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Transcript of Bio Chip Report
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Biochips
Chapter 1
INTRODUCTION
Most of us wont like the idea of implanting a biochip in our body that identifies us
uniquely and can be used to track our location. That would be a major loss of privacy. But
there is a flip side to this! Such biochips could help agencies to locate lost children, downed
soldiers and wandering Alzheimers patients.
The human body is the next big target of chipmakers. It wont be long before biochip
implants will come to the rescue of sick, or those who are handicapped in someway. Large
amount of money and research has already gone into this area of technology.
A few US companies are selling both chips and their detectors. The chips are of size
of an uncooked grain of rice, small enough to be injected under the skin using a syringe
needle. They respond to a signal from the detector, held just a few feet away, by transmitting
an identification number. This number is then compared with the database listings of register
pets.
Biochips are devices that can contain anywhere from tens to tens of millions of
individual sensor elements (or biosensors). The sensors are packed together into a package
typically the size of a microscope slide. Because so many sensors can be put into such a
small area, a huge number of distinct tests can be done very rapidly.
Biochips are often made using the same microfabrication technology used to make
microchips. Unlike microchips, however, biochips are generally not electronic (although
they can be). The key premise behind biochips is that they can do chemistry on a small
scale. Each biosensor can be thought of as a "microreactor" which does chemistry designed
to sense a specific analyte. Biosensors can be made to sense a wide variety of analytes,
including DNA, protein, antibodies, and small biological molecules. Fluorescence is often
used to indicate a sensing event. Automated microscopy systems can be used to "read" the
chip, i.e. determine which sensors are fluorescing.
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A biochip is a collection of miniaturized test sites (microarrays) arranged on a solid
substrate that permits many tests to be performed at the same time in order to achieve
higher throughput and speed. 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 a few seconds. Biochip is a broad term indicating the use of microchip
technology in molecular biology and can be defined as arrays of selected biomolecules
immobilized on a surface. Biochip will also be used in animal and plant breeding, and in
the monitoring of foods and the environment.
Biochip is a small-scale device, analogous to an integrated circuit, constructed
of or used to analyze organic molecules associated with living organisms. One type of
theoretical biochip is a small device constructed of large organic molecules, such as
proteins, and capable of performing the functions (data storage, processing) of an
electronic computer. The other type of biochip is a small device capable of performing
rapid, small-scale biochemical reactions for the purpose of identifying gene sequences,
environmental pollutants, airborne toxins, or other biochemical constituents.
Figure 1: A Biochip
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Chapter 2
WORKING OF A BIOCHIP
The chip contains a 10 character alphanumeric identification code that is never
duplicated. When a scanner is passed over the chip, the scanner emits a 'beep' and your
number flashes in the scanner's digital display. Biochips concentrate thousands of different
genetic tests on a surface area of just a few square centimeters so that they can be analyzed
by computer within a very short space of time. On the one hand this makes the individual
genetic tests much cheaper and on the other hand, thanks to the capacity, many more tests
can be carried out.
Affymetrix invented the high-density microarray in 1989 and has been selling this
assay since 1994 under the name of Gene Chip. In this context, microarray means that the
genetic tests are organized (arrayed) in micrometer spacing (micro).As it was not
previously possible to go below the millimeter range, the description high density is
certainly justified. Experiments (e.g. measurement of gene activity or sequencing to
demonstrate mutations and polymorphisms) that could previously only be done
individually, one after the other, can now be carried out in large numbers at the same timeand in a highly automated manner.
Figure 2 : Biochip Technology
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Chapter 3
BIOCHIP ARCHITECTURE
The biochip implant system consists of two components:
a Transponder
a Reader/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.
3.1 Size
The size of Biochip is of a size of an uncooked rice grain size. It ranges from
2 inches to 12 inches.
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Figure 3.1 Actual size of chip
3.2 Components:
3.2.1 The transponder: The transponder is the actual biochip implant. It is a
passive transponder, meaning itcontains no battery or energy of it's own. In comparison, an
active transponder would provide its own energy source, normally a small battery. Because
thepassive biochip contains no battery, or nothing to wear out, it has a very long life, up to
99 years, and no maintenance.
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.
The biochip-transponder consists of four parts:
computer microchip
antenna coil
capacitor and
glass capsule.
Figure 3.2.1: Components of biochip
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
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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.
Figure 3.2.2: Computer Microchip
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".
Antenna Coil:This is normally a simple, coil of copper wire around a ferrite or iron
core. This tiny, primitive, radio antenna "receives and sends" signals from the reader or
scanner.
Figure 3.2.3: Antenna Coil
Tuning Capacitor: The capacitor stores the small electrical charge (less than 1/1000 of
a watt) sent by the reader or scanner, which activates the transponder. This "activation"
allows the transponder to send back the ID number encoded in the computer chip.
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Because "radio waves" are utilized to communicate between the transponder and reader,
the capacitor is "tuned" to the same frequency as the reader.
Figure 3.2.4: Tuning Capacitor
Glass Capsule:The glass capsule "houses" 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. 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 polypropylene polymer sheath is attached to one end of the
capsule. This sheath provides a compatible surface which the bodily tissue fibers bond orinterconnect, resulting in a permanent placement of the biochip.
The biochip is inserted into the subject with a hypodermic syringe. Injection is safe
and simple, comparable to common vaccines. Anesthesia is not required nor recommended.
In dogs and cats, the biochip is usually injected behind the neck between the shoulder blades.
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Figure 3.2.5: Biochip with the Syringe
3.2.2 The Reader/ Scanner:
The reader consists of an exciter coil which creates an 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.
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Figure 3.2.6 : Reader
3.3 Cost:
Biochips are not cheap, though the price is falling rapidly. A year ago, human
biochips cost $2,000 per unit. Currently human biochips cost $1,000, while chips for mice,
yeast, and fruit flies cost around $400 to $500.
The price for human biochips will probably drop to $500 this year. Once all the
human genes are well characterized and all functional human SNPs are known,
manufacture of the chips could conceivably be standardized.
Chapter 4
BENEFITS OF BIOCHPS
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1) With a biochip, tracing of a person/animal, anywhere in the world
is possible: Once the reader is connected to the internet,satellite and a
centralized database is maintainedabout the biochipped creatures, It is always
possible to trace out the personality intended.
2) A biochip can store and update financial, medical, demographic
data, basically everything about a person:An implanted biochip can be
scanned to pay forgroceries, obtain medical procedures, and conductfinancial
transactions. Currently, the in use,implanted biochips only store one 10 to 15 digits.
If biochips are designed to accommodate with more ROM & RAM there is
definitely anopportunity.
3) A biochip leads to a secured Ecommerce systems :Its a fact; the world
is very quickly going to adigital or E-economy, through the Internet. It isexpected
that by 2008, 60% of the Business transactions will be performed through the
Internet. The E-money future, however, isn'tnecessarily secure. The Internet wasn't
built to beFort Knox. In the wrong hands, this powerful toolcan turn dangerous.
Hackers have already broken into bank files that were 100% secure. A biochip is
the possible solution to the "identification and security" dilemma faced by the
digital economy. This type of new bio-security device is capable of accurately
tracking information regarding what users are doing, and who are to accurately
trackinformation regarding what users are doing, andwho is actually doing it.
4) Biochips really are potent in replacing passports, cash and
medical records: The really powered biochip systems can replace cash,
passports, medical & other records! Its no more required to carry wallet full cash,
credit/ATM cards, passports & medical records to the market place. Payment
system, authenticationprocedures may all be done by the means Biochips.
5) Medicinal implementations of Biochips : A New Era Proposed by
US- Biochip as Glucose Detector : The Biochip can be integrated with a
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glucose detector. The chip will allow diabetics to easily monitor the level of the
sugar glucose in their blood. Diabetics currently use a skin prick and a hand-held
blood test, and then medicate themselves with insulin depending on the result.
The system is simple and works well, but the need to draw blood means that most
diabetics don't test themselves as often as they should. Although they may get away
with this in the short term, in later life those who monitored infrequently suffer
from blindness, loss of circulation, and other complications. The solution is more
frequent testing, using a less invasive method. The biochip will sit underneath the
skin, sense the glucose level, and send the result back out by radio - frequency
communication.
Proposed principle of Glucose detection:
A light-emitting diode (LED) in the biochip starts off the detection process. The
light that it produces hits a fluorescent chemical: one that absorbs incoming light
and re -emits it at a longer wavelength. The longer wavelength of light is then
detected, and the result is sent to a control panel outside the body. Glucose is
detected because the sugar reduces the amount of light that the fluorescent chemical
re-emits. The more glucose there is the less light that is detected.
6) Biochip as Oxygen sensor : The biochip can also be integrated with an
oxygen sensor .The oxygen sensor will be useful not only to monitor breathing in
intensive care units, but also to check that packages of food, or containers of
semiconductors stored under nitrogen gas,remain airtight.
Proposed principal of Oxygen sensor in Biochip:
The oxygen-sensing chip sends light pulses out into the body. The light is absorbed
to varying extents, depending on how much oxygen is being carried in the blood,
and the chip detects the light that is left. The rushes of blood pumped by the heartare also detected, so the same chip is a pulse monitor.
7) Biochip as an Blood Pressure sensor: In normal situations, The Blood
Pressure of a healthy Human being is 120/80 mm of Hg. A Pressure ratio lower than
this is said to be Low BP condition & A Pressure ratio more than this is High
BP condition. Serious Effects will bereflected in humans during Low & High BPconditions; it may sometimes cause the death of a Person. Blood Pressure is
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checked with BPApparatus in Hospitals and this is done only when the patient is
abnormal. However, a continuousmonitoring of BP is required in the aged people
&Patients.
A huge variety of hardware circuitry (sensors) is available in electronics to detect
the flow of fluid. Its always possible to embed this type of sensors into a biochip.
An integration of Pressure (Blood Flow) detecting circuits with the Biochip can
make the chip to continuously monitor the blood flow rate & when the pressure is in
its low or high extremes it can be immediately informed through the reader hence to
take up remedial measures.
Chapter 5
APPLICATIONS OF BIOCHIP
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5.1 Genomics
Genomics is the study of gene sequences in living organisms and being able to read
and interpret them. The human genome has been the biggest project undertaken to date but
there are many research projects around the world trying to map the gene sequences of
other organisms. The use of Biochip facilitate: Automated genomic analysis including
genotyping, gene expression DNA isolation from complex matrices with aim to increase
recovery efficiency DNA amplification by optimizing the copy numberDNA hybridization
assays to improve speed and stringency.
5.2 Proteomics
Proteome analysis or Proteomics is the investigation of all the proteins present in a cell,
tissue or organism. Proteins, which are responsible for all biochemical work within a cell,
are often the targets for development of new drugs. The use of Biochip facilitate:
High throughput proteomic analysis.
Multi-dimensional micro-separations (pre LC/MS) to achieve high plate number.
Electro-kinetic sample injection for fast, reproducible, samples.
Stacking or other pre-concentration methods (as a precursor to biosensors) to
improve detection limits.
Kinetic analysis of interactions between proteins to enable accurate, transport-free
kinetics.
5.3 Cellomics
Every living creature is made up of cells, the basic building blocks of life.. Cells are
used widely by for several applications including study of drug cell interactions for drug
discovery, as well as in bio-sensing. The use of Biochip facilitates:
Design/develop: "lab-in-cell" platforms handling single or few cells with
nanoprobes in carefully controlled environments.
Cell handling, which involves sorting and positioning of the cells optimally using
DEP, optical traps, etc.
Field/reagent based cell lyses, where the contents of the cell are expelled out by
breaking the membrane, or increase the efficiency of transfection using
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reagents/field.
Intracellular processes to obtain high quality safety/toxicity ADME/T data.
5.4 Biodiagnostics and (Nano) Biosensors
Biodiagnostics or biosensing is the field of sensing biological molecules based on
electrochemical, biochemical, optical, luminometric methods. The use of Biochip facilitate:
Genetic/Biomarker Diagnostics, development of Biowarfare sensors which involves
optimization of the platform, reduction in detection time and improving the signal-to-noise
ratio
Selection of detection platform where different formats such as lateral flow vs.
micro fluidics are compared for ease/efficiency Incorporation of suitable sensing
modality by evaluating tradeoffs and down select detection modes(color/
luminometric, electrochemical, biochemical, optical methods) for specific need.
5.5 Protein Chips for Diagnosis and Analysis of Diseases:
The Protein chip is a micro-chip with its surface modified to detect various disease
causing proteins simultaneously in order to help find a cure for them. Bio-chemical
materials such as antibodies responding to proteins, receptors, and nucleic acids are to be
fixed to separate and analyze protein.
5.6 Biochips can detect cancers before symptoms develop
In their fight against cancer, doctors have just gained an impressive new weapon to
add to their arsenal. 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 tumour, 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.
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"Antibodies are the guardians of what goes on in the body," said 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's
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.
By using cancer patients' own auto-antibodies as a diagnostic tool, doctors could
potentially tailor treatments based on their personal autoantibody profile. "This technology
is really designed to take advantage of the information contained within the patient's own
biology," Barder said. "What 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 contain grids of small wells or dots, each of which contains a protein, antibody
or nucleic acid that can bind to a target antigen or DNA sequence
Chapter 6HUMAN INTERFACE TO BIOCHIP
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Biochips provide interfaces between living systems and electro-mechanical and
computational devices. These chips may be used in such varied applications as artificial
sensors, prosthesis, portable/disposable laboratories or even as implantable devices to
enhance human life. Biochips promise dramatic changes in future medical science and
human life in general. With the advances of bio and nano technologies two strong
paradigms of integrated electronic and life are emerging. Biosensor chips can provide the
construction of sophisticated human sensing systems such as nose and ears. The second
paradigm is chips for sensing biology that will provide for interactions with living bodies
and build new diagnosis tools (such as diabetes glucose meters) or new medicines (such as
a bio-assay chip). A tiny microchip, the size of a grain of rice, is simply placed under the
skin. It is so designed as to be injected simultaneously with a vaccination or alone."
Figure 6.1 : Human interfacing of biochips
The biochip is inserted into the subject with a hypodermic syringe. Injection is safe
and simple, comparable to common vaccines. Anesthesia is not required nor recommended.
In dogs and cats, the biochip is usually injected behind the neck between the shoulder
blades.
The syringe used is of a normal size syringe and the chip can be placed below the
skin layer very easily.
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Figure 6.2 : Syringe used to implant the biochip
First Implant of Biochip:On May 10 2002, three members of a family in Florida ("medical pioneers,"
according to a fawning report on the CBS Evening News) became the first people to
receive the implants. Each device, made of silicon and called a VeriChip, is a small radio
transmitter about the size of a piece of rice that is injected under a person's skin. It transmits
a unique personal ID number whenever it is within a few feet of a special receiver unit.
VeriChip's maker describes it as "a miniaturized, implantable, radio frequency
identification device (RFID) that can be used in a variety of security, emergency andhealthcare applications.
THE AGILENT 2100 BIOANALYZER
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The Agilent 2100 bioanalyzer is the industrys only platform with the ability to
analyze DNA, RNA, proteins and cells. Through lab-on-a-chip technology the 2100
bioanalyzer integrates sample handling, separation, detection and data analysis onto one
platform. It moves labs beyond messy, time consuming gel preparation and the subjective
results associated with electrophoresis. And now, with our second generation 2100
bioanalyzer, we have integrated an easier way to acquire cell based parameters from as few as
20,000 cells per sample.
The process is simple: load sample, run analysis, and view data. The 2100 bioanalyzer
is designed to streamline the processes of RNA isolation, gene expression analysis, protein
expression, protein purification and more. One platform for entire workflow!
Research by Willson Research Group
-The University of Texas at Austin
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Most biochips are 2D arrays of sensors placed carefully in a grid arrangement. The
position of the sensor on the chip determines its function. For example, a sensor at the x-y
coordinate (4,5) might sense the antibody for HIV, while the sensor at (7,3) might sense the
antibody for an influenza virus. To place the sensors in precise coordinates, sophisticated
and expensive microdeposition techniques are used. The sensors are essentially placed oneat a time, orserially, on the chip. Thus, throughput and yield tend to be low.
We are developing a biochip that indexes sensor function to itsshape, instead of its position
on the chip. Thus, the sensors can be placed anywhere. Image recognition software can then
used to read the chip. The shaped sensors are made via novel contact lithography. The
benefits of this approach are multifold:
1. The sensors can be batch produced and then assembled togetherin parallel,
providing high throughput and high yield.
2. The sensors can be packed very tightly together, unlike those deposited with micro
deposition systems.
3. The sensors are 3D in nature, and thus provide a higher signal than 2D sensors of
other chips.
4. Almost any chemistry can be incorporated into the sensors. Most biochips use only
one type of chemistry.
5. Because the sensors are produced offline and assembled later, they can be custom
tailored for their specific application.
CONCLUSION
Biochips are fast, accurate, miniaturized, and can be expected to become
economically advantageous attributes that make them analogous to a computer chip. One
expects to see an accelerated trend of ultra-miniaturization, perhaps involving entirely
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novel media, and an increased ability to analyze not only genetic material but also other
types of biologic molecules. One expects, too, an eventual harmonization of technologies,
so that dominant fabrication strategies will emerge, at least for certain types of applications,
including a favored format for genetic analysis and another for antibodies and other
proteins. Since the potential applications are vast, both for research and for clinical use, the
potential markets for biochips will be huge, a powerful driving force for their continued
development.
REFERENCES
1) About Biochips :http://en.wikipedia.org/wiki/Biochip
2) Components of a biochip : http://www.av1611.org/666/biochip.html
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http://en.wikipedia.org/wiki/Biochiphttp://en.wikipedia.org/wiki/Biochiphttp://www.av1611.org/666/biochip.htmlhttp://en.wikipedia.org/wiki/Biochiphttp://www.av1611.org/666/biochip.html -
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3) Application of biochips in biotechnology :
http://pharmaexecnews.com/biotechnology/biotechnology-applications-biochip-
technology/
4) Article on biochips :
http://www.nature.com/nbt/journal/v18/n10s/full/nbt1000_IT43.html
5) Biochip technology in cancer detection :
http://www.ncbi.nlm.nih.gov/pubmed/11327117
http://www.anl.gov/Media_Center/News/2008/ES080509.html
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http://pharmaexecnews.com/biotechnology/biotechnology-applications-biochip-technology/http://pharmaexecnews.com/biotechnology/biotechnology-applications-biochip-technology/http://www.nature.com/nbt/journal/v18/n10s/full/nbt1000_IT43.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/11327117http://www.anl.gov/Media_Center/News/2008/ES080509.htmlhttp://pharmaexecnews.com/biotechnology/biotechnology-applications-biochip-technology/http://pharmaexecnews.com/biotechnology/biotechnology-applications-biochip-technology/http://www.nature.com/nbt/journal/v18/n10s/full/nbt1000_IT43.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/11327117http://www.anl.gov/Media_Center/News/2008/ES080509.html