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Chapter

Biosensors: Design, Development


and Applications
Phumlani Tetyana, Poslet Morgan Shumbula
and Zikhona Njengele-Tetyana

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.

Keywords: bio-receptor, transducer, bio-sensing, analyze

1. Introduction

The importance of monitoring vital processes and parameters in various indus-


tries has led to the discovery of small analytical devices known as biosensors. The
emergence of these devices has provided solutions to various applications including
drug discovery, disease diagnosis, biomedicine, food safety and processing, environ-
mental monitoring, defence, and security [1, 2] as depicted. Biosensors are analytical
devices used to investigate the presence of an analyte of interest in a sample. By
definition, these are self-sufficient integrated devices that provide qualitative and
semi-quantitative analytical data through the use of a biological recognition element
that is coupled to a transduction element. The sole purpose of these analytical devices
is to rapidly provide accurate and reliable information about an analyte of interest in
real time [3–6].
Generally, biosensors are composed of three main components as depicted in
Figure 1. These include a biological sensing element, physicochemical detector
or transducer and a signal processing system [7]. Biological sensing elements are
used to interact with the analyte of interest to generate a signal. Sensing elements
normally include materials such as tissues, microorganisms, organelles, cell recep-
tors, enzymes, antibodies, and nucleic acids. The signal generated through the
interaction of the sensing element and the analyte of interest is then transformed
to a measurable and quantifiable electrical signal via the transducer. The signal

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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

A successful biosensor is composed of two main components, mainly a bio-


logical receptor or sensor element and a transducer. A signal processing unit that
usually contains a display or printer is normally used in conjunction to a biosensor
as depicted in Figure 2.

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Figure 2.
Biosensor design showing the various components necessary for generating a signal. Picture adapted from [6].

2.1 Biological receptor

This component is also known as a sensor or detector element and is responsible


for sensing or detecting the presence and/or the concentration of the target analyte
or substance. This is a biological component, which serves as a biochemical receptor
that specifically recognizes the target analyte [15]. When the biological receptor
interacts with a target analyte, it generates a signal in the form of light, heat, pH,
charge or mass change [10]. This material should be highly specific, stable under
storage conditions and must be immobilized. Furthermore, the biological receptor
should be capable of selectively detecting the target compound or analyte in the test
sample. According to Paddle [16], the biological receptor determines the sensitivity
of the entire device through the generation of the physicochemical signal that is
monitored by the transducer [16, 17].
This component can be a tissue, microorganism, organelle, cell receptor,
enzyme, antibody or nucleic acid etc. These can be grouped into two categories,
namely catalytic and non-catalytic receptors [18]. The catalytic group of biological
receptors are used in devices intended for continuous monitoring of substances
at millimolar or micromollar concentrations. These include enzymes, tissues and
microorganisms. The non-catalytic group is used mainly in biosensor devices that
measure analytes such as steroids, drugs, and toxins etc. which usually occur at very
low concentrations (micro to picomollar range). These are non-reusable devices
which can only be used once and discarded thereafter. Such receptors include
antibodies, antigens, nucleic acids etc. [17, 19, 20].

2.2 Transducer

A transducer forms the second main component in the design of a biosensor.


Generally, a transducer is a material that is capable of converting one form of
energy to another [10]. In a biosensor, a transducer is responsible for converting
the biochemical signal received from the biological receptor, which is a result of the
interaction between the target analyte and the biological receptor, into a measur-
able and quantifiable signal which can be piezo-electrical, optical, electrochemical
etc. The transducer detects and measures the change that occurs during biological
receptor – analyte interaction [21]. An example of a transducer is a pH sensor in
a glucose biosensor. An enzyme, known as glucose oxidase, is used as a biologi-
cal receptor which binds glucose and converts it to gluconic acid in the presence
of oxygen. The pH sensor (transducer) then detects the change in pH (due to

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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].

3. Working principle of a biosensor

As indicated in the aforementioned sections, a biosensor comprises of a biologi-


cal receptor coupled with a transducer and signal processing unit, and thus oper-
ate on the basis of signal transduction. The combination of these components is
designed to convert the biological response into a corresponding electrical response
and ultimately a measurable output. In simpler terms, biosensors are responsible
for the quantitative analysis of a molecule by relating its biological action into a
measurable signal [25]. Initially, the molecule of interest in the test sample binds
or interacts specifically with the biological receptor, resulting in a physiological
change. This further alters the physicochemical properties of the transducer that
is in close proximity to the biological receptor. This further leads to a change in the
optical or electronic properties of the transducer which is further converted into an
electrical signal which is detectable [26].
The signal generated by the transducer can either be a current or voltage,
depending on the type of biological receptor. If the output from the transducer is in
the form of a current, then this will be converted into an equivalent voltage. Also,
the output voltage is usually very low and masked by a high frequency noise signal,
which then requires further alterations, processing and amplification through
various filters within the signal processing unit. Finally, the output generated from
the signal processing unit should be comparable to the biological quantity being
measured [27].

4. Important characteristics of biosensors

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

This is considered as the most important characteristic of a biosensor. The


sensitivity of a biosensor is defined as the relationship between the change in
analyte concentration and the intensity of the signal generated from the transducer.
Ideally, a biosensor should generate a signal in response to small fluctuations in
the concentration of the target analyte. Depending on the application, biosensors
are required to detect analytes in the ng/ml or fg/ml concentration ranges. This is
usually important for medical applications and environmental monitoring purposes
[28, 29].

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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signal or response is generated from interactions with an analyte that is different


from the target analyte such is termed a false positive result. This is common in
biosensors with poor selectivity, thus failing in clinical applications. Selectivity is
a very important feature especially in medical applications where the test sample
or sample matrix, usually blood or urine, contains numerous molecules that are
quite similar to the target analyte and compete for binding to the biological receptor
[22, 30].

4.3 Stability

Stability of the biosensor is a very important characteristic especially for


biosensors used for continuous monitoring. This feature determines the
ability of the biosensor device to resist change in its performance over a period
of time in response to interruptions arising from external factors. These can be
in the form of temperature, humidity or other environmental conditions. Such
interruptions have the potential to induce inaccuracies in the output signal dur-
ing measurement, thereby affecting the precision and accuracy of the biosensor
device [10]. This is because transducers and other electronic components that
comprise the biosensor device are mostly temperature sensitive and this can
greatly influence their stability. Also, temperature can affect the integrity of
the biological receptor as this component tends to degrade with fluctuations in
temperature [22].

4.4 Detection limit

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].

4.6 Response time

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].

4.7 Range or linearity

Biosensor linearity determines the accuracy of the signal obtained, in


response to a set of measurements with differing concentrations. This attribute
gives insight into the resolution of the biosensor, defined as the minimal
change in the target analyte concentration that will elicit a response from the
biosensor. This is a very important attribute for a biosensor since most applica-
tions require a biosensor to measure a target analyte over wide concentration
ranges [10, 22].

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5. Considerations for biosensor design

The first step in developing a biosensing device involves investigating the


target analyte and understanding how this analyte interacts with certain
biological molecules. Once this has been established, the following tasks are
critical:

a. Selection of a biological receptor: the specificity and selectivity of a biosen-


sor to the analyte of interest is dependent upon the biological receptor used.
A suitable receptor with high affinity for the analyte is thus recommended.
Having knowledge of the advantages and disadvantages of various biological
receptors in different biosensor applications is very important in selecting a
suitable receptor [9, 15, 28].

b. Selection of a suitable immobilization method: for any biological molecule to


operate reliably as a biological receptor, it requires attachment onto the surface
of a transducer. This process is known as immobilization. Various methods
have been used for this task and include adsorption, entrapment, covalent
attachment, micro encapsulation and cross linking [31, 32].

c. Selection of a transducer element: the transducer element greatly


influences the sensitivity of the biosensor device. Employing the right
transducer will result in a device with increased sensitivity while the
sensitivity is more likely to be compromised by the use of an ineffective
transducer [33, 34].

6. Classification of biosensors

Biosensors are classified according to their biological receptors or transducer


elements. Figure 3 displays a flowchart illustrating the different types of
biosensors based on the biological receptors and transducer elements [35]. Some
of the biosensors shown in the figure will be discussed further in subsequent
sections.

Figure 3.
Flowchart showing the various types of biosensors classified based on their transducing elements and biological
recognition elements [36].

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6.1 Classification based on biological receptors

6.1.1 Enzyme based biosensors

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].

6.1.2 DNA based biosensors

Another group of biosensors based on a biological receptor is DNA biosen-


sors. The most attractive feature of biosensors is the high selectivity of biosensors
for their target analytes in a matrix of chemical or biological elements. DNA
biosensors, which use nucleic acids as their biological receptors, detect proteins
and non-macromolecular compounds that interact with certain DNA fragments
known as DNA probes or DNA primers. The interaction observed stems from the
formation of stable hydrogen bonds between the double helix nucleic acid strands
[41]. To develop DNA biosensors, immobilization of the probe becomes the most
crucial step. The strong pairing of lined up nucleotide strands between bases in
their complementary parts influences biosensors based on DNA, RNA, and peptide
nucleotide acids to be the most sensitive tool [42]. Lucarelli et al. reported that
probes, which are short oligonucleotides capable of hybridization with individual
areas of the target nucleotide sequence, together with various chemical composition
and conformational arrangements, were employed in the development of DNA
biosensors. Extremely high sensibility and selectivity is needed to maximize the
hybridization efficiency and minimize non-specific binding [43].

6.2 Biosensors based on transduction element

The most commonly applied classification of biosensors is based on the type of


transduction element used in the sensor. These biosensors are grouped into three
main categories, known as electrochemical biosensors, mass-based biosensors and
optical-based biosensors. The working principles of each of the three biosensors are
different and can thus be implemented in a variety of applications. Below is a brief
description of the different types of biosensors and their working mechanisms.
Some of the subclasses under the types of biosensors will also be explained.

6.2.1 Electrochemical biosensors

Electrochemical biosensors, which are the best in the detection of hybridized


DNA, DNA binding drugs, glucose concentration, etc., measure the electrical

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potential difference caused by an interaction between an analyte and the


membrane/sensor surface. There is proportionality between the electrical potential
difference and the logarithm of the electrochemically active concentration of
the material. The current flowing through the system or the potential difference
between the electrodes as a result of the redox reactions involving the analyte
are employed for its quantification in the sample. Electrochemical biosensors
have gained popularity as compared to optical biosensors in the sense that they
do not suffer from the many disadvantages optical biosensors experience. They
have a more stable output, high sensitivity, fast response and are not prone to
interferences. Electrochemical measurements are mostly preferred for sensing
applications [44–47]. Electrochemical biosensors can further be classified into
various types based on the measuring electrical parameters. These include
conductimetric, amperometric, potentiometric and impedimetric sensors [48].

6.2.1.1 Conductometric biosensors

Conductometric biosensors measure the electrical conductivity of the solution


in the course of a biochemical reaction. When electrochemical reactions produce
ions or electrons, the overall conductivity or resistivity of the solution changes. Due
to poor signal-to-noise ratio, they are less commonly used in biosensing applica-
tions, particularly when the biological receptor used is an enzyme. However, these
biosensors remain useful in the detection of affine interactions [49, 50].

6.2.1.2 Potentiometric biosensors

Potentiometric biosensors measure changes in pH and ion concentrations result-


ing from antigen/antibody interactions. Although potentiometric biosensors are
the least common of all biosensors, different strategies for the development of these
biosensors are found. The working principle relies on the fact that when a voltage is
applied to an electrode in solution, a current flow occurs because of electrochemical
reactions. The voltage at which these reactions occur indicates a particular reaction
and particular analyte. Some of the known potentiometric biosensors include those
used for the detection of Neisseria meningitides, Brucella melitensis and Francisella
tularensis species [51, 52]. Similarly, Hu et al. included a light-addressable potentio-
metric sensor in a microfluidic system to monitor the metabolism of human breast
cancer cells in real time [53].

6.2.1.3 Amperometric biosensors

This is perhaps the most common electrochemical detection method used


in biosensors. This high sensitivity biosensor can detect electroactive species
present in biological test samples [54]. Amperometric-based biosensors detect the
difference in current potentials during redox reactions when antigen/antibody
pairing occurs. The most common amperometric biosensors use the Clark oxygen
electrode. Amperometric biosensors have been developed for the indirect detection
of E. coli by Nakamura and co-workers [55]. Another amperometric biosensor for
the detection of Salmonella Species was developed by Brookes and colleagues [56].

6.2.1.4 Impedimetric biosensors

Impedimetric-based biosensors monitor changes in impedances upon antigen/


antibody interaction. Impedance, which usually employs a circuit bridge as a
measurement tool, is well suited for detection of bacteria in clinical specimens, to

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monitor quality and to detect specific food pathogens. Moreover, these biosensors
are useful in controlling industrial microbial processes [57].

6.2.2 Mass based biosensors

Piezoelectric biosensors are a group of analytical devices working on a principle


of affinity interaction recording. A piezoelectric platform or piezoelectric crystal is
a sensor part working on the principle of change in oscillations due to mass bound
on the piezoelectric crystal surface. Piezoelectric biosensors, which are considered
as mass-based biosensors, produce an electrical signal when a mechanical force is
applied. An example of piezoelectric biosensor is the quartz crystal microbalance
(QCM) model. The working principle of QCM is depicted in Figure 4. Quartz
crystal microbalance (QCM) is a very popular tool that is used extensively in the
electronic industry. Currently, these tools are used as attenuators in electronic
devices and they have a typically fundamental mode frequency of 1–20 MHz.
Though higher frequencies provide good opportunities for a sensitive assay, QCM
with high frequencies have been reported to exhibit several drawbacks such as
their fragility and also the technologically demanding equipment needed for their
manufacture [58]. The basic material used in the development of the QCM sensor
consists of quartz crystal, which is equipped with metal electrodes. A sensitive
coating material on the sensor surface is used to enable detection of the target
analyte in the environment. An appropriate electronic circuit is necessary to make
conversion of the measured quantity to an electrical signal [59].

6.2.3 Optical biosensor

Optical biosensors are based on the interaction of a sensing element with


electromagnetic radiation. They consist of a light source, as well as numerous
optical components to generate a light beam with specific characteristics and to
beeline this light to a modulating agent, a modified sensing head along with a
photodetector. An optical surface plasmon resonance (SPR) biosensor can detect
the refractive index changes on the surface of sensor chips, label-free and in
real-time. Although different optical methods such as absorption, fluorescence,

Figure 4.
Basic working principle of Quartz Crystal Microbalance (QCM) sensor [59].

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luminescence, internal reflection, surface plasmon resonance, or light scattering


spectroscopy utilized herein are becoming popular, fluorescence and surface
plasmon resonance enabled spectroscopies still remain the most and widely
researched and applied methods [60, 61].

6.2.3.1 Surface plasmon resonance based biosensors

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

Conventional ‘off-site’ analysis requires the samples to be sent to a laboratory for


testing. These methods allow the highest accuracy of quantification and the lowest
detection limits, but are expensive, time consuming and require the use of highly
trained personnel. Due to the above drawbacks, there has been a great interest in
the technology of biosensors. There has been a phenomenal growth in the field of
biosensor development in recent years with emerging applications in a wide range

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of disciplines. These include environmental monitoring, disease detection, food


safety, defence, drug discovery and many more as depicted in Figure 5 below.
A summary of the few and selected representatives and examples of developed
applications of biosensors is given below.

7.1 Food industry

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

Environmental pollution has an impact on human health and can therefore


compromise the quality of life. Depending on the purpose, sensitive and selective
methods are needed for both quantitative and qualitative determination of target
analytes. Biosensors have found widespread use in environmental monitoring for
the detection of chemical agents, organic pollutants, potentially toxic elements and
pathogens that might pose a health hazard. Biosensors such as immunosensors,
aptasensors, genosensors and enzymatic biosensors are amongst the most preferred

Figure 5.
Various applications where biosensors have been used. Picture adapted from [76].

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for environmental monitoring. These are known to use antibodies, aptamers,


nucleic acids and enzymes as biological receptors. For example, a biosensor
was developed to detect pesticides such as organophosphate and carbamate and
also monitor their effects on the environment. Biosensors detect pollutants by
measuring colour, light, fluorescence or electric current [81–84].

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

Biosensors continue to offer solutions and control of various processes across


a range of applications. As technology advances, new methods that will result
in the development of even better biosensors are emerging, and these seek to
address all limitations associated with these devices. The development of biosen-
sors revolves around their sensitivity, specificity, cost effectiveness and ability to
detect small molecules. This is mostly determined by the right combination of a
biological receptor and a transducer element, components which form the basis of
a biosensor.

Acknowledgements

The authors would like to thank the DSI/Mintek Nanotechnology Innovation


Centre for financial assistance towards this project.

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Biosensors: Design, Development and Applications
DOI: http://dx.doi.org/10.5772/intechopen.97576

Conflict of interest

Authors report no conflict of interest.

Author details

Phumlani Tetyana1*, Poslet Morgan Shumbula2 and Zikhona Njengele-Tetyana3

1 Department of Science and Innovation/Mintek Nanotechnology Innovation


Centre, Advanced Materials Division, Mintek, Randburg, Johannesburg,
South Africa

2 Department of Chemistry, University of Limpopo, Sovenga, South Africa

3 Centre for Metal Based Drug Discovery, Advanced Materials Division, Mintek,
Randburg, Johannesburg, South Africa

*Address all correspondence to: phumlanit@mintek.co.za

© 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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References

[1] Monosik R, Stredansky M, Sturdik E. Nello Formisano and Pedro Estrela.


Biosensors — classification, Essays in Biochemistry. 2016;60;1-8.
characterization and new trends. Acta DOI: 10.1042/EBC20150001
Chimica Slovaca. 2012;5(1);109-120,
DOI: 10.2478/v10188-012-0017-z [11] Hughes WS. The potential difference
between glass and electrolytes in contact
[2] Turner APF. Biosensors: sense and with the glass. Journal of American
sensibility. Chem. Soc. Rev., 2013; 42; Chemical Society. 1922; 44; 2860-2867.
3184-3196. DOI:10.1039/c3cs35528d DOI: 10.1021/ja01433a021.

[3] Mehrotra P. Biosensors and their [12] Clark LC, Lyons C. Electrode
applications – A review. Journal of Oral systems for continuous monitoring
Biology and Craniofacial Research. cardiovascular surgery. Annuals of the
2016;6;153-159. http://dx.doi. New York Academy of Sciences. 1962;
org/10.1016/j.jobcr.2015.12.002 102; 29-45.

[4] Thevenot D.R., Toth K., Durst R.A.,


[13] Li Y-CE, Lee IC. The Current Trends
Wilson G.S. Electrochemical biosensors:
of Biosensors in Tissue Engineering.
recommended definitions and
Biosensors. 2020; 10(88); 1-22.
classification. Pure Appl Chem.
doi:10.3390/bios10080088
1999;71:2333-2348.

[5] Damiati S, Schuster B. [14] Korotkaya EV. Biosensors: Design,


Electrochemical Biosensors Based on Classification, and Applications in the
S-Layer Proteins. Sensors. 2020; 20; Food Industry. Foods and Raw
1721; doi:10.3390/s20061721 Materials. 2014;2 (2);161-171. DOI
10.12737/5476
[6] Sabr AKH. Biosensors. American
Journal of Biomedical Engineering. [15] Chaubey A, Malhotra BD. Mediated
2016; 6(6); 170-179. DOI: 10.5923/j. biosensors. Biosensors & Bioelectronics.
ajbe.20160606.03 2002; 17; 441-456. DOI.org/10.1016/
S0956-5663 (01)00313-X
[7] Malhotra S, Verma A, Tyagi N,
Kumar V. Biosensors: principle, types
[16] Paddle BM. Biosensors for chemical
and applications. Int. J. Adv. Res. Innov.
and biological agents of defence
Ideas Educ. 2017; 3 (2); 3639-3644
interest. Biosensors & Bioelectronics.
1996; 11 (11); 1079-1113. DOI:
[8] Malik P, Katyal V, Malik V, Asatkar A,
0956-5663/961515.00
Inwati G, Mukherjee TK.
Nanobiosensors: Concepts and
Variations. International Scholarly [17] Lowe CR. Biosensors. Trends in
Research Notices. 2013; 2013; doi. Biotechnology. 1984; 2(3); 59-65. doi.
org/10.1155/2013/327435 org/10.1016/0167-7799 (84)90011-8

[9] Grieshaber D, MacKenzie R, Voros J, [18] Castillo J, Gáspár S, Leth S,


Reimhult E. Electrochemical Biosensors Niculescu M, Mortari A, Bontidean I,
- Sensor Principles and Architectures. Soukharev V, Dorneanu SA,
Sensors. 2008; 8; 1400-1458. DOI: Ryabov AD, Csöregi E. Biosensors for
10.3390/s80314000 life quality Design, development and
applications. Sensors and Actuators B.
[10] Bhalla N, Jolly P, Formisano N, 2004; 102; 179-194. DOI:10.1016/j.
Estrela P. Nikhil Bhalla, Pawan Jolly, snb.2004.04.084

14
Biosensors: Design, Development and Applications
DOI: http://dx.doi.org/10.5772/intechopen.97576

[19] Arnold MA, Meyerhoff ME. 2011. p. 225-247. DOI: 10.1021/bk-2011-


Recent advances in the development 1062.ch011
and analytical applications of
biosensing probes, C R C Critical [27] Ali J, Najeeb J, Ali MA, Aslam MF,
Reviews in Analytical Chemistry. 1988; Raza A. Biosensors: Their
20; 149-196. doi.org/10.1080/ Fundamentals, Designs, Types and Most
00078988808048811 Recent Impactful Applications: A
Review. Journal of Biosensors &
[20] Pearson JE, Gill A, Vadgama P. Bioelectronics. 2017;8(1); 1-9. DOI:
Analytical aspects of biosensors. Annals 10.4172/2155-6210.1000235
of Clinical Biochemistry. 2000; 37;
119-145. [28] Saha K, Agasti SS, Kim C, Li X,
Rotello VM. Gold nanoparticles in
[21] Thevenot DR, Toth K, Durst RA, chemical and biological sensing.
Wilson GS. Electrochemical biosensors: Chemical Reviews. 2012; 112; 2739-2779.
recommended definitions and DOI: 10.1021/cr2001178
classification. Biosensors and
Bioelectronics. 2001; 16; 121-131. DOI. [29] Wang Y, Knoll W, Dostalek J.
org/10.1016/S0956-5663 (01)00115-4 Bacterial pathogen surface plasmon
resonance biosensor advanced by long
[22] Wilkins E, Atanasov P. Glucose range surface plasmons and magnetic
monitoring: state of the art and future nanoparticle assays. Analytical
possibilities. Medical Engineering and Chemistry. 2012; 84; 8345-8350. doi.
Physics. 1996; 18; 273-288. doi. org/10.1021/ac301904x
org/10.1016/1350-4533 (95)00046-1
[30] Polatoğlu I, Aydın L, Nevruz BC,
[23] Ramirez NB, Salgado AM, Özer S. A Novel Approach for the
Valdman B. The evolution and Optimal Design of a Biosensor.
developments of immunosensors for Analytical Letters. 2020; 1428-1445.
health and environmental monitoring: DOI:10.1080/00032719.2019.1709075
Problems and perspectives. Brazilian
Journal of Chemical Engineering. 2009; [31] Morales MA, Halpern JM. Guide to
26 (02); 227-249. DOI: 10.1590/ Selecting a Biorecognition Element for
S0104-66322009000200001 Biosensors. Bioconjugate Chemistry.
2018; 29(10); 3231-3239. doi:10.1021/acs.
[24] Sethi RS. Transducer aspects of bioconjchem.8b00592
biosensors. Biosensors & Bioelectronics.
1994; 9; 243-264. doi.org/10.1016/0956- [32] Korotkaya EV. Biosensors: Design,
5663 (94)80127-4 Classification, and Applications in the
Food Industry. Foods and Raw
[25] Soleymani L, Li F. Mechanistic Materials. 2014;2 (2);161-171. DOI
Challenges and Advantages of Biosensor 10.12737/5476
Miniaturization into the Nanoscale.
American Chemical Society Sensors [33] Sassolas A, Blum LJ,
2017;2 (4); 458-467. doi.org/10.1021/ Leca-Bouvier BD. Immobilization
acssensors.7b00069 strategies to develop enzymatic
biosensors. Biotechnology Advances.
[26] Njagi JI, Kagwanja SM. The 2012; 30; 489-511. DOI: 10.1016/j.
Interface in Biosensing: Improving biotechadv.2011.09.003
Selectivity and Sensitivity. In:
Helburn R, Vitha MF, editors. Interfaces [34] Morales MA, Halpern JM. Guide to
and interphases in Analytical Selecting a Biorecognition Element for
Chemistry. American Chemical Society; Biosensors. Bioconjugate Chemistry.

15
Nanopores

2018; 29(10); 3231-3239. doi:10.1021/acs. [43] Lucarelli F, Tombelli S, Minnuni M,


bioconjchem.8b00592. Marazza G, Mascini M. Electrochemical
and piezoelectric DNA biosensors for
[35] Mungroo NA, Neethirajan S. hybridisation detection. Analytica
Biosensors for the Detection of Chimica Acta. 2008; 609; 139-159. DOI:
Antibiotics in Poultry Industry. A 10.1016/j.aca.2007.12.035
Review. Biosensors. 2014; 4, 472-493.
DOI:10.3390/bios4040472 [44] Koyun A, Ahlatcolu E, Koca Y.
Biosensors and their principles. In A
[36] Najeeb MA, Ahmad Z, Shakoor RA, Roadmap of Biomedical Engineers and
Mohamed AMA, Kahraman R. A novel Milestones; Kara, S., Ed.; InTech:
classification of prostate specific antigen Rijeka, Croatia, 2012
(PSA) biosensors based on transducing
elements. Talanta. 2017; 168; 52-61. [45] Mungroo NA, Neethirajan S.
DOI: 10.1016/j.talanta.2017.03.022 Biosensors for the Detection of
Antibiotics in Poultry Industry. A
[37] Ferri S, Kojima K, Sode K. Review of Review. Biosensors. 2014; 4, 472-493.
glucose oxidase and glucose DOI: 10.3390/bios4040472
dehydrogenases. Journal of diabetes
science and Technology. 2011; 5; [46] Lazcka O, Del Campo FJ,
1068-1076. DOI: Munoz FX. Pathogen detection: A
10.1177/193229681100500507 perspective of traditional methods and
biosensors. Biosensors and
[38] Ali SMU, Nur O, Willander M, Bioelectronics. 2007; 22; 1205-1217. DOI:
Danielson B. A fast and sensitive 10.1016/j.bios.2006.06.036
potentiometric glucose microsensor
[47] Wang J, Rivas G, Cai X, Palecek E,
based on glucose oxidase coated ZnO
Nielsen P, Shiraishi H, Dontha N, Luo D,
nanowires grown on a thin layer wire.
Parrado C, Chicharro M, Farias P,
Sensors and Actuators B: Chemical.
Valera FS. DNA electrochemical
2010; 145; 869-874. DOI:10.1016/j.
biosensors for environmental
snb.2009.12.072
monitoring: a review. Analytical
Chimica Acta. 1997; 347; 1-8. DOI:
[39] Updike S, Hicks G. The enzymatic
10.1016/S0003-2670(96)00598-3.
electrode. Nature. 1967; 214; 986-988
[48] Huet AC, Fodey T, Haughey SA,
[40] Marquette CA. State of the art and
Weigel S, Elliott C, Delahaut P.
research advances in immunoanalytical Advances in biosensor based analysis for
systems. Biosensors and Bioelectronics. antimicrobial residues in foods. Trends
2005; 21; 1424-1433. DOI: 10.1016/j. in Analytical Chemistry. 2010; 29;
bios.2004.09.037 1281-1294. DOI: 10.1016/j.
trac.2010.07.017.
[41] Wang J. DNA biosensors based on
peptide nucleic acid (PNA) recognition [49] Karyakin AA, Ulasova EA,
layers - A review. Biosensors and Vagin MY, Karyakina, EE. Sensor
Bioelectronics. 1998; 13 (7-8); 757-762. (Sensor), 2002, no. 1, pp. 16-24
DOI: 10.1016/s0956-5663(98)00039-6.
[50] Korotkaya EV. Biosensors: design,
[42] Monošík R, Streďanský M, classification, and applications in the
Šturdík E. Biosensors-classification, food industry. Foods and raw materials.
characterization and new trends. Acta 2014; 2(2); 161-171. DOI: 10.12737/5476.
Chimica Slovaca. 2012; 5; 109-120. DOI:
https://doi.org/10.2478/ [51] Lee WE, Thomson HG, Hall JG,
v10188-012-0017-z. Fulton RE, Wong JP. Rapid

16
Biosensors: Design, Development and Applications
DOI: http://dx.doi.org/10.5772/intechopen.97576

immunofiltration assay of Newcastle [59] Yuwono AS, Lammers PS. Odor


disease virus using a silicon sensor. Pollution in the Environment and the
Journal of Immunological Methods. Detection Instrumentation. Agricultural
1993; 166; 123-131. DOI: Engineering International: the CIGR
10.1016/0022-1759(93)90336-6. Journal of Scientific Research and
Development. Invited Overview
[52] Thompson HG, Lee WE. Rapid Paper, 5
immunofiltration assay of Francisella
tularensis. Defence Research [60] Leatherbarrow RJ, Edwards PR.
Establishment Suffield. 1992; 1376: 1-17. Analysis of molecular recognition using
optical biosensors. Current Opinions in
[53] Hu N, Wu C, Ha D, Wang T, Liu Q , Chemical Biology. 1999; 3; 544-547.
Wang P. A novel microphysiometer DOI: 10.1016/s1367-5931(99)00006-x
based on high sensitivity LAPS and
micro-fluidic system for cellular [61] Bănică, F-G. (2012). What are
metabolism study and rapid drug chemical sensors? In: Chemical sensors
screening. Biosensors and and biosensors. Chichester: Wiley, 1-20
Bioelectronics. 2013; 40(1); 167-173.
[62] Handrigan JP. Rapid Detection of
DOI: 10.1016/j.bios.2012.07.010.
Food-Borne Pathogens. 2010. http://
www.johnpaulhandrigan.net/
[54] Reza KD, Azadeh A, Maryam N,
wp-content/uploads/2012/01/
Golnaz R, Morteza AA. Biosensors: John-Paul-Handrigan
Functions and Applications. Journal of
Biology and Today's World. 2013; 2 (1); [63] Formisano N, Jolly P, Bhalla N,
20-23. DOI: 10.15412/J.JBTW.01020105. Cromhout M, Flanagan SP, Fogel R,
Limson JL, Estrela P. Optimisation of an
[55] Nakamura N, Shigematsu A, electrochemical impedance
Matsunaga T. Electrochemical detection spectroscopyaptasensor by exploiting
of viable bacteria in urine and antibiotic quartz crystal microbalance with
selection. Biosensors and Bioelectronics. dissipation signals. Sensors and
1991; 6; 575-580. DOI: Actuators B. 2015; 220; 369-375. DOI:
10.1016/0956-5663(91)80022-p. 10.1016/j.snb.2015.05.049

[56] Brooks JL, Mirhabibollahi B, [64] Miroslav P. The Piezoelectric


Kroll RG. Experimental enzyme-linked Biosensors: Principles and applications.
amperometric immunosensors for the A review. International Journal of
detection of Salmonella in foods. Journal Electrochemical Science. 2017; 12;
of Applied Bacteriology. 1992; 73; 496-506. DOI: 10.20964/2017.01.44
189-196. DOI: 10.1111/j.1365-2672.1992.
[65] Kretschmann E. Determination of
tb02977.x
optical constants of metals by excitation
of surface plasmons. Zeitschrift für
[57] Silley P, Forsythe S. Impedance
Physik A Hadrons and nuclei. 1971;
microbiology: a rapid change for
241; 313-324
microbiologists Journal of Applied
Bacteriology. 1996; 80; 233-243. DOI: [66] Schasfoort RBM, Tudos AJ. (2008).
10.1111/j.1365-2672.1996.tb03215.x. How to construct an SPR assay? In Hand
book of Surface Plasmon Resonance;
[58] Miroslav P. The Piezoelectric RSC Publishing: Cambridge, UK,
Biosensors: Principles and applications. 2008; 3-9
A review. International Journal of
Electrochemical Science. 2017; 12; [67] Liedberg B, Nylander C,
496-506. DOI: 10.20964/2017.01.44 Lundstrum I. Surface plasmon

17
Nanopores

resonance for gas detection and [74] Thiel AJ, Frutos AG, Jordan CE,
biosensing. Sensors and Actuators B. Corn RM, Smith LM. In situ surface
1983; 4; 299-304. DOI: plasmon resonance imaging detection of
10.1016/0250-6874(82)80008-5 DNA hybridization to oligonucleotide
arrays on gold surfaces. Analytical
[68] Mungroo NA, Neethirajan S. Chemistry. 69, 4948-4956. DOI:
Biosensors for the Detection of 10.1021/ac0010431.
Antibiotics in Poultry Industry. A
Review. Biosensors. 2014; 4, 472-493. [75] Jordan CE, Corn RM. Surface
DOI: 10.3390/bios4040472 Plasmon Resonance Imaging
Measurements of Electrostatic
[69] Inamor K, Kyo M, Nishiya Y, Biopolymer Adsorption onto Chemically
Inoue Y, Sonoda T, Kinoshita E, Koike T, Modified Gold Surfaces. Analytical
Katayama Y. Detection and Chemistry. 1997; 69; 1449-1456. DOI:
quantification of on-chip 10.1021/ac961012z
phosphorylated peptides by surface
plasmon resonance imaging techniques [76] Singh S, Kumar V, Dhanjal DS,
using a phosphate capture molecule. Datta S, Prasad R, Singh J. Biological
Analytical Chemistry. 2005; 77; 3979- Biosensors for Monitoring and
3985. DOI: 10.1021/ac050135t Diagnosis. In: Singh J, Vyas A, Wang S,
Prasad R, editors. Microbial
[70] Ali SMU, Nur O, Willander M, Biotechnology: Basic Research and
Danielson B. A fast and sensitive Applications. Environmental and
potentiometric glucose microsensor Microbial Biotechnology. Springer;
based on glucose oxidase coated ZnO 2020. p. 317-335.
nanowires grown on a thin layer wire. DOI:10.1007/978-981-15-2817-0_14
Sensors and Actuators B: Chemical.
[77] Manikandan R, Charumathe N,
2010; 145; 869-874. DOI:10.1016/j.
Fariha BA. Applications of biosensors.
snb.2009.12.072
Bulletin of Scientific Research. 2019;
1(1); 34-40. DOI: 10.34256/bsr1915
[71] Kanoh N, Kyo M, Inamori K,
Ando A, Asami A, Nakao A, Osada H. [78] Wei N, Xin X, Du J, Li J. A novel
SPR imaging of photo-cross-linked hydrogen peroxide biosensor based on
small-molecule arrays on gold. the immobilization of hemoglobin on
Analytical Chemistry. 2006; 78; 2226- three-dimensionally ordered
2230. DOI: 10.1021/ac051777j. macroporous (3DOM) gold-
nanoparticle-doped titanium dioxide
[72] Hu N, Wu C, Ha D, Wang T, Liu Q , (GTD) film. Biosensors and
Wang P. A novel microphysiometer Bioelectronics. 2011; 26; 3602-3607.
based on high sensitivity LAPS and DOI: 10.1016/j.bios.2011.02.010
micro-fluidic system for cellular
metabolism study and rapid drug [79] Villalonga R, Díez P,
screening. Biosensors and Yáñez-Sedeño P, Pingarrón JM. Wiring
Bioelectronics, 2013; 40 (1); 167-173. horseradish peroxidase on gold
DOI: 10.1016/j.bios.2012.07.010 nanoparticles-based nanostructured
polymeric network for the construction
[73] Li Y, Liu X, Lin Z. Recent of mediatorless hydrogen peroxide
developments and applications of biosensor. Electrochimica Acta, 56,
surface plasmon resonance biosensors 4672-4677. DOI:10.1016/J.
for the detection of mycotoxins in ELECTACTA.2011.02.108
foodstuffs. Food Chemistry.132, 1549-
1554. DOI: 10.1016/j. [80] Rana JS, Jindal J, Beniwal V,
foodchem.2011.10.109 Chhokar V. Utility Biosensors for

18
Biosensors: Design, Development and Applications
DOI: http://dx.doi.org/10.5772/intechopen.97576

applications in Agriculture – A Review. ELISA for aqueous humor: IL-5, IL-10,


Journal of American Science. 2010; and IFN profiles in uveitis. Investigative
6(9); 353-375. Ophthalmology and Visual Science.
2006; 47; 272-277. DOI: 10.1167/
[81] Justino CIL, Duarte AC, iovs.05-0790.
Rocha-Santos TAP. Recent Progress in
Biosensors for Environmental [90] Caruso R, Trunfio S, Milazzo F,
Monitoring: A Review. Sensors. 2017; 17; Campolo J, De Maria R, Colombo T,
2918-2943. DOI:10.3390/s17122918 Parolini M, Cannata A, Russo C,
Paino R, Frigerio M, Martinelli L,
[82] Atkinson AL, Haggett BGD. Whole Parodi O. Early expression of proand
Cell Biosensors for Environmental anti-inflammatory cytokines in left
Monitoring. Sensor Review. 1993; 13(4); ventricular assist device recipients with
19 - 22. DOI.org/10.1108/eb007917 multiple organ failure syndrome.
American Society of Artificial Internal
[83] Nigam VK, Shukla P. Enzyme Based Organs. 2010; 56; 313-318
Biosensors for Detection of
Environmental Pollutants - A Review. [91] Caruso R, Verde A, Cabiati M,
Journal of Microbiology and Milazzo F, Boroni C, Del Ry S,
Biotechnology. 2015; 25(11); 1773-1781. Parolini M, Vittori C, Paino R,
https://doi.org/10.4014/jmb.1504.04010 Martinelli L, Giannessi D, Frigerio M,
Parodi O. Association of preoperative
[84] Tortolini C, Mazzei F.
interleukin-6 levels with interagency
Electrochemical biosensors for
registry for mechanically assisted
environmental monitoring.
circulatory support profiles and
International Journal of Environment
intensive care unit stay in left
and Health. 2012; 6(2); 93-110. https://
ventricular assist device patients. J Heart
doi.org/10.1039/B403975K.
Lung Transplant. 2012; 31(6); 625-633.
DOI: 10.1016/j.healun.2012.02.006
[85] Tothill IE. Biosensors for cancer
markers diagnosis. Seminars in Cell &
[92] Watson CJ, Ledwidge MT, Phelan D,
Developmental Biology. 2009; 20; 55-62.
Collier P, Byrne JC, Dunn MJ,
DOI: 10.1016/j.semcdb.2009.01.015
McDonald KM, Baugh JA. Proteomic
[86] Bohunicky B, Mousa SA. Biosensors: analysis of coronary sinus serum reveals
the new wave in cancer diagnosis. leucine-rich 2-glycoprotein as a novel
Nanotechnology, Science and biomarker of ventricular dysfunction
Applications. 2011; 4; 1-10. DOI: and heart failure. Circulation Heart
10.2147/NSA.S13465 Failure. 2011; 4; 188-197. DOI: 10.1161/
CIRCHEARTFAILURE.110.952200
[87] Bohunicky B, Mousa SA. Biosensors:
the new wave in cancer diagnosis. [93] Maurer M, Burri S, de Marchi S,
Nanotechnology, Science and Hullin R, Martinelli M, Mohacsi P,
Applications. 2011; 4; 1-10. DOI: Hess OM. Plasma homocysteine and
10.2147/NSA.S13465 cardiovascular risk in heart failure with
and without cardiorenal syndrome.
[88] Tothill IE. Biosensors for cancer International Journal of Cardiology.
markers diagnosis. Seminars in Cell & 2010; 141; 32-38. DOI: 10.1016/j.
Developmental Biology. 2009; 20; 55-62. ijcard.2008.11.131
DOI: 10.1016/j.semcdb.2009.01.015

[89] Ooi KGJ, Galatowicz G,


Towler HMA, Lightman SL, Calder VL.
Multiplex cytokine detection versus

19

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