Parallel Biomolecular Computation on Surfaces with Advanced Finite Automata

摘要

A biomolecular,programmable 3-symbol-3-state finite automaton is reported.This automaton computes autonomously with all of its components,including hardware,software,input,and output being biomolecules mixed together in solution.The hardware consisted of two enzymes:an endonuclease,Bbvl,and T4 DNA ligase.The software (transition rules represented by transition molecules) and the input were double-stranded (ds) DNA oligomers.Computation was carried out by autonomous processing of the input molecules via repetitive cycles of restriction,hybridization,and ligation reactions to produce a final-state output in the form of a dsDNA molecule.The 3-symbol-3-state deterministic automaton is an extension of the 2-symbol-2-state automaton previously reported,and theoretically it can be further expanded to a 37-symbol-3-state automaton.The applicability of this design was further amplified by employing surface-anchored input molecules,using the surface plasmon resonance technology to monitor the computation steps in real time.Computation was performed by alternating the feed solutions between endonuclease and a solution containing the ligase,ATP,and appropriate transition molecules.The output detection involved final ligation with one of three soluble detection molecules.Parallel computation and stepwise detection were carried out automatically with a Biacore chip that was loaded with four different inputs.