BIOSENSORS

Ms. Shivani Kumari

Bsc. Computer Science Department

Saint Mira’s College for Girls

Koregaon Park, Pune

Abstract: This document gives micro-organisms and markers that are

information about biosensors. Biosensors indicators of a disease in bodily fluids
(blood, urine, saliva, sweat). A typical
are nowadays used in biomedical diagnosis
biosensor is represented in figure1; it
as well as a wide range of other areas such consists of the following components.
as point-of-care monitoring of treatment and
disease progression, environmental 1.1 Analyte: A substance of interest that
needs detection. For instance, glucose is an
monitoring, food control, drug discovery,
‘analyte’ in a biosensor designed to detect
forensics and biomedical research. A wide glucose.
range of techniques can be used for the
development of biosensors. Their coupling 1.2 Bioreceptor: A molecule that
specifically recognizes the analyte is known
with high-affinity bimolecular allows the
as a Bioreceptor. Enzymes, cells, a tamers,
sensitive and selective detection of a range deoxyribonucleic acid (DNA) and antibodies
of analyte. We give a general introduction to are some examples of Bioreceptor. The
biosensors and biosensing technologies, process of signal generation (in the form of
including a brief historical overview, light, heat, pH, charge or mass change, etc.)
introducing key developments in the field upon interaction of the Bioreceptor with the
and illustrating the breadth of bimolecular analyte is termed bio-recognition.
sensing strategies and the expansion of 1.3 Transducer: The transducer is an
nanotechnological approaches that are now element that converts one form of energy
available. into another. In a biosensor the role of the
transducer is to convert the bio-recognition
Keywords: affinity reagents, biosensors, event into a measurable signal. This process
glucose sensor, nonmaterial’s, pregnancy of energy conversion is known as
test signalization. Most transducers produce
either optical or electrical signals that are
usually proportional to the amount of
1. Introduction
analyte–Bioreceptor interactions.
A biosensor is a device that measures
biological or chemical reactions by 1.4 Electronics: This is the part of a
generating signals proportional to the biosensor that processes the transduced
concentration of an analyte in the reaction. signal and prepares it for display. It consists
Biosensors are employed in applications of complex electronic circuitry that performs
such as disease monitoring, drug discovery, signal conditioning such as amplification
and detection of pollutants, disease-causing and conversion of signals from analogue
into the digital form. The processed signals demonstrated immobilization of the enzyme
are then quantified by the display unit of the invertase on aluminium hydroxide and
biosensor. charcoal. The first ‘true’ biosensor was
developed by Leland C. Clark, Jr in 1956 for
oxygen detection. He is known as the ‘father
of biosensors’ and his invention of the
oxygen electrode bears his name: ‘Clark
electrode’ [5]. The demonstration of an
amperometric enzyme electrode for the
detection of glucose by Leland Clark in
1962 was followed by the discovery of the
first potentiometric biosensor to detect urea
in 1969 by Guilbault and Montalvo, Jr [6].
Eventually in 1975 the first commercial
biosensor was developed by Yellow Spring
Instruments (YSI). Ever since the
development of the I-STAT sensor,
Figure 1 remarkable progress has been achieved in
the field of biosensors. The field is now a
Schematic representation of a biosensor multidisciplinary area of research that
bridges the principles of basic sciences
1.5 Display: The display consists of a user
(physics, chemistry and biology) with
interpretation system such as the liquid
fundamentals of micro/nano-technology,
crystal display of a computer or a direct
electronics and applicatory medicine. The
printer that generates numbers or curves
database ‘Web of Science’ has indexed over
understandable by the user. This part often
84000 reports on the topic of ‘biosensors’
consists of a combination of hardware and
from 2005 to 2015.
software that generates results of the
biosensor in a user-friendly manner. The
output signal on the display can be numeric,
graphic, tabular or an image, depending on 3. Characteristics of biosensors
the requirements of the end user.
There are certain static and dynamic
2. Historical background attributes that every biosensor possesses.
The optimization of these properties is
The history of biosensors dates back to as reflected on the performance of the
early as 1906 when M. Cremer [1] biosensor.
demonstrated that the concentration of an
acid in a liquid is proportional to the electric
potential that arises between parts of the 3.1 Selectivity
fluid located on opposite sides of a glass Selectivity is perhaps the most important
membrane. However, it was only in 1909 feature of a biosensor. Selectivity is the
that the concept of pH (hydrogen ion ability of a Bioreceptor to detect a specific
concentration) was introduced by Søren analyte in a sample containing other
Peder Lauritz Sørensen and an electrode for admixtures and contaminants. The best
pH measurements was realized in the year example of selectivity is depicted by the
1922 by W.S. Hughes [2]. Between 1909
interaction of an antigen with the antibody.
and 1922, Griffin and Nelson [3,4] first
Classically, antibodies act as Bioreceptor response of the sensor. Another factor that
and are immobilized on the surface of the can influence the stability is the affinity of
transducer. A solution (usually a buffer the Bioreceptor, which is the degree to
containing salts) containing the antigen is which the analyte binds to the Bioreceptor.
then exposed to the transducer where Bioreceptor with high affinities encourage
antibodies interact only with the antigens. either strong electrostatic bonding or
To construct a biosensor, selectivity is the covalent linkage of the analyte that
main consideration when choosing fortifies the stability of a biosensor.
Bioreceptor. Another factor that affects the stability of a
measurement is the degradation of the
3.2 Reproducibility
Bioreceptor over a period of time.
Reproducibility is the ability of the
3.4 Sensitivity
biosensor to generate identical responses
for a duplicated experimental set-up. The The minimum amount of analyte that can
reproducibility is characterized by the be detected by a biosensor defines its limit
precision and accuracy of the transducer of detection (LOD) or sensitivity. In a
and electronics in a biosensor. Precision is number of medical and environmental
the ability of the sensor to provide alike monitoring applications, a biosensor is
results every time a sample is measured required to detect analyte concentration of
and accuracy indicates the sensor's as low as ng/ml or even fg/ml to confirm
capacity to provide a mean value close to the presence of traces of analyte in a
the true value when a sample is measured sample. For instance, a prostate-specific
more than once. Reproducible signals antigen (PSA) concentration of 4 ng/ml in
provide high reliability and robustness to blood is associated with prostate cancer for
the inference made on the response of a which doctors suggest biopsy tests. Hence,
biosensor. sensitivity is considered to be an important
property of a biosensor.
3.3 Stability
3.5 Linearity
Stability is the degree of susceptibility to
ambient disturbances in and around the Linearity is the attribute that shows the
biosensing system. These disturbances can accuracy of the measured response (for a
cause a drift in the output signals of a set of measurements with different
biosensor under measurement. This can concentrations of analyte) to a straight
cause an error in the measured line, mathematically represented as y=mc,
concentration and can affect the precision where c is the concentration of the
and accuracy of the biosensor. Stability is analyte, y is the output signal, and m is the
the most crucial feature in applications sensitivity of the biosensor. Linearity of
where a biosensor requires long incubation the biosensor can be associated with the
steps or continuous monitoring. The resolution of the biosensor and range of
response of transducers and electronics analyte concentrations under test. The
can be temperature-sensitive, which may resolution of the biosensor is defined as
influence the stability of a biosensor. the smallest change in the concentration of
Therefore, appropriate tuning of an analyte that is required to bring a
electronics is required to ensure a stable change in the response of the biosensor.
Depending on the application, a good considered to be toxic materials of defense
resolution is required as most biosensor interest [14]; for use in artificial implantable
applications require not only analyte devices such as pacemakers [15] and other
detection but also measurement of prosthetic devices [16]; and sewage
concentrations of analyte over a wide epidemiology [17].
working range. Another term associated
with linearity is linear range, which is
defined as the range of analyte
concentrations for which the biosensor
response changes linearly with the
concentration.

4. Applications of biosensors
Biosensors have a very wide range of
applications that aim to improve the quality
of life. This range covers their use for
environmental monitoring, disease
detection, food safety, defense, drug
discovery and many more. One of the main
applications of biosensors is the detection of Major areas of applications for
bimolecules that are either indicators of a biosensors
disease or targets of a drug. For example,
electrochemical biosensing techniques can
5. Conclusions
be used as clinical tools to detect protein In vitro molecular biosensors are nowadays
cancer biomarkers [7–8]. Biosensors can ubiquitous in biomedical diagnosis as well
also be used as platforms for monitoring as a wide range of other areas such as point-
food traceability, quality, safety and of-care monitoring of treatment and disease
nutritional value [9,10]. These applications progression, environmental monitoring, food
fall into the category of ‘single shot’ control, drug discovery, forensics and
analysis tools, i.e. where cost-effective and biomedical research. Biosensor devices
disposable sensing platforms are required require the interaction of different
for the application. On the other hand, an disciplines and rely on very distinct aspects
application such as pollution monitoring such as the study of interactions of bio-
[10,11] requires a biosensor to function from recognition elements with bimolecular
a few hours to several days. Such biosensors analyte, immobilization of bimolecules on to
can be termed ‘long-term monitoring’ solid surfaces, development of anti-fouling
analysis tools. Whether it is long-term surface chemistries, device design and
monitoring or single shot analysis, fabrication, integration of biology with the
biosensors find their use as technologically devices, micro fluidics, on-chip electronics,
advanced devices both in resource-limited packaging, sampling techniques, etc.
settings and sophisticated medical set-ups:
e.g. with applications in drug discovery [12– The rapid development in the field of
13]; for the detection of a number of biosensors over the past decades, both at the
chemical and biological agents that are research and product development level, is
due mainly to: (i) developments in 4. Nelson J.M., Griffin E.G. Adsorption of
miniaturization and micro fabrication invertase. J. Am. Chem.
technologies; (ii) the use of novel bio- Soc. 1916;38:1109–1115. doi:
recognition molecules; (iii) novel 10.1021/ja02262a018 [Google Scholar]
nonmaterial’s and nanostructure devices;
and (iv) better interaction between life 5. Heineman W.R., Jensen W.B. Leland C.
scientists and engineering/physical Clark Jr. (1918–2005) Biosens.
scientists. Bioelectron. 2006;21:1403–1404. doi:
10.1016/j.bios.2005.12.005 [Google
A range of transduction techniques can be Scholar]
used in biosensing devices, including
electrochemical sensors (Chapter 8), field- 6. Guilbault G.G., Montalvo J.G., Jr Urea-
effect transistors (Chapter 9), optical sensors specific enzyme electrode. J. Am. Chem.
(Chapter 10) and acoustic-sensitive sensors Soc. 1969;91:2164–2165. doi:
(Chapter 11). Lateral flow systems (Chapter 10.1021/ja01036a083. [Google Scholar]
12) have great promise for the development
of inexpensive and easy to use point-of-care 7. Jolly P., Formisano N., Estrela P. DNA
sensors beyond the traditional pregnancy aptamer-based detection of prostate
tests, whereas lab-on-chip devices (Chapter cancer. Chem. Pap. 2015;69:77–89. doi:
13) integrate different micro fabrication 10.1515/chempap-2015-0025. [Google
techniques enabling biosensors to be Scholar]
employed in a wide range of applications
using minute sample volumes and minimum 8. Formisano N., Jolly P., Bhalla N.,
sample preparation. Cromhout M., Flanagan S.P., Fogel R. et
al. Optimisation of an electrochemical
impedance spectroscopy aptasensor by
exploiting quartz crystal microbalance
6. References with dissipation signals. Sens. Actuators
1. Cremer M. Über die Ursache der B. 2015;220:369–375. doi:
elektromotorischen Eigenschaften der 10.1016/j.snb.2015.05.049. [Google
Gewebe, zugleich ein Beitrag zur Lehre Scholar]
von den polyphasischen 9. Sharma T.K., Ramanathan R., Rakwal
Elektrolytketten. Z. Biol. 1906;47:562– R., Agrawal G.K., Bansal V. Moving
608. [Google Scholar] forward in plant food safety and security
2. Hughes W.S. The potential difference through nanobiosensors: adopt or adapt
between glass and electrolytes in contact biomedical
with the glass. J. Am. Chem. technologies? Proteomics. 2015;15:1680–
Soc. 1922;44:2860–2867. doi: 1692. doi: 10.1002/pmic.201400503
10.1021/ja01433a021. [Google Scholar] [Google Scholar]

3. Griffin E.G., Nelson J.M. The influence 10. Van Dorst B., Mehta J., Bekaert K.,
of certain substances on the activity of Rouah-Martin E., De Coen W., Dubruel
invertase. J. Am. Chem. P., et al. Recent advances in recognition
Soc. 1916;38:722–730. doi: elements of food and environmental
10.1021/ja02260a027. [Google Scholar] biosensors: a review. Biosens.
Bioelectron. 2010;26:1178–1194. doi:
10.1016/j.bios.2010.07.033 [Google 17. Yang Z., Kasprzyk-Hordern B., Frost
Scholar] C.G., Estrela P., Thomas K.V. Community
sewage sensors for monitoring public
11. Gavrilescu M., Demnerová K., health. Environ. Sci.
Aamand J., Agathos S., Fava F. Emerging Technol. 2015;49:5845–5846. doi:
pollutants in the environment: present and 10.1021/acs.est.5b01434 [Google Scholar]
future challenges in biomonitoring,
ecological risks and bioremediation. N.
Biotechnol. 2015;32:147–156. doi:
10.1016/j.nbt.2014.01.001. [Google
Scholar]
12. Bhalla N., Di Lorenzo M., Pula G.,
Estrela P. Protein phosphorylation analysis
based on proton release detection:
potential tools for drug discovery. Biosens.
Bioelectron. 2014;54:109–114. doi:
10.1016/j.bios.2013.10.037. [Google
Scholar]
13. Bhalla N., Formisano N., Miodek A.,
Jain A., Di Lorenzo M., Pula G., et al.
Plasmonic ruler on field-effect devices for
kinase drug discovery
applications. Biosens.
Bioelectron. 2015;71:121–128. doi:
10.1016/j.bios.2015.04.020. [Google
Scholar]
14. Paddle B.M. Biosensors for chemical
and biological agents of defence
interest. Biosens.
Bioelectron. 1996;11:1079–1113. doi:
10.1016/0956-5663(96)82333-5. [Google
Scholar]
15. Grayson A.C.R., Shawgo R.S.,
Johnson A.M., Flynn N.T., Li Y., Cima
M.J., et al. A BioMEMS review: MEMS
technology for physiologically integrated
devices. Proc. IEEE. 2004;92:6–21. doi:
10.1109/JPROC.2003.820534 [Google
Scholar]
16. Parker K.K., O'Grady M. Porous
electroactive hydrogels and uses thereof.
8,999,378 B2. U.S. Pat. 2015