Rapid isothermal amplification and portable detection system for SARS-CoV-2

Proc Natl Acad Sci U S A. 2020 Sep 15;117(37):22727-22735. doi: 10.1073/pnas.2014739117. Epub 2020 Aug 31.

Abstract

The COVID-19 pandemic provides an urgent example where a gap exists between availability of state-of-the-art diagnostics and current needs. As assay protocols and primer sequences become widely known, many laboratories perform diagnostic tests using methods such as RT-PCR or reverse transcription loop mediated isothermal amplification (RT-LAMP). Here, we report an RT-LAMP isothermal assay for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and demonstrate the assay on clinical samples using a simple and accessible point-of-care (POC) instrument. We characterized the assay by dipping swabs into synthetic nasal fluid spiked with the virus, moving the swab to viral transport medium (VTM), and sampling a volume of the VTM to perform the RT-LAMP assay without an RNA extraction kit. The assay has a limit of detection (LOD) of 50 RNA copies per μL in the VTM solution within 30 min. We further demonstrate our assay by detecting SARS-CoV-2 viruses from 20 clinical samples. Finally, we demonstrate a portable and real-time POC device to detect SARS-CoV-2 from VTM samples using an additively manufactured three-dimensional cartridge and a smartphone-based reader. The POC system was tested using 10 clinical samples, and was able to detect SARS-CoV-2 from these clinical samples by distinguishing positive samples from negative samples after 30 min. The POC tests are in complete agreement with RT-PCR controls. This work demonstrates an alternative pathway for SARS-CoV-2 diagnostics that does not require conventional laboratory infrastructure, in settings where diagnosis is required at the point of sample collection.

Keywords: COVID-19 diagnostics; RT-LAMP; SARS-CoV-2; point-of-care; smartphone reader.

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

  • Betacoronavirus / genetics
  • Betacoronavirus / pathogenicity
  • COVID-19
  • Coronavirus Infections / diagnosis*
  • Humans
  • Limit of Detection
  • Molecular Diagnostic Techniques / instrumentation
  • Molecular Diagnostic Techniques / methods*
  • Molecular Diagnostic Techniques / standards
  • Nasal Mucosa / virology
  • Pandemics
  • Pneumonia, Viral / diagnosis*
  • Point-of-Care Testing / standards*
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction / instrumentation
  • Reverse Transcriptase Polymerase Chain Reaction / methods*
  • Reverse Transcriptase Polymerase Chain Reaction / standards
  • SARS-CoV-2
  • Smartphone