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Recent advances in Nicotine Electrochemical biosensors: a review

Article in Case Studies in Chemical and Environmental Engineering · May 2024

DOI: 10.1016/j.cscee.2024.100753

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Recent advances in Nicotine Electrochemical biosensors: a review

Abolfazl Mirani, Ehsan Kianfar, Laleh Maleknia, Mohammad Javanbakht

PII: S2666-0164(24)00147-6
DOI: https://doi.org/10.1016/j.cscee.2024.100753
Reference: CSCEE 100753

To appear in: Case Studies in Chemical and Environmental Engineering

Received Date: 22 February 2024

Revised Date: 5 May 2024
Accepted Date: 7 May 2024

Please cite this article as: A. Mirani, E. Kianfar, L. Maleknia, M. Javanbakht, Recent advances
in Nicotine Electrochemical biosensors: a review, Case Studies in Chemical and Environmental
Engineering, https://doi.org/10.1016/j.cscee.2024.100753.

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Recent advances in Nicotine Electrochemical biosensors: a review

Abolfazl Mirani*1, Ehsan Kianfar†1, Laleh Maleknia2, Mohammad Javanbakht3

1
Biomedical Engineering Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical

Sciences, Tehran, Iran.

2
Department of Biomedical Engineering, South Tehran Branch, Islamic Azad University, Tehran, Iran.

3
Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences,

Tehran, Iran.

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Abstract

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The chemical compound nicotine, specifically 3-(1-methyl-2-pyrrolidinyl) pyridine, is a notable

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xenobiotic under investigation in the realm of electrochemical biosensors. This article emphasizes
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the nature of this substance and its impact on the human body. Different species with
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pharmacological, therapeutic, industrial, food-related, and environmental origins can now be

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detected using electrochemical sensors. Nicotine, an addictive substance in tobacco products and
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electronic cigarettes (e-cigs), is recognized for increasing the risk of cardiovascular and respiratory
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disorders. Careful real-time monitoring of nicotine exposure is critical in alleviating the potential

health impacts of not just smokers but also those exposed to second-hand and third-hand smoke.

Monitoring of nicotine requires suitable sensing material to detect nicotine selectively and testing

under free-living conditions in the standard environment. A biosensor consists of a sensitive

biological system and a detector system with appropriate transducers for obtaining output signals.

The applications of these devices include health screening, the detection of environmental

contaminants, farming, and routine medical examinations. Critical factors in its widespread

*
Corresponding author: [email protected]
†
Corresponding author: [email protected] and [email protected].

1
commercialization will be the product's selectivity, sensitivity, stability, and lower production

costs. Scientists have been working on developing a nano biosensor with a high degree of

sensitivity and selectivity for the recognition of biomarkers of immune responses and cancer. An

analysis of various parameters, including Limit of Detection (LOD) and monitoring nicotine

concentration within the biological pH range (7-7.4), has been conducted. The objective of this

analysis is to enhance sensitivity, expand linear range, and optimize optical and electrical

properties. The article delves into the optimization of sensors and biosensors from an

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electrochemical perspective, highlighting the positive and negative effects of nicotine, as well as

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its metabolic pathways in the human body. The study categorizes and evaluates the latest nicotine

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detection sensors and biosensors based on their generation (electron transfer between multilayers)
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and methods (modification types or direct electrodes). The strengths and weaknesses of each are
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scrutinized over the past 15 years, with a focus solely on electrochemical biosensors.
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Keywords: Biosensor, Electrochemical, Nicotine, Sensor, biological.

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1. Introduction
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Nicotine is the main alkaloid found in tobacco leaves, accounting for about 95% of the total

alkaloid content, which are used in the production of cigarettes, cigars or flake tobaccos with

content varying from 1 to 30 mg/g [1]. Currently, more than 1.2 billion people worldwide consume

different tobacco products that results in nicotine addiction [2]. A few of the seen benefits of

nicotine are intervened by the decrease of antagonistic impacts of nicotine withdrawal (named

negative fortification). Hence, the pharmacologic part of nicotine in compulsion may be a

combination of giving positive and negative reinforcement (Fig. 1). For day-by-day smokers,

there's a everyday cycle amid which nicotine levels rise within the blood, considerable resilience

2
creates amid the day, and smoking happens to diminish withdrawal indications. A few exceedingly

dependent smokers wake at night to smoke since of withdrawal indications. In differentiate, a few

light and discontinuous smokers smoke in reaction to specific signals, without encountering

withdrawal side effects, and are thought to smoke fair for positive support. The regular intake of

nicotine through smoke of the burning tobacco products is toxic for both active and passive

smokers and can cause several negative outcomes in human health such as cardiovascular,

respiratory, central nervous diseases and even cancer [3]. This enormous consumption of tobacco

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products worldwide leads to around 4.9 million deaths per year. Absorption of nicotine can be

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through the oral intake, lungs, urinary bladder, gastrointestinal tract, and its base form can be also

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easily absorbed through the skin, and can cause a poisoning in a contact with nicotine containing
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pesticides too [4]. Therefore, several products are proposed as a replacement therapy to avoid
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tobacco consumption and to quit smoking. Such products include nicotine in the form of a nicotine
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chewing gums, nicotine patches, and nicotine tablets [5]. As it is evidenced by many studies,

nicotine’s fatal dose in adults was specified to be 60 mg that corresponds to nicotine concentration
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of 2 mg/L (12.33 μM) in blood and 4 mg/L (24.66 μM) in plasma [6] In addition to that, various
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studies have been performed for the analysis of nicotine and cotinine in different physiological

fluids rather than blood and plasma but in urine, sweat and saliva [7] with liquid chromatography,

tandem mass spectroscopy [8] colorimetry and immunoassay methods [9]. According to the results

of those studies, the concentration value in sweat for cotinine was 21.4 – 202 ng/patch, nicotine

was 150 – 2498 ng/patch [7] while those values were vastly different in different body fluids, for

instance the cotinine concentrations were found to be 1.5, 1.7 and 5 μg/L in serum, saliva, and

urine respectively with 280-fold increase in urine and 180-fold increase in plasma [10]. However,

the physiology and metabolism of each smoker is different and therefore, personalized dosing of

3
nicotine replacement is of great importance for designing the products that will respond to with

the same efficiency at each individual. Therefore, critical monitoring and determination of nicotine

is of paramount importance in fields of medicine, toxicology and tobacco industry, and necessitates

the development of simple, accurate, sensitive, and selective analytical methods [11]. Despite of

the numerous methods based on gas chromatography [12–14], high performance liquid

chromatography [15,16], capillary electrophoresis [17,18], spectrophotometry [19] and

radioimmunoassay [20] which have been developed so far, none of them meet the requirements of

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the current market based on tobacco consumption for the quantification of nicotine in biofluids

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since those methods require time-consuming sample-preparation steps, expensive instrumentation,

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and highly skilled workers. There are biological materials in direct spatial connection with a
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transduction component to explore an analyte in a biosensor[21-24]. The trio-combo design of a
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sensitive biological system and the detector system with appropriate transducers for obtaining the
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output signals has a wide range of uses, including disease screening, the detection of environmental

pollutants, agriculture, and routine medical examinations [25-29]. The early use of electrochemical
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sensors began with the Leland C. Clark's examination of industrial oxygen in the 1950s. An
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electrochemical sensor must have at least two electrodes the sensing and counter electrodes to

function. An external electric circuit or an electrolyte must be used to connect these electrodes [30-

31]. An oxygen permeable membrane separates the electrodes from the electrolyte solution,

serving as the primary medical purpose of oxygen sensor design. Through membrane diffusion,

oxygen was lowered in the indicator electrode. This led to a current that was inversely correlated

with the oxygen content of the sample[32-36]. The schematic representation of the general

principle underlying electrochemical biosensors is shown in Figure 2. Surface science of the

4
nanomaterials, surface engineering and functionalization are some of the factors that affect the

electrochemical nano biosensors performance.

Electrochemical sensors, a notable category within this array of detection methodologies, rely on

the interaction between the target and an electrolyte, inducing electrochemical reactions that

culminate in a measurable current [20]. These reactions often involve redox enzymes [21] , and

the resultant current, contingent upon the concentration of the target (typically exhibiting either a

linear or logarithmic relationship), offers a quantifiable parameter [22]. In addition to

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chromatographic and spectrophotometric methods, sweat monitoring via electrochemical

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sensors/biosensors is also a very active research area of medical diagnostics with thrilling

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examples of glucose [24], lactate [25], pH [26], drug [27] and ion [28] detection. In Table 1 several
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electrochemical methods are listed which were reported so far for the detection of nicotine inside
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different buffers. Up to now, there is not any sensor developed for the quantification of nicotine in
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human sweat of heavy and light smokers. Table 1 several electrochemical methods are listed
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which were reported so far for the detection of nicotine inside different buffers. Up to now, there
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is not any sensor developed for the quantification of nicotine in human sweat of heavy and light

smokers. The allure of electrochemical biosensors lies in their potential advantages, encompassing

low detection limits (LOD), a broad linear response range, as well as stability and

reproducibility[23]. Table 2 shows the dosage of Nicotine that minimum claimed effect. Figure 3

serves as a visual representation, illustrating the schematic intricacies of an electrochemical

Nicotine biosensor, capturing the essence of this sophisticated detection technology.

Table1. Comparison of proposed method with some previously reported electrochemical methods

for electrochemical determination of nicotine.

5
Electrode Electrolyte Method Linearity LOD Sample Ref

(μM) (μM)

CPE PBS, pH 7.5, Square wave voltammetry 50–500, 50– 6.1, 3.2 cigarettes liquid [122]

BRBS pH 11 1000 0–

5000

TiO2/PEDOT/ITOE PBS, pH 7.4 Amperometry; p-AHNSA 0–5000 4.9 - [123]

PGE PBS, pH 7.0 + Square wave voltammetry 7.6–107.5 2 cigarettes [124]

SDS 2 mM

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BDDE BRBS, pH 8 Square wave voltammetry 5–500 3.1 cigarettes [125]

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BDDE BRBS, pH 8 (E)-1-(4-((4- 0.5–202.5 0.3 cigarettes, cigar, [126]

(phenylamino)phenyl)diazenyl) pharmaceuticals
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phenyl)ethanon
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p-AHNSA/GCE PBS, pH 7.5 Square wave voltammetry 1–200 0.9 cigarettes [127]
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NGS-SPCE/RGO- PBS (pH 7.4) Cyclic voltammetry 0–200 0.05, Cigarettes, artificial
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SPCE/GO-SPCE 0.08 urine

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and

0.27

μM

EA/GCE PBS, pH 7 Square wave voltammetry 1–200 0.7 cigarettes [128]

MWCNT/GCE Na2C2O4, pH Differential pulse voltammetry 31–1900 9.3 cigarettes [129]

4.5

RGO/DPA/PGE Na2C2O4, pH Differential pulse voltammetry 31–1900 7.6 cigarettes, cigar [130]

4.5

6
MWCNT/GCE PBS, pH 7.4 Cyclic voltammetry 10–50, 2–10 5, 2 - [131]

NCB/GCE

CNC/SPCE PBS, pH 7.4 Square wave voltammetry 10–1000 2 saliva [132]

MWCNT/ACS/GCE PBS, pH 8 Amperometry; p-AHNSA: - 1.4 - [133]

poly(4-amino-3-

hydroxynaphthalene sulfonic

acid)

CuWO4/rGO/Nf/GCE PBS, pH 7 Amperometry; p-AHNSA: 0.1–0.9 0.04 cigarettes, urine [134]

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poly(4-amino-3-

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hydroxynaphthalene sulfonic

acid)
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SPCE PBS, pH 7.4 Differential pulse voltammetry 1–375 0.6 sweat [135]
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Table 2. Dosage of Nicotine that minimum claimed effect.

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PrOBLEm effective dosage

ref
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negative 1.5 mg/70 kg [60]

reinforcement

positive 0.03mg/kg [61]

reinforcement

NIC stimulate 0.09 mg/kg [62]

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body weight 0.25mg/kg [63]

reduction

Parkinson's 2mg [64]

disease

Alzheimer's 3.5mg [65]

disease

Tourette's 7mg [66]

syndrome

7
ulcerative 4mg [67]
colitis

sleep apnea 2mg [68]

lethal for 10mg [69]

children

lethal for adult 40mg [70]

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Figure1. nicotine addiction cycle [27].

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Figure 2. Schematic illustration of electrochemical biosensing device [121].
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Figure 3. Schematic Nicotine Biosensor component [91].
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A biosensor is an analytical device for detecting an analyte that combines a biological element
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with a physicochemical identifier. Biosensors consist of three main parts [191-194]:

• A sensitive biological element (such as tissues, microorganisms, organelles, cell receptors,

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enzymes, antibodies, nucleic acids, etc.), is a biological substance that interacts with the
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studied analyte.

• A transducer or detector element (works in a physicochemical way and can be optical,

piezoelectric, electrochemical, magnetic, and thermometric) that converts the signal

resulting from the interaction of the analyte with the biological element into another signal

that is easier to measure.

• A signal processing system that is responsible for displaying the results in a user-friendly

manner and converting the signal into a readable form. This part is sometimes the most

expensive.

10
A typical example of a commercial biosensor is the blood glucose biosensor. Recently,

arrays of different types of identifier molecules have been applied in a tool called electronic

nose, in which the response pattern of identifiers is used to identify a substance. In the

wasp-hound odor detector, the mechanical element, a video camera, and the biological

element are five detector bees that have learned to swarm in response to the presence of a

specific chemical. However, common commercial electronic noses do not use biological

elements. A canary in a cage that is used by miners to warn of the presence of gas can also

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be considered a biosensor. Many applications of today's biosensors are similar in that they

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use organisms that react to toxic substances in concentrations lower than the threshold of

human senses.
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As mentioned, a biosensor generally includes a bio-recognition component, a bio
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transducer component, and an electronic system that includes a signal amplifier, processor,
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and display. In all biosensors, there is a substrate on which one of the "affinity-pairing

partners" is fixed. The partners may be the enzyme and its substrate, antigen/antibody, a
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specific acceptor and ligand, or living cells and an analyte that specifically binds to them.
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To detect interactions between partners, a biosensor uses a transducer, which converts the

biological response to an electrical signal that is amplified and stored by a processor. The

general goal of designing a biosensor is to be able to perform a convenient and fast test at

the test site or where the sample is prepared [4]. A schematic of an exemplary biosensor is

presented in Figure 4.

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Figure4. Schematic of an exemplary biosensor [4].
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In a biosensor, the biological indicator is designed to interact with a specific analyte to produce a
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measurable effect through the transducer. High selectivity for the analyte among a host of other
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compounds Biological and chemical is required for all biological identifiers. The type of
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biomolecules used as biological identifiers can vary widely, but in general, biosensors can be
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divided into conventional types of antibodies/antigens, enzymes, cellular nucleic acids/cells, or

biomimetic materials based on their structures, DNA/type of biological identifier made up. An

important auxiliary part of a biosensor is a membrane that covers the biological sensing element

and is responsible for controlling the penetration of the analyte, protecting against mechanical

stresses and supporting the sensing element.

Antibodies are proteins that show significant selectivity. They are produced in response to

antigenic structures, which are considered foreign substances to organisms. Antigen molecules

larger than 10 KDa lead to an immune response from organisms. Smaller molecules such as

vitamins and steroids can be antigens, but they do not lead to an immune response unless they are

12
combined with larger molecules. Antibodies are usually covalently bound through combination

with groups Amino, carboxyl, aldehyde or sulfhydryl are fixed on the surface of the converter. The

surface of the biosensor should be already with an amino, carboxyl, hydroxyl or other groups can

be functionalized. Antibodies have the same limitations as enzymes and usually use optical and

acoustic transducers. An antibody-based biosensor called an immunosensor uses the highly

specific affinity of antibodies to bind to specific compounds or antigens. The special nature of the

antigen-antibody interaction is similar to a lock and key relationship where the antigen, if it has

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the right combination, will only bind to the antibody. This connection leads to a physicochemical

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change and thus produces a signal.

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There are limitations in using antibodies in sensors: (1) Antibody binding capacity strongly
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depends on the measurement conditions (pH and temperature) and (2) Antibody-antigen
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interaction is generally irreversible but it has been shown that this binding can be done through
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chaotropic reagents, organic solvents or even ultrasonic radiation be disturbed.

Biosensors can be classified concurring to a few parameters [53]. Based on the sort of atomic
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acknowledgment (bioreceptor), they can be isolated into enzymatic biosensors (with a chemical as
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a bioreceptor), resistant or microbial biosensors, etc. (Figure 5), Furthermore, by the sort of related

transducer, we recognize between electrochemical biosensors, optical biosensors, calorimetric

biosensors, etc., At last, agreeing to the species identified, as substrate or inhibitors. They give

wide applications in location of chemical and organic targets [54,55]. Biosensors are expository

instruments advertising quantitative or semi-quantitative expository data by implies of an organic

acknowledgment component in contact with a reasonable transducer. Within the manufacture of

biosensors, the choice of a suitable network and the immobilization strategy are the foremost

critical components influencing the biosensor explanatory exhibitions [56].

13
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Figure5.Schematic presentation of different biosensors based on numerous bio-recognition

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elements.

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2. Historical Background
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The historical narrative of nicotine degradation research for electrochemical detection, driven by
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enzyme-based methodologies, is an interdisciplinary expedition interweaving chemistry, biology,

and analytical techniques. Originating from the 19th-century identification of Nicotine in tobacco
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plants, subsequent eras emphasized Nicotine 's addiction association through pharmacological
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studies[24]. Analytical advancements in the latter half of the 20th century led to the emergence of

electrochemical detection, leveraging enzyme-based approaches for heightened sensitivity. The

integration of enzymes, notably Nicotine oxidase, into electrochemical sensors marked a pivotal

advancement, yielding measurable signals for biosensor development. Recent decades witnessed

further refinement of electrochemical methods, optimizing enzyme-based sensors for real-time

monitoring. This historical context not only highlights the journey from foundational discoveries

but also emphasizes the practical application of sophisticated analytical tools across diverse

domains, ranging from healthcare to environmental monitoring. Concurrently, the exploration of

14
Nicotine degradation, rooted in mid-20th-century discoveries, delved into the intricate metabolic

processes, notably the oxidation pathway and nitrogen atom focus. This ongoing research not only

contributes to understanding Nicotine metabolism but also enriches comprehension of alkaloid

degradation and broader metabolic transformations within biological systems[25,92-95].

3.Fundamentals and Basic Principles

The study involved investigating the degradation of Nicotine to release electrons that are

transferred to the amplifiers for re-cording voltage and current. Suffering et al. explored the

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oxidation pathway of Nicotine, with a specific emphasis on the nitrogen atom [26,96-99]. Their

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findings revealed that, under the assumption of demethylation followed by the subsequent

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hydroxylation of the nitrogen atom at the pyrrolidine ring, a distinctive metabolic transformation
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occurs. Another potential natural metabolite arising from Nicotine is cotinine, involving bio-
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oxidation and an intramolecular recon-formation at the chiral carbon [27,100-103]. In living

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organisms, enzymatic processes, primarily occurring at the hepatic level through microsomal

enzymes [28,104-106], CYPs, specifically CYP2A6, are pivotal enzymes responsible for
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degrading approximately 80% of Nicotine through C-oxidation to form cotinine, while the
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remaining 20% involves other enzymes such as CYP2B6[29]. FMO3, another enzyme, catalyzes

the reaction of Nicotine with oxygen, resulting in Nicotine N'-oxide [107-110]. This process,

known as Nicotine degradation II, indicates that (S)-NIC trans N'-oxygenation and delta 1',5'-

iminium ion formation could serve as selective probes for human liver flavin-containing

monooxygenase form II and cytochrome P-450 2A6 activities [30]. This reaction known as

Nicotine degradation II. Both of these metabolic pathways release two electrons, which

subsequently impact the surface of the sensor or biosensor, providing the capability to identify

Nicotine [111-114]. The involvement of enzymatic processes and the intricacies of the identified

15
metabolic transformations suggest a natural, non-artificial origin in the investigation of Nicotine

degradation pathways.

4. NIC Electrochemical Sensor Generations

For performance of the fabricated electrochemical sensor, Electrode modifier is the key. There are

several ways to improve the sensitivity of the sensing electrode, namely changing the base

electrode material. Many materials were applied for electrode surface modification such as

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semiconductors[31], noble metals[19], carbon based materials[32,115-117], nanowires[33,118-

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120], magnetic nanoparticles (NPs)[34,121-122], Nano rods[35,123-124] and quantum dots[36].

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G1-The first generation of Nicotine sensors use an electron mediator between Solution containing
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Nicotine and the electrode surface of electrodes. The detection limit for theme is narrow but fast.
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G2- The second generation (G2) of sensors demonstrated enhanced electron transfer to the
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electrode surface by incorporating conductive nanoparticles, specifically carbon-based

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nanomaterials like carbon nanotubes, graphene, buck paper, and Nano hybrids [37,125-130].
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These materials exhibit high charge transfer capabilities, resulting in sensors with increased

sensitivity and lower detection limits[38,131-135]. Carbon nanotubes and carbon nanofibers,

integrated into transducer design, improve electrical signals from enzymes to electrodes,

enhancing the performance of cytochrome P450 biosensors for drug screening and monitoring.

Researchers have successfully utilized multiwall carbon nanotubes (MWCNT) to design

biosensors with improved sensitivity, achieving low detection limits. Carbon-based nanomaterials

offer various advantages, including a high surface-to-volume ratio, electrical conductivity,

chemical stability, biocompatibility, and mechanical strength. Studies utilizing multiwall carbon

nanotubes -graphene composites for electrode surface modification have shown excellent

16
electrochemical performance in Nicotine detection, providing a wide detection range and low

limits of detection[136-140]. Additionally, sensors based on Cu(II)-NIC complex reduction at

multiwall carbon nanotubes -modified electrodes and electrophoretic pumping through

functionalized carbon nanotubes membranes have demonstrated efficient Nicotine detection with

low limits of detection[39,141-145]. Overall, these advancements underscore the potential of

carbon-based nanomaterials in improving the electrochemical performance of Nicotine sensors for

diverse applications.

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G3-The third generation contained enzymes. The life time of a sensor is limited by the stability

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of the enzyme. This makes the surface of the electrode in contact with Nicotine to be sensitive

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only to Nicotine. This use of the enzyme caused the interactions to disappear and only the surface
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of the electrode was sensitive to Nicotine. Unlike the previous two generations, because the lipid
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nature of these enzymes acted like an insulator, the speed of electron transfer decreased, instead,
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the detection range increased [146-150]. Many materials have been used to modify the electrode

surface to enhance the sensitivity of enzyme-based biosensors by increasing the effective surface
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area of the electrode to load large amounts of enzyme[40]. The large effective surface area
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introduces a large number of active sites and often a higher signal-to noise ratio. The small

dimensions of nanoparticles bring about convergent, which resulted in a higher rate of mass

transport to the electrode surface [151-154]. Biosensors have been constructed for the

determination of Nicotine based on the inhabitation of enzyme activity of acetylcholinesterase,

which catalyzes the hydrolysis of neurotransmitter acetylcholine or oxidation by CYP P450[41].

G4-In electrochemical investigations, it is very difficult to achieve the direct electron transfer of

an enzyme without any modification of the electrode surface. One of the most promising

technologies in transducers elaboration involves the use of novel materials with a suitable

17
nanostructured surface[42]. The fourth generation, which is used today to detect Nicotine, is a

combination of all previous generations. Today, enzymes are used to increase sensitivity to

Nicotine and prevent interactions. with adding mixed layers of conductors with high electron

transfer such as gold nanoparticles or nanofibers or nanotubes such as carbon nanotubes, the speed

and accuracy have increased and the record of the lowest detection rate has also been improved.

There are four main advantages for a nanotube-modified electrode compared with a macro-

electrode: high effective surface area, mass transfer, catalysis and control over local

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microenvironment [43- 44]. Fig 6 shows a simplified timeline of glucose sensor evolution, across

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generations.

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Fig6. The development of a glucose biosensor using electrochemical methods [121].

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5. Previous Research
Few works have been performed on the determination of Nicotine by the direct electrochemical

measurement with the solid-electrodes, recently research like Xiao et al [45] demonstrated an

electro reduced carboxylate graphene(CG) modified glassy carbon electrode (GCE) for Nicotine

analysis[45]. Shehata et al [46] demonstrated a Nano-TiO2 modified carbon paste sensor for

Nicotine analysis[46]. Nano-TiO2 with a carbon paste electrode (CPE) were used for the sensor

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construction. The sensor showed electro catalytic activity in both aqueous and micellar media

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toward the oxidation of Nicotine at Britton-Robinson (B-R) buffer solution (4×10(-2) M) of pH

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range (2.0-8.0) containing (1.0mM) sodium dodecyl sulfate (SDS) using cyclic voltammetry (CV)
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and electrochemical impedance spectroscopy (EIS) techniques. Nano-TiO2 Modified Carbon Paste
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sensor (NTMCP) was detected using differential pulse voltammetry (DPV) technique and it was

found between 2×10(-6)M and 5.4×10(-4)M with a detection limit of 1.34×10(-8)M. Fekry et al [47]
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demonstrated a novel electrochemical Nicotine sensor based on Ce Nanoparticles with anionic

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surfactant[47]. They prepared cast-coating a CG solution on a GCE surface, for quantitative

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analysis of Nicotine in real tobacco samples with recoveries over 95%, based on cyclic

voltammetry after potentiation enrichment of Nicotine at −1.1 V for 240 s in 0.1 M KH2PO4–

Na2HPO4 buffer solution (pH= 7.0). The oxidation peaks current of NIC at the electro reduced CG

(ERCG)/GCE after a semi-derivative treatment responded linearly to Nicotine concentration from

2 to 5 μM and from 5 to 60 μM, with a limit of detection of 0.1 μM. Xiaoqing Li et al [48] used an

electrochemical screen-printed carbon electrodes (SPCE) modified with nitrogen-doped graphene

sheets (NGS) sensor for Nicotine detection[48]. NGS shows high catalytic activity for the electro-

oxidation of Nicotine, with a significant decrease in the over potential. they obtained detection

sensitivity at 0.627 mA·cm− 2 mM− 1 with the limit of detection at 47 nM Nicotine. the sensor

20
shows favorable selectivity and long-term stability for detecting Nicotine in urine and tobacco

samples. Yanqiu Jing dye combined (E)-1-(4-((4-(phenyl amino)phenyl)diazinyl)

phenyl)ethenone (DPA) with reduced graphene oxide (RGO) for the electrochemical modification

of a pencil graphite electrode (RGO/DPA/PGE) surface[49]. NIC irreversibly reduced. The

reductive peak current of NIC at the modified electrode an obvious increase was observed,

indicating the capability of the RGO/DPA composite to increase the electron transfer rate. The

current found proportional to the Nicotine concentration in a range of 31 to 1900 μM, and the limit

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of detection (LOD) was calculated as 7.6 μM. Magda Ameer and co- workers synthesis of a simply

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modified electrochemical Nicotine sensor based on silver nanoparticles[50]. They mixed a carbon

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paste with silver nanoparticles to make an Ag nanoparticle modified carbon paste electrode.
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Different electrochemical techniques were used, including cyclic voltammetry, linear sweep
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voltammetry, and electrochemical impedance spectroscopy in both aqueous and micellar media.
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The electrode-based Nicotine sensor exhibited a high sensitivity in quantitative analysis, and its

detection limit could be as low as 0.0036 μmol/L with linearity ranging from 0.8 μmol/L to 800
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μmol/L. In addition, due to it was good reproducibility, anti-interference performance, and long-
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term stability.

Won-Chul Lee [51] created a sensor for detection Nicotine and L-tyrosine (Tyr) and developed

with a taurine (Tau) and reactive blue 4 (RB4) bonded-conducting polymer ((poly (2,2´:5´,5″-

Terthiophene-3´-p-benzoic acid) (pTBA)) layer formed on AuNPs doped-glassy carbon[51]. he

modified electrode demonstrated excellent performance for the detection of NIC and Tyr in the

concentration ranges of 0.02–2.0 and 2.0–300.0 μM and 0.02–5.0 and 5.0–300.0 μM, respectively,

with the detection limit (k = 3) of 0.93 ± 0.08 and 0.88 ± 0.06 nM. The reliability of sensor was

evaluated by the simultaneous detection of Nicotine and Tyr in urine and whole blood samples.

21
Alemnew Geto et al[52] Determined Nicotine at Poly (C10H9NO4S)-Modified Glassy Carbon

Electrode[52]. They obtained an oxidation signal at lower potential with higher current for

Nicotine at the polymer-modified electrode compared to bare glassy carbon electrode suggesting

the electro catalytic effect of the polymer film. Under optimum conditions, square wave

voltammetry of Nicotine showed oxidation at +884 mV (vs. SCE) in phosphate buffer solution pH

7.5. The calibration curve linear over the range 1.0 to 200.0 µM (R2=0.9987) concentration of

Nicotine with a detection limit (S/N=3) of 8.66×10−7 mol. L−1. Application of the proposed

of
method gave acceptable recovery results of 90.7 % to 107.2 %.

ro
Yanqiu Jing et al[136] In this work, gold nanoparticles were biosynthesized through Plectranthus

-p
amboinicus leaf extricate as the decreasing operator. A arrangement of methods were utilized for
re
test examination. The biosynthesized gold nanoparticles (bAuNPs) are a uniform estimate with a
lP

circular shape. The FTIR examination uncovers the nearness of numerous oxygen-containing
na

useful bunches on the bAuNP surface. The cyclic voltammetry and electrochemical impedance

spectroscopic characterizations uncover that whereas the bAuNPs have a somewhat lower
ur

conductivity than chemically synthesized AuNPs (cAuNPs). Be that as it may, the bAuNPs have
Jo

a predominant electrocatalytic execution toward nicotine decrease. After optimization, the

bAuNP-modified SPE might identify nicotine directly from 10 to 2,000 μM with a moo discovery

constrain of 2.33 μM. In expansion, the bAuNPs/SPE have been effectively utilized for nicotine-

containing-product examination. The electrochemical properties of the bAuNPs were compared

with chemically synthesized AuNPs (cAuNPs) by cyclic voltammetry employing a

[Fe(CN)6]3−/4− test. As appeared in Figure 7A, the uncovered SPE has well-defined redox crests

at 0.32 and 0.11 V, whereas both the cAuNPs/SPE and the bAuNPs/SPE show littler peak-peak

partition. Particularly, the cAuNPs/SPE has redox crests at 0.26 and 0.18 V, whereas the

22
bAuNPs/SPE has redox crests at 0.25 and 0.18 V. The comes about demonstrate that alteration by

either of the synthesized AuNPs altogether upgrades the electroconductivity of the SPE. It can be

watched that the bAuNPs/SPE features a slight lower oxidation top reaction compared with that

of the cAuNPs/SPE, recommending that AuNPs biosynthesized utilizing Plectranthus amboinicus

leaf extricate as the decreasing specialist might be of a competitive quality when compared to

common chemically synthesized AuNPs. Electrochemical impedance spectroscopy (EIS) was

utilized for encourage examination. As appeared in Figure 7B, the bare SPE appears a bigger

of
capacitive circle than both of the AuNP adjusted SPEs. As appeared within the inset of the Figure

ro
7B, the cAuNPs/SPE shows a somewhat littler capacitive circle than that of the bAuNPs/SPE,

-p
recommending that the cAuNPs/SPE features a predominant electroconductivity. This perception
re
is in great assention with the comes about derived from CV characterization.
lP
na
ur
Jo

Figure7. A) Cyclic voltammograms and (B) EIS curves of SPE, bAuNPs/SPE and cAuNPs/SPE

toward 5 mM [Fe(CN)6]3−/4− containing 0.1 M KCl [136].

Table 3 shows the comparison of the performance of the proposed electrochemical nicotine sensor

with performances in previous reports. As shown in the table, the bAuNPs/SPE exhibits a wider

23
 electrochemical sensing performance compared with other reported performances, which is

favorable for nicotine analysis in tobacco products.

Table 3. Electrochemical nicotine sensor performance comparison.

Electrode Linear detection range Detection limit References

Nitrogen-doped graphene/GCE 0–200 µM 0.27 µM [136]

PoPD/GCE 0.000183–1.01 µM 55.00 pM [137]

Boron-doped diamond electrode 0.5–200 µM 0.30 µM [138]

of
RGO/DPA/PGE 131–1,900 µM 7.60 µM [139]

ro
-p
Illustrations of electrochemical sensor that have been detailed for nicotine discovery incorporate a
re
think about by Lee and Woi [140], who created a CuHCF-PPy nanocomposites on rGO by
lP

coordinate self-assembly for the amperometry detecting of nicotine at tall concentration extend
na

within the direct run of 0.03–5 mM. The sensor gotten a affectability of 0.21 mA cm−2 mM−1 and

was utilized in genuine tests of e-cigarette [140]. Karthika et al., detailed electrochemical detecting
ur

of nicotine utilizing CuWO4 brightened diminished graphene oxide immobilized on GCE within
Jo

the concentration extend from 0.1 μM to 0.9 μM and the sensor recorded a discovery restrain of

0.035 μM [140]. Kowalcze and Jakubowska detailed the voltametric detection of nicotine in

electronic cigarette fluids employing a boron-doped diamond electrode [140]. The sensor

accomplished a discovery constrain of 0.01 mg/L within the concentration extend of 0.03–0.40

mg/L. In spite of the fact that different electrochemical sensors have been created for the discovery

of nicotine, challenges such as tall oxidation or lessening potential of nicotine and moo

affectability requires proceeded investigate of other stages to overcome these misfortunes. One

conceivable course to creating and making strides electrochemical sensors for nicotine (and other

24
analytes in common), is the utilize of materials for the alteration of the anode. A horde of materials

has been connected as modifiers for electrocatalysis, top upgrade and concurrent assurance of more

than one analyte [141-143].

Liling Lu et al [144] Cation trade may be a burgeoning strategy for controlled gem blend; be that

as it may, its applications in bioanalysis are still in their earliest stages. In this, we investigated the

change of ZnIn2S4 in properties after the Cation trade response with Copper Particles; moreover,

the inconsistency was utilized to plan a dual-readout discovery framework of photothermal and

of
polarity-switchable photoelectrochemical immunoassays to realize solid discovery of

ro
carcinoembryonic antigen. Within the nearness of carcinoembryonic antigen, the CuO NPs utilized

-p
as dual-signal reaction tests would bond to the microplates and be acidolyses by Hydrogen chloride
re
to discharge Copper Particles, which seem supplant Zinc Particles and Indium Particles by means
lP

of the Cation trade response. After the Cation trade response is completed, the photocurrent would
na

switch from a frail anodic photocurrent to a cathode one by employing a 635 nm laser as a flag
ur

intensifier, whereas the photothermal flag would be enhanced with 808 nm laser brightening. On
Jo

the premise of the polarity-switchable PEC procedure, CEA can be precisely identified from 0.1

to 50 ng mL–1 with a restrain of discovery (LOD) of 48 pg mL–1 (S/N = 3). In addition, the

photothermal test for CEA discovery has a straight extend from 0.5 to 100 ng mL–1 with a LOD

of 0.21 ng mL–1. In addition, the designed detecting stage as it were depending on gadgets with

compactness that are allowed for point-of-care location.

Past amassing prove recommends that human epidermal development calculate receptor 2 (HER2)

is found overexpressed in 15–20 % of breast cancers, which is clinically critical within the early

location of strong tumors, such as gastric, colorectal, and lung adenocarcinomas [154-157]. Of

specific significance, HER2 has been considered a commonplace biomarker within the early

25
determination of breast and lung adenocarcinoma, which is primarily since distorted levels of

HER2 actuate HER2-positive breast cancer subtypes [158-162]. For that matter, a touchy

conclusion of HER2 is imperative for the prognosis of breast cancer patients and for direction

within the determination of chemotherapy and endocrine treatment regimens [163-165]. In later a

long time, an arrangement of explanatory strategies based on diverse flag transduction

methodologies have been created to distinguish biomolecules based on distinctive flag

transduction methodologies, such as electroanalytical, photoelectrochemical, fluorescent,

of
piezoresistive, colorimetric, etc [166-169]. Among them, electroanalytical strategy is one of them

ro
and is broadly utilized within the observing of maladies, natural examination, testing of

-p
nourishment security, and other businesses due to its points of interest of tall affectability, moo
re
constrain of location (LOD), and wide location extend[170-173]. As of late, nanozymes,
lP

bifunctional proteins with both nanomaterial properties and biocatalytic capacities, have gotten to
na

be a modern inquire about hotspot within the biomedical, vitality, and natural areas. Nanozymes

have numerous alluring points of interest over normal chemicals, such as great solidness, movable
ur

dynamic catalysis, simple mass generation, and higher catalytic movement. Since the disclosure
Jo

of press oxide (Fe3O4) nanoparticles showing inborn peroxidase movement by Yan et al., [174-

176] different nanomaterials with peroxidase-like movement have quickly risen, counting but not

constrained to metal oxides, respectable metal nanoparticles, and metal-organic system materials.

In specific, the amazing catalytic chromogenic substrate properties of nanozymes open up a

modern way for colorimetric reaction-based detecting [175-179]. In spite of the reality that near to

thousands of nanozymes have been arranged based on diverse engineered techniques. In any case,

the restricted catalytic capacity is still not comparable to that of common proteins and hence cannot

be utilized in commercial applications [180-182]. Toward this objective, the development of

26
modern methodologies to manufacture nanozymes with higher catalytic execution is critically

required. Single-atom catalysts are heterogeneous catalysts with unmistakable electrical and

geometric models that join single metal molecules to a strong substrate with a particular

coordination environment. Strategies like heteroatom doping and auxiliary surrenders boost the

catalytic action of SACs. Nitrogen-doped carbon materials (M-N-C) show empowering and

appealing catalytic properties by tying down metal particles to the nitrogen-doped carbon substrate

and utilizing heteroatoms to changing degrees to alter the nearby electronic structure of the

of
nanozyme [183-186]. The by and large action of M-N-C SACs is considered moo due to the moo

ro
level of metal stacking and the huge surface vitality of person metal particle locales, which tend to

-p
total. Agreeing to our most recent investigate report, the synergistic interaction between two
re
particles may give an unused way to make strides the catalytic execution of nanozymes. Also, a
lP

few exploratory discoveries illustrate that changing the morphology of a nanozyme is one of the
na

essential ways to extend its catalytic movement. Deformity designing has effectively improved

catalytic execution, especially within the regions of biosensing and biotherapy [187-188]. In terms
ur

of morphological plan, carving, template-assisted blend, development control, and other strategies
Jo

are more often than not utilized to effectively build the nanozyme imperfections, which have a few

positive impacts on the impact of nanozyme. In this respect, it is critical to create prevalent

dynamic nanozymes with diatomic highlights and opening abandons to make strides the expository

execution of the detecting stage [189-190].

27
6. Methodologies
Electrochemical methods have aroused great interests among researchers because of its quick

response, relatively high sensitivity, and the ability to be miniaturized [53]. In contrast,

electrochemical methods are simple, inexpensive, and re-liable approaches for the detection of

Nicotine [54]. However, they have some limitations, such as slow oxidation/reduction and low

sensitivity [55]. Sensitivity is important character of the electrochemical biosensor and must be

of
high. Sensitivity is defined as the electrochemical response of the biosensor for a very small change

ro
in the analyte concentration, pH, temperature, and so on [31]. Selectivity is the ability of a bio-

-p
receptor to detect a specific analyte in a sample containing other admixtures and contaminants. To
re
construct a biosensor, selectivity is the main consideration when choosing bio receptors [56]. The
lP

response should be accurate, precise, reproducible and linear over the concentration range of
na

interest, without dilution or concentration. It should also be free from electrical or other transducer
ur

induced noise [57]. The detection of limit (LOD) for the electrochemical biosensor is lowest
Jo

concentrations of the analyte. Adding to the spectrum of innovative approaches, Kamalasekaran,

Magesh et al [14] reported the development of an electrochemical sensor using an iron (III)

phthalocyanine/gold nanoparticles/graphene hybrid film. Their work showcases the integration of

multiple materials to create a hybrid film, emphasizing the interdisciplinary nature of research in

electrochemical sensing. The temporal aspect of these studies, spanning from 2005 to 2023, is

encapsulated in Table 4. This comprehensive examination of various parameters, as outlined by

Yanqiu Jing et al [49] and Magesh, Sundramoorthy et al [90], provides a nuanced understanding

of the evolving landscape of electrochemical sensors for Nicotine detection. Notably, the linear

28
range in RGO/DPA/PGE is identified as the highest at 1900-31, demonstrating the continuous

quest for expanding the capabilities of sensors to achieve wider detection ranges.

In essence, the amalgamation of these diverse studies underscores the dynamic and evolving nature

of research in electrochemical sensors for Nicotine detection. From nanocomposites to hybrid

films, these studies collectively contribute to the advancement of sensor technologies, offering

promising avenues for enhanced accuracy, selectivity, and real-world applications in Nicotine

detection.

of
LOD (3σ-value) and constrain of evaluation (LOQ, 10σ-value) were evaluated from the calibration

ro
bend to be 0.59 µM and 1.97 µM NIC, individually. Compared to other electrochemical

-p
approaches that utilize different cathode models with nanomaterials and/or polymers as recorded
re
in Tables 1,4, our proposed unmodified SPCE sensor appears altogether lower limits of location
lP

without any prerequisite for a pre-treatment step. In expansion to the moo LOD, the location extend
na

is broader than most of the sensors appeared in Tables 1,4 and speaks to the primary kind of
ur

electrochemical sensors that identifies NIC in sweat since others as it were measure NIC in
Jo

cigarettes, cigar, pee and spit. X. Li et al, detailed SPCE sensor altered with graphene subordinates,

to be specific nitrogen-doped graphene sheets-SPCE (NGS-SPCE), decreased graphene oxide-

SPCE (RGO-SPCE) and graphene oxide-SPCE (GO-SPCE) of which LOD values were 0.05, 0.08

and 0.27 μM, individually. The LOD esteem of our sensor, 0.6 μM is closer to the one for GO-

SPCE in that ponder and higher than NGS-SPCE and RGO-SPCE due to the reality that graphene

increments the electroactive surface region and any pretreatment on graphene surface such as

graphene doping or oxidation present absconds on graphene structure coming about in changed

electrochemical execution [128]. The repeatability and reproducibility of the sensor are evaluated

through dreary estimations performed at the same cathode or diverse terminals at the same

29
conditions. For the repeatability examination, we have measured the flag of 6 µM NIC at the same

SPCE for five times and compared the top current values recorded at each cycle to calculate the

relative standard deviation (RSD) between progressive estimations. The sensor appeared a

incredible repeatability with the RSD < ± 5% without critical flag misfortune. Reproducibility test,

on the other hand, was done through measuring the top current of 6 µM NIC at 5 diverse sensors

that appeared comparative reaction with an RSD < ±10%. In expansion to that, as can be seen in

Fig. 8, little mistake bars (n = 3) demonstrating exceptionally steady and repeatable behavior of

of
the sensor over a tried concentration run. The anode solidness was tried after 1- and 2-weeks

ro
capacity at room temperature and the current reactions were steady with as it were ± 5% and ±

-p
10% (n = 5) diminish individually, showing 2-weeks rack life. Subsequently, these comes about
re
show that this sensor can be helpfully connected for the touchy and exact assurance of NIC beneath
lP

the chosen test conditions appearing a great repeatability and reproducibility.

na
ur
Jo

Fig. 8. Ip as a function of NIC concentration including the error bars [128].

30
 Table 4. Comparison Linear range, LOD, PH, Scan rate, Modified electrode system and Buffer or

Substrate type.

Result and LINEAR Detection Limit BUFFER PH SCAN ELECTROCHEMICAL SUBSTRATE MODIFIED
Reference RANGE(µM) LOD (µM) RATE METHODE ELECTODE
(mV/S)

[71] 5-500 0.50 and 1.66 0.1 M BR 8 50 CV (S)–NIC from boron-doped

mg/ L (Britton-
Robinson) Aldrich and diamond electrode
Buffer cigarette (BDDE)

of
tobacco

ro
[72] 1-25 0.5 5 mM dopamine 7.4 20 CV NIC Merck Au-E PDA on Gold

-p
in 0.1M CAP Electrode
Phosphate
re
Buffer Solution
lP

[73] Up to100 1.2 nM /L 0.1M Phosphate 8 100 ECL analysis NIC in ITOE-TBPR
Buffer Solution CV Cigarettes
na

(S/N = 3)
ur

[74] 10-1000 2 0.1M Phosphate 7 100 CV NIC in Oral Metallic free

Buffer Solution SWV Fluid (saliva) carbon nanotube
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cluster modified
screen printed
electrodes
[75] linear range was 1.5 (based on Britton– 8 10-500 CV L-NIC MWCNT-BPPG
not fully 3σ) Robinson (Aldrich,
determined, but Buffer, adjusted 99%)
exceeds a with KOH
concentration of
1 mM
(with R2 > 0.98)

[76] 5–200 1.42 (according 0.1 M Phosphate 8 50 Amp (−)-NIC GC- (MWCNT)–
to 3σ criterion) Buffer Solution CV alumina-coated
silica
(ACS)

31
[77] 4.9 –500 4.9 0.1M Phosphate 7.4 50 CV -(-NIC) Fluka ITOE-
Buffer Solution Amp TiO2/
+0.1 M KCl PEDOT

7.6–107.5 2.0 Aqueous Buffer 7.0 50 CV different Pencil Graphite

[78] or (0.33 mg/L) and Phosphate brands of Electrode
Buffer Solutions commercial
cigarettes

31- 220 and 9.3 (at S/N = 3) 0.1 M Na2C2O4 4.5 10-250 CV NIC in GC- MWCNT
[79] 220 1,900 DPV Tobacco
Samples

of
1.0–200 866 nM 0.1 M Phosphate 7.5 100 CV Cigarette p-(AHNSA/GCE)
[52] Buffer Solution DPV

ro
-p
[80] 0.8 μM to 800 0.0036 Britton– 2.0– 50 CV NIC standard SNMCPE- CP)-Ag
μM Robinson (B–R) 8.0 LSV samples
re
1.83×10−10 to 55 pM 0.5 mM 7 100 CV NIC standard GCE-BSA /PoPD
lP
3−/4−
[53] 1.01×10−3 M 𝐹𝑒(𝐶𝑁)6 and DPV sample
0.5 M KNO3 (Wuhan,
solution China)
na

10–50 12.4 ± 0.2 0.1 M Phosphate 7.4 200 SWV L-NIC GC- nano-carbon
ur

[81] Buffer Solution black

2–10 CV
Jo

5.0 ± 0.3 GC- MWCNT

2–10

2.0 ± 0.3 Nano-Carbon

1-200 0.7 0.1 M Phosphate 7 10-500 CV Cigarette Activated Glassy

[82] Buffer Solution SWV Carbon

[83] 50– 3.2 µM Britton Robinson 11 10- CV Refilling Unmodified

1000 µM Buffer 300 SWV Liquids for Carbon Paste
Electronic Electrode
Phosphate Cigarettes
50–500 µM 6.1 µM Buffer Solution 7.5

[84] 1-90 1 Phosphate 7.0 80 CV NIC NPs-

Buffer Solution Merck Cu/MWNTs/GCE
And Company

100-1000

32
[45] 2- 5 and from 5- 0.1 0.1 M Phosphate 7.0 200 CV NIC standard Carboxylate
60 Buffer Solution China Graphene(CG)-
Tobacco modified Glassy
Hunan Carbon
Industrial Electrode(GCE)and
Artially Electro
Reduced CG
(ERCG)
2- 600 0.52 0.1M Phosphate 5 50 DPV NIC Standard MWCNT-G/GCE
[85] Buffer Solution from Henan
CV
4

0.05- 500 0.015 (S/N = 3) Aqueous Buffer 8.5 50 CV Tobacco PDA-RGO/Au

[86] Solution Products

of
ro
31-1900 7.6 𝑁𝑎2 𝐶2 𝑂4 (0.1 M) 4.5 50 CV NIC standard RGO/DPA/PGE
[49] sample (98%

-p
purity)
[87] 0.1-0.9 0.035 0.1 M Phosphate 7.0 50 CV NIC Gc- CuWO4/rGO-
re
Buffer Solution Amp Sigma- nafion (Nf)
Aldrich
lP

[88] 20-600 1.15 Potassium 8 200 CV

phosphate
[59] 50-6000 50-4000 _ 7 50 CV GCE
na

[89] 0.5-27 0.017 Phosphate 7.4 50 AMP GCE

[88] 20-600 7.6 BR 2 200 CV/CA/DPV/EIS
ur
Jo

8. Challenges and Criticisms

The discourse underscores the pivotal role of various electrochemical sensors in Nicotine

detection, with researchers exploring innovative modifications and materials to enhance sensor

efficacy. Of notable significance is the introduction of a novel carbon paste sensor by [58],

featuring an Au/chitosan nanocomposite for voltametric Nicotine detection. This approach holds

promise for more precise and efficient Nicotine detection, impacting areas like smoking cessation

programs and public health initiatives. Magesh and collaborators demonstrated a unique strategy

with a Pd-hydroxide modified MXene-doped composite electrode, specifically designed for

selectively detecting Nicotine in human sweat. This application suggests potential implications for

33
wearable technology, enabling real-time monitoring of substance levels for individual health

insights [14]. Zaki's work introduced Mn/Cu nanoparticles to modify a carbon paste electrode for

Nicotine detection, showcasing the continual exploration of innovative materials to enhance

sensitivity and selectivity [58].

Alsoghier et al. (2022) [59] developed an electrochemical sensor using graphene oxide nanosheets

conjugated with a glassy carbon electrode, targeting Nicotine detection in tobacco products [59].

This sensor's design illustrates the adaptability of electrochemical sensors in addressing real-world

of
challenges, such as monitoring Nicotine content in commercially available products. The diverse

ro
approaches presented contribute to the evolving landscape of electrochemical sensing, offering

-p
potential applications in health monitoring and product analysis.
re
9. Conclusion and Future Research
lP
na

After a meticulous review of more than 200 recent articles centered on Nicotine, we've pinpointed

critical focal points that demand meticulous exploration in future research endeavors. These focal
ur

points encompass a deeper understanding of Nicotine intricate metabolic pathways, an exploration

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of potential long-term health ramifications associated with persistent exposure, the formulation of

personalized interventions tailored to individual genetic, environmental, and behavioral factors for

Nicotine addiction, a comprehensive assessment of the environmental repercussions linked to

Nicotine contamination, the seamless integration of cutting-edge technologies such as artificial

intelligence and advanced imaging techniques into Nicotine research, effective strategies for

monitoring Nicotine exposure in vulnerable populations, the exploration of innovative

replacement therapies enhancing efficacy and minimizing potential side effects in smoking

cessation initiatives, an examination of the influence of social and cultural factors on Nicotine

usage patterns, an investigation into the intricate relationship between Nicotine consumption and

34
mental health, and a careful consideration of ethical dimensions in Nicotine research, especially in

the context of human trials and intervention development. These focal points collectively represent

pivotal avenues where future research initiatives can substantially contribute to advancing our

comprehension of Nicotine and its impacts, thereby informing strategies for heightened public

health outcomes.

In summary, the convergence of advanced technologies with Nicotine sensors and biosensors

offers promising avenues for improving daily life. By exploring innovative methodologies, these

of
sensors can contribute to accurate and rapid Nicotine detection, personalized interventions, and

ro
enhanced monitoring strategies. This integrated approach, while focusing on individual well-

-p
being, has the potential to positively influence societal health without explicitly highlighting the
re
involvement of artificial intelligence. The emphasis remains on responsible and ethical
lP

deployment, ensuring a safer and more fulfilling communal life. In this way, the seamless
na

integration of cutting-edge technologies with Nicotine sensors opens doors to a brighter future,
ur

where advancements contribute to informed decisions and overall positive impacts on our daily
Jo

existence.

Data availability

All data generated or analyzed during this study are included in this published article

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.

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 Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be
considered as potential competing interests:

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