BIOCHIP TECHNOLOGY

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A seminar report on
BIOCHIP TECHNOLOGY
DEPARTMENT OF COMPUTER SCIENCE & ENGINEERING
SRI VASAVI ENGINEERING COLLEGE
Pedatadepalli, Tadepalligudem-534101,
W.G.Dist, AndhraPradesh,
Submitted By
P.NAVYA SRI
(14A81A05A3)

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INDEX
Chapter No Content Name Page No
ABSTRACT
1.
INTRODUCTION 1
1.1 What is a biochip? 1
1.2Generation/History 2
2. HOW DOES A BIOCHIP WORK 3
3.
BIOCHIP ARCHITECTURE 4
3.1Size 4
3.2 Components 4
3.3 Cost 6
4.
APPLICATIONS OF BIOCHIP 7
4.1Genomics 7
4.2 Proteomics 7
4.3Cellomics 7
4.4 Biodiagnostics and (Nano) Biosensors 8
4.5 Protein Chips for Diagnosis and Analysis of Diseases 8
5. HUMAN INTERFACE TO BIOCHIP 9
6. BIOCHIPS CURRENTLY UNDER DEVELOPMENT 13
7.
ADVANTAGES & DISADVANTAGES 15
7.1 Advantages 15
7.2 Disadvantages 15
8. DEVELOPMENTS & PROJECTS 17
9. CONCLUSION 19

3. 3
10. REFERENCES 20
LIST OF FIGURES
Figure No Figure Name Page No
Fig 1.1 Biochip 1
Fig 3.1 Actual size of chip 4
Fig 3.2 Components 5
Fig 5.1 Human interfacing of Biochip 9
Fig 5.2 Syringe to implant Biochip 10
Fig 5.3 Reader or Scanner 11
Fig 6.1 The S4ms Chip Sensing Oxygen or Glucose 14

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ABSTRACT
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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1.INTRODUCTION
1.1 What is a 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 1.1Biochip

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1.2Generation/History
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, continued down this road by allowing researchers to amplify minute
amounts of DNA to quantities where it could be detected by standard laboratory methods. A
further refinement was provided by Leroy Hood's 1986 method for fluorescence-based DNA
sequencing, which facilitated the automation of reading DNA sequence.
Further developments, such as sequencing by hybridization, gene marker
identification, and expressed sequence tags, provided the critical technological mass to
prompt corporate efforts to develop miniaturized and automated versions of DNA sequencing
and analysis to increase throughput and decrease costs. In the early and mid-1990s,
companies such as Hyseq and Affymetrix were formed to develop DNA array technologies.

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1. HOW DOES A BIOCHIP WORK
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) in
micro metre spacing(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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2. 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.
3.1Size
The size of Biochip is of a size of an uncooked rice grain size. It ranges from 2inches
to 12inches.
Fig 3.1 actual size of chip
3.2 Components
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’s own energy source, normally a small battery. Because the
passive biochip contains no battery, or nothing to wear out, it has a very long life, up to 99
years, and no maintenance. Being passive, it's inactive until the reader activates it by sending
it a low-power electrical charge. The reader "reads" or

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Fig 3.2 Components
"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.
Computer Microchip: The microchip stores a unique identification number from 10 to
15 digits long. The storage capacity of the current microchips is limited, capable of storing
only a single ID number. AVID (American Veterinary Identification Devices), claims their
chips, using a nnn-nnn-nnn format, has the capability of over 70 trillion unique numbers. The
unique ID number is "etched" or encoded via a laser onto the surface of the microchip before
assembly. Once the number is encoded it is impossible to alter. The microchip also contains
the electronic circuitry necessary to transmit the ID number to the "reader".
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.
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

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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.
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. Then,
prices for biochips, like the prices for computer memory chips, would fall through the floor.

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4. APPLICATIONS OF BIOCHIP
4.1Genomics
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 .
4.2 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 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
4.3Cellomics
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:
 Design/develop "lab-in-cell" platforms handling single or few cells with nanoprobes
in carefully controlledenvironments.

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 Cell handling, which involve 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
4.4 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.
microfluidics are compared for ease/efficiency Incorporation of suitablesensing modality by
evaluating tradeoffs and downselect detection modes(color / luminometric, electrochemical,
biochemical, optical methods) forspecific need.
4.5 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.

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5. 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. According to AVID "Once implanted, the identity tag is virtually
impossible to retrieve. The number can never be altered."
Fig 5.1 Human interfacing of Biochip

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The syringe used is of a normal size seringe & the chip can be placed below the skin
layer very easily.
Fig 5.2 Syringe to implant 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 and healthcare
applications.
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.
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.

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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 boldly tissue fibers bond or interconnect,
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.
Fig 5.3 Reader or Scanner

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The reader
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.
How it works
The reader generates a low-power, electromagnetic field, in this case via radio signals,
which “activates” the implanted biochip. 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, except metal.

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6. BIOCHIPS CURRENTLY UNDER DEVELOPMENT
1. Chips that follow footsteps
2. Glucose level detectors
Chips that follow footsteps
The civil liberties debate over biochips has obscured their more ethically benign and
medically useful applications. Medical researchers have been working to integrate chips and
people for many years, often plucking devices from well known electronic appliances. Jeffry
Hausdorff of the Beth Israel Deaconess Medical Center in Boston has used the type of
pressure sensitive resistors found in the buttons of a microwave oven as stride timers. He
places one sensor in the heel of a shoe, and one in the toe, adds a computer to the ankle to
calculate the duration of each stride. “Young, healthy subjects can regulate the duration of
each step very accurately,” he says. But elderly patients prone to frequent falls have
extremely variable stride times, a flag that could indicate the need for more strengthening
exercises or a change in medication. Hausdorff is also using the system to determine the
success of a treatment for congestive heart failure. By monitoring the number of strides that a
person takes, can directly measure the patient’s activity level, bypassing the often-flowed
estimate made by the patient.
Glucose level detectors
Diabetics currently use a skin prick and a handheld blood test, and then medicate
themselves with the required amount of insulin. The system is simple and works well, but the
need to draw blood means that most diabetics do not test themselves as often as they should.
The new S4MS chip will simply sit under the skin, sense the glucose level, and send the
result back out by radio frequency communication. A light emitting diode starts off the
detection process. The light that it produces hits a fluorescent chemical: one that absorbs the
incoming light and re-emits it at a longer wavelength. The longer wavelength of light is
detected, and the result is send to a control panel outside the body. Glucose is detected
because the sugar reduces the amount of light that a fluorescent chemical re-emits. The more
glucose is there the less light that is detected. S4MS is still developing the perfect fluorescent
chemical, but the key design innovation of the S4MS chip has been fully worked out. The
idea is simple: the LED is sitting in a sea of fluorescent molecules. In most detectors the light

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source is far away from the fluorescent molecules, and the inefficiencies that come with that
mean more power and larger devices. The prototype S4MS chip uses a 22 microwatt LED,
almost forty times less powerful than a tiny power-on buttons on a computer keyboard. The
low power requirements mean that energy can be supplied from outside, by a process called
induction. The fluorescent detection itself does not consume any chemicals or proteins, so the
device is self sustaining
Fig 6.1 The S4ms Chip Sensing Oxygen or Glucose
Typical Problem of BIOCHIPS
 A chip implant would contain a person’s financial world, medical history health care
it would contain his electronic life.
 If cash no longer existed and if the world’s economy was totally chip oriented; —
there would be a huge "black-market" for chips! Since there is no cash criminals
would cut off hands and heads, stealing "rich-folks" chips.
 It is very dangerous because once kidnappers get to know about these chips, they will
skin people to find them,"

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7. ADVANTAGES & DISADVANTAGES
7.1 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
reference laboratories and has access to real sample material from a wide selection of
hosts and viruses.
 To rescue the sick
 To find lost people.
 To locate downed children and wandering Alzheimer’s Patients.
 To identify person uniquely.
 They can perform thousands of biological reactionsoperations in few seconds.
 In monitoring health condition of individuals in which they are specifically employed.
 They can perform thousands of biochemical reactions.
7.2 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.
 They raise critical issues of personal privacy.
 They mark the end of human freedom and dignity.
 They may not be supported by large % of people.

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 There is a danger of turning every man, women, and Child into a controlled slave.
 Through cybernitic biochip implants people will think and act as exactly pre-
programmed.
 They can be implanted into one’s body without their knowledge.

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8. DEVELOPMENTS & PROJECTS
View of the Future
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. Beyond that, 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.
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

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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 custom
tailoredfor their specific application.

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9. 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 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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Biomolecular Separation and Analysis. Caister Academic.
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