A COVID-19 rapid antigen test employing upconversion nanoparticles

The COVID-19 pandemic has underscored the critical need for rapid and accurate diagnostic tools. Current methods, including Polymerase Chain Reaction and rapid antigen tests (RAT), have limitations in speed, sensitivity, and the requirement for specialized equipment and trained personnel. Nanotechnology, particularly upconversion nanoparticles (UCNPs), offer a promising alternative due to their unique optical properties. UCNPs can convert low-energy near-infrared light into higher-energy visible light, making them ideal for use as optical probes in single molecule detection and point of care applications. This study, initiated in early 2020, explores the opportunity of using highly doped UCNPs (40%Yb³⁺/4%Er³⁺) in lateral flow assay (LFA) for the early diagnosis of COVID-19. The UCNPs-based LFA testing demonstrated a minimum detection concentration of 100 pg/mL for SARS-CoV-2 antigen and 10⁵ CCID₅₀/mL for inactivated virus. Clinical trials, conducted in Malaysia and Western Australia independently, showed that the technique was at least 100 times more sensitive than commercial RAT kits, with a sensitivity of 100% and specificity of 91.94%. The development process involved multidisciplinary collaborations, resulting in the Virulizer device, an automated strip reader for point-of-care testing. This work sets a reference for future development of highly sensitive and quantitative RAT, aiming for the Limits of Detection in the range of sub-ng/mL.