This document discusses biochips and their development. It begins with an introduction to biochips, noting they are miniaturized laboratories that can perform hundreds or thousands of biochemical reactions simultaneously. This enables rapid screening of biological analytes for various purposes. The document then provides history on the development of biosensor technologies and microarray fabrication techniques. It also discusses various types of microarrays beyond DNA, including protein, antibody, and chemical compound microarrays. Ethics regarding biotechnology development are briefly covered.

1. BIO CHIP
INTRODUCTION
Bio(synthetic) Engineering is a fundamental approach to engineering based on an
important lesson from biology: that the processes used to assemble or synthesize a
complex system can make the resulting system more robust, evolvable, adaptive, and
richly functional. Therefore, Bio(synthetic) Engineering aims to develop synthesis
processes analogous to those occurring in biological growth, neural and cognitive
development, and molecular scale self-assembly in living systems. Such developmental
processes are also subject to evolutionary optimization. Importantly, however, these
synthesis processes are not restricted to biological materials (such as proteins) or to
mimicry of biological solutions to engineering problems (biomimetics): Transistors are
much faster than nerve synapses, and jet engines are much more powerful than muscles.
But the system design principles behind brains and muscles are much more advanced
than anything in current engineering practice.
Examples of biosynthesis in nature include the construction of wood, teeth, bones, hard
shells, spider webs, and many other materials, minerals and mechanical structures. The
same is true, on a grander scale, for the construction of nervous systems, brains, and
cognition. Morphogenesis--the generation of multicellular form by signaling between
cells that can grow, divide, and specialize--couples with molecular assembly at the
cellular and subcellular scale to perform fabrication of organic, mineral, and
computational structures in an efficient, adaptive and optimizable way from elementary
building units. Upon injury, aspects of the developmental self-fabrication process can be
restarted to effect repair, resulting in a robust and fault-tolerant system. Evolution takes
1

2. particular advantage of the developmental process to make large-scale, systematic
improvements to a complex system by optimizing its growth rules, in addition to its
individual components.
With Bio(synthetic) Engineering, we seek to apply these system design
principles to the best available technologies at every level of system organization from
devices through distributed intelligence. This novel approach is expected to first become
cost-effective for the extremely challenges that arise in space exploration. Table 1
contrasts conventional engineering, biomimetic, and our preferred biosynthetic
approaches to engineering autonomous systems at different levels of design from
molecular-scale devices to intelligent and distributed systems.
airplane example
Fixed-wing airplanes Flapping-wing airplanes Biofabricated, sensor-covered wings
for airplanes Device level Si chip devices Si/Biomolecular doping experiments (Bell
Labs) Modified PS1 proteins; self-assembled PS1 structures
Fluid actuators Hydraulics Fractal hydraulics nanofluidics Fluid pumps Turbo pumps
LVADS artificial heart Functional prestressed tubule for Computational level Chip
design Artificial neural nets Evo-devo-neuro nets Artificial Brains Control software with
human in the loop Standard structured networks with hidden layers and Hebbian learning
Evolved networks grown with a developmental process .
Cognitive systems Expert systems, Artificial intelligence Cognitive science, mind design
Evolvable statistical inference systems Distributed systems Static, centrally controlled
systems Flocking robots, without shared understanding of mission goals Simple bio-
swarm agents and structures: dynamic, self-organizing, autonomic communication
control and navigation
Space applications of biosynthetic engineering will be systemic. They will include
reduction of launch mass and power requirements for ambitious planetary exploration
and space observatory projects. Increased autonomy, smarter spacecraft, and lighter and
smarter mechanical, power, and instrument systems will also result. For human
spaceflight, intelligent subsystems that support, understand, and cooperate with living
systems from plants to astronauts will vastly amplify the capabilities of each human
being in space. For robotic mission elements, eventually, launch mass will be nearly
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3. eliminated by enabling self-fabrication to proceed in situ on other solid bodies in the solar
system.
HISTORY
The development of biochips has a long history, starting with early work on
the underlying sensor technology. 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 Schultz, 1996. 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 Clark, 1962. The enzyme
functioned in the presence of glucose to decrease the amount of oxygen available to 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.
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 Nelson, 2000. The development of sequencing techniques in 1977 by Gilbert
Maxam, 1977 and Sanger Sanger, 1977 working separately 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. First, in1983 Kary Mullis invented
the polymerase chain reaction PCR technique Nelson, 2000, a method for amplifying
DNA concentrations. This discovery made possible the detection of extremely small
quantities of DNA in samples. Second, in 1986 Hood and coworkers devised a method to
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4. label DNA molecules with fluorescent tags instead of radiolabels Smith, 1986, thus
enabling hybridization experiments to be observed optically.
The rapid technological advances of the biochemistry and semiconductor
fields in the 1980's led to the large scale development of biochips in the 1990's. At this
time, it became clear that biochips were largely a "platform" technology which consisted
of several separate, yet integrated components. Figure shows the makeup of a typical
biochip platform. The actual sensing component (or "chip") is just one piece of a
complete analysis system. Transduction must be done to translate the actual sensing event
(DNA binding, oxidation/reduction, etc.) into a format understandable by a computer
(voltage, light intensity, mass, etc.), 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 microarraying, to signal
processing -- require a true multidisciplinary approach, making the barrier to entry steep.
One of the first commercial biochips was introduced by Affymetrix. Their "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) (Cheng, 2001). The chips are produced
using microlithography techniques traditionally used to fabricate integrated circuits
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 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. Cancer diagnosis
through DNA typing is just one market opportunity. A variety of industries currently
desire the ability to simultaneously screen for a wide range of chemical and biological
agents, with purposes ranging from testing public water systems for disease agents to
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5. 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. The particular sensing and transduction techniques
chosen depend on factors such as price, sensitivity, and reusability.
MICROARRAY FABRICATION
The micro array -- 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 micro technology |micromechanical devices that
performer assist signal transduction. Surface chemistry is used to covalent bond
covalently bind]the sensor molecules to the substrate medium. The fabrication of micro
arraysis non-trivial and is a major economic and technological hurdle that may ultimately
decide the success of future biochip platforms. The primary manufacturing challenge is
the process of placing each sensor at a specific position (typically on a Cartesian grid) on
the substrate. Various mean sexist to achieve the placement, but typically roboticmicro-
pipetting (Schema, 1995) or micro -printing (MacBeath, 1999) systems are used to place
tinyspots of sensor material on the chip surface. Because 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
byAffymetrix in which a series of microlithography steps is used toCombinatorial
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6. chemistry|combinatorially synthesize hundreds of thousands of unique, single-
strandedDNA sensors on a substrate one nucleotide at atime (Fodor, 1991; Pease, 1994).
One lithography step is needed per base type; thus, a totalof four steps is required per
nucleotide level. Although this technique isvery powerful in that many sensors can be
created simultaneously, it iscurrently only feasible for creating short DNA strands (15-25
nucleotides).Reliability and cost factors limit the number of photolithography steps
thatcan be done. Furthermore, light-directed combinatorial synthesis techniquesare not
currently possible for proteins or other sensing molecules.
As noted above, most microarrays consist of a Cartesian grid of sensors.
Thisapproach is used chiefly to map or "encode" the coordinate of each sensorto its
function. Sensors in these arrays typically use a universal signalingtechnique (''e.g.''
fluorescence), thus making coordinates their onlyidentifying feature. These arrays must
be made using a serial process(''i.e.'' requiring multiple, sequential steps) to ensure that
each sensoris placed at the correct position.
Random" fabrication, in which the sensors are placed at arbitrarypositions on
the chip, is an alternative to the serial method. The tedious and expensive positioning
process isnot required, enabling the use of parallelized self-assembly techniques. Inthis
approach, large batches of identical sensors can be produced; 1998) Each bead was
uniquelyencoded with a fluorescent signature. However, this encoding scheme is
limited in the number of unique dye combinations that be can be used andsuccessfully
differentiated." sensors from each batch are then combined and assembled into an array.
Anon-coordinate based encoding scheme must be used to identify each sensor. Asthe
figure shows, such a design was first demonstrated (and later commercialized by
Illumina) using functionalized beads placed randomly in thewells of an etched fiber
opticcable
Protein Biochip Array and Other Micro array Technologies
Microarrays are not limited to DNA analysis; protein microarrays, antibody
microarray, Chemical Compound Microarray can also be produced using biochips.
6

7. Randox Laboratories Ltd. launched Evidence®, 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. Performing multiple analyses
simultaneously, described as multiplexing, allows a significant reduction in processing
time and the amount of patient sample required. Biochip Array Technology is a novel
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.
In sandwich assays an enzyme-labelled antibody is used; in competitive assays
an enzyme-labelled 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 detect and
quantify very low levels of light. The test regions are located using a grid pattern then the
chemiluminescence signals are analysed by imaging software to rapidly and
simultaneously quantify the individual analytes
BIOETHICS
When the question of ethics come up there is never a clear cut answer, nor
should there be. Since no one has actually implemented many types of future
biotechnology, interpreting moral issue at this point is very difficult. However, this
debate is relevant today and it is critical to begin debate now. Arthur Caplan of
University of Pennsylvania School of Medicine explains that “Crossing into this area will
be so startling, so momentous, and so socially unnerving that the prospect of doing so
demands proactive ethical, theological, and scientific discussion.”
7

8. Bioethics is the collaborative investigation of biology, scientific technology,
and ethical issues. Van Potter’s definition in 1971 states that bioethics is “biology
combined with diverse humanistic knowledge forging a science that sets a system on
medical and environmental priorities for acceptable survival.”
Genetic research has many life altering benefits. Genetic research can be used to
prevent genetic defects, eliminate disease and replace vital organs. This will save many
lives. However, we must realize the potential impact on life itself. Scientists are advised
to come up with plans and submit these plans to associated groups with both scientific
and ethical expertise for review, before entering into development of new biotechnology.
Reviews should be conducted nationally and or internationally. As well, the development
should be contained in strict biological confinement until the implications are understood.
Ethics is concerned with what is morally good and bad or right and wrong.
Obviously,with regards to bioethics there is a thin line between what is ethical and what
is not. Scientists have an ethical obligation as do individuals to do what is right. There is
no question whether or not biotechnology is a powerful new tool for modifying living
organisms to benefit humankind. However, because biotechnology is so new to us we
have yet to understand the risks involved with altering organisms..
BIO CHIP
The development of biochips is a major thrust of the rapidly growing
biotechnology industry, which encompasses a very diverse range of research efforts
including genomics, proteomics, computational biology, 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 microminiaturization. The merging of these
two fields in recent years has enabled biotechnologists to begin packing their traditionally
bulky sensing tools into smaller and smaller spaces, onto so-called biochips. These chips
are essentially miniaturized laboratories that can perform hundreds or thousands of
simultaneous biochemical reactions. Biochips enable researchers to quickly screen large
8

9. numbers of biological analytes for a variety of purposes, from disease diagnosis to
detection of BIOTERRORISM agents.
bio - combining form ( Environment ) (Health and Fitness) (Science and Technology)
Part of the words biology and biological, widely used as the first element of compounds
relating to biology or biotechnology; frequently used as a shortened form of
biological(ly). Etymology: Formed by abbreviating biology and biological; in both words
this part is ultimately derived from Greek bios 'life'. History and Usage: Compounds
relating to 'life' have been formed on bio- in English for over three centuries, and even the
ancient Greeks used it as a combining form. During the second half of the twentieth
century, however, advances in biotechnology and the increasing interest in green issues
caused a proliferation in popular language of compounds in these areas, alongside the
continuing use of bio- in scientific terminology . Like eco-, bio- was particularly
productive in the late sixties and early seventies, and many of the compounds which had
been well known then came back into fashion during the eighties, often undergoing
further development. The development of plastics and other synthetic products which
were biodegradable, that is, those that would decompose spontaneously and hence not
become an environmental hazard , led during the eighties to the verb biodegrade.
Biomass, originally a biologists' term for the total amount of organic material in a given
region, was later also used of fuel derived from such matter (also called biofuel, or, in the
case of the mixture of methane and other gases produced by fermenting biological waste,
biogas; this was burnt to produce what became known as bioenergy). By contrast,
biofeedback, the conscious control of one's body by 'willing' readings on instruments
(such as heart-rate monitors) to change , reappeared in the eighties as one of the
techniques used in autogenic training. Computer scientists continued to speculate that
micro-organisms could be developed that would function like the simple logic circuits of
conventional microelectronics, thus paving the way for biocomputing with biochips.
9

10. Biological warfare, a more disturbing application of biotechnology, became sufficiently
familiar to be abbreviated as biowar. Concern about the effect of even peaceful
technology on the biosphere (the component of the environment consisting of living
things) was expressed in the philosophy of biocentrism, in which all life, rather than just
humanity, is viewed as important ( much as in Gaia theory). Direct and sometimes violent
Chip and inductor inside of glass container, less than 1/4 of inch long
opposition to such aspects of biological research as animal experimentation and
genetic engineering was organized by biofundamentalists. As a result of the Green
Revolution, the public was made more aware of the threat posed by intensive cultivation
of particular species to biodiversity, the richness of variety of the biosphere. Towards the
end of the decade bio- began to be used indiscriminately wherever it had the slightest
relevance, either frivolously or because of its advertising potential (just as biological had
once been a glamorous epithet for washing powder). The prefix is sometimes even used
as a free-standing adjective in this sense, meaning little more than 'biologically
acceptable'. Examples include biobeer, biobottom (an 'eco-friendly nappy cover'), bio
house, bio home, bioloo, bioprotein, and bio yoghurt. The term bio-chip, coined only
about four years ago, already means different things to different people.
BIOCHIP DEFINITION
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
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11. in one second, a biochip can perform thousands of biological reactions, such as decoding
genes, in a 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 determines
the characteristics of an organism. Effectively, it is used as a kind of "test tube" for real
chemical samples. A specially designed microscope can determine where the sample
hybridized with DNA strands in the biochip. 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. The microchip is described
as a sort of "word search" function that can quickly sequence DNA.
Human chip
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 taken
BIOCHIP IMPLANTS
"We're from the government and we are here to help you." The dangers of
incrementalism and sub-dermal biochip implants is becoming increasingly clear. It is also
increasingly clear that privacy has become an anachronism. The privacy the founding
fathers so cherished is about to become a footnote in history. Many are aware of the
unbridled abuse of the alleged single-purpose Social Security number. The persistent
push for a national identification card (complete with biometric elements) is barely a step
away from sub-dermal biochip implants.
11

12. All the assaults on our privacy have a "reasonable" rationalization. Now we have a classic
example of the "reasonable" rationalization of incrementalism. Foreign executives and
other individuals who are frequent kidnapping targets in Latin America will soon be able
to use implantable ID chips and personal GPS devices in an attempt to thwart their
abductors. Gosh-oh-gee-golly! Thanks! Applied Digital Solutions announced recently it
had reached an agreement with a distributor to sell its VeriChip and Digital Angel
products in three South American countries. Of course, for security reasons, the company
refuses to discuss any particulars including the names of the countries or the distributor.
This isn't black helicopter stuff folks, and it's not far off in the future evil disguised as
benign assistance is knocking on the door NOW.
Digital Angel is set to fly soon. Implant technology (as in sub-dermal biochip implants) is
about to be beta tested on humans. Applied Digital Solutions will begin beta testing on
humans an implant technology capable of allowing users to emit a homing beacon, have
vital bodily functions monitored and confirm identity when making e-commerce
transactions. So notwithstanding the protestations of privacy advocates or religious critics
who warn of the Bible's book of Revelation and the mark of the beast, the first production
run of Digital Angel devices has begun. Applied Digital Solutions snatched up the patent
rights to the miniature digital transceiver it has named Digital Angel. Now they are ready
to kick off a sea-change marketing blitzkrieg. The company plans to market the device
for a number of uses, including as a tamper-proof means of identification for enhanced e-
business security. If you've just returned from the Amazon or depend on the mainstream
media to inform you, you may not be up to speed yet. Or, if you are a liberal socialist
democrat you might be in denial.
Here's the deal. Digital Angel sends and receives data and can be continuously
tracked by global positioning satellite technology. When implanted within a body, the
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13. device is powered electromechanically through the movement of muscles and can be
activated either by the wearer or by a monitoring facility.
According to ADS Chairman and Chief Executive Officer Richard Sullivan,
"We believe its potential for improving individual and e-business security and enhancing
the quality of life for millions of people is virtually limitless Although we're in the early
developmental phase, we expect to come forward with applications in many different
areas, from medical monitoring to law enforcement. However, in keeping with our core
strengths in the e-business-to-business arena, we plan to focus our initial development
efforts on the growing field of e-commerce security and user ID verification."
This is better than any national ID card. This whiz-bang little device will send
a signal from the person wearing Digital Angel to either a computer or the e-merchant
with whom he is doing business in order to verify his identity. But e-commerce is only
the tip of the invasion-of-privacy iceberg. According to the patent on this hoped-to-be
ubiquitous sliver of silicon, it is described as a rescue beacon for kidnapped children and
missing persons. The implant will save money by reducing resources used in rescue
operations for athletes, including mountain climbers and skiers. Already they are
spinning and manufacturing reality:
Law enforcement can use the implant to keep track of criminals under house arrest.
It will reduce emergency response time by immediately locating individuals in distress.
The device also has the capacity to monitor the user's heart rate, blood pressure and other
vital functions. Beyond just mere medical readouts, could it also analyze variances and
become an ipso facto lie detector?
Peace of mind is a big selling point for this so-called "advancement." They tell us, "Your
doctor will know the problem before you do," provided someone is monitoring your
13

14. medical data when you get sick. We've been cautioned that our would-be controllers
would incrementally introduce this ID/tracking/monitor/locator: First, It's been suggested,
they would implant those who could not refuse (prisoners, and the military). Then, they
would build a case for potential or feared kidnap victims. At first, it would be voluntary.
Then, it would be required for "certain services." Eventually, it would be mandatory, and
probably implanted at birth. Referring to the threat of kidnapping, the patent itself says,
"Adults who are at risk due to their economic or political status, as well as their children
who may be at risk of being kidnapped, will reap new freedoms in their everyday lives by
employing the device."
According to Digital Angel executives, one inquirer/prospect is the U.S. Department of
Defense, not directly but through a contractor. American soldiers may be required to
wear the implant so their whereabouts and health conditions can be accessed at all times.
HEALTH CHIPS
This chip is used for the health purpose to identify the disease DOCTORS are to implant
computerised sensors into patients to enable them to monitor chronic conditions minute-
by-minute from miles away.
The sensors detect tiny changes in metabolism and transmit data, via a mobile phone, to
the patient’s doctor.
Scientists at Imperial College London who invented the device believe it will enable
some patients to lead a normal life while being kept under constant watch.
It has the potential to be developed into a complete body sensor that could be implanted
into normally healthy people to pick up early signs of disease.
The sensor, which includes a Pentium microprocessor just 2mm square, will initially be
implanted in diabetics. Trials will begin by Christmas at St Mary’s hospital, London. The
implant will be programmed to send an emergency text message via a mobile phone,
alerting medical staff to changes in blood-sugar levels.
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15. If the problem is serious, the patient will be given immediate medical advice. Once
patients become familiar with the system, they could monitor their condition themselves
The only restriction is that the computer’s low power output means that it needs a
receiver — generally a mobile phone — to be within a metre of the patient to pick up the
sensor’s wireless signal from its miniaturised antenna.
Chris Toumazou, director of the Institute of Biomedical Engineering at Imperial, is
hoping eventually to link the sensor to an insulin pump that can be operated remotely by
a doctor. The sensor could also be used to protect people with heart and respiratory
diseases. The researchers are exploring ways to detect chemical changes in a patient’s
blood.
“The computer in your body can take away anxiety and allow medics to take control of
your care from miles away,” said Toumazou.
More than 17.5m people in Britain have one or more chronic diseases of varying severity
figure that is set to soar as the elderly population grows over the coming decades. If many
of these patients could be turned into experts monitoring their own conditions with
minimal intervention by doctors or nurses, it could free up significant NHS resources.
15

16. The aim is also to develop the system so that the sensor can provide prompts to patients
to take medication.Pathology departments are under particular pressure because of the
increase in the number of chronically ill patients who need regular blood tests.
Oracle, the technology company that is backing the project, has designed the software to
be compatible with the NHS’s new £6.5 billion computer system. This will allow the data
to be stored on a patient’s record and accessed by healthcare staff nationwide.
DRUG DISCOVERY
biochips and systems that are being used for accelerating the research processes and
capabilities of bio-pharmaceutical drug discovery. This study has found that the total
biochip market size in 2001 is about $740 million and may more than triple in revenues,
to about $2.47 billion in 2006. The 5-year CAGR is 27.3%. This market includes biochip
systems, Lab-on-a chip devices, microarrays, protein chips and other related
technologies.
In particular, biochip technologies will continue to help pharma companies. Facing near
term product pipeline challenges, Pharma companies have seen their R&D costs explode
as their delivery of new drug products have declined. Many of their current high priced
$billion -plus blockbuster drugs will reach their patent expirey dates by 2005-2006 and
draw competition from generic drug makers. These companies have tried growing
through M&As, but their growth has not increased. As a result, pharma companies have
increasingly become a source of strong research and financial partners with many of the
companies in the biotechnology industry. Pharma companies are motivated to become
customers and partners of biochip companies because these companies have technologies
that might help the big pharma companies become more productive and deliver more
than one product, in a shortened time frame rather than in the current 10-15 year drug
development process.
16

17. Accelerating the drug making process means turning to modern industrialization of R&D,
using genomics and proteomics technologies, and other capabilities that bio-chip
companies can provide. This report targets these important issues with interesting and
useful findings. This study uses more than 46 figures and tables to illustrate the findings
The wealth of data in the tables summarizes 90 alliance deals, over 375 patents, reviews
recent patent disputes, includes categorized lists of microarray products, technologies and
75 web links.
BIO CHIP TECHONOGOLY
Current Trends
Biochip technology is currently experiencing a series of rapid growth spurts that promise
to propel biochips to the forefront of medical and practical applications. "The explosion
of genetic sequence information and its availability in both public and corporate
databases has resulted in the gradual shift towards gene function-oriented studies. Gene
sequence data alone is of relatively little clinical use unless it is directly linked to disease-
relevant information that has diagnostic or therapeutic value. For gene function studies,
what is required is information regarding gene function, which begins by analyzing the
actual patterns of transcription and translation of the genetic message."
DNA-based biochips are used primarily for analysis. "One type of application focuses on
the detection of mutations in specific genes obtained from test tissue. Such mutations can
be a marker of the onset of a particular disease, such as cancer, and their detection serves
as a diagnostic tool". Some examples of applications come from one of the founding
companies in the development of biochip technology, Affymentrix. The Affymetrix
GeneChips, are the only commercially viable biochips on the market. "The p53
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18. GeneChip is designed to detect single nucleotide polymorphisms of this tumor-suppressor
gene. The HIV GeneChip is designed to detect mutations in the HIV-1 protease and also
the reverse transcriptase genes. Finally, the P450 GeneChip focuses on mutations of key
liver enzymes that metabolize drugs". Moreover, "Affymetrix has a number of additional
GeneChips in development, including ones for the breast cancer gene BRCA1, for
bacterial pathogen identification, and also second-generation HIV biochips for the
detection of additional HIV genes".
Other applications also utilize biochip technology. In addition to biochips that identify
and categorize diseases, biochips are being used for a variety of operations that stretch
beyond medical applications. An example of said application is "Caliper's (Palo Alto,
CA) LabChip, which uses microfluidics technology to manipulate minute volumes of
liquids on chips with no moving parts. Applications include chip-based PCR, as well as
high throughput screening assays based on the binding of drug leads with known drug
targets. Orchid BioComputer (Princeton, NJ) is another microfluidics chip company that
has developed a technology it calls Chemtel, which integrates microfluidic distribution,
temperature modulation, detection system and drive electronics on a single chip. Potential
applications are in drug screening and clinical diagnostic areas, as well as in DNA
mutation and expression analysis". In tandem with the electronic assays Orchid
BioComputer and Caliper are developing, wide ranges of companies are using biochip
technology to investigate "expression profile analysis and broader screening and
diagnostics applications". These functions include the use of biochip technology in
forensics, applying DNA from a particular crime scene on a biochip and using suspect
DNA to connect a culprit to the crime scene. In addition, biochips are being investigated
for possible use in organ match identification, general identity testing, and ecological
testing. "Companies involved in the development of the technical aspects of chip design,
structure and function itself, such as microfluidic applications that are essential for the
miniaturization of the large number of assays carried out on chips". The leadership these
companies take in developing second and third generation biochips are paramount for the
continued development of novel uses for biochip technology.
18

19. One of the challenges to the biochip industry continues to be consistent standardization of
materials used to interpret results. This is important because "when genetic diagnostic
applications are at stake, important clinical decisions (should be based) on the
interpretation of gene chip readouts, and these results need to be independent of the
manufacturer of the biochip".
However, there is work being done to address issues of standardization. "An example of
an effort to address this issue is the formation of the Genetic Analysis Technology
Consortium (GATC) by Affymetrix and Molecular Dynamics Inc. (Sunnyvale, CA). The
aim of this group is to establish an industry standard for the reading and analysis of
multiple types of chips by the same chip readers and detection reagents. Other companies
in the field are considering whether to join or not. An important factor in the current
debate is that different chips have different characteristics and therefore strengths and
weaknesses, and are useful for different things, which may attenuate somewhat the need
for absolute standardization".
Market Analysis
For years industries have been using Michael Porters five forces to define industry
competition. While Biochip technology is only a decade old it has quickly emerged as a
technological force. As a result of the relative youth of this industry we have taken a
novel approach to determining the competitive landscape. Many of the current
participants are recent start-ups, yet some key members of this group are already publicly
traded. As such, they post quarterly reports that include an analysis of what they believe
to be their key threats, opportunities, strengths, and weaknesses. By surveying several of
these players it becomes clear that certain competitive trends have already developed.
This type of analysis is particularly important because it allows firms to see how they can
strategically manage their businesses in ways that play to their strengths. Please use the
subheadings to explore how the biochip industry has developed with regards to each of
Michael Porter's five forces. As you peruse these sections keep in mind that strategic
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20. positioning can be as important as innovation in determining success and failure of any
business endeavor.
CONCLUSION
"Biochips will evolve both in terms of their physical characteristics and also in terms of
the assays they carry out". Biochips will consistently grow smaller and more powerful
with each new generation of biochip created. Additionally, with the development of
specialty biochips, based from various organic materials can lead to new developments
and utilizations. One encouraging development is protein-based biochips. "The so-called
patterning of proteins on various chip substrates is the focus of intense research, with
examples including the development of 3-dimensional patterning vs. nano-patterning on
single layers. These biochips would be used to array protein substrates for drug lead
screening, antibodies for diagnostic purposes, where the biochip then is also a biosensor,
enzymes for catalytic reaction analysis and other applications".A broad "technology
platform", biochip technology will redefine "genetic diagnostics, because of their
reproducibility, low cost and speed.
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