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Respirocytes from Patterned Atomic Layer Epitaxy: The Most Conservative Pathway to the

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

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Respirocytes from Patterned Atomic Layer Epitaxy: The Most Conservative Pathway to the

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  1. 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

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

  3. 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

  4. Protein engineering Difficult: must solve protein folding problem Sensitive to small changes in sequence or environment Low temperature process, but low performance properties

  5. 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

  6. 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

  7. 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

  8. Diamondoid Mechanosynthesis Adding two carbon atoms at a time Theory confirmed by 100,000 hours CPU time 2009 experiment funded by UK EPSRC

  9. Tip-Based Nanofabrication DARPA’s Goal: • Automated, parallel nanofabrication • Position, size, shape, and orientation • In-situ detection & repair • AFM/STM or similar scanning probes

  10. TBN with Lasers 300nm • 3–5 ns pulse • NSOM based ablation • FWHM of 90 nm • Film of unsintered, 1–3 nm gold nanoparticle encapsulated by hexanethiol

  11. 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)

  12. Tip-Based Nanofabrication:Atomically 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

  13. 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

  14. Patterned Si ALE Joe Lyding UIUC

  15. Patterned Si ALE Room Temperature 10-8 Torr disilane 10 minutes/row 5V, 1nA; 7V .1nA; & 6V 1nA 6nm high features Joe Lyding UIUC

  16. Tip Arrays • MEMS • 55,000 tips • 15 nm resolution • Fast

  17. Freitas Respirocytes • Atomically Precise Diamondoid • 1000 nm (1 μm); 1000 atm • Requirements Analysis: What & How • Subsystems

  18. Red Blood Cell Function

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

  20. 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)

  21. Hemoglobin Saturation: Bohr Effect • Lower pH -> lower saturation • Higher CO2 -> more oxygen delivered • Higher temperature also shifts curve right Hemoglobin % Saturation partial pressure oxygen (mm Hg)

  22. Oligosaccharide and Rhesus Protein Coating

  23. Perfluorocarbons PFCs dissolve > 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)

  24. Respirocyte Subsystems • Pressure Vessels • Pumps • Power • Communications • Sensors • Onboard Computation

  25. 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)

  26. High-Pressure Output O2 Input CO2 Intake O2 Output CO2 Low-Pressure Lung Capillaries Body Tissue Capillaries Location Dependent Pressure

  27. Ratiometric Oxygen Nanosensor Ruthenium-DPP (Oxygen sensitive dye) PEBBLE nanosensor Oregon Green Dye

  28. Nanoscale pH Sensor • Zinc Oxide Nanowires • AlGaN/GaN junctions • Field tested outdoors

  29. Selective Pumps Water Pump

  30. Neon Pump

  31. Selective Pump:Combined 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

  32. Selective Oxygen Rotor Oxygen released by Hemoglobin Oxygen bound by Hemoglobin Lower pH higher temperature mechanisms 6 nm

  33. Blood Plasma Cascaded Selective Rotors

  34. Kinesin 2 ATP/cycle 2 steps/cycle(rotation/slide) 16 nm per cycle 100 steps/second ~5 picoNewtons 40% efficient

  35. Kinesin-based Motors

  36. Glucose → ATP PH Three out of 10 enzymes have been attached 40% efficient

  37. Carbon Dioxide Return • Carbonic anhydrase • 1 million times faster • 30,000 daltons • Issues: • Detecting CO2presence • Getting CO2 out of heme

  38. Bicarbonate Sequestering CmpA Protein Highly selective 452 residues ≈ 52,000 daltons

  39. Selective Carbon Dioxide Rotor HCO3— captured by CmpA HCO3— released by CmpA Location switch CO2 catalyzed by carbonic anhydrase 5 nm

  40. Non-Selective Pumps 3-valve peristaltic Micropump Piezoelectric 100 V (peak-to-peak) 100 Hz 17.6 microliters/minute

  41. Selective Membranes Denissov, Molecular Sieves for Gas Separating Membranes

  42. Computation:Quantum Dot Cellular Automata • Arbitrary Boolean logic • Single electron charge • Very low power consumption

  43. 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

  44. Thank you! • Questions? Tihamer Toth-Fejel Tihamer.Toth-Fejel gd-ais.com

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