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Abstract
The ability to detect even the slightest physiological change in the human
body with high sensitivity and accurately monitor processes that impact human
nature and their surroundings has led to an immense improvement in the quality
of life. Biosensors continue to play a critical role across a myriad of fields includ-
ing biomedical diagnosis, monitoring of treatment and disease progression, drug
discovery, food control and environmental monitoring. These novel analytical
tools are small devices that use a biological recognition system to investigate or
detect molecules. This chapter covers the design and development of biosensors,
beginning with a brief historical overview. The working principle and important
characteristics or attributes of biosensors will also be addressed. Furthermore, the
basic types of biosensors and the general applications of these biosensors in various
fields will be discussed.
1. Introduction
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Figure 1.
Basic scheme of a biosensor. Picture adapted from Korotkaya [14] with modifications.
processing system therefore amplifies the electrical signal and conveys it to a data
processor that produces a measurable signal in the form of a digital display, print
out or color change [8, 9].
The concept of a biosensor is an ancient phenomenon. The first reported
concept of a biosensor dates back to 1906 when Cremer [10] discovered that the
concentration of an acid suspended in an aqueous solution is equivalent to the
electric potential generated between sections of the solution when separated by a
glass membrane. This led to the development of the concept of pH by Soren Peder
Lauritz Sorensen in 1909, which was followed by the development of an electrode
to measure this pH in 1922 by Hughes [11]. This paved way for the development
of what is known as a “true biosensor” in 1959 by Leland C. Clark, Jr., who is
affectionately known as the “father of biosensors”. Clark developed a sensor for
detecting glucose in biological samples, using a glucose oxidase electrode that
detects the presence of either oxygen or hydrogen peroxide. Since then, great strides
have been made in developing highly sensitive and selective biosensing devices [12,
13]. The emphasis of this chapter is on the design, development and applications of
biosensors. Various components that constitute a biosensor as well as the working
principle of biosensors will be presented. Moreover, various types of biosensors will
be highlighted and various fields where these devices are used will also be discussed.
2. Biosensor design
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Figure 2.
Biosensor design showing the various components necessary for generating a signal. Picture adapted from [6].
2.2 Transducer
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production of gluconic acid) and converts it into a voltage change [22, 23]. The
following features are recommended when a transducer is designed; specificity to
the target analyte, analyte concentration range, response time and suitability for
practical applications. Ideally, a transducer should be highly specific to the analyte,
give measurement at the lowest analyte concentration within the shortest time
possible [24].
Owing to the nature of the applications in which biosensors are used in, several
characteristics or parameters have to be met when a biosensor is designed. These
characteristics define the performance and usefulness of a biosensor.
4.1 Sensitivity
4.2 Selectivity
This refers to the ability of the biosensor to selectively bind and respond only
to the desired analyte, in the presence of other molecules or substances. When a
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4.3 Stability
A detection limit is defined as the lowest concentration of the target that is able
to elicit a measurable signal or response. Ideally, a biosensor should have the lowest
detection limit, especially if it is to be used in medical applications where the target
analyte might be present at very low concentrations [22].
4.5 Reproducibility
This is also one of the most important features in biosensing, and refers to the
ability of the biosensor device to produce matching output signals or results in
duplicate experimental runs. The capability of the biosensor to meet this criteria
relies on the transducer which is required to perform in a precise and accurate
manner [10].
This property determines the time it takes for the biosensor to generate a signal
or response following the interaction of the biological receptor with the target
analyte [26, 27].
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6. Classification of biosensors
Figure 3.
Flowchart showing the various types of biosensors classified based on their transducing elements and biological
recognition elements [36].
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These type of biosensors form the most researched and reported biosensors
based on biological receptors [37, 38]. Enzyme biosensors, useful tools for monitor-
ing rapid changes in metabolite levels in real-time, include pure enzyme prepara-
tions or biological processes. They have been derived on immobilization processes
such as van der Waals forces, ionic or covalent bonding. In 1967, Updike and Hicks
[39] successfully developed a working electrode for the detection of glucose levels
and this is considered the first biosensor in the world. The well-known enzymatic
biosensors today are glucose and urea biosensors. However, glucose biosensors
are most popular among researchers and are reportedly the mostly commercial-
ized biosensors. The glucose biosensor, which was developed by Clark, is made up
of glucose oxidase immobilized within a dialysis membrane which is integrated
inside oxygen electrodes. Enzymatic biosensors are known for their prolonged use
and reusability due to the fact that enzymes used as biological receptors cannot be
consumed. Thus, the detection limit and the lifetime of enzyme based biosensors is
greatly enhanced by the stability of the enzyme [40].
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monitor quality and to detect specific food pathogens. Moreover, these biosensors
are useful in controlling industrial microbial processes [57].
Figure 4.
Basic working principle of Quartz Crystal Microbalance (QCM) sensor [59].
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Over the last two decades, surface plasmon resonance (SPR) based biosensors
have emerged as important and useful tools due to their unique features for
real-time and label-free detection of biomolecular interactions [62, 63]. SPR
technology has opened a new avenue for many important applications in the field
of sensing due to their attractive sensing capabilities, light weight, compactness
and easy implementation [64–67]. The SPR phenomenon has been widely used
in biosensing, chemical sensing and environmental sensing applications such as
protein–protein hybridization [68, 69], enzyme detection [70, 71] and protein-DNA
hybridization. Surface plasmon resonance (SPR), as a physical phenomenon, is not
restricted only to events occurring in thin planar metal films. A broad spectrum
of differently nanostructured surfaces as well as noble metal nanoparticles are
frequently employed for fabrication of SPR-based assays [72–75].
However, conventional commercial SPR-based biosensors and experimental
devices are often represented by instruments, which utilize Kretschmann’s scheme
of plasmon excitation [65]. SPR-based biosensors can be employed to characterize
interactions between biomolecules immobilized onto the metal film sensor surface
and their counterparts in liquid sample in real time and without labelling. Indeed,
these biosensors are actively used to measure binding constants, kinetics of
biomolecular interactions and to perform concentration measurements [66]. In
turn, these applications make SPR-based biosensors very useful in pharmacological,
biomedical, environmental and food studies.
The first practical sensing application of SPR sensors for biomolecular detection
was reported by Liedberg and Nylander in 1983 [67]. Since then, SPR biosensors
have experienced rapid development in the last two decades and have become a
valuable platform for qualitative and quantitative measurements of biomolecular
interactions with the advantages of high sensitivity, versatile target molecule
selection, and real-time detection. For this reason, SPR sensors are now widely
adopted for meeting the needs of biology, food quality and safety analysis, and
medical diagnostics.
Over the past decade, many SPR sensors have been reported in applications
such as biomolecular interaction analysis, medical diagnostics, environmental
monitoring, and food safety [69, 71, 73] Traditional SPR devices generally require
expensive equipment, complicated optics, and precise alignment of the components
[74, 75], features that hinder the development of a portable device. Current portable
SPR devices still require a portable computer to run the instrument and are about
the size of a lunch box.
7. Applications of biosensors
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Biosensors have been used extensively in the food industry for quality control
and assurance purposes. These include applications in the agricultural field during
crop production and also during food processing. Quality control remains a major
part of food production and is responsible for the production of healthy food with
a prolonged shelf life and also complies with regulations. Biosensors have been
used as on-line or at-line quality sensors that make it possible for quality sorting,
automation and reduction of production cost and production time. Also, biosensors
have been developed to detect particular compounds in foods. These devices detect
chemicals or biological agents that contaminate food or might indicate the presence
of unwanted substances in food. Moreover, biosensors have been developed for
monitoring and estimating cross-contamination of surfaces and food products
[77–80].
7.2 Environment
Figure 5.
Various applications where biosensors have been used. Picture adapted from [76].
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7.3 Medical
Most of the biosensors reported in the past years are found to be based on the
phenomena of molecular interactions which are essentially employed in various
forms at different scales. In the discipline of medical science, the applications
of biosensors are growing rapidly. Some of the applications that have benefited
from the emergence of biosensors include cancer detection and monitoring,
cardiovascular disease monitoring, and diabetes control. Cancer diagnosis and
treatment are of great interest due to the widespread occurrence of the diseases,
high death rate, and recurrence after treatment. In medicine, biosensors can be used
to monitor blood glucose levels in diabetics, detect pathogens, and diagnose and
monitor cancer progression [85]. The use of emerging biosensor technology could
be instrumental in early detection of cancer for effective treatment administration
[86]. By measuring levels of certain proteins expressed and/or secreted by tumor
cells, biosensors can detect presence of a tumor, whether benign or cancerous, and
also give information of whether treatment is effective in reducing or eliminating
such cancerous cells [87, 88].
Cardiovascular diseases, which are the primary cause of death are still
considered as one of the biggest dilemma the world is facing with about one million
people suffering from it. The ability to detect such diseases earlier may result in the
reduction of mortality cases. Some of the sensing techniques that have been used
herein include immunoaffinity column assay, fluorometric assays, and enzyme-
linked immunosorbent assay [89–91]. However, the above techniques are laborious,
and therefore require well trained and qualified personnel and are time consuming.
Therefore, biosensors are being used for the detection of cardiac markers and
early diagnosis. Biosensors have been reported to offer vast advantages over
conventional diagnosis assays since they are established on electrical measurements
and also employ biochemical molecular recognition elements which gives a desired
selectivity with a particular biomarker of interest [92, 93].
8. Conclusions
Acknowledgements
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Conflict of interest
Author details
3 Centre for Metal Based Drug Discovery, Advanced Materials Division, Mintek,
Randburg, Johannesburg, South Africa
© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms
of the Creative Commons Attribution License (http://creativecommons.org/licenses/
by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
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