Configurable Full Subtractor and Adder by Lego-like Mixing and Matching of Engineered Bacteria in an Artificial Neural Network Type Architecture

Abstract One of the long-term goals of synthetic bioengineering is to create configurable and programmable biological systems by just mixing and matching "LEGO"-like bio-modules. Here, we introduce a configurable and modular multi-cellular system where, from a small library of nine discrete engineered bacterial cells, a full subtractor, which subtract binary numbers and a full adder, which adds binary numbers can be built on demand by just mixing and matching seven appropriate cell types in a culture. Here, each set of engineered bacteria was modelled as an ‘artificial neuro-synapse’ that, in a co-culture, formed a single layer artificial neural network (ANN) type architecture that worked as a biochemical full subtractor or full adder. The system is configurable with interchangeable cellular modules, whereby through simply interchanging two cell types in the subtractor culture, a full adder can be built and vice versa. This Lego-like mix and match system is mathematically predictive, and the physical scaling up of the whole system was achieved by directly applying mathematical scale up of the cellular modules. This work provides a flexible and scalable means to build complex cellular functions and may have significance in biocomputer technology development, multi-cellular synthetic biology, and cellular hardware for ANN.