A glucose meter interface for point-of-care gene circuit-based diagnostics
Evan Amalfitano, Margot Karlikow, Masoud Norouzi, Katariina Jaenes, Seray Cicek, Fahim Masum, Peivand Sadat Mousavi, Yuxiu Guo, Laura Tang, Andrew M. Sydor, Duo Ma, Joel D. Pearson, Daniel Trcka, Mathieu Pinette, Aruna Ambagala, Shawn Babiuk, Bradley Pickering, Jeffrey L. Wrana, Rod Bremner, Tony Mazzulli, David Sinton, John H. Brumell, Alexander A. Green, Keith Pardee
Abstract
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.