M.Sc Thesis | |

M.Sc Student | Soreni-Harari Michal |
---|---|

Subject | DNA Based Advanced Parallel Biomolecular Computing Machines |

Department | Department of Chemistry |

Supervisor | PROFESSOR EMERITUS Ehud Keinan |

The first nanoscale, programmable
2-state-2-symbol finite automaton that computed autonomously with all of its
components, including hardware, software, input and output being biomolecules,
mixed together in solution was recently presented (Benenson, Y. et al., *Nature*,
2001, *414*, 430). The hardware consisted of a restriction nuclease and a
ligase, while the software (transition rules) and the input were
double-stranded (ds) DNA oligomers. Computation was carried out by processing
the input molecule via repetitive cycles of restriction, hybridization, and
ligation reactions to produce a final-state output in the form of dsDNA
molecules.

We increased the levels of
complexity and mathematical power of these automata by the design of a
3-state-3-symbol automaton having as many as 27 possible transition rules and a
remarkable number of 939,524,089 syntactically distinct programs. This number
is significantly larger than the corresponding number of 765 available programs
with the previously reported 2-symbol-2-state device. Restrictions at the
beginning of the symbol domain, 1 basepair deeper, and 2 basepairs deeper into
the domain represent the three internal states, S_{0}, S_{1}
and S_{2}, respectively. The applicability of this design was further
amplified by employing surface-anchored input molecules, using the surface
plasmon resonance (SPR) technology to monitor the computation steps in real
time. Computation was performed by alternating the feed solutions between *Bbv*I
endonuclease and a solution containing ligase, ATP and appropriate transition
molecules. The output detection involved final ligation with one of three soluble
detection molecules. Parallel computation and real-time detection were carried
out automatically with a Biacore chip that carried 4 different inputs.