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

What is Nanotechnology www.phys.psu.edu www.nasa.gov www.purdue.edu 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

10 millions times smaller What is Nanoscale ww.mathworks.com Fullerenes C60 www.physics.ucr.edu 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

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)

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

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

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.

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.

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

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

Gold(Au) Nanoparticles (and silver)

Outline Motivation History Colloids Nucleation Growth Coagulation Procedure Viewing the particles

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

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

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

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

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

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

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

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

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).

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.

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

Targeted Delivery to Tumors

Integration of three elements

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

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

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

Fluorophores and Drugs Selectively Dissociate Inside Cells

Control of Surface Charge

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

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: 10.1021/nl060275y

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

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: 10.1021/nn900002m

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

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)