Leecture III

History
ynman in 19
959, many sccientists starrted workingg on this excciting
After thee lecture by Richard Fey
new field
d of physics. It was inteeresting not only
o
becausee it was new
w and they w
were bored oof the
old fieldss, but also because this science
s
work
ked at a veryy small scalle where the classical law
ws of
physics start
s
misbehaaving.
But one of the majorr problems wasw how are we going to study succh small objects if we caannot
see them
m? This remained a probllem for abou
ut 26 years bbefore Gerd B
Binning andd Heinrich R
Rohrer
invented the STM to see and man
nipulate indiividual atom
ms.
This wass one of the most importtant mileston
nes in Nanootechnology as after thiss, the advancces in
nano-tech
h happened in leaps an
nd bounds. After just 4 years of the discoveery of the S
STM,
[5]
researcheers at the Ricce Universitty discovered
d Fullereness (The C-60 carbon allottrope) , which is
now
w used to maake carbon nnanotubes, oone of
the m
most ubiquiitous nano-m
materials. Thhen in
19899, a very interesting thing happened;
IBM
M spelled ouut its logo using 35 xxenon
atom
ms demonstrrating how nnano-particlees can
be m
manipulated for our ownn use giving out a
messsage that Y
Yes, It is possible.[6]
In 1991, the carbon Naanotube [7] was
creaated, which was an im
mportant steep in
Image courtesyc
IBM
M
moddern computting and elecctronics. Beccause
of this carbbon nanotubee, super-faast computerrs are
now posssible; it hass also been in use for light weighht and duraable structurres and in ttissue
engineeriing to act as
a a scaffold
d and will be
b used in tthe near futture by NASA for its sspace
stations.
Dr. Chad
d Mirkin haas made innumerable co
ontributions to the fieldd of Nanoteechnology, w
which
started in
n 1995 from
m group dev
vised a DNA-based meethod for asssembling nnanoparticless into
[8]
macrosco
opic materiaals . They observed
o
thaat a solutionn of DNA-asssembled naanoparticles w
when
heated, tu
urns from reed to blue. This
T made way
w for the eexploitation of the opticaal, optoelecttronic
and mateerial propertiies of small colloidal paarticles of m
metals and seemiconductoors, which w
were a
manifestaation of theiir nanoscopicc size. Gold colloidal naanoparticles were assem
mbled with thhe aid
of DNA strands to fo
orm macrosccopic aggreg
gates which ppossessed m
modified optical and strucctural
propertiees. Gold nan
noparticles were
w
surfacee engineeredd with non-ccomplementaary DNA strrands

with thio
ol groups at one end which have afffinity for golld. Then to the solutionn containing these
engineereed particles,, if DNA strrands complementary too the surfacee oligonucleotides are addded,
the particcles form an
n aggregate. The process of aggregaation can bee simply revversed by theermal
denaturattion. This strategy
s
find
ds applicatio
on in fieldss like chem
mical sensingg, microimaaging,
spectrosccopic enhanccement etc.
In 1997,, he used marcaptoalk
kyloligonucleeotide-modiified gold nnanoparticlee probes forr the
sensitive, colorimetrric detection
n of upto 10
0 femtomolees of polynuucleotides[9]. When a siinglestranded oligonucleo
otide is introd
duced into th
he solution oof these partticles, hybriddization resuults in
the form
mation of a polymeric network off particles. T
This alters their structtural and opptical
propertiees which is visible
v
as color change.
One of th
he path-breaaking eventss was the inv
vention of D
Dip-Pen Nannolithography (DPN) in 1995
[1
10]
by Dr. Ch
had Mirkin . It is a bo
ottom-up app
proach whereein material is always addded to a surrface.
DPN is a tip-based liithography teechnique thaat enables m
multi-componnent depositiion of an arrray of
materialss (eg gold, siilicon, plastiic etc.) at naanoscale. DP
PN can fabriccate multipleexed, custom
mized
patterns with
w sizes raanging from 50 nm to 10
0 m. Somee applicationns of DPN innclude: Biosensor
functionaalization, Naanoscale Sen
nsor Fabricattion, Nanosccale Protein C
Chip.

Illustration of DPN liquid

l
deposittion
(Image Courtesy: ww
ww.nanoink.n
net)

In 2001,, he publishhed a paper which caterred to

the phhotoinduced conversioon of ssilver
nanospheeres to naanoprisms. In this, timedependennt Ultra-vioolet spectrooscopy is used
which drrives the connversion proocess. This ccould
be utilizzed in the developmennt of diagnnostic
labels onn the basis oof nanoparticcle shape innstead
of nanopaarticle compposition.

The gold
d nanoparticlles have beeen worked up
pon intensivvely and enggineered accoordingly to aallow
for the seensitive deteection of a nu
ucleic acid. These nanopparticles havve replaced fflouorophorees for
the nucleeic acid deteection due to
o a three-fold increase inn the sensitiivity and theeir ability too alter
the meltiing profiles of the targett nucleic aciid. Using theese nanopartticles, even single nucleeotide
differencces can be traced whicch was not possible uusing other detection m
methods. Thhis is
particularrly advantag
geous in caase of geneetic diseasess which aree a manifestation of siinglenucleotid
de polymorp
phisms. Mirrkin extendeed the use oof nanotechhnology for the detectioon of
[11]
proteins . He madee use of speccific antibody
y labelled m
magnetic nanooparticles foor the same. H
Here,
the targett protein is sandwiched
s
between
b
maagnetic nanopparticles labbeled with a specific antiibody
and targeet-specific oligonucleoti
o
ide. These complexed
c
pprobes are thhen separateed using maagnets
and the oligonucleotide released is subseq
quently sequuenced whicch reveals thhe presence of a

specific protein for which the oligonucleotide has affinity. This method allows for the detection
of protein concentrations as low as 30 attomolar due to natural amplification which is result of
the presence of a large number of oligonucleotides per nanoparticle. Development of
nanoparticle probes for the highly sensitive detection of nucleic acids and proteins has been a
major breakthrough the field of medical diagnostics and therapeutics. Identification of cancer
cells, presence of a pathogenic genetic component etc. are all possible by making use of these
nanoparticles.
In the winter of the 2000, Professor F. C. Simmel found a novel use of nanotechnology in
biotechnology he observed that Molecular recognition between complementary DNA strands
allowed assembly on a nanometre scale[12]. For example, DNA tags can be used to bring together
the assembly of colloidal particles, and DNA templates can direct the growth of semiconductor
nanocrystals and metal wires. DNA could be used to make ordered assortments of tiles, linked
rings and polyhedra. This meant that the construction or creation of active devices was also a
possibility--for example, a nanomechanical switch, whose conformation is changed by a
transition in the handedness or chirality of the DNA double helix. Professor Simmel also
demonstrated that, the construction of a DNA machine in which the DNA acts as 'fuel' is also a
very realistic possibility. A machine can be made form 3 strands of DNA in the form of a pair of
tweezers. It may be closed and opened by addition of auxiliary strands of 'fuel' DNA.

Fig1: a)) Molecular tw

weezer structure formed byy hybridizatioon of oligonuccleotide strannds A, B and C
C. b)
Closin
ng and openin
ng the molecu
ular tweezers. Closing strannd F hybridizzes with the ddangling ends of
strands B and C (show
wn in blue an
nd green) to pull
p the tweezeers closed. Hy
Hybridization w
with the overhhang
section
n of F (red) allows
a
F stran
nd to remove F from the tw
weezers, formiing a double--stranded wasste
product F and allowin
ng the tweezerrs to open. Co
omplementary
ry sections off B, C, F and F that hybridiize to
close and op
pen the tweezeers are colourred as in Figuure 1. (Image Courtesy: Na
Nature[13])

In 1999,, Nanotech consumer products

p
fin
nally started making ann appearancee in the maarket.
Nanosph
here, founded
d by Dr Chaad Mirkin in
n 1999, ventu
tures into addvanced mollecular diagnnostic

platforms by making use of the Verigene system. It enables us to detect diseases at an early stage
and makes way for a more targeted treatment due to high sensitivity to direct nucleic acids and
proteins testing.
Nanoink was the second company to come into the picture in 2002 and was involved in
nanometer-scale manufacturing and developing applications for life sciences, engineering,
pharmaceutical and education industries by making use of DPN.
Next came Aurasense which allowed for the interrogation of genetic expression in live cells for
the first time by manufacturing biocompatible nanoparticles that served as novel assays within
living cells. It rendered the use of carriers and transfection agents unnecessary which evoked
immune responses and had toxic effects. One of their products was a nanoparticle that mimics
the natural function of HDL ("good" cholesterol).
Latest was AuraSense Therapeutics' which specializes in uniquely engineered Spherical Nucleic
Acid (SNA) constructs that possess unparalleled biocompatibility and versatility as
therapeutics. It is very promising for combating the most threatening diseases, including heart
disease, cancer, skin conditions and bacterial infection.
One of the latest revolutionizing works in the field of nanotechnology has been on Graphene.
Graphene is one of the allotrope of carbon along with diamond, graphite and fullerene. It is a flat
monolayer of atoms tightly packed into 2-D hexagonal lattice and is known for being the
building block for various graphitic substances of any dimensionality; it can be transformed into
0-D fullerenes, rolled to form 1-D nanotubes or stacked into 3-D graphite. Theoretically,
grapheme has been known and studied for more than sixty years and is used for reasoning
properties of materials based on carbon. Graphene had been assumed not to exist freely in nature
and was believed to be unstable when carved into curved structures such as soot, fullerenes and
nanotubes. Now suddenly, three years ago, the vintage model became a reality when grapheme
in the free state was found unexpectedly. The follow-up experiments by Andre Geim and
Konstantin Novoselov at the University of Manchester confirmed that the charge carriers in
graphene were massless Dirac fermions and won them a Nobel Prize in Physics in 2010 for
groundbreaking experiments regarding the two-dimensional material graphene"[14].

Fig 2: Mo
other of all grraphitic formss. Graphene is
i a 2D buildiing material ffor carbon maaterials of all other
dimensionalities. It can
c be wrappeed tp into 0D buckyballs, rrolled into 10 nanotubes orr stacked intoo 3D
graphite
g
(Ima
age Courtesy:: Nature)

The histo
ory of nano
otechnology has emergeed from matterials and m
mechanical engineering. The
hallmark
k of nanotech
hnology is th
hat it is difficcult to definee it as a disttinct field, duue to the muultiple
methods and techniq
ques rooting from a variety of brancches. This haas led to em
mergence of ffields
like Nan
noBiotechnollogy.and Biionanotechno
ology whichh are mostlly used inteerchangeablyy and
refer to th
he cross-roaads of Biotecchnology and
d Nanotechnnology. Thouugh whenever a distinctiion is
required,, it is based
d on whetheer the focus is on applyying biologyy or the stuudy of bioloogical
phenomeenon using nanotechnolo
n
ogy.