Biomolecular Computing - Bionanoelectronics: Bioinquiring and Bioinspired Devices - page 201

that of p q; the enzyme E cuts the implication molecule at the recognition site
in the query and releases a ssDNA, which hybridizes with the auxiliary matching
strand to form q?.
These simple biomolecular logical operations can be used to implement logic
programs, which consists of a finite set of facts and rules ( Ran et al. 2009 ).
In this sense, a query is answered by the output of a logic program, query
reduction being the basic step of logical deduction. In Ran et al. ( 2009 ), a four-
step cascaded deduction experiment was implemented in which the half time of
a logical deduction was 3 min and the query molecule was able to perform many
cleavage operations without needing an external supply and without undergoing
change. The experiment was designed such that different fluorescent molecules,
with different light emission wavelengths, can signify different assumptions. Such
logical programs with clear semantics can develop high-level languages, which
could be compiled into executable programs.
A programmable 3-symbol-3-state automaton, consisting of biomolecules in
solution that represent hardware, software, input, and output components, has been
demonstrated in Soreni et al. ( 2005 ). The hardware is composed of two enzymes
(a ligase and a restriction nuclease), and the software, surface-anchored input, and
output molecules are dsDNA strands, the computation being implemented via cycles
of restriction, hybridization, and ligation induce by the order and type of transition
molecules introduced in solution. The readout of the result and the monitoring of
the computation are performed by surface plasmon resonance technology. Each
symbol is encoded in a 6-bp sequence, and each state is represented by the
depth of the cut performed by a restriction molecule in the symbol domain. An
input molecule contains a recognition site for the restriction nuclease, several
symbols, and a terminator domain, the software consists of a set of nine transition
molecules with a 5-bp recognition site and a unique 4-bp sticky end separated by
a spacer that contains up to 4 bp. The readout is done by three detection molecules
with matching sticky ends to corresponding ends generated by restriction of the
terminator molecule. The detection molecules produce different surface plasmon
resonance responses upon hybridization with one of the three symbol sequences.
A program consists of selecting a subset from the 27 possible transition rules
and choosing the accepting internal states; there are 137,781 syntactically distinct
programs. The program ends when there are no transition molecules left that match
the sticky end of the input or when the terminator domain is restricted, producing
sticky ends that encode the final output state. Parallel computing is possible if the
input molecules are immobilized.

7.5 Biomolecular Memory Devices

DNA scaffolds that support arrays of independently and reversible addressable sites
can be used as rewritable memories. Such a device, consisting of three independent
addresses representing eight states, was demonstrated with a one-dimensional array