Biochips seminar report

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ACKNOWLEDGEMENT
I take this opportunity to express my heartfelt gratitude towards the Department
of Computer, JIEMS, Akkalkuwa that gave me an opportunity for presentation
of my seminar in their esteemed organization.
It is a privilege for me to have been associated with Mr. Shah Idris, my guide
during this seminars work. I have been greatly benefited by his valuable suggestions
and ideas. It is with great pleasure that I express my deep sense of gratitude to him
for his valuable guidance, constant encouragement and patience throughout this
work.
I express my gratitude to Prof. Patel Suhel I [CO HOD] for his constant
encouragement, co-operation, and support and also thankful to all people who have
contributed in their own way in making this seminar success.
I take this opportunity to thank all our classmates for their company during the
course work and for useful discussion I had with them.
Under these responsible and talented personalities, I was efficiently able to
complete seminar in time with success.
Mr.Golam Murshid
(B.E. CO)

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Table of Content
SR NO. CONTENT PAGE NO
1 Abstraction 4
2 Introduction 5
3 Literature survey 6
4 Methodology 9
5 Framework 12
6 Advantages and disadvantages 15
7 Future Scope 16
8 Conclusion 18
9 References 19

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Table of Figure
SR NO. NAME OF FIGURE
PAGE
NO
1 Biochips 5
2 Human interfacing of Biochips 7
3 Actual size of chip 8
4 Syringe to Implant Biochip 9
5 Components 10

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Chapter 1: - Abstraction
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. 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. Biochips helped to dramatically
accelerate the identification of the estimated 80,000 genes in human DNA, an ongoing
world-wide research collaboration known as the Human genome project. Developing a
biochip plat-form incorporates electronics for addressing, reading out, sensing and
controlling temperature and, in addition, a handheld analyzer capable of multiparameter
identification. The biochip platform can be plugged in a peripheric standard bus of the
analyzer device or communicate through a wireless channel. Biochip technology has
emerged from the fusion of biotechnology and micro/nanofabrication technology.
Biochips enable us to realize revolutionary new bioanalysis systems that can directly
manipulate and analyze the micro/nano- scale world of biomolecules, organelles and
cells.

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Chapter 2: Introduction
What is biochip?
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 andthe 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.
Fig: Biochips

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Chapter 3: Literature survey
The development of biochips has a long history, starting with early work on the
underlying sensor technology.Biochip was originally developed in in 1983 for
monitoring fisheries,the rapid technological advances of the biochemistry and
semiconductor fields in the 1980s led to the large scale development of biochips in
the 1990s. At this time, it became clear that biochips were largely a "platform"
technology which consisted of several separate, yet integrated components. Today,
a large variety of biochip technologies are either in development or being
commercialized. Numerous advancements continue to be made in sensing research
that enable new platforms to be developed for new applications. Biochip was
invented in 4G generation & the development is still continued, due its various
applications. Biochips are also continuing to evolve as a collection of assays that
provide a technology platform. One interesting development in this regard is the
recent effort to couple so-called representational difference analysis (RDA) with
high-throughput DNA array analysis. The RDA technology allows the comparison
of cDNA from two separate tissue samples simultaneously.It is important to realize
that a biochip is not a single product, but rather a family of products that form a
technology platform. Many developments over the past two decades have
contributed to its evolution.In a sense, the very concept of a biochip was made
possible by the work of Fred Sanger and Walter Gilbert, who were awarded a Nobel
Prize in 1980 for their pioneering DNA sequencing approach that is widely used
today. DNA sequencing chemistry in combination with electric current, as well as
micropore agarose gels, laid the foundation for considering miniaturizing molecular
assays. Another Nobel-prize winning discovery, Kary Mullis's polymerase chain
reaction (PCR), first described in 1983, detected by standard laboratory methods
sequencing.

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3.1 Human interface to Biochip:
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."
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. Trovan, Ltd., markets an implant, featuring a patented
"zip quill", which you simply press in, no syringe is needed
Fig: Human Interfacing of Biochips

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3.2First implant of Biochips:
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 and healthcare applications. The syringe used is of a normal
size seringe & the chip can be placed below the skin layer very easily.
Fig: Syringe to Implant Biochip

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Chapter 4: Methodology
Biochip Architecture:-
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.
4.1 size:
The size of Biochip is of a size of an uncooked rice grain size. It ranges
from 2inches to 12inches.
Fig: Actual size of chip
4.2 component:
The transponder: The transponder is the actual biochip implant. It is a passive
transponder, meaning it contains no battery or energy of it's own. In comparison, an
active transponder would provide it is own energy source, normally a small battery.

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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. 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 the glass capsule.
Fig: component
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 circuit 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.

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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.
Because "radio waves" are utilized to communicate between the transponder and
reader, the capacitor is "tuned" to the same frequency as the reader.
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 or interconnect, resulting in a permanent placement of the
biochip.
4.3 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. Then, prices for biochips, like the prices for
computer memory chips, would fall through the floor.

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Chapter 5: Framework
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 centimetres so that they can
be analysed 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.
Biochips concentrate thousands of different genetic tests on a surface area of just afew
square centimetres so that they can be analysed by computer within a very shortspace
of time. On the one hand this makes the individual genetic tests much cheaperand on
the other hand, many more tests can be carried out.Affymetrix invented the “high-
density microarray” in 1989 and has been selling thisassay since 1994 under the name
of GeneChip® (figure 1). In this context,microarray means that the genetic tests are
organised (arrayed) inmicrometrespacing(micro).As it was not previously possible to
go below the millimetre range,the description “high density” is certainly justified.
Experiments (e.g. measurement ofgene activity or sequencing to demonstrate mutations
and polymorphisms) that couldpreviously only be done individually, one after the other,
can now be carried out inlarge numbers at the same time and in a highly automated
manner.

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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.
5.2Proteomics:
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
microseparations (pre LC/MS) to achieve high plate number
 Electrokinetic sample
injection for fast,
reproducible, samples
 Stacking or other
preconcentration methods (as a precursor to biosensors)
to improve detection limits
 Kinetic analysis of
interactions between proteins to enable accurate, transport-free kinetics

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5.2 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 biosensing. The use of Biochip facilitate:
Biochip /Applications of Biochip
 Design/develop
"lab-in-cell" platforms handling single or few cells with nanoprobes
in carefully controlledenvironments.
sorting and positioning of the cells optimally using DEP, optical traps
etc.
 Field/reagent based cell lysis,
where the contents of the cell are expelled out by breaking the
membrane, or increase the efficiency of transfection using
reagents/field
 Intracellular processes to obtain
high quality safety/toxicity ADME/T data
5.3 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.
microfluidics are compared for ease/efficiency Incorporation of suitablesensing
modality.

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Chapter 6: Advantages and
Disadvantages
Advantages:
 .The ability to detect multiple viral agents in parallel e.g. differential diagnosis
of agents from other diseases that cause similar clinical symptoms, or the
recognition of complex mixtures of agents.
 .Clarification of syndromes of unknown aetiology .Increase speed of
diagnosis of unknown pathogens ("future proofed" surveillance tools).
 .Viral typing (AIV, FMDV, Rabies)
 .Drive policy for diagnostics and disease control.
 .Epidemiological tracing
 .Interagency collaboration. The consortium consists of National, EU and OIE
referencelaboratories and has access to real sample material from a wide
selection of hosts and viruses.
Disadvantages:
 .These methods have problems that a DNA chip cannot be fabricated at high
density and mass production is limited. Thus, these methods are applicable to
fabrication of a DNA chip for study.
 .Meanwhile, the DNA chip and the DNA microarray have different fabrication
methods but are similar in that different oligonucleotides are aligned on a
square spot having a certain size in a check pattern.

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Chapter 7:-Future Sope
The immediate prospects for biochip technology depend on a range of technologic and
economic issues. One is the question of chip reusability. Current biochips are of
necessity disposable, in part because the current devices are not physically robust. For
example, nucleic acid probes tend to break away from a supporting glass plate. A
decade from now, this problem may have been better addressed, making the chips
more reusable, and perhaps at the same time permitting probes with longer spans of
genetic data than are feasible today. In this way, a manufacturing improvement might
facilitate more powerful forms of genetic analysis.
On the other hand, it may be better to manufacture biochips so inexpensive that they
can be used once and then discarded. Another issue is biochip versatility. Current
biochips are single-purpose, hardwired devices. Even if future biochips do not become
programmable, in the fashion of computer chips, they may become usable for multiple
purposes, such as the analysis of a tissue sample for
numerous pathogens. An overarching issue is standardization. For diagnostic purposes,
any medical test should be administered, and its results interpreted, in a standardized
way.
It seems desirable for biochips performing different tests to have an output detectable by
the same readout device. Hence, a race is underway to create a biochip platform or
motherboard capable of handling a wide range of biochips, irrespective of the internal
details of a given chip's function. In particular, two companies, Affymetrix and Molecular
Dynamics, have formed the Genetic Analysis Technology Consortium, or GATC (a name
that also represents the four nucleotides that carry genetic code in DNA). The hope is to
establish industry-wide standards for the reading of biochips.

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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 one at a time, or serially, on the chip. Thus, throughput and yield tend
to be low.
Theyare developing a biochip that indexes sensor function to its shape, instead of its
position on the chip. Thus, the sensors can be placed anywhere. Image recognition
software can then then used to read the chip. The shaped sensors are made via a novel
contact lithography. The benefits of this approach are multifold:
 The sensors can be batch produced and then assembled together in parallel,
providing high throughput and high yield.
 The sensors can be packed very tightly together, unlike those
deposited with microdeposition systems.
 The sensors are 3D in nature, and thus provide a higher signal than 2D
sensors of other chips.
 Almost any chemistry can be incorporated into the sensors. Most biochips use
only one type of chemistry.
 Because the sensors are produced offline and assembled later, they can be
customtailoredfor their specific application.

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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 ultraminiaturization, perhaps involving entirely 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 .

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References
1. Marshall,A., Hodgson, J., DNA chips: An array of possibilities, Nature
Biotechnology, 1998, 16: 27.
2. Kricha, L.J., Miniaturization of analytical systems, Clinical Chemistry, 1998, 44
: 2088.
3. VahidBemanian, Frøydis D. Blystad, Live Bruseth, Gunn A. Hildrestrand, Lise
Holden, Endre Kjærland, Pål Puntervoll, Hanne Ravneberg and Morten Ruud,
"What is Bioethics?" Dec 1998.
4. Fan et al. (2009). "Two-Dimensional Electrophoresis in a Chip".Lab-
on-a-Chip Technology: Biomolecular Separation and Analysis.
Caister Academic.
5. Herold, KE; Rasooly, A (editor) (2009). Lab-on-a-Chip Technology:
Fabrication and Microfluidics

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