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108 p-cresol IEEESJ paper 2022

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IEEE SENSORS JOURNAL
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Plasmon-Based Tapered-in-Tapered Fiber
Structure for p-Cresol Detection: From Human
Healthcare to Aquaculture Application
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Index Terms — Gold nanoparticles (AuNPs), localized surface plasmon resonance (LSPR), optical fiber biosensors,
p-cresol, tapered-in-tapered structure, tyrosinase enzyme.
Manuscript received 22 July 2022; revised 16 August 2022; accepted
16 August 2022. This work was supported in part by the DoubleHundred Talent Plan of Shandong Province, China; in part by the Special
Construction Project Fund for Shandong Province Taishan Mountain
Scholars; in part by Liaocheng University under Grant 318051901,
Grant 31805180301, and Grant 31805180326; in part by the Natural
Science Foundation of Shandong Province under Grant ZR2020QC061;
in part by The Science and Technology Plan of Youth Innovation
Team for Universities of Shandong Province under Grant 2019KJJ019;
and in part by the Fundacao para a Ciencia e a Tecnologia under
Grant CEECIND/00034/2018 and Grant 2021.00667.CEECIND, within
the scope of the i3N projects LA/P/0037/2020, UIDB/50025/2020,
UIDP/50025/2020, and DigiAqua Project PTDC/EEI-EEE/0415/2021.
The associate editor coordinating the review of this article and approving
it for publication was Prof. Agostino Iadicicco. (Santosh Kumar and
Yu Wang contributed equally to this work.) (Corresponding authors:
Santosh Kumar; Ragini Singh; Bingyuan Zhang.)
Santosh Kumar, Yu Wang, Muyang Li, Qinglin Wang, and
Bingyuan Zhang are with the Shandong Key Laboratory of Optical Communication Science and Technology, School of Physics Science and
Information Technology, Liaocheng University, Liaocheng 252059, China
(e-mail: santosh@lcu.edu.cn; 1605438881@qq.com; 1807415142@
qq.com; wangqinglin@lcu.edu.cn; zhangbingyuan@lcu.edu.cn).
S. Malathi is with the Department of Electrical, Electronics and Communication Engineering, M. S. Ramaiah University of Applied Sciences,
Bengaluru 560058, India (e-mail: malathi.ec.et@msruas.ac.in).
Carlos Marques is with the Department of i3N and Physics, University
of Aveiro, 3810-193 Aveiro, Portugal (e-mail: carlos.marques@ua.pt).
Ragini Singh is with the College of Agronomy, Liaocheng University,
Liaocheng 252059, China (e-mail: singh@lcu.edu).
Digital Object Identifier 10.1109/JSEN.2022.3200055
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Abstract —The development of a p-cresol biosensor for
aquaculture, marine life, and healthcare applications is
described in this study. The biosensor is based on localized surface plasmon resonance (LSPR) and employs a
novel tapered-in-tapered fiber (TiTF) probe. Gold nanoparticles (AuNPs) and copper oxide nanoflowers (CuO-NFs) on
TiTF structures are immobilized on this probe. The developed probe’s performance was evaluated by measuring the
response to a variety of p-cresol solution concentrations.
Combining AuNPs and CuO-NFs improves the sensitivity
and anti-interference capability of the sensing probe. When
the p-cresol solution reacts with the tyrosinase enzyme, the
refractive index on the sensing region of the probe changes,
and the resulting spectrum varies. The linear range, the limit
of detection (LoD), and sensitivity of the proposed sensor are 0–1 mM, 0.14 mM, and 3.8 pm/mM, respectively. The probe is
subjected to extensive testing, including LoD, repeatability, reusability, stability, selectivity, and pH testing, that all obtain
satisfactory results.
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Santosh Kumar , Senior Member, IEEE, Yu Wang , Muyang Li, Qinglin Wang, S. Malathi,
Carlos Marques , Ragini Singh , and Bingyuan Zhang
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I. I NTRODUCTION
RESOLS are methylated phenol derivatives that exist
in three different isomers [meta-(m-), ortho-(o), and
para-(p-)]. Phenolic compounds are widely used as a building
block in a variety of industries, including pesticides, dyes,
coatings, and oil refining, and thus are found in a higher
amount in wastewater released from these industries [1]. Additionally, leakage accidents also increased the possibility of
phenols being released into the surrounding environment. Due
to their high solubility in water (870 mM for phenol and
200 mM for cresols), phenol and cresols can persist in high
concentrations in aquatic environments [2]. Accidental leaks
of phenol and cresols into the sea or a river can significantly
increase the cresol concentrations in aquatic systems, causing
high toxicity to aquatic organisms [2], [3], posing a problem
for fish health and consequently, for humans who consume a
fish as food. Cresol has a maximum permissible concentration
of 0.027 μM for fish culture.
Phenol concentrations of 1.06 μM are sufficient to alter
the flavor of fish flesh [4]. The different phenol compounds
can be classified according to their lethal concentrations for
fish as follows: hydroquinone (2 μM), naphthols (14–28 μM),
phenol, cresol, and xylenol (18–180 μM), and resorcine and
pyrogallol (80–400 μM). Furthermore, phenols are anesthetics
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1558-1748 © 2022 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission.
See https://www.ieee.org/publications/rights/index.html for more information.
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that affect the central nervous system [5]. The clinical signs
of intoxication are characterized by increased activity and irritability, leaping out of the water, loss of balance, and muscular
spasms. In addition to a conspicuous whitening of the skin
that is heavily coated with mucus, high temperatures may
cause hemorrhages on the underside of the body. Long-term
exposure to low concentrations causes dystrophic to necrobiotic changes in the brain, parenchymatous organs, circulatory
system, and gills [4].
At the same time, it is a critical challenge for humans as
well, as its high level of consumption through shellfish and
sea fish may be alarming. Low concentrations of p-cresol
have been shown to cause skin irritation as well as blood
vessel damage through endothelial cells [6], [7]. High levels
of p-cresol have the potential to cause serious health problems such as organ dysfunction, liver disease, and even death
[8], [9]. In addition to its presence in shellfish and sea fish,
it has been reported that p-cresol can occasionally be found
in certain flavoring agents and also used as a precursor in
some traditional treatments, both of which could result in its
ingestion [10].
As a result, numerous researchers are collaborating to
develop a highly selective and sensitive biosensor capable
of monitoring p-cresol in real-time. Various techniques have
been described previously for measuring cresol, including
high-performance liquid chromatography (HPLC) [10], fluorescence [11], and gas chromatography–mass spectrometry
[12]. All of these approaches and procedures, however, are
flawed and have shortcomings such as a narrow detection
range, low reproducibility, and a high cost. Fiber-optic sensors
thrive due to their competitive advantages that include high
sensitivity, specificity, portability, flexibility, low cost, and
label-free detection [13], [14]. Various types of optical fiber
structures also established up to this point, including core
mismatch [15], [16], fiber ball structure [17], U-shaped [18],
[19], [20], long period gratings [21], and taper structure [22],
[23], for sensing applications. Previously, it was proposed to
use gold nanoparticles (AuNPs) to detect biological substances
via nano-plasmonic sensing and those experimental results
were found to be satisfactory [24]. Now, we have adopted an
innovative structure called a tapered-in-tapered fiber (TiTF)
that involves drawing a 40-μm taper into the center of
an 80-μm taper fiber structure.
Localized surface plasmon resonance (LSPR) is caused
by the interaction of conduction electrons of noble metal
nanoparticles (MNPs) and evanescent waves (EWs) outside
the optical fiber. Fiber-optic sensing probes can be made
using LSPR sensors impregnated with precious MNPs [25],
[26], [27]. The particle size, shape, structure, and dielectric
properties of metal nanomaterials all have an effect on the
resonant frequency of the LSPR phenomenon [28]. MNPs
exhibit strong absorption bands in the visible and infrared
wavelength ranges, which makes them an ideal candidate
for biosensing [29]. AuNPs are one of the most frequently
used nanomaterials today and are being thoroughly investigated in a variety of sectors [24]. For example, it has a
long history of success in disease diagnostics [30], catalysis [31], and biosensing [32]. Additionally, copper oxide
nanoflowers (CuO-NFs) are used as excellent semiconductor oxide with high biocompatibility, providing an effective
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platform for enzyme functionalization to enhance sensing
performance [33].
As a result, AuNPs and CuO-NFs provide a more versatile framework for the development of biosensors capable of
detecting p-cresol. The optical fiber-based plasma biosensor is
cost-effective, portable, simple to use, and responsive, as well
as capable of being used for online remote sensing [29], [34].
The presence of p-cresol has been determined using the
tyrosinase enzyme [35]. In this experiment, the interaction of
p-cresol solution with tyrosinase enzyme altered the refractive
index (RI) surrounding the probe, and the corresponding spectra were recorded. The relationship between p-cresol solution
concentration and peak wavelength shift was determined after
data processing.
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II. E XPERIMENTAL S ECTION
A. Materials and Methods
Step single-mode fiber (SMF, 9/125 μm) was used
for the fabrication of the TiTF (80 μm–40 μm–80 μm)
structure, as the fundamental fiber. The following
chemicals were used to prepare the AuNP solution:
hydrogen tetrachloroaurate (HAuCl4 ), trisodium citrate
(Na3 C6 H5 O7 H2 O), and deionized (DI) water. CuO-NFs were
synthesized using copper nitrate (Cu(NO3 )2 ) and sodium
hydroxide (NaOH). Acetone, hydrogen peroxide (H2 O2 ),
sulfuric acid (H2 SO4 ), 3-mercaptopropyl trimethoxysilane
(MPTMS), and ethanol were used to clean the fibers and
immobilize AuNPs/CuO-NFs on the TiTF area. The tyrosinase
enzyme was functionalized with 11-mercaptoundecanoic acid
(MUA),
N-(3-dimethylaminopropyl)-N-(3-dimethylamino
propyl)-N -ethylcarbodiimidehydrochloride
(EDC),
and
N-hydroxysuccinimide (NHS). The tyrosinase enzyme
(T3824-25KU, Sigma-Aldrich, Shanghai) is a biomolecule
that is used to specifically detect the presence of p-cresol.
Phosphate-buffered saline (PBS) solution is used to prepare
the p-cresol solution for testing. To prepare the artificial urine
solution, reagents such as urea, sodium chloride (NaCl),
potassium chloride (KCl), creatinine, and bovine serum
albumin (BSA) were required. Other reagents, including
L-alanine, β-cyclodextrin, uric acid, and glycine, were also
used to do the selective test. These are frequently found in the
urine solution. DI water was used as a solvent to prepare the
majority of the aqueous solutions and to clean the glassware.
B. Fabrication and Sensing Mechanism of the Probe
We employed the superior combiner manufacturing system
equipment to fabricate the TiTF structure using bare SMF.
The structure contained 80-μm-diameter taper waist and then
taper to a 40 μm-diameter taper structure. To begin, the first
tapering procedure uses single-mode bare fiber to build a
tapering structure with an 80-μm continuous tapering waist,
and the second tapered structure is carried out on the basis
of the first one. The sensor’s sensitivity may be increased by
varying the propagation of conventional taper structure and
activating higher-order modes with the help of the proposed
sensor’s novel structure as shown in Fig. 1 [36].
After the above steps, the program executes to achieve
two tapering processes to fabricate the TiTF structure. In a
conventional taper structure, light propagates through the taper
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KUMAR et al.: PLASMON-BASED TiTF STRUCTURE FOR p-CRESOL DETECTION
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Fig. 1. Schematic of TiTF structure.
Fig. 2. (a) SEM image of the fiber probe. (b) Measured diameter of fabricated TiTF structure.
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area in two modes: a low-order mode and a high-order mode
that were supported by the core and cladding, respectively.
EWs describe the ease with which the strength of higher-order
modes can permeate the external medium. The proposed optical fiber biosensor is based on EWs and changes due to
changes in RI of surroundings [37]. The optical phenomenon
generated by the collective oscillations of free electrons in a
metal nanostructure surrounded by a dielectric is induced by
the interaction of electromagnetic radiation from light with
MNPs. This oscillation reaches its maximum amplitude at
a specific wavelength known as the resonance wavelength,
thereby generating LSPR phenomena [26]. The TiTF sensing
area in the fiber structure is extremely reliable and dynamic.
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C. Characterization of Tapered-in-Tapered Structure
For this, two reliable characterization and measurement
tools were used to characterize the fabricated sensing probe
structure. Fig. 2(a) demonstrates the intuitive SEM image of
the sensing area of the TiTF structure at lower magnification. Additionally, the diameter scanning results for nine TiTF
structures were obtained using the CMS scan function to gain
a better understanding of the precise size and diameter details
of each structural component. It enables a more intuitive
understanding of the probe’s remarkable repeatability as shown
in Fig. 2(b).
D. Experimental Setup for p-Cresol Detection
Tungsten–halogen (HL-2000, USA) light was used to stimulate the LSPR. A spectrometer (USB2000+, USA) with a
detection range of 200–1000 nm was used to measure the
optical signal transmission intensities at the surface of TiTF
probes. The resulting data was collected with the help of the
OceanView-inbuilt program. A fusion splicer (FSM-100P+,
Japan) was used to connect the sensor probe to the spectrometer and the light source, resulting in an optical path.
Fig. 3 depicts the experimental setup used to measure the
concentration of the p-cresol solution.
E. Preparation of p-Cresol Solutions
To visualize the human fluid environment and obtain more
precise sensing results, artificial urine was used as the solvent
solution for the p-cresol molecules. To synthesize 100 mL
of artificial urine, the following ingredients were added to a
250-mL beaker, including urea, sodium chloride, potassium
chloride, creatinine, and BSA. An equal quantity of p-cresol
powder was dissolved in 60 mL of artificial urine to form a
1000-μM p-cresol solution. On this premise, artificial urine
was used to dilute the original solution, and p-cresol solutions
with concentrations of 100–900 μM were prepared.
F. Synthesis of AuNPs and CuO-NFs
In this work, two types of NPs were used to excite plasmons:
AuNPs and CuO-NFs. Turkevich’s method is commonly used
to synthesize AuNP solutions [15]. Chloroauric acid (150 μL,
100 mM) and DI water (14.85 mL) were mixed in a clean glass
container and kept for a vigorous boil. 1.8 mL (38 mM) of
trisodium citrate was added to the boiling solution and stirred
constantly. Thereafter, the colorless solution was turned to red
wine color while stirring.
CuO-NFs were synthesized using the approach mentioned
in [38]. First, 0.12-mM Cu(NO3 )2 was thoroughly dissolved in
2 mL of DI water at room temperature. Then 30 mL of ethanol
was added and heated at 75 ◦ C for 2 min. Then, ethanolic
NaOH solution (0.02 M) was added dropwise and mixed
continuously for 15 min. The solution obtained is cooled and
allowed to keep at room temperature. Then, using a centrifugal
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Fig. 3. Schematic of the experimental setup for p-cresol detection.
Fig. 4. AuNP/CuO-NF-immobilization steps on the fiber structure.
machine, CuO-NFs were centrifuged at a speed of 4000 rpm
for 2 min to obtain the final CuO-NFs and then cleaned
with ethanol and DI water sequentially, twice. Finally, the
supernatant was poured out and the white residual precipitate
was dried at 60 ◦ C for 12 h.
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G. Immobilization of AuNPs/CuO-NFs Over Fiber
Structure
Before coating the MNPs, the bare fiber’s surface was
thoroughly cleaned as described in [39]. After cleaning the
fiber with acetone for 20 min, it was submerged in piranha
solution (H2 SO4 :H2 O2 = 7:3) for 30 min to get a hydroxylated
probe. Thereafter, hydroxylated fibers were immersed in a 1%
ethanolic MPTMS solution for 12 h. MPTMS was used as
an adhesive to ensure that the AuNPs adhered to the surface
of the fiber and induced LSPR, which was essential for our
research. AuNP solution was used to develop the first layer of
the coating. After 12 h, the probe was dipped in AuNPs for
48 h, resulting in an AuNP-coated probe. Later on, CuO-NF
was coated to the AuNP-immobilized sensor structure. Before
proceeding, DI water was used to thoroughly rinse the AuNPcoated fiber structure. CuO-NFs were added at a concentration
of 1.5 mg/mL in DI water, and the probe was submerged for
6 min before being dried for 30 min. This process was repeated
three times to ensure the proper CuO-NF immobilization.
The chemical bonding changes that occur during the immobilization of NPs are illustrated in Fig. 4.
H. Enzyme Functionalization Over
NP-Immobilized Probe
The probe was immersed in a freshly prepared MUA (5 mL,
0.5 mM) ethanol solution for 5 h in order to layer it with
carboxyl groups. The probe was then immersed in an aqueous
solution of EDC (200 mM) and NHS (50 mM) for 30 min to
activate the carboxyl group. Finally, probes were rinsed with
DI water. The powdered enzyme was dissolved in 1 × PBS
(pH 7.4) to prepare the 1000 U/mL solution of the tyrosinase
enzyme. In this case, an acidic or alkaline environment could
impair enzyme activity, reduce its performance, or even cause
its inactivation; therefore, a neutral buffer was used to maintain enzyme activity. Finally, the probe was immersed in the
enzyme solution for 12 h at room temperature. Fig. 5 illustrates the changes in chemical bonding on the probe surface
that occur during enzyme functionalization.
III. R ESULTS AND D ISCUSSION
A. Characterization of NPs and NP-Coated Sensor
Structure
The first concern is the structural and geometrical characterization of NPs in an aqueous solution. In general, the
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Fig. 5. Enzyme functionalization process over the NP-coated fiber structure.
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Fig. 6. Characterization results. (a) Absorbance spectrum of AuNPs.
(b) TEM images of AuNPs. (c) Histogram of AuNPs. (d) TEM image of
CuO-NFs.
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color of the solution can be used to determine the size of the
synthesized AuNPs. The absorption spectra of AuNP aqueous
solution were analyzed using a UV–Vis spectrophotometer
to determine the resonance wavelength. The maximum peak
resonance wavelength of 519 nm is clearly visible in Fig. 6(a),
which indicates the synthesis of 10-nm AuNPs. The geometry
of AuNPs in solution was investigated using HR-TEM as
shown in Fig. 6(b). The result showed that AuNPs have a
spherical shape, are uniformly distributed in solution, and
have an average size of approximately 10 nm as shown in
Fig. 6(c). Furthermore, HR-TEM was used to characterize the
synthesized CuO-NFs, and the nanoflower images are depicted
in Fig. 6(d).
Additionally, this section includes scanning electron microscope images demonstrating the morphological characterization of nanomaterial adhesion on the optical probe surface.
In Fig. 7(a), the SEM result clearly depicts the image of
AuNP coating over fiber structure. It can be seen that AuNPs
are densely packed and evenly distributed across the surface
of the sensor probe, with no aggregation. Fig. 7(b) depicts the
Fig. 7. (a) SEM images showing the presence of AuNPs and (b) its
EDS result. (c) CuO-NFs and AuNPs and (d) its EDS result over fiber
structure.
presence of Au element content on the sensor probe’s surface.
Other elements are a result of the optical fiber and reagents
used in the synthesis process. The CuO-NF and AuNP immobilization over the TiTF sensor structure is shown in Fig. 7(c).
SEM-EDS was used to indicate the presence of AuNPs and
CuO-NFs on the probe surface as shown in Fig. 7(d).
B. Sensing Results
In this method, the transmission spectrum for p-cresol concentrations ranging from 0 to 1000 μM was determined by
using three sensor probes from the same set. These probes
were used to measure the transmission intensity. The sensor
readings for this enzyme-functionalized probe were acquired
and processed. Fig. 8(a) displays the final normalized readings
for the sensor in its entirety. The following are some of the
specific procedures used in the experiment: Before beginning
the experiment, one of the probes was chosen and immersed
in the PBS solution for about 10 min. After that, it was airdried. After that, the detection process was carried out starting
from lower to higher concentrations. When each solution’s
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Fig. 8. (a) Normalized sensing spectra and (b) linear fitting curve of the
probe.
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spectral line had reached a stable state, the spectrum was
recorded. The sensor probe was rinsed with the PBS solution
and then dried before measuring the new concentration. This
was done every time before measuring the new concentration.
This process helps to remove the previously attached p-cresol
analyte particles from the sensor probe so that it can be
used for new sensing. The detection of the other two fiber
structures was accomplished through the implementation of
the same method that was previously described. Following
that, the sensing spectrum was drawn based on the average of
the three different sets of experimental data. In Fig. 8(b), the
sensor probe’s linear regression graph is displayed. The linear
regression equation is λ = 0.0038C + 647.26, the probe’s
sensitivity is 3.8 pm/μM, and the linear coefficient is 0.9872,
as indicated by the result.
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C. Reproducibility and Reusability Test
The reproducibility and reusability of the fiber-optic sensor
are used to determine the feasibility of commercialization. The
reproducibility test was conducted using two sensor probes in
a 600-μM p-cresol solution.
In other words, two probes were used to determine the
600-μM p-cresol solution’s transmitted intensity spectrum.
As shown in Fig. 9(a), the peak wavelengths of the LSPR
spectra of both probes are the same, indicating that the probe
is reproducible.
To determine reusability, a fiber sensor is sequentially tested
with the same concentration of the p-cresol solution. To begin,
the sensor was used to detect the concentration of a 600-μM
solution. Following the measurement, the probe was rinsed
Fig. 9. (a) Reproducibility and (b) reusability results of the probe.
with 1 × PBS solution. After allowing the probe to dry
naturally, the same p-cresol solution was used to detect it
again. Similarly, to the 600-μM concentration, the other concentration (800 μM) was also examined. The final test results
are depicted in Fig. 9(b). It can be demonstrated that the probe
is reusable. The developed optical fiber sensor can also be
regenerated to reduce costs and speed up the commercialization process [40].
D. pH Test and Stability
It is well established that different pH solutions can have
a different effect on the sensor’s reliability. To investigate the
effect of pH on the probe’s characteristics, p-cresol solution in
five different solvents was dissolved with varying pH values.
These solvents included acetic acid (pH-4), ethanol (pH-6),
1 × PBS (pH-7.4: pH level comparable to that found in
aquaculture fish tanks), and potassium hydroxide (KOH,
pH-10, 14). In the solvents described above, the maximum
concentration of p-cresol that can be dissolved is 1000 μM.
The peak wavelength difference is calculated between the
highest and lowest concentrations (0 μM). Fig. 10(a) illustrates the graph used to determine the appropriate solvent. The
result showed that when p-cresol was dissolved in a 1 × PBS
(pH 7.4) solution, the wavelength difference is maximum. This
also indicates that the proposed sensor will be suitable for
clinical applications, as the pH of human serum falls within
this range.
The sensor’s detection performance was validated in the
subsequent experiment using PBS as a buffer solution.
To begin, a small amount of PBS is dropped near the sensor to
form a stable transmission spectrum. The reaction solution is
absorbed from the probe, and it is allowed to dry at room
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Fig. 11.
Selectivity test of the sensor in the presence of various
interferents.
TABLE I
C OMPARATIVE A NALYSIS W ITH VARIOUS
P ROPOSED P -C RESOL S ENSORS
Fig. 10. (a) pH test and (b) stability test of the proposed sensor.
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temperature. The same experiment was repeated ten times
to confirm the probe’s stability as shown in Fig. 10(b). The
standard deviation (SD) of the ten peak wavelengths was
calculated as 0.1808. A lower SD indicates that the probe is
more stable, in general. According to the data, the difference
in peak resonance wavelengths between the two measurements
is quite small. Similarly, the limit of detection (LoD) is a fixed
value calculated by 3 × SD/sensitivity [35]. The changes in the
RI of the surrounding medium have an effect on the sensitivity
of the LSPR sensor, which is quantified by the amount of
peak wavelength shift that occurs. According to the linear plot
shown in Fig. 8(b), the sensitivity is 3.8 pm/μM. As a result,
it is determined that the LoD of this probe is 142.73 μM.
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E. Selectivity Test
Selectivity testing is a critical component for evaluating a
sensor’s performance. In principle, these sensors are designed
to recognize p-cresol molecules specifically due to tyrosinase
enzyme deposition in the sensing region. To verify this statement, a variety of interfering biomolecules such as uric acid,
L-alanine, β-cyclodextrin, glycine, and glucose were selected
for detection at concentrations ranging from 0 to 1000 μM
within the linear range of p-cresol solutions. The difference
in peak wavelengths between the two concentrations was calculated, and the result is illustrated in Fig. 11. The results
clearly indicate the high selectivity of the proposed sensor
probes toward p-cresol.
F. Comparison With Existing p-Cresol Biosensors
The current state of research on para-cresol sensors is discussed in terms of nanomaterials, technology, linear range, and
LoD characteristics. For instance, several of the sensors listed
in Table I are based on differential pulse voltammetry (DPV),
lossy mode resonance (LMR), surface plasmon resonance
(SPR), and HPLC, among others. These systems, however,
have shortcomings such as difficult measurement stages, a high
cost, lengthy operation steps, and a timeline.
Our sensor is simple to construct, cost-effective, and has
a wide linear range that covers the entire range of p-cresol
concentrations in humans and fish (0–1 mM).
IV. C ONCLUSION
This article describes the development of a p-cresol sensor
based on the novel TiTF structure and LSPR phenomena.
To activate the LSPR phenomena, AuNPs and CuO-NFs were
immobilized on fiber probes. To determine the performance
of the developed probe, its reaction to various concentrations of the p-cresol solution has been evaluated. Additionally, the linear range (0–1 mM), LoD (0.14 mM), sensitivity
(3.8 pm/mM), repeatability, reusability, stability, selectivity,
pH test, and comparison to other sensors were evaluated.
Additionally, this research paves the way for a high-potential
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