Nanobiosensor

Chapter 1

INTRODUCTION

The most widely accepted definition of a biosensor is: “an analytical device
which incorporates a biologically active element with an appropriate physical
transducer to generate a measurable signal proportional to the concentration of
chemical species in any type of sample”
Biomedical engineering is the application of engineering principles and
techniques to the medical field. The development of biomedical engineering is
responsible for improving healthcare diagnosis, monitoring and therapy. Biosensors
are analytical devices those are used to detect the sensitive biological elements such as
tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids,
etc.
There is no doubt that the increase interest for the development of new materials
applicable in electroanalytical techniques has been associated with the necessity of
control specific molecules present in the environment or in more recently efforts, the
human body. This includes the possibility to improve the quality of life by
development of efficient electrochemical devices and biodevices. More than the use
electrochemical devices to detect analytes is the challenge to develop more sensitive
and selective electrochemical devices that provide the possibility to detect small
quantities of molecules utilizing efficient transducing elements and specific
recognition materials for biosensing. The so called electrochemical biosensors are
based on a specific biological recognition element such as enzymes, antigens or
another biological molecule that interacts directly with a transducer element . In
general, a typical biosensor is composed for five parts (as illustrated in Fig. 1). (1)
Bioreceptors that bind of specific form to the analyte. (2) An electrochemically active
interface where specific biological processes occur giving rise to a signal. (3) A
transducer element that converts the specific biochemical reaction in an electrical
signal that is amplified by a detector circuit using the appropriate reference. (4) A

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signal processor (e.g. computer software) for converting the electronic signal to a
meaningful physical parameter describing the process being investigated, and finally,
(5) An proper interface to present the results to the human operator. Currently, the
biosensors can be applied to a large variety of samples including body fluids, food
samples, cell cultures and be used to analyze environmental samples.

1.1 Components of a typical biosensor

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1.2 Basic scheme of biosensor.

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CHAPTER 2
BACKGROUND

Biosensor, like any other instrument, has evolved throughout history. Anecdotally we
could say that the first biosensors were the canaries, as these birds were used in coal
mines to detect toxic gases. The canaries are dying earlier than people in the presence
of carbon monoxide and methane and are usually the most time singing that they did
not became an audible alarm. But beyond this anecdotal fact, one can say that the
father of these devices is Leland C. Clark Jnr., who in 1956 completed its work with
the electrode of O2, but not content with the idea of expanding its use to measure more
analytes in the human body sensors in 1962 proposed making “smarter”.
Subsequently, Guilbault and Montalvo detailed the first potentiometric enzyme
electrode based on immobilization of urease on ammonium-selective electrode. In
1975 this became a commercial reality, putting on sale the first glucose analyzer based
on amperometric detection of hydrogen peroxide in Ohio. This was the first biosensor
for sale of many that would be marketed later. In 1987 through the use of
electrochemical mediators immobilized enzyme are screen printed able to build the
“pen” for personal monitoring of blood glucose. Currently there are many biosensors
in which combine the wide diversity of biological components using various types of
transducers.
Medical physics is an area of increasing importance in hospitals and in
health-related occupations. Physics is used in medicine to diagnose illness and
disorder and to design appropriate treatment and solutions. Biomedical engineering is
a field of research of high importance in any sense around the world. Biomedical
engineering is also a very sensitive field of engineering measurement where delay of a
second can cause someone life’s to death. So Real time computing has great
importance in the field of biomedical engineering. There are always sensitive cases
where it needs to follow up the pulse rate, blood pressure etc for every single moment.
If one data is missed or cannot be processed in due time by the machine (biomedical
instrument) it may cause serious impact on the patient’s body. So real time patient

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monitoring or medicine testing equipment has great importance in healthcare. As we

know Bangladesh is very good in pharmaceuticals research and development. But due
to lack of medicine testing equipment they cannot prosper as expected. Cost effective
patient monitoring system has also great importance for giving proper treatment to
every people of the country. A real time patient monitoring and medicine testing
equipment will fulfill all the needs.

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Chapter 3
SYSTEM ANALYSIS

The analysis of the system is necessary to gain the prime objective properly. By
analyzing the system we get three major parts.

System Analysis

Biosensor Signal processing Visual representation

This part is consisting Transducer will send a RT Linux will receive

of bioreceptor measurable signal
and transducer. which is an Analog
Bioreceptor is a bio signal to signal
molecule that processing hardware.
recognizes the target After filter,
analyte and Transducer amplification and
is capable of noise cancellation the
converting the bio signal will be sent to
recognition event DAQ which will
into a measurable convert the signal to
signal. digital numeric value
and send to RT
Linux.
the signal from the
DAQ, process it and
then link to Linux GUI
to show it. Linux GUI
will be capable of
collecting, comparing,
analyzing the signal
and also process the
signal as necessary to
show it in the graphical
Interface System
Analysis Signal
processing Visual
Representation
Biosensor

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Chapter 4
BIOSENSORS
Elements of biosensors:
The major parts of the systems and also the components of the parts have been briefly
described below in the diagram.

Bioelement Transducer
Analyte
Electrical
signal

Biosensor
4.1 Block diagram of biosensor

Elements of Biosensor: A biosensor is consisting of two element bio-element and

sensor-element.
Bioreceptor is the bio-element and transducer is the sensor-element.
1. Bioreceptor: The bioreceptor is a bimolecular that recognizes the target analyte. It
can be enzyme, antibody, tissue, etc.
2. Transducer: The transducer should be capable of converting the bio recognition
event into a measurable signal. Typically, this is done by measuring the change that
occurs in the bioreceptor reaction. The signal can be electric potential, electric current,
mass, temperature, viscosity etc.

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Signal and different types of sensors:

Signals Sensors

ECG signal ECG Electrodes

Cardiac Output (CO) CBF sensor

measurement (flow
meter signal)

EMG signal measurement SX230 Electrode

Blood Pressure measurement

Respiratory Rate Rainbow Acoustic Sensor

Blood Pressure measurement Sphygmomanometer

Oxygen Saturation Pulseoximeter

Heart Rate Pulseoximeter

Body temperature LM35

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Chapter 5

SIGNAL PROCESSING
Signal processing is one of the major parts of the nanobiosensor. Signal will be
processed in two phase. First phase is analog signal processing coming from the
transducer of the biosensors. Second phase is digital signal processing and data
acquisition system. Data acquisition system will send digital numeric value to the RT
Linux.
Analog signal processing: The analog signal processing (ASP) will be done
immediately after the signal comes from transducer of the biosensor. The transducer
gives a signal that is electric in form. The signal will be filtered first. After the filter
process amplification will be done to increase the intensity of the signal. Then it is
needed to cancel the noise of the signal to get a proper signal. This whole process is
the ASP for the project.
.

Raw Filter Amplifi Noise Send the

signal cation cancellati data to
on DAQ

5.1 Analog Signal Processing

Data Acquisition: Data acquisition is the process of sampling signals that measure
real world physical conditions and converting the resulting samples into digital
numeric values that can be manipulated by a computer. Data acquisition systems
typically convert analog waveforms into digital values for processing.
The components of data acquisition systems include:
 Sensors that convert physical parameters to electrical signals.
 Signal conditioning circuitry to convert sensor signals into a form that can be
converted to digital values.

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 Analog-to-digital converters, which convert conditioned sensor signals to

digital values.
DAQ hardware is what usually interfaces between the signal and a PC. It could be in
the form of modules that can be connected to the computer's ports (parallel, serial,
USB). DAQ cards contain multiple components (multiplexer, ADC, DAC, TTL-IO,
high speed timers, RAM).
We will use the DAQ card which has 16 channels. The DAQ will convert the analog
signal to digital and make it appropriate so that can be manipulated by the computer.
After digitization, DAQ will send the data to Real Time Linux. The 16 channels of the
DAQ will bring the signal from 16 biosensors.

5.2 iWorx Data Acquisition System (HAI 118)

Visual representation

Visual representation is necessary to make the data accessible to the doctor and researcher.
Visual representation of data depends on three things. Initially the data will be received by RT
Linux. Since the data will be shown in a real time presentation it is needed to make a link to real
time data and graphical interface in Linux.

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RT Linux: Real time Linux will take the data passed from data acquisition card. After
processing the data in real time , RT-Linux will be linked to Non real time GUI in Linux to show
the output in user friendly way . RT Linux has now been used extensively in research purpose of
developing real time system.

Real Time Real Time Linux

Task 1
Task 0

Real Time Kernel (Virtual Machine Layer)

DAQ Interrupt control Hardware Target platform

5.3 Real time tasking in RT Linux.

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Reason behind RT Linux: There is a significant need for an open source hard real-
time experiment interface system that is free from the some limitations. It provides a
flexible, modular, and powerful general-purpose hard real-time experiment interface
system that is freely available to the scientific community. Let’s think of an ECG
simulator, a machine is continuously taking samples (heart bit rate) from human heart
which is brought through a 16 channel data acquisition card and passed it to computer.
Now The computer must receive the input from the data acquisition board, process the
signal to determine the input amplitude and send it to the simulator to obtain the
graphical representation of the patients heart condition which we call electro
cardiogram (ECG).This total analysis should be done let in 1ms.If somehow the
computer miss any of the samples or fail to analyze the signal within the predefined
time limit the consequence can be unpredictable. This is why the real Time analysis
comes in necessity. RT Linux can give nanosecond precision which is very much
suitable for biomedical experimentation. So as a sensitive biomedical issue RT Linux
is very much appropriate for the system. Another good reason for using RT Linux is it
is open source.
Linux GUI: The graphical user interface will be developed in Linux to show the
output. Linking Linux GUI to RT Linux is very much necessary for the process.
Linking will be done in GNU C programming language. Graphical interface will be
developed in QT creator and KDevelop. QT creator and KDevelop is open source
graphical interface development environment in Linux. The GUI will collect, show
and manage the data coming from RT Linux. The GUI will have option for saving data
so that it can be used in future for research work.

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Chapter 6
TYPES OF NANOBIOSENSOR
(BASED ON TRANSDUCER USED)
Transducer is an analytical tool which provides an output quantity having a given
relationship to the input quantity. Biosensors can be classified according the
transduction method they utilize. Most forms of transduction can be categorized in
four main classes: electrochemical, optical, piezoelectric and thermal detection.
1. Electrochemical
According to its type of operation, electrochemical sensors can be divided in two
groups: amperometric and potentiometric. In the case of the former, the response is
linear function of the concentration of the compound of interest. In the later, the
response (a voltage) is a logarithmic function of the concentration. Currently available
commercial electrodes basically belong to four types: those detecting cat ions, anions
and gases, and platinum electrodes which measure the current in redox reactions. The
ion selective electrodes, as well as those measuring pH, CO2 and NH4+ use the
potentiometric principle. Another important class of potentiometric transducers are
semiconductor devices, such as field transistors (FETs), of which there are two main
types: metal oxide (MOSFETs) and ion-selective (ISFETs). On the other hand,
platinum electrodes, and those measuring O2 and H2O2, use the ampreometric
principle.

F
i
g
u
r
e
6.1 Potentiometric Nanobiosensor

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6.2 amperometric nanobiosensor

2. Optical
Conventional optical transducers were originally used for the measurement of
dissolved O2, CO2, and pH. Several types of photometric behavior are useful for the
construction of biosensors, namely: Visible/Ultraviolet absorption, Fluorescence,
Chemi or bioluminescence, Reflection spectroscopy and laser light scattering. The
principle of measurement is an immobilized reagent, able to interact with the analyte,
forms a complex with distinctive optical properties which can hence be monitored by
the sensor. Usually, the biological element is immobilized at one end of an optical
fiber, with both the excitation and detection components located at the other end. For
absorption-fluorescence-based transducers, the most widely used system has been
NAD(P)+/NAD(P)H-dependent dehydrogenases because NAD(P)H is known to
absorb light strongly at 340 nm and fluoresce at 460 nm. Luminescence and reflection
spectroscopy have been particularly useful in immunoassays. The main principle
involves the labeling of an antigen with a substance (like luminol or its derivatives)
which, when oxidized, produces visible light, and the labeling of the antibody with a
fluorescence compound such that emission from the luminol will excite fluorescence.
A similar approach can be used with firefly luciferins.

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6.3 Optical Nanobiosensor

3. Thermal
As most biologically-catalyzed reactions generate heat, the accurate measurement of
this heat generation, together with the specifically of the biological element, can be
used to construct a biosensor. Basically, this device is a small alorimeter,instrumented
with highly sensitive thermometers, usually able to detect temperature changes in the
range of 0.0001-0.050C. This technique can detect analyte concentrations as low as
10-5M.

4. Piezoelectric
Piezoelectric transducers are the smallest of balances. Crystals, such of those of quartz
have no center of symmetry and produce an electrical signal when stressed
mechanically (i.e. by applying some pressure on them). A crystal oscillates at a certain
frequency, which can be modulated by its environment. When the crystal is coated
with some material, the actual frequency depends on the mass of the crystal and the
coating. The resonant frequency can be measured with great accuracy hence making it
possible to calculate the mass of analyte adsorbed onto the crystal surface. This means,
that with these devices, detection limits are down to the pictogram level.
Antibodies,enzymes and antigens have been used as biological elements in these
devices.

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Chapter 7
APPLICATIONS

1. Health care
• Measurement of metabolites
• Drug discovery
• Diabetes
• Insulin therapy
• Artificial pancreas
2. Industrial process control
• Industrial bioprocess control and monitoring
• Bioreactor control
• On-Line control
• Off-Line control
3. Military applications
4. Environmental monitoring
• Air and water monitoring
• Tuning to application.

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An example of a microfluidic-based biosensor that can be incorporated onto a wristwatch. The

lab-on-a-chip system relies on manipulation of small volumes of fluid in microchannels using
microvalves

7.1 Glucose Biosensor

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Chapter 8
ADVATAGES AND DISADVANTAGES
Advantages:
 In a biosensor, no involvement of exogenous molecules of labels such as
conjugation with enzyme, radioactive fluorescence, or chemiluminescence
molecules.
 It is a detection of the target molecules, a key factor in early detection of
diseases such as breast cancer and AIDS.
 Rapid and high-throughput detection
 Detection processes are simple, user friendly, fast, and cost effective
 Reduced material requirement to fabricate, and easier recycling
 Novel properties and new capabilities
 Repetitive, portability, and stability.

Disadvantages
 Nanobiosensors are very sensitive and error prone.
 Nanobiosensors are still under infancy stage

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CONCLUSION
Nanotechnology is revolutionizing the development of biosensors in recent years.
Nanobiosensor research focuses on developing innovative technologies that have the
ability to make significant contributions in the areas of human and animal disease
marker detection, promising therapeutic compound identification and analysis, nano-
and biomaterials characterization, and biocatalyst development. These technologies
take the form of nanometrically engineered, biologically active surfaces, or liquid-
solid interfaces, and the tools necessary to characterize them. The emergence of
nanotechnology has opened up new horizons for the development of nanosensors and
nanoprobes with submicron-sized dimensions, that are suitable for
intracellularmeasurements. The attention is being focussed on the study of various
nanoeffects, such as the quantum size effect,mini size effect, surface effect, and
themacro-quantum tunnel effect, that is unique to nanomaterials, and is actually their
most attractive aspect. New nanomaterials and nanostructures need to be explored for
use in biosensors. Preferably, nanotechnology-based biosensors should be integrated
within tiny biochips with on-board electronics, sample handling and analysis. This will
greatly enhance their functionality, by providing devices that are small, portable, easy
to use, low cost, disposable, and highly versatile diagnostic instruments. Laser
nanosensors can be used for the in vivo analysis of proteins and biomarkers in
individual living cells. Even though a wide range of nanobiosensors have been
developed in the past two decades, the futuristic goal of low-cost, high throughput,
multiplexed clinical diagnostic lab-on-a-chip devices is yet to be truly realized. It is
still unclear which nanobiosensor architectures are best matched to which diagnostic
tasks.Moreover, nanobiosensors that are functional in the lab may not be of use in the
field or clinic for several reasons.Well-structured interdisciplinary research programs
that involve, life science researchers, engineers and physicians have to be conducted,
to reveal more refined and affordable biosensors.

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FUTURE SCOPE
The tremendous advancement in the sensor technologies are due to the great
technological demand for rapid, sensitive, and cost-effective biosensor systems in vital
areas of human activity such as health care, genome analysis, food and drink, the
process industries, environmental monitoring, defense, and security. At present, the
nanotechnology-based biosensors are at the early stage of development. The vast
applications of nanotechnology in such diverse fields such as semiconductors,
biological and medical devices, polymer composites, optical devices, dispersions, and
coatings are amazing.

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