Glycan-Based Flow-Through Device for the Detection of SARS-COV-2.

Alexander N Baker,Sarah-Jane Richards,Caroline I Biggs,Simone Dedola,Panagiotis G Georgiou,Muhammad Hasan,Alexander J Zwetsloot,Dimitris Grammatopoulos,Sarojini Pandey,Anne Straube,Matthew I Gibson,Neil R Anderson,Ashfaq Ahmad,Robert A Field,Marc Walker,Collette S Guy

doi:10.1021/acssensors.1c01470

Abstract

The COVID-19 pandemic, and future pandemics, require diagnostic tools to track disease spread and guide the isolation of (a)symptomatic individuals. Lateral-flow diagnostics (LFDs) are rapid and of lower cost than molecular (genetic) tests, with current LFDs using antibodies as their recognition units. Herein, we develop a prototype flow-through device (related, but distinct to LFDs), utilizing N-acetyl neuraminic acid-functionalized, polymer-coated, gold nanoparticles as the detection/capture unit for SARS-COV-2, by targeting the sialic acid-binding site of the spike protein. The prototype device can give rapid results, with higher viral loads being faster than lower viral loads. The prototype’s effectiveness is demonstrated using spike protein, lentiviral models, and a panel of heat-inactivated primary patient nasal swabs. The device was also shown to retain detection capability toward recombinant spike proteins from several variants (mutants) of concern. This study provides the proof of principle that glyco-lateral-flow devices could be developed to be used in the tracking monitoring of infectious agents, to complement, or as alternatives to antibody-based systems.

Highlights

The COVID-19 pandemic, and future pandemics, require diagnostic tools to track disease spread and guide the isolation of (a)symptomatic individuals
The cost-effectiveness and clinical usefulness of Lateral-flow diagnostics (LFDs) have been demonstrated by malaria rapid diagnostic tests,[19,20] in the diagnosis of cutaneous leishmaniasis[21] and in comparisons with more expensive RTPCR approaches for Ebola diagnosis.[22]
We have demonstrated a prototype flow-through device, which is capable of detecting SARS-COV-2 by exploiting the interaction between α-N-acetyl neuraminic acid and the viral spike protein

Summary

Introduction

The COVID-19 pandemic, and future pandemics, require diagnostic tools to track disease spread and guide the isolation of (a)symptomatic individuals. We develop a prototype flow-through device (related, but distinct to LFDs), utilizing N-acetyl neuraminic acid-functionalized, polymer-coated, gold nanoparticles as the detection/capture unit for SARS-COV-2, by targeting the sialic acid-binding site of the spike protein. The cost-effectiveness and clinical usefulness of LFDs have been demonstrated by malaria rapid diagnostic tests,[19,20] in the diagnosis of cutaneous leishmaniasis[21] and in comparisons with more expensive RTPCR approaches for Ebola diagnosis.[22] the appeal of LFDs in the COVID-19 pandemic is that their low cost and rapid turnaround time may enable mass testing of large populations.[23] This could find asymptomatic individuals spreading the virus, who would not be identified by symptomatic RT-PCR testing only,[24−26] currently the preferred option in most healthcare systems. The first LFDs for the COVID-19 pandemic were designed to detect antibodies in patient blood samples produced in response to SARS-COV-2 infections.[27−29] These were intended to report if a patient has previously been infected; not to indicate active infection, so could not effectively be used in screening/triage settings or mass testing for active infections

Methods

Results

Conclusion