1. DNA Based Self-Assembly and Nano-Device: Theory and Practice Peng Yin Committee Prof. Reif (Advisor), Prof. Agarwal, Prof. Hartemink Prof. LaBean, Prof. Turberfield, Prof. Yan 1

2. 2 There's Plenty of Room at the Bottom Richard P. Feynman, 1959 “…a field, in which little has been done, but in which an enormous amount can be done in principle” Nanofabrication Nanocomputation Nanorobotics Nanodiagnostics/ therapeutics Nanoelectronics Nanoworld (1 m = 10 9 nm)

3. There's Plenty of Room at the Bottom 3 Nanoworld (1 m = 10 9 nm) ?

4. There's Plenty of Room at the Bottom 4 How to build things?How to make things move (and do work)? How to compute? Nanoworld (1 m = 10 9 nm)

5. DNA 101: DNA – Not merely secret to life 5 Self-Assembly ! Information encoding: bases: A, T, C, G Complementarity of bases: A – T; C – G Complementary single strands Duplex 2 nm 3.4 nm

6. DNA 101: Self-assembly 6 ( Excerpted from Seeman 03 ) Single strand DNA as Smart glues

7. DNA Based Self-Assembly & Nano-Device: Theory & Practice 7 How to build?How to compute? Self-AssemblyNano-Device Theory & Practice ComputerModelingMathematicalAnalysis How to move? DNA Based Biochem. Lab Fabrication TheoreticalDesign

8. Roadmap: DNA Based Self-Assembly & Nano-Device 8 Complexity - Error Correction – Nanorobotics - Nanocomputing Complexity of Self-Assembly Nanocomputing Device Nanorobotics Device Error Resilient Self-Assembly

9. Roadmap: DNA Based Self-Assembly & Nano-Device 9 Complexity Complexity - Error Correction – Nanorobotics - Nanocomputing Complexity of Self-Assembly Nanorobotics Device Nanocomputing Device Error Resilient Self-Assembly

10. 10 Complexity of Graph Self-Assembly in Accretive Systems and Self-Destructible Systems Joint with Reif, Sahu Reif, Sahu, & Yin (2005) Submitted to FNANO 2005 Complexity Complexity - Error Correction – Nanorobotics - Nanocomputing

11. Accretive Graph Assembly System 11 Graph Weight function Temperature Temperature: τ = 2 Seed vertex Seed vertex Sequentially constructible?

12. Problems, Results, & Contributions 12 Problems Accretive Graph Assembly Problem Complexity Complexity - Error Correction – Nanorobotics - Nanocomputing Contributions Cooperative effects of attraction and repulsion General setting of graphs Dynamic self-destructible behavior in DGAP model Results AGAP is NP-complete Planar AGAP is NP-complete #AGAP/Stochastic AGAP is #P-complete DGAP is PSPACE-complete Self-Destructible Graph Assembly Prob.

13. Roadmap: DNA Based Self-Assembly & Nano-Device 13 - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing Complexity of Self-Assembly Nanorobotics Device Nanocomputing Device Error Resilient Self-Assembly

14. 14 Compact Error Resilient Computational DNA Tilings Joint with Reif, Sahu Reif, Sahu, & Yin (2004) DNA 10 - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing

15. Computational Tilings 15 ( Excerpted from Yan et al 03 ) Tile Computational tiles (Winfree) Input 1 Input 2 Output 1Output 2 Output 1 = Input 1 XOR Input 2 Output 2 = Input 1 AND Input 2 - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing Pad

16. Binary counter 16 Computational tiles Frame tiles Seed tile - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing Binary counter

17. Error Error in Assembly 17 Computational tiles Frame tiles Seed tile Error! - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing Binary counter

18. Error Resilient Tilings by Winfree 18 Error rate    2 Assembly size increased by 4 ( Excerpted from Winfree 03 ) Original tiles: Error resilient tiles: - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing

19. Compact Error Resilient Computational Tiles 19 Original tiles: Error resilient tiles: XYZ XYYZ - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing

20. Compact Error Resilient Computational Tiles 20 Original tiles: Error resilient tiles: XYZ XYYZ - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing

21. Compact Error Resilient Computational Tiles 21 Assembly size not increased Two way overlay: error rate  (5%)   2 (0.25%) Three way overlay: error rate  (5%)   3 (0.0125%) Original tiles: Error resilient tiles: XYZ XYYZ Error checking pads - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing

22. Computer Simulation (Xgrow, Winfree) 22 - Error Correction – Complexity - Error Correction – Nanorobotics – Nanocomputing Three way overlay Winfree 2x2 construction Two way overlay No error correction Winfree 3x3 construction

23. Roadmap: DNA Based Self-Assembly & Nano-Device 23 Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing Complexity of Self-Assembly Nanorobotics Device Nanocomputing Device Error Resilient Self-Assembly

24. Nano-Device 24 An Autonomous Unidirectional DNA Walker Joint with Yan, Daniell, Turberfield, Reif ( R. Cross Lab ) Yin, Yan, Daniell, Turberfield, & Reif (2004) Angew. Chem. Intl. Ed. Yin, Turberfield, & Reif (2004) DNA 10 Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

25. Autonomous Unidirectional DNA Walker: Design 25 B C D A Track Anchorage A Walker * Ligase PflM I BstAP I Restriction enzymes Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

26. DNA 101: Enzyme Ligation, Restriction 26 Sticky ends Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing DNA ligase DNA restriction enzyme

27. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* DNA Walker: Operation 27 B C D A Track Anchorage A Walker * Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

28. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* A*B A C D DNA Walker: Operation 28 Ligase Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

29. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* A*B A C D DNA Walker: Operation 29 Ligase Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

30. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* A*B A C D DNA Walker: Operation 30 PflM I Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

31. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* B* A C D A DNA Walker: Operation 31 Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

32. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* B*C A A D DNA Walker: Operation 32 Ligase Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

33. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* B*C A A D DNA Walker: Operation 33 Ligase Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

34. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* B*C A A D DNA Walker: Operation 34 BstAP I Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

35. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* C* A B D A DNA Walker: Operation 35 Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

36. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* C*D A A B DNA Walker: Operation 36 Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

37. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* D* A B C A DNA Walker: Operation 37 Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

38. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* D*A C A B DNA Walker: Operation 38 Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

39. Valid hybridization: A* + B = A + B*  A*B B* + C = B + C*  B*C C* + D = C + D*  C*D D* + A = D + A*  D*A Valid cut: A*B  A + B*B*C  B + C* C*D  C + D*D*A  D + A* A* A B C D DNA Walker: Operation 39 Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

40. 40 DNA Walker: Experimental Design Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

41. 41 Autonomous Motion of the Walker Nanorobotics Complexity - Error Correction – Nanorobotics - Nanocomputing

42. Roadmap: DNA Based Self-Assembly & Nano-Device 42 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing Complexity of Self-Assembly Nanorobotics Device Nanocomputing Device Error Resilient Self-Assembly

43. Nano-Device 43 Designs of DNA Cellular Computing Devices Joint with Sahu, Turberfield, Reif Yin, Turberfield, Sahu, & Reif (2004) DNA 10 Yin, Sahu,Turberfield, & Reif (2005) Submitted to DNA 11 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

44. DNA Cellular Computing Devices 44 Self-assemblyNanoroboticsNanocomputation Reusable DNA computers ( Yan et al 03 ) ( Benenson et al 03 ) Complex motion Intelligent robotics devices Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

45. DNA Cellular Computing Devices 45 Finite state automataTuring machineCellular automata Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

46. Comp 101: Turing Machine 46 Tape Read/write head Transition rule Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

47. DNA Turing Machine: Structure 47 Turing machine Transition table: Rule molecules Turing head: Head molecules Data tape: Symbol molecules Autonomous universal DNA Turing machine: 2 states, 5 colors Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

48. Turing Machine: Operation 48 Turing machine Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

49. Turing Machine: Operation 49 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

50. Turing Machine: Operation 50 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

51. Turing Machine: Operation 51 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

52. Turing Machine: Operation 52 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

53. Turing Machine: Operation 53 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

54. Turing Machine: Operation 54 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

55. Turing Machine: Molecule Set 55 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing

56. Turing Machine: Molecule Set/Simulation 56 Nanocomputing Complexity - Error Correction – Nanorobotics - Nanocomputing 2 -Digit Binary Counter

57. Summary & Future 57 Robotics & Computing Complexity & Fault-Tolerance Complexity - Error Correction – Nanorobotics - Nanocomputing Software Tools: “Molecular compiler” - Rational design & Simulation Summary: Future: Mathematical Theory: General theory & Dynamic behavior Fault-Tolerance: Inspirations from fault tolerance theory & Biological systems Robotics Devices: Robotics lattice & Nanoparticle carrying/(un)loading Computing Devices: In silicon  in vitro  in vivo: “Doctor in a cell”

58. Summary & Future 58 Robotics & Computing Complexity & Fault-Tolerance Complexity - Error Correction – Nanorobotics - Nanocomputing Software Tools: “Molecular compiler” - Rational design & Simulation Summary: Future: Mathematical Theory: General theory & Dynamic behavior Fault-Tolerance: Fault tolerant theory & Biological inspiration Robotics Devices: Robotics lattice & Nanoparticle carrying/(un)loading Computing Devices: Intelligent robotics lattice & “Doctor in a cell” 58 ? There's Plenty of Room at the Bottom!