Electrochemical Control with High Spatiotemporal Resolutions for Extracellular pH Microenvironment

The local pH values and hence the pH microenvironment surrounding an organism critically affect its metabolism and physiology in both prokaryotes and eukaryotes. Despite the ubiquitous spatiotemporal heterogeneity of local pH conditions in biology, a biocompatible method that spatiotemporally programs the pH microenvironment remains elusive. Here we report an electrochemical approach that spatiotemporally controls pH microenvironments for potential microbial applications. A quinone-based redox couple undergoes electrochemical proton-coupled electron transfer (PCET) that releases or consumes protons and hence changes the local pH. We designed a biocompatible hydroquinone/quinone redox couple that has minimal interference with bacterial aerobic respiration thanks to its hydrophilic nature and the specially targeted redox potential. Deploying such a uniquely designed redox couple with interdigitated electrodes in a microfluidic device leads to electrochemical control of the pH microenvironment with fast temporal modulation (~10¹ s) and high spatial resolution (~10⁰ <i>μ</i>m) suitable for biological applications. The concept of deploying biocompatible electrochemistry offers a new venue toward perturbing biological microenvironments at the cellular if not subcellular level.