Respirocytes from Patterned Atomic Layer Epitaxy:

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• Respirocytes from Patterned Atomic Layer Epitaxy
• The Most Conservative Pathway to the
• Simplest Medical Nanorobot
• Tihamer Toth-Fejel
• Tihamer.Toth-Fejel gd-ais.com
• 2nd Unither Nanomedical and Telemedicine
  Technology Conference
• Quebec, Canada
• February 24-27, 2009

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Contents

• Technology
• Productive Nanosystems
• Bio-mimetic
• Scanning Probes
• Tip-Based Nanofabrication
• Patterned Atomic Layer Epitaxy
• Application
• Freitas Respirocytes
• Requirements
• Respirocyte subsystems

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Productive Nanosystems

• Size matters, atomic precision matters more.
• Automated nanoscale tools are most important.
• A closed loop of nanoscale components that make
  nanoscale components
• Approaches
• Biomimetic methods
• Protein engineering
• Bis-amino acid solid-phase self-assembly
• Structural DNA
• Scanning Probe Techniques
• Diamond Mechanosynthesis
• Patterned Atomic Layer Epitaxy

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Protein engineering
Difficult must solve protein folding
problem Sensitive to small changes in sequence or
environment Low temperature process, but low
performance properties
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Bis-amino acid Solid-phase Self-assembly

• Protein engineering
• Bis-amino acid Solid-phase Self-assembly
• Structural DNA

C. Schafmeister, Molecular Lego, Scientific
American, Feb 2007, 64-71
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Structural DNA
50 billion Smiley Faces in two hours By 1 person
with a glorified kitchen oven
Paul W. K. Rothemund, Folding DNA to create
nanoscale shapes and patterns, Nature Vol 440,16
March 2006
Courtesy Paul Rothemund
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Pixelated DNA and Positioning
Ke, et. al., Self-Assembled Water-Soluble Nucleic
Acid Probe Tiles for Label-Free RNA Hybridization
Assays, Science, Jan 11, 2008

courtesy Paul W. K. Rothemund
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Diamondoid Mechanosynthesis
Adding two carbon atoms at a time Theory
confirmed by 100,000 hours CPU time 2009
experiment funded by UK EPSRC
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Tip-Based Nanofabrication

• DARPAs Goal
• Automated, parallel nanofabrication
• Position, size, shape, and orientation
• In-situ detection repair
• AFM/STM or similar scanning probes

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TBN with Lasers
300nm

• 35 ns pulse
• NSOM based ablation
• FWHM of 90 nm
• Film of unsintered, 13 nm gold nanoparticle
  encapsulated by hexanethiol

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TBN with Dip Pen Nanolithography Scanning Probe
Epitaxy

• Reader tip integrated with synthesis tip
• Dual-tip scanning probes combine contact and
  non-contact modes
• Core-filled tip with aperture controls
  nanostructure deposition
• Control where, when, and how a reaction occurs on
  the nanometer scale
• 15 nm limit (so far)

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Tip-Based NanofabricationAtomically Precise
Manufacturing

• Produce 3D structures with top-down control and
  atomic precision.
• Inevitable result of continued improvements in
  ultra-precision manufacturing
• Integration of known techniques
• General manufacturing process

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Patterned Si ALE
A precursor gas is used to dose the surface.
Protected Si atoms are deposited only where H has
been removed.
Completed deposition is verified and then the
deprotection/patterning is repeated.
STM tip removes H atoms from the Si surface
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Patterned Si ALE
Joe Lyding UIUC
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Patterned Si ALE
Room Temperature 10-8 Torr disilane 10
minutes/row 5V, 1nA 7V .1nA 6V 1nA 6nm high
features
Joe Lyding UIUC
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Tip Arrays

• MEMS
• 55,000 tips
• 15 nm resolution
• Fast

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Freitas Respirocytes

• Atomically Precise Diamondoid
• 1000 nm (1 µm) 1000 atm

• Requirements Analysis What How
• Subsystems

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Red Blood Cell Function
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Hemoglobin

• O2 not soluble in water
• Four hemes one O2 each
• 68,000 daltons
• Lasts longer more effective inside cells

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Hemoglobin Saturation

• 150 quintillion (1018) hemoglobin molecules in
  100 ml whole blood
• Binding regulated by O2 partial pressure

Hemoglobin Saturation
partial pressure oxygen (mm Hg)
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Hemoglobin Saturation Bohr Effect

• Lower pH -gt lower saturation
• Higher CO2 -gt more oxygen delivered
• Higher temperature also shifts curve right

Hemoglobin Saturation
partial pressure oxygen (mm Hg)
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Oligosaccharide and Rhesus Protein Coating
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Perfluorocarbons

• PFCs dissolve gt 100x O2 than blood serum
• PFCs are hydrophobic require emulsifiers

• Perfluorocarbons surrounded by a surfactant
  (lecithin)
• Up to twice as efficient as RBC (at high partial
  pressure)
• No refrigeration required
• 1/40th size of RBC
• May increase risk of stroke in cardiac patients
• Short term (hours)

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Respirocyte Subsystems

• Pressure Vessels
• Pumps
• Power
• Communications
• Sensors
• Onboard Computation

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1000 nm Spherical Pressure Vessels
APM Diamond 1,000,000 MPa 5 nm (30 carbon
atoms) walls 10,000 atm (but diminishing returns
after 1000 atm) Silicon (Crystalline, low
defects) 30,000 MPa 10 nm walls 1,400 atm Blood
cells (or serum PFCs) 0.51 atm 0.13 atm
deliverable to tissues (less for PFCs)
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Location Dependent Pressure
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Ratiometric Oxygen Nanosensor
Ruthenium-DPP (Oxygen sensitive dye)
PEBBLE nanosensor
Oregon Green Dye
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Nanoscale pH Sensor

• Zinc Oxide Nanowires
• AlGaN/GaN junctions
• Field tested outdoors

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Selective Pumps
Water Pump
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Neon Pump
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Selective PumpCombined motor and rotor

• Sodium-Potassium Exchange Pump
• Small (12 nm diameter)
• 17 RMP (no load)
• 100 picoNewtons
• Runs on ATP
• Elegant
• Difficult to integrate with silicon shell

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Selective Oxygen Rotor
Oxygen released by Hemoglobin
Oxygen bound by Hemoglobin
Lower pH higher temperature mechanisms
6 nm
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Cascaded Selective Rotors
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Kinesin
2 ATP/cycle 2 steps/cycle(rotation/slide) 16 nm
per cycle 100 steps/second 5 picoNewtons 40
efficient
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Kinesin-based Motors
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Glucose ? ATP
PH
Three out of 10 enzymes have been attached
40 efficient
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Carbon Dioxide Return

• Carbonic anhydrase
• 1 million times faster
• 30,000 daltons
• Issues
• Detecting CO2 presence
• Getting CO2 out of heme

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Bicarbonate Sequestering
CmpA Protein Highly selective 452 residues
52,000 daltons
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Selective Carbon Dioxide Rotor
HCO3 captured by CmpA
HCO3 released by CmpA
Location switch
CO2 catalyzed by carbonic anhydrase
5 nm
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Non-Selective Pumps
3-valve peristaltic Micropump Piezoelectric 100
V (peak-to-peak) 100 Hz 17.6 microliters/minute
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Selective Membranes
Denissov, Molecular Sieves for Gas Separating
Membranes
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ComputationQuantum Dot Cellular Automata

• Arbitrary Boolean logic
• Single electron charge
• Very low power consumption

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Production Issues

• By 2012 Ten million atoms/hour (silicon)
• Nanoimprint lithography
• Multiple materials
• ALE does not work for complex proteins
• Bootstrapping
• Small STM arrays build larger STM arrays
• Build fabrication and assembly lines
• Smaller vacuum chambers

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Thank you!

• Questions?
• Tihamer Toth-Fejel
• Tihamer.Toth-Fejel gd-ais.com