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

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®

NANOWORLDSuperSharpSilicon®

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- 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, TOPSurfactant : 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 emissiond) High quantum yield

Quantum Yield ≥ 60 ~ 70 %

Single source excitation

QD Surface Coating for Biocompatibility ①

CdSe

ZnS

CdSe

ZnS

O P

O PO

POP

OP

OP

OP

CdSe O PO P

OPO

P

OP

OP

OP CdSe

ZnS

CdSe

ZnS

O P

O PO

POP

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

Y

Y

Y

YYY

Y

Organelle

+

QD-Antibodyconjugates

Antigen

QD

Y

Y

Y

Y

YYY

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

- 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

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Understanding Cancer and Related Topics

Understanding Nanodevices

Developed by:Jennifer Michalowski, M.S.Donna Kerrigan, M.S.Jeanne KellyBrian HollenExplains 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.

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What Is NanoBiotechnology?

NanodevicesNanoporesDendrimersNanotubesQuantum dotsNanoshells

Tennis ballA periodWhite blood cell

Water molecule

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Designing Nanodevices for Use in the Body

Too BigToo Small

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Manufacturing Nanodevices

Scattered X-rays

Atoms in crystal

Detector

NanodevicesCrystal White blood cell

CrystalX-ray beam

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Nanodevices Are Small Enough to Enter Cells

Cell

White blood cell

Water molecule

Nanodevices

Nanodevices

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Nanodevices Can Improve Cancer Detection and Diagnosis

ImagingNanoBiotechnology Physical Exam,Symptoms

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Nanodevices Can Improve Sensitivity

and determinewhich cells arecancerous orprecancerous.

Precancerous cells

Normal cells

Nanodevices could potentiallyenter cells

Precancerous cells

Normal cells

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Nanodevices Can Preserve Patients’ Samples

Cells from patientCells preserved

Active state preserved

Cells altered Active state lost

Additional tests

Cells from patient

Nanotechnology Tests

Traditional Tests

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Nanodevices Can Make Cancer TestsFaster and More Efficient

Patient A Patient B

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Cantilevers Can Make Cancer TestsFaster and More Efficient

Cancer cell

Watermolecule

NanodevicesCantilevers

Antibodieswith proteins

Antibodies

Whiteblood cell

Bent cantilever

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Nanopores

ASingle-strandedDNA molecule

Single-strandedDNA molecule

Whiteblood cell

Watermolecule

NanodevicesNanopores

Single-strandedDNA molecule

ATCGNanopore Nanopore

Nanopore

T

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Quantum DotsUltraviolet

light off

Whiteblood cell

Watermolecule

NanodevicesQuantum dots

Quantum dots emit light

Ultravioletlight on

Quantumdots

Quantum dotbead

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Quantum Dots Can Find Cancer Signatures

Cancer cells

Healthy cells

Quantum dot beads

Quantum dot beads

Healthy cells

Cancer cells

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Improving Cancer TreatmentNanotechnology TreatmentTraditional Treatment

Intact noncancerous cells

Noncancerous cells

Toxins Nanodevices

Cancercells

Dead noncancerous cells

Noncancerous cells

Drugs

Deadcancercells

Deadcancercells

ToxinsCancercells

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Nanoshells

Nanoshell

Whiteblood cell

Watermolecule

Nanodevices Nanoshells

Gold

Near-infrared light onNear-infrared light off

Nanoshell absorbs heat

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Nanoshells as Cancer TherapyNanoshells

Dead cancer cells

Nanoshells

Cancer cells

Healthy cells

Intact healthy cells

Near-infrared light

Healthy cells

Cancer cells

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Nanodevices as a Link BetweenDetection, Diagnosis, and Treatment

Nanodevice

Reporting

TargetingDetection

Imaging

NanoBiotechnologyCancer Treatment

Cancer cell

TraditionalCancer Treatment

Cancer cell

Drug

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Dendrimers

Dendrimer

Whiteblood cell

Watermolecule

Nanodevices Dendrimer

Cancer cell

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Dendrimers : Highly Branched Dendritic Macromolecules

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● 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

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Dendrimers as Cancer Therapy

Cell deathmonitor

Reporter

Therapeuticagent

Cancerdetector

Watermolecule

Whiteblood cell

Nanodevices Dendrimer

Manipulate dendrimers to release their contents only in the presence of certain trigger (molecules or light) caged molecules

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NanoBiotechnologies in Patient Care

Today 2020

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