Journal of Electroanalytical Chemistry 878 (2020) 114648

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Journal of Electroanalytical Chemistry

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

A novel electrochemical sensor based on Fe-doped MgNi2O3 nanoparticles

for simultaneous determination of dopamine, uric acid, nicotine and caffeine
over very wide linear ranges
S. Lokeswara Reddy a, C. Arul a, Liu Zhaoqi a,b, N. Lavanya c, C. Sekar a,
⁎
a
Department of Bioelectronics and Biosensors, Alagappa University, Karaikudi 630003, TN, India
b
Tangshan Polytechnic College, Tangshan, Hebei Province 063299, China
c
Sensobix Canada Inc, Toronto M1S0G4, Ontario, Canada

A R T I C L E I N F O A B S T R A C T

Article history: In this study, we have synthesized MgNi2O3 and Fe-doped MgNi2O3 by sol-gel method and characterized the products
Received 17 April 2020 by powder X-ray diffraction, UV–visible spectroscopy, vibrating sample magnetometer, X-ray photoelectron spectros-
Received in revised form 19 August 2020 copy, scanning and transmission electron microscopy for confirmation of morphology, optical, structural, and mag-
Accepted 2 September 2020
netic properties. An electrochemical sensor based on 2.5 wt% Fe doped MgNi2O3 nanoparticles modified glassy
Available online 05 September 2020
carbon electrode (GCE) has been fabricated and used for simultaneous electrochemical sensing of Dopamine (DA),
Keywords:
Uric Acid (UA), Nicotine (NIC), and Caffeine (CA) for the first time. The MgNi1.95Fe0.05O3 modified GCE shows four
Fe-MgNi2O3 nanoparticles strong well-defined separate oxidation peaks of DA, UA, NIC and CA in their mixture in both cyclic and square wave
Electrochemical sensor voltammetry studies in phosphate buffer saline (pH 7). Under optimized experimental conditions, oxidation currents
Stimulant drugs increased linearly with the increase in concentration over very wide ranges of 0.1–1000, 0.1–5000, 50–6000, and
Dopamine 50–4000 μM for DA, UA, NIC and CA and the corresponding lowest detection limits (LODs) were calculated as
Uric acid 0.017, 0.104, 0.098 and 0.276 μM (S/N = 3) respectively. These measurable concentration ranges and LODs are
much higher than the values ever reported in the literature for the sensor made of a simple stable electrode material
Fe-MgNi2O3 without requiring adhesives, enzymes or modifiers.

1. Introduction
Dopamine (DA) is one of the most important catecholamines produced
in the mammalian central nervous system and adrenal medulla. It is used
by the nervous system to exchange messages between neurons and plays a
crucial role in the unique human ability to think, plan and feel pleasure
[1]. For healthy adults, the normal concentration of plasma dopamine is
in the range of 0‐30 pg/mL. Abnormalities of DA in the human body can
cause some neurological diseases such as Parkinson's disease, Schizophrenia
and Huntington's disease [2–4]. In particular, it has been established that
there is a strong link between the excessive levels of DA and Schizophrenia,
a chronic psychotic disorder affecting millions of people worldwide [5].
Uric acid (UA), the primary by-product of purine metabolism, plays a signif-
icant role in the physiological functions of living organisms and is involved
in numerous biological processes [6]. In a normal state, uric acid concentra-
tion remains in a stable range, and extreme abnormalities in its level leads to
the possibility of several diseases, such as gout, pneumonia, diabetic, kidney
disease, high cholesterol, hypertension, and cardiovascular diseases [7].
Nicotine (NIC) is one of the toxic tobacco alkaloids present in tobacco
leaves and cigarette smoke. Its consumption or exposure leads to both a sed-
ative and a stimulant conditions in humans leading to increase in their
heart rate, heart muscle oxygen consumption rate, and heart stroke volume
[8]. The tobacco epidemic results in killing of more than 8 million people a
year around the world. Both direct exposure to tobacco and the non-
smokers being exposed to passive smoking are injurious to health. Apart
from its harmful effects, studies have also been carried out to know its me-
dicinal value with the disease like ulcerative colitis, Alzheimer's and
Parkinson's diseases [9,10]. Caffeine (CA) is one of the naturally occurring
alkaloids present in plant products and beverages, such as coffee, cola nuts,
cocoa beans, tea leaves, yerbamate, and guarana berries. Caffeine acts as
central nervous system stimulant that increases alertness, reduced sleep,
improves short term memory [11,12]. Therefore, caffeine has become the
most widely used drugs in the world and has many important pharmacolog-
ical effects such as the stimulation of central nervous system, diuresis, and a
positive effect on the cardiovascular system [13]. However, reports on
human and animal studies showed that caffeine produces mental and

⁎ Corresponding author.
E-mail addresses: Sekar2025@gmail.com, sekar2025@alagappauniversity.ac.in (C. Sekar).

http://dx.doi.org/10.1016/j.jelechem.2020.114648
1572-6657/© 2020 Elsevier B.V. All rights reserved.
S.L. Reddy et al.
behavioral effects that are similar to those of typical psychomotor stimulant
drugs such as amphetamine and cocaine [14].
All the above stated biomolecules DA, UA, NIC and CA are very impor-
tant and the presence of right quantity of these chemicals is essential for the
well health of the human. Rapid screening of these analytes in the physio-
logical fluids at an affordable cost and high precision are indispensible for
disease diagnosis and further medical treatments. Conventional analytical
methods based on chromatographic and spectroscopic techniques consume
longer time, require expertise and more expensive for large scale applica-
tions. Recently, electrochemical methods are gaining significance for
determination of large number of biomolecules either selectively or simul-
taneously due to its several advantageous features such as high sensitivity,
selectivity, specificity, easier electrode fabrication process, and cost effec-
tive. Though there exists a large number of modified electrodes [15–23],
there are certain issues like further improvement in sensing performances,
electrode fouling by oxidation products and requirement of a mediator or
binder for electrode stability. Hence, new materials or modification of
known materials with unique approaches, are essential for new electro-
chemical sensor fabrication devoid of the stated issues. We have recently
synthesized a relatively new material MgNi2O3 and demonstrated its suit-
ability for non-enzymatic electrochemical sensing of glucose and conducto-
metric determination of acetone [23].
In the present work, we report the preparation of Fe doped MgNi2O3
nanoparticles by sol-gel method and its applicability for the precise selec-
tive electrochemical determination of DA, UA, CA and NIC individually in
the presence of each other. The Fe-MgNi2O3 modified GCE exhibits a signif-
icant improvement in electrocatalytic effect towards the oxidation of these
molecules with lower overpotential, improved voltammetric responses and
well separated peaks for individual analytes in the mixed system. Simulta-
neous determination of all the four analytes over very wide linear ranges
has been realized in the phosphate buffer saline at neutral pH of 7.0. The
other key features of the proposed sensor is very wide linear dynamic
ranges, low detection limits, ease of preparation of electrode material and
direct electron transfer without any mediator or catalyst for simultaneous
determination of DA, UA CA and NIC.
2. Experimental
2.1. Materials
Nitrates of magnesium [Mg(NO3)2.6H2O, 99%], nickel [Ni(NO3)
2.6H2O, 98%], and aqueous ammonia [NH3, 25%] were procured from
Molychem, Mumbai. Ferric nitrate [Fe(NO3)3.9H2O,98%] made by Nice
Chemicals-Kochi and Citric acid [C6H8O7, 99%], PEG-6000 ([HO (C₂H₄O)
nH), and acetone [C3H6O, 99.5%] from SRL-Mumbai were used for the syn-
thesis of Fe-MgNi2O3. All these chemicals were used as received without
any further purification. PBS was prepared by mixing appropriate amount
of NaH2PO4 and Na2HPO4. Stock standard solutions of 5 mM each dopa-
mine, uric acid, caffeine, and nicotine were prepared by dissolving appro-
priate quantity of precursors in 10 mL of 0.1 M PBS (pH 7.0) and stored
at 4 °C. Demineralised water was used in all the experimental processes.
2.2. Instrumentation
The phase formation and crystalline nature were examined by powder
X-ray diffraction (XRD) (XPERTPRO X-ray diffractometer) using Cu-Kα ra-
diation (λ = 1.5406 Å) and crystallite sizes of the nanoparticles were calcu-
lated by Debye Scherer formula. Optical property was studied by UV–Vis
spectroscopy (Varian CARY-5000) equipped with Deuterium (UV) and
Tungsten lamps (VIS-NIR). Magnetic measurements were carried out at
room temperature in a vibrating sample magnetometer (VSM) (Cryogenic,
UK). X-ray photoelectron spectroscopic analysis was carried out using
ESCALAB 250XI Base system with UPS and XPS image mapping containing
XR6 Micro-focused monochromatic X-ray source (Al Kα XPS) XR4 Twin
Anode Mg/Al (300/400 W). The morphology and particle size of the nano-
particles were analyzed by field-emission scanning electron microscopy
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Journal of Electroanalytical Chemistry 878 (2020) 114648
(Quanta FEG 250) and high resolution-transmission electron microscopy
(HR-TEM, Talos F200S).
2.3. Material preparation
Pure MgNi2O3 (Mg-123) and 2.5% Fe-MgNi2O3 (Fe-Mg-123) nanoparti-
cles were synthesized by sol-gel method [24]. 1 M of nitrate solutions of
Mg, Ni and Fe were prepared individually and stoichiometric amount of
these solutions were mixed thoroughly for about 30 min. Citric acid
(C6H8O7) was used as a reducing agent and the pH of the solution was
found to be 3. This pH was increased to 8–8.5 by adding required amount
of ammonia solution, after a while 10 ml of PEG-6000 solution was
added as a surfactant and stirred for 30 min. The mixture was then kept
at 80°C under continuous stirring and finally, the product was obtained
by removing gel and unreacted impurities, if any, by washing repeatedly
in water and acetone. Finally, the powder samples were annealed at
600 °C for 2 h in an ambient atmosphere. MgO and NiO nanoparticles
were also synthesized by similar procedure in order to ensure the phase pu-
rity and to compare the sensing performance of the MgNi2O3 in its pure and
doped form.
2.4. Fabrication of the modified electrodes
Glassy carbon electrodes polished with 0.05-μm alumina powder slurry
and cleaned with demineralized water were used in the electrochemical
measurements. About 1 mg of samples were dispersed in 1 mL water indi-
vidually and ultra-sonicated for 20 min at room temperature to disperse
the nanoparticles homogeneously throughout the solvent. The film was
coated by drop casting 10 μL of dispersion on the polished surface of GCE.
3. Results and discussion
3.1. Powder X-ray diffraction analysis
Fig. 1A shows the powder XRD patterns of MgNi2O3 and 2.5% Fe-
MgNi2O3 samples indicating that the compounds crystallize in cubic struc-
ture with the space group Fm3m. All the observed diffraction peaks could be
assigned to the major phase according to the JCPDS data (card no 00–034-
0410) and the absence of any additional peaks confirms the phase purity of
the synthesized materials. Average particle sizes were calculated using
Debye Scherer formula.
D = k λ/β cos θ.
where D is the crystallite size, λ is the X-ray wavelength (1.54 Å), θ is
the diffraction angle, β is the full width at half maximum (FWHM) and k
is a constant (0.89). The estimated values of 70 nm and 41 nm for
MgNi2O3 and 2.5% Fe-MgNi2O3 respectively indicate a significant reduc-
tion in the growth due to the addition of Fe as dopant.
3.2. Optical property of MgNi2O3
Being a new material, optical absorption behavior of MgNi2O3 in its
pure and doped form (2.5% Fe) was evaluated by UV–Vis DRS spectros-
copy. Band gap energy was calculated by using Kubelka-Munk equation.
hv FðRÞ ¼ ðAhν−EgÞn=2
where ν is the light frequency, F(R) is the Kubelka-Munk function, A is
the proportionality constant and Eg is the band gap energy. Eg of
semiconductor-based catalysts was calculated from the graph plotting be-
tween [F(R). hν]1/2 versus hν as shown in Fig. 1B. The calculated Eg values
of 2.4 eV and 2.1 eV for MgNi2O3 and 2.5% Fe-MgNi2O3 respectively indi-
cate that the direct band gap energy decreases due to Fe loading into
MgNi2O3.
S.L. Reddy et al.
Fig. 1. (A) Powder XRD pattern, (B) UV–Visible spectra and (C) Magnetic properties of MgNi2O3 and 2.5% Fe-MgNi2O3 NPs.
3.3. Magnetic measurements
Fig. 1C shows the field dependent magnetization (M-H) curves of pure
and Fe doped MgNi2O3 samples measured using VSM at room temperature.
A typical superparamagnetic material does not possess any remnant
magnetisation (MR), coercivity (HC) and should exhibit a perfect S-type hys-
teresis pattern from M vs. H study. As expected, the pristine MgNi2O3 NPs
revealed the M-H behavior typical of a superparamagnet and the saturation
magnetization of (MS) was found to be about 2.582 × 10−3 emu/gn [25].
On the other hand, Fe-doping (wt. 2.5%) induces ferromagnetism and that
the Ms value is reduced to 1.772 × 10−3 emu/g for Fe-doped Mg-123 sys-
tem. The observed minute hysteresis in the M-H curve could be attributed
to the double interaction between ferromagnetic Fe ions, reduced crystal-
lite size and doping induced defects and/or oxygen vacancies in the parent
Mg-123 system. The results confirm, in agreement with the powder XRD
data, that the intended dopant Fe entered into the lattice of Mg-123 crystal
system.
3.4. X-ray photoelectron spectroscopy analysis
Elemental composition and its chemical states in the synthesized
Fe-MgNi2O3 NPs have been carried out using XPS. Fig. 2A shows a typical
core level photoelectron spectrum of the undoped and 2.5% Fe-doped
MgNi2O3 NPs. The spectra of Mg (1 s) shows a strong peak between
1003.3 and 1003.6 eV confirming the presence of Mg in the MgNi2O3 sam-
ple. In the case of Fe-doped sample, the peak intensities got increased, but
the sharpness of the peak is reduced [Fig. 2B]. For Ni, a sharp Ni2p3/2
peak appeared at 853.7 eV, and its satellite peak [Fig. 2C] appeared with
binding energy of 1.9 eV above the main line confirming the oxidation
state of Ni is 2+. Fe 2p spectrum of 2.5% Fe-MgNi2O3 [Fig. 2D] exhibits
two Fe2p peaks, 2p3/2, 2p1/2 doublet and their two satellite peaks at
higher binding energies.
The difference in binding energy between Fe2p3/2 (710.5 eV) and
Fe2p1/2 (723.6 eV) is 13.1 eV, which suggests that the Fe is in 2+ oxidation
state. The high-resolution spectra of oxygen (O 1 s) indicate a strong peak at
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Journal of Electroanalytical Chemistry 878 (2020) 114648
529.15 eV and two weak satellite peaks at 530.4 eV and 533.25 eV corre-
sponding to the O2− ions in the MgNi2O3 system [Fig. 2E]. The XPS and
XRD investigations concurrently confirm that the Fe2+ ions have been in-
corporated into MgNi2O3 lattice by substituting Ni2+ ions. Though there
is no carbon in both the pure and 2.5% Fe-MgNi2O3 samples, the XPS
data shows [Fig. 2F] a carbon peak (1 s) at 284.8 eV which might have orig-
inated from the environment during the film deposition process.
3.5. Surface morphology and compositional analyses
FE-SEM images of the pure MgNi2O3 (Fig. 3A&B) and 2.5% Fe-MgNi2O3
(Fig. 3C&D) show that both the compounds crystallized as near spherical
nanoparticles and that they are homogeneously distributed over the entire
scanned surface. Close observations show that the undoped MgNi2O3 NPs
were larger in sizes and, that the Fe doping led to reduced particle size
with high porosity. As compared with prisitne MgNi2O3, the Fe doped
MgNi2O3 has a very good structural confinement effect so that its particu-
lates are smaller, and are porous in nature.
The TEM images [Fig. 4 A&B] confirm the formation of Fe-MgNi2O3
NPs in spherical shape and that the particle sizes has been reduced from
70 nm for pure Mg-123 to an average size of 40 nm for Fe-doped Mg-123.
Notably, three different lattice fringes can be observed in the HR-TEM pic-
ture of the compound. The calculated d-spacing values of these lattice
fringes [Fig. 4C] 0.24, 0.14 and 0.20 nm correspond to the (111), (220)
and (200) planes of Fe-MgNi2O3 NPs, respectively. The d spacing values ob-
served are in good agreement with the d spacing values obtained in the XRD
pattern. The lateral size of the Fe-MgNi2O3 NPs is consistent with SEM anal-
ysis. To ensure the presence of Mg, Ni, Fe, and O in the composite, TEM-
EDAX and elemental mapping were recorded at the particular location
[Fig. 4D]. The elemental mapping revealed the uniform distribution and
that there are no other impurities in the samples as shown in Fig.S1.
3.6. Electrochemical properties of MgNi2O3 and Fe-MgNi2O3 NPs
Electrochemical properties of pristine MgNi2O3 and 2.5% Fe doped
MgNi2O3, MgO and NiO were measured by modifying GCEs through drop
S.L. Reddy et al.
Fig. 2. XPS spectra of Fe doped MgNi2O3 NPs; (A) full scan, (B) high resolution spectra of Mg 1 s, (C) Ni 2p, (D) Fe 2p, (E) O 1 s and (F) C 1 s.
casting 10 μL of each sample dispersed in demineralised water and drying
the modified electrodes at room temperature. Cyclic voltammograms
(Fig.S2A) were recorded for (a) pristine GCE and (b) MgNi2O3, (c) Fe-
MgNi2O3, (d) MgO and (e) NiO modified GCEs in 1 M KCl containing
1 mM of [Fe(CN)6]3−/4− at 50 mVs−1. The peak current (Ipa) values of
bare GCE, MgNi2O3, and Fe-MgNi2O3 modified GCEs were observed as
20.80, 22.05 and 23.68 μA respectively. When compared to MgNi2O3/
GCE, F-MgNi2O3/GCE exhibited higher peak current. The charge trans-
port process at the electrode/electrolyte interface of the modified elec-
trodes was investigated by measuring charge transfer resistance (Rct)
values. Fig.S2B shows the impedance spectra obtained for modified
GCEs at scanning frequencies from 100 kHz to 0.1 Hz. Rct values were
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Journal of Electroanalytical Chemistry 878 (2020) 114648
obtained by Randles equivalent circuit [RS(QCPE(RctW)], where RS is
the solution resistance, W is the Warburg impedance and QCPE is the
constant phase element (CPE). The (Rct) values of bare GCE, MgNi2O3,
Fe-MgNi2O3, MgO and NiO modified GCEs have been calculated as
579.6, 329.6, and 298.0, 1215 and 114.4 Ω/cm2 respectively. It can
be noticed that the Fe-doping into MgNi2O3 reduced the resistance
value of pristine Mg-123 system confirming improved electron transfer
process due to doping [23]. Both the EIS and CV results suggest that
the electron transfer rate at the 2.5% Fe-MgNi2O3/GCE is higher than
that MgNi2O3/GCE.
The effective surface area of modified GCEs were estimated using
Randles-Servik equation.
S.L. Reddy et al.
Fig. 3. FE-SEM images of undoped MgNi2O3 (A&B) and 2.5% Fe-MgNi2O3 NPs (C&D).
Ip ¼ 2:69  105 AD1=2 n3=2 v1=2 C
where A represents the area of the electrode (cm2), n is the number of
electrons participating in the reaction (n = 1), D is the diffusion coefficient
of the molecule in solution (6.70 × 10−6 cm2 s−1), C is the concentration
(1 mM) and υ is the san rate (V s−1). The electrochemical surface area
values were calculated as 0.135, 0.142, 0.141 and 0.152 cm2 for MgO,
NiO, MgNi2O3 and Fe-MgNi2O3 modified GCEs respectively. It can be no-
ticed that the Fe-MgNi2O3/GCE has higher surface area than that of the
bare GCE and pristine MgNi2O3 modified GCE.
3.6.1. Electrochemical oxidations of DA, UA, NIC and CA on Fe-MgNi2O3/GCE
The electrocatalytic activities of DA, UA, NIC and CA at the Fe-
MgNi2O3/GCE were investigated by SWV. Fig. 5A shows the SWVs of
100 μM DA, 300 μM UA, 300 μM NIC, and 500 μM CA recorded at bare
GCE, MgNi2O3, and Fe-MgNi2O3/GCEs in 0.1 M PBS (pH 7.0). In case of
Fe-MgNi2O3/GCE, four strong well resolved oxidation peaks of DA, UA,
NIC and CA have been observed at 0.143 V, 0.276 V, 0.86 V and 1.354 V
respectively with significant potential separation of 0.133 V between DA-
UA and 0.494 V for NIC-CA which are large enough for simultaneous deter-
mination of the four analytes. From these results, we concluded that the Fe-
MgNi2O3/GCE shows improved oxidation towards all the four analytes
when compared with the bare GCE and pure MgNi2O3. It was also noticed
that there is a significant negative shift in the oxidation potential of DA and
UA, while that of NIC and CA remained almost unchanged.
3.6.2. Effect of scan rate and pH on the oxidations of DA, UA, NIC and CA
From Fig. 5B, the effect of scan rate on the redox peak currents of DA, UA,
NIC and CA at the Fe-MgNi2O3/GCE were investigated at different scan rates
in the range of 50–500 mV/s. Oxidation peak currents increases proportion-
ally with the increase in scan rate due to the improved electron transportation
5
Journal of Electroanalytical Chemistry 878 (2020) 114648
and adsorption rate of analytes at higher potential. The redox currents were
found to be proportional to square root of the scan rate, which suggests a
diffusion-controlled process on the modified electrode surface.
The solution condition (pH) plays the most vital role on the perfor-
mance of an electrochemical sensor. Generally, the pH affects many chem-
ical and biological processes in the given aqueous medium. The analytes
chosen for the present investigation (DA, UA, NIC and CA) have to be mea-
sured in the blood serum or urine. Therefore, we have investigated the ef-
fect of pH on the anodic peak current and potential of the analytes in PBS
at Fe-MgNi2O3/GCE by SWV over the range of pH values from 3 to 10.
From Fig. 6, it can be seen that the anodic peak currents of all the four
analytes reach maximum at pH 7.0, and then decreases gradually with fur-
ther increase of pH of the solution containing DA, UA and NIC.
In case of CA, there has been a significant enhancement in the oxidation
current when the pH was raised from acidic to neutral and continued to re-
main in the higher scale for further increment of pH of the solution. This
anomaly can be explained as follows; Caffeine or trimethoxylxanthine is
an alkaloid from the xanthine groups whose reaction with the electrode ma-
terial Fe-MgNi2O3 seems to depend much on solution condition. In acidic
pH, activity of H+ ion is high, which limits the oxidation of caffeine. On
the other hand, at neutral and alkaline pH conditions, OH− activity is
higher which makes easy coordination of OH− with the C8 carbon of the
caffeine. Hence, neutral and alkaline pH yielded enhanced electrochemical
oxidation of caffeine. The oxidation potentials of DA, UA, NIC and CA are
found to be pH dependent (Fig. 6) indicating that the protons take part in
the electrode reactions (Scheme 1).
3.6.3. Selective and simultaneous sensing of DA, UA, NIC and CA at
Fe-MgNi2O3/GCE
As the target analytes DA, UA, NIC and CA coexist in the extracellular
fluid of human body and the oxidation potentials of DA and UA are very
S.L. Reddy et al. Journal of Electroanalytical Chemistry 878 (2020) 114648

Fig. 4. HR-TEM images of 2.5% Fe-MgNi2O3 NPs; TEM-EDAX elemental mapping of the main elements Mg, Ni, Fe and O.

Fig. 5. (A) SWV obtained for the mixture of 100 μM DA, 300 μM UA, 300 μM NIC and 500 μM CA in 0.1 M PBS (pH 7.0) at (a) bare, (b) MgNi2O3/GCE, and (c) 2.5%
Fe-MgNi2O3/GCE at a scan rate of 50 mV/s. (B) CV response of 2.5% Fe- MgNi2O3/GCE at 50–500 mV−1 in 0.1 M PBS (pH 7.0).

6
S.L. Reddy et al. Journal of Electroanalytical Chemistry 878 (2020) 114648

Fig. 6. Effect of pH on SWV peak currents (A) and peak potential (B) towards the oxidation of 100 μM DA, 300 μM UA, 300 μM NIC and 500 μM CA in 0.1 M PBS.

close to each other, their interferences should be excluded. In case of NIC oxidation process of one-analyte as a function of its concentration while
and CA, their oxidation potentials are well separated from each other and keeping the concentration of the other three analytes at fixed values.
so, it is easy to investigate the selectivity by individually and simulta- As can be seen in Fig. 7, the peak currents increase with the increase in
neously. SWV has been chosen to investigate the changes in the electro- concentration over the range of 0.1 to 1000 μM for DA, 0.1 to 5000 μM for

Scheme 1. Plausible reaction mechanism for electro-oxidation of DA, UA, NIC and CA at the Fe-MgNi2O3/GCE

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S.L. Reddy et al. Journal of Electroanalytical Chemistry 878 (2020) 114648

Fig. 7. SWVs obtained for various concentrations of (A) Dopamine (0.1 to 1000 μM) in the presence of 300 μM UA, NIC, and CA, (B) Uric acid (0.1 to 5000 μM) in the presence
of 100 μM DA, 300 μM NIC and CA, (C) Nicotine (50 to 6000 μM) in the presence of 100 μM DA, 25 μM UA, (D) Caffeine (50 to 4000 μM) in the presence of 100 μM DA,
300 μM UA, 500 μM NIC, at 2.5% Fe- MgNi2O3 modified GCE in 0.1 M PBS (pH 7.0) and the inset plots show the oxidation peak current against the concentration of DA,
UA, NIC and CA.

Table 1
Comparison of different chemically modified electrodes for the determination of DA, UA, NIC and CA with 2.5% Fe-MgNi2O3/GCE.
Electrode Linear range (μM) Limit of detection (μM) Ref.

DA UA NIC CA DA UA NIC CA
a
Fe3O4@CNT-N/GCE 2.5–65 2.5–85 – – 0.05 0.047 – – [2]
b
Pd-rGO/GCE 0.45–421 6–469.5 – – 0.18 1.6 – – [3]
c
GO/GCE 0.1–80 – – – 0.08 0.11 – – [4]
d
HA/GCE – – – 0.142 – – [7]
e
β-CD/CQDs/GCE 4-220 0.3–200 – – 0.14 0.01 – – [13]
f
Co-MOF/GO/GCE 0.2-80 0.8–200 – – 0.05 0.1 – – [14]
g
MWCNT/GCE – – 31–1900 – – – 9.3 – [17]
h
ITO/TiO2/PEDOT – – 0–5000 – – – 4.9 – [18]
i
Nano-TiO2/CP – – 2-540 – – – 0.013 – [19]
j
MWCNT/Cu-NPs/GCE – – 1–1000 – – – 1.0 – [20]
k
HA-GN-MWCNT – – 0.3-179.5 4–205 – – 0.21 1.42 [21]
l
BQ/CPE – – 500-8000 – – – 51 [22]
m
Au/Pd NPs-GRF – – 0.03–938.97 – – – 0.006 [23]
n
Fe-MgNi2O3 0.1-1000 0.1-5000 50–6000 50–4000 0.017 0.104 0.098 0.276 This work
a
Fe3O4@CNT-N /GCE: Fe3O4-Nitrogen doped CNT modified Glassy carbon electrode.
b
Pd-rGO/GCE: Palladium nanoparticles-reduced grapheme oxide modified GCE.
c
GO/GCE: Graphene oxide/Glassy carbon electrode.
d
HA/GCE: Hydroxyapatite/ Glassy carbon electrode.
e
β-CD/CQDs/GCE: Poly(Β-cyclodextrin)/carbon quantum dots/Glassy carbon electrode.
f
Co-MOF/GO/GCE: Co(II)-metalorganic framework (ZIF-67)-graphene oxide.
g
MWCNT/GCE: Multiwalled carbon nanotubes/GCE.
h
ITO/TiO2 /PEDOT: Indium tin oxide/titanium dioxide/poly(3,4-ethylenedioxythiophene).
i
Nano-TiO2/CPE: Nano‑titanium dioxide modified carbon paste electrode.
j
MWCNT/Cu-NPs/GCE: Multiwalled carbon nanotubes/Copper nanoparticles.
k
HA-GN-MWCNT/GCE: Hydroxyapatite/ Graphene-Multiwalled CNTs.
l
BQ/CPE: 1,4-benzoquinone modified carbon paste electrode.
m
Au/Pd NPs-GRF: Gold/Palladium nanoparticles-Graphene Flakes.
n
Fe-MgNi2O3: Iron (II) doped MgNi2O3.

8
S.L. Reddy et al. Journal of Electroanalytical Chemistry 878 (2020) 114648

Fig. 8. SWVs obtained for simultaneous determination of dopamine (0.1 to 1000 μM), uric acid (0.1 to 2000 μM), nicotine (50 to 2500 μM), caffeine (50 to 2500 μM) at
2.5% Fe- MgNi2O3 modified GCE in 0.1 M PBS (pH 7.0) at various concentrations and the below plots show the oxidation peak current against the concentration of DA,
UA, NIC and CA.

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S.L. Reddy et al. Journal of Electroanalytical Chemistry 878 (2020) 114648

Table 2
Determination of DA, UA, NIC and CA in real samples by standard addition method.
Sample Added (μM) Found (μM) RSD % Recovery %

Dopamine 60 55.54 5.46 92.56

70 67.6 2.46 96.57
Uric acid 300 298.32 0.4 99.44
500 502 0.28 100.4
Nicotine 300 297.8 0.54 99.27
400 404.29 0.75 101.07
Caffeine 350 349.81 0.04 99.95
450 451.08 0.17 100.24

Ipa; NIC ðμAÞ ¼ 1:2778 þ 6:342CNIC R2 ¼ 0:993 and


Ipa; CA ðμAÞ ¼ 2:4801 þ 2:465CCA R2 ¼ 0:996 respectively

The lowest detection limits were calculated for DA, UA, NIC and CA as
Fig. 9. Anti-interference ability of the 2.5% Fe-MgNi2O3/GCE towards the oxidation 0.017, 0.104, 0.098 and 0.276 μM (S/N = 3), respectively. The electro-
of 100 μM DA, 300 μM UA, 300 μM NIC and 500 μM CA in 0.1 M PBS (pH 7). chemical sensing performance of the new Fe-MgNi2O3 modified GCE in
comparison with a number of other electrodes reported in literature is
presented in Table 1.
UA, 50 to 6000 μM for NIC and 50 to 4000 μM for CA with the correspond- It can be seen that the fabricated Fe-MgNi2O3/GCE has improved
ing linear functions of. sensing performances with very wide linear ranges when compared to
many other modified electrodes reported in the literature. The results


Ipa; DA ðμAÞ ¼ 2:453 þ 1:0773CDA R2 ¼ 0:993 are very exciting in view of the fact that the electrode is free of any me-
diator or enzyme or modifier and that the Fe-MgNi2O3 film drop casted

on GCE remained stable even after prolonged measurements. The high
Ipa; UA ðμAÞ ¼ 5:739 þ 3:485CUA R2 ¼ 0:997
performance of the sensor could be attributed to the synergistic effect

Fig. 10. SWVs obtained for various concentrations of real samples; (A) dopamine (0.1 to 100 μM), (B) uric acid (0.5 to 800 μM), (C) nicotine (0.5 to 200 μM), (D) caffeine (50
to 500 μM) at Fe- MgNi2O3/GCE in 0.1 M PBS (pH 7.0).

10
S.L. Reddy et al.
of composition and structure, and the dopant induced oxygen vacancy,
increased active sites, large specific surface area and porosity on the sur-
face [18,19].
In order to explore the possibility of using the 2.5% Fe-MgNi2O3/GCE
for the simultaneous determination of DA, UA, NIC and CA, the oxidation
peak current responses of all the four biological species have been moni-
tored by square wave voltammetry by simultaneously changing the concen-
tration of DA, UA, NIC and CA in the mixture. As can be seen, four well
defined SWV oxidation peaks were obtained at 0.12, 0.26, 0.84 and
1.35 V corresponding to the electro-oxidation of DA, UA, NIC and CA
respectively.
As can be seen in Fig. 8, the peak currents increase with the increase in
concentration over the range of 0.1 to 1000 μM for DA, 0.1 to 2000 μM for
UA, and 50 to 2500 μM each for NIC and CA with the lowest detection limits
of 0.020, 0.094, 0.0576 and 0.1326 μM (S/N = 3), respectively. The corre-
sponding linear functions were,

and the values lie between 92.6% and 101.07%. The recovery data lie in the
Ipa; DA ðμAÞ ¼ 7:718 þ 3:214CDA R2 ¼ 0:99

the determination of DA, UA, NIC and CA in biological fluids with adequate
Ipa; UA ðμAÞ ¼ 9:334 þ 2:812CUA R2 ¼ 0:99


Ipa; NIC ðμAÞ ¼ 9:306 þ 1:841NIC R2 ¼ 0:98 and


Ipa; CA ðμAÞ ¼ 5:232 þ 4:619CCA R2 ¼ 0:984 respectively
It can be noticed that the LODs for all the four analytes are nearly in
the same order for both the simultaneous and independent measure-
ments. However, the linear ranges are lesser for the case of NIC and
CA in the simultaneous sensing when compared to their individual
analyses.
Moreover, it was noted that the pristine glassy carbon electrode also ex-
hibits high electrocatalytic activity with sharp peaks with good separation
between analytes. To highlight the promoting effect of Fe-MgNi2O3, a sys-
tematic study has been made with the bare GCE at different concentrations
of DA, UA, NIC and CA and the calibration curves obtained were compared
with that of Fe-MgNi2O3 modified GCE (see Fig. S3A&B). Though we have
obtained all the four oxidation peaks at bare GCE, calibration curves give a
clear indication that the Fe-MgNi2O3 modified GCE has improved sensing
characteristics, wider linear ranges, high reproducibility and selectivity
compared with that of pristine GCE. The results further open up new oppor-
tunities aimed at rational synthesis and design of new oxide-based sensing
materials targeted towards simultaneous detection of multi-analytes. The
present sensor based on the new electrode materials Fe-MgNi2O3 will be
useful for applications in the pharmaceutical industry and biomedical
diagnosis.
3.6.4. Anti-interference ability of the 2.5% Fe-MgNi2O3/GCE
The anti-jamming ability of the fabricated electrode was tested to-
wards the detection of DA, UA, NIC, and CA from potential interferents
by square wave voltammetry (Fig. 9). No significant change in the
current response was observed for the mixture of 100 μM DA, 300 μM
UA, 300 μM NIC and 500 μM CA in the presence of 100-fold excess of
ascorbic acid, folic acid, glucose, hypoxanthine, Na+, K+, lactose,
L-adrenaline, L-tryptophan, riboflavin and urea indicating that the pres-
ent modified electrode is highly selective towards the determination of
DA, UA, NIC and CA in the presence of several common interferents.
3.6.5. Reproducibility and stability
To evaluate the reproducibility of 2.5% Fe-MgNi2O3/GCE, the peak cur-
rents of 25 successive measurements by CV in a solution of 0.1 mM DA,
0.5 mM UA, 0.4 mM NIC and 0.4 mM CA were determined. The relative
standard deviations (RSD) of 3.17%, 2.78%, 4.17% and 2.51% were ob-
tained for DA, UA, NIC and CA respectively. Stability of the fabricated elec-
trode was tested by measuring CV in PBS containing 0.1 mM DA, 0.5 mM
UA, 0.4 mM NIC and 0.4 mM CA in three different electrodes (Fig. S3).
The results showed a loss of 0.99%, 1.57%, 1.2% and 1.94% from their
11
Journal of Electroanalytical Chemistry 878 (2020) 114648
initial values after 25 continuous cycles. These results indicate that the
2.5% Fe-MgNi2O3/GCE electrode has a good reproducibility, stability and
does not undergo surface fouling.
3.6.6. Application of 2.5% Fe-MgNi2O3/GCE for real sample analyses
In order to explore the analytical applicability of proposed 2.5% Fe-
MgNi2O3 modified GCE for determination of DA, UA, NIC and CA in phar-
maceutical formulations, human urine, cigarette and coffee powder sam-
ples were chosen as real samples and SWV response was monitored with
different concentrations of dopamine injection, human urine, cigarette ex-
tract, coffee extract samples in 20 ml of 0.1 M of PBS (pH 7.0). Standard ad-
dition method was adopted for such real sample analysis and the results
obtained are displayed in Fig. 10. SWVs of unspiked and spiked samples
were obtained under optimum conditions and the results observed are sum-
marized in Table 2. Recovery values were calculated based on this method
acceptable range, thus the developed sensor can be successfully utilized for
accuracy.
4. Conclusions
A new non-enzymatic electrochemical sensor based on Fe-doped
MgNi2O3 modified glassy carbon electrode has been fabricated successfully
and its application for simultaneous determination of four important bio-
molecules DA, UA, NIC and CA has been realized for the first time. A variety
of physical characterization data of synthesized Fe-MgNi2O3 NPs confirmed
that the dopant ion Fe2+ replaces the intended target site (Ni2+) and that
the crystal structure of MgNi2O3 was retained up to the maximum loading
of 2.5 wt% Fe. The Fe-MgNi2O3 modified GCE exhibited an excellent elec-
trocatalytic activity towards the oxidation of DA, UA, NIC and CA. More-
over, large peak separations between DA, UA, NIC and CA allow the
modified electrode to determine the analytes either individually or simulta-
neously with high sensitivity and selectivity. Besides, the 2.5% Fe-
MgNi2O3/GCE exhibits wide linear ranges and low detection limits for
the simultaneous determination of DA (0.1 to 1000 μM & 0.017 μM), UA
(0.1 to 5000 μM & 0.104 μM), NIC (50 to 6000 μM & 0.098 μM) and CA
(50 to 4000 μM & 0.276 μM) respectively. The fabricated sensor was
shown to be useful for the detection of DA, UA, NIC and CA in pharmaceu-
tical and biological samples with satisfactory results.
Declaration of Competing Interest
The authors declare that they have no known competing financial inter-
ests or personal relationships that could have appeared to influence the
work reported in this paper.
Acknowledgement
Authors SL, CA and CS acknowledge Government of India sponsored
projects; Ministry of Human Resource Development (MHRD) Rashtriya
Uchchatar Shiksha Abhiyan (RUSA 2.0) [No. F.24-51/2014- U, Policy
(TN Multi-Gen), dated 09.10.2018]; Department of Science and Technol-
ogy (DST)-Promotion of University Research and Scientific Excellence
(PURSE) [Phase 2/38(G) dated: 21.02.2017)]; Council of Scientific & In-
dustrial Research (CSIR) (No. 03(1419)/18/EMR-II dated: 04.06.2018)
for the financial assistance.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.jelechem.2020.114648.
S.L. Reddy et al.
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