Improving the Performance of DNA Strand Displacement Circuits by Shadow Cancellation

DNA
strand displacement circuits are powerful tools that can be
rationally engineered to implement molecular computing tasks because
they are programmable, cheap, robust, and predictable. A key feature
of these circuits is the use of catalytic gates to amplify signal.
Catalytic gates tend to leak; that is, they generate
output signal even in the absence of intended input. Leaks are harmful
to the performance and correct operation of DNA strand displacement
circuits. Here, we present “shadow cancellation”, a
general-purpose technique to mitigate leak in catalytic DNA strand
displacement circuits. Shadow cancellation involves constructing a
parallel shadow circuit that mimics the primary circuit and has the
same leak characteristics. It is situated in the same test tube as
the primary circuit and produces “anti-background” DNA
strands that cancel “background” DNA strands produced
by leak. We demonstrate the feasibility and strength of the shadow
leak cancellation approach through a challenging test case, a cross-catalytic
feedback DNA amplifier circuit that leaks prodigiously. Shadow cancellation
dramatically reduced the leak of this circuit and improved the signal-to-background
difference by several fold. Unlike existing techniques, it makes no
modifications to the underlying amplifier circuit and is agnostic
to its leak mechanism. Shadow cancellation also showed good robustness
to concentration errors in multiple scenarios. This work introduces
a direction in leak reduction techniques for DNA strand displacement
amplifier circuits and can potentially be extended to other molecular
amplifiers.