Parallel Biomolecular Computation on Surfaces with Advanced Finite Automata

Abstract

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, BbvI, 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.

Control of Noise in Chemical and Biochemical Information Processing

“…Furthermore, the biocatalytic nature of many utilized biomolecular processes, offers certain advantages for analog noise control in the binary-gate circuit design paradigm. [17] Proteins/enzymes [5][6][7][8][9][10][11][12][14][15][16][17][19][20][161][162][163][164][165] and DNA/RNA/DNAzymes [6,7,[166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182] have been extensively used for gates, for realizing small networks and computational units, and for systems motivated [183] by applications.…”

In Vivo Information Processing Using RNA Interference

“…Impressive results have been obtained in the construction of logic gates [4,[13][14][15], bistability [6,16], oscillations [17], molecular memory [18], and state machines [19,20]. Among these approaches, synthetic transcriptional control based on integration of interchangeable regulatory and protein-coding DNA sequences (i.e., Biobricks [21]) has emerged as a candidate design approach that can implement in vivo many of the good engineering practices described above.…”

Biomolecular Finite Automata

“…Significant expansion of the complexity of the above-described automata was achieved by the demonstration that a type-II four-cutter endonuclease could restrict a 6-bp symbol in three distinguishable modes [35]. Three internal states, S 0 , S 1 , or S 2 , could thus be represented by restriction at the beginning of the symbol domain, 1-bp deep or 2-bp deep into that domain, respectively ( Figure 9.11).…”

“…In 2011, a new molecular cryptosystem for images [43] based on two-symbol two-state finite automata [22,35,44,45] was demonstrated. The automata representing the software were programmed by the choice of several molecules from a library of eight TMs, representing eight transition rules.…”

“…Insertion of these plasmids into living onion cells resulted in either green fluorescent or cyan fluorescent cells as phenotypical output signals. The mathematical model, as well as its implementation using DNA molecules, was based on previously reported finite automata [22,35,44]. Two enzymes, endonuclease and a DNA ligase, as well as ATP, represented the hardware, whereas the automaton software was programmed by the choice of several molecules from a library of eight TMs, representing eight transition rules.…”