applications of nanotechnology in diagnostic pathology

1. D R . E K I R A N K U M A R
P R O F E S S O R O F P A T H O L O G Y
G A Y A T R I V I D Y A P A R I S H A D M E D I C A L
C O L L E G E
V I S A K H A P A T N A M
NANOTECHNOLOGY IN
DIAGNOSTIC PATHOLOGY

2.  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 even at an atomic
level.
 Collective term for a range of technologies, techniques and
processes that involve the manipulation of matter at the
smallest scale

3.  It is the creation and utilization of materials, devices, and
systems through the control of matter on the nanometer (1
billionth of a meter, 10-9)-length scale.
 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.
 Nanotechnology-on-a-chip is a general description that can be
applied to several methods.

4.  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.
 Cell Repair Machines - “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 tissue by tissue, they…will be able to repair whole
organs…they will restore health.” - Drexler, 1986

5.  Nanotechnology is defined by the National
Nanotechnology Initiative (NNI) as “the
understanding and control of matter at dimensions
between approximately 1 and 100 nm, where unique
phenomena enable novel applications.

6.  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.

7. NANOTECHNOLOGY APPLICATIONS
 Information Technology, Energy
 Medicine , Consumer Goods
 Smaller, faster, more energy efficient and powerful computing and
other IT-based systems
More efficient and cost effective technologies for energy production −
Solar cells − Fuel cells − Batteries − Bio fuels
 •Foods and beverages −Advanced packaging materials, sensors, and
lab-on-chips for food quality testing •Appliances and textiles −Stain
proof, water proof and wrinkle free textiles •Household and cosmetics
− Self-cleaning and scratch free products, paints, and better cosmetics
 Medical applications - Cancer treatment •Bone treatment •Drug
delivery •Appetite control •Drug development •Medical tools
•Diagnostic tests •Imaging

8. Nanotechnology for Medical Diagnosis and
Therapeutics
 Provides new materials with novel properties and
function for various biomedical applications such as
diagnostics, drug delivery, therapy, tissue engineering
and biosensors.
 In medical diagnosis, covers all fields for imaging,
measuring, and manipulating matter at the nanoscale
and has important application in diagnosis, prevention
and treatment.
 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.

9. NANOCHIP

10. Approaches in nanotechnology
 There is variety of methods to synthesize
nanoparticles such as physical, chemical and
biological synthesis.
 The common ways to produce nanomaterials are :
1. Bottom up
2. Top down

11.  Bottom up:
 Different materials and devices are constructed from
molecular components of their own.
 They chemically assemble themselves by recognizing
the molecules of their own breed.
 Examples of molecular self assembly are
Watson crick base pairing
Nanolithoghraphy

12. Top down:
 Nano objects and materials are created by larger
entities without bouncing its atomic reactions
 Usually top down approach is practiced less as
compared to the bottom up approach.

14.  Nanotechnology
Nanodevices
Nanomaterial
NEMS
MEMS
Polymer
Non
polymer
-Carbon
tubes
-Metallic
-Nano
rods
Dendrimer

15. NANO DEVICES
 Solid-state techniques can also be used to create
devices known as Nanoelectromechanical
systems or NEMS
 Related to Microelectromechanical systems or
MEMS.
 MEMS became practical once they could be
fabricated using modified semiconductor device
fabrication technologies, normally used to make
electronics

16. Nanoelectromechanical
systems

17. NANOMATERIALS
 Materials having unique properties arising from
their nanoscale dimensions.
 EXAMPLE:
1. Carbon nanotubes
2. Nanorods
3. Nanoscale Cantilevers
4. Nanopores
5. Nanoshells
6. Dendrimers

18. CARBON NANOTUBE
 Carbon nanotubes are allotropes of carbon with a
cylindrical nanostructure.
 They have length-to-diameter ratio of upto
132,000,000:1.
 Nanotubes are members of the fullerene structural
family. Their name is derived from their long, hollow
structure with the walls formed by one-atom thick sheets
of carbon, called graphene.

19.  Properties of carbon nanotubes-
Highest strength to weight ratio. Helps in creating
light weight space crafts.
Easily penetrate membranes such as cell walls.
Helps in cancer treatment.
Electrical resistance changes significantly when
other molecules attach themselves to the carbon
atoms.

20. NANOTUBES-MARKING MUTATIONS
 Helps identify DNA changes associated with cancer.
 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.

21. Carbon nanotube

22.  Using a nano tube tip, the physical shape of the DNA
can be traced.
 A computer translates this information into
topographical map.
 The bulky molecules identify the regions on the map
where mutations are present.
 These techniques will be important in predicting the
disease.

23. NANORODS
It is one of the types of nanoscale objects.
 Dimensions range from 1–100 nm.
 They may be synthesized from metals or
semiconducting materials.

24.  A combination of ligands act as shape control agents
and bond to different facets of the nanorod with
different strengths.
 This allows different faces of the nanorod to grow at
different rates, producing an elongated object

26.  USES:
In display technologies, because the reflectivity of
the rods can be changed by changing their
orientation with an applied electric field.
In microelectromechanical systems (MEMS).

27.  In cancer therapeutics. These are tiny crystals that
glow when these are stimulated by ultraviolet light.
 The latex beads filled with these crystals when
stimulated by light, the colors they emit act as dyes
that light up the sequence of interest.

28.  Combining different sized quantum dots within a
single bead, probes can be created
 Probes release a distinct spectrum of various colors
and intensities of lights, serving as sort of spectral
bar code.

29. 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.

31. NANOPORES
 Tiny hole in a thin membrane, enough to allow a
single molecule of DNA to pass through.
 Powerful sensors of molecules and ions.
 Extracted from living organisms or fabricated using
nanotechnology.
 DNA sequencing can be made more efficient by
allowing one strand to pass at a time

32.  Shape and electrical properties of each base on the
strand can be monitored.
 Used to decipher the encoded information, including
errors in the code known to be associated with
cancer.

34. NANOSHELLS
 Nanoshells are miniscule beads coated with gold.
 By manipulating the thickness of the layers, the
beads can be designed that absorb specific
wavelength of light.
 Nanoshells that absorb near infrared light that can
easily penetrate several centimeters in human tissues
are most useful

35.  Absorption of light by nanoshells creates an intense
heat that is lethal to cells.
 Nanoshells can be linked to antibodies that recognize
cancer cells.
 In laboratory cultures, the heat generated by the
light-absorbing nanoshells has successfully killed
tumor cells while leaving neighboring cells intact.

38. MAGNETIC NANOPARTICLES (MNPs)
 MNPs are employed in biosensors, magnetic
resonance imaging and nanoelectronics.
 MNPs commonly consist of magnetic element such
as iron, nickel, and their derivatives.
 MNPs are 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.

39. Super-paramagnetic iron oxide nanoparticles
(SPIONs)
 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.
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 is used in biosensors it improves the
sensitivity and selectivity of diagnosis

40. CIRCULATING TUMOR CELLS
 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.

41. QUANTUM DOTS
 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.

42. GRAPHENE OXIDE
 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 millilitre of
blood sample

43. GOLD AND SILVER NANOPARTICLES
 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 labeling and
biosensing.
 The Silver nanorods in a diagnostic system are being
used to separate viruses, bacteria and other
microscopic components of blood samples.

44. Gold Nanoparticle Tumor Detection
 Functionalization of the nanoparticle with an
antibody specific to the tumor antigens
 Then detect the nanoparticle by some spectroscopic
technique.

45. Gold nanoparticle

46.  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.

47. NANOCHIP
 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.

48. MICROFLUIDICS (LAB ON A CHIP)
 The newest technologies within nanodiagnostics involve
microfluidics 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

49. DENDRIMERS
 Hyperbranched tree like structure
 Three different regions:
Core moiety
Branching unit
Closely packed surface
 Less than a size of 10nm

51.  Uses of dendrimers:
Long circulatory and controlled delivery of bioactive
material
Targeted delivery of bioactive particles to
macrophages
Liver targeted delivery

52. NANOMEDICINE
Nanometer-sized particles have optical, magnetic,
chemical and structural properties with potential
applications in medicine.
Drug delivery
Medical imaging
Diagnosis and sensing
Therapy

53. Drug Delivery
 A nanoparticle carries the pharmaceutical agent inside
its core, while its shell is functionalized with a ‘binding’
agent
 Through the ‘binding’ agent, the ‘targeted’ nanoparticle
recognizes the target cell. Interacts with cell membrane.
 Ingested inside the cell, and interacts with the
biomolecules inside the cell where it breaks, and the
pharmaceutical agent is released.

54.  Nanoparticles for drug delivery can be
metal
polymer
lipid-based
 Example :
SiRNA encapsulated, and functionalized with an
specific antibody.

56. PLATELET MIMICRY
 Nanoparticles coated with the membrane of blood
platelets are shielded from the body’s immune
responses, and possess platelet-like binding
properties that allow them to target desired cells and
tissues.

58. Applications in Surgery
 Minute surgical instruments and robots can be made
to perform microsurgeries.
 Will be Precise and accurate, targeting
 Visualization of surgery can also be improved by
Nanocameras
 Computers can be used to control the nano-sized
surgical instruments.
 Surgery could also be done on tissue, genetic and
cellular levels.

59. Miscellaneous Applications of
Nanotechnology
 Snapshots of the human body for better understanding
 The workings of cells, bacteria, viruses etc can be better
explored.
 The causes of relatively new diseases can be found and
prevented.
 Genome sequencing can be made much easier.
 Biological causes of mental diseases can be monitored
and identified
 Tissue engineering could also be done using nano-
materials.

60. LIMITATIONS
 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.
 Carbon nanotubes could be as harmful as asbestos if
inhaled in sufficient quantities.

61. SUMMARY
 Utilisation of nano sized particles at molecular level
 Approaches
 Examples:
1. Carbon nanotubes
2. Nanorods
3. Nanoscale Cantilevers
4. Nanopores
5. Nanoshells
6. Dendrimers
Bottom up
Top down

62.  Uses :
 Diagnostics
 Drug delivery
 Therapy
 Biosensors
 DNA mapping
 Institutes of Nanoscience and Technology
 Jawaharlal Nehru Centre For Advanced Scientific
Reasearch
 Amrita Centre for Nanosciences

63. 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.

64. 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.

65.  REFERENCES
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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