Designing a self-regulating biomolecular comparator

A major goal of biomolecular engineering is to build large systems of reactions with controlled input-output behavior. One challenge is that some reactions within such a system can be unreliable, so that rectification of these signals will be needed. Biomolecular oscillators, for example, typically have fluctuations in the amplitude response that can limit its ability to control downstream processes. In this paper, we describe a simple reaction module, or biomolecular comparator, that can take such signals as input and produces a square wave-like output. The comparator produces an output at a constant high level whenever the source input is above some predefined threshold concentration and a constant low signal otherwise. This functionality is verified though simulations and theoretical analysis. We also discuss important constraints on the comparator´s design. This work could make it possible to develop precise oscillatory molecular signals that allow for the dynamic control of synthetic biomolecular systems.