Replacing the function of failed biological tissue - and -

1. Replacing the function of failed biological tissue - and - A technology push in the direction of bio-medicine at the molecular scale J.N. Randall, Jim Von Ehr, Josh Ballard, James Owen, Udi Fuchs, Rahul Saini, and SergiyPryadkin Zyvex Labs Richardson, Texas jrandall@zyvexlabs.com

2. What’s Zyvex? Zyvex Corporation 1997 – 2007 • Zyvex Instruments – Richardson Texas • Nanoprobing tools – Acquired by DCG Systems 2010 • Zyvex Technologies – Columbus Ohio • Carbon Nanotube / Polymer Composites • ZyCraft – a Global Company • Independent Unmanned Surface Vehicles • Zyvex Labs – Richardson Texas • Atomically Precise Manufacturing • Healing the Blind

3. History of Commercializing Nanotech • Zyvex Technologies has developed the world’s leading CNT enhanced composites: • Zyvex Instruments has developed the world’s leading nanoprobing technology: • Zyvex Labs is developing Atomically Precise Manufacturing: 3nm 3nm 3nm

4. Nano Retina Innovative Sight Restoration John N. Randall Nano Retina Executive Vice President

5. Causes of Blindness in the US 67% possibly treatable by Nano Retina

6. Worldwide Artificial Retina Market Limited treatments currently available

7. Second Sight’s Argus II • 4-8 hour surgery • Wires come in and out of the sclera • Electrodes sit at the surface of the retina

8. Limited spatial resolution at retina surface Surface electrode excites nerve bundles

9. Nano Retina advantages • 600 penetrating electrodes stimulate bipolar region. • Normal optics of the eye are used (no camera) • Power is delivered by IR laser through the pupil. • Tiny package is implanted in 30 minutes, with local anesthetic, on an outpatient basis.

10. Operation Principles Bio Retina implant • External image received by Bio Retina thru the eye’s optics. • Bio Retina converts the image to neuron stimulation. • Bio Retina stimulates the retinal neurons connected to the brain. • Ordinary looking eyeglasses hold the laser power source. • Invisible infrared laser powers the Bio Retina wirelessly. 5 IR laser beam 3 2 4 Retina 1 • Benefits: • Light and long lasting • Simple implantation • Uses the eye’s optics

11. Bio Retina Functional Blocks Imager Analog processing Neuron Stimulators Electrodes ANR1 VLSI • 576 pixels • Ultra low power • Proven miniaturization X 100,000 =

12. Packaging Concept • Record Multi-Electrode Array • Dense feedthrough array • 676 penetrating electrodes • In-vivo demonstrated • Dense package • Sealed & Durable • Biocompatible • 3.5 X 4.5 mm

13. Eyeglasses concept Battery Control unit • Normal vision & IR implant powering • Integrated structure • Battery included • Eye safe Dichroic reflector Prism Collimator Laser diode

14. In-Vivo InitialStudy Outcomes • 30-min surgery technique • Desirable implant adhesion • No adverse effects Histology Implantation Extraction Study approach • Implantation procedure development • Six-week chronic study of pigs

15. Sight Resolution • Resolution is a key performance parameter • Argus II resolution is 20/1260 only with black and white pixels (6x10) • Bio Retina I targets 576 pixels possibly providing 20/260 functional vision • Bio Retina II aims for 20/20 gray scale vision enabling facial recognition ? 20/1260 20/260 20/20 Ambulatory Vision - Follow line Functional Vision – Watch TV Argus I Argus II BRI I BRI II

16. Restoring Sight to the Blind

17. Founders The Company The Team Yossi Gross, Rainbow Medical CTO Efi Cohen-Arazi, Rainbow Medical CEO Jim R. Von Ehr, Zyvex labs CEO Ra’anan Gefen Managing director • Prof. Yael Hanein, VP • John Randall Executive VP Advisors • Alon Harris, • Indiana University • Barbara Marie Wirostko, Utah University • Dov Weinberger, • Rabin Medical Center • Raul Saini • Mechanical director Tuvia Liran VLSI director • Jeffery Grossman VP Business Development • Shelley Fried, Harvard Medical School Richard B. Rosen, NY Eye & Ear Infirmary • Laura Ben Haim Ophthalmology researcher • Leonid Yanovitch Lab engineer • Dorit Raz Prag Preclinical director

18. 1910 to 2010 How did we go from horse carriages, manually operated telephone exchanges, and life expectancy of 50 to space tourism, gps cell phones, and life expectancy of 80 in only 100 years?

19. Manufacturing Precision improved 100,000-fold in past 100 years Norio Taniguchi’s Chart on Machining Precision Machining Accuracy 0.1mm 0.01mm x 1mm x Ultraprecision manufacturing (extreme accurate manufacturing) 0.1mm x x 0.01mm o 1nm x Atomic Distance 19001920 1940 1960 1980 2000

20. 1961 Fairchild Integrated Circuit

22. Technology nodes in ICs

23. Manufacturing Precision improved 100,000-fold in past 100 years Norio Taniguchi’s Chart on Machining Precision Machining Accuracy 0.1mm 0.01mm x 1mm x Ultraprecision manufacturing (extreme accurate manufacturing) 0.1mm x x 0.01mm o 1nm x Atomic Distance 19001920 1940 1960 1980 2000

24. Absolute Precision Manufacturing • Atomic Precision: +/- one atom • Absolute precision: No variation • Everything is exactly the same size

25. Atom-by-Atom Manipulation Richard Feynman – “I am not afraid to consider the final question as to whether, ultimately – in the great future – we can arrange the atoms the way we want” - 1959 “STM” – Nobel Prize in Physics 1986 Don Eigler spells out IBM in atoms 1989

26. Our Goal: Reliable Versatile Atom-by-Atom Manufacturing

27. Atomically Precise Manufacturing Consortium Committed to bringing atom-by-atom manufacturing tools to market Universities: University of Texas at Dallas Bob Wallace, Yves Chabal, KJ Cho, JF Veyan, University of Illinois at UC Joe Lyding University of North Texas Rick Reidy, Maia Bischof, David Jaeger Colorado School of Mines Brian Gorman University of Texas at Austin S. V. Sreenivasan State Agency: North Texas RCIC Maria Smith International Collaborators: Univ. New South Wales Michelle Simmons Wolfgang Klesse University College London David Bowler University of Nottingham Prof. Moriarty Richard Woolley Future Collaborators: Your Institution Your name here Industry: Zyvex Labs J. Randall, J. Von Ehr, J. Ballard, R.Saini, J. Owen, Udi Fuchs S. Manning IC Scanning Probe Instruments Neil Sarkar Molecular Imprints Inc. S. V. Sreenivasan Tiptek Inc. Scott Lockledge Nanoretina RaananGefen National Labs: NIST Rick Silver, Jason Gorman

28. Making AXA Manufacturing a Reality

29. Developing a system from the ground up for complete freedom – not force-fitting off-the-shelf systems • UHV STM System • 2 Lyding Scanners • Field Ion Microscope • Closed loop heating • In-situ tip & sample prep • Automated dosing • Custom control system • Custom software • Remote operation • Two Systems Fully Operational Vibration Isolation Software system with growing capabilities

30. Material System: Si(100)2x1-H STM Image of Si(100)2x1-H Dimer rows spaced 0.77nm apart. Dimer rows switch direction with each atomic layer. This surface has been highly studied, making studies easier to understand. 12 nm

31. Details: Crystal Silicon Surface – Pixels formed from 2 dimers Identifying Pixels on Si Surface Depiction of Surface of “Si (100) 2x1” Fourier analysis allows us to identify the pixels on the Si surface. We can associate a design grid with the Si lattice, and use the lattice as a global fiducial grid. • Each surface atom has 1 unfilled bond: • When bare, the atom is reactive • With H there, the atom is “passive” • Two atoms form one surface dimer. • We define one pixel as two adjacent dimers

32. AP H depassivation with STM Hersam and Lyding UIUC 3nm Zyvex Labs

33. Using, creep and drift correction and alignment to the lattice, more accurate litho is possible. Theory Experiment Atomic precision pattern placement over small area. Have currently extended to roughly 40x40nm area.

34. Automated Vector Compiler

35. How to do Hello Kitty Optimize Write Distances Determine all possible vectors Subtract longest vector from pattern Optimize Step Distances Put longest vector in master vector list Find vector with nearest start or end point to end of previous vector Remove vector from search list #1 DR saturated #1 DR unsaturated (126, 133, 208, 133) (126, 132, 208, 132) (126, 131, 208, 131) (126, 130, 208, 130) (126, 129, 208, 129) (122, 129, 122, 153) (121, 129, 121, 153) (120, 129, 120, 153) (67, 160, 100, 160) (67, 161, 100, 161) (67, 162, 100, 162) (67, 163, 100, 163) (67, 164, 100, 164) (67, 165, 100, 165) (67, 166, 100, 166) (67, 167, 100, 167) (100, 133, 100, 168) (67, 133, 100, 133) (67, 133, 67, 168) (67, 168, 100, 168) Perform Litho Input Vector List (Find pixel info) Write vectors Step in scan mode

36. Patterned Epitaxy Dose Dose Dose Dose Litho Litho Litho Litho Litho Owen et al. J. Vac. Sci. Technol. B 29 06F201  (2011)DOI: 10.1116/1.3628673

37. Atom-by-Atom Manufacturing • 2 nm epitaxial growth, automated, overnight process with system cycling through: • Imaging • Litho • Depo

38. New Device Regime! Simmons has shown high-precision 2D placement of dopants in silicon leads to remarkable devices • Insulating, semiconducting, and metallic regions created in single crystal silicon • A new device regime with: • NO Metal Oxide Semiconductor interface

39. Pattern Transfer ALD of metal oxide H H H H H H H Metal precursor Zyvex Labs H2O H H H H H H H MO2 UT Dallas RIE NIST Hard Etch Masks

40. AFM of Patterns after ALD

41. Linewidth Dependence of RIE a b c d e 100 nm Lines written with FE mode litho can easily be controlled down to 10 nm, but edges matter

42. Sharpened edges patterns b a 59 52 46 40.7 nm 34 28 16 12 0

43. Closeups of NI

44. Case Study: Master Nanoimprint Templates Polymer AP Structures • Products • Molecular binding sites • Nanopore membranes • Catalysts • Nanooptical elements • NOT VLSI • Some loss of fidelity: • From Si structure to template • From Master to Daughter • Imprint Process • Pattern Transfer

45. Case Study: Nano Mechanics MEMS Oscillators are orders of magnitude better than electronic oscillators in terms of their quality factor and produce much better filters. BUT semiconductor processing has terrible relative precision making the control of frequency poor. • Atom by atom manufacturing would produce • An oscillator with a near terahertz frequency • Excellent control over frequency • Extremely high Q • Myriad applications such as ultra low power radios and extremely sensitive sensors

46. Nano Bio Uses Structures that interact in extremely precise ways with specific molecules: Ultra precise molecular filtering Precisely designed binding sites for ultra effective drugs to enhance or block protein action Designed enzymes

47. Case Study: DNA “Nanopore” for Ultra-High-Speed DNA Sequencing DNA readout mechanisms are extremely sensitive to distance Currently far too much variation Game Changer: AXA Manufactured “Nanopore” DNA Sequencers Atomic precision will enable speeds needed for ultra low cost True “personalized medicine” and tailored treatments – a medical revolution Optimized crops Rapid identification of evolving diseases

48. Concept: Molecular Specific Filtering Molecule B can not pass through pores in membrane Molecule A passes through pores in membrane The ability to control a molecules ability to pass through the filter Can be based on shape of the pore as well as the size And possibly the surface chemistry of the membrane and pores

49. Selective Depassivation R = SH, NO2, NH2, CH3, COOH, etc. OH OH CH3

50. Investigate Bio molecular Interactions Distance selectable With atomic resolution OH CH3