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Programmable and autonomous computing machine made of biomolecules

Abstract

Devices that convert information from one form into another according to a definite procedure are known as automata. One such hypothetical device is the universal Turing machine1, which stimulated work leading to the development of modern computers. The Turing machine and its special cases2, including finite automata3, operate by scanning a data tape, whose striking analogy to information-encoding biopolymers inspired several designs for molecular DNA computers4,5,6,7,8. Laboratory-scale computing using DNA and human-assisted protocols has been demonstrated9,10,11,12,13,14,15, but the realization of computing devices operating autonomously on the molecular scale remains rare16,17,18,19,20. Here we describe a programmable finite automaton comprising DNA and DNA-manipulating enzymes that solves computational problems autonomously. The automaton's hardware consists of a restriction nuclease and ligase, the software and input are encoded by double-stranded DNA, and programming amounts to choosing appropriate software molecules. Upon mixing solutions containing these components, the automaton processes the input molecule via a cascade of restriction, hybridization and ligation cycles, producing a detectable output molecule that encodes the automaton's final state, and thus the computational result. In our implementation 1012 automata sharing the same software run independently and in parallel on inputs (which could, in principle, be distinct) in 120 μl solution at room temperature at a combined rate of 109 transitions per second with a transition fidelity greater than 99.8%, consuming less than 10-10 W.

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Figure 1: Finite automata with two states (S0 and S1) and two symbols (a and b).
Figure 2: Design details and mechanism of operation of the molecular finite automaton.
Figure 3: Running automaton programs on inputs.
Figure 4: Verification of the operation mechanism.

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Acknowledgements

We thank I. Sagi and A. Yonath for use of their laboratory for our first set of experiments, and S. Shuping, A. Regev and N. Kessler for assistance and advice. E.K. is the incumbent of the Benno Gitter and Ilana Ben-Ami Chair of Biotechnology, Technion. Z.L. is the Incumbent of The Maxwell Ellis Professorial Chair in Biomedical Research. This work was supported by the Dolphi and Lola Ebner Center for Biomedical Research.

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Correspondence to Ehud Shapiro.

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Benenson, Y., Paz-Elizur, T., Adar, R. et al. Programmable and autonomous computing machine made of biomolecules. Nature 414, 430–434 (2001). https://doi.org/10.1038/35106533

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