A glucose meter interface for point-of-care gene circuit-based diagnostics

Amalfitano, Evan; Karlikow, Margot; Norouzi, Masoud; Jaenes, Katariina; Cicek, Seray; Masum, Fahim; Sadat Mousavi, Peivand; Guo, Yuxiu; Tang, Laura; Sydor, Andrew; Ma, Duo; Pearson, Joel D.; Trcka, Daniel; Pinette, Mathieu; Ambagala, Aruna; Babiuk, Shawn; Pickering, Bradley; Wrana, Jeff; Bremner, Rod; Mazzulli, Tony; Sinton, David; Brumell, John H.; Green, Alexander A.; Pardee, Keith

Recent advances in cell-free synthetic biology have given rise to gene circuit-based sensors with the potential to provide decentralized and low-cost molecular diagnostics. However, it remains a challenge to deliver this sensing capacity into the hands of users in a practical manner. Here, we leverage the glucose meter, one of the most widely available point-of-care sensing devices, to serve as a universal reader for these decentralized diagnostics. We describe a molecular translator that can convert the activation of conventional gene circuit-based sensors into a glucose output that can be read by off-the-shelf glucose meters. We show the development of new glucogenic reporter systems, multiplexed reporter outputs and detection of nucleic acid targets down to the low attomolar range. Using this glucose-meter interface, we demonstrate the detection of a small-molecule analyte; sample-to-result diagnostics for typhoid, paratyphoid A/B; and show the potential for pandemic response with nucleic acid sensors for SARS-CoV-2.