Talanta Open 9 (2024) 100276

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Talanta Open
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Recent update on biomimetic sensor technology for cancer diagnosis

Priyanku Pradip Das a, Rupak Nagraik b, Avinash Sharma b, Tarun Kumar Upadhyay c,
H. Lalhlenmawia d, Deepak Balram e, Kuang-Yow Lian e, **, Jay Singh f, Deepak Kumar a, *
a
Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh 173229, India
b
School of Biotechnology, Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh 173229, India
c
Department of Life Sciences, Parul Institute of Applied Sciences & Research and Development Cell, Parul University, Vadodara, Gujarat 391760, India
d
Department of Pharmacy, Regional Institute of Paramedical and Nursing Sciences, Zemabawk, Aizawl, Mizoram 796017, India
e
Department of Electrical Engineering, National Taipei University of Technology, Taipei 106, Taiwan, ROC
f
Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India

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

Keywords: Biomimetic sensors are devices that replicate biological receptors and enzymes with extraordinary accuracy and
Biomimetic sensitivity by taking their cues from nature’s effective mechanisms. They enable quick diagnosis and better
Sensor treatment options by providing non-invasive detection of cancer-specific biomarkers in physiological fluids. This
Cancer
review addresses numerous optical and electronic biomimetic sensor types and emphasizes the benefits of their
Diagnosis
Aptamers
usage in cancer diagnostics. Some of the recognition components used in biomimetic sensors are aptamers,
Artificial intelligence molecularly imprinted polymers (MIPs), and immunomimetic sensors. The widespread use of biomimetic sensors
for cancer diagnostics has promise despite obstacles like specificity and cost-effectiveness. The use of wearable
technology and artificial intelligence improves individualized cancer management even further. The overall
objective of this review is to comprehensively explore the field of biomimetics sensors in the context of cancer
diagnostics, highlighting their various types and recognition components and to emphasize on the significant
benefits of biomimetics sensors, such as their accuracy and sensitivity, in enabling non-invasive detection of
cancer-specific biomarkers. Overall, biomimetic sensors are a revolutionary development that advances our
understanding of early cancer detection, improved patient outcomes, and enhanced healthcare.

1. Introduction [4]. Aerobic glycolysis, an altered metabolic phenomenon also known as

the “Warburg effect” is often displayed by cancer cells [5].
The mystery of how cancer develops is not mysterious anymore as The recruitment of pre-existing blood vessels in the formation of new
various studies since the last two decades have spearheaded the research blood vessels that occurs in both normal cells and tumour cells is termed
on how cancer develops right to the molecular level. The cells of a as angiogenesis [6]. Upregulation of VEGF, fibroblast growth factor
normal healthy body live in a complex, interconnected relationship, (FGF), platelet-derived growth factor (PDGF), and angiopoietins, and
regulating one another’s proliferation. This communication between downregulation of antiangiogenic factors, e.g., angiostatin, endostatin,
cells maintains the tissue size and architecture according to the body’s and thrombospondin, causes the occurrence of neoplastic vasculariza­
needs. This communication is severed by cancerous cells as they become tion [7]. Stimulation of VEGF expression is influenced by tumor
incompetent to follow the rules of the cells in the vicinity. They become microenvironment which include factors, like hormones (e.g., proges­
more dangerous when they start to spread this uncontrolled prolifera­ terone, estrogen), hypoxia, growth factors (e.g., endothelial growth
tion agenda to the neighbour cells thus forming masses in nearby and factor, transforming growth factor-β, FGF, PDGF, insulin-like growth
distant tissues [1–3]. Cancer can arise from a plethora of reasons and factor-1) and cytokines (e.g., interlukin-1 and interlukin-6) [8]. The
combinations like genetics, environment and lifestyle. Carcinogens (e.g., extracellular matrix, stromal cells, such as fibroblasts, adipocytes, neu­
tobacco, radiation), hereditary reasons (e.g.., BRCA mutations for breast ral and neuroendocrine cells, endothelial cells, and pericytes, as well as
and ovarian cancers) and viral infections (e.g., HPV for cervical cancer) other cell types, make up the complex network known as the tumor

* Corresponding author.
** Co-corresponding author.
E-mail addresses: [email protected] (K.-Y. Lian), [email protected] (D. Kumar).

https://doi.org/10.1016/j.talo.2023.100276
Received 28 August 2023; Received in revised form 7 November 2023; Accepted 5 December 2023
Available online 7 December 2023
2666-8319/© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
P.P. Das et al. Talanta Open 9 (2024) 100276

microenvironment, which controls the progression of cancer cells from 1010 M− 1 in a 10 mM phosphate buffer. Remarkably, this value
invasion to intravasation and metastasis. This is a dynamic area, because remained largely consistent even when the measurements were per­
both stromal and epithelial processes are reversible at the interface formed in the presence of 1 % (Ka 1.5 × 1010 M− 1) and 10 % (Ka 1.4 ×
between the stroma and the inflammation [9]. Studies done to under­ 1010 M− 1) human serum. This shows that the presence of human serum
stand the molecular pathogenesis of cancer has aided in the develop­ did not significantly affect the MIP’s ability to bind to AFP. Furthermore,
ment of vaccines and drugs that neutralize VEGF activity. Wright et al., the researchers tested the selectivity of their MIP by assessing its re­
demonstrated this by combining Bevacizumab, which is a recombinant sponses to other proteins like human serum albumin and
humanized monoclonal antibody of the IgG1 isotype that binds to all prostate-specific antigen. These tests revealed that the MIP’s response to
forms of VEGF inhibiting endothelial cell proliferation with 5-fluoro­ these proteins was minimal, highlighting its excellent selectivity for AFP
uracil which resulted in a treatment which showed convincing anti­ [21,22]. Biomimetic sensors have found applications not only in the
tumor activity in 67 % of test patients [10]. field of robotics and artificial intelligence but also in wearables, as
Due to such complex situations, it is of paramount importance that evidenced by Shahinpoor’s research. Shahinpoor showcased the utili­
cancer should be diagnosed as early as possible. Early detection provides zation of ionic polymeric-conductor composites (IPCCs) as biomimetic
improved and wide range of treatment options. These treatments have a sensors, enabling their use in robotic actuators and artificial muscles
higher rate of success at early stages of cancer since at the initial stages [23]. Currently, few wearables and portable cancer detectors are already
cancer is confined to a localized area [11]. Early detection also related to being used such as iTBra which uses a patented Cyrcadia Health Circa­
survivability rates as detection of cancer at its early stages ensures that it dian Biometric RecorderTM system for sensing circadian temperature
can be prevented from spreading further into different tissues and lymph changes with breast tissues for detection of breast cancer and this system
nodes hence, improving long-term survival [12]. Due to these early in­ can also be incorporated with smartphones for aletrs about changes
terventions, less invasive and less aggressive treatments can be per­ detected [24]. Similarly, another device called Violet® Plus which can
formed thus reducing the burden of costly treatments and furthermore, just be clipped on to any clothing, uses a microprocessor to detect the
improving the quality of life since, aggressive treatment options tend to amount of UV rays falling on the skin to alert the user through mobile
leave considerable side-effects [13,14]. Furthermore, early detection based app about the excess UV rays to protect them from overexposure
has the potential to permanently rid a patient of cancer which is even and developing skin cancer [25]. Hence, biomimetics have a very
more so beneficial for cancers such as skin cancer, where complete promising future in medical and other fields.
remission can be achieved through early surgical procedure [15]. Bio­
mimetics is the branch of studying how a biologically natural substance 2.2. Biological inspiration: Mimicking nature’s sensing mechanisms
or material function and how its biological mechanisms and process
work in order to synthesis similar products by artificial mechanism In the wild animals are subjected heavily by the “survival of the
which mimic the natural ones making them a valuable tool for sensor fittest” law. Hence, animals have evolved and developed such sophisti­
technology to detect specific molecules and replicating natural stimuli cated sensing organs to respond to various stimuli and to detect even the
system of a living organism and thus making then a tremendous leap for minute change in their surrounding environment to survive another day.
medical applications such as cancer diagnosis [16,17]. Such sensing ability has been studies rigorously by researcher to
In this review, we provide a comprehensive introduction to cancer implement these abilities into biomimetics sensors and help humankind.
diagnosis, emphasizing the importance of early detection. It highlights
the need for innovative technologies, such as biomimetic sensors, to 2.2.1. Echolocation-inspired sensors
address the challenges in cancer detection and management. Animals like bats and dolphins are known to manoeuvre around their
surroundings by using acoustic means of navigation. Using this intricate
2. Biomimetic sensor technology: Concepts and principle system many SONAR systems are designed for underwater navigation
[49,50]. One such demonstration of bio-inspired sonar is in advanced
2.1. Overview of biomimetic sensors sonar systems involving moving sonar capable of decoding the acous­
tical glints [49,51]. This was done to avoid collision by fully interpreting
Biomimetic sensor technology is a futuristic approach that derives the environment using a device to localize and classify random objects in
inspiration from nature itself. Medical diagnostics, environment moni­ the surrounding [49,52].
toring and robotics are some of the fields that have benefited manyfold
from this mimicry of the already efficient mechanisms of living organ­ 2.2.2. Insect olfaction inspired sensors
isms [18]. Mimicking the extremely efficient biological receptors in In nature many insects such as honeybees, moths and butterflies,
organisms are what biomimetics are designed to do. Biomimetics are have a highly intricate and sensitive olfactory system allowing them to
designed to function in such a way that they perform the tasks such as of detect pheromones release by potential mates and from certain flowers
enzymes with very high precision and efficiency just as much as real over long distances. Studies have been performed to mimic these ol­
enzymes would do so [19]. Biomimetic sensors have been a tremendous factory receptors to design artificial “electronic noses” capable of
advantage for early detection of many medical conditions, especially sensing specific odorants with accurate precision [53–55]. A specific
cancer. These sensors can detect biomarkers specific to cancer and olfactory biosensor utilizing odorant-binding proteins (OBPs) was
provide a non-invasive diagnosis method as opposed to traditional created by Lu et al. They immobilized OBPs, specifically Acer-ASP2 from
methods, enabling early treatment options [20]. One such research honeybees, onto interdigitated gold electrodes. This biosensor was
performed by Horikawa et al., the researchers developed a method to employed to detect ligands associated with floral odors and pheromones
create highly sensitive and selective Molecularly Imprinted Polymers through electrochemical impedance sensing. Additionally, docking
(MIPs) for detecting alpha-fetoprotein (AFP), a crucial biomarker for studies were conducted to confirm the effectiveness of this biosensor
liver tumors. They accomplished this by chemically linking two easily [56].
detachable functional molecules to AFP. Afterward, through a multi-step
process known as post-imprinting modification (PIM), they embedded 2.3. Advantages/applications of biomimetic sensors for cancer diagnosis
two other molecules into the AFP-imprinted polymers. These added
molecules served different purposes: one was responsible for binding There are several advantages of biomimetic sensors for cancer
specifically to AFP, while the other played a role in translating AFP diagnosis. A few will be discussed here.
binding into a change in fluorescence. Using fluorescence microscopy, Biological systems have several biomarkers when cancer develops.
they determined the affinity constant (Ka) for AFP binding to be 1.5 × Even though the body has defence mechanisms in place to counter

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cancerous cells, they however sometimes fail to do so. That is where specific wavelength by photonic bandgap material. The working prin­
biomimetic sensors take over as they can identify these biomarkers, such ciple is that the sensor has receptors on the surface and when bio­
as proteins or nucleic acids, even at low concentrations, hence making molecules bind to them the refractive index near the surface of the
early diagnosis and accurate identification of cancer [57]. sensor changes thus generating an impulse that is measured with very
Traditional cancer detection techniques are very invasive and mostly high sensitivity [69,70]. Photonic crystals are artificially made materials
induce after treatment side-effects. To counter this, biomimetic liquid- with a periodic arrangement of dielectric or metallic nanoscale struc­
based approaches were developed to non-invasively identify these bio­ tures. A protonic bandgap arises due to this periodicity, through which a
markers present in bodily fluids like urine, blood and saliva [58]. range of wavelength cannot propagate through the crystal [71]. When
Biomimetic sensors are very sensitive and has high specificity hence exposed to vaariations in the refractive index of its surrounding, sucha as
making them more reliable over traditional methods [59]. Biomimetic the presence of specific molecules or change in temperature, the pho­
sensors are also able to detect cancer biomarkers in early stages thus tonic bandgap shifts [72] and these shifts are detected by the sensor
making traditional treatment more effective [60]. Biomimetics sensors using various measurement techniques, such as monitoring the reflec­
can also be integrated with nanotechnology to improve their sensitivity tance or transmittance of light through the photonic crystal. This shift in
and selectivity which lacks in traditional treatments [61]. Li et al., bandgap is directly proporational to the concentration of the target
provided an illustrative example of biomimetic nanoparticles by analyte, making it a sensitive and versatile sensing equipment [73].
creating an innovative vaccine. They encased a magnetic nanocluster There are many materials used to fabricate photonic crystal sensors
(MNC) with a tumor cell membrane modified with azide. Prior to this, which selection depends on the specific application and desired sensor
the nanocluster’s surface had been coated with an immune-boosting properties. Some materials used are Silicon [74], Silicon Nitride (Si3N4)
agent known as toll-like receptor agonist CpG oligodeoxynucleotide [75], Gallium Arsenide [76], Chalcogenic glasses [77]. In a study by
(CpG-ODN), and the cancer cell membrane was adorned with Shao et al., researchers developed a highly sensitive photonic crystal
anti-CD205. This engineered design granted the nano-vaccine the biosensor for the detection of cancer-specific exosomes. The biosensor
unique ability to be specifically recognized by CD8+ cells. Its efficacy showed excellent specificity in discriminating cancer-derived exosomes
was clearly demonstrated in both preventive and therapeutic contexts in from healthy exosomes, offering a potential tool for early cancer diag­
five different cancer models [62]. Another such biomimetic nanotech nosis [78].
was demonstrated by Zhang et. al., the researchers successfully created
versatile artificial antigen-presenting cells (aAPCs) with multiple func­ 3.1.2. Surface plasmon resonance (SPR) sensors
tions. They achieved this by designing a biomimetic magnetosome, As the name itself states, SPR works on the principle of surface
which entailed encasing magnetic nanoclusters with modified whole plasmon resonance as shown in Fig. 1. Plasmonic resonance changes
blood cell membrane (WBCM) using azide. They then employed occur when the refractive index near a metal surface changes, indicating
copper-free click chemistry to attach T-cells to these nano aAPCs. These the presence of bound target molecules [79,80]. Liu et al., introduced a
biomimetic aAPCs displayed remarkable capabilities in both expanding noteworthy application of Surface Plasmon Resonance (SPR) in their
and activating cytotoxic T-cells with a specific response to antigens. work. They designed an innovative SPR biosensor that could monitor the
Furthermore, they efficiently guided cytotoxic T-lymphocytes (CTLs) to secretion of proteomic biomarkers from cells. To demonstrate the
tumor locations using magnetic resonance imaging and magnetic con­ concept, they measured the secretion of vascular endothelial growth
trol. In an experimental model involving murine lymphoma, these factor (VEGF) from live SKOV-3 ovarian cancer cells. This demonstra­
T-cells effectively restrained tumor growth, underscoring the consider­ tion was particularly relevant because certain cancer cells exhibit the
able potential of the aAPC platform for T cell-based cancer immuno­ abnormal production of large amounts of VEGF, which contributes to
therapy [63]. their ability to metastasize [81]. Stojanović et al., reported that Surface
Point-of-Care diagnostic devices are currently very popular and Plasmon Resonance Imaging (SPRi) can serve as an effective method for
effective. Portable diagnostic devices not only save a visit to medical identifying apoptosis by measuring the release of cytochrome C. This
centres but also allow real-time analysis and rapid results. This is accomplishment involved the attachment of cytochrome C to an SPR
particularly useful in the case of cancer diagnosis where early inter­ sensor coated with antibodies specifically designed to recognize cyto­
vention can tremendously impact on patient outcomes [64]. One such chrome C. Subsequent experiments involved the use of supernatants
research to detect specific DNA sequences of bladder cancer done by from MCF7 breast cancer cells exposed to cell culture medium, both with
Zhang et al., where they modified GC surfaces with CdTe and without substances like paclitaxel, Trastuzumab, or Trastuzumab
QDs-semiconductors that serve to increase the electrode area-for the T-DM1, within the SPRi instrument. Notably, the most substantial SPRi
subsequent immobilisation of a DNA probe, an electrochemical responses were observed on sensor spots that were coated with
biosensor was created. Target DNA sequences were then hybridised in
the following step, and methylene blue was then employed to acquire
electrochemical data using differential pulse voltammetry. The sensor’s
simplicity of use, superior selectivity and sensitivity, quick reaction, and
inexpensive cost make it valuable for achieving successful outcomes in
the medical industry [65,66].

3. Types of biomimetic sensors for cancer diagnosis

3.1. Optical biomimetic sensors

Optical technologies devised by drawing inspiration from natural

organisms and their way of perceiving and interacting with light. Many
organisms, such as butterflies, beetles, house flies, squid and even
humans have exceptional optical prowess [67,68].
Few optical biomimetics include:

3.1.1. Photonic crystal sensors

Based on the concept of selectively trapping and guiding light of Fig. 1. Basic working principle of SPR sensors [40,41].

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anti-cytochrome C antibodies. This observation underscores the signif­

icance of cytochrome C release as a meaningful biomarker for tracking
the progression of apoptosis. Furthermore, when live MCF7 cells were
introduced into the SPRi instrument and exposed to cell culture medium
with or without paclitaxel, robust SPRi responses were observed on
sensor spots coated with antibodies targeting a protein called EpCAM,
either alone or in combination with anti-cytochrome C antibodies. This
finding highlights the capacity to monitor the apoptotic process in
real-time, without the need for conventional fluorescent labels or
staining techniques [82]. In another study, Liu et al., developed a highly
sensitive and compact SPR biosensor to capture exosomes and analyze
the proteins they contain for diagnosing cancer. To ensure its accuracy,
the biosensor’s performance was fine-tuned using glycerol solutions.
This tuning revealed a remarkable detection sensitivity of 9.258 × 103
%/RIU and a resolution of 8.311 × 10− 6 RIU. In the context of lung
cancer as the focus, this compact SPR biosensor impressively identified
Fig. 3. Basic working principle of field-effect transistor (FET) sensors. image
the levels of a specific protein, EGFR, within A549 exosomes, even at
(modified) used courtesy of Huijunan [CC BY-SA 4.0] [43].
incredibly low concentrations of 2 × 1010 exosomes per milliliter. The
results showed a strong signal-to-noise ratio (SNR) of 27 and a coeffi­ 1
cient of variation (CV) of 16.6 %. Importantly, this biosensor’s sensi­ limit of 10 fg ml− PSA for any FET sensor [88].
tivity outperformed the traditional ELISA method, which could only
achieve detection at 4 × 1010 exosomes per milliliter with a CV of 54.3 3.2.2. Impedance-based sensors
% [83]. These sensors measure the impedance, i.e., the opposition that a
material presents to the flow of an alternating current in various mate­
3.1.3. Fluorescence-based sensors rials such as tissues upon target molecule binding to the sensor surface.
Fluorescent labels or quantum dots are used to detect and quantify Changes in impedance indicates the concentration of target molecule
target molecules in fluorescence-based biomimetics (Fig. 2). Detection present [89,90]. Its potential was demonstrated by Soares et al., they
occurs when change in fluorescence intensity occurs when target devised a biosensor that could detect PCA3. The single-stranded DNA
molecule binds to the sensor surface [84]. A study done by Mizutani (ssDNA) probe layer was mounted on a layer-by-layer (LbL) film of
et al., demonstrated a fluorescence resonance energy transfer (FRET) chitosan (CHT) and carbon nanotubes (MWCNT) to create the bio­
biosensor by detecting the activity of BCR-ABL kinase in liver cells. sensors. They exhibit strong PCA3 selectivity, which was shown by
Detection of cancerous and drug-resistant cells, and the evaluation of polarization-modulated infrared reflection absorption spectroscopy
kinase inhibitor efficacy was facilitated by this biosensor [85]. (PM-IRRAS) and impedance studies [91].

4. Biomolecules and biomimetic recognition elements

3.2. Electronic biomimetic sensors
4.1. Aptamers for cancer biomarkers
3.2.1. Field-effect transistor (FET) sensors
Transistors with specific biological recognition element on the gate Biosensors that can bind to specific target molecules with high af­
surface is the working principle of FET sensors (Fig. 3). Label-free finity and are made of short, single-stranded nucleic acid (DBA or RNA),
detection is obtained when target molecule binds to the recognition are known as Aptamers [92–94]. Iterative rounds of selection and
element causing a change in electrical properties of the transistor [86, amplification of aptamers with high binding affinity to the target
87]. One demonstration of FET biosensor was done by Hossain et al., the molecule is how aptamers are selected and this process is called SELEX
researchers demonstrated a highly sensitive tungsten diselenide (WSe2) (systematic Evolution of Ligands by Exponential enrichment) [92,95,96]
field-effect transistor (FET) biosensor for label-free detection of (Fig. 4).
early-stage prostate cancer. A modified FET channel was used by In a study conducted by Shigdar et al., they highlighted that
attaching monoclonal antibodies of prostate specific antigen (anti-PSA), Epithelial cell adhesion molecule (EpCAM) is commonly overexpressed
then treating it with bovine serum albumin, ensuring specific binding in most solid cancers and has been recognized as a marker for cancer
between anti-PSA and PSA with a groundbreaking first ever detection stem cells. To target EpCAM, they utilized a systematic evolution of li­
gands via exponential enrichment (SELEX) approach to extract a 40-base
RNA aptamer from a random oligonucleotide library. This aptamer was
specifically designed to bind to EpCAM, offering potential applications
in cancer research and therapy [97].

4.2. Molecularly imprinted polymers (MIPs)

Molecularly Imprinted Polymers (MIPs) are synthetically made

substances that have recognition sites that are tailor-made into them to
selectively bind to specific target molecules. Templates, which are
monomers polymerized in the presence of target molecule is the process
of creating MIPs knowns as molecular imprinting (Fig. 5). Due to this
polymerization process, specific binding cavities are formed within the
polymer matrix enabling the MIP to rebind the template molecule with
high affinity and selectivity, like how antibodies recognize antigens in
the immune system [98–101]. Parisi and colleagues conducted a study
Fig. 2. Basic working principle of fluorescence-based sensors [42]. in which they introduced a novel Magnetic Molecularly Imprinted

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Fig. 4. An overview of SELEX process [44,45].

Fig. 5. Schematic representation of MIP preparation [46].

Polymer (MMIPs) designed for the sustained delivery of 9H-carbazole in can be an antigen such as bacteria, viruses, toxins, flower pollens, and
cancer treatment. In vivo experiments done using cell lines, such as HeLa even cancer cells. They play the crucial role of defenders of the body
and MCF-7, revealed not only effective selective recognition and from harmful invaders [103–106].
controlled release properties but also a strong magnetic response, indi­ Antibodies act by recognising and binding to specific antibodies and
cating the MMIPs’ high inhibitory activity against the tested cell lines. this binding is highly selective, as one antibody will recognize and bind
This inhibition led to a significant growth arrest, causing apoptosis, as to only one type of antigen or its closest groups of antigens [107–110].
compared to the control group [102]. Immunomimetic sensors are biosensors that mimic the antibody-
antigen interaction of the body and the property of natural antibodies
of detecting target molecules, known as analytes [111,112]. Natural
4.3. Antibodies and immunomimetic sensors antibodies can be very expensive to isolate, hence, to overcome this
immunomimetic sensors were invented that employ synthetics recog­
The bodies of living organisms produce special proteins, known as nition elements like peptides, aptamers, MIPs and other biomimetics
antibodies or immunoglobulins (Ig), by the immune system when the molecules to replicate the antibody-antigen interaction [113–115]
body is attacked by foreign materials known as antigens. Any substance

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the product molecule that gives a measurable signal in its presence [135,
136] and is working principle given in Fig. 7. A substrate is typically
used on which the recognition element reacts with to produce a desired
molecule which will generate a detectable signal, such as a colour
change, electrochemical signal or fluorescence [132,137,138]. And
lastly, signal transductor, which detects the generated signal and coverts
into a measurable output [139].

Fig. 6. Schematic representation of how a synthetic antibody mimetic binds to

4.6. Plant-based biosensors
immune cells and facilitates the targeting of cancerous cells [47].

Although plant-based biosensors have rarely been used as cancer

(Fig. 6). biomarker detectors, however, they are used to device many other types
In one such study Dan et al., developed a unique graphene sheet of biosensors [140].
sensor platform and functionalized carbon nanospheres (CNSs) labelled Plant-based enzymes offer various benefits, including robust stabil­
with horseradish peroxidase-secondary antibodies (HRP-Ab2) were ity, significant enzymatic activity in natural conditions, durability,
employed to create an electrochemical immunosensor for the sensitive consistent experimental results, ready availability and affordability of
detection of the cancer biomarker AFP. The highly improved sensitivity plant tissues, circumventing the need for enzyme extraction and puri­
for the cancer biomarker was established on a dual signal amplification fication processes, and the presence of cofactors within the same enzyme
method. First, the synthesized CNSs produced a uniform and narrow size tissue; nonetheless, they are limited by reduced specificity and pro­
distribution, allowing for many HRP-Ab2 binding events on each longed response times [140]. Plant based biosensor have given in
nanosphere. Through "sandwich" immunoreactions, the multi- Table 1.
bioconjugates of HRP-Ab2-CNSs were applied to the electrode surface
to increase sensitivity. Second, functionalized graphene sheets utilized
5. Challenges and future prospect
in the biosensor platform increased the surface area to catch lots of
primary antibodies (Ab1), increasing the detection response [116].
Since the previous two decades, a great deal has been learned about
the molecular mechanisms underlying the development of cancer. As a
4.4. DNA-based SEnsors result, cancer diagnosis has advanced significantly. Cells in a healthy
organism maintain a harmonious relationship by communicating with
DNA plays a crucial role in oncology. As of today, it is very well one another to regulate growth and proliferation. Cancer, however,
known that genes and DNA are one of the main causes of cancer upsets this balance by causing unchecked cell growth and the develop­
[117–119]. Tumor cells (CTC) and tumour DNA (ctDNA) freely circulate ment of tumors in surrounding and distant tissues. Since cancer is
the blood stream in the case of methylated DNA mutation [120–124]. To initially restricted to a localized area, early discovery is essential since it
overcome the limitations of ctDNA identifications by PCR methods [120, increases treatment options and survival rates. Biomimetic sensors
125–127], a novel PNA-based biosensor for DNA detection was created provide creative approaches for early cancer detection by taking cues
by integrating the capacity of an anti-5-methylcytosine monoclonal from nature’s effective methods. These sensors exhibit remarkable
antibody (mAb) to identify methylated DNA with the coupling of the specificity, sensitivity, and precision in their imitation of biological re­
plasmonic characteristics of AuNPs and the single-base mismatch ceptors and enzymes. They can non-invasively identify cancer-specific
recognition ability of PNA probes, achieved by linking PNA probes with biomarkers in human fluids, facilitating quick diagnosis and treat­
AuNPs. This biosensor enables the concurrent detection of both ment. There are numerous uses for biomimetic sensors in optical, elec­
tumor-specific mutations in ctDNA and epigenetic modifications (ctDNA trical, and impedance-based sensing, each with special benefits for
methylation) within the PIK3CA gene [120,128]. cancer diagnosis. Prospects for individualized cancer management
include wearable technology, multimodal sensing, and integration with
4.5. Enzyme-based sensors artificial intelligence. Advances in nanotechnology, bioinformatics, and
liquid biopsies provide promise for the wider application of biomimetic
Enzymes are biological catalysts that serves similarly to chemical sensors in cancer diagnostics, ultimately improving patient outcomes
catalysts, i.e., they selectively bind to the reactants and catalyse the and healthcare. Despite limitations in specificity, stability, and cost-
reaction to achieve the final product in a much efficient way and rate effectiveness.
[129–131]. Enzyme-based biosensors try to mimic this system by uti­
lizing recognition elements to detect specific target molecules 6. Conclusion
[132–134].
Enzyme-based sensors have a few key components, these being. A In conclusion, biomimetic sensor technology is like a gift from nature
recognition element (enzyme) that binds to the target molecule or for the fight against cancer. These sensors, which draw their design cues
reactant molecule and catalyses the reaction, and this reaction produces from the effective workings of living things, are non-invasive and
capable of identifying cancer-specific markers in our bodily fluids. They
aid in the early detection of cancer and increase the chances of recovery
by providing better therapeutic options. Scientists are working hard to
improve these sensors’ efficiency and affordability; despite the diffi­
culties they face. Personalized cancer treatment and a healthier future
for all are now a step closer thanks to biomimetic sensors.

Declaration of Competing Interest

The authors declare that they have no known competing financial

interests or personal relationships that could have appeared to influence
Fig. 7. Working principle of enzyme-based biosensors [48]. the work reported in this paper.

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Table 1
Following are some plant-based biosensors invented along the years.
Sl Phytochemical selected Plant part/tissue used Function of the biosensor Refs.
No.

1 Polyphenol oxide-containing Banana pulp Named as Bananatrode, a Clark-type oxygen electrode was utilized to gauge the depletion [26]
tissues (PPO) of oxygen as dopamine underwent conversion into 1,2-benzoquinone.
Banana pulp To measure the reduction of a quinone derivative back to catechol at negative potentials, [27]
as opposed to monitoring oxygen consumption, resulting in a much faster response time of
just a few seconds.
Avocado tissue Catalysing the oxidation of paracetamol into N-acetyl-p-benzoquinone to mitigate the [28]
hepatotoxic effects of paracetamol.
Palm fruit fibres Catalysing the oxidation of epinephrine to form electrochemically reduced epinephrine [29]
quinone.
Potato tissue Detecting atrazine in water samples by exploiting the herbicides’ capability to hinder PPO. [30]
2 Acid phosphatase-containing Potato slices with addition of The enzyme AF aided in the conversion of glucose-6-phosphate into glucose, which was [31,
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3 Oxalate oxidase-containing tissues Spinach tissue To detect the presence of oxalate in urine during kidney lesions. [33]
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