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Current Pharmaceutical Biotechnology, XXXX, XX, 1-16 1
REVIEW ARTICLE
1389-2010/XX $65.00+.00 © XXXX Bentham Science Publishers
Overview of Advancement in Biosensing Technology, Including its
Applications in Healthcare
Sakshi Mishra1 and Rohitas Deshmukh1,*
1Institute of Pharmaceutical Research, GLA University, Mathura- 281406, India
Abstract: Clinical analysis necessitates using rapid and dependable diagnostic methodologies and
approaches. Biomarkers may be an appropriate choice to fulfill this objective, as they are designed
uncomplicated in use, specialized for the desired metabolite, susceptible to ongoing analysis and
providing excellent outcomes, relatively affordable in the budget, and easily accessible. Biosens-
ing devices are increasingly extensively utilized for treatment, and therefore a variety of applica-
tions such as prudence treatment and illness advancement surveillance, environment sensing,
product standard, medicine development, toxicology, and scientific engineering. Biosensors can
be developed using a wide variety of ways. Its combination with high-affinity macromolecules
enables them to monitor a diverse variety of solutes in a specific as well as responsive manner.
Enhanced sensing innovation leads to the detection of infection as well as the monitoring of peo-
ple's reactions after treatment. Sensing tools are essential for a range of low and better implantable
implants. Nanosensors offer a lot of prospects because they are simple, flexible, yet economical to
develop. This article presents a detailed overview of breakthroughs in the subject and demonstra-
tions of the variety of biosensors and the extension of nanoscience and nanotechnology methodol-
ogies that are applicable today.
A R T I C L E H I S T O R Y
Received: March 14, 2022
Revised: March 17, 2022
Accepted: March 31, 2022
DOI:
10.2174/1389201023666220610163343
Keywords: Alzheimer’s disease, biosensors, optical biosensors, cardiovascular disease, electrochemical biosensors,
immunological biosensors, COVID-19.
1. INTRODUCTION
A sensor is an electrochemical cell that, using an optimal
method of a specific biological network as well as an electri-
cal and chemical transmitter, responds to an analyte in a suit-
able sample and translates its concentration as an electronic
signal. These instruments are projected to play a progressive-
ly essential role in the generation of analytical data in all
fields of endeavour, from medical to combat activities [1].
Leland C. Clark Jr., an American biochemist, 1962 intro-
duced the first biosensor that eventually captured scientific
concern enormously [2]. He was also regarded as the “father
of biosensors” for the invention of the Clark electrode, an
oxygen biosensor [3]. Immunosensors are being used in
therapeutic intervention, pharmaceuticals, and biological and
medical management, which has aroused much interest in
this subject. Biosensors have proven beneficial in the
diagnostic system, prophylaxis, rehabilitative process, health
records tracking, and healthcare.
Due to their vast potential, the biosensor devices exert
extensive benefits in fields like medicine and nanotech-
nology and are adopted for endless pharmaceutical industries
*Address correspondence to this author at the Institute of Pharmaceutical
Research, GLA University Mathura - 281406, India; Tel: +91-798736712;
E-mails: rohitas.deshmukh@gla.ac.in and rahi18rahi@gmail.com
and associated fields like metabolic engineering, plant
biology, food industry, veterinary, pollution control, etc. The
major applications Fig. (1) include the screening of disease,
diagnostics of disease, other healthcare monitoring,
therapeutic analysis, etc. [2].
Fig. (1). Applications of the biosensor in healthcare. (A higher reso-
lution / colour version of this figure is available in the electronic
copy of the article).
2 Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX Mishra and Deshmukh
Blood glucose monitoring for diabetes management is the
most prevalent use of biosensors. The development of en-
hanced glucose biosensors has been expedited due to a surge
in demand [4]. 2004 marked the demand and supply of glu-
cose biosensors, as around 85% of the global biosensor mar-
ket [5]. Biomarkers may be used to identify microbes as well
as parasites. Individuals may develop healthier lifestyles by
exercising regularly and using activity monitors. Individuals
working in the healthcare field might also be benefited
from such products. Smart sensors detect substances without
requiring the physical species to collect blood. Individuals
are often obliged to remain in a hospital to monitor their me-
tabolism continually [6].
The mediators are brilliant in anticipating real-time in
vivo measurements and opt to spot drug targets in modest
quantities. Therefore, exposing antibodies in the wake of
carcinoma or inflammatory disorders can only detect and
control the diseases in their early stage [7]. Many efforts
have been made to develop a diminutive model inserted in
vivo. These models can electrically detect the differences in
the biological environments [8, 9]. Optical techniques like
surface plasmon nanoparticles, nanotubes, nanocantilevers,
etc., are used to serve such purposes [10]. The abutting tech-
nique that is set up is quantum dot nanocrystals. As soon as
ultraviolet light hits these artificial nanoparticles, fluores-
cence is emitted and causes selective detection of molecules
through Forster resonance energy transfer [11].
Strategies have now been made to develop implantable
biosensors with the considerable signal strength to transport
them into the body for diagnosis. Quick response, ability to
detect non-polar compounds that are difficult to measure by
other conventional devices, fast and sharp measurement,
increased specificity, low amount of reagent usage for cali-
bration, and the sustainability of these detectors straightly
categorize it a prevalent choice for in vivo screening and
treatment. Biochemical diagnosis and bioelectronics
have become increasingly important due to the challenges of
persistent unhealthy lifestyles. Current biological discoveries
can have a significant impact on traditional diagnostic meth-
ods. Among the most important advantages of diagnostic
analysis, accuracy, individualized medication, and quick
testing are common. All of this allows for a prognosis that
would be considered accurate and reliable, as it is not reliant
on exterior clinical signs or the recipient's treat-
ment understanding [12].
Sophisticated bimolecular-based detectors require re-
search, innovation, and marketing to meet various healthcare
needs. Wearable sensors are comfortably utilized inside the
person and thus are widely employed for numerous
healthcare and routine surveillance systems. It is critical to
enhance this innovation and identify appropriate elements for
connecting sensors and attaching them to surfaces. Im-
munosensors are used in various fields, including DNA, in-
telligent textiles, the automobile industry, and a seemingly
endless list of others. Because of the wide range of uses for
biosensors, it's critical to comprehend the prospective, usage,
and technological advancements. This paper explored replac-
ing the tedious traditional method of laboratory analysis with
advanced, précised nanodevices, along with their applica-
tions in medical diagnostics, which only a few papers illumi-
nated to fill the literature gap [4].
2. WHAT IS A BIOSENSOR?
A biosensor is an analytical device that detects the con-
centration of an analyte like biomolecules or microorganisms
through a physiochemical detector [2, 13, 14]. The primary
characteristics of a biosensor include stability, ultra-
sensitivity 4, specificity 2, reproducibility, response time,
accuracy, reliability, simplicity, etc. It should not be affected
by physical properties like gravity, temperature, or pH, and
the construction should be miniaturized [2].
The term “biosensor” was first coined by Karl Camman
in 1977, and its definition was framed by IUPAC (Interna-
tional Union of Pure and Applied Chemistry) due to some
disagreement with Camman [15]. “A standard definition of
biosensor now is as follows: “A biosensor is a self-contained
integrated device capable of providing specific quantitative
or semi-quantitative analytical information using a biological
recognition element (biochemical receptor), which is re-
tained in direct spatial contact with a transduction element.
Because of their ability to be repeatedly calibrated, we rec-
ommend that a biosensor be clearly distinguished from a
bioanalytical system, which requires additional processing
steps, such as reagent addition. A device that is disposable
after one measurement, i.e., single-use, and unable to moni-
tor the analyte concentration continuously or after rapid and
reproducible regeneration should be designated as a single-
use biosensor”.
Since biosensors are employed in both engineering and
biological fields, the transducer, display, material, and im-
mobilization device alterations have gained huge scholarly
attention in the past few years [2]. The materials usage of
biosensors is broadly divided into the biocatalytic group,
including enzymes, cells, deoxyribonucleic acid (DNA),
aptamers; bio affinity group, including antibodies and nucle-
ic acids; transducer components such as nanoparticles, semi-
conducting material; an electronic unit that comprises a pro-
cessor, amplifier as well as signal display and microbe based
containing microorganisms [2]. The analyte is the element
that is to be detected. For example, in a glucose biosensor,
glucose is the analyte [13]. Bioreceptor is the element whose
main function is to mark the analyte substance. In biosen-
sors, a biorecognition device is coupled with a transducer.
The biorecognition compound imparts analyte molecule
specificity in a biosensor [16]. The transducer is a compo-
nent that converts the form of energy. In biosensors, it acts as
a medium of conversion of bio-recognition function into a
quantifiable signal. A segment of biosensor electronics con-
figures the yielded signals to detect correlative signals and
display them digitally through an installed display sys-
tem. The display unit in the biosensor has two primary parts,
software and hardware. It illustrates lines in the binary,
graphical, figure, or tabular form that the user documents as
per their need. They also have printers attached directly to
generate the result [13]. A schematic of the classical biosen-
sor is shown in Fig. (2). and step involved in the signal pro-
cessing of any biosensor is given in Fig. (3).
CMOS- based biosensor unit or microsensor system is a
combination of electronics and transducers. This has been
Overview of Advancement in Biosensing Technology Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX 3
addressed to a vast extent in applications like detection of the
concentration of biological analyte, fermentation process
biosensing technology for food safety, medical diagnostics,
biodefence/biosensing, metabolic engineering, agriculture,
diseases such as diabetes, cardiovascular risk, cancer, point-
ers of diseases in biofluids sweat, saliva, urine, and blood [2,
13-17].
3. TYPES OF BIOSENSORS
3.1. Electrochemical Biosensors
This biosensor category accounts for a very long term to
extend a broad spectrum of utilization in different fields.
Several studies elucidated that such devices are well-known
forums for developing and progressing emerging sensing
devices [18]. It comprises semi-conductors and screen-
printed electrodes, as demonstrated in Fig. (4) [19, 20].
Moreover, findings led to a more profound understanding of
alteration with metal nanoparticles for sensing even micro-
scopic biomolecules [18]. The electro analysis includes de-
tection of major or minor changes like shape, size, polarity,
proportion, complexes due to antigen-antibody interactions,
dielectric constant, dissipation factors, etc. They are broadly
categorized into four classes:
• A potentiometric sensor, in which the alteration in
electrical potential is regulated by FET (field-effect
transistor), is ultra-sensitive for particular DNA (de-
oxyribonucleic acid), nucleotide as well as ion con-
centration [19]. In simple words, potentiometric sen-
sors deliver data regarding ion exertion in specific
electrochemical reactions [21].
• Amperometric sensor facilitates adequate efficacy for
fast multipoint analysis. It maintains a repeated meas-
urement of the current produced due to electro-active
species [21]. It also tracks the diffusion of specific bi-
omolecules. The main component of the amperomet-
ric sensor array is the microelectrode, which inter-
prets steady-state current and is simple and easy to
understand. Moreover, it is a time-saving technique
[19-22].
• The cyclic voltammetry sensor is the most widely
used biosensor [19-22]. It is an analytical technique
used to obtain data of a specific analyte, employing
Fig. (2). The figure of a simple biosensor with components. (A higher resolution / colour version of this figure is available in the electronic
copy of the article).
Fig. (3). A pictorial description of the different steps involved in the signal processing of any biosensor. (A higher resolution / colour version
of this figure is available in the electronic copy of the article).
4 Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX Mishra and Deshmukh
fluctuating potential and mapping the proceeding cur-
rent. Hence it resembles amperometric devices in
such ways [21-23].
• Impedimetric transducers sensor- They include actu-
alizing electric charge-based capacitance measure-
ment to comprehend a label frank thoroughly inter-
spersed capacitance biosensor [19-22].
These biosensor devices have been widely adopted to
document various biological analytes, including ion
channels, transporter proteins, biomolecules by the tumor
cell, receptors, enzymes, and nucleic acid [24, 25].
Fig. (4). Electrochemical biosensor. (A higher resolution / colour
version of this figure is available in the electronic copy of the arti-
cle).
3.2. Piezoelectric Biosensors
A typical piezoelectric biosensor device is a quartz crys-
tal biosensor commonly used as a diagnostic tool for manag-
ing infectious diseases with faster action, enhanced sensitivi-
ty, comparatively low cost and fewer time requirements.
They have been adopted widely due to their label-free strate-
gies [19, 26, 27]. It is also known as magnetic biosensors
since it identifies alterations in magnetically induced activi-
ty.
The primary principle of piezoelectric devices is the
tracking of affinity interaction. The piezoelectric material is
a sensor division based on the fundamentals of distortion
oscillations impacted by a mass constrained on the piezoe-
lectric crystal exterior part, as shown in Fig. (5) [28]. The
classic piezoelectric crystals are gallium orthophosphate,
gallium nitride, zinc oxide, topaz, mineral berlinite, lead ti-
tanate, potassium sodium tartrate, quartz, polylactide, poly-
vinylidene difluoride [28-35]. These materials are regarded
as optical anisotropic materials due to no centre of sym-
metry, and the characteristics change with changing axes
[28]. Due to the short detection time required for quantifica-
tion of a large category of an analyte, this type of biosensing
device displays a broad range of applications in addition to
cells and hormones [36-38].
3.3. Optical Biosensors
The working of an optical biosensor depends on the al-
teration in optical properties that takes place on the exterior
Fig. (5). Piezoelectric biosensor. (A higher resolution / colour ver-
sion of this figure is available in the electronic copy of the article).
plane of the transducer due to the interaction of target bio-
molecules with a device used for specifying, ultimately re-
sulting in the formation of a complex [19, 39]. It produces
optical signals equivalent to the concentration of target bio-
molecules. The compounds utilized for biorecognition are
cells, tissues, antigens, antibodies, and enzymes, as demon-
strated in Fig. (6) [40].
This type of biosensor is broadly categorized into 2 frac-
tions: direct biosensors and indirect biosensors. The indirect
biosensor suffers imprecise binding and multiplies the cost
of reagents that are to be employed for the detection process
[37]. Some more biosensors are present in the bibliography
and now offered for sale are “optrode-based optical biosen-
sors, evanescent wave optical biosensors, time-resolved fluo-
rescence, the resonant mirror optical biosensor, interferomet-
ric biosensors and surface plasmon resonance biosensors”
[41]. These are the most accepted types of biosensors due to
flexible detection characteristics and can detect multipoint
analytes, too [23]. The glucose biosensor has the biggest
commercial market among all the categories of biosensors to
date. Moreover, some limitations are being argued, including
binding of marker with reactant during antigen-antibody
reaction affect the results of the detector [19, 40-42].
3.4. Immunosensors
These biosensors are affinity-based biosensors that use
biorecognition elements for detecting analytes more precise-
ly. The work has been picturized through block diagram Fig.
(7). The elements utilized for such purposes are proteins,
nucleic acids, and antibodies. In this methodology, a trans-
ducer is bonded up with immunochemical complexes. Many
disease-causing proteins like Human Chorionic Gonadotro-
pin (HCG), platelet-derived growth factor, carbohydrate an-
tigen, carcinoembryonic antigen, interferon-γ, urinary lac-
toferrin, etc., can be expressed with this type of biosensor.
Analysis of the immuno-biosensors can be helpful in the
detection of diabetes, Human Immunodeficiency Virus
(HIV), tuberculosis, Urinary Tract Infection (UTI), cancer,
and pregnancy testing [43].
3.5. Thermometric Biosensors
Thermometric Biosensors detect the alteration in the
amount of heat of biological fluid in response to biological
reactions. This type of biosensor is also useful in measuring
Overview of Advancement in Biosensing Technology Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX 5
Fig. (6). Optical biosensor. (A higher resolution / colour version of this figure is available in the electronic copy of the article).
Fig. (7). Immunosensors. (A higher resolution / colour version of this figure is available in the electronic copy of the article).
Fig. (8). Thermometric biosensor. (A higher resolution / colour version of this figure is available in the electronic copy of the article).
6 Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX Mishra and Deshmukh
the level of serum cholesterol; sensitivity analysis of urea,
glucose, as well as penicillin G. Thermometric biosensor, has
a wide range of applications which includes multianalyte
assays of various elements, environmental impact assess-
ment, therapeutic management, the response of enzyme and
observation, analysis of hybrid sensitivity, etc. [41]. A sche-
matic diagram has been picturized in Fig. (8).
4. MECHANISM OF BIOSENSORS
4.1. Principle of Biosensors
Generally, a specific enzyme is denatured and trans-
formed into complementary electrical signals due to junction
with a transducer. This process is known as Electro- enzy-
matic approach [44, 45]. In this discipline, the substance of
interest binds with the biological element to obtain a lumi-
nous analyte molecule that can be detected. Picturized
through block diagram in Fig. (9) [44].
One of the classic examples of the biological counter is
the oxidation of biological materials. Oxidation functions
like a catalyst and affects the pH of the biofluids. The differ-
ences in pH will precisely hamper the current transmittance
tendency of the enzyme, which is one more time absolutely
associated with the enzyme that needs to be analyzed. The
resultant current is directly proportional to analyte biomole-
cules (enzyme). The electrical signals are amplified, inter-
preted, and lastly displayed in terms of voltage for a clear
illustration of the users [45].
4.2. Working of Biosensors
The distribution of biologically sensitive elements such
as cell receptors, tissues, enzymes, antibodies, microorgan-
isms, etc., along with an installed transducer, alters the bio-
logical material into an analogous electrical signal. Based on
the nature of the enzyme, the resultant signal of the transduc-
er can be current or voltage [45]. In case the resultant signal
is voltage, then there is no complication. In case the resultant
output happens to be current, then, first of all, it should be
transformed into an equal amount of voltage. This is done
with the help of a transimpedance amplifier, an Op-Amp-
Based current to voltage converter. As the voltage signal has
a small magnitude, it overlays larger frequency sound sig-
nals. It then reaches the amplifier, which is transferred to
Low Pass RC Filter [45, 46].
The electrical signal generated by the transducer is inter-
mittently mitigated and is superimposed to a moderately
spiked measure. Moreover, the conversion of the signal con-
sists of reducing a position baseline signal collected from a
linked transducer in the absence of catalyst integument [44].
In addition, stagnant tones of biosensor counteraction auto-
matically gratify the electrical sound-out filtration problem
[44-47]. In this phase, the absolute output would be an
equivalent signal. On the other hand, it is transformed statis-
tically. It is then credited to the microprocessor stage. In this
junction, the signal is illuminated and altered to approved
units, and then it reaches the amplifier where information is
stored [44].
5. SIGNIFICANCE OF BIOSENSORS IN THE MEDI-
CAL DIAGNOSIS
There is a considerable body of literature on biomarkers
about their usefulness in various industries, the most promi-
nent being pharmaceutical and diagnostic centres. The pro-
gress of biosensors started just after their development. It
gained global scientific attention from various fields like
forensics medicine [48, 49], chemistry, biology [50, 51],
physics, environment, food industry [52, 53], etc. Bi-
omarkers have been seen as useful in various industries, the
most prominent of which are pharmaceutical and diagnostic
centres. Infection recognition, ocular prostheses, contrast
imaging during MRIs, cardiac diagnostics, medical mycolo-
gy, surveillance systems, and other large disciplines are
competently assisted by bio-sensing. With outstanding pub-
lic care, such comprehensive possibilities raise health to an
unprecedented level [54]. The most recent COVID-19 epi-
demic is extremely contagious and is triggered by a recently
Fig. (9). The basic principle of biosensor. (A higher resolution / colour version of this figure is available in the electronic copy of the article).
Overview of Advancement in Biosensing Technology Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX 7
identified Covid strain that has now spread over the globe. A
closer look at the literature on numerous infections like avian
influenza, SARS, Hendra, Nipah, and others has piqued peo-
ple's curiosity [55]. Among various utilities of biosensors,
medical examination has emerged as a prominent area of
application due to its high demand for rapid examination
with respect to selectivity, stability, distinction, and modifi-
cation, as well as profitability in the biosensor circuit. The
introduction of advanced detection segments and the practice
of nanotechnology have caused rapid enhancement and mod-
ification of biosensors. Additionally, the analytical behaviour
of biosensors has enhanced its attainment in recognition par-
ticularity along with this consolidation. These features ena-
ble biosensors for relevant point-of-care testing as it gets
easier to accomplish multi-analyte analysis immediately [53-
56]. There are various kinds of biosensors such as optical
[51, 52, 57, 58], electrochemical [49, 56, 59] piezoelectric
[57, 58, 60, 61], magnetic [61-64], micromechanical [60, 61,
65, 66] and thermal for utilization in therapeutic examina-
tion. As a result, biosensors offer enormous prospective for
detecting viral disease outbursts. Some other important fea-
tures of the sensor include its capacity to monitor cardiac
problems. Cardiac illnesses are the leading source of mortali-
ty globally and cost the lives of nearly 17 million people
annually. The use of diagnostics in biosensors is critical in
the coronary heart event clinical insurgency. In order to get
the error-free detection of cardiac disorders, a model with
distinct sensors with appropriate surface chemistries and
nonmaterial is critical. [63-65, 67-70]. Diabetes frequency or
diabetic sufferers' use of bio-sensors is crucial to corporate
earnings worldwide. The demand for rapid and prophylactic
diabetes detection is growing. Blood glucose may now be
monitored in the immanence of various barriers beyond tem-
perature gradients, thanks to advancements in immunosen-
sors. The ever-increasing body of literature shows that the
biosensing device's selectivity and reliability with mini-
mal specimen proportion are constantly improving. They are
already widely used in the diabetic domain, with a grow-
ing business forecast in the upcoming decade. Featuring tre-
mendous potential for monitoring, therapy, diagnostics, and
exercise, using portable digital components is an integral
fraction of the comprehensive health service. Such devices
help to increase prophylactic activities and a greater under-
standing of individual health, using a combination of therapy
alternatives in the infirmary and primary care rooms. The
industry is driven by technological advancements and the
rising usage of biosensors in various uses. Wearable sens-
ing devices were shown to improve the standard of living
[71]. In addition, the usage of fitness trackers reduces the
financial share of fitness. Therefore, the growing number
of senior individuals and rising smart wearable preferences
amongst youngsters could expand market segments. Biosen-
sors are an effective approach to diagnosing ailments, dis-
covering microorganisms, and even identifying dangerous
substances in humans and the environment. Biomedical re-
search employs wearable sensors to diagnose conditions as
promptly as possible to give comprehensive health care. Ge-
netic markers and electrochemical biomaterials are utilized
in oncology to provide a quicker and more effective diagno-
sis. Metal-specific transistors in biomarkers can sense dan-
gerous metal concentrations in water. It also can analyse bio-
recognition elements like proteins, antibodies, and biomole-
cules, and locate harmful diseases [72, 73]. The additional
benefit of adopting biomaterials identification is the retrieval
time. The metabolite is usually diagnosed instantly and im-
mediately produces a measurable signal. Biomaterials are
increasingly widely employed in wearable electronics for
point-of-care assessment. Biosensors can be found in
tools that quantify glucose, alcoholism, maternity, and more.
Various scientists employed wearable sensors to track and
measure joint movement in numerous medical tasks. Using a
sphygmomanometer in the household is regarded as one of
the simplest orders to manage a healthy life [74].
Bioengineering advancement has brought hospital testing
equipment that could be utilised to monitor wellness. The
above technology enables doctor’s check-ups to be per-
formed privately, resulting in a significant boost to the
standard of diabetic care. These tools gained notice in oth-
er patient-centred quality of care and produced incentives for
developing enough sensitive tests to diagnose health condi-
tions [75]. It appeals to medical personnel because it reduces
the threat of infection and the expenses involved with the
sanitation of pharmaceutical products. Retractable detectors
are patient-friendly since they are more compatible with the
deformation of the body [76].
5.1. Cardiovascular
A series of recent studies have indicated that heart dis-
eases and stroke are some of the major illuminators of mor-
bidity and mortality worldwide. According to the World
Health Organization (WHO), 17.7 million people died from
heart events (CVD) in 2015, accounting for 31% of all fatali-
ties worldwide. (WHO 2017). About 7.4 million of these
deaths were caused by cardiovascular events, while 6.7 mil-
lion have been caused by stroke [70]. For a favourable fore-
cast of CVD or stroke, quick and prompt detection is im-
portant. Many cardiovascular genetic markers have been
recognized under this reference, including brain natriuretic
peptide, myoglobin, cardiac troponin I (cTnI), C-reactive
Protein (CRP), and interleukins, and interferons, which have
been identified employing electro-optic (colorimetric, spec-
troscopy, luminescence, surface plasma resonance (SPR),
and fibre optics/bio-optrode) and acoustic (CMOS compati-
ble acoustic particle velocity sensors) [77]. Many cardiovas-
cular genetic markers have been recognized under this refer-
ence, including brain natriuretic peptide, myoglobin, cardiac
troponin I (cTnI), C-Reactive Protein (CRP), and interleu-
kins, and interferons, which have been identified employing
electro-optic (colorimetric, spectroscopy, luminescence, Sur-
face Plasma Resonance (SPR), and fibre optics/bio-optrode)
and acoustic (CMOS compatible acoustic particle velocity
sensors), electrochemical biosensors (potentiometric, volt-
ammetry and impedimetric transducers), and magnetic-based
biosensors. Despite the tremendous progress that has been
made in biosensor generations, there are still some funda-
mental restrictions 70. Several theories have proposed that
most designed biomaterials use a traditional technique,
where testings are conducted in labs and outcomes are ob-
tained after many hours or days. Patients must also convene
two criteria for CVD diagnosis: elevated serum indicator
values, typical muscle aches, a diagnostic Electrocardiogram
(ECG) changes. However, 50% of subjects with CVD
brought to emergency rooms had a normal ECG rhythm,
8 Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX Mishra and Deshmukh
making CVD detection further challenging [78]. As a result,
there is an urgent need for an even more specific, efficient,
yet less expensive screening tool that could also aid in the
legitimate evaluation of patients of CVD sufferers' wellbeing
[77].
Breakthroughs in robotics and machine learning, as well
as its effective use in biological engineering, offer new do-
mains and tools for developing innovative modelling, and
predicting approaches for therapeutic application, covering
cardiac disorders [79, 80]. Keele University's myocardial
statistics, the Ministry of the United Kingdom's Congenital
Heart Disease datasets (CHD), and Cleveland's heart disease
assessment data frame from California University in Ervin,
among others, have indeed been generated. They save evi-
dence that is openly available for AI-assisted predicting of
heart disease. The above technique could be employed to
build a Point-Of-Care (POCT) tester, which can still be uti-
lized as a critical clinical instrument in areas wherein minor
necessities remain lacking. Seminal contributions have been
made by Chang et al., who invented an XPRIZE DeepQTri-
corder biosensor constituting AI that can effectively identify
12 serious ailments (anaemia, urinary tract infection, diabe-
tes, atrial fibrillation, stroke, sleep apnoea, tuberculosis,
Chronic Obstructive Pulmonary Disease (COPD), pneumo-
nia, otitis media, leucocytosis, and hepatitis A) as well as
obtain five real-time vital signs like blood pressure, ECG,
body temperature, respiratory rate, and oxygen saturation.
The development of AI-enabled biomaterials, also known as
next-generation biosensors, is undoubtedly among the prom-
ising solutions to the existing difficulties [70]. The working
and area of application have been demonstrated in Fig. (10).
Furthermore, AI may aid in developing even more economi-
cal healthcare instruments for tracking heart rhythm, pulse,
and pleural fluids in real-time [81]. Nonetheless, this study
will focus on current advancements in wearable devices for
cardiovascular problems and big data [77].
Fig. (10). Application of biosensors in cardiovascular disease. (A
higher resolution / colour version of this figure is available in the
electronic copy of the article).
5.2. Genetic Diseases
Since the introduction of bioimaging with biomolecu-
lar/biosensing material, deeper comprehension of cells and
several other components, such as DNA, RNA, and miRNA,
has been discovered [82, 83]. However, an entire genomic
strategy and improved optical-based genomic biomaterials
are essential to alter this industry. This section reviews re-
cent literature on optical biosensors using a mix of fluores-
cence and tiny molecules as a more significant technique in
respect of functionality and responsiveness [84, 85]. Target-
ing nucleic acids is a further promising area of biosensor
technology development. Mitochondrial miRNA expression
is a well-known biomarker for detecting the development of
an ailment, as regulating it enhances the potency of gene
therapy in hereditary diseases. Northern blotting, microar-
rays, and polymerase chain reaction are commonly used to
detect miRNAs. Technological advances allow the develop-
ment of suitable electrochemical sensors for miRNA algo-
rithms relies on label-free analysis employing guanine oxida-
tion following the formation of a hybrid between the miRNA
and its inosine replacement capture probe [84, 86]. Such
innovations result from current fabrication techniques that
advance electrochemical-based diagnostic innovations in
healthcare.
Inorganic substances biosynthesis via microbes pro-
cessing plants, limited supply, and concentration of organic
ingredients are frequent complaints. Employing genomic
biomarkers to control and maintain the production of specific
organic ingredients is indeed an efficient technique to allevi-
ate those impediments. The utmost prominent breakthroughs
in creating genomic biomarkers enabling organic substances
biotransformation in microbes are important considerations.
The hereditary constituent selection methodologies and
building concepts remain an open interest for developing and
assessing biological biosensing devices specifically were key
tenets taken into consideration. It is the most novel ad-
vancement of biological biotech on signalling pathways and
riboswitches in organic substances' biosynthesis. Finally,
designers assess the problems and possibilities in developing
genomic biomaterials for organic product biosynthesis in
microbes [87]. For the identification of many disorders,
DNA Template (or RNA) patterns, diagnostic testing, and
sensing of biological nucleotides have become extremely
crucial [84, 85].
In recent decades, tremendous advances have been
achieved in the formulation and implementation of genomic
biosensing again for the biogenesis of organic chemicals.
The selection and implementation of genomic biomaterials
are fraught with difficulties. A more systematic and theoreti-
cal analysis is required to enhance and increase methodolo-
gies for promptly constructing genomic wearable sensors,
developing sensors featuring special attributes, such as fre-
quency response, responsiveness, and reaction conditions,
and building multigene-controlling biological signal sensors.
These tactics could also be utilized to make the design and
use of molecular biosensors easier [85].
5.3. Alzheimer’s Disease
Alzheimer's Disease (AD) is among the most frequent
type of dementia, and researchers feel that diagnosing it
prematurely with precise genetic biomarkers is the key to
managing and perhaps eradicating it [88-90]. Timely screen-
ing of Alzheimer's disease employing biomarkers is possible.
Overview of Advancement in Biosensing Technology Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX 9
Amyloid-beta (A) peptide, total tau protein (t-tau), phos-
phorylated tau protein (p-tau), and other variables are poten-
tial indications of Alzheimer's disease [88-91]. A metabolite
developed by Amyloid Precursor Protein (APP) is particular-
ly soluble in CSF as well as plasma samples [92]. These di-
agnostic tools have good selectivity for distinguishing Hy-
pertension from several types of dementias. As a result, dif-
ferent biological recognition systems based on muscle bio
samples containing hydrolysed metabolites are indeed devel-
oped to automatically recognize Alzheimer's disease [89].
The steps of working are demonstrated in Fig. (11).
Biomarkers are substances that help us to figure out dis-
ease processes and build novel screening tests by analysing
and identifying them. Various chemicals and genetic altera-
tions have been found as credible and medically significant
AD markers in numerous investigations [88-90]. Biosensors
are incredibly prospective instruments that assist in preclini-
cal AD detection since these devices allow quantification of
various extremely sensitive indicators at a low price and
have a strong potential for accessibility, making them an
ideal point-of-care diagnosis strategy. The ability to use in-
credibly simple biofluids that leads to an efficient and local-
ized examination of subjects, as well as the ongoing discov-
ery of novel specific and sensitive biomarkers, has expanded
the accessibility of such devices [88].
Immunosensors are anticipated to help in the clinical
prediction of a greater population of clients and even the
regular testing of the condition's progression. These ad-
vancements will provide further information regarding the
onset of AD research and the analysis of the efficacy of vari-
ous medicines, enabling the creation of further effective
therapies and the hunt for a remedy. Studies suggest signifi-
cant progress toward making AD disease marker assays gen-
erally available as point-of-care products [89]. Nevertheless,
more steps are needed, particularly in developing wearable
sensors that could be bulk material available at lower prices
and with excellent accuracy [88, 90, 93].
Amyloid-beta peptide 1-42 (A42) is a precision for Alz-
heimer's disease primitive diagnosis (AD). As a result, it is
critical to design a quick and reliable technique for identify-
ing A42. This study has constructed a disposable biomarker
for recognition of A42 using magnetized nitrogen-doped
graphene (MNG) customized Au electrode. The specialized
biological sensing component for A42 that has been coupled
to the interface of MNG is A 1-28 (Aab) antibodies. The
biosensors may be easily built in the effect of magnetic
nanostructures on MNG, the electrode capping layer while
necessitating an electrode drying procedure, reducing the
processing system and making apprehension easier. The re-
cyclable bioassay displayed superior accuracy and consisten-
cy in the spectrum of 5pg mL1 to 800pg mL1, spanning the
trimmed limit of A42 and achieving a threshold of 5pg mL1.
Moreover, the constructed immunoassay for A42 identifica-
tion also enhances recognition rate and yet minimizes ex-
penses and twitch reflexes, indicating its utility in diagnosis
[93]. Examining the produced nano biosensors' detecting
method in genuine blood plasma revealed their therapeutic
utility for automatic recognition of Alzheimer's disease in
upcoming times [90].
5.4. Utilization of Biosensors in COVID-19 Detection
Due to fast response time, cheap pricing, the convenience
of being used, and the potential for POC usage, biotechnolo-
gies about definitive microbiological interaction provide
another efficient replacement of existing practices enabling
early screening of COVID-19. Merely 2 articles have been
published discussing affinity-based biomarkers for COVID-
19 monitoring.
Seo and his colleagues presented a novel FET-based bio-
sensor to diagnose the SARS-CoV-2 viruses. The device's
perceiving strip is a graphene film customized with a SARS-
CoV-2 spike antibody that has already been successfully
attached to the graphene plate interface. The instrument re-
portedly identifies the SARS-CoV-2 antigen spike protein
Fig. (11). Application of biosensor in Alzheimer’s disease. (A higher resolution / colour version of this figure is available in the electronic
copy of the article).
10 Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX Mishra and Deshmukh
using phosphate-buffered saline at quantities minimal as 1
fg/mL, which is significantly smaller than the ELISA plat-
form's simulation result. It is picturized in Fig. (12). The
sensors were also evaluated in the universal transport medi-
um (UTM), which is utilized to isolate nasopharyngeal sam-
ples during a true medical examination [94]. The COVID-19
FET sensing devices effectively distinguish antigenic sub-
stances in serum specimens without pre-treatment because
none of the chemicals present in UTM influenced the read-
ings. Additionally, there was no detectable merging between
the device and the MERS-CoV protein [95].
Fig. (12). Application of biosensor in COVID-19. (A higher resolu-
tion / colour version of this figure is available in the electronic copy
of the article).
Qiu and his colleagues suggested a dual biosensor that
combines the plasmonic photothermal (PPT) phenomenon
with the LSPR sensory transmission on even a single chip.
Through creating Au-S interactions between the AuNIs and
the thiolic groups of cDNA, the biosensor chip is redesigned
as a two-dimensional arrangement with gold nano islands
(AuNIs) and subsequently characterized amidst complemen-
tary DNA (cDNA) terminals. Non-specific interaction reac-
tions are reduced by correct layer modification, enhancing
the biosensor's responsiveness. The cramped limit of the
dual-functional biomarker was 0.1 pM to 1 mM, amidst a
concentration limit of 0.22 pM.
The AuNIs chips in situ PPT augmentation dramatically
increased fusion dynamics and nucleotide monitoring speci-
ficity. Several quasi molecular markers from SARS-CoV or
SARS-CoV-2 have been examined and distinguished,
demonstrating the biosensor's strong tolerance for cross-
reactive and interfering patterns [96].
Path Sensors Inc. has oriented the creation of a "Canary"
rapid detector for diagnosing the new SARS coronavirus.
The suggested technology uses a fibroblast biosensor that
combines viral capturing with data acquisition and delivers a
response in 3 to 5 minutes. The Path Sensors gadget will not
just be used to analyse specimens but also to monitor air
quality in critical areas like healthcare, businesses, and res-
taurants. By the end of July 2020, an additional biosensor
certification report was displayed [94-97].
5.5. Other Applications
In the biological sciences, biosensors have several intri-
guing uses. In this review, some of the most deployment
scenarios are described in Table 1 [98-119].
6. BIOSENSOR FOR MEASURING NON-PHYSICAL
QUANTITIES
Yokogawa introduced molecular spectroscopic sensing
devices to perceive and recognize normally undetectable
data. It serves as one alternative for measuring quasi varia-
bles like functioning and effectiveness, which is strenuous to
estimate to date. The above innovation has increased sensi-
tivity and high-speed molecular spectroscopy potential that
identify trace-amount attributes and record microscopic
phase variations caused by molecule collisions. Yokogawa
designed a detector and created a demonstration of a portable
molecular spectroscopic device by incorporating multiple
indigenously advanced systems: spectroscopic analysis,
spectrum analysis, and nanophotonics.
As a working prototype, the model was going to test the
lycopene composition of tomatoes in a non-destructive way.
It's crucial not just to demonstrate components and their re-
spective compositions and to depict how things interact at
the cellular scale. This gadget is anticipated to be adopted for
product testing and inventory control. This innovation can
benefit several businesses likely to flourish in upcoming
years, particularly in moderate surgical therapies, such as
cancer detection by blood collection and genetic testing
[120].
6.1. Future Scope
Genetically modified proteins are introduced into cultures
ex vivo or in vivo to create cell and tissue-based biosensors.
With biophotonics as well as other physical principles, these
tools empower a scholar to persistently and non-invasively
monitor hormone levels, medication, or toxicity. In this way,
the perspective can be useful in aging studies [121, 122].
Biosensors are deployed in marine structures to detect
eutrophication using nitrite and nitrate sensors. For genome
identification, sensing devices premised on nucleotide re-
combination identification were already evolved; the Monte-
rey Bay Aquarium Research Research's "Environmental
Sample Processor" aims to computerize the identification of
harmful algae in vivo from pontoons utilizing ribosomal
RNA examinations, which is a significant advance within
that area. One of several biggest objectives is to use bi-
omarkers to monitor pollution, contaminants, and poisons
[123]. The majority of previous research has documented
that the use of nanoparticles in biosensors opens the door to
developing a new generation of biosensor innovations.
Nanotechnology increases the structural, electrical, photonic,
and rheological holdings of biomaterials, opening the way
for solitary biomaterials and sensing grids exhibiting maxi-
mum bandwidth. Historically, there has been a great deal of
confusion in the literature regarding biomolecules having
unique structural features, and it's still a big task to figure out
how to integrate the form and composition of nanoparticles
and biomaterials to make single-molecule multi-use nano-
composites, nano-structured films, as well as nanoelectrodes.
Overview of Advancement in Biosensing Technology Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX 11
Fabrication, evaluation, metadata management, the advent of
affordable nanostructures, nanomaterial customization, and
the principles dictating the performance of such microscopic
aggregates on the surface of electrodes are all major obsta-
cles to current approaches [124]. Impediments include find-
ing solutions to improve the signal-to-116-noise ratio and
signal transduction and amplification [125].
Biosensors have driven themselves in the most useful
manner in various industries, the most prominent of which
are pharmaceutical and patient care. Illness identification,
ocular prosthetics, differential scanning during MRIs, cardi-
ac diagnoses, therapeutics, surveillance systems, and other
broad categories of biosensor applications are effectively
serviced. With great social services, such comprehensive
qualities elevate medicinal science to a different extreme.
COVID-19 is an extremely contagious outbreak driven by a
recently found coronavirus propagated globally. In recent
years, numerous viral infections like avian influenza, SARS,
Hendra, Nipah, and others have been encountered in the ex-
tant research and sparked major attention. As a result, bio-
sensors offer enormous prospective for detecting viral and/or
bacterial infections. Future research can concentrate on deci-
phering the engagement technique amongst nanostructures
and macromolecules on the surface of electrodes or nanolay-
ers, as well as utilizing innovative features to create a new
generation biosensor. On the other hand, nanomaterial-based
biosensors have a lot of promise and will soon be widely
used in diagnostic techniques, reviewed process monitoring,
and weather remediation [126].
Metabolomic approaches could be used in the upcoming
time to investigate a growing number of options for produc-
ing customized medications, devices, and assays. Research-
ers envision the use of a revolutionary advance in biological
specimen collection. Surgically implanted biomaterials em-
ploy the potential to significantly speed up the development
of customized therapeutics. This would allow scientists to
precisely track the impact of potential treatments on physiol-
ogy and determine whether a drug can progress commercial-
ly. Furthermore, sensing chip technology could also be im-
planted into an organism to discover complicated plasma
DNA alterations before the onset of clinical manifestations.
Biosensor technology has been utilized in low-cost, bidirec-
tional care-point equipment. It also detects implanted devices
in real-time [127]. Since artificial armbands have been in-
stalled within a wireless wearable, it can detect substances
including saliva and expelled dew breath, as well as plasma
and interstitium. A number of critical operational glitches,
like increasing detector endurance, must be addressed. Digi-
tal systems will be able to measure many physiological fac-
tors simultaneously and send the information to a mobile
application for the long term. The advancement of
such innovation would result in a significant expansion in the
medical field and increased individual contentment. Na-
nosensors, including the Internet, AI, and 5G, have made
this industry highly trustworthy, delicate, and personalised
[128]. Biotechnologies provide a deep mechanistic under-
standing of natural components at the cellular scale. There
are many applications for these research devices in medical,
product safety industries, agribusiness, environment man-
agement, and the investigation of cellular mechanisms. Basic
understanding enables the growth of cellular systems – criti-
cal in the discovery and delivery of pharmaceuticals, the
detection of microorganisms, pharmacogenomics, and other
biotechnological procedures [129].
CONCLUSION
Identifying and treating certain illnesses early on in their
evolution is critical, enabling patients to receive effective
therapy. Introducing simple, precise, and outlay detection
technologies such as biosensors is critical to efficiently iden-
Table 1. Different types and applications of biosensors.
Transduction
Biosensor Type
Applications
Refs.
Electrochemical
Anti-cholinesterases inhibitor biosensors
Analysis of insecticide
[98]
Hba1c biosensor
Glycosylated hemoglobin test
[99]
Piezoelectric biosensors
Identification of carbamic acid as well as phosphate esters
[100]
Uric acid electrochemical biosensors
Examination of many of the medical deformities including investigation of
heart-related disorders
[101, 102]
Glucose oxidase electrode biosensors (GOx)
Glucose testing in a diabetic patient's clinical specimen
[103]
Quartz-crystal biosensors
Protein identification in solutions with an extremely elevat-
ed responsiveness
[104]
Optical
Polyacrylamide gel biosensors
Biological materials sequestration
[105]
Silicon biosensor
In the treatment of tumours, biomedical imaging, and theranostics
[106, 107]
Microfabricated biosensor
In the field of innovative drug delivery, including visual rectification
[108]
Fluorescence tagged/ Genetically encoded
biosensor
Analysis of the cell's numerous cellular mechanisms with its structural
components
[109-111]
Electrochemical or optical
Nanomaterials-based biosensors
For analysis and medicine release
[112-119]
12 Current Pharmaceutical Biotechnology, XXXX, Vol. XX, No. XX Mishra and Deshmukh
tify diseases. Biosensors have expanded to various medical
applications that aid clinicians and patients in various ways,
including disease control, therapeutic interventions, prophy-
lactic therapy, individual health records, and illness evalua-
tions. Nanomaterials have also seen a lot of use in the crea-
tion of biosensors in recent decades. Such instruments ought
to continually evolve with simplicity, responsiveness, and
simultaneous evaluation of various variables, including the
unification of several processes on the same chip to reach the
requirements of a reliable screening aid. Electrostatic com-
bined with optic sensors are frequently used in clinical
pharmaceutical labs to assess systems in the body, such as
hyperglycaemia, lactic acid, urea, and creatinine, as well as
for glucose POC monitoring. Biosensors aren't as common
as traditional diagnostic procedures because of selectivity
concerns with numerous indicators. Near-patient diagnostics
in myocardial & some other cancer indicators show good
responsiveness with quicker processing. Melanoma laborato-
ry studies are now a central priority, featuring better simplic-
ity of operation and rapid gaffe screening of diagnostic
markers. This type of study aims to provide bioimaging
technologies enabling genetic detection in local healthcare
institutions and among the underprivileged. It mandates the
continual discovery for assessment of indicators, as well as
the creation of agonists for such genetic markers, specimen
process conditions, and the potential to multiplex the analy-
sis of numerous tumor indicators simultaneously. Investigat-
ing the genomic fingerprints of something like the malignant
spectrum and sensors has created new possibilities for using
biomaterials to diagnose tumours. The ultimate purpose is to
improve the selectivity of DNA immunosensors such that
they can identify a specific component in a relevant collec-
tion of samples. Substituting specimen processing or attenua-
tion stage, minimizing specimen, eluent quantity, and ac-
complishing sensor gratification in drug trials, POC molecu-
lar evaluation involves ultrasensitive transducer advanced
technologies, easily replaceable biological sensing factors,
microelectronics, assimilation, and robotization of new tech.
The invention of a biomarker well with the aforementioned
properties is the primary stumbling block to the fast evolu-
tion of such products at a reasonable price. Nanostructures
and lab-on-chip-evaluating devices are two promising ap-
proaches that offer homogeneous sensor formats, microscop-
ic manufacturing, and legitimate surveillance of macromole-
cules. Furthermore, the price must be modified to be availa-
ble to all demographics while maintaining high test control.
The introduction of therapeutically effective biomaterials in
the industry at an affordable rate necessitates a coordinated
wide range of outcomes.
LIST OF ABBREVIATIONS
AD = Alzheimer's Disease
CVD = Cardiovascular Disease
WHO = World Health Organization
ECG = Electrocardiogram
CHD = Congenital Heart Disease
POC = Point-of-care
CONSENT FOR PUBLICATION
Not applicable.
FUNDING
None.
CONFLICT OF INTEREST
The author(s) declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
The authors are grateful to the IPR, at GLA University in
Mathura, India, for providing the necessary facilities and
support to carry out this research.
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