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Nanotechnology
 Creation of useful materials, devices, and systems
through the manipulation of matter on nanometer
scale.
- Generally nanotechnology deals with structures sized
between 1 to 100 nanometer in at least one dimension.
 Ability to design systems with defined structure and
function on the nanometer scale.
 Involves developing materials, devices within that
size, and analytical tools (methodology), which can be
used for analysis and measurement on a molecular scale
 Interdisciplinary area :
Biology, Physics, Chemistry, Material science, Electronics,
Chemical Engineering, Information technology
Nanotechnology Plays by Different Rules
Normal scale
Nanoscale
Analytical methods and Nano-sized materials
 Analytical tools : Atomic force microscopy(AFM), Electron
microscopy (EM)
 Nano-sized materials
 Unusual and different property
- Semiconductor nanocrystals:
Size-dependent optical property
- Nanoparticles:
Magnetic nanoparticles (Ferromagnetic,
superparamagnetic), Gold, Carbon nanotubes,
Quantum dots (Semiconductor nanocrystals)
Future implications of nanotech
 Nanotechnology may be able to create many new
materials and devices with a vast range of applications,
such as in medicine, biomaterials, electronics, and energy
production.
 Nanotechnology raises many of the same issues as with
any introduction of new technology, including concerns
about the toxicity and environmental impact of
nanomaterials, and their potential effects on global
economics.
Nano-Biotechnology
 Integration of nano-sized/structured materials, nanoscale analytical tools, and nano-devices into biological
sciences for development of new biomaterials and
analytical toolkits as well as for understanding life
science
 Use of bio-inspired molecules or materials
 Typical characteristics of Biological events/materials
- Self assembly
- Highly efficient : high energy yield
- Very specific : extremely precise
 Bio-molecules
Proteins, DNA, RNA, Aptamers, Peptides, Antibody, Virus
Nano-Bio Convergence
Bio-inspired device and system
Bio-Technology
Nano-Technol
Molecular Imaging
Molecular Switch
DNA barcode
Biochip / Biosensor
Nanotherapy /
Delivery
Bionano-machine /
Nano-Robot
Applications and Perspectives of Nanobiotechnology
 Development of tools and methods
- More sensitive
- More specific
- Multiplexed
- More efficient and economic
 Implementation
 Diagnosis and treatment of diseases
- Rapid and sensitive detection (Biomarkers, Imaging)
- Targeted delivery of therapeutics
 Drug development
- Understanding of life science
Examples

Nano-Biodevices
 Nano-Biosensors
 Imaging with nanoparticles
 Analysis of a single molecule/ a single cell
Issues to be considered
 Synthesis or selection of nano-sized/ structured
materials
 Functionalization with biomolecules or for
biocompatibility
 Integration with devices and/or analytical tools
 Assessment : Reproducibility, Toxicity
 Implementation
The size of Things
NanoBiotech was initiated by the development of AFM
that enables imaging at atomic level in 1980
AFM (Atomic Force Microscope)
One of the foremost tools
for imaging, measuring, and
manipulating matters at the nanoscale.
 A cantilever with a sharp tip (probe)
at its end that is used to scan
the specimen surface
 When the top is brought into a close
proximity of a sample surface,
force between the tip and sample leads
to a deflection of the cantilever according to
Hooke’s law
 Deflection is measured using a laser spot
reflected from the top surface of the
cantilever into an array of photodiode
VEECO
TESPA®
VEECO
TESPA-HAR®
NANOWORLD
SuperSharpSilicon®
Tip length : 10 m
Radius : 15~20 nm
Tip length :10 m
(last 2 m 7:1)
Radius : 4~10 nm
Tip length :10 m
Radius : 2 nm
Example showing the resolution
of protein structure by AFM
Image of ATP synthase composed of 14subunits
Molecular imaging
 Biomedical & Biological Sciences :
 Ultra-sensitive imaging of biological targets under non-invasive in-vivo
conditions
 Fluorescence, positron emission tomography, Magnetic resonance
imaging
 Ultra-sensitive imaging
- Cancer detection, cell migration, gene expression, localization of
proteins, angiogenesis, apotosis
- MRI : Powerful imaging tool as a result of non-invasive nature,
high spatial resolution and tomographic capability
Resolution is highly dependent on the molecular imaging agents
 Signal enhancement by using contrast agents : iron oxide nanoparticles
Semiconductor Nanocrystals
Quantum Dots
- Properties and Biological Applications
Synthesis of CdSe/ZnS (Core/Shell) QDs
Step 1
CdO
+ Se
CdSe
Solvent : TOPO, HAD, TOP
Surfactant : TDPA, dioctylamine
Step 2
CdSe/ZnS
5.5 nm
(red)
ZnS
ZnEt2 + S(TMS)2
CdSe
Growth temperature
 140 ℃ (green)
200 ℃ (red)
Ar
Thermocouple
Se solution
CdO solution
320 ℃
20 nm
Bawendi et al. J. Am. Chem. Soc. (1994)
Optical Properties Of Quantum Dots
a) Multiple colors
b) Photostability
c) Wide absorption and narrow emission d) High quantum yield
Quantum Yield ≥ 60 ~ 70 %
Single source excitation
QD Surface Coating for Biocompatibility ①
NH2
NH2
Encapsulation with the hydrophobic core of a micell
NH2
+
Coating with PC
P P
O O
P
O
CdSe O P
OP
O
O P
P
CdSe QDs
N
+
P
P
O O
ZnS
P
O OP
ZnS
O
O
P
Coating of the outer shell
with ZnS
OP
OP
O
P
O
P
NH2
OP
CdSe
CdSe
NH2
N
+
OP
O
P
O
N
NH2
P
+
N
P
CdSe/ZnS core-shell
+
N
NH2
NH2
Quantum Dots Encapsulated in
Phospholipid Micelles
PEG-PE (n-poly(ethylenglycol)phosphatidylethanolamine): micell-forming hydrophilic
polymer-grafted lipids  comparable to natural lipoproteins
PEG : low immunogenic and antigenic, low non-specific protein binding
PC : Phosphatidylcholine
Dubertret et al. Science (2002)
In Vivo Cell Imaging
Y
+
QD
Organelle
QD-Antibody
conjugates
Antigen
Y
▲ 3T3 cell nucleus stained
with red QDs and
microtubules with green QDs
QD
Organelle
- Multiple Color Imaging
- Stronger Signals
Wu et al. Nature Biotech. 2003 21 41
In Vivo Cell Imaging
Live Cell Imaging
Quantum Dot Injection
▶ Red Quantum Dot locating
a tumor in a live mouse
Cell Motility Imaging
10um
◀ Green QD filled
vesicles move toward to
nucleus (yellow arrow) in
breast tumor cell
Alivisatos et al., Adv. Mater., 2002 14 882
Biosystems
• Inherent capabilities of molecular recognition
and self-assembly
• Attractive template for constructing and
organizing the nano-structures
• Proteins, toxin, coat proteins of virus etc.
α -Hemolysin: Self-Assembling Transmembrane Pore
 A self-assembling bacterial exo-toxin produced by some
pathogens like Staphylococcus aureus as a way to obtain
nutrients  lysis of red blood cells
 Alpha-hemolysin monomers bind to the outer membrane
of susceptible cells.
 Monomers oligomerize to form a water-filled heptameric
transmembrane channel that facilitates uncontrolled
permeation of water, ions, and small organic molecules.
 Rapid discharge of vital molecules, such as ATP,
dissipation of the membrane potential and ionic gradients,
and irreversible osmotic swelling leading to the cell wall
rupture (lysis), can cause death of the host cell.
- Mushroom-like shape
with a 50 A beta-barrel stem
- Narrowest part (1.4 nm in diameter) of
channel at the base of stem
Biotechnological applications :Stochastic sensors
 A molecular adaptor is placed inside its engineered stem, influencing
the transmembrane ionic current induced by an applied voltage
 Reversible binding of analytes to the molecular adaptor transiently
reduces the ionic current
- Magnitude of the current reduction : type of analyte
- Frequency of current reduction intervals: analyte concentration
Stochastic Sensors
a : Histidine captured metal ions (Zn+2, Co+2, mixture )
b: CD captures anions (promethazine, imipramine, mixture)
c : biotin ligand
DNA sequencing
 Transmembrane pore can conduct big (tens of kDa) linear
macromolecules like DNA or RNA
 Eelectrophoretically-driven translocation of a 58-nucleotide DNA
strand through the transmembrane pore of alpha-hemolysin
 Changes in the ionic current by the chemical structure of individual
strands
 Nucleotide sequence directly from a DNA or RNA strand
 A single nucleotide resolution
Understanding Cancer and Related Topics
Understanding Nanodevices
Developed by:
Jennifer Michalowski, M.S.
Donna Kerrigan, M.S.
Jeanne Kelly
Brian Hollen
Explains nanotechnology and its potential
to improve cancer detection, diagnosis,
and treatment. Illustrates several
nanotechnology tools in development,
including nanopores, quantum dots, and
dendrimers.
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What Is NanoBiotechnology?
Water
molecule
Nanodevices
Nanopores
Dendrimers
Nanotubes
Quantum dots
Nanoshells
White
blood cell
A period
Tennis ball
Designing Nanodevices for
Use in the Body
Too Small
Too Big
Manufacturing Nanodevices
X-ray
beam
Crystal
Crystal
Scattered
X-rays
Detector
Nanodevices
Atoms
in crystal
White
blood cell
Nanodevices Are
Small Enough to Enter Cells
Cell
Nanodevices
Nanodevices
Water
molecule
White
blood cell
Nanodevices Can Improve Cancer
Detection and Diagnosis
NanoBiotechnology
Imaging
Physical Exam,
Symptoms
Nanodevices Can Improve Sensitivity
Nanodevices
could potentially
enter cells
Precancerous cells
Normal cells
and determine
which cells are
cancerous or
precancerous.
Precancerous cells
Normal cells
Nanodevices Can
Preserve Patients’ Samples
Traditional Tests
Cells from patient
Cells altered
Active state lost
Nanotechnology Tests
Cells from patient
Cells preserved
Active state preserved
Additional tests
Nanodevices Can Make Cancer Tests
Faster and More Efficient
Patient A
Patient B
Cantilevers Can Make Cancer Tests
Faster and More Efficient
Cancer cell
Antibodies
with proteins
Antibodies
Bent cantilever
Water
molecule
White
blood cell
Nanodevices
Cantilevers
Nanopores
Single-stranded
DNA molecule
A
T
C
G
Nanopore
Singlestranded
DNA
molecule
A
Nanopore
T
Nanopore
Single-stranded
DNA molecule
Water
molecule
Nanodevices
Nanopores
White
blood cell
Quantum Dots
Ultraviolet
light off
Quantum dot
bead
Water
molecule
Ultraviolet
light on
Quantum
dots
Nanodevices
Quantum dots
Quantum dots
emit light
White
blood cell
Quantum Dots Can
Find Cancer Signatures
Quantum dot beads
Cancer cells
Healthy cells
Cancer cells
Quantum dot beads
Healthy cells
Improving Cancer Treatment
Traditional Treatment
Drugs
Nanotechnology Treatment
Toxins
Nanodevices
Cancer
cells
Cancer
cells
Noncancerous cells
Dead
cancer
cells
Dead noncancerous cells
Toxins
Noncancerous cells
Dead
cancer
cells
Intact noncancerous cells
Nanoshells
Near-infrared light off
Nanoshell
Near-infrared light on
Gold
Nanoshell absorbs heat
Water
molecule
Nanodevices
Nanoshells
White
blood cell
Nanoshells as Cancer Therapy
Nanoshells
Nanoshells
Cancer cells
Cancer
cells
Healthy cells
Healthy cells
Near-infrared light
Dead cancer cells
Intact healthy cells
Nanodevices as a Link Between
Detection, Diagnosis, and Treatment
Traditional
Cancer Treatment
NanoBiotechnology
Cancer Treatment
Cancer cell
Cancer cell
Nanodevice
Drug
Imaging
Reporting
Detection
Targeting
Dendrimers
Cancer cell
Dendrimer
Water
molecule
Nanodevices
Dendrimer
White
blood cell
Dendrimers : Highly Branched Dendritic
Macromolecules
Poly (amido amine) Dendrimers
● Characteristics
 Monodisperse macromolecule
 Globular (Spherical)
 Facile surface bio-functionalization
 Similar molecular size to biomolecules
(Glucose oxidase 65.27.7 nm)
● Applications
Vehicles for delivery of genes and
drugs
4.5 nm
G4 Poly(amidoamine)
Dendrimer
Biomimetic catalysts
(Peptides-, Glycodendrimers)
Medical applications (MRI contrast
enhancer)
Molecular carriers for chemical
catalysts
(Core, Peripheral)
Dendrimers as Cancer Therapy
Manipulate dendrimers to release their contents only in the
presence of certain trigger (molecules or light)  caged molecules
Therapeutic
agent
Cancer
detector
Cell death
monitor
Reporter
Water
molecule
Nanodevices
Dendrimer
White
blood cell
NanoBiotechnologies in Patient Care
Today
2020
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