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, nano-scale 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

Molecular Switch

DNA barcode

Molecular Imaging

Biochip / Biosensor

Nanotherapy /

Delivery

Bio-Technology Nano-Technol

Bionano-machine /

Nano-Robot

Bio-inspired device and system

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)

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

One of the foremost tools for imaging, measuring, and manipulating matters at the nanoscale.

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

- Properties and Biological Applications

Semiconductor Nanocrystals

Quantum Dots

Synthesis of CdSe/ZnS (Core/Shell) QDs

Step 1

CdO + Se CdSe

Step 2

ZnEt2 + S(TMS)2 CdSe

ZnS

Solvent : TOPO, HAD, TOP Surfactant : TDPA, dioctylamine

Growth temperature 140 ℃ (green) 200 ℃ (red)

Ar

320 ℃

CdO solution

Se solution

Thermocouple

20 nm

CdSe/ZnS 5.5 nm (red)

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

CdSe

ZnS

CdSe

ZnS

O P

O P

OPO

P

OP

OP

OP

CdSe O P

O PO

POP

OP

OP

OP

CdSe

ZnS

CdSe

ZnS

O P

O P

OPO

P

OP

OP

OP

NH2

NH2

NH2

NH2

+N

+N

+N

+N

NH2

NH2

NH2

NH2

+N

CdSe/ZnS core-shell Quantum Dots Encapsulated in

Phospholipid Micelles

CdSe QDs

Dubertret et al. Science (2002)

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

Encapsulation with the hydrophobic core of a micell

Coating with PC

Coating of the outer shell with ZnS

QD

Y

Organelle

+

QD-Antibody conjugates

Antigen

QD

Y

Organelle

▲ 3T3 cell nucleus stained with red QDs and microtubules with green QDs

In Vivo Cell Imaging

Wu et al. Nature Biotech. 2003 21 41

- Multiple Color Imaging - Stronger Signals

In Vivo Cell Imaging

Quantum Dot Injection

▶ Red Quantum Dot locating a tumor in a live mouse

Live Cell Imaging

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

• Inherent capabilities of molecular recognition and self-assembly

• Attractive template for constructing and

organizing the nano-structures

• Proteins, toxin, coat proteins of virus etc.

Biosystems

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

- Magnitude of the current reduction : type of analyte

- Frequency of current reduction intervals: analyte concentration

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

Biotechnological applications :Stochastic sensors

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.

These PowerPoint slides are not locked files. You can mix and match slides from different tutorials as you prepare your own lectures. In the Notes section, you will find explanations of the graphics.

The art in this tutorial is copyrighted and may not be reused for commercial gain. Please do not remove the NCI logo or the copyright mark from any slide. These tutorials may be copied only if they are distributed free of charge for educational purposes.

What Is NanoBiotechnology?

Nanodevices Nanopores Dendrimers Nanotubes Quantum dots Nanoshells

Tennis ball A period White blood cell

Water molecule

Designing Nanodevices for Use in the Body

Too Big Too Small

Manufacturing Nanodevices

Scattered X-rays

Atoms in crystal

Detector

Nanodevices Crystal White blood cell

Crystal X-ray beam

Nanodevices Are Small Enough to Enter Cells

Cell

White blood cell

Water molecule

Nanodevices

Nanodevices

Nanodevices Can Improve Cancer Detection and Diagnosis

Imaging NanoBiotechnology Physical Exam, Symptoms

Nanodevices Can Improve Sensitivity

and determine which cells are cancerous or precancerous.

Precancerous cells

Normal cells

Nanodevices could potentially enter cells

Precancerous cells

Normal cells

Nanodevices Can Preserve Patients’ Samples

Cells from patient Cells preserved

Active state preserved

Cells altered Active state lost

Additional tests

Cells from patient

Nanotechnology Tests

Traditional 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

Water molecule

Nanodevices Cantilevers

Antibodies with proteins

Antibodies

White blood cell

Bent cantilever

Nanopores

A Single-stranded DNA molecule

Single-stranded DNA molecule

White blood cell

Water molecule

Nanodevices Nanopores

Single-stranded DNA molecule

A T C G Nanopore Nanopore

Nanopore

T

Quantum Dots Ultraviolet

light off

White blood cell

Water molecule

Nanodevices Quantum dots

Quantum dots emit light

Ultraviolet light on

Quantum dots

Quantum dot bead

Quantum Dots Can Find Cancer Signatures

Cancer cells

Healthy cells

Quantum dot beads

Quantum dot beads

Healthy cells

Cancer cells

Improving Cancer Treatment

Nanotechnology Treatment Traditional Treatment

Intact noncancerous cells

Noncancerous cells

Toxins Nanodevices

Cancer cells

Dead noncancerous cells

Noncancerous cells

Drugs

Dead cancer cells

Dead cancer cells

Toxins Cancer cells

Nanoshells

Nanoshell

White blood cell

Water molecule

Nanodevices Nanoshells

Gold

Near-infrared light on Near-infrared light off

Nanoshell absorbs heat

Nanoshells as Cancer Therapy Nanoshells

Dead cancer cells

Nanoshells

Cancer cells

Healthy cells

Intact healthy cells

Near-infrared light

Healthy cells

Cancer cells

Nanodevices as a Link Between Detection, Diagnosis, and Treatment

Nanodevice

Reporting

Targeting Detection

Imaging

NanoBiotechnology Cancer Treatment

Cancer cell

Traditional Cancer Treatment

Cancer cell

Drug

Dendrimers

Dendrimer

White blood cell

Water molecule

Nanodevices Dendrimer

Cancer cell

Dendrimers : Highly Branched Dendritic

Macromolecules

● Characteristics

Monodisperse macromolecule

Globular (Spherical)

Facile surface bio-functionalization

Similar molecular size to biomolecules

(Glucose oxidase 65.27.7 nm)

Molecular carriers for chemical

catalysts

(Core, Peripheral)

Medical applications (MRI contrast

enhancer)

Biomimetic catalysts

(Peptides-, Glycodendrimers)

Vehicles for delivery of genes and

drugs

Poly (amido amine) Dendrimers

4.5 nm

G4 Poly(amidoamine)

Dendrimer

● Applications

Dendrimers as Cancer Therapy

Cell death monitor

Reporter

Therapeutic agent

Cancer detector

Water molecule

White blood cell

Nanodevices Dendrimer

Manipulate dendrimers to release their contents only in the

presence of certain trigger (molecules or light) caged molecules

NanoBiotechnologies in Patient Care

Today 2020

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