Smart Nano Surgeon

1. Smart Nano Surgeon EE235 Final Project May. 12th 2009 Infinite Plus One (I.P.O) Jun-suk Hong-ki Jong-Sun

2. Motivation - Today’s climate • Many diseases are threatening human all over the world. Especially, cancer, AIDS, tumor are extremely dangerous • Brand “new” diseases such as SARS, “mad-cow” disease, and Swine Influenza (SI) are breaking out. May.12th. 2009

3. Introduction: NANO in Bio-medicine • Small volume of reagent samples, required for analysis. • Low power consumption, lasts longer on the same battery. • Less invasive, hence less painful. • Integration permits many systems built on a single chip. • Batch processing can lower costs significantly. • Existing nanotechnology can be used to make these devices. May.12th. 2009

4. Market Analysis May.12th. 2009

5. Nanotechnology Market $2.6 trillion in 2014 $30 billion in 2005 $14 billion in 2004 Nanotechnology Very fruitful market area Nano-enabled products have the price premium of 11% Lux Research, Nanotechnology Report, 4th, 2006 May.12th. 2009

6. Health Care Nanotechnology Product Needs 50% increase annually! Lux Research, Nanotechnology Report, 4th, 2006 May.12th. 2009

7. National Health Expenditures • $2.4 trillion in 2008 • $4.2 trillion in 2017 • Our target market: • about $100 billion size • Projected to reach $4.3 trillion by 2017 (19.5% of GDP) • 4.3 times the amount spent on national defense • An outlook for the future 10~20 years ahead. Health Affairs, 2008 May.12th. 2009

8. Market Increase of Nano robot & MEMS 15% increase annually! Lux Research, Nanotechnology Report, 4th, 2006 May.12th. 2009

9. Competitor Analysis Drug delivery: Works well like tablets, but limited target, operation Human doctors: Great, but have limitation for major new disease since they cannot go into Human body Competitors Capsule Endoscope: Great for taking pictures, communication by RFID but low quality, no control Nano Bug: Not realized yet, too conceptual May.12th. 2009

10. Basic Concept May.12th. 2009

11. Blueprint of Nano Surgeon 10-20 years in the future… What do we mean by a nanosurgeon? Imagine… • …a EMT/first responder better able to address medical emergencies before arriving at the hospital with a simple injection. • …a self-administered at-home first-aid kit capable of “surgery.” • …persistent in vivo health monitoring. • …surgery/repair on the cellular and molecular scale. or… May.12th. 2009

12. 40 years ago May.12th. 2009

13. Now, and Future. Our Surgeon will • Mobility/Control • Biomotor • Magnetic movement • Catalytic pump • Action • Drug release • Cauterization • Ablation • Targeting/Sensing • Antigen targeting • Navigation via chemotaxis May.12th. 2009

14. Applications of Nano Surgeon May.12th. 2009

15. Targeting May.12th. 2009

16. Targeting [] Purpose • Gradient detection – navigation via chemotaxis • Target locking (site specificity) – Action trigger (drug release), accumulation (selective ablation). [] Sensing requirements • Very low detection limit. • Label-free detection. • High specificity, low NSB. • Consistent, reliable signal output. • Size! (nano) May.12th. 2009

17. Targeting [] Sensors + Nano • High field enhancement (optical) • Better mass sensitivity (cantilever) ∆z = L2/t2 ∆s • ‘bulk’ depletion/accumulation (nanowire) May.12th. 2009

18. Targeting [] Nanowire field-effect sensor • Surface chemistry to covalently link antibody receptors to nanowire. Influenza A single virus particle detection in dilute solution. Patolsky F. et.al. PNAS 2004;101:14017-14022 May.12th. 2009

19. Targeting [] Nanowire field-effect sensor • ≈100 virus particles per μl (≈0.16 fM) • Consistent signal change (≈20 nS) and duration (≈20 s) • High sensitivity with decreased sensing area low NSB • Linear response May.12th. 2009

20. Targeting [] Nanowire field-effect sensor • Detection limit: down to 10 fM and below shown • Label-free! • High specificity, low NSB. • Consistent, reliable signal output. • Size: down to 2-3nm wires. 2µm sensors demonstrated. May.12th. 2009

21. Detection Limit Comparison [] FOM • RIU, pg-mm-2, cfu/mL, µM… Dec. 10th. 2008 May.12th. 2009

22. Targeting [] Selective Functionalization May.12th. 2009

23. Targeting [] Selective Functionalization May.12th. 2009

24. Targeting [] Ligand-mediated hinge-bending May.12th. 2009

25. Control May.12th. 2009

26. Current Technology of moving/control Switzerland, ETH, Dr. Nelson Magnetic Helmholtz Robot Controlling Nanoscale Robots Japan, Dr. Sudo Magnetic swimming Robot Isarel, Dr. Solomon Fluidic Control Canada, Dr. Martel MRI based nano robot May.12th. 2009

27. Principle of MRI Previous use: Limited to diagnostic Hardware: Commercial MRI machines can be used to generate required magnetic field. Commercial 3T MRI (Phillips) May.12th. 2009

28. Common Coil Design to Control in vivo Robot The Helmholtz Coil Pair www.oersted.com/helmholtz_coils_1.shtml The Magnetic Field Created by Helmholtz Coil Pair http://hyperphysics.phy-astr.gsu.edu/hbase/magnetic/helmholtz.html The Maxwell Coil Pair and Direction of Current Flow http://physics-nmr.la.asu.edu/probes/hightemp/Images/maxwellpair.jpg May.12th. 2009

29. Magnetic Gradient Field Microrobot movement with changing magnetic field Microrobot movement with changing magnetic field May.12th. 2009

30. Video Clip Nano Robotics Lab, Prof. M. Sitti, Carnegie Mellon University May.12th. 2009

31. Action May.12th. 2009

32. Action • For better treatment, • We need ‘smart’ drug injection Drug delivery Drug release May.12th. 2009

33. Smart Drug delivery • Biocompatibiliy • Control over size • Reproducibility Nanofabrication May.12th. 2009

34. Smart Drug delivery Nano-porous silicon-based particle • Biocompatible • Photolithography-based fabrication • Nitride deposit • Patterning • Anodizing (pores) • Electropolishing • porous silicon particle Cohen et. al., Biomedical Microdevices 5:3, 253-259,2003 May.12th. 2009

35. Smart Drug delivery Nano-porous silicon-based particle • Biocompatible • Photolithography-based fabrication • Nitride deposit • Patterning • Anodizing (pores) • Electropolishing • porous silicon particle • Recently 1.6µm • Not flat shape Cohen et. al., Biomedical Microdevices 5:3, 253-259,2003 May.12th. 2009

36. Smart Drug release • Biophysical barriers • Osmotic pressure • Diffusion How to overcome? May.12th. 2009

37. Smart Drug release • Penentration enhancer • Fenestration • Conjugate molecular track movement • Abraxane – breast cancer medicine • 50% improved dosages May.12th. 2009

38. Option • MRI resolution enhancing nanoparticles • Gadolinium-based, iron oxide based superparamagnatic nanoparticles May.12th. 2009

39. Issues, Future & Conclusion May.12th. 2009

40. Critical Issue: Power May.12th. 2009

41. Critical Issue: Power-Biomolecular motor May.12th. 2009

42. If power issue is solved, Novineon, Germany SINTEF, Norway May.12th. 2009

43. Future Progress [1] Immerging Technologies • Nanoscale High Efficient VCSELS: Use of laser for tissue burning • SOC Level Integration: Self-decision of Smart Nanosurgeon • Miniaturization of Devices: Limit of total device is 1 um • Complex Synchronized Control: Control team of several nano surgeon devices • Self Sufficient Power Supply [2] Additional Applications • Smart Toothpaste: Nano robots to clean mouth overnight • Nano Plastic Surgeon: Termination of fat cells or shifting/alternation of bones will lead to precise plastic surgery • Health Monitoring System: Nano robots kept in living organ to monitor status May.12th. 2009

44. Business Plan -Chemical Sensor Development (Macro  Micro) Optimization - System design - Sampling/Drug Delivery Optimization (Micro) Basic Methodology(Macro) - MRI control Advanced Methodology(Micro) - MRI control Power Source (Macro) :Bio Battery :Wireless power supply Power Source (Micro) :Bio Battery :Wireless power supply Animal Experiment :Sensing/Actuation/Cure :Compatibility Human Experiment :Sensing/Actuation/Cure :Compatibility May.12th. 2009

45. Conclusion - S.W.O.T Analysis May.12th. 2009

46. We need money !! New Technology New Technology Conventional Technology Conventional Process Nano Surgeon The mainstream market The chasm The early market Current Status • Early Market Stage: Need R&D funds to build core competence, aiming for the chasm stage May.12th. 2009

47. References S. Park et al, 2005 IEEE/RSJ International Conference, 2005 N. Haas, et al, BME 200/300 Design U of Winconsin –Madison, 2008 J. B. Mathieu, G. Beaudoin, IEEE Transaction on Biomedical Eng. Vol 53, No2, 2006 Z. Li et al, Applied Physics A, Vol. 80, 2005 A.K. Singh et al, Biosensors & Bioelectronics, Vol. 14, 1999 R. Bogue, Industrial Robot: An International Journal, 2008 K. B. Yesin, Experimental Robotics, 2006 K. B. Yesin, MICCAI, 2005 M. Sitti et al, IEEE International conference on Robotics and Automation, 2008 K. Ishiyama et al, IEEE transactions on Magnetics, 1996 M. Sitti, Nature, 2009 M. Sitti et al, Applied Physics Letter, 2009 May.12th. 2009

48. References Keehan, S., et al., Health Affairs Web Exclusive W146: 21 February 2008. Patolsky, F., et al., Proc. Natl. Acad. Sci. USA, 2004, 101, 14017. Patolsky, F., et al., Materials Today, 2005, 8 (4), 20-28. Sundararajan, S., et al., Nano Lett., 2008, 8 (5), 1271-1276. Yake, A., et al., Biomacromolecules, 2007, 8 (6), 1958-1965. Ferrari et al., Nature Revies, Vol. 5, March 2005, 161-171 Grayson et al., Proceedings of the IEEE, Vol. 92, No. 1, January 2004 Green et al., Annals of Oncology 17, June 2006, 1263-1268 Serda et al., Biomaterials Vol. 30, 2009, 2440-2448 Harisinghani et al., the New England Journal of Medicine, Vol. 348, No. 25, June 2003 Santini et al., Nature, Vol. 397, January 1999 Cohen et al., Biomedical Microdevices, 5:3, 2003, 253-259 May.12th. 2009

49. Where do you want to invest your $$$? May.12th. 2009

50. Where do you want to invest your $$$? May.12th. 2009