Bio-molecular Circuit Design with Electronic Circuit Software and Cytomorphic Chips

We have previously described a technique for rigorously converting arbitrary biological circuits to electronic circuit schematics that represent them exactly and quantitatively [1], [5], [12]. The technique enables us to simulate and model an experimental microbial synthetic microbial amplifier with electronic circuits in Cadence, a widely used integrated-circuit design tool for very-large-scale silicon chips [2]. Our model is in excellent accord with measured biological data for both the closed-loop and open-loop operation of the biological operational amplifier. In addition, because chemical reaction flux and electronic transistor current obey the same Boltzmann laws of thermodynamics, such analog circuit schematics can be emulated rapidly in custom integrated circuit cytomorphic silicon chip hardware [4]–[9] including sophisticated nonlinear, stochastic, non-modular, and dynamical effects. We show that we can rapidly simulate and fit experimental biological data from our synthetic microbial operational amplifier with cytomorphic chips. Since cytomorphic chips are an example of digitally programmable analog chips [10], [11], they are easily amenable to electronic evolution, parameter exploration, and machine learning. The use of industry-standard circuit software and the rapid emulation on digitally programmable cytomorphic silicon chips suggests that biological design of synthetic circuits can be automated onto electronic platforms in the future.