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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
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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”
Nanoworld (1 m = 109 nm)
Nanofabrication
Nanorobotics
Nanocomputation
Nanoelectronics
Nanodiagnostics/ therapeutics
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There's Plenty of Room at the Bottom
Nanoworld (1 m = 109 nm)
?
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There's Plenty of Room at the Bottom
Nanoworld (1 m = 109 nm)
How to build things?
How to make things move
(and do work)?
How to compute?
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DNA 101: DNA – Not merely secret to life
•
•
Information encoding: bases: A, T, C, G
Complementarity of bases: A – T; C – G
Complementary single strands
3.4
nm
Duplex
Self-Assembly !
2 nm
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DNA 101: Self-assembly
Single strand DNA
as
Smart glues
(Excerpted from Seeman 03)
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DNA Based Self-Assembly & Nano-Device: Theory & Practice
DNA Based
How to build?
Self-Assembly
How to move?
How to compute?
Nano-Device
Theory & Practice
Theoretical
Design
Mathematical
Analysis
Computer
Modeling
Biochem. Lab
Fabrication
Complexity - Error Correction – Nanorobotics - Nanocomputing
Roadmap: DNA Based Self-Assembly & Nano-Device
• Complexity of
Self-Assembly
• Error Resilient
Self-Assembly
• Nanorobotics
Device
• Nanocomputing
Device
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Roadmap: DNA Based Self-Assembly & Nano-Device
• Complexity of
Self-Assembly
• Error Resilient
Self-Assembly
• Nanorobotics
Device
• Nanocomputing
Device
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Self-Assembly
Complexity of Graph Self-Assembly in
Accretive Systems and Self-Destructible Systems
Joint with
Reif, Sahu
Reif, Sahu, & Yin (2005) Submitted to FNANO 2005
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Accretive Graph Assembly System
Seed
vertex
Graph
Temperature:
τ=2
Seed
vertex
Temperature
Weight
function
Sequentially
constructible?
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Problems, Results, & Contributions
Problems
• Accretive Graph Assembly Problem
• Self-Destructible Graph Assembly Prob.
Results
• AGAP is NP-complete
• Planar AGAP is NP-complete
• #AGAP/Stochastic AGAP is #P-complete
• DGAP is PSPACE-complete
Contributions
• Cooperative effects of attraction and repulsion
• General setting of graphs
• Dynamic self-destructible behavior in DGAP model
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Complexity - Error Correction – Nanorobotics – Nanocomputing
Roadmap: DNA Based Self-Assembly & Nano-Device
• Complexity of
Self-Assembly
• Error Resilient
Self-Assembly
• Nanorobotics
Device
• Nanocomputing
Device
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Complexity - Error Correction – Nanorobotics – Nanocomputing
Self-Assembly
Compact Error Resilient Computational
DNA Tilings
Joint with
Reif, Sahu
Reif, Sahu, & Yin (2004) DNA 10
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Complexity - Error Correction – Nanorobotics – Nanocomputing
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Computational Tilings
Tile
(Excerpted from Yan et al 03)
Computational tiles (Winfree)
Pad
Output 2
Output 1
Input 2
Input 1
Output 1 = Input 1 XOR Input 2
Output 2 = Input 1 AND Input 2
Complexity - Error Correction – Nanorobotics – Nanocomputing
Binary counter
Binary counter
Computational tiles
Seed tile
Frame tiles
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Complexity - Error Correction – Nanorobotics – Nanocomputing
Error in Assembly
Binary counter
Computational tiles
Seed tile
Error!
Frame tiles
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Complexity - Error Correction – Nanorobotics – Nanocomputing
Error Resilient Tilings by Winfree
Original tiles:
Error resilient tiles:
(Excerpted from Winfree 03)
• Error rate   2
• Assembly size increased by 4
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Complexity - Error Correction – Nanorobotics – Nanocomputing
Compact Error Resilient Computational Tiles
Original tiles:
Error resilient tiles:
X
Y
XY
Z
YZ
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Complexity - Error Correction – Nanorobotics – Nanocomputing
Compact Error Resilient Computational Tiles
Original tiles:
Error resilient tiles:
X
Y
XY
Z
YZ
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Complexity - Error Correction – Nanorobotics – Nanocomputing
Compact Error Resilient Computational Tiles
Original tiles:
Error resilient tiles:
X
Y
XY
Z
YZ
Error checking
pads
• Assembly size not increased
• Two way overlay: error rate (5%)  2 (0.25%)
• Three way overlay: error rate  (5%)  3 (0.0125%)
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Complexity - Error Correction – Nanorobotics – Nanocomputing
Computer Simulation (Xgrow, Winfree)
Three way overlay
Winfree 3x3 construction
Winfree 2x2 construction
Two way overlay
No error correction
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Roadmap: DNA Based Self-Assembly & Nano-Device
• Complexity of
Self-Assembly
• Error Resilient
Self-Assembly
• Nanorobotics
Device
• Nanocomputing
Device
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Nano-Device
(R. Cross Lab)
An Autonomous Unidirectional DNA Walker
Joint with
Yan, Daniell, Turberfield, Reif
Yin, Yan, Daniell, Turberfield, & Reif (2004) Angew. Chem. Intl. Ed.
Yin, Turberfield, & Reif (2004) DNA 10
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Complexity - Error Correction – Nanorobotics - Nanocomputing
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Autonomous Unidirectional DNA Walker: Design
Restriction enzymes
PflM I
Walker
Anchorage
A*
B
Track
C
BstAP I
D
A
Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA 101: Enzyme Ligation, Restriction
Sticky ends
DNA ligase
DNA restriction enzyme
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
Walker
B*CB + C*
D*AD + A*
Anchorage
A*
B
Track
B* + C = B + C* B*C
D* + A = D + A* D*A
C
D
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
A*B
C
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
D
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
C
A*B
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
D
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
PflM I
A*B
C
D
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
B*
A
C
D
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
A
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
D
B*C
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
A
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
D
B*C
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
BstAP I
A
D
B*C
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
C*
A
B
D
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
A
B
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
C*D
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
D*
A
B
C
A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
A
B
C
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
D*A
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Walker: Operation
• Valid hybridization:
A* + B = A + B* A*B
C* + D = C + D* C*D
• Valid cut:
A*B  A + B*
C*D  C + D*
B* + C = B + C* B*C
D* + A = D + A* D*A
B*CB + C*
D*AD + A*
A*
A
B
C
D
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Complexity - Error Correction – Nanorobotics - Nanocomputing
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DNA Walker: Experimental Design
Complexity - Error Correction – Nanorobotics - Nanocomputing
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Autonomous Motion of the Walker
Complexity - Error Correction – Nanorobotics - Nanocomputing
Roadmap: DNA Based Self-Assembly & Nano-Device
• Complexity of
Self-Assembly
• Error Resilient
Self-Assembly
• Nanorobotics
Device
• Nanocomputing
Device
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Nano-Device
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
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Cellular Computing Devices
Self-assembly
Nanorobotics
Nanocomputation
(Benenson et al 03)
(Yan et al 03)
Complex motion
Intelligent robotics devices
Reusable DNA computers
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Cellular Computing Devices
Finite state automata
Turing machine
Cellular automata
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Comp 101: Turing Machine
Read/write head
Tape
Transition rule
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Complexity - Error Correction – Nanorobotics - Nanocomputing
DNA Turing Machine: Structure
Turing machine
Transition table: Rule molecules
Turing head: Head molecules
Data tape: Symbol molecules
Autonomous universal DNA Turing machine: 2 states, 5 colors
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Turing Machine: Operation
Turing machine
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Turing Machine: Operation
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Turing Machine: Operation
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Turing Machine: Operation
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Turing Machine: Operation
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Turing Machine: Operation
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Turing Machine: Operation
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Turing Machine: Molecule Set
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Turing Machine: Molecule Set/Simulation
2 -Digit Binary Counter
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Summary & Future
Summary:
Complexity & Fault-Tolerance
Robotics & Computing
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”
Software Tools: “Molecular compiler” - Rational design & Simulation
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Complexity - Error Correction – Nanorobotics - Nanocomputing
Summary &
Future
Summary:
There's Plenty of Room at the Bottom!
Complexity & Fault-Tolerance
Future:
Robotics & Computing
?
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”
Software Tools: “Molecular compiler” - Rational design & Simulation
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