Bio Chips

1. INTRODUCTION

Most of us won’t like the idea of implanting a biochip in our body that

identifies us uniquely and can be used to track our location. That would be a major

loss of privacy. But there is a flip side to this! Such biochips could help agencies to

locate lost children, downed soldiers and wandering Alzheimer’s patients.

The human body is the next big target of chipmakers. It won’t be long

before biochip implants will come to the rescue of sick, or those who are

handicapped in someway. Large amount of money and research has already gone

into this area of technology.

Anyway, such implants have already experimented with. A few US

companies are selling both chips and their detectors. The chips are of size of an

uncooked grain of rice, small enough to be injected under the skin using a syringe

needle. They respond to a signal from the detector, held just a few feet away, by

transmitting an identification number. This number is then compared with the

database listings of register pets.

Daniel Man, a plastic surgeon in private practice in Florida, holds the patent

on a more powerful device: a chip that would enable lost humans to be tracked by

satellite.

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2. BIOCHIP DEFINITION

A biochip is a collection of miniaturized test sites (micro arrays) arranged

on a solid substrate that permits many tests to be performed at the same time in

order to get higher throughput and speed. Typically, a biochip’s surface area is not

longer than a fingernail. Like a computer chip that can perform millions of

mathematical operation in one second, a biochip can perform thousands of

biological operations, 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 specifically designed microscope can determine where the sample

hybridized with DNA strands in the biochip. Biochips helped to dramatically

increase the speed of the identification of the estimated 80,000 genes in human

DNA, in the 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.

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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.

Motorola, Hitachi, IBM, Texas Instruments have entered into the biochip

business.

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3. STRUCTURE AND WORKING OF AN ALREADY

IMPLANTED SYSTEM

The biochip implants system consists of two components: a transponder

and a reader or scanner. The transponder is the actual biochip implant. The

biochip system is radio frequency identification (RFID) system, using low-

frequency radio signals to communicate between the biochip and reader. The

reading range or activation range, between reader and biochip is small, normally

between 2 and 12 inches.

3.1 The transponder

The transponder is the actual biochip implant. It is a passive transponder,

meaning it contains no battery or energy of its own. In comparison, an active

transponder would provide its own energy source, normally a small battery.

Because the passive contains no battery, or nothing to wear out, it has a very long

life up to 99 years, and no maintenance. Being passive, it is 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 biochips. The communication between biochip and reader is via

low-frequency radio waves. Since the communication is via very low frequency

radio waves it is nit at all harmful to the human body.

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The biochip-transponder consists of four parts; computer microchip,

antenna coil, capacitor and the glass capsule.

3.2 Computer microchips

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”.

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BIOCHIP & SYRINGE

3.3 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.

3.4 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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3.5 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.

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3.6 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.

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3.7 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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4. BIOCHIPS CURRENTLY UNDER DEVELOPMENT

1. Chips that follow footsteps

2. Glucose level detectors

3. Oxy sensors

4. Brain surgery with an on-off switch

5. Adding sound to life

6. Experiments with lost sight

4.1 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.

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“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.

4.2 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.

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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

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.

LED

FLUORESCENT
MOLECULES
OPTICAL
FILTER

PHOTODIODE DETECTOR

THE S4MS CHIP SENSING OXYGEN OR GLOUCOSE

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4.3 Oxy Sensors:

A working model of an oxy sensor uses the same layout. With its current

circuitry, it is about the size of a large shirt button but the final silicon wafer will

be less than a millimeter square. The oxygen sensors will be useful not only to

monitor breathing inside intensive care units, but also to check that packages of

food, or containers of semiconductors stored under nitrogen gas remain airtight.

Another version of an oxygen sensing chip currently under development

sends light pulses out into the body. The light absorbed to varying extends,

depending on how much oxygen is carried in the blood, and this chip detects the

light that is left. The rushes of blood pumped by the heart are also detected, so the

same chip is a pulse monitor. A number of companies already make large scale

versions of such detectors.

The transition of certain semiconductors to their conducting state is

inherently sensitive to temperature, so designing the sensor was simple enough.

With some miniature radio frequency transmitters, and foam-rubber earplugs to

hold the chip in place, the device is complete. Applications range from sick

children, to chemotherapy patients who can be plagued by sudden rises in body

temperature in response to their anti-cancer drugs.

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4.4 Brain surgery with an on-off switch:

Sensing and measuring is one thing, but can we switch the body on and off?

Heart pacemakers use the crude approach: large jolts of electricity to synchronize

the pumping of the heart. The electric pulses of Activa implant, made by US-based

Medtronics Inc., are directed not at the heart but at the brain. They turn off brain

signals that cause the uncontrolled movements, or tremors, associated with disease

such as Parkinson’s.

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Drug therapy of Parkinson’s disease aims to replace the brain messenger

dopamine, a product of brain cells that are dying. But eventually the drug’s effects

wear off, and the erratic movements come charging back.

The Activa implant is a new alternative that uses high-frequency electric

pulses to reversibly shut off the thalamus. The implantation surgery is far less

traumatic than thalamatomy, and if there are any post-operative problems the

stimulator can simply be turned off. The implant primarily interferes with aberrant

brain functioning.

4.5 Adding sound to life

The most ambitious bioengineers are today trying to add back brain

functions, restoring sight and sound where there was darkness and silence. The

success story in this field is the cochlear implant. Most hearing aids are glorified

amplifiers, but the cochlear implant is for patients who have lost the hair cells that

detect sound waves. For these patients no amount of amplification is enough.

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THE CLARION COCHLEAR IMPLANT

THE CIRCUITRY OF THE IMPLANTED PART OF THE COCHLEAR

IMPLANT

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The cochlear implant delivers electrical pulses directly to the nerve cells in

the cochlea, the spiral-shaped structure that translates sound in to nerve pulses. In

normal hearing individuals, sound waves set up vibrations in the walls of the

cochlea, and hair cells detect these vibrations. High-frequency notes vibrate nearer

the base of cochlea, while low frequency notes nearer the top of the spiral. The

implant mimics the job of the hair cells. It splits the incoming noises into a number

of channels (typically eight) and then stimulates the appropriate part of the cochlea.

The two most successful cochlear implants are ‘Clarion’ and ‘Nucleus’.

4.6 Experiments with lost sight

With the ear at least partially conquered, the next logical target is the eye.

Several groups are working on the implantable chips that mimic the action of

photoreceptors, the light-sensing cells at the back of the eye. Photoreceptors are

lost in retinitis pigmentosa, a genetic disease and in age related macular

degeneration, the most common reason for loss sight in the developed world.

Joseph Rizzo of the Massachusetts Eye and Ear Infirmary, and John Wyatt of

Massachusetts Institute of Technology have made a twenty electrode 1mm-square

chip, and implanted it at the back of rabbit’s eyes.

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The original chip, with the thickness of human hair, put too much stress on

the eye, so the new version is ten times thinner. The final setup will include a fancy

camera mounted a pair of glasses. The camera will detect and encode the scene,

then send it into the eye as a laser pulse, with the laser also providing the energy to

drive the chip.

Rizzo has conformed that his tiny array of light receivers (photodiodes) can

generate enough electricity needed to run the chip. He has also found that the

amount of electricity needed to fire a nerve cell into action is 100-fold lower than

in the ear, so the currents can be smaller, and the electrodes more closely spaced.

For now the power supply comes from a wire inserted directly in the eye

and, using this device, signals reaches the brain.

Eugene de Jaun of Hopkins Wilmer Eye Institute is trying electrodes,

electrodes inserted directly in to the eyes, are large and somewhat crude. But his

result has been startling. Completely blind patients have seen well-defined flashes,

which change in position and brightness as de Jaun changes the position of the

electrode or amount of current.

In his most recent experiments, patients have identified simple shapes

outlined by multiple electrodes.

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In one US project chips are implanted on the surface of the retina, the

structure at the back of the eyes. The project is putting its implants at the back of

the retina, where the photoreceptors are normally found.

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5. THE AGILENT 2100 BIOANALYZER

The Agilent 2100 bioanalyzer is the industry’s only platform with the

ability to analyze DNA, RNA, proteins and cells. Through lab-on-a-chip

technology the 2100 bioanalyzer integrates sample handling, separation, detection

and data analysis onto one platform. It moves labs beyond messy, time consuming

gel preparation and the subjective results associated with electrophoresis. And

now, with our second generation 2100 bioanalyzer, we have integrated an easier

way to acquire cell based parameters from as few as 20,000 cells per sample.

The process is simple: load sample, run analysis, and view data. The 2100

bioanalyzer is designed to streamline the processes of RNA isolation, gene

expression analysis, protein expression, protein purification and more. One

platform for entire workflow!

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6. BIOCHIPS IN NONINFECTIOUS DISEASES

6.1 Biochips and Proteomics

Biochip technology was largely established by the development of micro

array biochips for genomics research. The emergence of the biochip was perhaps

an inevitable development, an expansion of existing chemistries and concepts into

the information rich world of genomics. The GeneChip, developed at Affymax,

remains the best known example of a biochip.

The essential property of a biochip is the use of solid phase support and

interfacial chemistry to capture molecules from a sample and present them for

analysis. The use of a solid support provides the separation and isolation of an

analyst, and creates the opportunity for high density micro arrays of sampling sites.

Combined with scalable production techniques, often borrowed from

semiconductor fabrication, it also offers the potential of high sample throughput.

There are no absolute restriction on the types of molecules that can be analyzed

using a biochip, only technical problems related to binding, retention and assay.

With the maturing of genomics, some limitations of genome-based research

have become apparent. Although extremely useful, characterization of a cell based

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upon its genes or gene transcripts is only an indirect view. From an engineering

perspective, the complete state of cell might be defined by its molecular

composition. While this includes DND, RNA, small molecules, and ions, this state

is defined by proteins and peptides. Consequently, proteomics, the systems level

study of proteins, represents a direct view of the state of a cell and its parent

organism. With some abstraction, in clinical practice the protein profile obtained

from a biological sample may be seen as synonymous to the phenotype and overall

health state of a patient.

6.2 SELDI Protein Biochips

A major challenge in molecular biology, and particularly biochip

development, is the detection of analytics present in mixtures at extremely low

concentrations. Mixtures create limitations for the optical detection methods

typically used with biochips, while low concentrations present problems when

traditional separation techniques, such as 2-D electrophoresis, are applied.

Surface Enhanced Laser Desorption Ionization Time-of-Flight Mass

Spectroscopy (SELDI-TOF MS) was developed in the last decade as a powerful

tool for overcoming these limitations, and is now being commercialized by several

companies.

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 Bio Chips

With a SELDI protein biochip, proteins are captured at a target site using

techniques that are similar to traditional chromatographic techniques, the analysis

of the biochips, however, is quite different. Instead of optical detection, the bound

proteins are combined with a charge and energy transfer molecule and assayed

using laser desorption ionization time-of-flight mass spectroscopy. With TOF MS,

it becomes possible to simultaneously identify hundreds or thousands of proteins

and peptides bound to a single site. TOF MS is also capable of detecting analytes

present in nanomole to sub-femtomole quantities, corresponding to millimolar to

Pico molar concentrations in a typical biological sample. Because of these

capabilities, SELDI biochip surfaces can be prepared with diverse chemistries that

have varying degrees of protein-binding specificity, and their selectivity may be

further enhanced through variations in protein capture and retention protocols.

6.3 Bioinformatics with SELDI Biochips

In practice, the SELDI-TOF technique provides mass spectra of proteins

unmatched in both its sensitivity and its ability to identify hundreds of proteins

simultaneously. A collection of protein mass spectra can be obtained from diverse

biochip surfaces, using varied protein binding protocols, creating a protein map.

The information in this protein map combines protein molecular weight with

chemical knowledge derived from the protein binding interactions at the biochip

surface.

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Protein maps are rich descriptions of the biological sample, which

characterize the psychological state of a patient. Their information destiny and

complexity often defies simpler linear analysis. In order to best utilize this data,

LumiCyte has developed software that incorporates the latest techniques for data

base mining, pattern recognition, and artificial intelligence. Some of the challenges

include managing large volume data sets, searching for reproducible patters in

data, which has variable alignment and instrument artifacts, and dealing with the

inherent variability present in biological samples. Classification and analysis

methods that have been successful include both trained artificial intelligence tools,

such as support vector machines and genetic algorithms, as well as unsupervised

cluster analysis.

Applying these tools to the differential analysis of protein maps rapidly

uncovers the extent and nature of protein variations. This analysis can be applied to

samples from multiple patients of differing phenotypes, where it leads to early

detection of disease, even in asymptomatic patients. It also provides a powerful

tool for discriminating between physiologically distinct diseases that present

similar or even identical symptoms. With samples from a single patient, analysis of

protein maps reveals early onset of disease, disease progression, and the patient’s

response to therapy.

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6.4 Challenges of protein biochips

A number of challenges remain that define the current boundaries of SELDI

biochip technology. For physical scientists, the optimization of surfaces that

capture and present proteins is an ongoing activity, and the development of TOF

MS for detection over an even wider dynamic range is essential to find rare,

important proteins in the presence of ubiquitous, common proteins. For biological

scientists, sequencing proteins that are discovered with SELDI-TOF MS and

interpreting the complex network of revealed proteins are tasks that expand with

every new sample set.

For applied mathematicians and software engineers, creating new pattern

recognition tools is important as we attempt to identify weaker and weaker signals

in the protein map capture.

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7. DNA BIOCHIPS

A new DNA biochip developed by Tuan Vo-Dinh and colleagues at the

Department of Energy’s (DOE) Oak Ridge National Laboratory (ORNL) could

revolutionize the way the medical profession performs tests on blood. Instead of

patient having to wait several days for the results form a laboratory, they are

virtually immediate with the matchbox-sized biochip. And it requires less blood

with no sacrifice on accuracy.

In addition to time savings, the DNA biochip eliminates the needs for

radioactive labels used for detection. This greatly reduces cost and potential health

effects to technicians and lab workers handling samples and performing tests. It

also reduces disposal costs because chemically labeled blood must be handled

according to strict regulations.

To be useful for detecting compounds in a real-life sample, a biosensor must

be extremely sensitive and able to distinguish between, for example, a bacteria,

virus or chemical or biological species. ORNL’s DNA biochip does that.

Unlike other biosensors based on enzyme and antibody probes, The DNA

biochip is a gene probe-based biosensor.

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8. CONCLUSION

Within ten years you will have a biochip implanted in your head consisting

of financial status, employment and medical records.

Even in a grocery store, sensor will read the credit chip and will

automatically debit the account for purchase.

A biochip implanted in our body can serve as a combination of credit ca5rd,

passport, driver’s license and personal diary. And there is nothing to worry about

losing them.

It is said that by 2008, all members of typical American family including

there pets will have microchips under their skin with ID and medical data

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9. REFERENCES

• www.eurobiochips.com

• www.whatis.com/definition

• www.drugandmarket.com

• www.biochips.org

• www.knowledgefoundation.com

• www.bioarraynews.com

• www.biochips.ifrance.com

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ACKNOWLEDGEMENTS

I express my sincere thanks to Prof. M.N Agnisarman Namboothiri

(Head of the Department, Computer Science and Engineering, MESCE),

Mr. Zainul Abid (Staff incharge) for their kind co-operation for presenting the

seminar.

I also extend my sincere thanks to all other members of the faculty of

Computer Science and Engineering Department and my friends for their co-

operation and encouragement.

RAKESH RAVINDRAN

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ABSTRACT

The human body is the next big target of chipmakers. It won’t be long

before biochip implants will come to the rescue of sick, those who are lost, gunned

soldiers and wandering mental patients etc.

Medical researchers have been working to integrate chips and people for

many years, often plucking devices from well known electronic appliances.

Biochips are being used to genetic, toxicological, protein and biochemical

researches. It can also be used to rapidly detect chemical agents used in biological

warfare so that defensive measures can be taken. Currently implanted systems have

got a range of about two to twelve inches.

The civil liberties debate over biochips has obscured more ethically benign

and medically useful applications. By using Agilent 2100 Bioanalyzer streamline

processes of RNA isolation, gene expression analysis, protein expression, protein

purification and more.

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 Bio Chips

CONTENTS

1. INTRODUCTION
2. BIOCHIP DEFINITION
3. STRUCTURE AND WORKING OF AN ALREADY IMPLANTED
SYSTEM
3.1 THE TRANSPONDER
3.2 COMPUTER MICROCHIP
3.3 ANTENNA COIL
3.4 TUNING CAPACITOR
3.5 GLASS CAPSULE
3.6 THE READER
3.7 HOW IT WORKS
4. BIOCHIPS CURRENTLY UNDER DEVELOPMENT
4.1 CHIPS THAT FOLLOW FOOTSTEPS
4.2 GLUCOSE LEVEL DETECTORS
4.3 OXY SENSORS
4.4 BRAIN SURGERY WITH AN ON-OFF SWITCH
4.5 ADDING SOUND TO LIFE
4.6 EXPERIMENTS WITH LOST SIGHT
5. THE AGILENT 2100 BIOANALYZER
6. BIOCHIPS IN NONINFECTIOUS DISEASES
6.1 BIOCHIPS AND PROTEOMICS
6.2 SELDI PROTEIN BIOCHIPS
6.3 BIOINFORMATICS WITH SELDI BIOCHIPS
6.4 CHALLENGES OF PROTEIN CHIPS
7. DNA BIOCHIPS
8. CONCLUSION
9. REFERENCE

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