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

Nat Commun. 2021 Feb 1;12(1):724. doi: 10.1038/s41467-020-20639-6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biosensing Techniques / instrumentation
  • Biosensing Techniques / methods*
  • COVID-19 / diagnosis
  • COVID-19 / epidemiology
  • COVID-19 / virology
  • Gene Regulatory Networks / genetics*
  • Glucose / analysis*
  • Glucose / metabolism
  • Humans
  • Nucleic Acids / analysis*
  • Nucleic Acids / genetics
  • Pandemics
  • Point-of-Care Systems*
  • Point-of-Care Testing*
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / physiology
  • Typhoid Fever / blood
  • Typhoid Fever / diagnosis
  • Typhoid Fever / microbiology

Substances

  • Nucleic Acids
  • Glucose