Physics

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Physics and Medicine at the Nanoscale by Harry
C. Dorn Virginia Tech Professor of
Chemistry CSAND Director
College of Science
College of Natural Resources
College of Engineering
College of Agriculture Life Sciences
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Nanotechnology
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Richard Feynman Theres Plenty of Room at the
Bottom Cal Tech, Dec. 29, 1959
Why cant we write the entire 24 Volumes of the
Encyclopedia Brittanica on the head of a
pin? How do we write small?
Miniaturizing the Computer? Problems of
Lubrication A hundred Tiny Hands Atoms in a
Small World
Origins of Nanotechnology
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Nanotechnology A Matter of Size and Control
Think very small (nano 1 billionth of a
meter) 10 H atoms or, 1 human hair
100,000 nanometers!
The precise, highly controlled assembly of
atoms and molecules into new materials and
devices with unique, possibly revolutionary
properties

• Carbon Nanotubes
• 100 times stronger than steel
• Conduct electricity better than copper
• Conduct heat better than diamonds
• Depending on current, can either -
  Act as a metal (conductor) - Act as
  semiconductor (transistor)
• Markets now exist for nanotubes as raw
  material

Individual iron atoms positioned in an oval
corral on a copper surface, using a scanning
tunneling microscope --IBM Almaden Research Center
Single wall carbon nanotube with attached protein
receptors
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Nanotechnology Why the Excitement?

• The ability to make things that are much
  stronger, lighter, cheaper and energy efficient
• Entirely new capabilities that are not possible
  with todays technology
• A truly transformative impact on nearly every
  dimension of our society and economy

Space elevator
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Nanotechnology Future Vision 2015
Tissues and organs artificially grown on
nanopatterned scaffolds
Major applications
anticipated in Biomedicine
Defense/ Homeland Security
Electronics/ Information Technology
Energy/ Environment
Nanostructured capsules deliver drugs directly to
diseased tissue
Optoelectric retinal implants for the blind
Nanocoatings produce body friendly, longer
lasting implants
Cochlear implants to restore hearing
Nanostructured materials reduce total weight
carried from 120 to 50 pounds
Chameleon uniform changes colors with background
Ultralightweight power pack driven by fuel cell
with nanomembranes
Weapon fires superpenetrating projectiles or
non-lethal net of carbon nanofibers
Sensors imbedded in clothing monitor vital signs,
detect toxins
Nanomuscles add strength and endurance when
needed
Nanofibers in fabric can close to block
chemicals, or stiffien to form a splint
MIT, Institute for Soldier Nanotechnologies
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MedicalNanotechnologyApplications
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Total Hip Replacement-Osteolysis
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Therapeutics
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Sensors

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Integrated Devices
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Imaging
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Magnetic Resonance
Imaging (MRI)
Hyperpolarized 129Xe(g)
Hyperpolarized 129Xe_at_C60 ?

Xe_at_C60 Discovered by Cross and Saunders (Yale)
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New NanoMaterials
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Allotropes of Carbon (Pre-1985)
Diamonds Cubic, Crystalline sp3 hybridized High
Melting Point Hardness 10
Graphite Hexagonal, Black Sheets sp2
hybridized High Melting Point Hardness 1-2

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Carbon Nanomaterials
Nanomaterials
Nanotubes
Fullerenes
Nanoparticles
Planar Device
Biological
Si-Based Materials
SWNT
MWNT
Carbon
Non-Carbon
Empty Cage
Endohedrals
Nano-machines
DNA
Non-TNT
TNT
Carbonaceous nanomaterials
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New Carbonaceous Materials
Bethune, Dorn, Stevenson Nature 1994 Stevenson,
Balch, Bible, Dorn, et al Nature 1999
Iijima, et al Nature 1993 Bethune, et al Nature
1993
Smalley, et al Nature 1985
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Smalley, Kroto, and Curl (1984-5)
Laser Apparatus
Large Fullerenes
C60, Fullerenes, BuckyBalls!
0.2 m
0.7 nm
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Carbon Nanotubes
Single-wall Carbon NanotubesA Major Application
Two-dimensional imaging of electronic
wavefunctions in carbon nanotubes S.G. LEMAY, et
al. Nature 412, 617 - 620 (2001)
TU Delft/Gripp Design Nature 412 (2001)
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Single Wall Carbon Nanotubes (Don Bethune, IBM)
Jan 93 2 Co burn rubbery soot and spider
web structures
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Single Wall Carbon Nanotubes
0 1 2 3 Diameter (nm)
- Bethune, et al., Nature 363, 605 (1993)

• Iijima Ichihashi, Nature 363, 603 (1993) - Fe
  catalyst, with methane

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Peapods Metallofullerene-loaded Nanotubes
Chemistry in Confined Environments
Single Molecule and Single Atom Studies
B.W. Smith, M. Monthioux, and D. E. Luzzi, Nature
396, 323 (1998).
B.W. Smith, D. E. Luzzi, and Y. Achiba, Chem.
Phys. Lett 331, 137 (2000).
R. Russo, D. E. Luzzi, H. Dorn, MRS (2001).
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Carbon Nanocity bound ?

• Science
• Technical demos prototype device
  development
• Materials Chemical Applications
• Follow-on to Si?

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NASA Space Elevator
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Discovery of Trimetallic Nitride Template
(TNT)Endohedral Metallofullerenes1109
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Unoptimized Production of Sc3N_at_C80
m/e1109
Stevenson, Dorn Anal. Chem. 1994
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Kratschmer-Huffman Electric-Arc Synthesis
Source of nitrogen?
Air leak! nitrogen, oxygen H. C. Dorn 1109 Hahn
Hall!
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Trimetallic Nitride TemplateMetallofullerenes
A3N_at_C80
Sc3N_at_C80 is the third most abundant fullerene or
endohedral metallofullerene !
Stevenson, Balch, Bible, and Dorn, Nature 1999
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Rotational Dynamics Sc3N_at_C80Molecular Gyroscope?
Cluster (Sc3N)
Cage (C80)
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TNT MetallofullerenesEncapsulation of Other
Metals
Various combinations A3, A2B, AB2
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Thermal Stability Summary
1) In Air Sc3N_at_C80 Stable to 653-673 K Dorn,
et al Am. Inst. of Phys., 135-141, (2000). 2)
Raman and Infrared Study of Sc3N_at_C80, Reversible
to 650 K Krauss, Kuzmany, J. Chem. Phys.
(2001) 3) In Peapods Sc3N_at_C80 (in vacuo)
Stable Above 1400 K R. Russo, D. E. Luzzi, H.
Dorn, MRS (2001)
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Charge Transfer Model
Six electrons transferred from the cluster to the
cage. Results in a closed shell electronic
structure (A3N)6C806-.
Minimum Bond Resonance Energies Higher Number
Lower Reactivity C60 (Ih) 0.0822???
High Reactivity C70 (D5h) 0.0519???
C76 (D2) 0.0074??? C78 (D3h)
0.0795??? C84 (D2) 0.0819???
C806- (Ih) 0.1931??? Low Reactivity
J. Aihara, Phys. Chem., Chem. Phys., 2001, 3,
1427.

• A3N_at_C80 Low reactivity!

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Separation of Lu3N_at_C80 from crude soot
HPLC trace
Functionalized resin
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Separation of Lu3N_at_C80 from Crude Soot
HPLC trace
Functionalized resin
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Cage Variations (Symmetry) in TNT
Metallofullerenes
Sc3N_at_C78 (D3h)
Sc3N_at_C68 (D3)
Sc3N_at_C80 (Ih)
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Nano and Macro Hexagon and Pentagon Motifs
Devils Postpile National Monument, CA
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Multi-ModalDiagnostic and TherapeuticAgents
Virginia Tech and Medical College of Virginia
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Nanoscale Physics and Medicine
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A NEW NANOSPHERE PLATFORM MULTI-MODAL
FUNCTIONALIZED METALLOFULLERENES (fMFs)

• MULTI-MODALITY DIAGNOSTICS
• MGd, MRI CONTRAST
• MLu, X-RAY CONTRAST
• M Tb FLUORESCENCE
• M166Ho,177Lu RADIOLABEL
• DUAL DIAGNOSTIC AND THERAPEUTIC AGENTS
• M166Ho,177Lu RADIOISOTOPES
• PHOTODYNAMIC THERAPY
• TARGETED DELIVERY APPROACHES
• BONE VECTOR
• BLOOD BRAIN BARRIER
• DIRECT TUMOR INFUSION

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ENDOHEDRAL METALLOFULLERENE MRI Contrast Agents

• Shinohara (Nagoya), Wilson (Rice), and
  Bolskar (TDA) groups have reported significant
  increases in the 1H MRI T1 spin-lattice
  relaxivity rates for Gd_at_C82(OH)n and
  Gd_at_C82(CO2H)n derivatives in comparison with
  commerical agents

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Commerical MRI Contrast Agents
Caravan, et al, Chem Rev., 1999
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Inner and Outer Sphere Spin-Lattice (T1) and
Spin-Spin (T2) Relaxation Mechanisms
DI
Gd3
Ds
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Endofullerenes Outer Sphere Relaxation
DI
Gd3
Ds
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Gd3N-Functionalized Metallofullerenes (fMF)
Contrast Agents

• Poor
• Relaxivity!

Excellent Relaxivity
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Magnetic Susceptibilty (SQUID) of A3_at_C80 (Ohio
State)

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r1 and r2 1H Relaxivities of M3N-fMF and
Gd-DTPA MRI Contrast Agents
r1(1/T1), r2(1/T2)
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Relaxivity Properties of Gd3N-fMF
Non-Linear Relaxivity (2.4 T)

• The relaxivity is concentration dependent
• and dramatically increases with dilution.
• This behavior (40-75 increase at low dilution)
  was observed at all magnetic field strengths
  (0.35, 2.4, and 9.4 T). (upper right)
• A temperature dependent study at 9.4 T for a high
  concentration sample (0.202 mmol)
• also demonstrates slightly increasing r1 values
  with increasing temperature. (lower right)
• These results are inconsistent with a model
  where the molecular correlation ?r is the
  controlling factor for relaxivity at these field
  strengths.
• A model where water exchange is the controlling
  factor is consistent with the markedly improved
  relaxivity at lower concentrations where
  molecular cluster, aggregation, or micelle
  formation is discouraged and water accessibility
  to the carbon cage is improved.

Temperature Dependence
High Field (9.4T) and High Concentration (0.202
mM)
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In Vitro MRI (2.4 T) T1w Images of Gd-DTPA and
Gd3N-fMF Aqueous Solutions
Outer Ring Gd-DTPA (Decreasing Clockwise) 5.0
mM 3.0 mM 1.0 mM 0.70 mM 0.50 mM 0.30 mM
0.10 mM 0.050 mM
Inner Ring Gd3N-fMF (Decreasing Clockwise)
0.202 mM 0.101 mM 0.0505 mM 0.0252 mM
0.0126mM 0.0063 mM 0.0032 mM 0.0016 mM
0.0016 mM
3.34 mM
0.0033 mM
1.67 mM
De-ionized Water Bath
0.0065 mM
Saline Filled Tubes
1.1133 mM
0.013 mM
0.835 mM
0.0261 mM
0.4175 mM
0.0522 mM
0.2088 mM
0.1044 mM
August 14, 2003
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Direct Tumor Infusion Studies of Gd3N-fMF
Virginia Commonwealth University Medical College
of Virginia Campus NMR Research Laboratory Jim
Tatum, MD, William Broaddus Panos Fatouros,
Ph.D., Frank Corwin, M.S.
.
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Agarose Gel T1w Images of Bilateral Infusion of
0.0261 mM Gd3N-fMF (right) and 1mM Gd-DTPA (left)
Displayed Times are in minutes post beginning of
infusion. Infusion was applied for 120 minutes at
0.2 uL/min for Gd-DTPA (left) and 0.5 uL/min for
Gd3N-fMF (right)
60 min
45 min
30 min
15 min
120 min
75 min
90 min
105 min
180 min
135 min
150 min
165 min
240 min
195 min
210 min
225 min
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Agarose Gel T1w Images of Bilateral Infusion
of 0.0261 mM Gd3N-fMF (right) and 0.026 mM
Gd-DTPA (left)
Displayed Times are in minutes post beginning of
infusion. Infusion was applied for 150 minutes at
0.5 uL/min.
60 min
45 min
30 min
15 min
120 min
75 min
90 min
105 min
180 min
135 min
150 min
165 min
240 min
195 min
210 min
225 min
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Rat Brain T1w Images of Direct Infusion (0.2
ml/min) of 0.0131 mM Gd3-fMF (left) and 0.50 mM
Gd-DTPA (right)

90 min
30 min
120 min
60 min
150 min
75 min
175 min
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T1w-MRI Images (2.4 T) Rat Tumor Delineation by
Infused Gd3N-fMF
Baseline
e
Baseline
12 min 0.2 uL/min
22 min 1.0 uL/min
37 min 2.0 uL/min
14 Days Post Tumor Implantation, Infused 12 ml of
0.013 mM Gd3N-fMF
18 Days Post Tumor Implantation 4 days Post
Infusion of Gd3N-fMF
51 min 5.0 uL/min
62 min 0.2 uL/min
85 min 0.5 uL/min
98 min 0.5 uL/min

123 min 0.5 uL/min
133 min 0.5 uL/min
17 Days Post Tumor Implantation 3 days Post
Infusion of Gd3N-fMF
19 Days Post Tumor Implantation 5 days Post
Infusion of Gd3N-fMF
August 15, 2003
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Rat Brain 2.4 T MRI Image Comparison
Gd-DTPA and Gd3N-fMF
Baseline
e
Baseline
12 min 0.2 uL/min
22 min 1.0 uL/min
37 min 2.0 uL/min
18 Days iv injection, T1w Gd-DTPA, Image taken
immediately after injection (0.2mM/kg body
weight)
19 Days Intracerebral infusion, T2W imaging 5
days post Gd3N- fMF infusion. Note the
(darkened) tumor outline on the lower right side
of the image
51 min 5.0 uL/min
62 min 0.2 uL/min
85 min 0.5 uL/min
98 min 0.5 uL/min
123 min 0.5 uL/min
133 min 0.5 uL/min
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Nanomanufacturing
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NANOMANUFACTURING CHALLENGES

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Acknowledgements

• Virginia Tech
• Prof. Harry Gibson
• Prof. Rick Davis
• Dr. Erick Iezzi (University of Pittsburgh)
• Prof. Marion Ehrich
• Tom Glass
• Kim Harich
• IBM Almaden
• Dr. Don Bethune
• University of Virginia
• Prof. Robert Hull
• Emory Henry College
• Prof. Jim Duchamp
• University of Calif., Davis
• Prof. Alan Balch
• Ohio State University
• Prof. John Pennigton
• Southern Mississippi University
• Prof. Steven Stevenson

• Financial Support
• National Science Foundation
• ( NUE, NIRT)
• Carilion Biomedical Center
• Virginia Tech Center for
• Self-Assembled NanoDevices
• (CSAND)

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Acknowledgements

• Thanks to the Steering and Local
  Arrangement Committees
• Looking to the
• Next 100 Years
• in Physics Conference