Semisynthetic sensor proteins enable metabolic assays at the point of care

Science. 2018 Sep 14;361(6407):1122-1126. doi: 10.1126/science.aat7992.

Abstract

Monitoring metabolites at the point of care could improve the diagnosis and management of numerous diseases. Yet for most metabolites, such assays are not available. We introduce semisynthetic, light-emitting sensor proteins for use in paper-based metabolic assays. The metabolite is oxidized by nicotinamide adenine dinucleotide phosphate, and the sensor changes color in the presence of the reduced cofactor, enabling metabolite quantification with the use of a digital camera. The approach makes any metabolite that can be oxidized by the cofactor a candidate for quantitative point-of-care assays, as shown for phenylalanine, glucose, and glutamate. Phenylalanine blood levels of phenylketonuria patients were analyzed at the point of care within minutes with only 0.5 microliters of blood. Results were within 15% of those obtained with standard testing methods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioluminescence Resonance Energy Transfer Techniques*
  • Biosensing Techniques*
  • Blood Glucose / analysis
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Glutamic Acid / blood
  • Humans
  • Monitoring, Physiologic / methods*
  • NADP / metabolism
  • Oxidation-Reduction
  • Phenylalanine / blood
  • Phenylketonurias / blood
  • Phenylketonurias / diagnosis
  • Point-of-Care Testing*
  • Tetrahydrofolate Dehydrogenase / chemistry*
  • Tetrahydrofolate Dehydrogenase / genetics

Substances

  • Blood Glucose
  • Escherichia coli Proteins
  • Glutamic Acid
  • Phenylalanine
  • NADP
  • Tetrahydrofolate Dehydrogenase