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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)

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


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

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 Numerous advancements continue to be made in
chain reaction (PCR) technique, a method for amplifying sensing research that enables new platforms to be
DNA concentrations. This discovery made possible the developed for emerging applications. Cancer diagnosis
detection of extremely small quantities of DNA in through DNA is just one market opening. A variety of
samples [6]. In 1986 Hood and co-workers devised a industries currently desire the capability to simultaneously
method to label DNA molecules with fluorescent tags screen for a wide range of chemical and biological agents,
instead of radiolabels, thus enabling hybridization with purposes ranging from testing public water systems
experiments to be observed optically. The rapid for disease agents to screening airline cargo for
technological advances of the biochemistry and explosives. Pharmaceutical companies wish to
semiconductor fields in the 1980s led to the huge scale combinatorially screen drug candidates against target
development of biochips in the 1990s. At this time, it enzymes. To achieve these ends, DNA, RNA, proteins,
became obvious that biochips were largely a platform and even living cells are being employed as sensing
technology which consisted of several separate, yet mediators on biochips. Numerous transduction methods
integrated components. Figure 1 shows the makeup of a can be employed including surface plasmon resonance,
typical biochip platform. The actual sensing component fluorescence, and chemiluminescence [7]. The particular
(or the "chip") is just one piece of a complete analysis sensing and transduction techniques chosen depend on
system. Transduction must be done to translate the actual factors such as price, durability, and reusability.
sensing event (DNA binding, oxidation or reduction, etc.)
into a format understandable by a computer, which then II. T HE MAKING O F B IOCHIP
enables additional analysis and processing to produce a
final, human readable output. The multiple technologies The microarray the dense, two-dimensional grid of
needed to make a successful biochip from sensing biosensors is the critical component of a biochip platform.
chemistry, to micro arraying, to signal processing, Typically, the sensors are deposited on a flat substrate,
requires a true multidisciplinary approach [4]. One of the which may either be passive (e.g. silicon or glass) or
first commercial biochips was introduced by Affymetrix. active, the latter consisting of integrated electronics or
This "GeneChip" products contain thousands of individual micromechanical devices that perform or assist signal
DNA sensors for use in sensing defects, or single transduction. Surface chemistry is used to covalently bind
nucleotide polymorphisms (SNPs), in genes such as p53 (a the sensor molecules to the substrate medium. The
tumor suppressor) and BRCA1 and BRCA2 (related to fabrication of microarrays is non-trivial and is a major
breast cancer). The chips are produced using economic and technological hurdle that may ultimately
microlithography techniques traditionally used to fabricate decide the success of future biochip platforms[8]. The
integrated Circuits. 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
Figure 1: The Biochip Platform total of four steps are required per nucleotide level.
Although this technique is very powerful in that many
Biochips are a platform that require, in addition to sensors can be created simultaneously, it is currently only
microarray technology, transduction and signal processing feasible for creating short DNA strands (15–25
technologies to output the results of sensing experiments. nucleotides). A reliability and cost factor restricts the
Today, a variety of biochip technologies are either in number of photolithography steps that can be done.
development or being commercialized.

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 In sandwich assays an enzyme-labeled antibody is used,
techniques are not currently possible for proteins or other in competitive assays an enzyme labeled antigen is used.
sensing molecules. On antibody-antigen binding a chemiluminescence
As mentioned above most microarrays consist of a reaction produces light. Detection is by a charge-coupled
cartesian grid of sensors. This approach is used mainly to device (CCD) camera. The CCD camera is a sensitive and
map or encode the coordinate of each sensor to its high resolution sensor able to accurately sense and
function. Sensors in these arrays typically use a universal quantify very low levels of light. The test regions are
signaling technique (e.g. fluorescence), thus making located using a grid pattern then the chemiluminescence
coordinates their only identifying feature. These arrays signals are analyzed by imaging software to rapidly and
must be made using a serial process (i.e. requiring simultaneously quantify the individual analytes.
multiple, sequential steps) to ensure that each sensor is
placed at the correct position. IV. B IOCHIP T ECHNOLOGY AND IT C OMPONENTS
Random fabrication, in which the sensors are placed at
arbitrary positions on the chip, is an alternative to the The current biochip implant system is actually a fairly
serial method. The tedious and expensive positioning simple device. Today’s, biochip implant is basically a
process is not required, enabling the use of parallelized small (micro) computer chip, inserted under the skin, for
self-assembly techniques. In this approach, large batches identification purposes. The biochip implant system
of identical sensors can be produced; sensors from each consists of two components; a transponder and a reader or
batch are then combined and assembled into an array. A scanner. The transponder is the actual biochip implant.
non-coordinate based encoding scheme must be used to The biochip system is a radio frequency identification
identify each sensor. As the figure shows, such a design (RFID) system, using low-frequency radio signals to
was first demonstrated (and later commercialized by communicate between the biochip and reader. The reading
Illumina) using functionalized beads placed randomly in range or activation range, between reader and biochip is
the wells of an etched fiber optic cable[10]. Each bead small, normally between 2 and 12 inches.
was uniquely encoded with a fluorescent signature. The transponder: The transponder is the actual
However, this encoding scheme is restricted in the number biochip implant. It is a passive transponder it contains no
of unique dye combinations that can be used and battery or energy of it's own. In comparison, an active
successfully differentiated. transponder would provide it’s own energy source,
normally a small battery. Because the passive biochip
III. B IOCHIP ARRAY T ECHNOLOGIES contains no battery, or nothing to wear out, it has a very
long life, up to 99 years, and no maintenance overheads.
Microarrays are not limited to DNA analysis, protein Being passive, it's inactive until the reader activates it by
microarrays, antibody microarray and chemical compound sending it a low-power electrical charge. The reader
microarray but can also be produced using biochips. "reads" or "scans" the implanted biochip and receives
Randox Laboratories Ltd. has launched the first protein back data (in this case an identification number) from the
Biochip Array Technology analyzer in 2003. In protein biochip. The communication between biochip and reader
Biochip Array Technology, the biochip replaces the is via low-frequency radio waves.
ELISA plate or cuvette as the reaction platform. The
biochip is used to simultaneously analyze a panel of A. Components of Biochip
related tests in a single sample, producing a patient The biochip-transponder consists of four parts; computer
profile. The patient profile can be used in disease microchip, antenna coil, capacitor and the glass capsule.
screening, diagnosis, monitoring disease progression or
monitoring treatment [11]. Performing multiple analyses B. Computer Microchip
simultaneously, described as multiplexing, and allows a The microchip stores a unique identification number from
significant drop in processing time and the amount of 10 to 15 digits long. The storage capacity of the current
patient sample required. Biochip Array Technology is a microchips is limited, capable of storing only a single ID
fresh application of a familiar methodology, using number. AVID (American Veterinary Identification
sandwich, competitive and antibody capture Devices), claims their chips, using a nnn-nnn-nnn format,
immunoassays. The difference from conventional has the capability of over 70 trillion unique numbers. The
immunoassays is that the capture ligands are covalently unique ID number is etched or encoded via a laser onto
attached to the surface of the biochip in an ordered array the surface of the microchip before assembly. Once the
rather than in solution. 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

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

International Journal of Emerging Technology and Advanced Engineering
Website: www.ijetae.com (ISSN 2250-2459, Volume 2, Issue 3, March 2012)
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
Figure 5: The Biochip Reader Schabacker, who developed the technology. In addition to
Eprogen, three other companies have licensed biochips.
V. MAJOR ROLE O F B IOCHIP IN MEDICAL F IELD One of these companies, Akonni Biosystems of Frederick,
Md., has already produced dozens of assays, which it
In their fight against cancer, doctors have just gained an markets under the TruArray® brand name. Similarly
impressive new weapon to add to their armory. Safeguard Biosystems, licensed biochips for veterinary
Researchers at the U.S. Department of Energy's Argonne diagnostic applications. When a biochip is tailored to
National Laboratory have developed a chip that can save detect upper respiratory diseases which is exposed to a
lives by diagnosing certain cancers even before patients swab when taken from a patient's mouth, for instance, the
become symptomatic. The new technology, known as a binding patterns of the proteins or nucleic acids in the
biochip, consists of a one-centimeter by one centimeter array cause the dots to "light up" when scanned and
array that comprises anywhere between several dozen and analyzed with a computer. Computer algorithms decode
several hundred dots or small drops. Each of these drops the dot pattern produced by the biochip. The computation
contains a unique protein, antibody or nucleic acid that of statistical likelihood of each possible infection and
will attach to a particular DNA sequence or antigen. provide this information to the doctor.
A tumor, even in its earliest asymptomatic phases, can Suppose someone shows up to the hospital with an
slough off proteins that find their way into a patient's upper respiratory infection ailment. The first thing a
circulatory system. These proteins trigger the immune doctor is going to want to know is whether the infection is
system to kick into gear, producing antibodies that viral or bacterial, this is especially true in pediatrics. And
regulate which proteins belong and which do not. ideally, they'd really like to have a single test that they can
Antibodies are the guardians of what goes on in the body," run very rapidly that will identify exactly which disease
as mentioned by Tim Barder, president of Eprogen, Inc., you have from a dozen top targets.
which has licensed Argonne's biochip technology to The development of products like TruArray will soon
search for new biomarkers that indicate cancer. If a revolutionize doctors' ability to quickly diagnose a number
cancer cell produces aberrant proteins, then it is very of diseases. For example, while existing rapid strep tests
likely that the patient will have an antibody profile that performed by many pediatricians take only a few minutes
differs from that of a healthy person. You can look for to process, they yield so many false negatives those
similarities and differences in autoantibody profiles to doctors routinely send out the samples for subsequent
look for clues and markers that provide early indicators of rounds of more thorough, time consuming and expensive
disease. analysis [3].
In their hunt for cancer indicators, Eprogen uses a Platform lies in the fact that we can screen a single
process called 2-dimesional protein fractionation, which sample for multiple viral and bacterial infections at the
sorts thousands of different proteins from cancer cells by same time. Soon, doctors will no longer need to order as
both their electrical charge and their hydrophobicity or many expensive and time-consuming tests, and can
stickiness. instead obtain accurate diagnoses that will enable them to
The 2-D fractionation process creates 960 separate quickly provide their patients with targeted treatment
protein fractions, which are then arranged in a single strategies. Though the analysis of a sample on a biochip
biochip containing 96-well grids. Eprogen scientists then can take 30 minutes, scientists can have much more
probe the microarrays with known serum or plasma auto- confidence in the accuracy of the diagnosis. Biochips give
antibodies produced by the immune systems of cancer us the ability to run a test that allows your doctor to figure
patients. 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 If cash no longer existed and if the world’s economy
authoritatively explain you, they might also be used for was totally chip oriented; — there would be a huge
patients who exhibit symptoms of much more serious "black-market" for chips! Since there is no cash and no
infections. By adding just a few more drops to the chip's other bartering system, criminals would cut off hands and
array, Schabacker claimed, lab technicians could test for a heads, stealing "rich-folks" chips.
whole slate of biotoxins and especially virulent diseases
from the plague to smallpox to anthrax [4]. VII. CONCLUSION
Other infections, such as those caused by Multidrug
Resistant Tuberculosis (MDR-TB) and the often deadly Biochips promises to bring genomics, the study of all
Methicillin-resistant Staphylococcus aureus (MRSA), can the genes in existing organisms, out of the research
be quickly diagnosed with biochips like Akonni's laboratory and into the everyday practice of medicine. If
TruArray assay, according to Daitch. genomics delivers on its promise, health care will shift
The most important thing with these types of infections from a focus on detection and treatment to a process of
is that you have to be right and get the answer quickly. prediction and prevention. The biochip space lies at the
Some of the tests out there, though marginally quicker intersection between high technology chip
than ours, are so inaccurate that they're almost useless. manufacturing, signal processing, software skills and
Especially when you're talking about anthrax or plague, more traditional molecular biology and genomics. The
you have to be confident in your diagnosis or else risk market for biosensors and biochips is interdisciplinary
causing a panic. and growing and has applications in a number of core
research areas. This paper presents a valuable context
VI. B IOCHIP IS UP TO T HE MARK O F T HE MONSTER addition for those in both academia and industry. As
this fast maturing field already boasts sales of products,
The biochip technology was originally developed for biochips are likely to have a significant business future.
monitoring fisheries as mentioned, it’s use now includes, We can expect that advances in microfluidic biochip
over 300 zoos, over 80 government agencies in at least 20 technology will enable the miniaturization of devices
countries, pets also , electronic branding of horses, that will allow highly sensitive analysis of complex
monitoring lab animals, fisheries, endangered wildlife, biological interactions in real time that to with a low
automobiles, garment tracking, hazardous waste and cost perception.
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 [1] Cady, NC (2009). "Microchip-based PCR Amplification Systems".
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[9] K. L. Michael, L. C. Taylor, S. L. Schultz, and D. R. Walt,
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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

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.