nanotechnology in medicin

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INTRODUCTION

Nanotechnology:-

Nanotechnology is defined as the study and use of structures between 1

nanometer and 100 nanometers in size. To give you an idea of how small that is,

it would take eight hundred 100 nanometer particles side by side to match the

width of a human hair .

Nanotechnology involves manipulating properties and structures at the

nanoscale, often involving dimensions that are just tiny fractions of the width of

a human hair. Nanotechnology is already being used in products in its passive

form, such as cosmetics and sunscreens, and it is expected that in the coming

decades, new phases of products, such as better batteries and improved

electronics equipment, will be developed and have far-reaching implications.

One area of nanotechnology application that holds the promise of providing

great benefits for society in the future is in the realm of medicine.

Nanotechnology is already being used as the basis for new, more effective drug

delivery systems and is in early stage development as scaffolding in nerve

regeneration research. Moreover, the National Cancer Institute has created the

Alliance for Nanotechnology in Cancer in the hope that investments in this

branch of nanomedicine could lead to breakthroughs in terms of detecting,

diagnosing, and treating various forms of cancer.

Nanotechnology medical developments over the coming years will have a wide

variety of uses and could potentially save a great number of lives.

Nanotechnology is already moving from being used in passive structures to

active structures, through more targeted drug therapies or “smart drugs.” These

new drug therapies have already been shown to cause fewer side effects and be

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more effective than traditional therapies. In the future, nanotechnology will also

aid in the formation of molecular systems that may be strikingly similar to

living systems. These molecular structures could be the basis for the

regeneration or replacement of body parts that are currently lost to infection,

accident, or disease. These predictions for the future have great significance not

only in encouraging nanotechnology research and development but also in

determining a means of oversight. The number of products approaching the

FDA approval and review process is likely to grow as time moves forward and

as new nanotechnology medical applications are developed.

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WHAT IS MEDICAL NANOTECHNOLOGY?

Medical nanotechnology is a branch of nanotechnology which applies principles

in this field to health care issues. Nanotechnology is a broad spectrum of

scientific endeavours which involves manufacturing and machining which take

place on a molecular scale. There are a number of potential applications for

medical nanotechnology, and in its early phases, many people were quite

excited about the huge changes which could occur in the medical world with the

assistance of medical technology.

Because nanotechnology operates on such a small scale, it offers the

opportunity to create precisely targeted surgical instruments, drug delivery

systems, and implants. Nanobots, for example, could be used to perform a non-

invasive medical imaging study inside the body, or to perform surgical

procedures. Nanomaterials can also be implanted into the body; for example,

someone with a badly damaged bone or joint could be treated with nanoparticles

which would promote new growth, regrowing the damaged tissue.

Medical nanotechnology also makes cell repair on a molecular level possible,

and provides a number of opportunities for medication administration. Drugs

developed through nanotechnology could directly penetrate cells, for example,

or nanoparticles could be designed to target cancer cells, delivering medication

or providing a focal point for radiation. Medical nanotechnology can also be

used to make biosensors which can be implanted into patients for monitoring,

along with medical devices which are designed to be permanently implanted

such as pacemakers.

This field also has a number of implications for prosthetics. Nanomaterials

could be used to give people greater control over prosthetic limbs, and

potentially to do things like restoring function to the eyes. Several militaries

have invested in medical nanotechnology for the purpose of developing new

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treatments for injured soldiers. The field also creates a potential for the

development of devices which could enhance human function, much to the

delight of science fiction authors around the world.

HISTORY OF NANOTECHNOLOGY

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A Short History of Nanotechnology

Year History

1959 Feynman gives after-dinner talk describing molecular machines

building with atomic precision

1974 Taniguchi uses term "nano-technology" in paper on ion-sputter

machining

1977 Drexler originates molecular nanotechnology concepts at MIT

1981 1.First technical paper on molecular engineering to build with atomic

precision

2.STM invented

1985 Bucky ball discovered1986 1.First book published

2.AFM invented

3.First organization formed

1987 1.First protein engineered

2.First university symposium

1988 First university course

1989 1.IBM logo spelled in individual atoms

2.First national conference

1990 First nanotechnology journal

1991 Carbon nanotube discovered

1992 1.First textbook published

2.First Congressional testimony

1994 1.Nanosystems textbook used in first university course

2.US Science Advisor advocates nanotechnology

1995 1.First think tank report2.First industry analysis of military applications

1996 1.First European conference

2.NASA begins work in computational nanotech

3.First nanobio conference

1997 1.First company founded: Zyvex

2.First design of nanorobotic system

1998 1.First NSF forum, held in conjunction with Foresight Conference2.First DNA-based nanomechanical device

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1999 1.First Nanomedicine book published

2.First safety guidelines

3.Congressional hearings on proposed National Nanotechnology

Initiative

2001 1.First report on nanotech industry

2.U.S. announces first center for military applications

2002 1.First nanotech industry conference

2.Regional nanotech efforts multiply

2003 1.Congressional hearings on societal implications

2.Call for balancing NNI research portfolio

2004 1.First policy conference on advanced nanotech2.First center for nanomechanical systems

2005 At Nanoethics meeting, Roco announces nanomachine/nanosystem

project count has reached 300

2006 National Academies nanotechnology report calls for experimentation

toward molecular manufacturing

2007 Feynman Prize in Nanotechnology awarded for construction of

molecular machine systems that function in the realm of Brownianmotion, and molecular machines based upon two-state mechanically

interlocked compounds

2008 1.Technology Roadmap for Productive Nanosystems released

2.Protein catalysts designed for non-natural chemical reactions

2009 1.An improved walking DNA nanorobot

2.Structural DNA nanotechnology arrays devices to capture

molecular building blocks

3.Design 'from scratch' of a small protein that performed the function

performed by natural globin proteins

4.Organizing functional components on addressable DNA scaffolds

2010 1.DNA-based 'robotic' assembly begins

2011 1.First programmable nanowire circuits for nanoprocessors

2.DNA molecular robots learn to walk in any direction along a

branched track

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3.Mechanical manipulation of silicon dimers on a silicon surface

NANOBIOSENSORS

INTRODUCTION:

A biosensor is generally defined as a measurement system that consists of a

probe with a sensitive biological recognition element, or bioreceptor, a

physicochemical detector component, and a transducer in between.

Nanosensors are any biological, chemical, or surgery sensory points used to

convey information about nanoparticle to the macroscopic world. Their use

mainly include various medicinal purposes and as gateways to building other

nanoproducts, such as computer chips that work at the nanoscale and

nanorobots.

Components:-

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1) BIORECEPTORS

2) TRANSDUCERS

3) DETECTORS

1. Bioreceptors:- It is a sensitive biological element. The interaction of an

analyte, e.g. a particular chemical component, virus or micro-organism, with the

bioreceptor is designed to generate an effect picked up by a transducer, which

converts the information into a measurable effect by the detector, for instance

an electric signal. Bioreceptors are used because of their specificity. They

enable measurement with minimum interference from other components in

complex mixtures. The bioreceptor is a biological molecule (e.g., an

antibody/antigen, DNA, protein, or enzyme), or a living biological system (e.g.,

cells, tissues, or whole organisms) that utilises a biochemical mechanism of

recognition. The sampling component of a biosensor contains a bio-sensitive

layer that can either contain bioreceptors or be made of bioreceptors covalently

attached to the transducer.

2. Transducer -Transduction can be accomplished by optical, electrochemical,

and mass detection methods.

3. Detection techniques:-

1. ELECTROCHEMICAL METHODS

Electrochemical biosensors are generally fairly simple devices. There are three

types utilising electrical current, potential or resistive changes:

1. Amperometric biosensors:- which determine the electric current associated

with the electrons involved in redox processes;

2. Potentiometric biosensors:- which use ion-selective electrodes to determine

changes in the concentration of chosen ions (e.g.hydrogen ions); and

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3.Conductimetric biosensors:- which determine conductance changes associated

with changes in the ionic environment.

Amperometric Biosensors

Enzyme-catalysed redox reactions can form the basis of a major class of

biosensors if the flux of redox electrons can be determined. Normally a constant

potential is applied between two electrodes and the current, due to the electrode

reaction, is determined. The potential is held relative to that of a reference

electrode and is chosen such that small variations do not affect the rate of the

electrode reaction. Direct electron transfer between the electrode and the redoxsite associated with the enzyme is kinetically hindered due to the distance

between them or the presentation of an unfavourable pathway for the electrons.

This can usually be addressed by the use of mediators and/or special electrode

materials.

Fig:- Amperometric glucose biosensor based on the oxygen electrode utilising

glucose oxidase (GOD).

Reactions:-

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The first and simplest biosensor was based on this principle. It was for

the determination of glucose and made use of the Clark oxygen electrode.

Figure shows a section through such a simple amperometric biosensor. A

potential of 0.6V is applied between the central platinum cathode and the

surrounding silver/silver chloride reference electrode (the anode). Dissolved

molecular oxygen at the platinum cathode is reduced and the circuit is

completed by means of the saturated KCl solution. Only oxygen can be reduced

at the cathode due to its covering by a thin Teflon or polypropylene membrane

through which the oxygen can diffuse but which acts as a barrier to other

electroactive species.

The biocatalyst is retained next to the electrode by means of

a membrane, which is permeable only to low molecular weight molecules

including the reactants and products. Glucose may be determined by the

reduction in the dissolved oxygen concentration when the redox reaction,

catalysed by glucose oxidase occurs:

It is fortunate that this useful enzyme is also one of the most stable

oxidoreductases found.

Potentiometric Biosensors

Changes in ionic concentrations are easily determined by use of ionselective

electrodes. This forms the basis for potentiometric biosensors. Many

biocatalysed reactions involve charged species, each of which will absorb or

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release hydrogen ions according to their pKa and the pH of the environment.

This allows a relatively simple electronic transduction using the commonest ion

selective electrode, the pH electrode. Potentiometric biosensors can be

miniaturised by the use of field effect transistors (FETs).

Fig :- A FET-based potentiometric biosensor.

Ion-selective field effect transistors (ISFETs) are low-cost devices that are in

mass production. Figure shows a diagrammatic cross-section through an npn

hydrogen ion-responsive ISFET with an approximately 0.025mm2 biocatalytic

membrane covering the ion-selective membrane. The build-up of positive

charge on this surface (the gate) repels the positive holes in the p-type silicon,

causing a depletion layer and allowing the current to flow. The reference

electrode is usually an identical ISFET without any biocatalytic membrane. A

major practical problem with the manufacture of such enzyme-linked FETs

(ENFETs) is protection of the silicon from contamination by the solution, hence

the covering of waterproof encapsulant. Because of their small size, they only

require minute amounts of biological material and can be produced in a form

whereby they can determine several analytes simultaneously. A further

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advantage is that they have a more rapid response rate compared with the larger,

sluggish ion-selective electrode devices. The enzyme may be immobilised to the

silicon nitride gate using polyvinylbutyral deposited by solvent evaporation and

cross-linked with glutaraldehyde. Such devices still present fabrication

problems such as reproducibility, drift, sensitivity to light and the need for on-

chip temperature compensation.

Conductimetric Biosensors

Many biological processes involve changes in the concentrations of ionic

species. Such changes can be utilised by biosensors that detect changes inelectrical conductivity. A typical example of such a biosensor is the urea sensor,

utilising immobilised urease and used as a monitor during renal surgery and

dialysis. The reaction gives rise to a large change in ionic concentration at pH

7.0, making this type of biosensor particularly attractive for monitoring urea

concentrations.

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Fig:- Parts of a conductimetric biosensor electrode arrangement. (a) Top view;

(b) cross-sectional view. The tracks are about 5 mm wide and the thicknesses of

the various layers are approximately SiO2 0.55 mm, Ti 0.1 mm, Pt 0.1 mm, Au

2 mm.

An alternating field between the two electrodes allows the conductivitychanges

to be determined while minimising undesirable electrochemical processes. The

electrodes are interdigitated to give a relatively long track length (B1 cm) within

a small sensing area (0.2mm2). A steady-state response can be achieved in a

few seconds, allowing urea to be determined within the range 0.1–10mM. The

output is corrected for non-specific changes in pH and other factors by

comparison with the output of a non-enzymic reference electrode pair on the

same chip. The method can easily be extended to use other enzymes and

enzyme combinations that produce ionic species, for example amidases,

decarboxylases, esterases, phosphatases and nucleases. As molecular iodine

molecules change the conductivity of iodine-sensitive phthalocyanine films,

they may be used in peroxidase-linked immunoassays where the peroxidase

converts iodide ions to iodine. Conductimetric biosensors have also be devised

to determine DNA hybridisation.

2. PIEZOELECTRIC BIOSENSORS

The piezoelectric effect is due to some crystals containing positive and negative

charges that separate when the crystal is subjected to a stress, causing the

establishment of an electric field. As a consequence, if this crystal is subjected

to an electric field it will deform. An oscillating electric field of a resonant

frequency will cause the crystal to vibrate with a characteristic frequency

dependent on its composition and thickness and also the way in which it has

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been cut. As this resonant frequency varies when molecules adsorb on the

crystal surface, a piezoelectric crystal may form the basis of a biosensor. Even

small changes in resonant frequencies are easy to determine with precision and

accuracy using straightforward electronics. Differences in mass, even as small

as 1 ng cm–2, can be measured when adsorbed on the sensing surface. Changes

in frequency are generally determined relative to a similarly treated reference

crystal but without the active biological material. As an example, a biosensor

for cocaine in the gas phase may be made by attaching cocaine antibodies to the

surface of a piezoelectric crystal. This biosensor changes frequency by about 50

Hz for a 1 ppb atmospheric cocaine sample and can be reused after flushing for

a few seconds with clean air. The relative humidity of the air is important,

because if it is too low the response is less sensitive and if it is too high the

piezoelectric effect may disappear altogether. Cocaine in solution can be

determined after drying such biosensors.

Enzymes with gaseous substrates or inhibitors can also be attached to suchcrystals, as has been proved by the production of biosensors for formaldehyde

incorporating formaldehyde dehydrogenase and for organophosphorus

insecticides incorporating acetyl cholinesterase. One of the drawbacks

preventing the more widespread use of piezoelectric biosensors is the difficulty

in using them to determine analytes in solution. The frequency of a piezoelectric

crystal depends on the liquid’s viscosity, density and specific conductivity.

Under unfavourable conditions, the crystal may cease to oscillate completely.

There is also a marked effect of temperature due to its effect on viscosity. The

binding of material to the crystal surface may be masked by other

intermolecular effects at the surface and bulk viscosity changes consequent

upon even small concentration differences. There is also the strong possibility

of interference due to non-specific binding.

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Antibody–antigen binding can be determined by measuring the frequency

changes in air after drying the crystal. Such procedures, although sensitive, are

difficult to reproduce repetitively, as the antibody layer may be partially lost

when the antigen is removed. However, oneshot biosensors have been

developed, using this principle, for the detection of several food contaminants

such as enterobacteria.

Fig:- A surface acoustic wave (SAW) biosensor

Piezoelectricity is also utilised in surface acoustic wave (SAW) devices

where a set of interdigitated electrodes is microfabricated at each end of a

rectangular quartz plate (Figure 18.12). Binding of molecules to the surface

affects the propagating wave, generated at one end, such that its frequency is

reduced before reception at the other. The sensitivity of these devices is

proportional to their frequency and dependent on minimising the interference

from non-specific binding.

3. OPTICAL BIOSENSORS

Optical biosensors (also called optodes) have generated considerable interest,

particularly with respect to the use of fibre optics and optoelectronic

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transducers. These allow the safe non-electrical remote sensing of materials in

hazardous or sensitive (i.e. in vivo) environments. An advantage of optical

biosensors is that no reference sensor is needed; a comparative signal is

generally easily generated by splitting the light source used by the sampling

sensor. A simple example of an optical biosensor is the fibre optic lactate sensor

which senses changes in molecular oxygen concentrations by determining its

quenching of a fluorescent dye:

Fig:- A fibre optic lactate biosensor

quenching and consequentially causing an increase in the fluorescence output.

Simple colorimetric changes can be monitored in some biosensor

configurations. A lecithin biosensor has been developed containing

phospholipase D, choline oxidase and bromothymol blue. The change in pH,

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due to the formation of the acid betaine from the released choline, causes a

change in the bromothymol blue absorbance at 622 nm. Gasphase reactions can

also be monitored. For example, alcohol vapour can be detected by the colour

change of a dry dispersion of alcohol oxidase and peroxidase plus the redox dye

2,6-dichloroindophenol.

One of the most widely established biosensor technologies is the lowtechnology

single-use colorimetric assay based on a paper pad impregnated with reagents.

This industry revolves mainly round blood and urine analysis with test strips

costing only a few cents. A particularly important use for these colorimetric test

strips is the detection of glucose. In this case, the strips contain glucose oxidase

and horseradish peroxidase together with a chromogen (e.g. o-toluidine) which

changes colour when oxidised by the peroxidase-catalysed reaction with the

hydrogen peroxide produced by the aerobic oxidation of glucose:

The colour produced can be evaluated by visual comparison with a test

chart or by the use of a portable reflectance meter. Many test strips incorporate

anti-interference layers to produce more reproducible and accurate results. It is

possible to link up luminescent reactions to biosensors, as light output is a

relatively easy phenomenon to transduce to an electronic output. As an

example, the reaction involving immobilised (or free) luciferase can be used to

detect the ATP released by the lysis of microorganisms:

This allows the rapid detection of urinary infections by detecting the microbial

content of urine samples.

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NANOPARTICLES

In nanotechnology, a particle is defined as a small object that behaves as

a whole unit in terms of its transport and properties. Particles are further

classified according to size : in terms of diameter, coarse particles cover a range

between 10,000 and 2,500 nanometers. Fine particles are sized between 2,500

and 100 nanometers. Ultrafine particles, or nanoparticles are sized between 100

and 1 nanometers.

Nanoclusters have at least one dimension between 1 and 10 nanometers and a

narrow size distribution. Nanopowders are agglomerates of ultrafine particles,

nanoparticles, or nanoclusters. Nanometer-sized single crystals, or single-

domain ultrafine particles, are often referred to as nanocrystals.

Nanoparticle research is currently an area of intense scientific interest due to a

wide variety of potential applications in biomedical, optical and electronic

fields.

Properties of Nanoparticles:-

A nanometer is one-billionth of a meter (10-9 m); a sheet of paper is about

100,000 nanometers thick. These nanoparticles give us the ability to see cells

and molecules that we otherwise cannot detect through conventional imaging.

The ability to pick up what happens in the cell, to monitor therapeutic

intervention and to see when a cancer cell is mortally wounded or is actually

activated is critical for the successful diagnosis and treatment of this disease.

For drug delivery in cancer we have “Nano scale devices”. Nanoscale devices

are 102 to 104 times smaller than human cells but are similar in size to large

biomolecules such as enzymes and receptors. Nanoscale devices smaller than 50

nm can easily enter most cells, and those smaller than 20 nm can move out of

blood vessels as they circulate through the body. Nanodevices are suitable to

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serve as customized, targeted drug delivery vehicles to carry large doses of

chemotherapeutic agents or therapeutic genes into malignant cells while sparing

healthy cells.

Quantum Dots (QDs)

Quantum dots are unique in their far reaching possibilities in many avenues of

medicine. A QD is a fluorescent nanoparticle that has potential to be used as a

sensitive probe for screening cancer markers in fluids, as a specific label for

classifying tissue biopsies and as a high resolution contrast agent for medical

imaging, which is capable of detecting even the smallest of tumors. These particles have the unique ability to be sensitively detected on a wide range of

length scales, from macroscale visualization, down to atomic resolution using

electron microscopy. Using Quantum dots (QDs), the drug delivery particles are

injected in to blood stream until they find the cancer cells, to which the

antibodies adhere. Infrared light shining on the suspected cancer site penetrates

the tissues and cause the quantum dots to radiate photons. The photons pinpointthe cancer cell’s location and also cause the release of the Taxol (an

anticancerous drug), which can then attack and kill the cancer cells. Quantum

dots are tiny crystals that glow when stimulated by ultraviolet light. The

wavelength, or color, of the light depends on the size of the crystal. Latex beads

filled with these crystals can be designed to bind to specific DNA sequences. By

combining different sized quantum dots within a single bead, scientists can

create probes that release distinct colors and intensities of light. When the

crystals are stimulated by UV light, each bead emits light that serves as a sort of

spectral bar code, identifying a particular region of DNA. The diversity of

quantum dots will allow scientists to create many unique labels, which can

identify numerous regions of DNA simultaneously. This will be important in the

detection of cancer, which results from the accumulation of many different

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changes within a cell. Another advantage of quantum dots is that they can be

used in the body, eliminating the need for biopsy.

Nanotechnology may also be useful for developing ways to eradicate

cancer cells without harming healthy, neighboring cells. Scientists hope to use

nanotechnology to create therapeutic agents that target specific cells and deliver

their toxin in a controlled, time-released manner.

CONCLUSION

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Nanotechnology is definitely a medical boon for diagnosis, treatment and

prevention of cancer disease. It will radically change the way we diagnose, treat

and prevent cancer to help meet the goal of eliminating suffering and death

from cancer. Although most of the technologies described are promising and fit

well with the current methods of treatment, there are still safety concerns

associated with the introduction of nanoparticles in the human body.

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nanotechnology in medicin

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