Biomedical Engineering Reference
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cannot open stems efficiently, while some loops favor alternative conformations
with deoxyribozymes. The functioning of the gates is also autonomous. That is,
once adding the inputs to the solution, no more human intervention is required [ 52 ].
17.3
Complex Circuits for Game-Playing Molecular
Automata
Molecular automata are autonomous machines that are able to analyze a series of
stimuli and leave an observer with an impression of a meaningful response to inputs.
Using deoxyribozyme-based logic gates, molecular automata were constructed to
play games, as an unbiased test of the complexity that can be achieved by a new
computation medium.
The first deoxyribozyme-based molecular automaton, called MAYA, plays a
symmetry-pruned restricted game of tic-tac-toe [ 43 , 53 , 54 ]. This simplification
allowed programming the automaton to play 19 legal games. MAYA consists of
nine wells numbered sequentially with 1-9 corresponding to the tic-tac-toe game
broad. Each well contains its own precisely defined set of DNA logic gates in
solution. Human intentions are communicated to automaton through adding the
input oligonucleotide coded to a particular human move into all wells. MAYA
carries out an analysis of the input by the human opponent and indicates a move
by fluorescence signaling in a response well. The cycle of human player input
followed by automaton response continues until there is a draw or a victory for the
automaton. MAYA incorporates 23 molecular logic gates, 1 active deoxyribozyme,
1 fluorescent-labeled substrate, and 8 input oligonucleotides.
The second molecular automaton, MAYA-II, is built to play all 76 permissible
tic-tac-toe games, without MAYA's limitations [ 44 , 53 , 54 ]. MAYA-II is more user-
friendly, displaying both players' moves in 2 different fluorescent colors. The result
design calls for 128 molecular logic gates, 1 active deoxyribozyme, 2 fluorescent-
labeled substrates, and 32 inputs. The success of MAYA-II indicates the maturity
of the deoxyribozyme-based logic gates as a modular, “plug and play” computing
system. By integrating more than 100 logic gates, MAYA-II represents the first
medium-scale integration of molecular logic gates in solution. The significance of
MAYA-II is that it shows that large-scale, high-level computing using molecular
logic gates is reasonable.
Our newest molecular automaton, MAYA-III [ 45 , 55 ], is a protoautomaton which
can be trained in a series of sessions with an operator to become an automaton. For
demonstration, we defined a game called tit for tat and trained MAYA-III to play
interactively with a human according to specified favorable strategies. The game of
tit for tat is played on a board split into four fields. The human player nominates any
square, and the automaton chooses a free square. The automaton wins by having the
same number of squares as the human player at the end. The game has 81 winning
strategies, and each strategy has 8 possible game plays.
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