MatE 297 Term Paper A Technical Review on Application of Nano Technology on Biotechnology.

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Oct 23, 2013 (3 years and 11 months ago)

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MatE 297








Lau, Yu Kei Kent

Term Paper











A Technical Review on Application of N
ano
Technology on B
iotechnology.


Introduction


Recent development and advance on nanotechnology has brought new insight
into the area of biotechnology.

The detect
ion and formulation of various chemical
and biological agents using nanostructured materials is a hot topic under discussion.


Due to the comparable size of biomolecule such as antibodies, peptides and DNA
with nanoparticles, the understanding of the self
assembly of these materials and the
cause and cure of the related disease is relying on the understanding

of nano
particle
formation and
utilizations
.

A main focus of biotechnology is to discover the cause of
genetic disease, to develop a cure and to devel
op an effective delivery device of the
cure.
This paper serves to review and summarize
these recent developments

in a three
steps approach: 1.)
the detection of diseases by nanoscale devices,
2.) the
nanofabrication

of synthetic protein polymer, and 3.) t
he discoveries on
nanoscale
drug deliveries devices.



Nano

Biosensors



Based on high specificity of biological reactions for detecting target analytes,
b
iosensors are
useful research tools to discover genetic abnormalities and
physiological disease
.

Bio
sensors

couple a bio
logical recognition element wit
h a
physical transducer that
translates

the bio
-
recognition event in
to

a
measurable

effect,
such as
electrical signal, an optic
al emission or a mechanical motion.

Progress in
nanotechnologies allows devel
opment of highly sensitive sensors with the addition
advantages of miniaturization.

These miniaturized biosensor provides on the target
analysis based on microelectronics and related micro
-
electromechanical system
(MEMS).



A new class of promising nanobi
o
-
sensor to detect biomolecular interaction
with great accuracy is the microcantilever

[1]
.

This new class of highly sensitivity
biosensors can perform local, high resolution and label
-
free molecular recognition
measurement.

Mechanisms of these biosensor
s are

based on cantilever in atomic
force microscopy (AFM).

Basic mechanism of these sensors is the bending induced
in the cantilever when a biomolecular interaction ta
kes place on its surface.

The
nanomechanical motion is often coupled to an optical or
piezo
-
resistive read
-
out
system.

Figure 1 shows the schematics of microcantilever.





Figure 1. A schematic of cantilever bending due to biomolecular interaction between an immobilized
interaction between the receptor and its target. Only a specific ta
rget can induce the stress change on
the cantilever. Figure reprint from Ref [1]



As

derived from standard AFM
, optical read
-
out is one of the most common
schemes for detecting the movement of microcantilevers.

Laser deflection on the

m
icrocantilever is
detected by sensitive photodetector.

An alternative to optical read
out is piezo
-
resistive read
-
out.

The mechanism of this read
-
out is based on resistively
changes on the cantilever as a result of surface stress change.

For piezo
-
resistivity to
be obser
vable, the electrical conductivity along the thickness of the cantilever has to
be asymmetric, which is often accomplished by differential doping of the material.


The current scale of the cantilevers is in microns, but with the success in the
nanotechnolo
gy, reduction in scale can provide the advantage of multiple detection in
one device and local on
-
site detection.




In rece
nt years, applications of gold nanoparticles
have
also
been extended to
the
research of

DNA functioning
and detection of proteins in
volved in cancers.

Examples of t
hese diagnostic tools
involved the use of gold particle particles bound to
a DNA
-
probe [2].

Gold nanoparticles are manufactured to contain a
ligand with
biomolecule, typically a
specific sequence of DNA nucleotides.

The D
NA in question
will bind to the gold particle if the DNA
has

the target sequence.

The binding of these
nanoparticles will result in an aggregation.

Based on
surface plasmon resonance of
gold nano
particles, an aggregation of gold particles will result in
a color change.


One
of t
hese researches
is the
Qdot™
by Invitrogen
.

The significance of this bi
omarker is
its nanoscale size (
comparable to protein) and the tuneability to produce different
wave length.

The structure of Qdot™ and color scheme is shown i
n Figure 2.






Figure 2. Structure of Q
dot™ by I
nvitrogen and
schematic of
difference in color due to
core size
difference.

Figure reprint from www.invitrogen.com.



Other theoretical development in nano
-
diagnostics also includes a
ntibodies
labelled with magnetic nanoparticles
.


Upon

exposed to a magn
etic field, these
anibodies

respond with a strong magnetic signal if they are reacting

with certain
substances.

Furthermore
, gold nanoshells linked to specific antibodies

that target
tumors

could, when hit by infrared light, heat up to destroy growths sel
ectively.


Currently, different medium of nano materials such as nanotubes, nanoparticles,
nanowires, and nanoporous materials are also examined for biocompatibility and
subsequent detection [2].




The advantage
s

of these nano
-
biosensor
s

are mainly driven

by their high
-
throughput
and the ability to perform In Vivo analysis
.

These analyses are in real
time and do

not require labeling of the
target.

Economically, arrays of nanosenors can
be fabricated in tens of thousands of units.



Development of synth
etic polymer


Recently new and exciting opportunities for bionanofabrication have emerged
in the fields of synthetic biology and recombinant protein engineering.

Although
bionanofabrication is still at its infancy, it has a wild scope of applications and
promising future.

The field of synthetic

polymer can be ranged from genetic
engineering, biomolecule fabrications to tissue engineering.



More recently, the research area of nanobiotechnology has been
broadening

to
genetic engineering.

Genetic material
s can be characterized as repeating units of
monomers in nanoscales.

The possibility of modifying genes in nucleotide level is
driven by the advance of the before mentioned nano
-
biosensor [3]
.


DNA strands
,
which have complementary sticky
-
end overhangs,
c
an be fabricated and
self
-
assemble
into a branched junction.

These branched junctions can further self
-
assemble into
DNA nanogrids owing to the orientation of the complementary sticky ends
.


Micropatterned DNA arrays have been proposed to

be used as templ
ates for high
-
throughput gene synthesis and protein expression.


As compare to traditional
P
olymerase Chained Reaction (PCR)
, this process can have much higher production
rate and thus provide a significant economical advantage.




Fig
ure

3
. TEM images o
f nanotubes and nanovesicles from a surfactant
-
like peptide

V6D. The
sample was flash frozen in liquid propane (

180

C) to preserve the structure formed in solution. (B)
Molecular modeling of cut
-
away structures of a nanotube and a nanovesicle formed from surfactant
-
like peptides. Color code: red, polar heads; green, nonpolar tails. The modeled dimension is 50

100
nm
in diameter. Figure reprint from Ref [4]


Another group of material focused in nanofabrica
t
ion is peptides [4].

Peptides
are short chains of nucleic acids which are fragment of proteins and can form
biological entities such as antibodies. Researches
h
ave shown various types of self
-
assembling peptide systems with capabilities to form twisted
β
-
sheets, to undergo
conformational changes, to bind to specific surfaces, and to construct nanotubes and
nanovesicles (Fig. 3).

Each of these supramolecular formations is governed

by the
properties of the peptide units.

The research in nanofabrication c
an be further
extend
ed
to
tissue engineering [5].
Since the morphology and

patterning of the tissue

is determined by it microstructures, the researcher focused on

various methods on
controlling polymeric substrates and fabricate the materials into micro
-

and
nanometric patterns.


Nanoscale Drug Delivery Devices


In addition to the potential improvements in the diagnostic field,
nanotechnology offers advantages that allow a more targeted drug delivery and a
more controllable release of a therapeutic compoun
d.

The aim of targeted drug
delivery and a controlled release is to better manage drug pharmacokinetics,
non
-
specific toxicity

and biorecognition of systems.

Cancer treatment often involves the
administration of inhibitors to block overreaction or overpr
oduction of cancer cells.

A controlled and precise release of inhibitors is essential in preventing damage or side
effects bring to surrounding or non
-
targeted cells.

In nanoscale drug delivery, the
inhibitor is suitably encapsulated, in nanoparticulate
form,
and then specifically target
cancer cells based on the biomolecular interaction between the coating layer and the
target.

This specific targeting prevents premature degredation and size effects caused
to surrounding cells.

The

use of

nanoscale devi
ces offers direct on site drug delivery
and provide direct release
, and thus increase patient acceptabilty

[6].

Figure 4

shows
a schematic of these delivery systems.



Fig
ure

4
.

Nanoscale drug delivery system for direct on
-
site release. Reprint f
rom R
ef [6]



The route of administration is another key for a therapeutic success.

The focus
of nanoscale delivery system is to cross a specific barrier, such as the blood
-
brain
barrier, and to prevent degradation during the process.

In general, gastrointest
inal
administration is noninvasive to the patient; however, the enzymatic digestion in the
intestinal tract can cause degradation to the drug.

Intravenous administration is direct
and can be applied to unconscious patients; however, repeated administratio
n is
invasive and often cause discomfort to the patient.

Pulmonary administration (by
inhalation) can be a focus of these nanoscale delivery systems.

This administration
route is noninvasive and is relatively fast coupled with oxygen delivery system.
Na
nocarrier can be used to
prevent degradation and facilitate the nasal or pulmonary
crossover.



Conclusion


The advance in nanotechnology has opened up various opportunities,
especially in the area of biotechnology.

In this review, three areas of bioapp
lication
of nanotechnology have been examined.

These included nanoscale biosensors, nano
-
syntheic
polymers,

an
d nano
scale

drug delivery systems.

However, there is still a
huge gap between concepts and clinical realities
.




The main challenge, as faced i
n other fields of nanotechnology application, is
the material property change in reduced size.

The reliability of the nanobiosensor lies
on the understanding of material science in such a small scale. Also, in reduced scale,
the quality control to manufac
ture consistent repeatable units is expensive and
difficult.
A specific problem faced by the biological application is that

the natural
immune system can block out the nanodevices and polymers if they are not well
coated or disguised.

Future research nee
d to focus on the
stabilizing the nanomaterial
in the In Vivo environment and also on inexpensive quality control.

























Reference:

1.

L.G. Carrascosa, M. Moreno, M. Álvarez and L.M. Lechuga

Nanomechanical
biosensors: a new sensing tool

TrAC Trends in Analytical Chemistry, Volume 25, Issue 3, March 2006, Pages 196
-
206



2.
Susan A. Greenfield

Biotechnology, the brain and the future



Trends in Biotechnology, Volume 23, Issue 1, January 2005, Pages 34
-
41



3.

Dominic C. Chow, Matthew S.
Johannes, Woo
-
Kyung Lee, Robert L. Clark, Stefan
Zauscher and Ashutosh Chilkoti
Nanofabrication with biomolecules

Materials Today, Volume 8, Issue 12, Supplement 1, December 2005, Pages 30
-
39



4.
P. Chen

Self
-
assembly of ionic
-
complementary peptides: a p
hysicochemical
viewpoint

Colloids and Surfaces A: Physicochemical and Engineering Aspects, Volume 261,
Issues 1
-
3, 1 July 2005, Pages 3
-
24



5.
N. Gadegaard, E. Martines, M.O. Riehle, K. Seunarine and C.D.W. Wilkinson

Applications of nano
-
patterning to ti
ssue engineering



Microelectronic Engineering,
In Press, Corrected Proof
, Available online 20
February 2006,




6.

Ulrich Pison, Tobias Welte, Michael Giersig and David A. Groneberg

Nanomedicine for respiratory diseases

European Journal of Pharmacology,
Volume 533, Issues 1
-
3, 8 March 2006, Pages
341
-
350