Design and Analysis of Genetically Encoded Counters

The ability to store and to act upon modest amounts of information within living systems would enable new approaches to the study and control of biological processes. We develop a hierarchical composition framework supporting the design and analysis of higher-order genetically encoded information storage systems using combinatorial counters as a test case. We first develop a set-reset latch design based on DNA inversion, a toggle flip-flop design based upon two set-reset latches having gated outputs, and an N-bit 2N state counter design built from N toggle flip-flops. Using computational modeling, we then show how increasing the output gating speed of set-reset latches extends the operable ranges of toggle flip-flops with respect to set-reset latch switching thresholds and toggle flip-flop input pulse height and frequency. Finally, we show how coupling of input/output operable ranges of toggle flip-flops determines the operable ranges of counters. Such frameworks support the comparative analysis of competing low-level designs and further enable engineers to make the best use of limited genetic components while avoiding unnecessary compositional failure.