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 machine, which stimulated work leading to the development of modern computers. The Turing machine and its special cases, including finite automata, operate by scanning a data tape, whose striking analogy to information-encoding biopolymers inspired several designs for molecular DNA computers. Laboratory-scale computing using DNA and human-assisted protocols has been demonstrated, but the realization of computing devices operating autonomously on the molecular scale remains rare. 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 microl 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.

DNA biomolecular-electronic encoder and decoder devices constructed by multiplex biosensors

“…1-11 A decade ago, for example, Adleman performed a now-classic experiment in which computations were conducted using DNA molecules, demonstrating that biology can provide new computing substrates. [12][13][14][15] In the decade since Adleman's invention, reports have been made of a wide and diverse range of DNA logic devices. [16][17][18][19][20][21][22] Winfree, Stojanovic, Willner, Katz and their co-workers have, for example, developed optically reported 'AND' , 'OR' and 'SET-RESET' logic gate operations.…”

Computing by polymerase chain reaction

“…Since then, a great deal of research has been carried on and many technical and theoretical achievements have been reached in DNA computing [12,[3][4][5]. Recently, new research perspectives have emerged that widen the possibilities of this field, among them: DNA self-assembly [21,22,15], DNA automata [2], and tools for DNA and RNA manipulation inspired by algorithmic analyses [17,11].…”

Molecular implementation of simple logic programs

“…(Who is Mortal?). This biomolecular computing system compares favourably with previous approaches in terms of expressive power, performance and precision 2,4,8,9,11,12,19 . A compiler translates facts, rules and queries into their molecular representations and subsequently operates a robotic system that assembles the logical deductions and delivers the result.…”

“…Biomolecular implementations of finite automata 8,9 and logic gates 4,10-13 have already been developed [14][15][16][17][18] . Here, we report an autonomous programmable molecular system based on the manipulation of DNA strands that is capable of performing simple logical deductions.…”