Redox-enabled Electronic Interrogation and Feedback Control of Hierarchical and Networked Biological Systems

Abstract

We enable microelectronic devices to interrogate biology's molecular communication, perform computations, and in real time control biological systems, including at several hierarchical levels: proteins, cells, and cell consortia. A key driver is establishing electronic access to and from biology's native redox networks. First, redox-mediated electro-biofabrication facilitates facile assembly of biological components onto microelectronic systems, then electrode-actuated redox allows digital programming of enzyme activity, and further, redox-mediated electrogenetics facilitates closed-loop electronic control of cellular function. Specifically, we show algorithm-based feedback control of enzyme activity, cellular genetic circuits (via eCRISPR) and cell consortia behavior, all enabled by electronic data transfer. We further demonstrate electronic switching of cell-cell quorum sensing communication from one autoinducer network to another, creating an electronically controlled "bilingual" cell. We suggest these methodologies will not only help us to better understand biological systems, but design and control those currently unimagined.