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More than the eye can see: shedding new light on SARS-CoV-2 lateral flow device-based immunoassays

DOI: 10.1021/acsami.1c04283 DOI Help

Authors: Garrit Koller (Kingʼs College London) , Alexander P. Morrell (Kingʼs College London) , Rui Pedro Galão (Kingʼs College London) , Suzanne Pickering (Kingʼs College London) , Eithne Macmahon (Kingʼs College London; Guyʼs and St Thomasʼ NHS Foundation Trust) , Joanna Johnson (Guyʼs and St Thomasʼ NHS Foundation Trust) , Konstantin Ignatyev (Diamond Light Source) , Stuart J. D. Neil (Kingʼs College London) , Sherif Elsharkawy (Kingʼs College London) , Roland Fleck (King's College London) , Pedro Miguel Pereira Machado (Kingʼs College London) , Owen Addison (Kingʼs College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acs Applied Materials & Interfaces

State: Published (Approved)
Published: May 2021
Diamond Proposal Number(s): 28216

Abstract: Containing the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an unprecedented challenge due to high horizontal transmissivity and asymptomatic carriage rates. Lateral flow device (LFD) immunoassays were introduced in late 2020 to detect SARS-CoV-2 infection in asymptomatic or presymptomatic individuals rapidly. While LFD technologies have been used for over 60 years, their widespread use as a public health tool during a pandemic is unprecedented. By the end of 2020, data from studies into the efficacy of the LFDs emerged and showed these point-of-care devices to have very high specificity (ability to identify true negatives) but inadequate sensitivity with high false-negative rates. The low sensitivity (<50%) shown in several studies is a critical public health concern, as asymptomatic or presymptomatic carriers may wrongly be assumed to be noninfectious, posing a significant risk of further spread in the community. Here, we show that the direct visual readout of SARS-CoV-2 LFDs is an inadequate approach to discriminate a potentially infective viral concentration in a biosample. We quantified significant immobilized antigen–antibody-labeled conjugate complexes within the LFDs visually scored as negative using high-sensitivity synchrotron X-ray fluorescence imaging. Correlating quantitative X-ray fluorescence measurements and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) determined numbers of viral copies, we identified that negatively scored samples could contain up to 100 PFU (equivalent here to ∼10 000 RNA copies/test). The study demonstrates where the shortcomings arise in many of the current direct-readout SARS-CoV-2 LFDs, namely, being a deficiency in the readout as opposed to the potential level of detection of the test, which is orders of magnitude higher. The present findings are of importance both to public health monitoring during the Coronavirus Disease 2019 (COVID-19) pandemic and to the rapid refinement of these tools for immediate and future applications.

Journal Keywords: SARS-CoV-2; lateral flow device; immunogold; gold nanoparticles; antigen test; X-ray fluorescence; specificity; sensitivity

Diamond Keywords: COVID-19; Viruses

Subject Areas: Materials, Biology and Bio-materials

Instruments: I18-Microfocus Spectroscopy

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Infectious Diseases Pathogens Material Sciences Nanoscience/Nanotechnology

Technical Tags:

Imaging X-ray Fluorescence (XRF)