Search for: All records

Rationally designed molecular circuits describable by well-mixed chemical reaction kinetics can realize arbitrary Boolean function computation yet differ significantly from their electronic counterparts. The design, preparation, and purification of new molecular components poses significant barriers. Consequently, it is desirable to synthesize circuits from an existing “fridge” inventory of distinguishable parts, while satisfying constraints such as component compatibility. Heuristic synthesis techniques intended for large electronic circuits often result in non-optimal molecular circuits, invalid circuits that violate domain-specific constraints, or circuits that cannot be built with the current inventory. Existing “exact” synthesis techniques are able to find minimal feedforward Boolean circuits with complex constraints, but do not map to distinguishable inventory components. We present the Fridge Compiler, an SMT-based approach to find optimal Boolean circuits within a given molecular inventory. Empirical results demonstrate the Fridge Compiler’s versatility in synthesizing arbitrary Boolean functions using three different molecular architectures, while satisfying user-specified constraints. We showcase the successful synthesis of all 256 three-bit and 65,536 four-bit predicate functions using a large custom inventory, with worst-case completion times of only seconds on a modern laptop. In addition, we introduce a unique class of cyclic molecular circuits that cover a larger number of Boolean functions than their conventional counterparts over a common inventory, often with significantly smaller implementations. Importantly, and absent in previous approaches specific to molecular circuits, the Fridge Compiler is logically sound, complete, and optimal for the user-specified cost function and component inventory. 

A barrier to wider adoption of molecular computation is the difficulty of implementing arbitrary chemical reaction networks (CRNs) that are robust and replicate the kinetics of designed behavior. DNA Strand Displacement (DSD) cascades have been a favored technology for this purpose due to their potential to emulate arbitrary CRNs and known principles to tune their reaction rates. Progress on leakless cascades has demonstrated that DSDs can be arbitrarily robust to spurious "leak" reactions when incorporating systematic domain level redundancy. These improvements in robustness result in slower kinetics of designed reactions. Existing work has demonstrated the kinetic and thermodynamic effects of sequence mismatch introduction and elimination during displacement. We present a systematic, sequence modification strategy for optimizing the kinetics of leakless cascades without practical cost to their robustness. An in-depth case study explores the effects of this optimization when applied to a typical leakless translator cascade. Thermodynamic analysis of energy barriers and kinetic experimental data support that DSD cascades can be fast and robust.