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 Technology Productive Nanosystems Bio-mimetic Scanning Probes Tip-Based Nanofabrication Patterned Atomic Layer Epitaxy Application Freitas Respirocytes Requirements Respirocyte subsystems
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
Protein engineering Difficult: must solve protein folding problem Sensitive to small changes in sequence or environment Low temperature process, but low performance properties
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
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
Pixelated DNA and Positioning courtesy Paul W. K. Rothemund Ke, et. al., Self-Assembled Water-Soluble Nucleic Acid Probe Tiles for Label-Free RNA Hybridization Assays, Science, Jan 11, 2008
Diamondoid Mechanosynthesis Adding two carbon atoms at a time Theory confirmed by 100,000 hours CPU time 2009 experiment funded by UK EPSRC
Tip-Based Nanofabrication DARPA’s Goal: Automated, parallel nanofabrication Automated, parallel nanofabrication Position, size, shape, and orientation Position, size, shape, and orientation In-situ detection & repair In-situ detection & repair AFM/STM or similar scanning probes AFM/STM or similar scanning probes
TBN with Lasers 3–5 ns pulse NSOM based ablation FWHM of 90 nm Film of unsintered, 1–3 nm gold nanoparticle encapsulated by hexanethiol 300nm
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) 15 nm limit (so far)
Tip-Based Nanofabrication: Atomically Precise Manufacturing Produce 3D structures with top-down control and atomic precision. Produce 3D structures with top-down control and atomic precision. Inevitable result of continued improvements in ultra-precision manufacturing Inevitable result of continued improvements in ultra-precision manufacturing Integration of known techniques Integration of known techniques General manufacturing process General manufacturing process
Patterned Si ALE STM tip removes H atoms from the Si surface 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.
Patterned Si ALE Joe Lyding UIUC
Patterned Si ALE Joe Lyding UIUC Room Temperature Torr disilane 10 minutes/row 5V, 1nA; 7V.1nA; & 6V 1nA 6nm high features
Tip Arrays MEMS MEMS 55,000 tips 55,000 tips 15 nm resolution 15 nm resolution Fast Fast
Freitas Respirocytes Atomically Precise Diamondoid Atomically Precise Diamondoid 1000 nm (1 μm); 1000 atm 1000 nm (1 μm); 1000 atm Requirements Analysis: What & How Subsystems
Red Blood Cell Function
O 2 not soluble in water O 2 not soluble in water Four hemes; one O 2 each Four hemes; one O 2 each 68,000 daltons 68,000 daltons Lasts longer & more effective inside cells Lasts longer & more effective inside cells Hemoglobin
Hemoglobin Saturation 150 quintillion (10 18 ) hemoglobin molecules in 100 ml whole blood 150 quintillion (10 18 ) hemoglobin molecules in 100 ml whole blood Binding regulated by O2 partial pressure Binding regulated by O2 partial pressure Hemoglobin % Saturation partial pressure oxygen (mm Hg partial pressure oxygen (mm Hg)
Hemoglobin Saturation: Bohr Effect Lower pH -> lower saturation Lower pH -> lower saturation Higher CO 2 -> more oxygen delivered Higher CO 2 -> more oxygen delivered Higher temperature also shifts curve right Higher temperature also shifts curve right Hemoglobin % Saturation partial pressure oxygen (mm Hg partial pressure oxygen (mm Hg)
Oligosaccharide and Rhesus Protein Coating
Perfluorocarbons PFCs dissolve > 100x O 2 than blood serum PFCs are hydrophobic & require emulsifiers Perfluorocarbons surrounded by a surfactant (lecithin) Perfluorocarbons surrounded by a surfactant (lecithin) Up to twice as efficient as RBC (at high partial pressure) Up to twice as efficient as RBC (at high partial pressure) No refrigeration required No refrigeration required 1/40 th size of RBC 1/40 th size of RBC May increase risk of stroke in cardiac patients May increase risk of stroke in cardiac patients Short term (hours) Short term (hours)
Respirocyte Subsystems Pressure Vessels Pumps Power Communications Sensors Onboard Computation
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)
Location Dependent Pressure Output O 2 Input CO 2 High-Pressure Low-Pressure Intake O 2 Output CO 2 Body Tissue Capillaries Lung Capillaries
Ratiometric Oxygen Nanosensor PEBBLE nanosensor Ruthenium-DPP (Oxygen sensitive dye) Oregon Green Dye
Nanoscale pH Sensor Zinc Oxide Nanowires Zinc Oxide Nanowires AlGaN/GaN junctions AlGaN/GaN junctions Field tested outdoors Field tested outdoors
Selective Pumps Water Pump
Neon Pump
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
Selective Oxygen Rotor Oxygen bound by Hemoglobin Oxygen released by Hemoglobin Lower pH higher temperature mechanisms 6 nm
Cascaded Selective Rotors
Kinesin 2 ATP/cycle 2 steps/cycle(rotation/slide) 16 nm per cycle 100 steps/second ~5 picoNewtons 40% efficient
Kinesin-based Motors
Glucose → ATP Three out of 10 enzymes have been attached PH 40% efficient
Carbon Dioxide Return Carbonic anhydrase 1 million times faster 30,000 daltons Issues: Detecting CO 2 presence Getting CO 2 out of heme
Bicarbonate Sequestering CmpA Protein Highly selective 452 residues ≈ 52,000 daltons
Selective Carbon Dioxide Rotor CO 2 catalyzed by carbonic anhydrase HCO 3 — released by CmpA Location switch 5 nm HCO 3 — captured by CmpA
Non-Selective Pumps 3-valve peristaltic Micropump Piezoelectric 100 V (peak-to-peak) 100 Hz 17.6 microliters/minute
Selective Membranes Denissov, Molecular Sieves for Gas Separating Membranes
Computation: Quantum Dot Cellular Automata Arbitrary Boolean logic Single electron charge Very low power consumption
Production Issues By 2012: Ten million atoms/hour (silicon) By 2012: Ten million atoms/hour (silicon) Nanoimprint lithography Nanoimprint lithography Multiple materials Multiple materials ALE does not work for complex proteins ALE does not work for complex proteins Bootstrapping Bootstrapping Small STM arrays build larger STM arrays Small STM arrays build larger STM arrays Build fabrication and assembly lines Build fabrication and assembly lines Smaller vacuum chambers Smaller vacuum chambers
Thank you! Questions? Questions? Tihamer Toth-Fejel Tihamer.Toth-Fejel gd-ais.com