NANOTECHNOLOGY IN

DIAGNOSTIC PATHOLOGY
DR MOHAMMAD AAMIR
3RD YEAR PG.
05-07-2017

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INTRODUCTION

The prefix “nano” derived from Greek word

“dwarf”, while the term “nanotechnology” was
coined by the Japanese researcher Norio
Tangiuch in 1974.
Nanotechnology refers to the constructing and
engineering of functional systems at a very
micro level or we can at an atomic level.

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A nanometer is a billionth of a meter. It's difficult to imagine anything so
small, but think of something only 1/80,000 the width of a human hair.
Ten hydrogen atoms could be laid side-by side in a single nanometer.
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HISTORY

The first concept of nanotechnology was given

was famous physicist Sr. Richard Feynman

Invention of scanning
tunneling microscope in
1981 and the discovery of
fullerene(C60) in 1985 lead
emergence of
Nanotechnology.
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More History, Continued

Eric Drexler, Continued

Cell Repair Machines
X
 “By working along molecule by
molecule and structure by
structure, repair machines will be
able to repair whole cells. By
working along cell by cell and
Figure : Stylized example of
tissue by tissue, they…will be able targeted cell repair.
to repair whole organs…they will
restore health.” - Drexler, 1986
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DEFINITION

 Nanotechnology is defined by the

National Nanotechnology Initiative
as
 “the understanding and control of
matter at dimensions between
approximately 1 and 100 nm, where
unique phenomena enable novel
applications”

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WHY NANOTECHNOLOGY?

 The physical and chemical properties of matter change

in the nanoscale.
 These changes involve quantum effects that are not
studied during traditional pathology training programs.
 In brief, as the size of a particulate approaches the
nanoscale, an increasing percentage of the atoms in
the material are at the particle surface.
 At a critical point the fundamental properties of
matter change.

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 The properties that change
include basic properties such
a melting point and color but
of greater importance to
pathologists are:

 Potential increases in the

physical size of each
molecular component as the
total number of molecular
components decreases.

 An increase in the fraction of

molecules on the surface of
the particle, and changes in
surface reactivity.
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NANOTECHNOLOGY APPLICATIONS

Information Technology Energy

• More efficient and cost
• Smaller, faster, more
effective technologies for
energy efficient and
energy production
powerful computing
− Solar cells
and other IT-based − Fuel cells
systems − Batteries
− Bio fuels

Medicine Consumer Goods

• Cancer treatment • Foods and beverages
−Advanced packaging materials,
• Bone treatment sensors, and lab-on-chips for
• Drug delivery food quality testing
• Appetite control • Appliances and textiles
• Drug development −Stain proof, water proof and
• Medical tools wrinkle free textiles
• Diagnostic tests • Household and cosmetics
• Imaging − Self-cleaning and scratch free
products, paints, and better
cosmetics 10
Nanotechnology for Medical
Diagnosis and Therapeutics

 Nanotechnology provides new materials with novel

properties and function for various biomedical
applications such as diagnostics, drug delivery, therapy,
tissue engineering and biosensors.
 Nanotechnology in medical diagnosis covers all field of
science for imaging, measuring, and manipulating
matter at the nanoscale and has important application
in diagnosis, prevention and treatment.

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 Medical application of nanotechnology has ability to
enable early detection, prevention, treatment and
follow up of many life-threatening disease including
cancer, cardiovascular disease, diabetes, Alzheimer’s
and AIDS as well as infectious diseases.

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Nanomaterials for medical diagnosis

 Nanomaterials exhibit higher chemical reactivity,

increased mechanical strength, faster electrical and
magnetic responses owing to its high surface to unit
volume ratio.
 Nanoparticles can attach to biomolecules, allowing
detection of disease biomarkers in a lab sample at a
very early stage.
 Because of their small size, nanomaterials can readily
interact with biomolecules and gaining access to so
many areas of the human body by passing through
intracellular spaces.
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 There is variety of methods to synthesize NPs such as
physical, chemical and biological synthesis.
 The common ways to produce nanomaterials are:
Top down Bottom up.

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Various nanodevices used in diagnostics

Cantilevers.
Nanopores.
Nanotubes.
Quantum dots.
Nanoshells.
Dendrimers.
Magnetic Nanoparticles.
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CANTILEVERS

 These tiny levers, which are anchored at one end, can

be engineered to bind to molecules that represent
some of the changes associated with cancer.
 They bind to altered DNA sequences or proteins that
are present in certain types of cancer.
 When these molecules bind to the cantilevers, surface
tension changes, causing the cantilevers to bend.
 By monitoring the bending of the cantilevers, scientists
can tell whether molecules are present.
 Scientists hope this property will prove effective when
cancer-associated molecules are present--even in very
low concentrations--making cantilevers a potential tool
for detecting cancer in its early stages. 16
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NANOPORES.

 Nanopores, tiny holes that allow DNA to pass through

one strand at a time, will make DNA sequencing more
efficient.
 As DNA passes through a nanopore, scientists can
monitor the shape and electrical properties of each
base, or letter, on the strand.
 Because these properties are unique for each of the
four bases that make up the genetic code, scientists
can use the passage of DNA through a nanopore to
decipher the encoded information, including errors in
the code known to be associated with cancer.
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NANOTUBES-MARKING MUTATIONS

 Another nanodevice that will help identify DNA

changes associated with cancer is the nanotube.
 Nanotubes are carbon rods about half the diameter of
a molecule of DNA that not only can detect the
presence of altered genes, but they may help to
pinpoint the exact location of those changes.
 To prepare DNA for nanotube analysis, scientists must
attach a bulky molecule to regions of the DNA that are
associated with cancer.
 They can design tags that seek out specific mutations in
the DNA and bind to them. 20
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NANOTUBES-MAPPING MUTATIONS.

 Once the mutation has been tagged, researchers use a

nanotube tip resembling the needle on a record player
to trace the physical shape of DNA and pinpoint the
mutated regions.

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 The nanotube creates a map showing the shape of the
DNA molecule, including the tags identifying important
mutations.
 Since the location of mutations can influence the
effects they have on a cell, these techniques will be
important in predicting disease

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NANOSHELLS

Nanoshells are miniscule beads coated with gold.

By manipulating the thickness of the layers
making up the Nanoshells, scientists can design
these beads to absorb specific wavelengths of
light.
The most useful nanoshells are those that absorb
near-infrared light, which can easily penetrate
several centimeters of human tissue.
The absorption of light by the nanoshells creates
an intense heat that is lethal to cells.

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DENDRIMERS

 Research is being done on a number of nanoparticles

created to facilitate drug delivery.
 One such molecule with potential to link treatment
with detection and diagnosis is known as a dendrimer.
 Dendrimers are man-made molecules about the size of
an average protein, and have a branching shape.
 This shape gives them vast amounts of surface area to
which scientists can attach therapeutic agents or other
biologically active molecules.
 Researchers aim eventually to create nanodevices that
do much more than deliver treatment.
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MAGNETIC NANOPARTICLES (MNP):

 MNPs are employed in multiple disciplines such as

biosensors, magnetic resonance imaging and
nanoelectronics etc.
 MNPs commonly consist of magnetic element such as
iron, nickel, and their derivatives.
 MNPs are versatile diagnostic tool as it is manipulated
using external magnetic field. This ‘action at a distance’
phenomenon combined with intrinsic penetrability of
magnetic field into human tissue enables their
detection in vivo using MRI.

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 Super-paramagnetic iron oxide
nanoparticles (SPION) are made
of an iron oxide core and coated
by either inorganic materials like
silica or organic materials such as
phospholipids, natural polymers
such as dextran or chitosan.

 SPIONs are a versatile agent for

early diagnosis of cancer,
atherosclerosis and other
diseases. 31
 Moreover, SPIONs are used as contrast agents for MRI
imaging and as an in-vitro application in bioassay by means
of a vehicle for the detection of biomarkers.
 When SPION used in biosensors it improves the sensitivity
and selectivity of diagnosis

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 Circulating tumor cells (CTCs) are a hallmark of invasive
behavior of cancer, responsible for the development of
metastasis. Their detection and analysis have significant
impacts in cancer biology and clinical practice.

 Nanotechnology shows strong promises for CTC enrichment

and detection owning to the unique structural and functional
properties of nanoscale materials.

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 QUANTUM DOTS (QD):

 Another minuscule molecule that will be used to detect

cancer is a quantum dot.
 Quantum dots are tiny crystals that glow when they are
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.
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Graphene oxide (GO):

 GO is thin layer of sp2 hybridized carbon, extensively

used for medical diagnosis due to its exciting
properties.
 The sheets of GO, on which attached antibody binds to
the cancer cells which then tag the cancer cells with
fluorescent molecules to make the cancer cells stand
out in a microscope.
 Besides, it can detect a very low level of cancer cells, as
low as 3 to 5 cancer cells in a one milliliter of blood
sample
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Gold Nanoparticles (AuNPs) and Silver
Nanoparticles (AgNPs):

 AuNPs are most attractive and extensively studied

nanomaterials in bio-analytical field for medical
diagnosis, owing to its fascinating features such as ease
of synthesis, high biocompatibility and non-cytotoxicity.
 AuNPs have biomedical applications in the areas:
labeling and biosensing.
 The Silver nanorods in a diagnostic system are being
used to separate viruses, bacteria and other
microscopic components of blood samples.

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Other Nanodiagnostic techniques

Nanochips
 One of the most common techniques used today to
analyze DNA sequences is hybridization, or the pairing
of separated strands of DNA with complementary DNA
strands of known sequence that act as probes.
 Currently, DNA chips called DNA micro array assays are
used to analyze DNA. Passive (non-electronic)
technologies can be slow, tedious, and prone to errors
because of nonspecific hybridization of the DNA.

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 A company called Nanogen has developed a product
called the “Nanochip” that employs the power of an
electronic current that separates DNA probes to
specific sites on the array based on charge and size.
 Once these probes are on specific sites of the
nanochip, the test sample (blood) can then be analyzed
for target DNA sequences by hybridization with these
probes.
 The DNA molecules that hybridize with target DNA
sequences fluoresce, which is detected and relayed
back to an onboard system through platinum wiring
that is present within the chip.
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MICROFLUIDICS (LAB ON A CHIP)

 The newest technologies within nanodiagnostics

involve microfluidic or “lab on a chip” systems, in which
the DNA sample is completely unknown.
 The idea behind this kind of chip is simple: the
combination of numerous processes of DNA analysis
are combined on a single chip composed of a single
glass and silicon substrate.
 The device itself is composed of microfabricated fluidic
channels, heaters, temperature sensors,
electrophoretic chambers, and fluorescence detectors
to analyze nanoliter-size DNA samples

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 This device is described as capable of measuring aqueous
reagent and DNA-containing solutions, mixing the solutions
together, amplifying or digesting the DNA to form discrete
products, and then separating and detecting those products.

 Using a pipette, a sample of DNA containing solution is

placed on one fluid-entry port and a reagent containing
solution on the other port. Capillary action draws both
solutions into the device, but hydrophobic patches
positioned just beyond the vent line in each injection channel
stop the samples.

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FUTURE OF NANOTECHNOLOGY

 Researchers aim eventually to create nanodevices that

do much more than to diagnose and deliver treatment
seperately.
 The goal is to create a single nanodevice that will do
many things:
 Assist in imaging inside the body,
 Recognize precancerous or cancerous cells,
 Release a drug that targets only those cells, and
 Report back on the effectiveness of the treatment.
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NANOARRAYS

 Microarrays are important tools for high-throughput

analysis of biomolecules. The use of microarrays for
parallel screening of nucleic acid and protein profiles
has become an industry standard.

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LIMITATION OF MICROARRAY AND IMPORTANCE OF
NANOARRAY

 A few limitations of microarrays are the requirement for

relatively large sample volumes and elongated incubation
time, as well as the limit of detection.
 In addition, traditional microarrays make use of bulky
instrumentation for the detection, and sample amplification
and labeling are quite laborious, which increase analysis cost
and delays the time for obtaining results.
 One strategy for overcoming these problems is to develop
nanoarrays, particularly electronics-based nanoarrays.
 With further miniaturization, higher sensitivity, and
simplified sample preparation, nanoarrays could potentially
be employed for biomolecular analysis in personal
healthcare and monitoring of trace pathogens.
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Possible concerns on Nanoparticles ?

 Experts report smaller

particles are more
bioactive and toxic.
Their ability to interact
with other living
systems increases
because they can easily
cross the skin, lung, and
in some cases the
blood/brain barriers.
Once inside the body,
there may be further
biochemical reactions
like the creation of free
radicals that damage
cells. 50
Institute for Occupational Safety and
Health (NIOSH) concerns on Nanoscience

 NIOSH hopes to: raise awareness of the occupational

safety and health issues involved with nanotechnology;
make recommendations on occupational safety and
health best practices in the production and use of
nanomaterials.

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CONCLUSION

 It has been proved that nanotechnology is a promising area

of scientific and technological advancement.
 In nanotechnology, big things are expected from really small
things.
 The introduction of biocompatible materials and devices
that are engineered on the nanometer scale that interact
with biological molecules and cells and provide specified
diagnostic, therapeutic, and imaging functions will utterly
change the way in which health care is provided in the
future.
 For nanotechnology to prosper there needs to be a true
unification of sciences, which will require a multidisciplinary
approach.
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REFERENCES

 1. The American Heritage® Dictionary of the English Language, 4th edition

Copyright © 2010 by Houghton Mifflin Harcourt Publishing Company.
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 3. Blaufox MD (2002) An ear to the chest: An illustrated history of the evolution
of the stethoscope. J R Soc Med. Dec 95: 626–627.
 4. Satvekar RK, Tiwale BM and Pawar SH*: Emerging Trends in Medical Diagnosis:
A Thrust on Nanotechnology.
 5. Anna Pratima Nikalje*: Nanotechnology and its Applications in Medicine

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