International Journal of Emerging Technology and Advanced Engineering

Website: www.ijetae.com (ISSN 2250-2459, Volume 2, Issue 3, March 2012)

Biochip Technology –A Gigantic Innovation

Prof. T.Venkat Narayana Rao1, Sai Sukruthi.G2, Gloria Raj3
Department of Computer Science and Engineering, Hyderabad Institute of Technology and Management [HITAM]
Gowdavally, R.R. District, A.P, India

tvnrbobby@yahoo.com
sukruthi363@gmail.com

Abstract— The development of biochips is a major drive of
the rapidly growing biotechnology industry, which
encompasses a very assorted range of research efforts
including genomics, proteomics, and pharmaceuticals,
among other activities. Advances in these areas are giving
scientists new methods for unraveling the complex
biochemical processes occurring inside cells, with the larger
goal of understanding and treating human diseases. At the
same time, the semiconductor industry has been steadily
perfecting the science of micro-miniaturization. The merging
of these two fields in recent years has enabled
biotechnologists to begin packing their traditionally bulky
sensing tools into smaller and slighter spaces i.e. so called
biochips. These chips are essentially miniaturized
laboratories that can perform hundreds or thousands of
simultaneous biochemical reactions. These paper insights on
how biochips enable researchers to quickly screen large
numbers of biological analytes for a variety of purposes,
from disease diagnosis to detection of bioterrorism agents.
Keywords: Biochips, genetic, DNA, Membrane, Micro
arraying.
I. INTRODUCTION AND H ISTORY OF B IOCHIP
A biochip is a collection of miniaturized test sites
(microarrays) arranged on a solid substrate that allows
many tests to be performed at the same time in order to
achieve higher throughput and pace [4]. Typically, a
biochip's surface area is no larger than a fingernail. Like a
computer chip that can perform millions of mathematical
operations in one second, a biochip can perform thousands
of biological reactions, such as decoding genes in few
seconds.
A genetic biochip is designed to freeze into place the
structures of many short strands of DNA
(deoxyribonucleic acid), the basic chemical instruction
that establishes the characteristics of an organism.
Effectively, it is used as a test tube for real chemical
samples[1]. A specially designed microscope can
determine where the sample hybridized with DNA strands
in the biochip. Biochips would help dramatically in
accelerating the identification of the estimated 80,000
genes in human DNA, an ongoing world-wide research
collaboration known as the Human Genome Project.
The microchip is described as a sort of word search
function that can quickly sequence DNA[2].
In addition to genetic applications, the biochip is being
used in toxicological, protein, and biochemical research.
Biochips can also be used to rapidly detect chemical
agents used in biological warfare so that defensive
measures can be considered. The development of biochips
has a long history, starting with early work on the
underlying sensor technology[3]. One of the first portable,
chemistry-based sensors was the glass pH electrode,
invented in 1922 by Hughes. Measurement of pH WAS
accomplished by detecting the potential difference
developed across a thin glass membrane selective to the
permeation of hydrogen ions; this selectivity was achieved
by exchanges between H+ and SiO sites in the glass. The
basic concept of using exchange sites to create
permselective membranes was used to develop other ion
sensors in subsequent years. For example, a K+ sensor was
produced by incorporating valinomycin into a thin
membrane. Over thirty years elapsed before the first true
biosensor (i.e. a sensor utilizing biological molecules)
emerged. In 1956, Leland Clark published a paper on an
oxygen sensing electrode. This device became the basis
for a glucose sensor developed in 1962 by Clark and
colleague Lyons which utilized glucose oxidase molecules
embedded in a dialysis membrane. The enzyme
functioned in the presence of glucose to decrease the
amount of oxygen existing in the oxygen electrode,
thereby relating oxygen levels to glucose concentration.
This and similar biosensors became known as enzyme
electrodes, and are still in use today[5]. In 1953, Watson
and Crick announced their discovery of the now familiar
double helix structure of DNA molecules and set the stage
for genetics research that continues to the present day .
The development of sequencing techniques in 1977 by
Gilbert and Sanger enabled researchers to directly read
the genetic codes that provide instructions for protein
synthesis. This research showed how hybridization of
complementary single oligonucleotide strands could be
used as a basis for DNA sensing. Two additional
developments enabled the technology used in modern
DNA-based biosensors.

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 International Journal of Emerging Technology and Advanced Engineering
Website: www.ijetae.com (ISSN 2250-2459, Volume 2, Issue 3, March 2012)
First, in 1983 Kary Mullis invented the polymerase
chain reaction (PCR) technique, a method for amplifying
DNA concentrations. This discovery made possible the
detection of extremely small quantities of DNA in
samples [6]. In 1986 Hood and co-workers devised a
method to label DNA molecules with fluorescent tags
instead of radiolabels, thus enabling hybridization
experiments to be observed optically. The rapid
technological advances of the biochemistry and
semiconductor fields in the 1980s led to the huge scale
development of biochips in the 1990s. At this time, it
became obvious that biochips were largely a platform
technology which consisted of several separate, yet
integrated components. Figure 1 shows the makeup of a
typical biochip platform. The actual sensing component
(or the "chip") is just one piece of a complete analysis
system. Transduction must be done to translate the actual
sensing event (DNA binding, oxidation or reduction, etc.)
into a format understandable by a computer, which then
enables additional analysis and processing to produce a
final, human readable output. The multiple technologies
needed to make a successful biochip from sensing
chemistry, to micro arraying, to signal processing,
requires a true multidisciplinary approach [4]. One of the
first commercial biochips was introduced by Affymetrix.
This "GeneChip" products contain thousands of individual
DNA sensors for use in sensing defects, or single
nucleotide polymorphisms (SNPs), in genes such as p53 (a
tumor suppressor) and BRCA1 and BRCA2 (related to
breast cancer). The chips are produced using
microlithography techniques traditionally used to fabricate
integrated Circuits.
Figure 1: The Biochip Platform
Biochips are a platform that require, in addition to
microarray technology, transduction and signal processing
technologies to output the results of sensing experiments.
Today, a variety of biochip technologies are either in
development or being commercialized.
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Numerous advancements continue to be made in
sensing research that enables new platforms to be
developed for emerging applications. Cancer diagnosis
through DNA is just one market opening. A variety of
industries currently desire the capability to simultaneously
screen for a wide range of chemical and biological agents,
with purposes ranging from testing public water systems
for disease agents to screening airline cargo for
explosives. Pharmaceutical companies wish to
combinatorially screen drug candidates against target
enzymes. To achieve these ends, DNA, RNA, proteins,
and even living cells are being employed as sensing
mediators on biochips. Numerous transduction methods
can be employed including surface plasmon resonance,
fluorescence, and chemiluminescence [7]. The particular
sensing and transduction techniques chosen depend on
factors such as price, durability, and reusability.
II. T HE MAKING O F B IOCHIP
The microarray the dense, two-dimensional grid of
biosensors is the critical component of a biochip platform.
Typically, the sensors are deposited on a flat substrate,
which may either be passive (e.g. silicon or glass) or
active, the latter consisting of integrated electronics or
micromechanical devices that perform or assist signal
transduction. Surface chemistry is used to covalently bind
the sensor molecules to the substrate medium. The
fabrication of microarrays is non-trivial and is a major
economic and technological hurdle that may ultimately
decide the success of future biochip platforms[8]. The
primary manufacturing challenge is the process of placing
each sensor at a specific position (typically on a Cartesian
grid) on the substrate. Various means exist to attain the
placement, but typically robotic micro-pipetting or micro-
printing systems are used to place tiny spots of sensor
material on the chip surface. As each sensor is unique,
only a few spots can be placed at a time. The low-
throughput nature of this process results in high
manufacturing costs.
Fodor and colleagues developed a unique fabrication
process (later used by Affymetrix) in which a series of
microlithography steps are used to combinatorially
synthesize hundreds of thousands of unique, single-
stranded DNA sensors on a substrate one nucleotide at a
time. One lithography step is needed per base type; thus, a
total of four steps are required per nucleotide level.
Although this technique is very powerful in that many
sensors can be created simultaneously, it is currently only
feasible for creating short DNA strands (15–25
nucleotides). A reliability and cost factor restricts the
number of photolithography steps that can be done.
 International Journal of Emerging Technology and Advanced Engineering
Website: www.ijetae.com (ISSN 2250-2459, Volume 2, Issue 3, March 2012)
Furthermore, light-directed combinatorial synthesis
techniques are not currently possible for proteins or other
sensing molecules.
As mentioned above most microarrays consist of a
cartesian grid of sensors. This approach is used mainly to
map or encode the coordinate of each sensor to its
function. Sensors in these arrays typically use a universal
signaling technique (e.g. fluorescence), thus making
coordinates their only identifying feature. These arrays
must be made using a serial process (i.e. requiring
multiple, sequential steps) to ensure that each sensor is
placed at the correct position.
Random fabrication, in which the sensors are placed at
arbitrary positions on the chip, is an alternative to the
serial method. The tedious and expensive positioning
process is not required, enabling the use of parallelized
self-assembly techniques. In this approach, large batches
of identical sensors can be produced; sensors from each
batch are then combined and assembled into an array. A
non-coordinate based encoding scheme must be used to
identify each sensor. As the figure shows, such a design
was first demonstrated (and later commercialized by
Illumina) using functionalized beads placed randomly in
the wells of an etched fiber optic cable[10]. Each bead
was uniquely encoded with a fluorescent signature.
However, this encoding scheme is restricted in the number
of unique dye combinations that can be used and
successfully differentiated.
III. B IOCHIP ARRAY T ECHNOLOGIES
Microarrays are not limited to DNA analysis, protein
microarrays, antibody microarray and chemical compound
microarray but can also be produced using biochips.
Randox Laboratories Ltd. has launched the first protein
Biochip Array Technology analyzer in 2003. In protein
Biochip Array Technology, the biochip replaces the
ELISA plate or cuvette as the reaction platform. The
biochip is used to simultaneously analyze a panel of
related tests in a single sample, producing a patient
profile. The patient profile can be used in disease
screening, diagnosis, monitoring disease progression or
monitoring treatment [11]. Performing multiple analyses
simultaneously, described as multiplexing, and allows a
significant drop in processing time and the amount of
patient sample required. Biochip Array Technology is a
fresh application of a familiar methodology, using
sandwich, competitive and antibody capture
immunoassays. The difference from conventional
immunoassays is that the capture ligands are covalently
attached to the surface of the biochip in an ordered array
rather than in solution.
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In sandwich assays an enzyme-labeled antibody is used,
in competitive assays an enzyme labeled antigen is used.
On antibody-antigen binding a chemiluminescence
reaction produces light. Detection is by a charge-coupled
device (CCD) camera. The CCD camera is a sensitive and
high resolution sensor able to accurately sense and
quantify very low levels of light. The test regions are
located using a grid pattern then the chemiluminescence
signals are analyzed by imaging software to rapidly and
simultaneously quantify the individual analytes.
IV. B IOCHIP T ECHNOLOGY AND IT C OMPONENTS
The current biochip implant system is actually a fairly
simple device. Today’s, biochip implant is basically a
small (micro) computer chip, inserted under the skin, for
identification purposes. The biochip implant system
consists of two components; a transponder and a reader or
scanner. The transponder is the actual biochip implant.
The biochip system is a radio frequency identification
(RFID) system, using low-frequency radio signals to
communicate between the biochip and reader. The reading
range or activation range, between reader and biochip is
small, normally between 2 and 12 inches.
The transponder: The transponder is the actual
biochip implant. It is a passive transponder it contains no
battery or energy of it's own. In comparison, an active
transponder would provide it’s own energy source,
normally a small battery. Because the passive biochip
contains no battery, or nothing to wear out, it has a very
long life, up to 99 years, and no maintenance overheads.
Being passive, it's inactive until the reader activates it by
sending it a low-power electrical charge. The reader
"reads" or "scans" the implanted biochip and receives
back data (in this case an identification number) from the
biochip. The communication between biochip and reader
is via low-frequency radio waves.
A. Components of Biochip
The biochip-transponder consists of four parts; computer
microchip, antenna coil, capacitor and the glass capsule.
B. Computer Microchip
The microchip stores a unique identification number from
10 to 15 digits long. The storage capacity of the current
microchips is limited, capable of storing only a single ID
number. AVID (American Veterinary Identification
Devices), claims their chips, using a nnn-nnn-nnn format,
has the capability of over 70 trillion unique numbers. The
unique ID number is etched or encoded via a laser onto
the surface of the microchip before assembly. Once the
number is encoded it is impossible to alter. The microchip
also contains the electronic circuitry necessary to transmit
the ID number to the reader.
 International Journal of Emerging Technology and Advanced Engineering
Website: www.ijetae.com (ISSN 2250-2459, Volume 2, Issue 3, March 2012)
C. Antenna Coil The biochip is inserted into the subject with a
This is normally a simple, coil of copper wire around a hypodermic syringe as shown in figure 4. Injection is safe
ferrite or iron core. This tiny, primitive, radio antenna and simple, comparable to common vaccines. Anesthesia
receives and sends signals from the reader or scanner. is not required nor recommended. In dogs and cats, the
biochip is usually injected behind the neck between the
D. Tuning Capacitor shoulder blades. Trovan, Ltd., markets an implant,
The capacitor stores the small electrical charge (less featuring a patented "zip quill", which you simply press
than 1/1000 of a watt) sent by the reader or scanner, which in, no syringe is needed. According to AVID "Once
triggers the transponder. This activation allows the implanted, the identity tag is virtually impossible to
transponder to send back the ID number encoded in the retrieve‖. The number can never be altered."
computer chip. As radio waves are utilized to
communicate between the transponder and reader, the
capacitor is tuned to the same frequency as the reader.

E. Glass Capsule
The glass capsule holds the microchip, antenna coil and
capacitor. It is a small capsule, the smallest measuring 11
mm in length and 2 mm in diameter, about the size of an
uncooked grain of rice as shown in figure 2 and 3. The
capsule is made of biocompatible material such as soda
lime glass. After assembly, the capsule is hermetically
(air-tight) sealed, so no bodily fluids can touch the
electronics inside. Because the glass is very smooth and
susceptible to movement, a material such as a Figure 4: Hypodermic Syringe
polypropylene polymer sheath is attached to one end of
the capsule. This sheath provides a compatible surface F. The reader
which the bodily tissue fibers bond or interconnect, The reader consists of an "exciter" coil which creates an
resulting in a permanent placement of the biochip. electromagnetic field that, via radio signals, provides the
necessary energy (less than 1/1000 of a watt) to "excite"
or "activate" the implanted biochip. The reader also
carries a receiving coil that receives the transmitted code
or ID number sent back from the "activated" implanted
biochip. This all takes place very fast, in milliseconds.
The reader also contains the software and components to
decode the received code and display the result in an LCD
display. The reader can include a RS-232 port to attach a
computer.

Figure 2: Actual Biochip Capsule G. How it works

The reader generates a low-power, electromagnetic
field, in this case via radio signals, which activates the
implanted biochip as depicted in figure 5. This activation
enables the biochip to send the ID code back to the reader
via radio signals. The reader amplifies the received code,
converts it to digital format, decodes and displays the ID
number on the reader's LCD display. The reader must
normally be between 2 and 12 inches near the biochip to
communicate. The reader and biochip can communicate
through most materials.

Figure 3. Components of a Biochip

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 International Journal of Emerging Technology and Advanced Engineering
Website: www.ijetae.com (ISSN 2250-2459, Volume 2, Issue 3, March 2012)
Figure 5: The Biochip Reader
V. MAJOR ROLE O F B IOCHIP IN MEDICAL F IELD
In their fight against cancer, doctors have just gained an
impressive new weapon to add to their armory.
Researchers at the U.S. Department of Energy's Argonne
National Laboratory have developed a chip that can save
lives by diagnosing certain cancers even before patients
become symptomatic. The new technology, known as a
biochip, consists of a one-centimeter by one centimeter
array that comprises anywhere between several dozen and
several hundred dots or small drops. Each of these drops
contains a unique protein, antibody or nucleic acid that
will attach to a particular DNA sequence or antigen.
A tumor, even in its earliest asymptomatic phases, can
slough off proteins that find their way into a patient's
circulatory system. These proteins trigger the immune
system to kick into gear, producing antibodies that
regulate which proteins belong and which do not.
Antibodies are the guardians of what goes on in the body,"
as mentioned by Tim Barder, president of Eprogen, Inc.,
which has licensed Argonne's biochip technology to
search for new biomarkers that indicate cancer. If a
cancer cell produces aberrant proteins, then it is very
likely that the patient will have an antibody profile that
differs from that of a healthy person. You can look for
similarities and differences in autoantibody profiles to
look for clues and markers that provide early indicators of
disease.
In their hunt for cancer indicators, Eprogen uses a
process called 2-dimesional protein fractionation, which
sorts thousands of different proteins from cancer cells by
both their electrical charge and their hydrophobicity or
stickiness.
The 2-D fractionation process creates 960 separate
protein fractions, which are then arranged in a single
biochip containing 96-well grids. Eprogen scientists then
probe the microarrays with known serum or plasma auto-
antibodies produced by the immune systems of cancer
patients.
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By using cancer patients own auto-antibodies as a
diagnostic tool, doctors could potentially tailor treatments
based on their personal autoantibody profile [6]. This
technology is really designed to take advantage of the
information contained within the patient's own biology
and what that makes this technique unique is that
scientists can use the actual expression of the patient's
disease as a means of obtaining new and better diagnostic
information that doctors could use to understand and fight
cancer better.
Biochips have already shown promise in diagnostic
medicine, according to Argonne biologist Daniel
Schabacker, who developed the technology. In addition to
Eprogen, three other companies have licensed biochips.
One of these companies, Akonni Biosystems of Frederick,
Md., has already produced dozens of assays, which it
markets under the TruArray® brand name. Similarly
Safeguard Biosystems, licensed biochips for veterinary
diagnostic applications. When a biochip is tailored to
detect upper respiratory diseases which is exposed to a
swab when taken from a patient's mouth, for instance, the
binding patterns of the proteins or nucleic acids in the
array cause the dots to "light up" when scanned and
analyzed with a computer. Computer algorithms decode
the dot pattern produced by the biochip. The computation
of statistical likelihood of each possible infection and
provide this information to the doctor.
Suppose someone shows up to the hospital with an
upper respiratory infection ailment. The first thing a
doctor is going to want to know is whether the infection is
viral or bacterial, this is especially true in pediatrics. And
ideally, they'd really like to have a single test that they can
run very rapidly that will identify exactly which disease
you have from a dozen top targets.
The development of products like TruArray will soon
revolutionize doctors' ability to quickly diagnose a number
of diseases. For example, while existing rapid strep tests
performed by many pediatricians take only a few minutes
to process, they yield so many false negatives those
doctors routinely send out the samples for subsequent
rounds of more thorough, time consuming and expensive
analysis [3].
Platform lies in the fact that we can screen a single
sample for multiple viral and bacterial infections at the
same time. Soon, doctors will no longer need to order as
many expensive and time-consuming tests, and can
instead obtain accurate diagnoses that will enable them to
quickly provide their patients with targeted treatment
strategies. Though the analysis of a sample on a biochip
can take 30 minutes, scientists can have much more
confidence in the accuracy of the diagnosis. Biochips give
us the ability to run a test that allows your doctor to figure
out exactly what you're suffering from during the time that
you're in his or her office.
 International Journal of Emerging Technology and Advanced Engineering
Website: www.ijetae.com (ISSN 2250-2459, Volume 2, Issue 3, March 2012)
While biochips will allow doctors to more quickly and
authoritatively explain you, they might also be used for
patients who exhibit symptoms of much more serious
infections. By adding just a few more drops to the chip's
array, Schabacker claimed, lab technicians could test for a
whole slate of biotoxins and especially virulent diseases
from the plague to smallpox to anthrax [4].
Other infections, such as those caused by Multidrug
Resistant Tuberculosis (MDR-TB) and the often deadly
Methicillin-resistant Staphylococcus aureus (MRSA), can
be quickly diagnosed with biochips like Akonni's
TruArray assay, according to Daitch.
The most important thing with these types of infections
is that you have to be right and get the answer quickly.
Some of the tests out there, though marginally quicker
than ours, are so inaccurate that they're almost useless.
Especially when you're talking about anthrax or plague,
you have to be confident in your diagnosis or else risk
causing a panic.
VI. B IOCHIP IS UP TO T HE MARK O F T HE MONSTER
The biochip technology was originally developed for
monitoring fisheries as mentioned, it’s use now includes,
over 300 zoos, over 80 government agencies in at least 20
countries, pets also , electronic branding of horses,
monitoring lab animals, fisheries, endangered wildlife,
automobiles, garment tracking, hazardous waste and
according to the experts.. To date, over 7 million animals
have been chipped. The major biochip companies are
A.V.I.D. (American Veterinary Identification Devices),
Trovan Identification Systems, and Destron-Fearing
Corporation. And according to most modern-day sayings
the implanted biochip is the soon-coming in humans also.
VII.COMMON MYTHS ABOUT BIOCHIPS IMPLANTS
A. With a biochip can be used to track you or your
pet’s location, anywhere in the world-
The current biochip and reader has a maximum range of
12 inches. Pet’s are located by shelters, vets and find a lost
pet and reading it’s biochip. The technology does not exist
to globally locate something as small as a biochip.
B. A biochip can store and update your financial,
medical, demographic data, basically everything about
you-
The common scenario is, an implanted biochip can be
scanned to pay for groceries, obtain medical procedures,
conduct financial transactions.
C. One major concern with a implanted biochip is theft-
According to the authorities a chip implant would
contain your financial world, medical history, health care
it would contain your "electronic life".
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If cash no longer existed and if the world’s economy
was totally chip oriented; — there would be a huge
"black-market" for chips! Since there is no cash and no
other bartering system, criminals would cut off hands and
heads, stealing "rich-folks" chips.
VII. CONCLUSION
Biochips promises to bring genomics, the study of all
the genes in existing organisms, out of the research
laboratory and into the everyday practice of medicine. If
genomics delivers on its promise, health care will shift
from a focus on detection and treatment to a process of
prediction and prevention. The biochip space lies at the
intersection between high technology chip
manufacturing, signal processing, software skills and
more traditional molecular biology and genomics. The
market for biosensors and biochips is interdisciplinary
and growing and has applications in a number of core
research areas. This paper presents a valuable context
addition for those in both academia and industry. As
this fast maturing field already boasts sales of products,
biochips are likely to have a significant business future.
We can expect that advances in microfluidic biochip
technology will enable the miniaturization of devices
that will allow highly sensitive analysis of complex
biological interactions in real time that to with a low
cost perception.
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Biographies

Professor T.Venkat Narayana Rao, received B.E in

Computer Technology and Engineering from Nagpur University,
Nagpur, India, M.B.A (Systems), holds a M.Tech in Computer Science
from Jawaharlal Nehru Technological University, Hyderabad, A.P., India
and a Research Scholar in JNTU. He has 20 years of vast experience in
Computer Science and Engineering areas pertaining to academics and
industry related I.T issues. He is presently Professor and Head,
Department of Computer Science and Engineering, Hyderabad Institute
of Technology and Management [HITAM], Gowdavally, R.R.Dist., A.P,
INDIA. He is nominated as Editor and Reviewer to 25 International
journals relating to Computer Science and Information Technology. He
is currently working on research areas which include Digital Image
Processing, Digital Watermarking, Data Mining, Network Security and
other Emerging areas of Information Technology. He can be reached at
tvnrbobby@yahoo.com

Sai Sukruthi.G, Student, Department of Computer

Science and Engineering, Hyderabad Institute of Technology and
Management [HITAM], JNTUH , Gowdavally, R R Dist, A.P, INDIA.

Gloria Raj, Student, Department of Computer

Science and Engineering, Hyderabad Institute of Technology and
Management [HITAM], JNTUH, Gowdavally, R R Dist, A.P, INDIA.

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