Biosensors in diagnostic purpose

Biosensors in diagnostic
purposes
By: Zeravan Ali Sulaiman

Contents:
 Introduction.
 Characteristics of a biosensor.
 Types of biosensors.
 Biorecognition elements.
 Biosensors for Diagnostic Applications.
• Biosensors for diabetes applications.
• Biosensors for cardiovascular diseases applications.
• Biosensors for cancer applications.
• Biosensors for detection of pathogens virus, bacteria,
protozoan.
 References.

Introduction:
 Biosensors are analytical devices that convert a biological response into an
electrical signal. Typically, biosensors should be extremely specific and
irrespective of physical limitations like pH, temperature and may be
recyclable.
 Practical approach to design a biosensor needs fabrication, immobilization,
transducing devices which altogether offers engineering of multidisciplinary
research in chemistry as well as in biology. The material needed in
biosensors are divided into four groups based on its working mechanism
like;
1. Biocatalytic i.e. enzymes based biosensors.
2. Bioaffinity group, i.e. involvement of antibodies, antigen and nucleic acid.
3. Microbes i.e. biosesnsors containing microorganisms.
4. Nanosensors i.e. sensors with active nanoparticle that usually increase
sensitivity and specificity towards early detection of disease.
 These various types of biosensors allow to sense levels of hormones, drugs,
toxins, pollutants, heavy metals, pesticide etc. with considerable precision.

 In the present review an attempt was made to highlight various
types of biosensors which have indispensable application in
medicines, for instance enzyme specific biosensors,
immunosensors, nano specific biosensors and DNA biosensors.
 Biosensors are devices that usually estimate the levels of biological
markers or any chemical reaction by producing the signals that are
mainly associated with the concentration of an analyte being in the
chemical reaction.
 Such biosensor usually help to monitor diseases, drug discovery,
detection of pollutants, detection of disease causing bacteria and
markers that typically indicate the diseased conditions, like body
fluids (saliva, blood, urine, sweat etc.). A common biosensor
depicted in Figure 1
Introduction:

Introduction:
Figure 1: Schematic diagram showing the components of a biosensor.

A typical biosensor consists of:
1. Analyte: A substance of interest which is needed to be detected, for
example glucose for diabetes.
2. Bioreceptor: A molecule which recognizes the analyte can be a
bioreceptor for example enzymes.
3. Transducer: It usually converts a bio recognition event into
measurable signal, known as signalization.
4. Electronics: It generally processes the transduced signal in display
form.
5. Display: Usually its liquid crystal display in combination with
hardware and software for generation of biosensor result into user
friendly manner.
Introduction:

1. Selectivity: This feature is most important in biosensor because this
depends on the potential of bioreceptor to detect the specific analyte in a
mixture of sample and contaminants. For example; specific interaction of
antibody with particular antigen.
2. Reproducibility: It is just reproducibility of biosensor to program
identical output after repetition of the experimental setup.
3. Stability: It is the ability of biosensor to be non-susceptible in ambient
conditions in and around the biosensing system. Any disturbance can
modulate the output signals of biosensor for its measurement which may
lead to error and can affect the efficiency of the biosensor. The transducer
and electronics can be temperature sensitive, which may create disturbance
in the performance biosensor. Therefore, precision tuning is must to ensure
stable output of a biosensor. In addition to these, another factor can
influence the biosensor which is the binding affinity of analyte towards the
bioreceptor. Thus, the biosensor needs to be highly stable to overcome these
issues.
Characteristics of a Biosensor:

4. Sensitivity: Sensitivity can be defined based on its limit of detection
(LOD). In many medical application, biosensors have to detect analyte as
small as in the range of concentration of ng/mL or fg/mL, to affirm the
existence of analyte in the sample. For example, in Prostate cancer, the
prostate specific antigen (PSA) concentration will have a value of nearly 4
ng/mL in blood, which needs to be detected with high precision.
5. Linearity: It attributes to the accuracy of the measured response. It can be
depicted mathematically as y=mc, where c is the concentration of the
analyte, y is the output signal and m is the affectability of the biosensor. A
little change in concentration of an analyte makes a difference in the yield of
the biosensor. Another term that is taken into
consideration associated with is the linearity in a linear range, which can be
defined by the small amount of change in concentration, giving a
considerable change in the signal.
Characteristics of a Biosensor:

Types of Biosensors:
Biosensors can be categorized according to the biological recognition
element (enzymatic, immuno, DNA and whole-cell biosensors) or the
signal transduction method (electrochemical, optical, thermal and mass-
based biosensors) .
1. Thermal or Calorimetric Sensors: These types of biosensors take
advantage of the fundamental properties of a reaction, that is, adsorption
and heat generation. As a result of biological reaction, the temperature
of the medium changes; this is measured and compared to a sensor with
no reaction to determine the analyte concentration. These biosensors are
most suitable for enzyme-based reactions. They are commonly used for
estimating pesticides and pathogen bacteria but also used to measure
serum cholesterol based on enzymatically produced heat of oxidation
and decomposition reaction.

2. Amperometric biosensors: are typically used to detect small
molecules by means of an enzyme, e.g., a peroxidase, catalyzing a
redox reaction. The amperometric biosensor for the detection of
glucose by means of glucose oxidase was not Only the first biosensor
principle introduced, it is still, after several improvements, the most
widespread biosensor.
3. Optical biosensor: detectors can generally be divided into labeled
and label-free. Labels are, e.g., fluorophores or nanostructured
materials such as nanoparticles, quantum dots or carbon nanotubes.
Detectors using labels typically use the evanescent field outside a
waveguide resulting from total reflectance within the waveguide. it is
advantageous to have large analyte molecules to detect, such as
proteins, as they lead to a higher change in the refractive index.

4. Piezoelectric Sensors: Piezoelectric sensors are also called mass sensors;
the working principle of these biosensors is based on the interaction
regarding the amount of analyte with the sensing element, usually a
vibrating piezoelectric (PZ) quartz crystal. When an analyte of interest binds
to the PZ sensing element, the resonant frequency of the PZ crystal changes.
This creates an oscillating voltage that is spotted by the acoustic wave
sensor. Widest use of these sensors has been in gas phase analyses. These
sensors have also the same limitations like that of optical sensors that also
require sophisticated instruments and are not easy to be
miniaturized.
5. Whole-cell biosensors: are done using isolated biological components
because of their easy preparation, immobilization, and increased stability.
New emerging effects-related parameters and signals are given by whole
cell biosensors using biological components like microorganisms, for
example, the so-called cyanobacteria electrode or as well-exposed cells in
so-called minireactors for indicator values of genotoxicity and
immunotoxicity.

6. Immunological biosensors: rely on highly speciﬁc immunological
system, i.e., antibody and antigen, to detect environmentally or clinically
relevant targets. Immunological biosensors are actually a new version of
enzyme-linked immunosorbent assay (ELISA), with reduced cost, improved
speed and operation convenience, and comparable or even higher sensitivity.
 The sensors may operate either as direct or as indirect sensors often
referred to homogeneous and heterogeneous immunosensors,
respectively.
 Immunosensors are currently been used for infectious diseases diagnosis.
7. Potentiometric biosensors: potentiometric biosensors are best suited to
detect small molecules. Detectors for potentiometric biosensors include the
family of field-effect transistors (FET) which have been gaining interest in
the past years due to newly developed nanomaterials, such as carbon or
silicon nanotubes and nanowires. They allow label-free detection, i.e., do not
require labeling with enzymes or nanoparticles to get a signal response,
which reduces the expenses.

 There are several applications of biosensor which has been
implemented in various fields like medical science, marine sector,
food industry, etc., and also these biosensors are programmed for
better sensitivity and linearity in comparison with traditional
methods.
 Biosensors have many uses in clinical analysis, general health care
monitoring, veterinary and agricultural applications, industrial
processing and monitoring, and environmental pollution control.
 In the present review, we are attempting to cover biosensors which
are related to the medical science.
Applications of biosensor:

 In the development of a biosensor, the biological recognition may
be based on a catalytic reaction or on an afﬁnity reaction with
biosensing elements that have been chemically synthesized,
naturally isolated, engineered, or present in their original biological
environment (Fig. 2).
Biorecognition elements:
Figure 2: Overview of the different biochemical receptors integrated in the transducer.

 Enzymes (and all biological elements based on the enzymes contained in
it, like tissues, cells, microorganisms) represent the class of what is now
called “catalytic recognition elements”.
 Commonly used biosensing elements are of two types, namely, catalytic
type and affinity type. The catalytic sensors include enzymes, microbes,
organelles, cells, or tissues. The affinity type sensors are antibodies,
receptors, and nucleic acids.
1. Enzymes: Enzymes like glucose oxidase (GOx), horseradish peroxidase,
and alkaline phosphatase have been widely used in many biosensor
studies.
2. Microbes: Microbes have been used as biosensing matrix in fabrication
of biosensors.
3. Organelles: Each organelle carries out specific function inside a cell and
hence can be utilized in biosensing the specific analyte. For example,
mitochondria can measure calcium concentration because of their ability to
concentrate calcium in them. This ability is used to detect the water
pollutants.

4. Cells and Tissues: Cells have the ability to modify as per the surrounding
environment for which they are subjected to be used as biosensing
component.
5. Antibodies: The antibody is a critical part of immunosensors. These
immunosensors utilize the principle of highly selective antigen-antibody
reaction.
6. Nucleic Acids: DNA is an appropriate candidate for biosensing because
of its specific ability of base pairing with complementary sequence.
7. New Receptors: Aptamers. Aptamers are regarded as a new frontier.
These are artificial single-stranded DNA or RNA ligands that can be
generated against amino acids, drugs, proteins, and other molecules.

Biosensors for Diagnostic Applications
 Different types of biosensors have been successfully
developed and applied to the medical field, for the
diagnosis of pathologies such as cancer, cardiovascular,
autoimmune and neurodegenerative diseases.
 Among the numerous mankind diseases, three of them are
relevant because of their worldwide incidence,
prevalence, morbidity and mortality, namely diabetes,
cardiovascular disease and cancer.

Biosensors for glucose measuring:
Glucose sensors are now widely available as small, minimally invasive
devices that measure interstitial glucose levels in subcutaneous fat.
Requirements of a sensor for in vivo glucose monitoring include
miniaturization of the device, long-term stability, elimination of oxygen
dependency, convenience to the user and biocompatibility. Long-term
biocompatibility has been the main requirement and has limited the use of in
vivo glucose sensors, both subcutaneously and intravascular, to short periods
of time. Diffusion of low-molecular-weight substances from the sample
across the polyurethane sensor outer membrane results in loss of sensor
sensitivity.
The glucose biosensor is the most widely used example of an
electrochemical biosensor which is based on a screenprinted amperometric
disposable electrode (figure 3). This type of biosensor has been used widely
throughout The world for glucose testing in the home bringing diagnosis to
on site analysis.
1. Biosensors for diabetes applications

1. Biosensors for diabetes applications
Figure 3: Biosensors for glucose measuring.

 Biosensors for cholesterol measurement comprise the majority of the
published articles in the field of cardiovascular diseases. In the fabrication
of cholesterol biosensor for the estimation of free cholesterol and total
cholesterol, mainly cholesterol oxidase (ChOx) and cholesterol esterase
(ChEt) have been employed as the sensing elements.
 Electrochemical transducers have been effectively utilized for the
estimation of cholesterol in the system. Based on number and reliability
of optical methods, a variety of optical transducers have been employed
for cholesterol sensing, namely monitoring: luminescence, change in
color of dye, fluorescence and others.
 Other cardiovascular disease biomarkers are also quantified. incorporated
streptavidin polystyrene microspheres to the electrode surface of SPEs in
order to increase the analytical response of the cardiac troponin T and
used an assay based on virus nanoparticles for troponin I highly sensitive
and selective diagnostic, a protein marker for a higher risk of acute
myocardial infarction.
2. Biosensors for cardiovascular diseases
applications


applications


Figure 4: Schematic diagram sandwich immunoassay using antigen/antibody binding
system 1 and avidin/biotin affinity binding (system 2) on the FMGC.
applications

b. ELISA based cardiac Biosensors:
 A novel digital style approach was used to detect an early cardiac marker
like heart-type fatty-acid binding protein (H-FABP) and C-reactive
protein (CRP). This type of biosensors was very quick and produced
result within 15 min by simple calculating the quantity of red lines on test
zone without the involvement of expensive device. The present biosensor
involved conjugation of the of H-FABP (i.e.anti-FABP-mouse-IgG) and
anti-mouse-IgG for CRP as depicted in Figure 5.
Figure 5: Schematic diagram of digital style rapid test.
applications

3. Biosensors for cancer applications:
 Biosensor-based detection becomes practical and advantageous for cancer
clinical testing, since it is faster, more user-friendly, less expensive and
less technically demanding than microarray or proteomic analyses.
 For cancer diagnosis multi-array sensors would be beneficial for multi-
marker analysis. A range of molecular recognition molecules have been
used for biomarker detection, being antibodies the most widely used.
more recently, synthetic (artificial) molecular recognition elements such
as nanomaterials, aptamers, phage display peptides, binding proteins and
synthetic peptides as well as metal oxides materials have been fabricated
as affinity materials and used for analyte detection and analysis.

 Viruses are infectious agents that may be responsible for several diseases
in humans, including Human Papilloma Virus (HPV), dengue virus and
hepatitis virus.
 Scientists developed an electrochemical biosensor for the detection of a
specific DNA sequence of the hepatitis B virus, using graphite electrodes
modified with poly (4-aminophenol), differential pulse voltammetry as
detection technique and ethidium bromide as hybridization label (Figure
6).
4. Biosensors for detection of pathogenic
virus:
Figure 6: Example of genossensor for detection of a specific DNA sequence.

bacteria:
 Pathogenic bacteria are important targets for detection in several
fields, such as medicine and food safety. Many biosensors
platforms have been developed for tuberculosis based on different
biological recognition elements and various transducers.
 Developed an electrochemical genosensor for M. tuberculosis based
on the immobilization of a specific sequence of the IS6110 gene
using a reduced graphene oxide-gold nanoparticle-modified
electrode as a sensing platform and gold nanoparticles–polyaniline
as a tracer label for amplification.

 Protozoa are one of the main classes of parasites that cause diseases in
humans. A wide variety of approaches have been applied to the
development of biosensors for the diagnosis of protozoan-caused diseases
such as malaria, leishmaniasis, American trypanosomiasis (Chagas
disease) and toxoplasmosis.
 Various biomarkers have been used to malaria diagnosis. Biosensors
based on the immobilization of aptamers with high affinity for lactate
dehydrogenase, another biomarker for malaria, has been reported in the
literature using electrochemical and colorimetric transducers.
 Describes the development of Plasmodium lactate dehydrogenase-specific
ssDNA aptamers by SELEX using magnetic beads. The selected aptamers
were characterized and used for the construction of an aptamer based
electrochemical sensor able to discriminate malaria positive samples from
non-infected sample (Figure 7).
protozoan:

protozoan:
Figure 7: Example of aptasensor for the diagnosis of malaria.

References:
1. Arora, R. and R. Saini, Biosensors: Way of diagnosis. International Journal of
Pharmaceutical Sciences and Research, 2013. 4(7): p. 2517-2527.
2. Patel, S., et al., Biosensors in health care: the milestones achieved in their
development towards lab-on-chip-analysis. Biochemistry research international,
2016. 2016.
3. Rodovalho, V., et al., Biosensors applied to diagnosis of infectious diseases–An
update. Austin J Biosens & Bioelectron, 2015. 1(3): p. 1015.
4. Metkar, S.K. and K. Girigoswami, Diagnostic biosensors in medicine–a review.
Biocatalysis and agricultural biotechnology, 2019. 17: p. 271-283.
5. Gouvêa, C., Biosensors for health applications2011: InTech.

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