The document summarizes the history and development of nanotechnology. It discusses how the concept was first developed by Richard Feynman in 1959, and the term was coined by Norio Taniguchi in 1974. It then outlines key milestones and advancements in the 1980s and beyond that helped establish nanotechnology as a field, including the invention of the scanning tunneling microscope in 1981 and discoveries of fullerenes in 1985 and carbon nanotubes. The document also provides examples of how nanotechnology is being applied in biology and medicine, such as using atomic force microscopes to image cells, optical tweezers to manipulate organisms, and quantum dots for labeling parasites.

1. Dr. Rajesh Karyakarte MD
Professor and Head,
Department of Microbiology,
Government Medical College,
Akola, Maharashtra, India

2.  Nanotechnology is the
understanding and control of
matter at dimensions between
approximately 1 and 100
nanometers, where unique
phenomena enable novel
applications. Encompassing
nanoscale
science, engineering, and
technology, nanotechnology Atomically precise
involves positioning of carbon
monoxide molecules
imaging, measuring, modeling, on a copper surface
and manipulating matter at this enables data storage
length scale. with bits smaller than
atoms
The National Nanotechnology Initiative, US.

3. The physicist Richard Feynman first developed the concept
'nanotechnology' (but he did not specifically use this term) in
a talk “There's Plenty of Room at the Bottom,” given at an
American Physical Society meeting at Caltech on December
29, 1959.
The Nobel Prize in Physics 1965 was awarded jointly to Sin-Itiro Tomonaga, Julian Schwinger and Richard
P. Feynman "for their fundamental work in quantum electrodynamics, with deep-ploughing consequences
for the physics of elementary particles".

4. Professor Norio Taniguchi of
the Tokyo Science
University, introduced the term
“nanotechnology”, in a 1974
paper. He described
nanotechnology as the
processing
of, separation, consolidation, an
d deformation of materials by
one atom or by one molecule."
N. Taniguchi, "On the Basic Concept of 'Nano-Technology'," Proc. Intl. Conf. Prod. Eng. Tokyo, Part
II, Japan Society of Precision Engineering, 1974

5. In the 1980s, Dr. K. Eric Drexler, promoted nanoscale
phenomena through books:
• Engines of Creation: The Coming Era of Nanotechnology
• Nanosystems: Molecular Machinery, Manufacturing, and
Computation
He was ultimately responsible for the term nanotechnology to
acquire its current sense.

6. Feynman Taniguchi Drexler

7. Nanotechnology developed in
early 1980s with two major
developments;
 the birth of cluster science and
 the invention of the scanning
tunneling microscope (STM).

8.  In physics, the term clusters denotes
small, multi-atom particles.
 Cluster science: studies the gradual
development of collective phenomena
which characterize a bulk solid.
 Collective phenomena (color, electrical
conductivity, and magnetic properties)
break down for very small cluster sizes.

9.  Scanning tunneling microscope (STM): is an
instrument for imaging surfaces at the atomic
level.
 Its development in 1981 earned its inventors, Gerd
Binnig and Heinrich Rohrer (at IBM Zürich), the
Nobel Prize in Physics in 1986

10.  The field of nanotechnology matured with
the discovery of fullerenes in 1985 and
carbon nanotubes a few years later.
Buckminsterfullerene C60 Carbon Nanotube

11.  The Atomic Force Microscope was
invented in 1986. It allowed for
unprecedented control over nanomaterial
design and characterization

12.  A nanometer is one-billionth of a meter.
 A single gold atom is about 1/3 of a nanometer in
diameter.
 A DNA double helix has a diameter of about 2 nm.
 Picornavirus is around 20 nm.
 Mycoplasma is around 200 nm in.
 A sheet of paper is about 100,000 nm thick.
 Fascinatingly, the beard of a man grows by a
nanometer in the time he takes to bring the razor
to his face for a shave

13.  Atomic Force Microscope
(AFM) has a fine pointed
tip attached to a Optical Tweezers
cantilever that moves
over or touches the
sample.
 The cantilever deflects
as the tip is pulled
toward or pushed away
from the surface.
 A laser is bounced off the
mirrored backside of the
cantilever onto a
photodiode to measure
this deflection
From Merz et al., Nature 407:98, 2000.

14.  Optical tweezers allow
manipulation and
simultaneous observation of
biological processes of living
microorganisms, as flagellate
protozoan.
 Optical tweezers have been
used to apply forces in the pN
(piconewtons) and to measure
displacements in nanometers
(nm) of a range of objects
ranging in size from 10 nm to
over 100 mm.

15. Optical Tweezers have been used:
 To insert DNA in cells and fertilization in vitro;
 To measure and compare cell displacements;
 To measure forces of cardiac muscle fibers;
 To measure the length of a DNA molecule;
 To study motility of human spermatozoa;
 To detect antigens at femtomolar level;
 To study bacterial flagella motors
 To study strength, elasticity and viscosity of RBCs;
 To study chemotaxis of Leishmania amazonensis and
Trypanosoma cruzi.

16.  Thomaz et al (2009) measured the propulsion forces of
the flagellum of T. cruzi .
 When T. cruzi is more than 50 μm away from the
midgut cells of reduviid bug (Rhodnius prolixus). It
showed an erratic movement.
 When less than 20 μm away from the midgut cells, T.
cruzi moved towards the cells.
 Maximum propulsive force of the flagellum was 0.8 pN.

17.  Nanoscope (AFM) can help in
studying living cells in gaseous
and liquid environments.
 Nanoscopes that are dedicated
to biological applications are
available commercially.
 Nanoscopes have many scan
modes for analysis.
 The intermittent contact
mode produces topological
information.
 Phase imaging allows for the
analysis of adhesive and
elastic properties, in addition. Nanoscope

18.  In parasitology, AFM was used to study the
structural organization of trypanosomatid
parasites by Dvorak and collaborators almost 10
years ago.
 This study was successful in drawing attention of
the parasitologists towards the potential of AFM.
 The published images however did not add
significant new information regarding the
structure of these parasites.
Dvorak, J. A., Kobayashi, S., Abe, K., Fujiwara, T., Takeuchi, T. and Nagao, E. (2000) The application of
the atomic force microscope to studies of medically important protozoan parasites. J. Elec.
Microsc. 49, 429–435.

19. Rocha et al, 2008 using similar methodology but with an
additional pretreatment step of treating the protozoal
cells with detergent, produced images wherein both the
cell surface and the intracellular structures of
Trypanosoma cruzi could be well recognized.
AFM image: flagellum of slightly
detergent-extracted T. cruzi.
A furrow along the major axis of the
flagellum with periodically organized
protrusions can be seen (arrowheads).
Rocha, G. M., Miranda, K., Weissmüller, G., Bisch, P. M., de Souza, W. (2008) Ultrastructure
of Trypanosoma cruzi revisited by atomic force microscopy. Microsc. Res. Tech. 71, 133–139.

20.  Joergensen et al (2010) studied the kinetics
of antibody binding to VAR2 Chondroitin
Sulfate A Plasmodium falciparum
erythrocyte membrane protein 1 antigen.
 Molecular modeling after nanoscopy indicate
that:
 PfEMP1 has a large size
 The architecture of the knobs
 facilitates cytoadhesion
 But reduces avidity of antibody-PfEMP1 binding.
Joergensen LM, Salanti1 A, Dobrilovic T, Barfod L, Hassenkam T, Theander TG, Hviid L, Arnot DE. The
kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigen and modelling of
PfEMP1 antigen packing on the membrane knobs. Malaria Journal 2010, 9:100.

21. Two Knobs
Two-color
enhanced three
dimensional
imaging
Topology
measurements of
the surface
bisected by the red
line shown in
Figure B.
AFM derived measurement of the dimensions of the knob structures on the
infected erythrocyte membrane.

22.  The knob in the infected RBC shown
previously is 120 nm in diameter and 24
nm high and its surface area is around
13,000 nm2.
 An estimated maximum of 110
VAR2CSA molecules could be tightly
packed onto a knob of the dimensions
shown in the figure.

23.  Knobs form at actin-spectrin-ankyrin
junctions and inter-knob distances are
related to the regular inter-junction
distances (100-200 nm).
 This makes antibody crosslinking of
PfEMP1 between different knobs on the
same erythrocyte by IgG1 (or even IgM)
antibodies effectively impossible.

24. Actin-spectrin-ankyrin junctions
• The erythrocyte membrane skeleton is organized as a polygonal network formed by
five to seven extended spectrin molecules linked to short actin filaments
approximately 40 nm in length .
• The spectrin-actin network of erythrocytes is coupled to the membrane bilayer
primarily by association of spectrin with ankyrin, which in turn is bound to the
cytoplasmic domain of the anion exchanger

25. • The light emitting Quantum dots consist of
semiconductor nano-crystals that are 1 to 10 nm
in diameter.
• QDs resist photobleaching and have higher
absorption coefficients than fluorophores.
• QD particle size determines wavelength of the
emitted light.
• By changing the sizes of QDs it is possible to
distinguish among different classes of target
molecules simultaneously, while using a single
excitation wavelength.

27. • Feder et al (2009) used Green –emitting
cadmium telluride quantum dots (CdTe
QDs) and Yellow-emitting cadmium selenide
quantum dot (CdSe QDs) to label T. cruzi.
• These QDs (0.2 μM) had no effects on the
development of T. cruzi.
• Further, due to the high photostability of the
QDs, in vivo imaging of long-term interaction
between T. cruzi and live cells of Rhodnius
prolixus was possible
Feder D, Gomes SAO, de Thomaz A.A, Almeida DB, Faustino WM, Fontes A., Stahl CV, Santos-
Mallet JR, Cesar CL. In vitro and In vivo Documentation of Quantum Dots Labeled
Trypanosoma cruzi & Rhodnius prolixus Interaction using Confocal Microscopy. Parasitology
Research. 2009;106 (1):85-93.

28. In vitro Interaction Assay showing Trypanosoma cruzi adhering to the
midgut epithelium of Rhodnius prolixus by fluorescent labeling with green
emitting CdTe quantum dots to acquire 3 frames per second confocal
fluorescence images (After Feder et al., 2009).

30. Nanotechnology in drug delivery and targeting. The major components are
either lipid or polymers (After Couvreur and Vauthier, 2006)

31. • Liposomes were proposed in 1974 by
Gregoriadis et al for drug delivery.
• Use of nanodevices, particularly
liposomes, has reduced the toxicity of
amphotericin B 50- to 70-fold in
leishmaniasis.
• Thus, more drug ( 5-fold) can be
administered.
• The liposome formulation, was marketed in
1996 under the brand name AmBisome®.

32.  In addition to reduction of the toxicity, these
nanosized liposomes are not immediately cleared
by the macrophages present in liver and spleen.
 Thus, majority of these liposomes carrying
amphotericin B remain in the blood circulation
and also achieve a high enough concentration in
infected tissues.
 This nanodevice formulation has one more
advantage of killing both phagocytized and non-
phagocytized parasites.

33.  The main problem with AmBisome® is its high cost.
 To overcome this problem, nanodisks (250 nm in
diameter, 3 nm in thickness) that require far less
lipids have been developed.