1. بنام خداوند جان آفرین Nano Particles in Nano-Biotechnology
Spring Semester Course (1389)
M. Habibi-Rezaei

2. What is Nanotechnology
Semiconducting metal junction formed by two carbon nanotubes
An engineered DNA strand
pRNA tiny motor
Nanotechnology is the creation of functional materials, devices and systems, through the understanding and control of matter at dimensions in the nanometer scale length (1-100 nm), where new functionalities and properties of matter are observed and harnessed for a broad range of applications

3. 10 millions times smaller
What is Nanoscale
ww.mathworks.com
Fullerenes C60
22 cm
12,756 Km
0.7 nm
1.27 × 107 m
0.22 m
0.7 × 10-9 m
10 millions times smaller
1 billion times smaller

4. Nanoscale Size Effect
Realization of miniaturized devices and systems while providing more functionality
Attainment of high surface area to volume ratio
Manifestation of novel phenomena and properties, including changes in:
- Physical Properties (e.g. melting point)
- Chemical Properties (e.g. reactivity)
- Electrical Properties (e.g. conductivity)
- Mechanical Properties (e.g. strength)
- Optical Properties (e.g. light emission)

5. Nanotechnology Applications
Information Technology
Energy
More efficient and cost effective technologies for energy production
Solar cells
Fuel cells
Batteries
Bio fuels
Smaller, faster, more energy efficient and powerful computing and other IT-based systems
Consumer Goods
Medicine
Foods and beverages
Advanced packaging materials, sensors, and lab-on-chips for food quality testing
Appliances and textiles
Stain proof, water proof and wrinkle free textiles
Household and cosmetics
Self-cleaning and scratch free products, paints, and better cosmetics
Cancer treatment
Bone treatment
Drug delivery
Appetite control
Drug development
Medical tools
Diagnostic tests
Imaging

6. Nanoscale Materials Bionanomaterials
Protein
Bionanomaterials
Biological materials utilized in nanotechnology
- Proteins, enzymes, DNA, RNA, peptides
Synthetic nanomaterials utilized in biomedical applications
- Polymers, porous silicon, carbon
nanotubes
Cross-linked enzymes used as catalyst – Univ. of Connecticut, Storrs , 2007
Enzymes are used as oxidation catalysts
Bone cell on porous silicon – Univ. of Rochester, 2007
Porous silicon (PSi)
Human cell on PSi

7. Nanoscale Materials
Nanoscale materials have feature size less than 100 nm – utilized in nanoscale structures, devices and systems Nanoparticles and Structures
A 3-dimensional nanostructure grown by controlled nucleation of Silicon-carbide nanowires on Gallium catalyst particles
– Univ. of Cambridge, 2007
Gold nanoparticles
– TU Dresden/ESRF, 2008
Silver nanoparticles – Northwestern Univ., 2002
A stadium shaped “quantum corral” made by positioning iron atoms on a copper surface – IBM Corp., 1993.

8. Nanoparticles Introduction
Diesel engines, among others, emit particles consisting of irregularly shaped solid carbon spherules agglomerated in clusters on which some hydrocarbons, sulphates and water condense. Particles are small existing in a sizes ranging from some nanometres to few micrometers.
Exhaust particles have gained the attention of research groups due to environmental and health issues. These particles are believed to be harmfull to humans and animals, to moddify the radiative tranfer of the earth and to damage monuments architectural values.

9. Nanotechnology in Health Care
Thermal ablation of cancer cells
Nanoshells have metallic outer layer and silica core
Selectively attracted to cancer shells either through a phenomena called enhanced permeation retention or due to some molecules coated on the shells
The nanoshells are heated with an external energy source killing the cancer cells
Thermal ablation of cancer cells assisted by nanoshells coated with metallic layer and an external energy source – National Cancer Institute

10. Nanoscale Processes and Fabrication
Top-down Approaches
Bottom-up Approaches
Optical and x-ray lithography
Layer-by-layer self assembly
E-beam and ion-beam lithography
Molecular self assembly
Scanning probe lithography
Direct assembly
Atomic force microscopic lithography
Coating and growth
Material removal and deposition
(Chemical, mechanical, or ultrasonic)
Colloidal aggregation
Printing and imprinting

11. Gold(Au) Nanoparticles (and silver)

12. Outline Motivation History Colloids Nucleation Growth Coagulation
Procedure
Viewing the particles

13. Motivation Some quacks still assert profound medicinal properties
Spherical nanoparticles can serve as biological tags for tracking purposes
The red color in stained glass windows is due to colloidal gold
Can be used for a new ultrasensitive and selective detection scheme for DNA
Gold nanorods can be bar-coded Au/Pt
OU NanoLab/NSF NUE/Bumm & Johnson

14. History Alchemists believed Au sols might be the “elixir of life”
Faraday researched many of the properties of colloidal gold in the 1850’s.
Mie’s theory of light scattering was developed to explain the color of colloidal gold.
Medical applications were developed that diagnosed certain diseases based on the interaction of colloidal gold and spinal fluids
The first comprehensive investigation using the electron microscope began in 1948 at Princeton University and RCA Labs

15. The Optics of Gold and Silver Nanoparticles
The color of the sol arises from a combination of absorption and scattering of light and depends on particle size
More specifically it is due to a resonance of the free electrons in the metal particle. The light’s electromagnetic field causes them to slosh back and forth (plasmon oscillations).
At a characteristic frequency which depends of the size and the metal, the sloshing is the most intense. This is the frequency where plasmon oscillations are excited.
The plasmon resonance is easily seen in the extinction spectrum of the sol.
OU NanoLab/NSF NUE/Bumm & Johnson

16. Colloids
A colloid is a homogeneous dispersion of particles in a solution which are so small as to not settle out easily.
A sol is a specific type of colloid characterized as a solid dispersed in a liquid.
The colloid is stabilized by electric charges on its surface due to adsorbed ions. The charge causes the particles to repell each other. The both the Gold and Silver sols used here have a negative charge.
The particles experience the constant buffeting of Brownian motion which also helps to keep them in suspension.
Formulation of Au nanoparticles is a three step process: nucleation, growth, and coagulation

17. Nucleation
Nucleation is the creation of nuclei upon which growth can occur.
This is a redox reaction: oxidation of the citrate ion produces the necessary reducing reagent for the gold: acetone dicarboxylic acid.
The acetone dicarboxylic acid is the limiting reagent for nucleation
The formation of this molecule in the solution creates an induction period before which no product can be seen.
The nature of the nucleation curve is evidence of an autocatalytic reaction.
That is to say it has a rapid growth after the induction period followed by a linear portion and then decay

18. Nucleation (cont.)
A type of polymerization (complexation) occurs in which the gold ions coordinate with acetone dicarboxylic acid and join together.
When the “polymer,” or complex, reaches a critical mass that is just greater its thermodynamic stability, reduction to metallic gold occurs, yielding the nuclei .
Reduction is the rate determining step in the kinetics of the reaction.
The less citrate in the mixture, the larger the particles will be in size

19. Growth
Growth is the addition of more gold particles to the existing nuclei.
The process of growth stops when all of the gold is used.
The rate of growth is a first order in the gold nuclei size.
Having the equation dD/dt = kD, where k is a constant whose value is independent of particle size

20. Coagulation
Creation of the larger gold particles, such as 20 nm, requires a coagulation of multiple (smaller) twins of various shapes
A conglomeration of multiple nuclei into particles can be large enough to disturb the stability and fall out of the colloid
Control of the coagulation process during preparation determines the size, structure, and size distribution of the particle
Once the preparation of the gold nanoparticles is complete, the absence of coagulation insures its stability

21. Procedure Bring to a boil 50 ml of 0.25 mM chlorauric acid solution
Add 160 μl to 1.0 ml of 34 mM sodium citrate solution to the boiling solution while stirring
After a minute will be faint blue and then darkening over 5 min to a brilliant red
The size of the gold nanoparticles can be controlled by varying the amount of sodium citrate solution.
The following procedure can grow controlled sizes from 147 nm (0.16 ml) down to 16 nm (1.0 ml).

22. Uses of Silver Nanoparticles
No more smelly socks - inhibits bacteria that causes foot odour by resisting stains and water absorbance.
Antibacterial properties added to athletic wear, bandages (especially burn victims) and cleaning products.
Sterilizes water better than chlorine.
Curtains embedded with Ag nanoparticles reduce infectious microbes in hospitals.
Deactivates HIV by inhibiting the virus from attaching to the host with undetectable levels of cytoxicity.
Two brands of sock lost nearly 100% of their silver content within four washings, while two other brands lost less than 1% over the same number of washings.

23. Seeing is believing Tunability
can make silver nanoparticles with various sizes.
each size can absorb light differently.
can make them for the visible spectrum.
Left to Right
10 nm
30 nm
100 nm

25. Targeted Delivery to Tumors

26. Integration of three elements

27. Many Different Length Scales
10cm
100mm
1cm
1mm

28. Relative Size of Nanoparticles
Nanoparticle with a 2 nm core and an octanethiol functionalized monolayer

29. Making Gold Nanoparticles
AuCl4- salts are reduced using NaBH4 in the presence of thiol capping ligands
The core size of the particles formed can be varied from <1 nm to ~ 8 nm
The surface functionality can be controlled through the choice of thiols

30. Fluorophores and Drugs Selectively Dissociate Inside Cells

31. Control of Surface Charge

32. Nanotechnology in Health Care
Treatment
Targeted drug delivery
Nanoparticles containing drugs are coated with targeting agents (e.g. conjugated antibodies)
The nanoparticles circulate through the blood vessels and reach the target cells
Drugs are released directly into the targeted cells
Targeted drug delivery – Targeted drug delivery using a multicomponent nanoparticle containing therapeutic as well as biological surface modifying agents – Mauro Ferrari, Univ. of Cal. Berkley

33. Nanoscale Devices and Integrated Nanosystems
Nanochip
Currently available microprocessors use resolutions as small as 32 nm
Houses up to a billion transistors in a single chip
MEMS based nanochips have future capability of 2 nm cell leading to 1TB memory per chip
A MEMS based nanochip
– Nanochip Inc., 2006
Nanoelectromechanical System (NEMS) Sensors
NEMS technology enables creation of ultra small and highly sensitive sensors for various applications
The NEMS force sensor shown in the figure is applicable in pathogenic bacteria detection
A NEMS bacteria sensor
– Nano Lett., 2006, DOI: /nl060275y

34. Nanoscale Devices and Integrated Nanosystems
Nanophotonic Systems
Nanophotonic systems work with light signals vs. electrical signals in electronic systems
Enable parallel processing that means higher computing capability in a smaller chip
Enable realization of optical systems on semiconductor chip
A silicon processor featuring on-chip nanophotonic network – IBM Corp., 2008
Fuel Cells
Fuel cells use hydrogen and air as fuels and produce water as by product
The technology uses a nanomaterial membrane to produce electricity
Schematic of a fuel cell
– Energy solution center Inc.
500 W fuel cell – H2economy.com

35. Nanoscale Devices and Integrated Nanosystems
Lab on Chip
A lab on chip integrates one or more laboratory operation on a single chip
Provides fast result and easy operation
Applications: Biochemical analysis (DNA/protein/cell analysis) and bio-defense
Lab on chip gene analysis device – IBN Singapore, 2008
Drug Delivery Systems
Impact of nanotechnology on drug delivery systems:
Targeted drug delivery
Improved delivery of poorly water soluble drugs
Co-delivery of two or more drugs
Imaging of drug delivery sites using imaging modalities
Targeted drug delivery
– ACS Nano 2009, DOI: /nn900002m

36. Nanotechnology in Health Care
Nanotechnology offers tools and techniques for more effective detection, diagnosis and treatment of diseases
Detection and Diagnosis
Lab on chips help detection and diagnosis of diseases more efficiently
Nanowire and cantilever lab on chips help in early detection of cancer biomarkers
The microfluidic channel with nanowire sensor can detect the presence of altered genes associated with cancer – J. Heath, Cali. Insti. of Technology
The nanoscale cantilever detects the presence and concentration of various molecular expressions of a cancer cell – A. Majumdar, Univ. of Cal. at Berkeley

37. Nanotechnology Health and Environmental Concerns
Human and the environment come under exposure to nanomaterials at different stages of the product cycle
Nanomaterials have large surface to volume ratio and novel physical as well as chemical properties which may cause them to pose hazards to humans and the environment
Health and the environmental impacts associated with the exposure to many of the engineered nanomaterials are still uncertain
The environmental fate and associated risk of waste nanomaterials should be assessed – e.g. toxic transformation, and interactions with organic and inorganic materials
Exposure of human and the environment to nanomaterials at different stages of product life cycle – US environmental protection agency, 2007 (epc.gov)