DNA Based Self-Assembly and Nano-

Device:

Theory and Practice

Peng Yin

Committee

Prof. Reif (Advisor), Prof. Agarwal, Prof. HarteminkProf. LaBean, Prof. Turberfield, Prof. Yan

1

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

NanoroboticsNanodiagnostics/ therapeutics

Nanoelectronics

Nanoworld (1 m = 109 nm)

There's Plenty of Room at the Bottom

3

Nanoworld (1 m = 109 nm)

?

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 = 109 nm)

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

DNA 101: Self-assembly

6

(Excerpted from Seeman 03)

Single strand DNA

as

Smart glues

DNA Based Self-Assembly & Nano-Device: Theory & PracticeDNA Based Self-Assembly & Nano-Device: Theory & Practice

7

How to build? How to compute?

Self-AssemblySelf-Assembly Nano-DeviceNano-Device

Theory & PracticeTheory & Practice

ComputerComputerModelingModeling

Mathematical Mathematical AnalysisAnalysis

How to move?

DNA BasedDNA Based

Biochem. Lab Biochem. Lab FabricationFabrication

TheoreticalTheoreticalDesignDesign

Roadmap: DNA Based Self-Assembly & Nano-Device

8Complexity - Error Correction – Nanorobotics - NanocomputingComplexity - Error Correction – Nanorobotics - Nanocomputing

• Complexity of

Self-Assembly

• Nanocomputing

Device

• Nanorobotics

Device

• Error Resilient

Self-Assembly

Roadmap: DNA Based Self-Assembly & Nano-Device

9Complexity Complexity - Error Correction – Nanorobotics - Nanocomputing

• Complexity of

Self-Assembly

• Nanorobotics

Device

• Nanocomputing

Device

• Error Resilient

Self-Assembly

Self-Assembly

10

Complexity of Graph Self-Assembly in

Accretive Systems and Self-Destructible Systems

Joint with

Reif, Sahu

Reif, Sahu, & Reif, Sahu, & YinYin (2005) Submitted to FNANO 2005 (2005) Submitted to FNANO 2005

Complexity Complexity - Error Correction – Nanorobotics - Nanocomputing

Complexity Complexity - Error Correction – Nanorobotics - Nanocomputing

Accretive Graph Assembly System

11

Graph Weight

function

Temperature

Temperature:

τ = 2

Seed

vertex

Seed

vertex

Sequentially

constructible?

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.

Roadmap: DNA Based Self-Assembly & Nano-Device

13Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

• Complexity of

Self-Assembly

• Nanorobotics

Device

• Nanocomputing

Device

• Error Resilient

Self-Assembly

Self-Assembly

14

Compact Error Resilient Computational DNA Tilings

Joint with

Reif, Sahu

Reif, Sahu, & Reif, Sahu, & YinYin (2004) DNA 10 (2004) DNA 10

Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

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

Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

Pad

Binary counter

16

Computational tiles

Frame tiles

Seed tile

Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

Binary counter

ErrorError in Assembly

17

Computational tiles

Frame tiles

Seed tile

Error!

Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

Binary counter

Error Resilient Tilings by Winfree

18

• Error rate 2

• Assembly size increased by 4

(Excerpted from Winfree 03)

Original tiles:

Error resilient tiles:

Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

Compact Error Resilient Computational Tiles

19

Original tiles:

Error resilient tiles:

X Y Z

XY YZ

Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

Compact Error Resilient Computational Tiles

20

Original tiles:

Error resilient tiles:

X Y Z

XY YZ

Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

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:

X Y Z

XY YZ

Error checking pads

Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

Computer Simulation (Xgrow, Winfree)

22Complexity - Error Correction – - Error Correction – Nanorobotics – Nanocomputing

Three way overlay

Winfree 2x2 construction

Two way overlay

No error correction

Winfree 3x3 construction

Roadmap: DNA Based Self-Assembly & Nano-Device

23Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Complexity of

Self-Assembly

• Nanorobotics

Device

• Nanocomputing

Device

• Error Resilient

Self-Assembly

Nano-Device

24

An Autonomous Unidirectional DNA Walker

Joint with

Yan, Daniell, Turberfield, Reif

(R. Cross Lab)

YinYin, Yan, Daniell, Turberfield, & Reif (2004) Angew. Chem. Intl. Ed., Yan, Daniell, Turberfield, & Reif (2004) Angew. Chem. Intl. Ed.

YinYin, Turberfield, & Reif (2004) DNA 10, Turberfield, & Reif (2004) DNA 10

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

Autonomous Unidirectional DNA Walker: Design

25

B C D A

Track

AnchorageA

Walker*

LigasePflM I

BstAP I

Restriction enzymes

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

DNA 101: Enzyme Ligation, Restriction

26

Sticky ends

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

DNA ligase

DNA restriction enzyme

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

DNA Walker: Operation

27

B C D A

Track

AnchorageA

Walker*

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

A*BAC D

DNA Walker: Operation

28

Ligase

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

A*BAC D

DNA Walker: Operation

29

Ligase

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

A*BAC D

DNA Walker: Operation

30

PflM I

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

B*

A C D A

DNA Walker: Operation

31Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

B*CA

AD

DNA Walker: Operation

32

Ligase

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

B*CA

AD

DNA Walker: Operation

33

Ligase

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

B*CA

AD

DNA Walker: Operation

34

BstAP I

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

C*

A B D A

DNA Walker: Operation

35Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

C*D AA B

DNA Walker: Operation

36Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

D*

A B C A

DNA Walker: Operation

37Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

D*ACA B

DNA Walker: Operation

38Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

• Valid hybridization:A* + B = A + B* A*B B* + C = B + C* B*CC* + D = C + D* C*D D* + A = D + A* D*A

• Valid cut:A*B A + B* B*CB + C*C*D C + D* D*AD + A*

A*

A B C D

DNA Walker: Operation

39Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

40

DNA Walker: Experimental Design

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

41

Autonomous Motion of the Walker

Complexity - Error Correction – Nanorobotics Nanorobotics - Nanocomputing

Roadmap: DNA Based Self-Assembly & Nano-Device

42Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

• Complexity of

Self-Assembly

• Nanorobotics

Device

• Nanocomputing

Device

• Error Resilient

Self-Assembly

Nano-Device

43

Designs of DNA Cellular Computing Devices

Joint with

Sahu, Turberfield, Reif

Yin,Yin, Turberfield, Sahu, & Reif (2004) DNA 10 Turberfield, Sahu, & Reif (2004) DNA 10

Yin,Yin, Sahu,Turberfield, & Reif (2005) Submitted to DNA 11 Sahu,Turberfield, & Reif (2005) Submitted to DNA 11

Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

DNA Cellular Computing Devices

44

Self-assembly Nanorobotics Nanocomputation

Reusable DNA computersReusable DNA computers

(Yan et al 03)

(Benenson et al 03)

Complex motionComplex motion

Intelligent robotics devicesIntelligent robotics devices

Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

DNA Cellular Computing Devices

45

Finite state automata Turing machine Cellular automata

Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Comp 101: Turing Machine

46

Tape

Read/write head

Transition rule

Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

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 colorsAutonomous universal DNA Turing machine: 2 states, 5 colors

Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Turing Machine: Operation

48

Turing machine

Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Turing Machine: Operation

49Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Turing Machine: Operation

50Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Turing Machine: Operation

51Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Turing Machine: Operation

52Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Turing Machine: Operation

53Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Turing Machine: Operation

54Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Turing Machine: Molecule Set

55Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

Turing Machine: Molecule Set/Simulation

56Complexity - Error Correction – Nanorobotics - Nanocomputing Nanocomputing

2 -Digit Binary Counter

Summary & Future

57

Robotics & ComputingComplexity & Fault-Tolerance

Complexity - Error Correction – Nanorobotics - NanocomputingComplexity - Error Correction – Nanorobotics - Nanocomputing

Software Tools: “Molecular compiler” - Rational design & Simulation

Summary:Summary:

Future: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”

Summary & Future58

Robotics & ComputingComplexity & Fault-Tolerance

Complexity - Error Correction – Nanorobotics - NanocomputingComplexity - Error Correction – Nanorobotics - Nanocomputing

Software Tools: “Molecular compiler” - Rational design & Simulation

Summary: Summary:

Future: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!