode
Concentration [mM]
a
Added glucose
[mM]
Determined by
glucometer
Determined at the
fabricated electrode
Recovery
[%]
RSD
[%]
Sample
Human serum samples
0
1
1
1
2
2
2
3
3
3
4
4
4
5
5
5
4.44 ꢁ 0.01
5.415 ꢁ 0.06
5.44 ꢁ 0.02
5.43 ꢁ 0.07
6.43 ꢁ 0.03
6.36 ꢁ 0.01
6.383 ꢁ 0.05
7.388 ꢁ 0.3
7.34 ꢁ 0.03
7.442 ꢁ 0.04
8.41 ꢁ 0.01
8.45 ꢁ 0.06
8.378 ꢁ 0.02
9.42 ꢁ 0.07
9.39 ꢁ 0.03
9.41 ꢁ 0.05
4.43 ꢁ 0.04
5.412 ꢁ 0.01
5.43 ꢁ 0.05
5.413 ꢁ 0.04
6.425 ꢁ 0.07
6.358 ꢁ 0.02
6.38 ꢁ 0.03
7.37 ꢁ 0.01
7.35 ꢁ 0.07
7.31 ꢁ 0.06
8.43 ꢁ 0.02
8.442 ꢁ 0.05
8.4 ꢁ 0.04
99.8
99.94
99.81
99.68
99.92
99.97
99.95
99.75
100.13
98.22
100.23
99.90
100.26
100.11
99.97
100.04
2.84
9.431 ꢁ 0.03
9.388 ꢁ 0.04
9.414 ꢁ 0.03
a
Number of
measurements ¼ 3.
a multisource synergistic electrocatalytic effect for TiO2 NW/ (against commercial glucometer). The average relative standard
PAPBA–Au TNC arising from the catalytic activity of TiO NW in deviation (% RSD) was estimated to be lesser than 5%. Simi-
2
axial and radial directions and deliberate dispersion of elec- larly, we tested sensor performance of the particularly fabri-
trocatalytic nanosized Au particles onto the electron mediating cated sensor for the determination of glucose in serum for three
conducting polymer (PAPBA) having boronic acid binding times using the DPV calibration curve (Fig. 8c(i)). The previously
groups to selectively bind glucose.
tested sensor was gently rinsed with the buffer solution aer
3.3.2. Selectivity. The selectivity of the sensor in an essen- each measurement. The results showed an average glucose
tial requirement for the practical application of electrochemical concentration of 4.43 ꢁ 0.04 mM with an RSD ¼ 2.68%. Besides,
glucose sensor. We evaluated the selectivity of the proposed the accuracy of the fabricated sensor was tested for the serum
2
TiO NW/PAPBA–Au TNC sensor towards 1 mM of glucose samples spiked with 1 mM, 2 mM, 3 mM, 4 mM and 5 mM of
current response upon addition of 0.1 M of the commonly co- standard glucose independently to the serum samples (Table 2).
existing interfering species such as ascorbic acid (AA), uric Each serum sample was spiked for three times. A good recovery
acid (UA) dopamine (DA), fructose (Fru), lactose (Lac), sucrose (98.2–100.26% with an RSD ¼ 2.84%) towards glucose was ob-
(Suc) and mannose (Mon). The current responses were tained at GCE/TiO
2
NW/PAPBA–Au TNC electrode. We
measured at 0.47 V. As shown in Fig. 9, it can be noticed that compared the determination results in blood samples detected
GCE/TiO2 NW/PAPBA–Au TNC electrode exhibited nearly from our experiments with those measured by the commercial
negligible current response with the addition of 0.1 mM of each glucometer and results are listed in Table 2. This comparison
interfering species. The results inform that the interfering indicates that the results obtained by electrochemical detection
substances contribute nearly 0.5–2.2% of the Di value with at the GCE/TiO
respect to the current corresponding to 1 mM glucose. The those obtained by a routine commercially available glucose
result suggested that TiO NW/PAPBA–Au TNC possessed strip. Thus, we demonstrate the reproducibility and accuracy of
excellent selectivity for the glucose detection. GCE/TiO NW/PAPBA–Au TNC electrode for the detection of
.3.3. Real sample analysis. In order to validate the GCE/ glucose practical samples.
2
NW/PAPBA–Au TNC electrode match well with
2
2
3
TiO NW/PAPBA–Au TNC electrode for the practical application
2
of glucose monitoring in blood serum samples, the fabricated
sensor was used for the detection of glucose in human blood
4. Conclusion
serum samples. The glucose level in the human blood serum The ternary nanocomposite (TNC), comprising of the surface
sample was pre-determined as 4.44 mM through a commercial area enriched 1D TiO -NWs, a glucose binding conducting
2
glucometer (CareCens™ N, GM5051A, I-SENS, Inc., Korea) polymer (PAPBA) and electrocatalytic Au NPs materials was
using a glucose strip. To evaluate the reproducibility of GCE/ utilized for the construction of a sensitive non-enzymatic
TiO NW/PAPBA–Au TNC electrode, three different electrodes glucose sensor. The TiO NW/PAPBA–Au TNC exhibited good
2
2
prepared under the same conditions were tested to detect the sensor characteristics towards electrochemical detection of
serum sample having a glucose concentration of 4.44 mM glucose. The TiO NW/PAPBA–Au TNC sensor outperforms the
2
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 2138–2147 | 2145

View Article Online
RSC Advances
Paper
reported TiO
2
based glucose sensors. The peak current for 16 J. Yang, L. C. Jiang, W. D. Zhang and S. Gunasekaran,
glucose oxidation showed a linear dependence with a concen-
Talanta, 2010, 82, 25–33.
tration of glucose in a wider range, 50 mM to 11 mM with a high 17 G. Gnana Kumar, G. Amala and S. M. Gowtham, RSC Adv.,
ꢀ
2
ꢀ1
sensitivity (66.8 mA cm mM ). The excellent sensor perfor-
mances (high sensitivity and wider linear range) at TiO NW/ 18 X. Lu, G. Wang, T. Zhai, M. Yu, J. Gan, Y. Tong and Y. Li,
PAPBA–Au TNC are due to synergistic roles of the components Nano Lett., 2012, 12, 1690–1696.
TiO NW, PAPBA, and Au NPs) in the newly synthesized TNC. 19 L. Hu, K. Huo, R. Chen, B. Gao, J. Fu and P. K. Chu, Anal.
Importantly, the peak current of glucose oxidation current was Chem., 2011, 83, 8138–8144.
not inuenced at TiO NW/PAPBA–Au TNC in the presence of 20 P. V. Suneesh, V. S. Vargis, T. Ramachandran, B. G. Nair and
electrochemical interfering substances, such as ascorbic acid T. S. Babu, Sens. Actuators, B, 2015, 215, 337–344.
AA), uric acid (UA) dopamine (DA), fructose (Fru), lactose (Lac), 21 H. D. Jang, S. K. Kim, H. Chang, K. M. Roh, J. W. Choi and
2017, 7, 36949–36976.
2
(
2
2
(
sucrose (Suc) and mannose (Mon). To note, TiO NW/PAPBA–Au
J. Huang, Biosens. Bioelectron., 2012, 38, 184–188.
2
TNC sensor exhibited a remarkable performance in the human 22 Z. D. Gao, Y. Han, Y. Wang, J. Xu and Y. Y. Song, Sci. Rep.,
serum sample and signies its utility for practical blood glucose
2013, 3, 3323.
detection.
23 L. Tian, W. Hu, X. Zhong and B. Liu, Mater. Res. Innovations,
2015, 3, 160–165.
2
4 X. Chen, G. Li, G. Zhang, K. Hou, H. Pan and M. Du, Mater.
Sci. Eng., C, 2016, 62, 323–328.
Conflicts of interest
There are no conicts to declare.
25 X. Y. Lang, H. Y. Fu, C. Hou, G. F. Han, P. Yang, Y. B. Liu and
Q. Jiang, Nat. Commun., 2013, 4, 2169.
2
6 X. C. Dong, H. Xu, X. W. Wang, Y. X. Huang, M. B. Chan-
Park, H. Zhang, L. H. Wang, W. Huang and P. Chen, ACS
Nano, 2012, 6, 3206–3213.
Acknowledgements
This work was supported by the Priority Research Center
Program through a National Research Foundation of Korea 27 J. Z. Chen, W. Y. Ko, Y. C. Yen, P. H. Chen and K. J. Lin, ACS
NRF) grant funded by the Ministry of Education, Science, and Nano, 2012, 6, 6633–6639.
Technology (2009-0093819) and National Research Foundation 28 S. Komathi, N. Muthuchamy, K. P. Lee and A. I. Gopalan,
(
of Korea (2014-R1A1A4A03004026).
Biosens. Bioelectron., 2016, 84, 64–71.
29 N. Muthuchamy, K. P. Lee and A. I. Gopalan, Biosens.
Bioelectron., 2017, 89, 390–399.
References
30 B. Deore and M. S. Freund, Analyst, 2003, 128, 803–806.
1
2
A. Heller and B. Feldman, Chem. Rev., 2008, 108, 2482–2505. 31 X. Wang, Y. Liu, L. Ren, H. Li and Z. Liu, Anal. Methods, 2013,
C. Chen, Q. Xie, D. Yang, H. Xiao, Y. Fu, Y. Tan and S. Yao,
RSC Adv., 2013, 3, 4473–4491.
5, 5444–5449.
32 S. Badhulika, C. Tlili and A. Mulchandani, Analyst, 2014, 139,
3
4
5
A. S. Kumar, P. Y. Chen, S. H. Chien and J. M. Zen,
Electroanalysis, 2005, 17, 210–222.
D. P. Manica, Y. Mitsumori and A. G. Ewing, Anal. Chem.,
3077–3082.
33 H. Torul, H. Çiçi, F. C. Dudak, Y. Adıg u¨ zel, H. Kulah,
˙I . H. Boyacı and U. Tamer, Anal. Methods, 2014, 6, 5097–
5104.
2003, 75, 4572–4577.
S. Komathi, A. I. Gopalan, N. Muthuchamy and K. P. Lee, RSC 34 Q. Wu, L. Wang, H. Yu, J. Wang and Z. Chen, Chem. Rev.,
Adv., 2017, 7, 15342–15351. 2011, 111, 7855–7875.
B. K. Jena and C. R. Raj, Chem.–Eur. J., 2006, 12, 2702–2708. 35 D. G. Hall, Boronic Acids: Preparation and Applications in
6
7
8
W. Liu, X. Wu and X. Li, RSC Adv., 2017, 7, 36744–36749.
X. Bo, J. C. Ndamanisha, J. Bai and L. Guo, Talanta, 2010, 82,
Organic Synthesis, Medicine, and Materials, Wiley-VCH,
Weinheim, Germany, 2011.
8
5–91.
36 R. Nishiyabu, Y. Kubo, T. D. James and J. S. Fossey, Chem.
Commun., 2011, 47, 1106.
9
L. M. Lu, H. B. Li, F. Qu, X. B. Zhang, G. L. Shen and R. Q. Yu,
Biosens. Bioelectron., 2011, 26, 3500–3504.
0 F. Cao, S. Guo, H. Ma, D. Shan, S. Yang and J. Gong, Biosens.
37 K. M. Manesh, P. Santhosh, A. Gopalan and K. P. Lee, Anal.
Biochem., 2007, 360, 189–195.
1
1
1
1
1
1
Bioelectron., 2011, 26, 2756–2760.
38 K. L. Adams, B. K. Jena, S. J. Percival and B. Zhang, Anal.
Chem., 2011, 83, 920–927.
39 X. Zhang, T. Zeng, C. Hu and S. Hu, Anal. Methods, 2016, 8,
1162–1169.
40 P. Daggumati, Z. Matharu and E. Seker, Anal. Chem., 2015,
87, 8149–8156.
41 S. D. Bull, M. G. Davidson, J. M. Van den Elsen, J. S. Fossey,
A. T. A. Jenkins, Y. B. Jiang, Y. Kubo, F. Marken, K. Sakurai,
J. Zhao and T. D. James, Acc. Chem. Res., 2012, 46, 312–326.
1 C. Karuppiah, S. Palanisamy, S. M. Chen, V. Veeramani and
P. Periakaruppan, Sens. Actuators, B, 2014, 196, 450–456.
2 L. Xu, Q. Yang, X. Liu, J. Liu and X. Sun, RSC Adv., 2014, 4,
1449–1455.
3 N. Q. Dung, D. Patil, H. Jung and D. Kim, Biosens.
Bioelectron., 2013, 42, 280–286.
4 A. I. Gopalan, N. Muthuchamy, S. Komathi and K. P. Lee,
Biosens. Bioelectron., 2016, 84, 53–63.
5 A. I. Gopalan, N. Muthuchamy and K. P. Lee, Biosens. 42 A. Pandya, P. G. Sutariya and S. K. Menon, Analyst, 2013, 138,
Bioelectron., 2017, 89, 352–360. 2483–2490.
2146 | RSC Adv., 2018, 8, 2138–2147
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
43 H. G. Lee, G. Sai-Anand, S. Komathi, A. I. Gopalan, 51 M. Long, L. Tan, H. Liu, Z. He and A. Tang, Biosens.
S. W. Kang and K. P. Lee, J. Hazard. Mater., 2015, 283, 400–
09.
4 M. Zhao, X. Wu and C. Cai, J. Phys. Chem. C, 2009, 113, 4987–
996.
5 C. Xiang, Y. Zou, S. Qiu, L. Sun, F. Xu and H. Zhou, Talanta,
013, 110, 96–100.
6 Z. Wang, S. Liu, P. Wu and C. Cai, Anal. Chem., 2009, 81,
638–1645.
7 W. Tang, L. Li and X. Zeng, Talanta, 2015, 131, 417–423.
Bioelectron., 2014, 59, 243–250.
52 C. Feng, G. Xu, H. Liu, J. Lv, Z. Zheng and Y. Wu, J. Solid State
Electrochem., 2014, 18, 163–171.
53 C. Feng, G. Xu, H. Liu, J. Lv, Z. Zheng and Y. Wu, J.
Electrochem. Soc., 2014, 161, B1–B8.
54 Z. Zhang, Y. Xie, Z. Liu, F. Rong, Y. Wang and D. Fu, J.
Electroanal. Chem., 2011, 650, 241–247.
4
4
4
4
4
2
1
55 C. Jiang, J. Zhu, Z. Li, J. Luo, J. Wang and Y. Sun, RSC Adv.,
2017, 7, 44463–44469.
4
4
8 X. Y. Pang, D. M. He, S. L. Luo and Q. Y. Cai, Sens. Actuators, 56 P. Si, S. J. Ding, J. Yuan, X. W. Lou and D. H. Kim, ACS Nano,
B, 2009, 137, 134–138. 2011, 5, 7617–7626.
9 J. H. Lopes, F. X. Colson, J. E. Barralet and G. Merle, Mater. 57 Q. Guo, L. Liu, M. Zhang, H. Hou, Y. Song, H. Wang,
4
5
Sci. Eng. C, 2017, 76, 991–996.
B. Zhong and L. Wang, Biosens. Bioelectron., 2017, 92, 654–
660.
58 A. I. Gopalan, K.-P. Lee, D. Ragupathy, S.-H. Lee and
J.-W. Lee, Biomaterials, 2009, 30, 5999–6005.
0 N. Q. Dung, D. Patil, T. T. Duong, H. Jung, D. Kim and
S.-G. Yoon, Sens. Actuators, B, 2012, 166–167, 103–109.
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 2138–2147 | 2147