Emergent digital bio-computation through spatial diffusion and engineered bacteria

Building computationally capable biological systems has long been an aim of synthetic biology. The potential utility of biocomputing devices ranges from biosafety and environmental applications to diagnosis and personalised medicine. Here we present work for the design of bacterial computers which use spatial patterning to process information. Our computers are composed of bacterial colonies which, inspired by patterning in embryo development, receive information in the form of diffusible morphogen-like signals. A computation is encoded by the physical locations of the input sources of morphogen and the output receiver colonies. We demonstrate, mathematically and with engineered Escherichia coli , the simple digital logic capability of single bacterial colonies and show how additional colonies are required to build complex functions. Inspired by electronic design automation, an algorithm for designing optimal spatial circuits computing two-level digital functions is presented. This enhances the capability of our system to complex digital functions without increasing the biological complexity. We extend our experimental system to incorporate biosensing colonies as morphogen sources, demonstrating how a diagnostic device might be constructed. Our approach will open up new ways to perform biological computation, with applications in bioengineering, biomaterials and biosensing. Ultimately, these computational bacterial communities will help us explore information processing in natural biological systems.