Predicated assembly and biomimetics in micronanomanufacture

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Avogadro Scale Engineering Fabricational
Complexity
Symposium on Digital Fabrication Pretoria, South
Africa June 29, 2006
Molecular Fabrication (Jacobson) Group
jacobson_at_media.mit.edu
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Complexity vs. Size
red blood cell 5 ?m (SEM)
diatom 30 ?m
DNA proteins nm
Simple molecules lt1nm
bacteria 1 ?m
m
SOI transistor width 0.12?m
Semiconductor Nanocrystal 1 nm
Circuit design Copper wiring width 0.1?m
Nanotube Transistor (Dekker)
IBM PowerPC 750TM Microprocessor 7.56mm8.799mm 6.
35106 transistors
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Caruthers Synthesis
DNA Synthesis
Error Rate 1 102
300 Seconds Per step
http//www.med.upenn.edu/naf/services/catalog99.pd
f
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Replicate Linearly with Proofreading and Error
Correction Fold to 3D Functionality
Error Rate 1 106
100 Steps per second
template dependant 5'-3' primer extension
5'-3' error-correcting exonuclease
3'-5' proofreading exonuclease

• Beese et al. (1993), Science, 260, 352-355.

http//www.biochem.ucl.ac.uk/bsm/xtal/teach/repl/k
lenow.html
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Resources for Exponential Scaling
Resources which increase the complexity of a
system exponentially with a linear addition of
resources
1 Quantum Phase Space 2 Error Correcting
Fabrication 3 Fault Tolerant Hardware
Architectures 4 Fault Tolerant Software or Codes
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Error Correction in Biological Systems
Fault Tolerant Translation Codes (Hecht) NTN
encodes 5 different nonpolar residues (Met, Leu,
Ile, Val and Phe) NAN encodes 6 different polar
residues (Lys, His, Glu, Gln, Asp and
Asn) Local Error Correction Ribozyme
1103 Error Correcting Polymerase 1108
fidelity DNA Repair Systems MutS
System Recombination - retrieval - post
replication repair Thymine Dimer bypass. Many
others
E. Coli Retrieval system - Lewin
Biology Employs Error Correcting Fabrication
Error Correcting Codes
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Threshold Theorem Von Neumann 1956
Probability of Individual Gate Working
n
n3
k
For circuit to be fault tolerant
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Threshold Theorem - Winograd and Cowan 1963
A circuit containing N error-free gates can be
simulated with probability of failure e using O(N
poly(log(N/e))) error-prone gates which fail
with probability p, provided p lt pth, where pth
is a constant threshold independent of N.
n
Number of gates consumed
k
Find k such that
Number of Gates Consumed Per Perfect Gate is
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Threshold Theorem Generalized
n
For circuit to be fault tolerant Pltp
k
Total number of gates
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Scaling Properties of Redundant Logic (to first
order)
P
A
Probability of correct functionality pA e
A (small A)
P1 pA e A
Area A
P2 2pA/2(1-pA/2)pA/22 eA (eA)2/4
Area 2A/2
Conclusion P1 gt P2
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Scaling Properties of Majority Logic
n segments
P
Total Area n(A/n)
A
Probability of correct functionality pA
To Lowest Order in A
Conclusion For most functions n 1 is optimal.
Larger n is worse.
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Fabricational Complexity

• Total Complexity
• Complexity Per Unit Volume
• Complexity Per Unit TimeEnergy
• Complexity Per unit Cost

Ffab ln (W) / a3 tfab Efab Ffab ln
(M)e-1 / a3 tfab Efab
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Fabricational Complexity
Total Complexity Accessible to a Fabrication
Process with Error p per step and m types of
parts is
A
G
T
C
A
G
A
T
A
C
G
T
A
A

A
G
T
A
G
C

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Fabricational Complexity
n
Fabricational Complexity for n-mer
Fabricational Cost for n-mer
Complexity per unit cost
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Fabricational Complexity
Non Error Correcting
A
G
T
C
A
G
T
C
Triply Error Correcting
A
G
T
C
A
G
T
C
n 300
P 0.9
P 0.85
n
p
n
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Deinococcus radiodurans (3.2 Mb,
4-10 Copies of Genome )
Uniformed Services University of the Health
Nature Biotechnology 18, 85-90 (January 2000)
D. radiodurans 1.7 Million Rads (17kGy) 200
DS breaks E. coli 25 Thousand Rads 2 or 3 DS
breaks
http//www.ornl.gov/hgmis/publicat/microbial/image
3.html
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D. radiodurans 1.75 million rads, 0 h
D. radiodurans 1.75 million rads, 24 h
photos provided by David Schwartz (University of
Wisconsin, Madison)
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Autonomous self replicating machines from random
building blocks
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Combining Error Correcting Polymerase and Error
Correcting Codes One Can Replicate a Genome of
Arbitrary Complexity
Basic Idea M strands of N Bases Result By
carrying out a consensus vote one requires only
To replicate with error below some epsilon such
that the global replication error is
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M ( of Copies of Genome)
N (Genome Length)
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Replication Cycle
p per base
p per base
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Information Rich Replication (Non-Protein
Biochemical Systems)
J. Szostak, Nature,409, Jan. 2001
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Combining Error Correcting Machinery and Error
Correcting Codes One Can Replicate a Machine of
Arbitrary Complexity
For Above Threshold M Copy Number
Jacobson 02
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BioFAB -Building a Fab for Biology-
MIT Molecular Machines (Jacobson) Group
jacobson_at_media.mit.edu
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MutS Repair System
Lamers et al. Nature 407711 (2000)
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Error Removal
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In Vitro Error Correction Yields gt10x Reduction
in Errors
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Error-Removal1000 bp Fluorescent Gene Synthesis
error-corrected (gt95 fluorescent)
error-enriched (lt10 fluorescent)
Native error rate
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Error Reduction GFP Gene synthesis
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Molecular Machines Group-MIT
Faculty Joseph Jacobson Research Scientists and
Post Docs Peter Carr Sangjun Moon Graduate
Students Brian Chow David Kong Chris Emig Jae
Bum Joo Jason Park Sam Hwang

• Air inlets
• Crushers
• Ganglion
• Multiple Visual sensors
• Muscles
• Pincers
• Sensory receptors
• Stridulatory pegs
• Wings

http//www.thetech.org/exhibits_events/traveling/r
obotzoo/about/images/grasshopper.gif