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Page 1: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

MIT Molecular Machines (Jacobson) Group [email protected]

3.9.13

Fabricational Complexity

Page 2: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

Itanium Quad TukwilaTransistor Count: 2BCost: ~$50

Si Wafer with Area sufficient for2 Billion TransistorsCost: ~$0.50

Flash MemoryTransistor Count: 2BCost: ~$3

SmartPhoneCost: ~$200

Sand (Chips and Screen)Cost: ~$0

Plastic Resin / Metal OreCost: ~$4

What Drives The Cost of Placing Atoms Where We Want Them? What are The Fundamental Limits?

Page 3: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

Fabricational Complexity

Fabricational Complexity Per Unit Cost

MpF N ln

N BLOCKS

Fabricational Complexity for N Blocks or M Types = NMln

Fabricational Cost for N Blocks = NNp

Where is the Yield Per Fabricational Step p

Complexity Per Unit CostComplexity Per Unit Time*Energy

A G C T

T C T G

C A C G

A

G

C

T

Page 4: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

Genome (Natural)

Chemical Synthesis

Semi-conductor Chip

High Speed Offset Web TFT DVD-6

Liquid Embossing

Design Rule Smallest Dimension (microns) 0.0003 0.0003 0.1 10 2 0.25 0.2Number of Types of Elements 4 4 8 6 8 2 4Area of SOA Artifact (Sq. Microns) NA 7.E+08 7.E+10 2.E+12 1.E+12 1.E+10 8.E+09Volume of SOA Artifact (Cubic Microns) 6.E+01 5.E+06 7.E+09 2.E+12 1.E+11 7.E+12 8.E+08Number of Elements in SOA Artifact 3.E+09 7.E+04 7.E+12 2.E+10 3.E+11 2.E+11 2.E+11Volume Per Element(Cubic Microns) 2.E-08 8.E+01 1.E-03 1.E+02 4.E-01 4.E+01 4.E-03Fabrication Time(seconds) 4.E+03 2.E+04 9.E+04 1.E-01 7.E+02 3 6.E+01Time Per Element (Seconds) 1.E-06 3.E+02 1.E-08 7.E-12 2.E-09 2.E-11 3.E-10Fabrication Cost for SOA Artifact($) 1.E-07 1.E+02 1.E+02 1.E-01 2.E+03 3.E-02 2.E-01Cost Per Element 3.E-17 2.E-03 2.E-11 6.E-12 6.E-09 2.E-13 1.E-12Complexity 4.E+09 9.E+04 2.E+13 4.E+10 6.E+11 1.E+11 3.E+11Complexity Per Unit Volume of SOA(um 3̂) 7.E+07 2.E-02 2.E+03 2.E-02 5.E+00 2.E-02 3.E+02Complexity Per Unit Time 1.E+06 6.E+00 2.E+08 3.E+11 9.E+08 4.E+10 5.E+09Complexity Per Unit Cost 4.E+16 9.E+02 1.E+11 3.E+11 3.E+08 4.E+12 1.E+12Cost Per Area NA 2.E-07 2.E-09 6.E-14 2.E-09 3.E-12 3.E-11

Complexity Per Unit Cost

Page 5: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

Printed Electronics

~Minutes ~ 3Weeks of 7x24 Processing

Lithography Printed Electronics

+

Liquid InorganicSemiconductors[1]

[1] Ridley et al., Science, 286, 746 (1999)Science 297,416 (2000)

Printing

Towards $10 Tablets & E Books

Page 6: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

Fabricational Complexity

Fabricational Complexity Per Unit Cost

MpF ln

N BLOCKS

Fabricational Complexity for N Blocks or M Types = NMln

Fabricational Cost for N Blocks w/ Error Correction = 1NpWhere is the Yield Per Fabricational Step p

Complexity Per Unit CostComplexity Per Unit Time*Energy

A G C T

T C T G

C A C G

A

G

C

T

Page 7: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

N Devices

Yielding N Devices with Error Correction(Why A Small Amount of Error Correction Has A Very Large Effect)

kNkN

Mk

ppMNM

NMY

)1()!(!

!][

][NY ]1[ NY ]3[ NY

Fraction of Chips with M or More Perfect Devices (i.e. N-M or Fewer Errors).

0.75 0.97 0.997 0.9998

0.5 0.85 0.97 0.99

0.25 0.60 0.84 0.95

0.1 0.33 0.60 0.80

0.01 0.06 0.16 0.32

Table 1. Yields as a function of the number of repaired errors.

]2[ NY

J. Jacobson 02/12/09

Page 8: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

http://laser.gist.ac.kr/board/bbs/board.php?bo_table=rese_02

http://www.sdtech.co.kr/data/file/pro03/1890065063_Z6N9yvt4_EC9DB4EBAFB8ECA780_1.jpg

Error Correcting Fabrication - TFT

http://www.sdtech.co.kr/device3.html

Page 9: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

Moore’s Law Without Moore’s 2nd Law

http://www.chipsetc.com/the-transistor.html

http://www.webenweb.co.uk/museum/comps.htm

Moore’s Law

Error Correcting Manufacturing

Super Geometric Scaling

• Error Corrected TFT• Error Corrected CMOS• Error Corrected DNA Synthesis

Exponential Resource -> Exponential Gain Linear Resource-> Exponential Gain

Page 10: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

DNA SynthesisChemical Synthesis

(Open Loop Protection Group)Biological Synthesis

(Error Correcting Polymerase)

Error Rate: 1:102

Throughput: 300 S per Base Additionhttp://www.med.upenn.edu/naf/services/catalog99.pdf

Throughput Error Rate Product Differential: ~108

template dependant 5'-3' primer extension

5'-3' error-correcting exonuclease

3'-5' proofreading exonuclease

Example: [A] Synthesize 1500 Nucleotide Base Gene. Error Rate = 0.99(0.99)1500 ~ 10-7. [B] 3000 Nucleotide Base Gene. (0.99)3000 ~ 10-13.

Error Rate: 1:106

Throughput: 10 mS per Base AdditionBeese et al. (1993), Science, 260, 352-355. http://www.biochem.ucl.ac.uk/bsm/xtal/teach/repl/klenow.html

Page 11: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

Error Correcting Gene Synthesis

Nucleic Acids Research 2004 32(20):e162

Lamers et al. Nature 407:711 (2000)

X

X

X

Nucleic Acids Research 2004 32(20):e162

Error Rate 1:104

Page 12: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

http://www.ornl.gov/hgmis/publicat/microbial/image3.html

Nature Biotechnology 18, 85-90 (January 2000)

Deinococcus radiodurans (3.2 Mb, 4-10 Copies of Genome )

D. radiodurans: 1.7 Million Rads (17kGy) – 200 DS breaksE. coli: 25 Thousand Rads – 2 or 3 DS breaks

photos provided by David Schwartz (University of Wisconsin, Madison)]

D. radiodurans 1.75 million rads, 0 h

D. radiodurans 1.75 million rads, 24 h

http://openi.nlm.nih.gov/imgs/rescaled512/1079854_1471-2180-5-17-11.png

Page 13: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

Atoms: ~ 20 [C,N,O]Complexion: W~ 320 x = 32

Product: C = 4 statesx = 2

x[Product / Parts] =~ .0625

Complexity (uProcessor/program):x ~ 1K byte = 8000

Product: C = 4 statesx = 2

x[Product / Parts] =~ .00025

DNA Polymerase

Nucleotides: ~ 1000Complexion: W~41000 x = 2000 = 2Kb

Product: 107 Nucleotidesx = 2x107

x[Product / Parts] =104

x >1 Product has sufficient complexity to encode for parts / assembler

Synthetic Complexities of Various Systems

Page 14: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

500 1000 1500 2000 2500 3000

0.2

0.4

0.6

0.8

1.0

Threshold for LifeWhat is the Threshold for Self Replicating Systems?

Measurement Theory

http://en.wikipedia.org/wiki/File:Stem-loop.svg

Error Correcting Exonuclease

(Ruler)

DNA

Number of Nucleotides

Prob

abili

ty o

f Sel

f Rep

licati

on

NN

N

N

kT

qp

qQp

qQ

kq

q

N/2

2/

2/Bond

/E-

-1 P :Yield Total

11 :Yield StepPer

:open bonds N/2 ally that Probabilit :sNucleotide N

3E e :Where

:open is bond single ay that Probabilit

Bond

Watson Crick .18 nm

How Well Can N Molecules Measure Distance?

/sandwalk.blogspot.com/2007/12/dna-denaturation-and-renaturation-and.html

Threshold length: 1541 bp for 50% yield. 379 bp for 10-6 yield.

Page 15: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

20 40 60 80 100 120

500

1000

1500

Threshold for LifeWhat is the Threshold for Self Replicating Systems?

Measurement Theory

Number of Nucleotides m Per Building Block

Min

imum

Mac

hine

Size

N

To b

e Se

lf-Re

plic

ating

mNmN

N

N

kT

qp

qQp

qQ

kq

q

/N/2/

2/

2/

Bond/E-

-1 P :Yield Total

11 :Yield StepPer

:open bonds N/2 ally that Probabilit

bonds N/2 snucleotide N3E e :Where

:open is bond single ay that Probabilit

Bond

Threshold for assembling blocks of m –mers (monomer, dimer , trimer etc.)The longer the block the greater the binding energy.

m N for 50% Yield Number of Build Steps

1 (A,G,T,C)

1541 1541

2 (AA,AG,AT …)

1381 691

3 (AAA,AAG…)

1286 429

10 994 100

50 564 12

100 336 4

123 245 2

Yield___ 50%___ 10%___ 1%___ 1E-6

Threshold Machine Complexity N for Self-Replication

Page 16: MIT Molecular Machines ( Jacobson ) Group  jacobson@media.mit.edu 3.9.13

NOTES