ashish goel, 1 the source of errors: thermodynamics rate of correct growth ¼ exp(-g a ) probability...

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Ashish Goel, [email protected] 1 The Source of Errors: Thermodynamics of correct growth ¼ exp(-G A ) ability of incorrect growth ¼ exp(-G A + G B ) traint: 2 G B > G A (system goes forward) ) Error probability ¸ exp(-G A /2) ) Rate has quadratic dependence on error probability ) Time to reliably assemble an n £ n square ¼ n 5 G A = Activation energy G B = Bond energy G A G B G A 2G B + Correct Growth Incorrect Growth

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Ashish Goel, 3 Example: Sierpinski Tile System

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Page 1: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 1

The Source of Errors: Thermodynamics

Rate of correct growth ¼ exp(-GA)

Probability of incorrect growth ¼ exp(-GA + GB)

Constraint: 2 GB > GA (system goes forward)

) Error probability ¸ exp(-GA/2)

) Rate has quadratic dependence on error probability) Time to reliably assemble an n £ n square ¼ n5

GA = Activation energy

GB = Bond energy

GA

GBGA

2GB

+

Correct Growth Incorrect Growth

Page 2: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 2

Error-Reducing Designs

Error correction via redundancy: do not change the model Tile systems are designed to have error correction mechanisms The Electrical Engineering approach -- error correcting codes

• But can not use existing coding/decoding techniques

Proofreading tiles [Winfree, Bekbolatov,’03]

Snake tiles [Chen, Goel ‘04]

Biochemistry techniques Strand Invasion mechanism

[Chen, Cheng, Goel, Huang, Moisset de espanes, ’04]

Page 3: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 3

Example: Sierpinski Tile System

00

0

1

1

1

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Page 4: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 4

Example: Sierpinski Tile System

0

1

1

1

0

0

0

0

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0

1

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0 00

00

Page 5: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 5

Example: Sierpinski Tile System

0

1

1

1

0

0

0

0

1

0

1

1

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0 00

00 0

Page 6: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 6

Example: Sierpinski Tile System

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

0

Page 7: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 7

Growth Error

0

1

1

1

0

0

0

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1

0

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1

1

1

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01

10

Page 8: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 8

Growth Error

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

0

mismatch

01

10

Page 9: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 9

Growth Error

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

010

Page 10: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 10

Growth Error

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

0

Page 11: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 11

Growth Error

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

0

Page 12: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 12

Proofreading Tiles

• Each tile in the original system corresponds to four tiles in the new system

• The internal glues are unique to this block

G1

G4

G3

G2

G1b

X4

X3

G2a

X2

G3b

G2b

G1a

G4a

X1

G4b

G3a

[Winfree, Bekbolatov, ’03]

Page 13: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 13

How does this help?

0

1

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Page 14: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 14

How does this help?

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

0

mismatch

Page 15: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 15

How does this help?

0

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1

0

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0

0

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1

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Page 16: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 16

How does this help?

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

0

No tile can attachat this location

Page 17: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 17

How does this help?

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

0

Page 18: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 18

How does this help?

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

0

Page 19: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 19

How does this help?

0

1

1

1

0

0

0

0

1

0

1

1

1

1

0

0

Page 20: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 20

Nucleation Error

Page 21: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 21

Nucleation Error

•First tile attaches with a weak binding strength

Page 22: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 22

Nucleation Error

•First tile attaches with a weak binding strength•Second tile attaches and secures the first tile

Page 23: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 23

Nucleation Error

•First tile attaches with a weak binding strength•Second tile attaches and secures the first tile•Other tiles can attach and forms a layer of (possibly incorrect) tiles.

Page 24: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 24

Snake Tiles

• Each tile in the original system corresponds to four tiles in the new system

• The internal glues are unique to this block

G1

G4

G3

G2

G1b

X1

X2

G2a

X3

G3b

G2b

G1a

G4a G4b

G3a

Page 25: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 25

How does this help?

•First tile attaches with a weak binding strength

Page 26: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 26

How does this help?

•First tile attaches with a weak binding strength•Second tile attaches and secures the first tile

Page 27: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 27

How does this help?

•First tile attaches with a weak binding strength•Second tile attaches and secures the first tile•No Other tiles can attach without another nucleation error

Page 28: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 28

Preliminary Experimental Results

(Obtained by Chen, Goel, Schulman, Winfree)

Page 29: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 29

Page 30: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 30

Page 31: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 31

Page 32: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 32

Page 33: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 33

Four by Four Snake Tiles

Page 34: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 34

Four by Four Snake Tiles

Page 35: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 35

Four by Four Snake Tiles

Page 36: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 36

Four by Four Snake Tiles

Page 37: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 37

Four by Four Snake Tiles

Page 38: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 38

Four by Four Snake Tiles

Page 39: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 39

Four by Four Snake Tiles

Page 40: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 40

Four by Four Snake Tiles

Page 41: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 41

Four by Four Snake Tiles

Page 42: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 42

Four by Four Snake Tiles

Page 43: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 43

Four by Four Snake Tiles

Page 44: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 44

Four by Four Snake Tiles

Page 45: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 45

Analysis Snake tile design extends to 2k£2k blocks.

Prevents tile propagation even after k+1 nucleation/growth errors The error probability changes from p to roughly pk

We can assemble an N£N square in time O(N polylog N) and it remains stable for time (N) (with high probability). Resolution loss of O(log N) Assuming tiles held by strength 3 do not fall off Matches the time for ideal, irreversible assembly Compare to N3 for basic proof-reading and N5 with no error-correction in

the thermodynamic model [Chen, Goel; DNA ‘04] Extensions, variations by Reif’s group, Winfree’s group, our

group, and others Recent result: Simple combinatorial criteria; Can avoid resolution loss

by using third dimension [Chen, Goel, Luhrs; SODA ‘08]

Page 46: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 46

Interesting Open Problems - I General theorems for analyzing reversible self-

assembly? Example: Imagine you are given an “L”, with each arm being

length N• From each “convex corner”, a tile can fall off at rate r• At each “concave” corner, a tile can attach at rate f > r• What is the first time that the (N,N) location is occupied?• We believe that the right answer is O(N), can prove O(N log N)

General theorems which relate the combinatorial structure of an error-correction scheme to the error probability? We have combinatorial criteria for error correction, but they

are not all encompassing

Page 47: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 47

Interesting Open Problems – IIRobust, efficient counting We replace a tile by a k £ k block, where k ! 1 as N ! 1

Or, by a k £ 1 block if we use the third dimension Codes (eg. Reed-Solomon) can do much better Can we use codes to design more efficient counters?

Specifically: Do there exist one-to-one functions (code-words)

W: {1,..N} ! {1..N2} such thatq Given a row of 2 log N tiles encoding W(k), there is some simple “tiling

subroutine” to assemble W(k+1) on topq Even if there are p log N errors in the tiling process for each row, this process

stops after “counting” from 1 to N Motivation: Correctly assembling large shapes up-to molecular precision will

be a new engineering paradigm – so an exciting opportunity for theoreticians

Page 48: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 48

(1,1)(1,0)(0,1)(0,0)(1,1)

(0,1)(1,1)(0,1)(1,1)(0,1)

(0,1)

(1,0)

(0,0)

(1,1)

(1,0)

(0,0)

(0,0)

(0,0)

(0,0)

(0,0) (0,0)

(0,0)

(0,1) (1,1) (0,0)

(1,1)

(1,0)

(1,1)

Another Mode of Error -- Damage

1W

1W

1W

1W

1W

1S1S1S1S1S1S

(1,1)

(1,0) (0,1)

(1,1)

(0,0)

(1,0)

S

S

1W

1S

(0,0)

(0,1)

(1,1)

(1,0)

Page 49: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 49

What went wrong? When tiles attach from unexpected directions the “correct” tile is

not guaranteed. Potential fix: Design systems more carefully so that the system can

reassemble from small pieces all over.

Previous work: [Winfree ’06] Rectilinear Systems that will grow back correctly as long as the seed remains in place by forcing growth only from the seed direction. Single point of failure: Lose the seed and the structure cannot regrow Akin to a lizard regenerating a limb

Our goal: Tile systems that heal from small fragments anywhere Akin to two parts of a starfish growing into complete separate starfish Almost a “reproductive property”

Page 50: Ashish Goel, 1 The Source of Errors: Thermodynamics Rate of correct growth ¼ exp(-G A ) Probability of incorrect growth ¼ exp(-G A

Ashish Goel, [email protected] 50

Two pieces of self-healing: Immutability and Progressiveness

Immutability: Only correct tiles may attach.

(As opposed to the Sierpinski example.)

Progressiveness: Eventually, all tiles attach.

(Provided one of a set of pieces containing enough information remains)

Example: The Chinese remainder counter is almost self-healing from any row