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A nanoscale programmable computing machine with input, output, software and hardware made of biomolecules Nature 414, 430-434 (2001) Kobi Benenson.

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Presentation on theme: "A nanoscale programmable computing machine with input, output, software and hardware made of biomolecules Nature 414, 430-434 (2001) Kobi Benenson."— Presentation transcript:

1 A nanoscale programmable computing machine with input, output, software and hardware made of biomolecules Nature 414, (2001) Kobi Benenson supervisor: Ehud Shapiro, Dept of Computer Science & Applied Math Acknowledgements: Ehud Keinan (Technion), Zvi Livneh (WIS), Tami Paz-Elizur (WIS), Rivka Adar (WIS), Aviv Regev (WIS), Irith Sagi (WIS), Ada Yonath (WIS)

2 Programmable Computer
“Medicine in 2050: Doctor in a Cell” Molecular Output Molecular Input Programmable Computer

3 Research goal: Design a simplest non-trivial molecular computing machine (two-state two-symbol finite automaton) that works on engineered inputs

4 Finite automaton: an example
An even number of b’s b S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 a a S0 S1 b Two-states, two-symbols automaton

5 Automaton 1 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 b a b
An even number of b’s S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 S0 b a b

6 Automaton 1 S0, b  S1 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 b a
An even number of b’s S0, b  S1 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 S0 b a b

7 Automaton 1 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 a b
An even number of b’s S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 S1 a b

8 Automaton 1 S1, a  S1 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 a b
An even number of b’s S1, a  S1 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 S1 a b

9 Automaton 1 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 b
An even number of b’s S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 S1 b

10 Automaton 1 S1, b  S0 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 b
An even number of b’s S1, b  S0 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 S1 b

11 Automaton 1 S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 The output
An even number of b’s S0, a  S0 S0, b  S1 S1, a  S1 S1, b  S0 S0 The output

12 Rationale for the molecular design

13 Rationale for the molecular design
CTGGCT GACCGA CGCAGC GCGTCG a b

14 Rationale for the molecular design
CTGGCT GACCGA CGCAGC GCGTCG a b S0, a S0, b GGCT CAGC

15 Rationale for the molecular design
CTGGCT GACCGA CGCAGC GCGTCG a b S0, a S0, b GGCT CAGC S1, a S1, b CTGGCT GA CGCAGC CG

16 Rationale for the molecular design
Transitions S0, b CAGCCTGGCTCGCAGCTGTCGC GACCGAGCGTCGACAGCG a b t

17 Rationale for the molecular design
Transitions S0, b CAGCCTGGCTCGCAGCTGTCGC GACCGAGCGTCGACAGCG a b t S0, b  S1

18 Rationale for the molecular design
Transitions S1, a CTGGCTCGCAGCTGTCGC GAGCGTCGACAGCG b t S0, b  S1

19 Rationale for the molecular design
Transitions S1, a CTGGCTCGCAGCTGTCGC GAGCGTCGACAGCG b t S1, a  S1

20 Rationale for the molecular design
Transitions S1, b CGCAGCTGTCGC CGACAGCG t S1, a  S1

21 Rationale for the molecular design
Transitions S1, b CGCAGCTGTCGC CGACAGCG t S1, b  S0

22 Rationale for the molecular design
Transitions S0, t TCGC S1, b  S0

23 Rationale for the molecular design
Transitions S0, t TCGC Output: S0

24 Rationale for the molecular design
Transition procedure: a concept S0, b CAGCCTGGCTCGCAGCTGTCGC GACCGAGCGTCGACAGCG a b t

25 Rationale for the molecular design
Transition procedure: a concept S0, b CAGCCTGGCTCGCAGCTGTCGC GACCGAGCGTCGACAGCG a b t GTCG 4 nt 8 nt S0, b -> S1

26 Rationale for the molecular design
Transition procedure: a concept GTCG 4 nt 8 nt CAGCCTGGCTCGCAGCTGTCGC GACCGAGCGTCGACAGCG b t S0, b -> S1

27 Rationale for the molecular design
Transition procedure: a concept S1, a CTGGCTCGCAGCTGTCGC GAGCGTCGACAGCG b t S0, b -> S1

28 Rationale for the molecular design
Transition procedure: a concept S1, a CTGGCTCGCAGCTGTCGC GAGCGTCGACAGCG b t S1, a -> S1

29 Rationale for the molecular design
Transition procedure: a concept S1, a CTGGCTCGCAGCTGTCGC GAGCGTCGACAGCG b t GACC 6 nt 10 nt S1, a -> S1

30 Rationale for the molecular design
Transition procedure: a concept GACC 6 nt 10 nt CTGGCTCGCAGCTGTCGC GAGCGTCGACAGCG t S1, a -> S1

31 Rationale for the molecular design
Transition procedure: a concept S1, b CGCAGCTGTCGC CGACAGCG t S1, a -> S1

32 Rationale for the molecular design
Transition procedure: a concept S1, b CGCAGCTGTCGC CGACAGCG t GCGT 8 nt 12 nt S1, b -> S0

33 Rationale for the molecular design
Transition procedure: a concept GCGT 8 nt 12 nt CGCAGCTGTCGC CGACAGCG S1, b -> S0

34 Rationale for the molecular design
Transition procedure: a concept S0, t TCGC Output: S0

35 Rationale for the molecular design
In situ detection S0, t Detection molecule for S0 output TCGC AGCG Output: S0

36 Rationale for the molecular design
In situ detection Reporter molecule for S0 output TCGC AGCG Output: S0

37 Inside the transition molecule
GTCG 4 nt 8 nt S0,b -> S1

38 GGATGACGAC CCTACTGCTG GTCG Inside the transition molecule FokI
4 nt GGATGACGAC CCTACTGCTG GTCG 8 nt S0,b -> S1

39 GGATGACGAC CCTACTGCTG GTCG Inside the transition molecule FokI
9 nt 4 nt GGATGACGAC CCTACTGCTG GTCG 8 nt 13 nt S0,b -> S1

40 GGATGACGAC CCTACTGCTG GTCG Inside the transition molecule FokI
9 nt 13 nt S0,b -> S1

41

42 Inside the transition molecule
GACC 6 nt 10 nt S1,a -> S1

43 GGATGACG CCTACTGC GACC Inside the transition molecule FokI
9 nt 6 nt GGATGACG CCTACTGC GACC 10 nt 13 nt S1,a -> S1

44 GGATGACG CCTACTGC GACC Inside the transition molecule FokI
9 nt 13 nt S1,a -> S1

45 Inside the transition molecule
8 nt GCGT 12 nt S1,b -> S0

46 GGATGG CCTACC GCGT Inside the transition molecule FokI S1,b -> S0
9 nt 8 nt GGATGG CCTACC GCGT 12 nt 13 nt S1,b -> S0

47 GGATGG CCTACC GCGT Inside the transition molecule FokI S1,b -> S0
9 nt 13 nt S1,b -> S0

48 GGATGACGAC CCTACTGCTG GTCG GGATGACG CCTACTGC GACC GGATGG CCTACC GCGT
Inside the transition molecule GGATGACGAC CCTACTGCTG S0 -> S1 GTCG S0 -> S0 GGATGACG CCTACTGC GACC S1 -> S1 GGATGG CCTACC S1 -> S0 GCGT

49 Transition rules: complete list

50 Automata programs used to test the molecular implementation

51 Transition molecules: complete list

52 Input and detection molecules

53 Experimental testing of automaton programs A1 – A6

54 Computations over 6-symbol long input molecules

55 Parallel computation

56 Identification of the essential components

57 Close inspection of the reaction intermediates

58 An estimation of system fidelity

59 Summary 1012 automata run independently and in parallel
on potentially distinct inputs in 120 ml at room temperature at combined rate of 109 transitions per second with accuracy greater than 99.8% per transition, consuming less than Watt.


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