Highly sensitive MEMS Biosensor for the detection of

Dengue Virus
A Major Project
Report
Submitted in partial fulfillment of the requirements for
the award of the degree of

Bachelor of Technology
in
Department of Electronics and Communications
By

A.Charitha 13003095
K.Praveena 13004124
M.Chandan 13004175
P.Phanindra 13004436

Under the supervision of

Mr.Syed Shameem
Assoc Professor

Department of Electronics and Communications

K L University, Green Fields,
Vaddeswaram- 522502, Guntur(Dist), Andhra Pradesh, India.
April 2017
 K L UNIVERSITY
GREEN FIELDS, VADDESWARAM

Declaration

The Project Report entitled “Highly Sensitive MEMS Biosensor for the detection of
Dengue Virus” is a record of bonafide work of “A.Charitha (13003095),K.Praveena
(13004124), M.Chandan(13004175), P.Phanindra(13004436)”, submitted in partial
fulfillment for the award of B.Tech in “Electronics & Communication Engineering”
to K L University. The results embodied in this report have not been copied from any
other department/University/Institute.

A.Charitha 13003095
K.Praveena 13004124
M.Chandan 13004175
P.Phanindra 13004436
 K L UNIVERSITY
GREEN FIELDS, VADDESWARAM

Certificate

This is to certify that the project report entitled “Highly Sensitive MEMS Biosensor
for the detection of Dengue Virus” is being submitted by “A.Charitha
(13003095),K.Praveena(13004124), M.Chandan(13004175), P.Phanindra(13004436)”
submitted in partial fulfilment for the award of B.Tech in “Electronics &
Communication Engineering” to K L University is a record of bonafide work
carried out under our guidance and supervision.

The results embodied in this report have not been copied from any other
department/University/Institute.

Signature of project guide Signature of H.O.D

Mr.Syed Shameem Dr.A.S.C.S.Sastry
 ACKNOWLEDGEMENTS

Working on this project which is taken from a real-time problem is interesting

and enduring. We have broadened our knowledge in the field of Satellite
Communications. Many helped us in this project directly or indirectly and we are
indebted to them. So we would like to extend our gratitude to them in this report.
Firstly we would like to extend our earnest gratitude to our guide Mr.Syed
Shameem, Assoc Professor, Department of ECE for her constant guidance, valuable
suggestions and facilities required to utilize in during the course of our project.
Furthermore we would like to thank Dr.P.Satyanarayana Professor, Dept of
ECE and Dr.A.S.C.S.Sastry, HOD, Department of ECE for their instructions and
support.
We would like to thank Dr. K. SubbaRao, Principal, College of Engineering
for providing us with adequate facilities, ways and means by which we are able to
complete our project.
We would like to thank the entire teaching and non-teaching faculty and all our
friends who helped us in this course of the project.

By
A.Charitha 13003095
K.Praveena 13004124
M.Chandan 13004175
P.Phanindra 13004436

i
 ABSTRACT

Micro-Electro-Mechanical-System (MEMS) is a fast technology that carried different

ideas in the fields like biomedical. MEMS got many applications in biomedical.
Dengue is a breakborne fever disease which is caused by dengue virus. This can be
detected using MEMS bio-sensor. In this paper we use cantilever mechanism for the
early stage detection of the disease. Here we use antibodies that are the bio-elements
in the biosensor. The cantilever simulation result includes displacement and
capacitance measurement which is the best method for dengue detection. Based on the
amount of the displacement we can identify the severity of the disease.

ii
 TABLE OF CONTENTS

Acknowledgement I
Abstract ii
List of Figures Vi
List of Tables Viii
List of symbols ix
List of Acronyms x

S.No Title Page No

1. Introduction
1.1 Dengue Virus 1
1.1.1 Dengue virus genome 1
1.1.2 Replication of dengue virus 2
1.1.3 Dengue Virus Testing 3
1.1.4 Symptoms of dengue fever 4
1.1.5 Test result mean 5
1.1.6 Elisa Test(PCR) 7
1.1.7 Reverse Transcriptase PCR 9
1.2 MEMS 10
1.3 Biosensors 11
1.4 MEMS based biosensor 12
1.5 Cantilever 13
2. Introduction to software
2.1 COMSOL 15
2.2 COMSOL Simulation 17
3. Literature survey 18
4. Theoretical Analysis
4.1 Principle of Microcantilever 20
4.2 Biosensing Technique of Cantilever 22

iii
5. Experimental Design
5.1 Design of Microcantilever 23
5.2 Design Implementation 25
5.3 Cantilever design 29
5.4 Proposed Technique 34
6. Simulations and Results 37
7. Conclusion and References
Conclusion 39
References 41

iv
 LIST OF FIGURES

S.No Figure No FIGURE TITLE Page No

1 Fig 1 Aedes Aegypti Mosquito 1
2 Fig 2 Dengue Virus Genome 2
3 Fig 3 Dengue Virus Structure 2
4 Fig 4 Reproduction of Dengue Virus 3
5 Fig 5 Symptoms of Dengue Fever 4
6 Fig 6 Schematic representation of biosensor 11
7 Fig 7 Elements of biosensor 12
8 Fig 8 Structure of Cantilever beam 14
9 Fig 9 Flow chart process for cantilever design 17
10 Fig 10 Immobilization of antibodies on cantilever surface 21
and bending after biomolecular interaction
11 Fig 11 Schematic representation of microcantilever 21
12 Fig 12 Specificity of analyte 22
13 Fig 13 Simple cantilever design 23
14 Fig 14 Point load is applied for simple cantilever design 24
15 Fig 15 Deflection due point load is applied 24
16 Fig 16 Cantilever with the separation of 1µm 25
17 Fig 17 Cantilever with the separation of 1µm with a 25

Displacement of 5.0956*10^6

18 Fig 18 Cantilever with the separation of 5µm 26

19 Fig 19 Cantilever with the separation of 5µm with a 26

Displacement of 5.3536*10^6

20 Fig 20 Plot for different eigen values Vs for different 28

Frequencies

21 Fig 21 Simple cantilever design 29

v
22 Fig 22 Cantilever with the force of 1N with a 29

Displacement of 1.6*10^-6

23 Fig 23 Cantilever with the force of 2N with a 30

Displacement of 3.19*10^-6

24 Fig 24 Cantilever with the force of 3N with a 30

Displacement of 4.79*10^-6

25 Fig 25 Cantilever with the force of 4N with a 31

Displacement of 6.39*10^-6

26 Fig 26 Cantilever with the force of 5N with a 31

Displacement of 7.98*10^-6

27 Fig 27 Graph between boundary load and 32

Displacement

28 Fig 28 Cantilever design 34

29 Fig 29 Displacement of cantilever before binding 34

30 Fig 30 Displacement of cantilever after antibody 35

Binding with NS1

31 Fig 31 Displacement of cantilever after antibody 35

Binding with IgG

32 Fig 32 Displacement of cantilever after antibody 36

Binding with IgM

vi
 LIST OF TABLES

S.No TABLE No TABLE NAME Page No

1 1 Result of antibody testing 6

2 2 Eigen values vs Displacement 27

3 3 Boundary load vs Displacement 32

4 4 Simulation results of cantilever beam 37

5 5 Difference between displacement of 37

Cantilever beam before and after binding

6 6 Functionality of LED 38

vii
 LIST OF SYMBOLS

Symbol Description
Hc Height of the Rain
H0 Isothermal height at sea level
L Length of the Slant path
 Angle of the elevation
AL Specific Attenuation
F Frequency in GHz
 Path elevation angle
D Diameter of the antenna
 Efficiency of the antenna
Deff Effective Diameter
HL Height of the turbulent layer
Nwet Wet term of radio refractivity
As Scintillation Fade depth

viii
 LIST OF ACRONYMS

VSAT Very Small Aperture Terminal

USAT Ultra Small Aperture Terminal
DTH Direct-To-Home
NGSO Non Geostationary Orbit
GSO Geostationary Orbit
FSS Fixed Satellite Service
LEO Low Earth Orbit
GEO Geostationary Earth Orbit
MEO Medium Earth Orbit
GPS Global Positioning System
DBS Direct Broadcast Satellite
ITU-R International Telecommunication Union Recommendation
FMT Fade Mitigation Techniques
MRR Micro Rain Radar
EIRP Effective Isotropic Radiated Power
LWC Liquid Water Content
ULPC Up Link Power Control
DLPC Down Link Power Control
TD Time Diversity
ARQ Automatic Repeat Request

ix
 CHAPTER 1
INTRODUCTION
 Introduction

1.1 DENGUE VIRUS:

Early stage detection is necessity for all non curable diseases in the present world.
The virus of dengue are individuals from the Flavivirus in the family Flaviviridae.
Dengue virus is considered as the major issue all over the world. Dengue is a
mosquito-borne tropical disease. Dengue is transmitted to the humans through an
infected mosquito. Incubation period starts when the dengue virus is transfer to the
humans. It normally lasts for 3-14 days. The clinical symptoms are high fever, bone
pain, headache, rashes. Dengue disease brought about by four firmly related infections
named as DEN-1, DEN-2, DEN-3, and DEN-4 infections are called serotypes. Each
has distinctive collaborations with the antibodies in human blood serum. The antigens
present in dengue virus are NS1, IgG and IgM.

Avoiding bitten by mosquitoes will be the best prevention for dengue fever since
there are no vaccines at present. Dengue shock syndrome and dengue hemorrhagic
fever are the forms that vary from mild to severe in dengue fever. Aedes aegypti and
aedes albopictus are the vectors for the transmission of dengue fever. Vectors are the
transmitters for any disease. In Asia, Africa, carribean countries the dengue is
restricted in these particular countries.

Fig.1 Aedes aegypti mosquito

1.1.1 Dengue virus genome:

Since the genome is capable of being translated into proteins, it is called as single
strand positive sense RNA. Genome consists of 10 proteins in which seven proteins

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 Introduction

are NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5 and three proteins are capsid,
membrane and envelope.

Fig.2 Dengue virus genome

Diameter of the dengue virus is 50 nm, and the shape of virus genome is spherical. The
structure of viral genome with C proteins is called nucleocapsid, which is surrounded by a
membrane named as viral envelope. It has a bilipid layer consists of E and M proteins. These
proteins prevent the entrance of virus into human cells by forming a protective layer.

Fig.3 Dengue virus structure

1.1.2 Replication of dengue virus:

When a human cell is attached by dengue virus, reproduction starts. The virus cell is
formed as a pouch when it is sealed. Sealing occurs when the human skin membrane
is folded around the virus after the attachment of virus to human skin. Endosomes are
usually referred as pouches since they carry big molecules for encouraging cell
growth. The dengue virus entry will be done in host cell when the normal process is
seized.

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 Introduction

Fig.4 Reproduction of dengue virus

Endocytosis is the process where host cell is attacked by the dengue virus. Cytoplasm
is released when the virus is went inwards into the host cell by fusing with endosomal
membrane. The viral genome is formed as the virus molecules are separated. It is
reproduced when viral RNA is capable of being translated and break into 10 proteins
which are discussed above.

As the dengue virus is replicating we have to control the reproduction of dengue virus
into the human body. So testing is required to detect or prevent the dengue fever.

1.1.3 Dengue virus testing :

When a person is attacked by the symptoms or possible identity to dengue, dengue

fever test is done. Laboratory tests are only possible since the symptoms are identical
to malaria and other diseases etc. Hence two tests are done for the detection of dengue
fever.

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 Introduction

1) Antibody testing:
This test is utilized to identify the present infection. There are 2 types of
antibodies in dengue virus. They are IgM and IgG. Identification of illness is
required for both the antibodies since they vary over the particular duration.
After the identification of disease, IgM antibodies are generated before IgG
and remains 7 to 10 days. After this there is typical decrease in IgM antibodies
since there will be increase in levels of blood. Then IgG antibodies will appear
after the IgM antibodies. But it appears in gradual and slow manner. There
will be an increase in infection and remains long time.
2) Molecular testing:
As fever occurs in a patient, it detects and relates the gene material in blood
till 7 days. PCR test is used in molecular testing.

Testing is done whenever the symptoms are appeared in human beings. Hence these
are the main symptoms through which we can detect the presence of virus.

1.1.4 Symptoms of dengue fever:

Fig.5.Symptoms of dengue fever

Depending on the severity of the disease the symptoms of dengue virus varies.

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 Introduction

There are three phases for dengue fever :

1) Febrile phase:
i) Sudden-onset fever.
ii) Headache.
iii) Mouth and nose bleeding.
iv) Vomiting.
v) Rashes.
vi) Diarrhea.
2) Critical phase:
i) Hypotension.
ii) Pleural effusion.
iii) Ascites.
iv) Gastrointestinal bleeding.
3) Recovery phase:
i) Altered level of consciousness.
ii) Seizures.
iii) Itching.
iv) Slow heart rate.

1.1.5 Test result mean:

Antibody test may be resulted as the titer which means either it contains IgG or IgM,
otherwise the tests may be declared as negative or positive.

If the IgG and IgM tests are positive then the person is affected recently by the virus.
If the antibody tests IgG is positive and IgM is negative then the person is affected by
the virus in past. Negative tests of both IgG and IgM can be reported as the person is
not affected by the virus and the symptoms are resulted as another disease.

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 Introduction

Results of antibody testing can be seen in the following table:

Table 1: Result of antibody testing

In molecular testing, PCR test is not upto extent. But this is the most accurate test
which detects the presence of virus. Similarly as in the antibody testing, if the test is
positive, then the result is concluded as the presence of dengue virus. If the test is
negative, then there is no infection.

At the duration of essential DENV contamination, IgM antibody is the first

immunoglobulin to show up while IgG antibody is noticed after the IgM antibody for
some days.

At the duration of DENV disease, IgG antibody shows up after onset of side effects
while IgM antibodies shows up following for some days at low titer or even
imperceptible in a few persons.

DENV NS1 is an exceptionally used glycoprotein which is communicated as both

proteins and membranes. Discharged NS1 has been distinguished going from 2–0.04
µg¨mL'1 in the serum of dengue-contaminated patients at the early phases of the
infection.

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 Introduction

1.1.6 ELISA TEST(PCR):

PCR method is a research center strategy method utilized for doing an extensive
number of duplicates of small areas of DNA from a little part of gene particle. Hence
the procedure is known as "intensifying" the DNA & empowers particular qualities
important to be identified.

The DNA is comprised of rehashing groupings of four parts – adenine, thymine,

guanine, and cytosine. These arrangements shape two strands that are stick together in
a twofold helix structure by hydrogen bonds. Every 50% of the helix is a supplement
to other helix. In people, it is distinction in the succession of the parts on each strand
of DNA that prompts the identity of every individual's gene cosmetics. The plan of
the bases in every quality is utilized to deliver RNA, which thus creates a protein.
There are around 25,000 qualities in a human genome, and articulation of these
qualities prompts the creation of an expansive number of proteins that make up our
bodies. The DNA of different living beings, for example, microscopic organisms and
infections is likewise made out of thousands of various qualities that code for
proteins.

The PCR method is done in a few stages in an instrument. That instrument increments
and decrements the temperature of the example at characterized interims at the
duration of technique.

1. The initial step or cycle of PCR is to isolate the strands of DNA by expanding the
temperature of the example that carries the DNA of intrigue. This is called denaturing
the DNA.

2. When the strands isolated, the specimen is cooled somewhat and forward and invert
preliminaries are summed and permitted to tie to the one DNA strand. Preliminaries
are small arrangements of parts are done particularly to perceive and tie to the area of
DNA to be intensified, which are the certain succession of parts those are a piece of
the quality or qualities of intrigue. Preliminaries are called "front" and "back" to the
course that the parts inside the segment of DNA are duplicated.

3. When two preliminaries append to each and every strand of the DNA, a DNA
compound that duplicates the DNA succession on every 50% of the helix for front to

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 Introduction

the invert preliminary, shaping two twofold strand areas of DNA, each and every with
single half and other single new half. Taq polymerase is a protein found in a
bacterium that develops in extremely heated water. Polymerases duplicate DNA does
new strands. The Taqpolymerase is particularly useful for research center testing in
the fact that it doesn't separate at high temperatures expected by PCR.

4. When warmth is connected once more, each of the two twofold strands isolate to
make four single strands and after cooling, the preliminaries and polymerase acts as to
do four twofold strand areas. These 4 strands ends up plainly eight in the following
cycle, eight wind up noticeably sixteen, etc.

5. In the range of 30 to 40 revolutions, upwards of a billion duplicates of the first

DNA segment can be delivered and are then accessible to be utilized as a part of
various atomic symptomatic tests. The procedure had been done and mechanized as a
billion duplicates of the first DNA will be created inside a couple of hours.

The above strategy can be utilized, for instance, to distinguish certain qualities in a
man's DNA, for example, these related with disease or hereditary issue, or it might be
utilized to recognize hereditary material of microscopic organisms or infections that
are bringing on a contamination.

These are only a couple of cases of lab tests that utilization PCR:

1) JAK2

2) KRAS

3) LYME DISEASE

4) PERTUSSIS

5) HPV

Constant PCR is like PCR aside from that information are acquired as the
intensification procedure is occurring (i.e., "continuous") instead of at an endorsed
endpoint and abbreviates the ideal opportunity for the test from overnight to a couple
of hours. This strategy is utilized to quantify DNA that is available in a specimen.

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 Introduction

1.1.7 Reverse Transcriptase PCR:

This strategy utilizes PCR to enhance RNA. RNA is a solitary stranded nucleic
corrosive particle and should be made into DNA before it can be enhanced. The
expansion of another strand that is the supplement of RNA is accomplished by the
catalyst called Reverse Transcriptase (RT) and an antisense (turn around)
groundwork. The preliminary ties to the single stranded RNA and the protein RT
duplicates the RNA strand to make a solitary stranded DNA, which it then duplicates
to make a twofold stranded DNA particle. The twofold stranded atom can now be
opened up by PCR. Location can likewise be by continuous techniques.

Here are two cases of research facility tests that utilization RT-PCR:

• HIV viral load

• HCV

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 Introduction

1.2 MEMS
Microelectromechanical systems are the innovation of small particles, especially those
with motion parts. It converges in the nanoscale into nanoelectromechanical systems
and nano-technology. MEMS are independent and particular from the speculative
vision of sub-atomic nanotechnology or sub-atomic gadgets. MEMS are comprised of
segments in the vicinity of 1 and 100 micrometers in size, and MEMS devices for the
most part range in size from 20 micrometers to a millimeter (i.e. 0.02 to 1.0 mm).
They more often than not comprise of a important unit that procedures information
(the microchip) and a few parts that interface with the surroundings, for example,
microsensors. The standard develops of traditional material science are not generally
adequate. In view of the huge surface region to volume proportion of MEMS, surface
impacts, for example, electrostatics and wetting command upon volume impacts, for
example, inactivity or warm mass.

MEMS are small micro machined systems that are typically framed on
small chips for various purposes. These are silicon based structures and are produced
by etching and fabrication techniques. Microactuators, microsensors, microelectronics
and microstructures are components of MEMS. MEMS are full-grown in the
developing field of medical and nanotechnology. MEMS are used to develop
microscale bio-sensors which will be used in lot of biological operations. It is also
used for several commercial and industry applications. In this paper, MEMS based
biosensor is used for fast detection of the dengue virus.

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 Introduction

1.3 BIOSENSORS:
A biosensor is a logical machine, utilized for the identification of an analyte, that joins
a natural segment with a physicochemical identifier. The touchy natural component
(e.g. tissue, microorganisms, organelles, cell receptors, catalysts, antibodies, nucleic
acids, and so forth.) is a naturally determined material or biomimetic part that
collaborates (ties or perceives) with the analyte review. The organically touchy
components can likewise be made by natural designing. The transducer or the finder
element(works in a physicochemical way,optical, piezoelectric,electrochemicaletc.)
changes the sign coming about because of the association of the analyte with the
natural component into another sign (i.e., changes) that can be all the more effectively
measured and evaluated. The biosensor peruser gadget with the related hardware or
sign processors those are fundamentally in charge of the show of the outcomes in an
easy to understand way. These now and again represents the most costly piece of the
sensor machine, nonetheless it is conceivable to produce an easy to use show that
incorporates transducer and delicate component. This had been risen as a subset of
mems gadget for applications in bio-medical technology and therapeutic machines.
The elements of biosensor are analyte, bio-element and transducer. An interaction of
analyte with the bio-element that makes an effect that the transducer that converts to
an electrical signal. The bio-element may be an protein, enzyme, an antigen or an
antibody etc. Biosensor have two functions i) change of biomolecular recognition to
electrical signal. ii) Bio-element that identifies the target analyte. For a maximum
throughput cantilever biosensor is used in any biomedical applications. Regarding a
physiological process, biosensor is utilized to detect, transmit and record the
information. Selectivity and specificity are the major constraints for the performance
of biosensors. There are different types of biosensors are present based on bio-
element and transducer. An ideal biosensor should contain the characteristics of
enough resolution, dynamic range, accuracy, repeatability and speed of response.

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 Introduction

Fig.6 Schematic representation of bio-sensor

1.4 MEMS BASED BIO-SENSOR:

A MEMS-based biosensor is a biosensor which is acknowledged by microfabrication
innovation and exploits the little size. It joins a natural segment with a physiochemical
detector, for example, a micro-operation. It is an uncommon class of synthetic sensor
that exploits the high taking and affectability of organically dynamic particles. It
includes immuno, protein and microorganism sensors. This comprises of 3 sections:
an analyte acknowledgment component, a transducer whose system might be
electrochemical, optical etc. When the analyte acknowledgment component, the
analyte is particularly perceived by a naturally touchy.

Fig.7 Elements of biosensor

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 Introduction

1.5 CANTILEVER:
Simulation displaying had been done utilizing COMSOL Multiphysics programming
since it has the ability for configuration, demonstrating, and reenactment of MEMS
applications. In this recreation, the cantilever is compelled towards one side and is
suspended free at the flip side.

The cantilever is an inflexible auxiliary component, for example, a bar or a plate,

moored at just a single end to a (normally vertical) bolster from which it is projecting.
Cantilevered bars are the most universal structures in the technology of
microelectromechanical systems. An early case of a MEMS cantilever is the
Resonistor, an electromechanical solid resonator. MEMS cantilevers are usually
created from silicon(Si), silicon nitride (Si3N4), or polymers. The creation procedure
ordinarily includes undermining the cantilever structure to discharge it, regularly with
an anisotropic wet or dry scratching system. Without cantilever transducers, nuclear
drive microscopy would not be conceivable. An extensive number of research
gatherings are endeavoring to create cantilever clusters as biosensorsfor restorative
analytic applications. MEMS cantilevers are likewise discovering application as radio
recurrence channels and resonators. The MEMS cantilevers are ordinarily made up of
asunimorphs or bimorphs.

The key favorable position of MEMS cantilevers is their inexpensiveness and

simplicity of creation in huge exhibits. The test for their useful application depends on
the square and cubic conditions of cantilever execution particulars on measurements.
These linear conditions imply that cantilevers are very delicate to variety in different
parameters, especially the thickness as this is by and large hard to precisely gauge. In
any case, it has been demonstrated that thickness of microcantilever will be definitely
calculated and then this variety may be evaluated. lingering stress can likewise be
troublesome, so it should be controlled.

1) COMSOL is a limited component analyser, and solves and recreation

programming for different material science and programming applications.
2) MEMS Module gives predetermined UIs related demonstrating apparatuses,
included to as material science interfaces, for an assortment of coupled

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 Introduction

physical science, including EMF structure, warm figures, or liquid structure

operations.

Fig.8 Structure of Cantilever beam

The main advantages of cantilever beam are

1) Easy to design
2) Requirement for the design will be one fixed support
3) These are tough and the span is higher than a simple beam.
4) Because of one fixed support, thermal coefficient and ground movement can
easily be calculated.

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 CHAPTER -2
INTRODUCTION TO SOFTWARE
 Introduction to Software

2.1 COMSOL:

COMSOL Multiphysics is an instrument used for demonstrating and reenacting

designing undertakings. The issues we need to resolve, in actuality, are constantly in
fact of multiphysics solution. In this manner it is required to consider connection
between at least two material science areas at one time. COMSOL Multiphysics
software is characterized for taking care of those unpredictable issues. This operation
gives one of a kind easy to understanding the work condition and furthermore gives
extensive variety of devices to the quick and the viable examination. COMSOL
Multiphysics permits you to limit the requirements for real models, abbreviate item
improvement times and accomplish considerable funds in the advancement procedure.
As this displaying approach helps you to grow better items and convey them speedier
to the present market condition.

PC replication has turned into a basic piece of science and designing. Advanced
investigation of segments, specifically, is imperative, when growing newly introduced
items or enhancing outlines. Now a days an expansive range of choices for
reenactment is accessible; specialists utilize anything from fundamental programming
dialects to different level packages executing developed techniques. In spite of the
fact that each of these procedures has its own one of a kind traits, they all consists a
typical concern: While taking what makes programming, it's useful to recollect the
objective: you need a model that precisely delineates what occurs in this present
reality. A PC recreation condition is just an interpretation of genuine physical laws
into their virtual shape. How much improvement happens in the interpretation
procedure decides the precision of the subsequent model. It would be perfect, then, to
have a reenactment domain that incorporated the likelihood to add any physical
impact to your model. That is what really matters to COMSOL. It's an adaptable stage
that permits even beginner clients to model all applicable physical parts of their plans.
Propelled clients can go further and utilize their insight to create modified
arrangements, pertinent to their one of kind conditions. With this sort of
comprehensive demonstrating condition, COMSOL gives you the certainty to
fabricate the model you need with certifiable accuracy. Certain attributes of
COMSOL wind up noticeably obvious with utilize. Similarity emerges among these.
COMSOL requires that each kind of recreation incorporated into the bundle can be
consolidated with some other. This strict prerequisite really reflects what occurs in

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 Introduction to Software

this present reality. For example in nature, power is constantly joined by some warm
impact; the two are completely good. Authorizing similarity ensures reliable
multiphysics models, and the learning that, even as the COMSOL group of items
grows, you never need to stress over making a disengaged demonstrate again. Another
perceptible characteristic of the COMSOL stage is flexibility. As your displaying
needs change, so does the product. On the off chance that you end up needing
including another physical impact, you can simply include it. In the event that one of
the contributions to your model requires a recipe, you can simply enter it. Utilizing
apparatuses like parameterized geometry, intelligent lattice, and custom solver
groupings, you can rapidly adjust to the recurring patterns of your prerequisites. 2 |
Introduction COMSOL Multiphysics additionally has a few critical thinking benefits.
When beginning another venture, utilizing COMSOL helps you comprehend your
issue. You can try out different geometrical and physical attributes of your model, so
you can truly focus on the imperative plan challenges. The adaptable way of the
COMSOL condition encourages advance examination by making "imagine a scenario
in which" cases simple to set up and run. You can take your reproduction to the
creation level by enhancing any part of your model. Parameter scopes and target
capacities can be executed appropriate in the UI. From beginning to end, COMSOL is
an entire critical thinking instrument. As you turn into a more experienced client of
COMSOL, your trust in PC reenactment will develop. You will end up being a more
productive modeler, and the outcomes will demonstrate it. The rest of this
acquaintance is committed with give you a solid head toward this objective. After a
general prologue to the UI, a few instructional exercises will make you stride by
venture through specimen models that highlight critical elements. The enlightening
outlines give you a thought of COMSOL's capacity by related documents, works, and
implicit alternatives. Before the end you will be well on your approach to receiving
every one of the rewards that COMSOL brings to the table.

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 Introduction to Software

2.2 COMSOL SIMULATION:

The cantilevers are profoundly delicate structure. They empower simple discovery
and precise estimation of number of atoms appending to the surface. The discovery
underneath 1×104 cells is exceptionally troublesome with electrochemical strategy.
The primary use is standpoint over different strategies is refinement of the example is
not used and non particular operation won’t happen.

Fig.9 Flowchart process for cantilever design

Department of K L University, ECE Page||17

 CHAPTER-3

LITERATURE SURVEY
 Literature survey

LITERATURE FROM PAPERS

P.G.Gopinadh, V.R.Anitha in [3] and others proposed a paper in which they had given
that MEMS sensors are of low cost, low power and easily integratable. They used
microcantilever on biosensor for which it is used for bio-sensing. They had designed a
block diagram for analyte detection. The description is as given below:

A MEMS-based biosensor is a biosensor which is acknowledged by

microfabrication innovation and exploits the little size. It joins a natural segment with
a physiochemical detector, for example, a micro-operation. It is an uncommon class
of synthetic sensor that exploits the high taking and affectability of organically
dynamic particles. It includes immuno, protein and microorganism sensors. This
comprises of 3 sections: an analyte acknowledgment component, a transducer whose
system might be electrochemical, optical etc. When the analyte acknowledgment
component, the analyte is particularly perceived by a naturally touchy. The elements
of biosensor are analyte, bio-element and transducer. An interaction of analyte with
the bio-element that makes an effect that the transducer that converts to an electrical
signal. The bio-element may be an protein, enzyme, an antigen or an antibody etc.
Biosensor have two functions i) change of biomolecular recognition to electrical
signal. ii) Bio-element that identifies the target analyte. This paper concludes that
comsol simulation is utilized for various recent technologies such as CMOS BIO-
MEMS and nanotechnology.

Mr.Gulshan, P.Thakare and others in [4] proposed a paper in which they concluded
that microcantilever is the best way for any disease applications rather than
conventional cantilever models. The paper that the published is described below:

Early stage detection is necessity for all non curable diseases in the
present world. Microelectromechanical systems are the innovation of small particles,
especially those with motion parts. It converges in the nanoscale into
nanoelectromechanical systems and nano-technology. MEMS are independent and
particular from the speculative vision of sub-atomic nanotechnology or sub-atomic
gadgets. MEMS are comprised of segments in the vicinity of 1 and 100 micrometers
in size, and MEMS devices for the most part range in size from 20 micrometers to a
millimeter (i.e. 0.02 to 1.0 mm). They more often than not comprise of a important
unit that procedures information (the microchip) and a few parts that interface with

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 Literature survey

the surroundings, for example, microsensors. The standard develops of traditional

material science are not generally adequate. In view of the huge surface region to
volume proportion of MEMS, surface impacts, for example, electrostatics and wetting
command upon volume impacts, for example, inactivity or warm mass.

His-Kai Wang in [6] published a paper named “Dengue Virus” in the year 2012, in
which he discussed about the tests to perform for the detection of virus. The
description of the paper is discussed below:

Dengue fever caused by the dengue virus is the intense flavivirus-

borne tropical infections with the four serotypes. Till now, there are no such accurate
demonstrative instruments accessible for checking the infection action of dengue
fever. It is expected to build up a symptomatic machine with the qualities of
cheapness, simplicity to-utilize and power for the identification of dengue fever. In
the review, we have built up an ELISA test indicative device arranged by means of
wax print strategy by utilizing channeled paper. The antigens that we focused to
evaluate in the support framework are both non-basic protein 1 with the location
furthest reaches of around 100 pg/mL and the envelope particle with the weakened
infection culture soup of around 1000 times of serotype 2 dengue infection (just 2 μL
test). By the test, we trusted that this review could give knowledge on the
improvement of in-vitro demonstrative gadgets for dengue fever and different
maladies in the distinctive seperations of prescription.

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 CHAPTER-4

THEORETICAL ANALYSIS
 Analysis

4.1 PRINCIPLE OF MICROCANTILEVER:

The microcantilever consists of movable and fixed part. The principle of

microcantilever based biosensor is to convert the biological interactions into
nanomechanical motion. On the surface of cantilever material creates the free energy
due to reaction between the analyte and probe coating and this causes the
nanomechanical motion. These nanomechanical interactions can cause changes
capacitance value or piezo resistance of microcantilever material. As the probe
coating material is a sensitive layer, it specifies the analyte interaction. The response
of microcantilever occurs when there is a change produced by the external stimuli on
sensing layer. The principle lies in the change of physical or chemical responses to
mechanical response. One surface of cantilever is coated with antibodies, proteins,
enzymes and the other surface is not coated. The microcantilever beam is deflected at
free end due to biological responses causes on the other end of cantilever. Coating a
small amount of area with probe material the extreme end of microcantilever
antibodies results in static bending and enables to catch the antibodies which will be
targeted.

Fig.10 Immobilization of antibodies on cantilever surface and bending after

biomolecular interaction

Bending of beam can be detected using piezo resistance, optical method and
capacitance. This bending mechanism is detected in pico and femto gram. When a

Page | 20
 Analysis

blood sample of a patient is placed on the cantilever, the antigen and antibody
interaction makes to bending of the cantilever and detects weather the dengue
infection is present or not. Factors such as poisons ratio, spring constant and young’s
modulus are used for purpose of measurement of microcantilever. For attaining
sensitivity antigen and antibody pairing is natural gift of science. User specifications
like frequency changes and mass differentiations different for the detection principle
of microcantilever. For unique analyte recognition, cantilever has different coatings.

Fig.11 Schematic representation of microcantilever

4.2 BIOSENSING TECHNIQUE OF CANTILEVER:

There is a need for constantly monitoring the human body so that the harmful
diseases are detected at the early stage. By considering the growing pollution and
lifestyle of the people, a person getting affected by a disease is very high and there are
no natural resources that are pure because of pollution. Microcantilever based sensor
is used to identify the presence of the any target analyte by different coatings of
different sensitive materials in which the material should have the high degree of
specificity. This sensor is used to detect the dengue disease by applying specific
antibodies on the microcantilever. There are a lot of samples such as enzymes,
antibodies and DNA can be examined in medical purposes with the help of these
biosensors. Some elements such as glucose, pH factors etc are already examined and
are detecting the diseases like Dengue, HIV, tuberculosis and other infectious
diseases at the early stage by these biosensors. When analytes are restricted to the

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 Analysis

probe coating surface, then only the surface reaction takes place. Microcantilevers
normally consists of the 10 to 500µm length, width of 100µm and thickness of 2µm.
Microcantilevers can make a transformation in medical period. When sensitive layer
applied on cantilever surface, target material is detected in microcantilever. Change in
properties like displacement, frequency detects the amount of target material used in
the cantilever. Change in properties occurs when the target molecules binds with the
coating material. The resulting change is measured when more target molecules binds
to coating material. The bending of microcantilever is equivalent to number of the
analyte atoms or molecules that binds to probe coating. Deflecting stiffness of the
cantilever can increase the functionality of cantilever sensitivity.

Fig.12 Specificity of analyte

Page | 22
 CHAPTER-5
EXPERIMENTAL DESIGN
 Design

5.1 DESIGN OF MICROCANTILEVER

The Cantilever design for the detection of dengue is designed. In this

design when the point load is applied, deflections occur. Based on the deflection of
cantilever the dengue is detected. Based on the frequency of deflection we can say
the severity of the disease. For a particular antigen we get a specific load or
weight, applying this point load on the cantilever we get the deflections.

In this, a basic cantilever is designed. The cantilever deflects with

different frequencies. All the deflections are showed for different egien
frequencies. The maximum frequency is 3.5747*10^6 when the egien frequency
is 1.250369e7.The minimum frequency is 3.3204*10^6 when the egien frequency
is 1.812068e6.

Materials used are: Quartz, HFO2, Gold

Fig:13 Simple cantilever design

Page | 23
 Design

Fig.14 Point load is applied for simple Cantilever

design

Fig.15 Deflection due point load is applied

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 Design

5.2 DESIGN IMPLEMENTATION:

Implementation of cantilever with different heights

Fig.16 Cantilever with the separation of 1µm

Fig.17 Cantilever with the separation of 1µm with a displacement of 5.0956*10^6

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 Design

Fig.18 Cantilever with the separation of

5µm

Fig.19 Cantilever with the separation of 5µm with a displacement of 5.3536*10^6

Page | 26
 Design

Displacement of variance heights of cantilever design:

Distance b/w plates Eiegen frequencies Displacement
(um) (um)
1 1.353544*e6 4.9056*e6
4.994634*e6 4.8386*e6
8.45598*e6 5.6956*e6
1.76545*e6 5.4137*e6
2.364296*e6 5.1863*e6
2.9138*e6 5.017*e6
2 1.355715*e6 5.0025*e6
5.00788*e6 4.9354*e6
8.468109*e6 5.1962*e6
1.76593*e7 5.522*e6
2.367538*e7 5.2887*e6
2.919909*e7 5.1185*e6
3 1.352926*e6 5.1116*e6
4.988565*e6 5.0408*e6
8.451913*e6 5.3095*e6
1.765132*e7 5.6414*e6
2.363302*e7 5.0439*e6
2.910927*e7 5.2288*e6
4 1.353443*e6 5.0968*e6
4.991503*e6 5.0267*e6
8.45989*e6 5.2942*e6
1.765333*e7 5.6247*e6
2.36422*e7 5.3884*e6
2.912644*e7 5.2121*e6
5 1.353504*e6 5.1569*e6
4.99591*e6 5.0869*e6
8.454721*e6 5.3966*e6
1.765564*e7 5.692*e6
2.36404*e7 5.4591*e6
2.914697*e7 5.27152*e6
Table 2: eigen values vs displacemnt

Page | 27
 Design

GRAPH:

Fig.20 Plot for different eigen values vs for different frequencies

Page | 28
 Design

5.3 Cantilever design

Fig.21 simple cantilever design

SIMULATIONS:

F=1N

Fig.22 Cantilever with the force of 1N with a displacement of 1.6*10^-6

Page | 29
 Design

F=2N

Fig.23 Cantilever with the force of 2N with a displacement of 3.19*10^-6

F=3N

Fig.24 Cantilever with the force of 3N with a displacement of 4.79*10^-6

Page | 30
 Design

F=4N

Fig.25 Cantilever with the force of 4N with a displacement of 6.39*10^-

6

F=5N

Fig.26 Cantilever with the force of 5N with a displacement of 7.98*10^-6

Page | 31
 Design

RESULTS:

The following table gives displacement when force is given

Boundary load(N) Displacement(µm)

1 1.60*(10^-6)
2 3.19*(10^-6)
3 4.79*(10^-6)
4 6.39*(10^-6)
5 7.98*(10^-6)
6 9.58*(10^-5)
7 1.12*(10^-5)
Table 3: boundary load vs displacement

Graphical representation:

Fig.27 Graph between boundary load vs displacement

Page | 32
 Design

ANALYSIS:

Capacitance & Voltage

C = εε0A/d

Where, ε is the dielectric constant of medium between plates and

ε = 8.85*10^-12 pF/m

A = the area of the plates and d the distance between

them. Consider A=8um*0.5um, d=5um

ε0 =8.85419 pF/m (Permittivity of free space)

ε=10(Permittivity of dielectric)

Then C=0.708pf

Then V=C/Q

Q= charge on capacitor plate

Page | 33
 Design

5.4 PROPOSED TECHNIQUE:

A simple cantilever beam with 25µm length, 105µm width and 15µm thickness
shown in figure 2.1 is arranged. Another three strips with measurements of 100µm
length, 25µm width and 2.5µm thickness is merged into the simple cantilever beam.
SiO2 is the material that is used for designing comprises properties such as thickness
of 2200 kg/m3, Young's modulus of 70 × 109 dad and Poisson's proportion of 0.17. A
channel of 75µm×15µm×1.5µm is taken on each strip to test the blood sample. The
deportation of blood sample gives the severity of the disease.

Fig.28 Cantilever design

Fig.29 Displacement of cantilever before binding

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 Design

Fig.30 Displacement of cantilever after antibody binding with

NS1

Fig.31 Displacement of cantilever after antibody binding with

IgG
The displacement of cantilever before binding with an antigen is shown. When an
NS1 antigen of 310KDa is applied, binding of antobody with antigen takes place. Due
to this there is an increase in the stress which results in the displacement of cantilever
beam as shown

Similarly Fig show the displacement of cantilever beam after binding with IgG and
IgM antigens respectively.

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 Design

Fig.32 Displacement of cantilever after antibody binding with IgM

Page | 36
 CHAPTER-6

SIMULATIONS AND RESULTS

 Results

DISCUSSION OF RESULTS

Binding of antigens with antibodies increases the displacement of the cantilever. The
results of the displacement before and after binding of antigens with antibodies is
shown in Table 1.

S.No Antigens Force (N) Total displacement (um)

Before binding After
binding
1 Ns1 5.471537097562324e- 3.76e-17 4.86e-16
21
2 IgG 2.866043241580265e- 3.76e-17 2.54e-16
21
3 IgM 1.589351252149056e- 3.76e-17 1.41e-15
20
Table 4: Simulation results of cantilever beam

The values of these displacements are used to detect weather the disease is
existence or not in the body. Table 2 gives the difference in the displacement before
and after binding of antibody with antigens. This difference in the displacement is
used for the detection of dengue virus. This technique of cantilever is an easy way to
identify the disease.

S.no Antigen Displacement (um)

1 NS1 4.484e-16
2 IgG 2.164e-16
3 IgM 1.372e-15
Table 5: Difference between displacement of cantilever beam before and after
binding

The material used in the cantilever for the detection is sio2. The usage of different
materials gives different values of displacement.

TRANSDUCER FOR CANTILEVER:

The displacement that is obtained results in the development of the capacitance. This
capacitance is used to generate the voltage using a transducer. Fig 3.1 shows the
representation of conversion of displacement to current. As the capacitance that is

Page | 37
 Results

generated is very less amplifier is used to amplify the voltage that is obtains from the
transducer. LED can be connected to the design at each beam so that the stage of the
disease can be identified easily.

Fig Block diagram of the functionality of LED

The fuctionality of this is shown in the Table 3. When an antibody gets binded with
the respective antigen, the respective beam gets deflected. Due to this the LED
connected to that beam glows. This is very easy to identify the stages of disease
without any effort. Using this LED's we can know the stage disease.

Stages Cantilever beam 1 Cantilever beam 2 Cantilever beam

3
1 1 0 0
2 0 1 0
3 0 0 1
Table 6: Functionality of the LED

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CHAPTER-7

CONCLUSION
 Conclusion

CONCLUSION

The design of the biosensor for the fast detection of dengue virus based on the
deflections of the cantilever is used to measure the displacements is more useful and
easy. Different stages of the dengue disease give different deflections which result in
the displacement. The displacement difference of cantilever beam before and after
binding of antibody with antigens are measured. It is acknowledged that this
cantilever design is more methodical to identify the presence of the dengue virus than
usual techniques. Microcantilever is more efficient than other conventional models.

Page | 39
REFERENCES
 References

REFERENCES

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book chapter 17, pp.139-183, 2008.

[2] C.Gerber, H.P.Lang and M.Henger “Nanomechanical cantilever array sensors”,

Handbook of technology, Springer, pp.443-459.

[3] P.G.Gopinadh, V.R.Anitha, “Microcantilever based biosensors for disease

detection applications”, JMB vol 4, no-4, august 2015.

[4] Mr.Gulshan, P.Thakare, Anupnage, “Design and analysis of high sensitive

biosensor using MEMS”, IJISET, vol 2 Issue 6, june 2015.

[5] U.Hashim, M.W.Al-Mufti and T.Adam, “simulation of nano lab on chip devices
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[6] His-kai wang, “dengue virus” ,(9.F.10): SC-70569, 2012.

[7] K.U.Kirstein, C.Vancura and Y.Li, “Monolithic rersonant-cantilever based CMOS

microsystem for biochemical-sensing” IEEE Transactions on circuits and systems,
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[8] H.S.Lang, M.Hegner, C.Gerber, “cantilever array sensors” Materials today, 2005.

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[10] P.Sangeetha and A.V.Juliet, “Biosensor for tuberculosis detection using MEMS
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[11] T.Thundat and K.M.Hansen, “Microcantilever biosensors,” Methods, col.37,

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[12] Yael Nemirosky, “NEMS/MEMS Cantilever based biosensor”.

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[14] Yuan, Qun-Feng Liu, chen-Lin Zhang, yu-wu, Yun-Jiang rao and Gang-Ding
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