Tighineanu Nanotechnologies in Medicine Lectures 3-4
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Transcript of Tighineanu Nanotechnologies in Medicine Lectures 3-4
Prof. Ion TighineanuAcademy of Sciences of Moldova
Advanced training Nano-bioengineering 2011-2012
Cuprins
1. Nanoscale-size-related phenomena
1. Wettability for cleaning, transport or water collection
1. Design and creation of bioinspired surfaces
1. Synthetic nanomaterials utilized in biomedicine – nanoparticles, polymers, porous materials, carbon nanotubes. Dendrimers
• 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)
Early Plasmonic Nanotechnology
The Lycurgus Cup Late Roman, 4th century, Probably made in Rome
(British Museum)Stained glass: Notre Dame
Cathedral Paris
Stained glass in medieval churches, glazes in ancient pottery were made with... plasmons
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
Nanoscale Devices and Integrated Nanosystems
− 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 NEMS bacteria sensor Nano Lett., 2006, DOI: 10.1021/nl060275y
Nanochip
Nanoelectromechanical System (NEMS) Sensors
A MEMS based nanochip – Nanochip Inc., 2006
− 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
Nanoscale Devices and Integrated Nanosystems
Nanophotonic Systems
A silicon processor featuring on-chip nanophotonic network – IBM Corp., 2008
− 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
− 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.
Fuel Cells
500 W fuel cell –
H2economy.com
Nanoscale Devices and Integrated Nanosystems
Lab on chip gene analysis device – IBN Singapore, 2008
Lab on Chip
Drug Delivery Systems
Targeted drug delivery – ACS Nano 2009, DOI: 10.1021/nn900002m
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
− 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
Information Technology Energy
MedicineConsumer Goods
• Smaller, faster, more energy efficient and powerful computing and other IT-based systems
• More efficient and cost effective technologies for energy production− Solar cells− Fuel cells− Batteries− Bio fuels
• 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
Nanotechnology Applications
Medical Nanotechnology or Nanomedicine
Nanomedicine is the application of nanotechnology in medicine, including to cure diseases and repair damaged tissues such as bone, muscle, and nerve
Key Goals for Nanomedicine
−To develop cure for traditionally incurable diseases (e.g. cancer) through the utilization of nanotechnology
−To provide more effective cure with fewer side effects by means of targeted drug delivery systems
Wettability is defined as the tendency of one fluid to spread on or adhere to a solid surface in the
presence of other immiscible fluids.
Small drops of three liquids - mercury, oil, and water - are placed on a clean glass plate. It is noted that the mercury retains a spherical shape, the oil droplet develops an approximately hemispherical
shape, but the water tends to spread over the glass surface.
The tendency of a liquid to spread over the
surface of a solid is an indication of the wetting
characteristics of the liquid for the solid. This
spreading tendency can be expressed in a
convenient way by measuring the angle of
contact at the liquid-solid surface.
The contact angle θ is considered as
a measure of wettability.
As the contact angle decreases, the wetting characteristics of the
liquid increase. Complete wettability would be evidenced by a zero
contact angle, and complete nonwetting would be evidenced by a
contact angle of 180°. There have been various definitions of
intermediate wettability but, in much of the published literature,
contact angles of 60° to 90° will tend to repel the liquid.
Interface energy:
If matter A and B are brought in contact, there is always a bond formation (at least van der Waals, materials could be also gas and liquid). The lowering of the potential energy that occurs during the interface formation, or the other way round, the energy that is needed to separate the two surfaces is called interface energy. Formation of a crack along the AB interface requires to overcome the interface energy by breaking the bonds. The energy between a solid or a liquid and a gas is often called surface energy.
In 1805, Thomas Young defined the contact angle θ by analyzing the forces acting on a fluid droplet resting
on a solid surface surrounded by a gas
where
= Interfacial tension between the solid and gas = Interfacial tension between the solid and liquid = Interfacial tension between the liquid and gas
Interfacial tension is the work required to create a unit area of new surface
σ So−σ Sw
=σ owcos θ
θwater
Oil
grain surface
oSσ
wSσ
owσ
cos So S w
ow
Young-Laplace equation
θwater
Oil
grain surface
θwater
Oil
grain surface
Water wet Oil wet
Dynamic contact angle experiments
Sliding Droplet: When a droplet is attached to a solid surface and the solid surface is tilted little by little, the droplet will lunge
forward and finally slide downward. The angles formed in the fore and the rear of the droplet lunging forward are respectively
called the Advancing Angle and the Receding Angle. The tilting angle of a solid surface when the droplet starts sliding
downward is called the Sliding Angle (t).
Superhydrophobicity and superhydrophilicity applied with capillaries
The wetting of a hydrophilic surface gives rise to an increase of the water level in a narrow tube, as there is an energy gain by wetting the surface. A force opposing this is finally gravity, limiting the height that can be reached. On the other hand,
on a hydrophobic surface of a capillary, it is possible to press the water out. These effects give rise to superhydrophobic and superhydrophilic surfaces.
Lotus effect: Selfcleaning of biological surfaces
When a droplet of water lands on the lotus leaf, it beads up, rolls off the leaf surface without leaving a trace of water behind
and washes away any dirt along its way. This self-cleaning property fascinated scientists for a long time until recently,
when scientists realized that this peculiar behaviour is due to the nanostructures present on the surface of the lotus leaf.
1. (Rain) Droplet falls on a surface
2. It forms a spherical surface.
3. It rolls over the surface even only very slightly tilted or from the momentum from falling.
4. The dropplet collects dust.
5. The droplet falls from the leave.
www.nature.com/nature/journal/v432/n7013/full/432036a.html
Water striders use surface tension to walk on the surface of a pond—Superhydrophobic setae on the tarsi keep the insect afloat while an
apical superhydrophilic claw penetrates the surface, allowing it to "grip" the water. The surface of the water behaves like an elastic film: the
insect's feet cause indentations in the water's surface, increasing its surface area. This represents an increase in potential energy through the surface tension of the water equal to the loss of potential energy
of the insect's lowered center of mass.
As the early morning fog drifts across the Namib Desert of south-west Africa, an army of spindly-legged beetles emerges from the sand. Accustomed to an average annual rainfall of one inch, these critters are eager to employ their water collection apparatus that makes them so unique. The process begins when heat is radiated from the matte black exoskeleton, resulting in a body temperature slightly lower than that of the surrounding air. With the beetle's body held at a 45° angle to the sand, the moist breeze contacts the cool exoskeleton and water condenses into small droplets. This beading effect is facilitated by a series of hydrophilic (water attracting) bumps surrounding by a waxy, hydrophobic (water repelling) surface on the insect's back. The droplets may grow to nearly a quarter of an inch, and then roll down to be gratefully sequestered by the beetle's mouthparts. And then it's back down the dunes and away from the morning sun for these diminutive hydroplants.
The Namib Desert Beetle laden with water droplets
http://renaturalist.blogspot.com/2011/03/namib-desert-beetle-recipe-for-water.html
Bio-Inspired Materials
Nanocomposites
• Structure + Multifunction
• Surface area and interfaces → 104 increase – Fundamentally alter polymer
– Small vol % → huge impacts on properties
• Strategy: – Design morphology and interphase
– Develop hybrid composites
In Nature, directional surfaces on insect cuticle, animal fur, bird feathers, andplant leaves are composed of dual micro-nanoscale features that tune roughness
and surface energy. Novel approaches for the design, synthesis, and characterization of new bioinspired surfaces demonstrating unidirectional surface have been demonstrated. The experimental approaches focus on bottom-up and top-down synthesis methods of unidirectional micro- and
nanoscale fi lms to explore and characterize their anomalous features. The theoretical component focuses on computational tools to predict the
physicochemical properties of unidirectional surfaces.
Bioinspired Directional Surfaces for Adhesion, Wetting, and Transporthttp://onlinelibrary.wiley.com/doi/10.1002/adfm.201103017/pdf
Engineered textured directional surfaces with asymmetric or periodic structures
http://onlinelibrary.wiley.com/doi/10.1002/adfm.201103017/pdf
In Nature, directional surfaces on insect cuticle, animal fur, bird feathers, andplant leaves are composed of dual micro-nanoscale features that tune roughnessand surface energy.
http://onlinelibrary.wiley.com/doi/10.1002/adfm.201103017/pdf
Bioinspired Directional Surfaces for Adhesion, Wetting, and Transport
Applications of bio-inspired special wettability. The summarized topics include three areas, the surfaces of superhydrophobicity, surfaces of patterned wettability and integrated multifunctional surfaces and devices. http://mipd.snu.ac.kr/upload/pnt11_2_1/bio_inspired_wettable_surfaces_and_patterned_wettability_%28advmat_2011_23_719%29.pdf
Super-amphiphobic textiles
Advanced Materials, 2011, 23, 719–734
Bioinspired functional living materials by incorporating microorganisms into polymer layers
http://www.pnas.org/content/109/1/90.figures-only
Synthetic materials used in medicine. Dendrimers
Nanoscale Materials
Bionanomaterials
1) Synthetic nanomaterials utilized in biomedical applications - Polymers, porous silicon, carbon nanotubes, nanodots, nanowires, nanomembranes etc.
2) Biological materials utilized in nanotechnology
- Proteins, enzymes, DNA, RNA, peptides etc.
Bone cell on porous silicon – Univ. of Rochester, 2007
Cross-linked enzymes used as catalyst – Univ. of Connecticut, Storrs , 2007
Human cell on PSi
Porous silicon (PSi)
Protein
Enzymes are used as oxidation catalysts
•The aim of nano-scientists is to virtually imitate nature.
• They are trying to construct objects out of their most basic components, atom by atom, the way that nature does.
•This offers an unprecedented degree of precision and control over the final product.
Equipment for Nanoparticles1.´Homogenizer
2. Ultra Sonicator
3. Mills
4. Spray Milling
5. Supercritical Fluid Technology
6. Electrospray
7. Ultracentrifugation
8. Nanofiltration
Homogenizer & Ultra Sonicator
M S Ramaiah Institute of Technology, Bangalore
• DNA molecule• DNA-nanoparticlecomplexes basedon Au-thiol binding• Nanoparticlelabeling for biochips• Labeling of singlemolecules• Devices, e.g.nanoelectronics.
DNA-nanoparticle complexes
DNA-coated gold nanoparticles (NPs) system that uses larger magnetic microparticles (MMPs) to detect
at tomolar (10-18) concentrations of serum proteins
Nanotechnology and diagnosticsDendrimers
Dendrimers, 1- to 10-nanometerspherical polymers of uniformmolecular weight madefrom branched monomers (Polyimido amine), are provingparticularly adept at providingmultifunctional modularity.
Dendrimers can serve as versatilenanoscale platforms for creatingmultifunctional devices capableof detecting cancer and deliverydrugs.
Huge surface leading to dramatic surface effects
• Surface vibrations • Surface engineering• Quantum size phenomena (antidot, antiwire…) Canham, 1990Good luminescence is indicative ofdefect-free material and well passivated surface
Nanoporous Materials behave like quasi-freezed Liquids!
Porous Si
• Luminescent quantum structures• Tunable pore dimensions (2 nm to 10 μm)• Compatible with Si fabrication technologies,
easily patterned• High surface area (200 m2/g or up to 103 m3/cm2)• Electrically addressable• Convenient fabrication of 1, 2, 2.5D optical
structures
Properties of Porous Si useful for Applications
Porous Si as electronic material 1. Light emitting diodes (1 % external quantum
efficiency)2. Waveguides (tunability of refractive index)3. Optical memory 4. Photonic bandgap structures (Photonic
Crystals)5. All optical switching (highly nonlinear optical
properties)6. Antireflection coatings (low refractive index) 1. Gas sensing (environmental monitoring)2. Microelectronics micro-capacitor (high
specific surface area)3. Buffer layer in nanoheteroepitaxy4. Biotechnology (tissue bonding)5. Biosensors (enzyme immobilization)6. Porous Si as explosive element
Porous Si Smart Dust
Prof. M. SailorUCSDUSA
Porous Silicon
Photonic Crystals in Silicon
PCs realization
AMAT, MPI Halle & Infineon
• An effective biomaterial must bond to living tissue - in other words, it has to be ‘bioactive’. The success of any medical implant depends on the behavior of cells in the vicinity of the interface between the host and the biomaterial used in the device. All biomaterials have morphological, chemical and electrical surface characteristics that influence the response of cells to the implant. The initial event is the adsorption of a layer of protein on to the biomaterial.
Porous Si as bioactive material
• The ability to culture mammalian cells directly onto PS, coupled with the material’s lack of toxicity, offers exciting possibilities for the future of biologically interfaced sensing. This could involve the development of biologically interfaced neural networks, or electronic sensing with signals being directly sent from a living system to a PS device.
• In this way, porous silicon has the potential to produce devices for replacing damaged tissues in the ear, eye, skin or nasal cavity. Such devices could, for example, receive optical information and convert this to a biological signal that would be passed into neural tissue as a substitute ‘sight’ sensation.
• 1 cm3 of porous Si contains up to 1000 m2 of internal surface
• About 20 % of the Si atoms are located at the surface of nanocrystals
• All surface is covered by monolayer of hydrogen ~ 1022 cm-3 (buffer layer)
• Contact on the atomic scale (~ 2 Å) between interacting oxygen or other oxidiser, hydrogen and Si atoms – chemical reaction is fast (gun powder: typical grain size is 1 μm)
• Porous Si is solid: no additional geometrical confinement to increase burning rate is required
Porous Si as explosive element
Structural properties of porous Si most essential for explosive interaction
Kovalev et al, Phys. Rev. Lett. 87, 68301 (2001).
Energy 7.5 kJ/gDuration 500 nsTemperature 7000 ºC
Michael J. Sailor Research GroupChemistry and Biochemistry
Nanostructured “Mother Ships”
for Delivery of Cancer Therapeutics
Nanodevices for In-vivo Detection & Treatment of Cancerous Tumors
Nano-Structured Porous SiliconApplied to Cancer Treatment
The Intersection of Solid State and Biological Information Systems
Snail neuron grown on a CMOS chip with 128x128 Transistors. The electrical activity of the neuron is recorded by the chip.
(Chip fabricated by Infineon Technologies)www.biochem.mpg.de/en/research/rd/fromherz/publications/03eve/index.html
V.V. Ursaki, I.M. Tiginyanu, O. Volciuc, V. Popa, V.A. Skuratov and H. Morkoç.
Applied Physics Letters, Vol. 90, 161908 (2007).
http://nanotechweb.org/articles/news/6/5/19/1
Radiation hardness evaluatedthrough excitonic luminescence 85 MeV Kr+15 ions130 MeV Xe+23 ions
Energy harvester for implantation applications
sapphire substrate
buffer GaN
AlGaN
GaN
µA
GaN nanocones
FLOW
Ti/Au contact
+ - Tangential flow lead to mechanical deformation of nanocones that will generate piezoelectricity at the base.
Charge separation is made by means of an AlGaN/GaN heterostructure.
Applications:
- Artificial pacemaker
- Implanted biosensors
- Flow transducers
Metal oxides
Gasbio
sensors
Membranes
Flatdisplays
Electronicdevices
Transparentelectrodes
IR filters,heat
mirrors
Magneticmemory
Fuel-cells
Metal oxides for various applications
Generating electricity through the deformation of a semiconducting and piezoelectric nanowire
Materials Today, Vol. 10, no 5, p. 20-28 (2007)
NATURE NANOTECHNOLOGY | VOL 5 | MAY 2010 366-373
SS
Organic-anorganic nanocomposites
Acad. A. Andriesh et al, Institute of Applied Physics, Academy of Sciences of Moldova
Eu(TTA)3 Phen-SBMA nanocomposite before (left) and after (right) excitation with UV radiation
29
The images of thin films Eu(TTA)3Phen-SBMA on silicon glass substrate without (a) and under UV
excitationЭлектрохимия. 2011, 47(4), 489–498
””ŞŞtiintiinţţa modernă şi tehnologia au a modernă şi tehnologia au
puterea de a modela lumea puterea de a modela lumea îîn care n care
trăim, trăim, îîn bine sau n bine sau îîn rău”n rău”
Frank WilczekFrank Wilczek, laureat al premiului
Nobel pentru Fizică în 2004